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THE 
 
 Untoward Effects of Drugs. 
 
 A Pharmacological and Clinical Manual. 
 
 BY 
 
 DR. L. LEWIN, 
 
 DOCENT OF MATERIA MHDICA, HYGIENE AND PUBLIC HEALTH IN THE UNIVERSITY Ol 1 BERLIN. 
 
 SECOND EDITION, REVISED AND ENLARGED. 
 
 TRANSLATED BY 
 
 J. MULHERON, M. D. 
 
 Prof 
 
 of Principles of Medicine, Materia Medica and Therapeutics in the 
 Michigan College of Medicine, Detroit, Michigan. 
 
 The Only English Translation Having the Author's Endorsement. 
 
 
 - 
 
 MAV 7 ,383'' 
 
 DETROIT, MICH., U. S. A.: 
 GEORGE S. DAVIS, MEDICAL PUBLISHER. 
 
 1883. 
 

 
 
 
 
 y 
 
 
 
 ./wtl 
 
 
 COPYRIGHT, 1883, 
 
 
 BY 
 
 GEORGE S. DAVIS, 
 
 DETROIT, MICH. 
 
 
3 
 
 PREFACE. 
 
 Occupying, as it does, a middle ground between pure experimentation 
 and empiricism, the science of materia medica is enriched alike from the 
 laboratory and observations at the sick bed. It is through a combination 
 of the results furnished through these two channels, that the typical modus 
 operandi of any individual drug can alone be determined. 
 
 There occur, however, now and then, in the therapeutical application 
 of certain drugs, certain deviations from this typical, and, to a degree, nor- 
 mal action, the correct perception and significance of which are not always 
 understood. But a knowledge of these is of the utmost importance to the 
 physician, as affording him an explanation of the causes of certain symp- 
 toms, and also furnishing him with a guide to his practical management of 
 them. 
 
 The records of the individual facts here indicated — the appearance of 
 abnormal effects of drugs — are scattered throughout the most diverse parts of 
 medical literature, and are either not at all or but superficially considered 
 in the manuals or text-books of materia medica. For this reason I have 
 for a long time been making a collection of these facts, examining them 
 critically, and making additions to this collection from my own personal ex- 
 perience. I have presented the results of this labor in this book in the 
 hope that they will meet a practical want, and at the same time stimulate 
 ethers to further observations in the same direction. 
 
 L. LEWIN. 
 
 Berlin, January, 1SS1. 
 
TRANSLATOR'S PREFACE. 
 
 When I saw the announcement of Dr. Lewin's book on ''Die 
 Nebenwirkungen der Arzneimittel," I was constrained from experi- 
 ence, both in private practice and in the capacity of teacher of 
 materia medica and therapeutics, to send for a copy. The necessity 
 of a treatise on the subject indicated by this title must have been felt 
 by all practitioners, for previous to the appearance of this book by 
 Dr. Lewin there was no systematic work of this nature, such infor- 
 mation as was extant existing merely as it was scattered in oc- 
 casional references in text books and periodical literature. . An ex- 
 amination of the work so convinced me of its great value as to 
 induce me to undertake the translation herewith presented, the 
 author's consent having been previously obtained. I am under 
 obligations to Dr. Lewin for his review of the proof sheets and his 
 endorsement of the translation. He has also made copious 
 additions to the original, so that the book as it now appears in 
 English is virtually a second and revised edition. 
 
 J. J. MULHRRON. 
 
 Detroit, Mich., December. 1882. 
 
INTRODUCTION 
 
 Medicines exert a localized influence in the animal economy, 
 i. <?., they influence, according to their chemical or physical pro- 
 perties, certain classes of cells or cellular tissue, chiefly or exclu- 
 sively. " Certain substances are possessed of an affinity for 
 specific parts of the system." From this fundamental view, 
 first enunciated by Virchow,* it follows that a whole series of 
 remedies may, in addition to their curative effects, give rise to 
 symptoms, either by direct or through reflex action upon similar 
 or dissimilar groups of cells, which should not have been occa- 
 sioned in securing the therapeutic effects of the remedy. In 
 this way, in the exhibition of opiates, for instance, are not 
 only the nerve centres and nerves affected, but also the periph- 
 eral nervous structure, and there follows in consequence, in 
 addition* to the more or less pronounced hypnotic effects of 
 the drug, a transitory impairment of the motor nerve supply of 
 the intestines, and through this, constipation. In the case of tar- 
 tar emetic, given internally, vomiting occurs in consequence of 
 irritation of the mucous lining of the stomach, but the drug, 
 through its direct effect on the cardiac tissue, causes also a 
 simultaneous reduction in the force of the heart's action. When 
 chloroform is given by inhalation we have a direct action on 
 the cerebro-spinal nerve centres, but particularly on the cerebrum; 
 at the same time we have a checking of the heart's action 
 through reflex action aroused by local contact of the drag on the 
 mucous lining of the air passages. While, therefore, under the 
 influence of opium and chloroform, similar nerve substance in dif- 
 ferent parts of the body suffers change, the antimony in tartar 
 
 . * Virchow, Specificer, und Specifisches. Archiv, für patholog. Anatomie, Bd 
 VI., 1354, p. 34. 
 
8 THE UNTOWARD EFFECTS OF DRUGS. 
 
 emetic affects tissue of a heterogeneous nature, as mucous mem- 
 brane and muscular tissue. In an analogous manner may sub- 
 stances possessed of an inherent property of influencing a still 
 greater variety of cellular formations, induce a corresponding 
 complexity of pathological conditions. But in spite of this these 
 operations are regarded as physiological, inasmuch as they are 
 inseparable from each other and are inherent as a whole to the 
 medicine employed. The individual symptoms are differentiated, 
 in respect to the claim of therapeutic action, only in so far as 
 a distinction is made between the characteristic action and un- 
 toward effects induced. 
 
 While nearly all the various medicinal agents, and in the 
 manner indicated, exert their typical inherent action on certain 
 groups of cells, each group, respectively, being a focus of dis- 
 ease, and thus act therapeutically, it is not infrequently evident 
 that in individual cases the desired localized action does not 
 obtain, the drug being in this regard inert. Thus chloroform 
 may fail to exert its hypnotic action, quinine to reduce an en- 
 larged spleen, and purgatives, even such as are classed as dras- 
 tics, to induce catharsis. 
 
 When the drug is up to the recognized standard as regards 
 its active principle — which must be assured in such cases — 
 this important abnormality, in a therapeutic sense, can only be 
 referred to the person in whom it is noted, whose organization 
 or the nature of whose diseased or healthy parts which it is de- 
 sired to influence, must present differences from corresponding 
 parts in other individuals. This same postulate may be pre- 
 dicated concerning such persons as present peculiarities of pre- 
 disposition to certain diseases, and who consequently are, for 
 instance, not susceptible to the contagious diseases e. g. f typhoid 
 fever, and so on. In such cases the immunity need not reside 
 in any grossly anomalous condition, but may, as will be indi- 
 cated in detail further on, be referred to textural and organic 
 variations which are still physiological. 
 
 It is manifest that if certain organs of individual persons 
 behave in a peculiar manner, as regards medicines, the rule of 
 whose action is to work definitely determined effects, thera- 
 
INTRODUCTION. 
 
 peutic experiments with such substances in such individuals, are 
 liable to lead to false conclusions. We have in this fact a pos- 
 sible explanation of the diametrically opposite effects which 
 have been frequently observed to follow one and the same 
 drug in different persons. 
 
 §3 
 
 Of far greater importance to the physician than the failure 
 of the drug to work its normal action, are the untoward ef- 
 fects which medicines have not infrequently been observed to 
 induce, effects which are either substituted for the normal ac- 
 tion or appear simultaneously with it. As an illustration of 
 such untoward action may be noted the eruption following the 
 administration of quinine, or in rare cases the undue effect of 
 the same drug on the organs of sight, as seen in long con- 
 tinued amaurosis. Cod liver oil, ordinarily so bland, may give 
 rise to a vesicular eruption, iodide of potassium may occasion 
 a hypersecretion from the mucous membrane of the eyes and 
 nose, and salicylic acid may, among other effects, cause diaph- 
 oresis and nervous disturbances. 
 
 The greatest variety of names may be found in medical 
 literature for these untoward symptoms following the exhibi- 
 tion of drugs. In Germany they have been and still are known as 
 "Nebenwirkungen," " physiologische Nebenwirkungen," or "Arz- 
 neisymptome " and are also spoken of as the "special" or "acci- 
 dental" or "peculiar" action of the drug. French authors re- 
 fer to them as "Inconvenients" or "Inconvenients therapeu- 
 tiques," as "Accidents" or "Cas d'accidents." In England they 
 are occasionally termed "unpleasant symptoms." 
 
 There has been some hesitation in regarding these " neben- 
 wirkungen" as poisonous effects. And very properly so, for we 
 are not justified in regarding one or more symptoms as the 
 effects of a poison, simply because they may not occur in 999 
 cases and yet appear in the thousandth. In addition to this 
 it may be noted that the majority of these untoward effects do 
 not, in any particular, correspond with the symptoms induced by 
 a poisonous dose of the drug, and that we cannot, at will, ef- 
 fect these untoward symptoms and especially such as manifest 
 themselves in cutaneous eruptions. These occur only under 
 
THE UNTOWARD EFFECTS OF DRUGS. 
 
 very definite individual conditions and can not, therefore, be 
 always excited through experimentation. There is, even to-day, 
 no lack of physicians who, still imbued with old time views 
 on humoral pathology, ascribe the occurrence of these untoward 
 effects of drugs to certain teleological conditions, even as they 
 w r ere formerly wont, in like manner, to regard hemorrhoidal 
 fluxes. Just as it was regarded as a fortunate circumstance 
 that the "vital principle" controlling the blood vessels, chose the 
 hemorrhoidal vessels through which to eliminate the " impuri- 
 ties"* so the untoward effects of medicines, especially those 
 manifesting themselves on the skin, were regarded as the evi- 
 dences of a struggle going on between the medicine and the 
 " disease elements" in the body, and more particularly in the blood, 
 functional changes, or material anatomical lesions in which latter 
 were an evidence of either the suppression or elimination of such 
 "elements" from the body. As opposed to this vitalistic humoral 
 pathology we have another theory on which to account for 
 these untoward effects, both such as manifest themselves as 
 almost constant attendants on drug action and those which 
 occur but seldom. The cause of these may reside in the individual^ 
 be due to circumstances of time and place, or be referable to the 
 inherent nature of the remedy. We shall now consider the former 
 of these causes. 
 
 §4 
 
 The natural peculiarity of each individual in respect to all 
 others may be either permanent or but temporary. It mani- 
 fests itself most markedly as the result of the manifold adven- 
 titious circumstances which are the usual causes of disease. 
 
 The same external conditions, operating on a number of per- 
 sons, may produce such a variety of results, that while some 
 may not be appreciably affected by them others may suffer 
 transient effects, and still others sustain permanent functional 
 derangement. Here there is evidently a wide range of indi- 
 vidual susceptibility to external influences. This susceptibility 
 may even become so marked, that causes which inherently oper- 
 ate within physiological limits may be productive of pathological 
 symptoms. The odor of the rose, the eating of a strawberry. 
 
 *Refer. b. O. Schuetz, Die Lehre von der Constitution. Berlin, 1872. 
 
INTRODUCTION. 
 
 etc., may in some excite certain nervous symptoms, palpable 
 cutaneous eruptions, for instance — a behavior which has been 
 regarded as a heightened individual irritability, or as an idiosyn- 
 crasy — while innumerable other persons will be in no wise thus 
 affected. 
 
 Analogous phenomena manifest themselves as a result of 
 the external or internal exhibition of medicines. The extract 
 of calabar bean instilled into • the eye excites only in certain 
 persons a burning sensation in the conjunctival sac, and an 
 increased secretion of tears ; morphia taken internally causes 
 only in excitable persons a spasm of accommodation ; and 
 Pilocarpin, in certain persons and in certain doses, excites pro- 
 fuse diaphoresis, literally bathing the individual in perspiration, 
 while in others, similar doses scarcely excite a slight transpi- 
 ration. We thus see, under conditions otherwise similar, varia- 
 tions in the operation of external influences on similar tissues, 
 which find their explanation only in the peculiarity of the in- 
 dividual. 
 
 But of what nature are these ? We are not yet in a posi- 
 tion to give an entirely satisfactory answer to this question. 
 It is only recently* that an attempt has been made, through 
 comparative anatomical examination of the physical behavior of 
 certain organs, as the heart, blood vessels, intestines, etc., in per- 
 sons of different ages and sexes to explain so-called constitutional 
 differences. Efforts have also been made, through experiment, to 
 throw light upon this obscure subject. Thus Albertonif found in 
 the effects of atropine on young dogs, an analogue to the obser- 
 vation that children, of from fifteen months to five years of age, 
 may take with impunity doses of the tincture of belladonna 
 which would give rise to many symptoms of poisoning in adults. 
 In the young dog o.oi to 0.02 gramme (gr. 1 to gr. J) of atro- 
 pine causes no disturbance of intelligence, but only a trifling indispo- 
 sition and slight excitement, while in older animals there is marked 
 disturbance of the intelligence. He discovers the reason of this dis- 
 crepancy in the difference in the degree of development and excit- 
 ability of the nervous system which exists between the young and 
 
 *Beneke, Die Anatomischen Grundlagen der Constitutions anomalien. Marburg 1878. 
 —Veröffentlichungen der Gesellschaft für Heilkunde in Berlin, IV., 1881, p. 10. 
 
 tAlbertoni Archiv, f. exper. Pathologie XV. p. 264. 
 
12 THE UNTOWARD EFFECTS OF DRUGS. 
 
 the adult animal. The experiments of Soltmann* may be adduced 
 in support of this view. This observer found that in dogs ten 
 days old electrical irritation of the cortex of the brain produced 
 no effect, and that the inhibitory apparatus of the heart in 
 newly born dogs is either not at all or but imperfectly developed. 
 The latter is demonstrated by the fact that electrical irritation 
 of the vagus causes no stoppage, or at most but a slight decrease 
 in the frequency of the cardiac contractions. The electrical ex- 
 citability of the motor nerves is also less in the new-born than 
 in adults. 
 
 There are further, as we shall see later on, a series of 
 physiological processes in the body which, under certain cir- 
 cumstances, may give it the character of specific predisposition, 
 and we are familiar with pathological conditions so insignificant in 
 their nature as not to be cognizable during life, which may, how- 
 ever, render the individual highly susceptible to irritation. But 
 do all of these circumstances suffice to explain what Virchow has 
 termed the " mystery of individuality ? " Certainly not. And if we 
 consider but a few of the details which may come under notice 
 here, if we, for instance, recall the limitless variability in the vas- 
 cular supply of the system, the variety of the arrangement of 
 glandular tissue in the glands, the' discrepancies of innervation 
 in individual organs, the differences in the size of their fila- 
 ments in the majority of individual nerves, and the diversity of 
 arrangement of the coarser and the finer fibers in correspond- 
 ing muscles in different persons, we must confess that we have 
 in these facts, instances not only of the unknown but also of the 
 unknowable. But we are not justified, on account of this, in deny- 
 ing general individuality, or in belittling its significance. For 
 the possibility of explaining is, as Virchow demonstrates, not yet 
 a scientific criterion, inasmuch as we know much empirically for 
 which we can find no warrant in reason. No exact investigation, 
 be it anatomical or physiological, pathological or therapeutical, has 
 as yet been able to lift the veil spread over the conditions of 
 individual peculiarity. It has in all ages been regarded as the 
 privilege of only the most favored geniuses or of the most 
 prolonged experience, to arrive at that delicate insight which 
 
 *Solt.-nann Jahrbuch f. Kinderheilkunde IX. 1875, XI. 1877 und XII Heft 1. 
 
INTRODUCTION. 13 
 
 permits of an approximate conception of the specific character 
 of the individual. 
 
 The fact that since the establishment of practical and de- 
 scriptive medicine, peculiarities of constitution have been recog- 
 nized and considered, is too well known to necessitate men- 
 tion. The doctrine of temperaments, the conception of a san- 
 guine, choleric, phlegmatic, and melancholic constitution under 
 the belief that these were severally dependent on a predomi- 
 nance of blood, bile, mucus and black bile in the individual, 
 remained for centuries a firm conviction amid the wreck of all 
 other medical theories; though this doctrine, the quintessence 
 of humoral pathology, is most one-sided and falsely based, it 
 is nevertheless in perfect harmony with all attempts to arrive 
 at a knowledge of minute individual peculiarities. 
 
 The factors which present themselves in connection with 
 the latter question cannot be of a gross nature. This has an 
 especial bearing on the specific peculiarities of individual organs. 
 And if there is aught to support the declaration of Virchow,* 
 that " the reaction of the tissues does not essentially depend 
 upon external influences but directly on their internal disposi- 
 tion," it is the individual peculiarities which the tissues of cer- 
 tain persons evince in regard to medicines. The external appli- 
 cation of tincture of iodine to the skin ordinarily gives rise 
 to but an erythema, and yet there are persons in whom an 
 application of the same preparation produces blisters and ex- 
 tensive oedema. Even a bland ointment composed of any 
 pleasant fresh fat excites inflammatory action when rubbed in- 
 to the skin of many persons. In such cases the cause can 
 only reside in some very slight, but chemically and physically 
 inexplicable, idiosyncrasy of the skin and its parts. When the 
 diversity of the chemical and physical relations of isomeric 
 bodies /. e. y bodies containing an equal percentage of elements, 
 are taken into consideration the difficulty of tracing such grave 
 functional disturbances to such slight deviations in the arrange- 
 ment and construction of the organ concerned is readily over- 
 come. In such cases by a mere change in the disposition of cer- 
 tain molecules, so great changes are produced in the body that 
 
 ♦Virchow, Krankheitswesen und Krankheitsursache, Arch, fürpathol. Anat, Bd. 79, H. 1, 
 p. 10. 
 
14 THE UNTOWARD EFFECTS OF DRUGS. 
 
 they appear as elementary differences. In spite of this the 
 number of carbon, hydrogen and oxygen atoms, as for instance 
 in pyrogallic acid and phloroglucin, and in hydrochinon, re- 
 sorcin and brenzcatechin remains the same. Perhaps we may 
 be led to recall through this the behavior of allotropic bodies, 
 which probably reveal, through but slight variations in molecular 
 arrangement of entirely similar chemical constituents, very diverse, 
 physical properties, as is seen in carbon in the forms of dia- 
 mond, graphite and coal. 
 
 We can conceive of certain organs of the bodies of a 
 group of persons, being so arranged by nature that although 
 entirely similar in chemical constitution and even in micros- 
 copical texture, they are still so different that they react under 
 the slightest irritation, or evince an unwonted reaction in the 
 presence of ordinary stimulation. 
 
 We have hitherto considered only individuals, or organs in 
 their variable relations to all others of a similar kind. Al- 
 though the differences which have been noted, are very marked, 
 they will nevertheless be found to be exceeded by those which 
 are manifested by similar and dissimilar organs of the same per- 
 son as the result of the external, specifically medicinal influence y 
 whether resulting directly through the action of the drug 
 or as a result of indirect, reflex action. There is even a dif- 
 ference in the physiological capability of individual organs of 
 similar nature in the same body. The degree of contractility 
 of the gastrocnemius of one side is rarely found under similar 
 external conditions to be equal to that of the opposite side, nor 
 is the irritability of a nerve identical with that of its correspon- 
 dent. The cause of this difference may be found in existing 
 inherent differences of development of the functional elements 
 of the parts, one muscle thus containing more primitive fibres 
 than the other, and the one nerve being endowed with more 
 nerve fibres than its fellow of the opposite side; it may also 
 result from a greater or less degree of perfection in the sev- 
 eral parts. The latter property is noticeable in a comparison of 
 the muscles of the extremities of the more greatly exercised 
 right side with those of the left. 
 
INTRODUCTION. 
 
 It is further a noticeable fact that similar but not corre- 
 sponding portions of the body, as for instance different group 
 of muscles, in the same manner differ in their functional ac- 
 tivities, without being diseased. In accordance with this fact 
 a given volume of the deltoid muscle exceeds in mechanical 
 executive ability a similar volume of the intercostal muscles. 
 
 We know that while the cardiac branches of the pneumo- 
 gastric can be irritated only by a very strong current the pul- 
 monary branches of the same nerve are endowed with an unusual 
 degree of irritability. These differences are still more marked 
 in apparatuses made up of different tissues, as for instance, 
 the joints. One is at first inclined to believe that there 
 exists a complete correspondence between the arrangement of 
 individual parts, and a similarity in their reaction against exter- 
 nal impressions. This, however, is not the case. In precisely 
 the same manner such intimate complexity of arrangement as 
 obtains in the instance cited — muscles, connective tissue, cartilage 
 and bone — in the most varied proportions, and revealing the 
 greatest differences with regard to the extent of their vascular 
 and nerve supply, are not to be placed side by side and are 
 certainly not to be held as of equal value. This is most clearly 
 manifest in any effort which may be made to secure identical 
 effects in these parts with the same drug, when they are dis- 
 turbed by disease. In such cases the most unexpected results 
 follow the most direct, application. An observation by Senator* 
 is very instructive in this connection. He found that in the 
 employment of carbolic acid by direct injection into the joints 
 in acute articular rheumatism, the most favorable effects were 
 apparent in the shoulder joint, then respectively in the knee, 
 wrist, elbow, and last of all in the hip joints. In the discussion 
 of this fact Senator adduces the following as important in occa- 
 sioning these peculiar conditions : anatomical differences, the 
 number and disposition of the vessels, or only unknown pecu- 
 liarities in the structure of the joints, without, however, de- 
 ciding in favor of any one of them. There are, indeed, so 
 many possibilities which suggest themselves in this connection, 
 and we are so far from understanding the most insignificant 
 
 ♦Senator, Berl. Klin. Wochenschr., 1876, p. 70. 
 
l6 THE UNTOWARD EFFECTS OF DRUGS. 
 
 of them that we are obliged to content ourselves with bring- 
 ing them as completely as possible within the range of our 
 observation. But even if in a particular case, we had proved, 
 for instance, an abnormal vascular distribution in the right 
 shoulder joint as compared with that of the left corresponding 
 joint, or a more perfect innervation of the knee-joint than ap- 
 pears in the elbow, we could even then but conjecture why the 
 same medicine applied to these parts produces different results, 
 why in one person it operates therapeutically and in another 
 produces effects exactly opposite. 
 
 A further investigation in this direction shows us that in 
 persons, happily few, with a special predisposition, the effects 
 of a drug, whether desirable or undesirable, appear so simul- 
 taneously in different parts, and occur so closely together, that 
 it is impossible to separate the one from the other. We know 
 of instances in which the exhibition of iodide of potassium for 
 the reduction of hypertrophied (hyperplastic) glands, as for 
 instance the thyroid or cervical, etc., while producing the 
 desired effects has also unhappily caused a serious atrophy of 
 glands which had hitherto been perfectly sound, e. g., the 
 mammae and testes. Such a change can, however, in our opin- 
 ion, only be brought about in organs which, although they 
 appear normal, have nevertheless essentially departed from the 
 normal standard. A merely slight departure from the normal 
 standard may subject them to influences to which they are not 
 ordinarily subject. 
 
 § 6 . 
 
 The differences in the reaction of certain persons or in- 
 dividual tissues of the same organism against certain medicinal 
 influences, which we have been considering in the foregoing 
 pages, reside in an organic constitutional tendency, which is 
 either congenital or acquired, and is unalterable. 
 
 There exists, however, a disposition which is but temporary. 
 This may have its foundation either in a greater abundance in the 
 system of chemical substances which cause an unusually prompt 
 solution of the medicines introduced, or which may unite with them 
 to form injurious compounds, or it may be conditioned on pre- 
 
INTRODUCTION. I? 
 
 existing pathological changes in the organs, to wit, diseases of 
 the inhibitory apparatus of the systej?i. 
 
 With regard to the former we shall consider the striking 
 observations of Mialhe.* He explains the abnormal reaction 
 on medicines, due to the difference in the mixture of animal 
 juices, rather as a " chemical idiosyncrasy" than as an 
 "idiopathic idiosyncrasy," which is to be regarded as the ex- 
 pression of differences in tissue construction. It is, for instance, 
 known that under certain circumstances insoluble medicines, as 
 oxide of iron, zinc, Kermes mineral, etc., excite effects in the 
 system quite different from those which usually follow the ad- 
 ministration of these substances — they excite baneful untoward 
 effects. The cause of this is to be found in excessive acidity 
 of the stomach, through which larger quanties of the drugs 
 named are dissolved. This difference in fluids which may be 
 regarded as the expression of local disturbances, is very intrinsi- 
 cally distinct from inherent humoral pathological dyscrasia, in 
 that it is quite temporary and may be obviated by the em- 
 ployment of chemical or dietetic means. 
 
 The consideration of such condition of the stomach renders 
 it easy in a given case to understand the action of a par- 
 ticular drug. Until even the present time, for instance, opinions 
 are divid3d as to the reason why the much used basic nitrate 
 of bismuth, the old magisterium bismuth, and sometimes even 
 in small doses, occasions violent irritation of the stomach and 
 bowels, as vomiting, diarrhoea, etc., and also general disturb- 
 ance, while in other cases large doses, 4 to 6 grammes, pro- 
 dace no abnormal effects. It has been conclusively proved 
 that the reiterated assertion that these untoward effects are due 
 to the lead or arsenic in the bismuth can not be true, the quanti- 
 ties thus contained being usually too small. A much more com- 
 mon cause is to be found in the undue quantity of the acids 
 of the stomach. When these exceed the normal it may be due 
 to a change of an innocuous basic salt into a corrosive neutral 
 substance, or through the action of water on the latter into a 
 poisonous acid salt, and thus, through absorption of the metal, 
 causing local as well as general poisonous effects. That the 
 
 ♦Mialhe, Die Receptirkunst, übers, von Biefel. Breslau. 1852, page 239. 
 
THE UNTOWARD EFFECTS OF DRUGS. 
 
 stomach may at different times, dependent on the individuality of 
 particular persons, the nutriment ingested, the state of diges- 
 tion, etc., contain different amounts of acids, is a fact which 
 can be so easily established, both clinically and experimentally, 
 as scarcely to require further mention. 
 
 The same is true of the intestinal juices. The greater or 
 lesser alkalinity of these involves the solubility of a great range 
 of mineral and vegetable substances, and in the presence of but 
 a slightly alkaline reaction the action of a drug may be en- 
 tirely suspended or it may be but partially operative, or through 
 an excessive alkalinity in the intestinal juices so great a quan- 
 tity of the drug exhibited may be dissolved as to cause a modi- 
 fication of the effects usually observed. The latter effects 
 may for instance, be noticed in the exhibition of the yellow 
 sulphuret of antimony. While usually only a very mild expec- 
 torant action is observed, there are cases in which the full 
 and pure action of antimony, vomiting, diarrhoea, and cardiac 
 sedation are noted. The cause of this is only referable to 
 increased alkalinity of the intestines through which a larger por- 
 tion of the drug is rendered absorbable. 
 
 The chloride of sodium present in the system exerts an 
 influence fully as marked as do the acidity of the stomach and 
 alkalinity of the intestines, and it is even more variable in its 
 quantity. When, for instance, calomel is exhibited, a difference 
 in its effects on individual functions is observable, according to 
 the quantity of common salt which may be present in the sys- 
 tem. In patients who have for a long time been on low, pos- 
 sibly saltless diet, calomel has scarcely any action, inasmuch as 
 a great part of the chloride has been, as it were, washed out 
 of the system by means of fluid diet and large quantities which 
 have been given to drink. On the other hand, as Mialhe has 
 observed, persons who have long subsisted on salted food, 
 sailors for instance, are very susceptible to calomel, the drug 
 being liable to cause in them symptoms of intestinal irritation 
 and a series of other unpleasant effects of mercury. 
 
 From these few facts, briefly stated, it will be seen that 
 many untoward effects are liable to attend the exhibition of 
 medicines. In most cases no peculiarity of constitutional ten- 
 dency is requisite. Pathological changes in the stomach and 
 
INTRODUCTION. IQ 
 
 bowels, and also febrile conditions, which modify the composi- 
 tion of the secretions of these organs, and even the unconscious 
 ingestion of some article of diet which forms deleterious com- 
 pounds with certain drugs, are liable to induce a predisposition 
 to untoward effects not contemplated. • 
 
 While changes may thus take place in different parts of 
 the body in which the necessary conditions exist for the for- 
 mation of tissue change, certain organs may at the time of the 
 administration of a particular drug be in such a patho- 
 logical condition, how slight soever this condition may be, 
 existing changes may be temporarily aggravated by the 
 medicine, or new pathological symptoms may develop in 
 the organ, which might not otherwise have supervened. A 
 few examples may be given in illustration of this. It is 
 known that potassic iodide is partially eliminated through 
 the mucous lining of the air passages and that it thus 
 occasionally gives rise to slight catarrhal symptoms, which, 
 not being very decided, disappear on suspension of the 
 drug. If, however, lesions exist coincidently with the action 
 of the iodide of potassium, it may, as has been at different 
 times observed, especially in syphilitics with laryngeal ulcer- 
 ation, give rise to oedema of the glottis which may 
 speedily prove fatal. In the same manner very small doses 
 of active cathartics, as elaterium, gamboge, etc., which if they 
 cause irritation of the intestines, do so within limits which are 
 to a degree physiological and but temporary, may, when there 
 is a previously existing abnormal condition of the mucous mem- 
 brane, excite a severe inflammatory condition of the tract, with 
 tenesmus, bloody stools, etc. Should the causative connection 
 between such effects of the medicine and the existing slight 
 organic changes not be understood, the new conditions thus 
 induced may be mistaken jfor a spontaneous disease of the por- 
 tion of the body attacked. 
 
 It is scarcely necessary to note that* such conditions as 
 menstruation, pregnancy, mental excitement, and intellectual ex- 
 ertion, insomnia, and even abstinence and digestion which may be 
 within physiological limits, are capable of modifying in various 
 ways the action of medicines. 
 
20 THE UNTOWARD EFFECTS OF DRUGS. 
 
 §7- 
 
 The third cause of a transitory predisposition to abnorma 1 
 action of medicines lies in disturbed regulation. Should any 
 other cause of disease attack a particular part of the body, 
 there arises a disturbance indicated by Schütz, on the strength 
 of views enunciated by Virchow : "But this disturbance is not 
 pathological should the regulation be easy. It is only when 
 the regulation is difficult or impossible that danger is liable 
 to supervene." The favorable or deleterious action of rem- 
 edial agents is also dependent on a good or bad regula- 
 tion. The latter is here to be regarded as identical with elim- 
 ination. Ordinarily calomel, for instance, in proper doses in- 
 duces by its action on the intestines, purgation. As soon as 
 this occurs the greater part of the drug is discharged from 
 the body with the feces, in the form of mercuric sulphide. 
 Should, however, purgation from any cause not occur the calo- 
 mel may remain in the intestines, chiefly in the csecum, where 
 by continuous contact with chloride of sodium it is changed 
 into corrosive sublimate and thus cause injurious t corrosion 
 and ulceration of the intestinal mucous lining. 
 
 Should the regulation be normal, or, more strictly, should 
 the secretory apparatus properly perform its function, even poi- 
 sonous substances may be for a long time ingested without 
 causing any disturbance — while if any of the excretory ducts 
 are closed poisonous symptoms immediately supervene. Her- 
 mann f has utilized this fact in explaining the intermittent 
 symptoms of lead poisoning. He give,s utterance to the opin- 
 ion that "while the lead cachexia must be regarded as the 
 effect of the diffusion of certain portions of lead in the body, 
 the additional affections must have a specific cause which in 
 spite of further developing lead poisoning, may finally disap- 
 pear. This cause he detects in a «transitory increase in the 
 quantity of lead in the system, due either to increase in the 
 supply or diminished elimination. He calls that condition of 
 saturnism, in which lead constantly circulates throughout the 
 body and in which the supply and elimination counterbalance 
 
 tHermann, Archiv, f. Anat. u. Physiologie, 1867, p. 64 und Lehrbuch der Toxico- 
 logic, Berlin, 1874, p. 205. 
 
INTRODUCTION. 2T 
 
 each other, "the state of compensation." We can thus under- 
 stand how "any momentary disturbance of the function 
 through which lead is eliminated from the body is followed 
 by an increased quantity of lead in the system and the 
 consequent development of new symptoms, which the ordinary 
 supply of lead could not account for." Thus is also ex- 
 plained how many persons manifest an apparent immunity 
 from the poisonous effects of lead, while others are seriously 
 affected by very small quantities. It has been demonstrated that 
 certain other medicines may give rise to undesirable untoward 
 symptoms, when the excretory apparatus is diseased and thus 
 but imperfectly discharges its functions. Thus Chauvet showed 
 that while in the healthy person, from a half to a third of the 
 sulphate of quinine ingested is eliminated, only from a fiftieth 
 to a tenth is excreted in patients suffering from interstitial ne- 
 phritis. The bromide of potassium, which is ordinarily eliminated 
 at the latest in twenty days, is not excreted . under thirty or thirty- 
 five days in cases of kidney disease. It is probably in this man- 
 ner that some of the untoward effects following the external 
 application of iodoform are produced, and particularly when, as in 
 the treatment of wounds, carbolic acid has been previously em- 
 ployed, the latter drug, as has been demonstrated, being prone 
 to cause irritation of the kidneys. It is not necessary that 
 the excretory ducts undergo pathological change, for even 
 within physiological limits the functions of organs may be sus- 
 pended, as may be seen in the case of the kidneys. Varia- 
 tions in the ■ temperature are followed by variations in the 
 quantity of urinary secretion and vicarious increase or diminu- 
 tion of perspiration. Thus is perhaps explained the fact that 
 lead colic occurs most frequently during the hot summer 
 months, when the quantity of urine voided is so markedly 
 reduced and the perspiration correspondingly increased. 
 
 In order to properly understand certain abnormal effects of 
 medicines, it is necessary to consider, in addition to the causes 
 indicated, that inherent property known as habituation. We know 
 that psychical impressions within the brgadest limits, from the 
 strongest desire to the intensest disgust, from the highest 
 
THE UNTOWARD EFFECTS OF DRUGS. 
 
 pleasure to the deepest sorrow, when their action is long con- 
 tinued, gradually lose their influence. We become accustomed 
 to them, and the measure of their effect, the subjective mani- 
 festations, which are commonly aroused by them become grad- 
 ually less and less and finally disappear altogether. We may 
 assume that in such cases the centres of sensation are, through 
 repeated excitation, deprived of their energy, i. e., they no 
 longer respond to ordinary impressions. The conduct of tissue, 
 muscle, for instance, under repeated electric currents, affords 
 an illustration of the fact here stated. Let the muscle be 
 caused to contract through frequent irritation of the nerve and 
 this contraction reaches its maximum of force at the beginning, 
 to be followed by a condition of fatigue. This condition will 
 continue until the muscle is afforded rest, that is time to get 
 rid of those products of waste which the exertion has in- 
 duced. 
 
 Precisely similar results may b£ reached by habituating 
 one's self to a succession of doses of medicines and drugs. 
 Instances of persons inuring themselves to certain poisons are 
 afforded us in ancient history. Thus we are told that Mithri- 
 dates having gradually accustomed himself to each of the 
 then known poisons to such an extent that he could take 
 large quantities with impunity, was finally unable to find a poi- 
 son with which to commit suicide. This somewhat extravagant 
 statement is, however, supported by what we see in our day of 
 the effects of such active' agents as alcohol, arsenic, opium and 
 morphia in particular individuals. The quantities- of these sub- 
 stances which are taken with apparent impunity, through a 
 gradual increase of the dose, are frequently from ten to twenty 
 times as large as would suffice to produce fatal effects in per- 
 sons not thus inured. Some substances, also, as many of the 
 class of laxatives and diuretics, are of such a nature that their 
 habitual use ultimately deprives them of all pharmacological 
 activity. Early in their employment their effect may be secured 
 by increase of dose, but eventually even this does not suffice. 
 We are familiar with these facts in the case, among others, of 
 rhubarb, castor oil, the neutral salts, acetate of potash, squills, 
 etc. 
 
 How are these peculiarities to be explained ? Granted that 
 
INTRODUCTION. 
 
 a given substance affects certain groups of cells, and we may 
 expect a normal result from the action of that substance in 
 the majority of instances : sleep will follow the use of mor- 
 phia and catharsis the exhibition of rhubarb. As, how- 
 ever, a long continued electrical current when passed through 
 a nerve or muscle will induce material changes in the same, 
 exhausting its excitability, so will certain medicines simi- 
 larly affect the tissues. The only difference between the two 
 cases is that whereas the muscles and nerves are very quickly 
 restored upon the removal of the electric current, either through 
 rapid elimination of the matter decomposed by the cur- 
 rent, or by a prompt replacement with new supplies, in the 
 case of the medicine restitution is effected only after a com- 
 plete removal of the disturbing factor from the part affected. 
 But since it requires some considerable time to wholly elim- 
 inate these drugs from the body, each new dose is almost sure 
 to overtake some remaining particles of the preceding dose, 
 and thus the affected tissue is to a degree kept under the 
 constant and unintermitting, exciting or benumbing influence of 
 the drug. Inasmuch as there is thus no relaxation in the 
 part its excitability is impaired, or in other words, a physiolog- 
 ical or artificial excitant will fail to longer call forth any ad- 
 equate reaction. Each further augmentation of the dose will, 
 it is true, excite temporary reaction, but the excitability will 
 only continue until it has again been dulled. A suspension of 
 the substance may be followed by complete restitution, and in 
 time the parts again respond normally to the action of the 
 drug. 
 
 The foregoing affords an insight into the possibility of 
 one's accustoming himself to the action of poisons. The grad- 
 ually increased exhibition of these will induce inactivity in those 
 groups of cells which are especially affected by them — they 
 are still susceptible to passive, vegetative impressions, but are 
 no longer capable of distinct, independent functional activity. 
 The poison in excessive doses affects the inert texture in a 
 manner identical with the action of the first small dose on nor- 
 mal tissue. 
 
 A poisonous action may, however, supervene after the per- 
 son has been inured to the deleterious agent, as when the dose 
 
2\ THE UNTOWARD EFFECTS OF DRUGS 
 
 has been so much increased as to attack the vegetative life of 
 the tissue, and thus destroy its existence. 
 
 But this is not the only manner in which untoward ef- 
 fects may supervene in the course of the habitual use of a 
 medicine. It is comprehensible, from the intimate connection 
 between individual tissues, how organs whose functions are 
 similar, are apt to be influenced by causes which operate upon 
 any one of them. It is in this manner that a permanent affec- 
 tion of the brain and spinal cord may induce an alteration 
 or disturbance in the peripheral nerves, in the heart's functions, 
 etc. Hence we notice in those who are addicted to the opium 
 habit that not only are there more or less severe cerebral 
 symptoms but also disturbances in the functions of digestion, 
 respiration, etc. Withdraw the disturbing medicinal agent, and 
 we have symptoms pointing to disturbances of the equilibrium 
 which has been created between the functions of different or- 
 gans. The most characteristic of these symptoms is the crav- 
 ing felt for the drug which has been withheld. This feeling, 
 reminds one of the desire for salt, when he has for any con- 
 siderable length of time been deprived of it. Just as salt is 
 an essential ingredient of the system and cannot be dispensed 
 with, so has the medicine which has been withdrawn become 
 through its long continued, accustomed employment an integral 
 part of certain tissues, and its absence will be as keenly felt as the 
 absence of an elementary constituent of the body. 
 
 The foregoing considerations are necessary to facilitate 
 our understanding of many of the abnormal effects which 
 are occasionally noticed to follow the exhibition of certain 
 drugs. It is plain enough, for instance, that when a given part 
 of the central nervous system has been lowered in its normal 
 functional activity by continued use of some substance operating 
 on it, the effect of any other substance which arouses it to 
 action must be abnormal. This latter substance will either 
 not act at all, or it will act perversely. An instance of this 
 is seen in the effects of opiates in drunkards, particularly when 
 attacked by delirium tremens, and those of chloroform in the same 
 class of individuals. The skin may also become accustomed to 
 certain drugs, which generally excite inflammation. It is a familiar 
 fact, for instance, that in many persons the application of petro- 
 
INTRODUCTION. 25 
 
 leum to the skin causes a vesicular eruption, which lasts for sev- 
 eral days. Should the article be reapplied after the skin has 
 been restored, the anticipated symptoms of inflammation may not 
 appear. The condition may, however, be such as to require sev- 
 eral inunctions to accustom the tissues of the skin to the irrita- 
 tion. 
 
 § 9. 
 
 The season, time of day and part of the world in which a medi- 
 cine is given are also factors of no mean importance in determining 
 the abnormal effects of medicines, which it becomes us to consider. 
 The influences of time and place, which are generally so little taken 
 into account, have an undoubted effect in modifying if not indeed 
 in determining many of the specific peculiarities of men. Hence the 
 old schools, as Virchow* points out, regarded man attentively as to 
 time and took into special consideration also the "epidemic consti- 
 tution." It is certainly a fact that many of the morbific influences 
 produce their effects only in certain localities and vary in their force 
 and consequences on the body, with variations in time. If then the 
 individual is thus affected by external influences it is comprehensible 
 how certain medicines may, in a like manner, be made to produce 
 abnormal or at leasts lightly abnormal effects. Careful, practical 
 observation has revealed differences of action in individual drugs 
 referable to the causes mentioned. Charvetf found that the effects 
 of opium varied with the time of day, the climate and the race of 
 the individual taking it. Thus the negro and Malay under the 
 influence of opium manifest symptoms of convulsions, delirium and 
 insanity, to which the Caucasian is not liable. Physicians have fre- 
 quently noted similar discrepancies in the English colonies. Accor- 
 ding to the observations of Lisfranc, the medicinal effects of the 
 chloride of barium are very variable, inhabitants of southern lati- 
 tudes being able to tolerate larger doses than those of the north. 
 
 These facts, whose number might be largely increased, merit a 
 fuller consideration by physicians, inasmuch as there is much, even 
 though groundless skepticism regarding them. We are convinced 
 that by a careful scrutiny of certain effects of medicines, in rela- 
 tion to the views above given, a large number of examples of 
 similar divergencies could be added to those detailed. 
 
 ♦Virchow, 1. c. Bd. VI., p. 29. 
 
 tCharvet. Die Wirkungen des Opiums auf d e thiensche Oeconomie.— Leipzig, 1827, 
 
20 THE UNTOWARD EFFECTS OF DRUGS. 
 
 In considering the diminished and deleterious effects of drugs, 
 the fact must also be taken into consideration that the cause may 
 also reside in the drug itself. The failure to secure the desired 
 effect of a drug, or the untoward effect of a drug or pharmaceuti- 
 cal preparation, is more frequently attributable to the drug itself 
 than is generally known or credited. The causes of this may be 
 various. Either the remedy (and this is particularly the case with 
 vegetable drugs) in its rata state, as put on the market, although 
 pure, is of an inferior grade, . or if originally of good 'quality lias 
 through long storage lost its virtue, or the medicinal part has been 
 mixed with foreign ingredients. Sometimes, too, the medicine is 
 modified in its efficiency by the method of its preparation. 
 
 It must be particularly borne in mind that in special cases the 
 physical or chemical distinction between good and bad drugs is 
 often difficult, and sometimes really impossible, and that likewise, 
 particularly in the case of medicines of vegetable and animal 
 origin, a very thorough study is necessary to qualify one for an 
 opinion on this point which shall be of any value. 
 
 The activity of drugs may likewise be conditioned on their 
 habitat. The respective commercial values of the different 
 varieties of opium, aloes, colocynth, etc., are dependent on the 
 countries whence they are derived, and this is generally the 
 best criterion of the worth or worthlessness of the article. 
 The difference in the effects of different varieties is sometimes 
 remarkable. While, for instance, the 0.06 to 0.12 gramme (1 
 to 2 grains) of Socotrine aloes is sufficient to bring about a 
 free evacuation of the bowels, the same effect can scarcely be 
 secured by a dose of, Arabian or Moka aloes of five times this 
 size. Many of our indigenous plants present similar variations. 
 Thus digitalis growing wild on hills is much more active than 
 that which is grown in the valley, or cultivated. Hemp, as grown 
 in this country, does not furnish the haschisch which is yielded 
 by the hemp grown in warmer latitudes, and the hemlock which 
 in this country yields coniin. is devoid of that principle when 
 grown in Scotland. The nature of the soil, atmospheric tem- 
 perature, season of the year, etc., are all so many factors in 
 determining variations in the activity of medicinal plants. The 
 
INTRODUCTION. 27 
 
 importance of the latter factor is particularly noticeable in many of 
 our more active plants, as has been fixed by definite observations. 
 We know that even the mountain digitalis, gathered in the mountain 
 ranges of central Germany, differs in its pharmacological properties 
 with the season of the year in which the leaves are picked. It is 
 most active when the plant is in full bloom and at the acme of its 
 vigor. The same is true of colchicin, it having been demon- 
 strated* that the root or seeds which are gathered when the plant 
 is in full bloom, contain the largest percentage of colchicin and are 
 the most active. The most marked instance of changes, as regards 
 the active principles of plants, is furnished in the case of momor- 
 dica elaterium. The juice of this drug when collected in July, 
 yields from 4 to 5 per cent, of elaterin; that from the fruit gath- 
 ered in August, yields but about 0.69 per cent., while the juice of 
 the squirting cucumber picked in September, is almost, if not en- 
 tirely destitute of this principle. These facts explain the apparent 
 contradictions in some of the older authors regarding the activity 
 of medicinal doses of elaterium. It follows, from the fact stated, 
 that 0.24 gramme (gr. jv) of elaterium from the juice of the fruit 
 gathered in July, is equally as effective as about 1.5 gramme (gr. 
 xxjv) of the August product, while doses of 4 grammes ( 3 j) and 
 more, of elaterium prepared from the September fruit, produces 
 hardly any appreciable effect. 
 
 Many drugs also undergo change through long storage, devel- 
 oping in some instances new and not infrequently deleterious 
 properties, through desiccation and the oxidizing influence of the 
 air. If, for instance, in the preparation of extract of hyos- 
 cyamus dried instead of recently gathered leaves are employed, 
 the product will be found to contain scarcely any hyoscyamus, 
 while the same quantity of fresh leaves will yield a decided 
 per centage. Ergot will lose its virtue unless carefully dried 
 and closely sealed. But it is in the pomegranate root bark 
 that the most decided changes in its activity due to such 
 causes are noticeable. While the freshly gathered root is a 
 reliable anthelmintic it is not only no longer active, but be- 
 comes an irritant emetic and disturbs digestion when old. A 
 better and more careful manipulation and preservation than has 
 been or is yet, in the opinion of experts (Fachmännern), cus- 
 
 *Schroff, Zeitschrift der Wiener Aerzte, Jahrg-. 7, Bd. 1., 1851 
 
28 THE UNTOWARD EFFECTS OF DRUGS. 
 
 tomary, would doubtless have saved many drugs, especially of 
 vegetable origin, from the fate of rejection as obsolete by the 
 medical profession. 
 
 Very many vegetable and other organic as well as inorganic 
 combinations are susceptible to change under the influence of 
 the atmosphere. It is well-known that under such conditions a 
 variety of deleterious products of chlorine are generated in 
 chloroform. According to French authors the emetic action of 
 morphia is due to a partial transformation into apomorphia, 
 and it has been shown* that Fowler's solution loses arsenious 
 acid in course of time, probably under the influence of organic 
 matter which has found its way into it. The acid is reduced 
 and escapes as arseniuretted hydrogen gas. The loss may in 
 this manner be very considerable. 
 
 A further possible cause of the occurrence of change of 
 action may reside in the fact that the drugs are mixed with 
 foreign ingredients, and thus sold are employed by the dis- 
 penser. It has been asserted on the authority of an expertf 
 that drugs in themselves of indifferent activity may be found 
 to be adulterated with belladonna, hellebore, etc., which, al- 
 though present in very minute proportions, necessitate great 
 care and intimate familiarity with the subject in order that 
 serious consequences may be averted. Finally, in so far as the 
 purity of the drug is concerned, we know that the therapeutic 
 activity, as also the objectionable properties of a variety of 
 vegetable alkaloids, — aconitin, digitalin, etc., as also other chemi- 
 cal combinations — are largely conditioned on the methods of 
 their preparation. 
 
 As opposed to variability in the effects of drugs detailed 
 above, attributable to the quality of the preparation employed, 
 are those certain effects which are due to the improper forms in 
 which they are given. Thus we note loss of appetite, gastric 
 oppression, diarrhoea, etc., in short the symptoms of catarrhal 
 change, which occasionaly ' supervene on the exhibition in the 
 form of powder, of substances which cause irritation through 
 adhesion of their minute particles to the mucous lining of the 
 alimentary tract. The administration of tannin, among other 
 
 *Bretet, Journal de Pharm, et Chimie. October, 1879. Page 355. 
 tMayer, Pharmaceutische Centralhalle, 29. Juli, 1880. 
 
INTRODUCTION. 
 
 drugs, in the form of powder, is not infrequently followed by 
 such symptoms. In this manner the exhibition of irritating 
 drugs in capsules, may set up functional disturbances in the 
 stomach and bowels. 
 
 § " : 
 
 A contemplation of the conditions above enumerated which 
 are liable to induce injurious untoward effects from drugs, will 
 convince one both of their great variety and of the necessity 
 which exists of a thorough knowledge of them. It is true, as a 
 general rule, that no permanent impairment of function is thus 
 caused; and yet there are many conditions under which such per- 
 manent change and even death may ensue. It is evident that 
 these considerations are vested with an importance, by no means 
 insignificant from a medico-legal point of view; and as a matter 
 of fact the literature of this country, as well as that of other 
 countries, furnishes abundant evidence corroborating this impor- 
 tance. There are cases on record in which a therapeutic pro- 
 cedure, conducted secundcm artem has been attended by results 
 sufficiently disastrous to bring the attending physician before a 
 court of law, and this in spite of the fact that the same pro- 
 cedure had previously been frequently resorted to by others. 
 When, for instance, after an enema of a solution of carbolic 
 acid, through some idiosyncrasy of the patient the amount ab- 
 sorbed proves fatal, or when, notwithstanding the purity of the 
 drug, a patient dies in the early stage of the administration of 
 chloroform, the cases should be regarded as accidents for which 
 no one can be held to account. The same is true of many 
 other medicines whose administration, under certain . circum- 
 stances, is followed by disastrous effects. There are well authen- 
 ticated cases on record in which death in children has followed 
 the employment of 0.006 and even 0.0007 gramme (grain ^L to 
 Yqö) °f opium. Were blame to be attached to the physician in 
 such case, he could never prescribe such drugs except under a 
 sense of grave personal danger. The surest safeguard against 
 the possibility of such responsibility would seem to lie in the 
 widest possible publicity of such accidents, thereby placing at 
 our disposal a greater amount of information in reference to 
 them than is now available. 
 
3c THE UNTOWARD EFFECTS OF DRUGS. 
 
 § I*. 
 
 it now remains for us to glance at the manner in which 
 the principal of the untoward effects of individual drugs recorded 
 in the literature of the subject, are produced. They may occur 
 either by direct action or through reflex influence. It is only 
 in a very few cases that we are able to determine with absolute 
 certainty, in which of these two methods these effects are in- 
 duced. This is partially conditioned on the manner in which a 
 given medicine is applied and on the method of its elimination 
 from the body. Thus irritating substances given by the stomach 
 may exert an abnormal influence on the intestines, and establish 
 a gastro-intestinal catarrh with its train of consequences. But 
 there may also, as, for instance, in the case of the antimonial prep- 
 arations, be set up a reflex influence on the heart from the local 
 changes induced in the stomach. This does not preclude the 
 possibility of a direct effect, through absorption, of the anti- 
 monial on the heart's action; as a matter of fact it sometimes 
 suffers change in just this manner. 
 
 It is also conceivable that in consequence of irritation caused 
 by a drug in the intestines or the larger bile ducts, a patho- 
 logical condition may, through reflex action, be engendered in the 
 skin. It is known* that other foreign irritating substances, such 
 as the proglottides of tapeworm, or biliary calculi may through reflex 
 action cause an eruption resembling urticaria. In an analogous 
 manner many 'material changes occur in other points at which 
 medicines are applied, as the subcutaneous cellular tissue, the 
 mucous membrane of the eye, the bladder or the rectum from 
 which reflex functional disturbances are set up in other organs, 
 and,, finally, while the substance is circulating in the blood 
 phenomena may present, which are different from those which are 
 primarily local and reflex. In this manner, for instance, the in- 
 stillation of atropia may give rise to conjunctivitis, which by re- 
 flex influence causes photophobia. But should the drug be ab- 
 sorbed through its entrance into the lachrymal ducts symp- 
 toms of general poisoning may supervene. In general, however, 
 so exact a differentiation is not possible. 
 
 'Litten, Oermatologis^he Beobachtungen, Charite-Annalen, IV., 1878, p. 194. 
 
INTRODUCTION. 3 1 
 
 As regards the influence which the manner in which a drug 
 is eliminated, may have in determining its untoward action, it 
 may be stated that, dependent on the individuality of the patient, 
 effects may be noted in the greatest variety of organs. We are 
 familiar with a number of drugs which never select other avenues 
 of elimination than the intestines and kidneys when given inter- 
 nally, and which select the latter channel when applied externally 
 or given subcutaneously. There are, however, also others, anti- 
 mony for example, which when applied externally are first dis- 
 charged through the stomach and bowels where they set up 
 pathological changes. It now only remains to mention those 
 drugs which ordinarily leave the system with the urine, but which 
 under any of the abnormal individual conditions detailed in the 
 preceding paragraphs, after their ingestion select the skin as the 
 place of their exit, and which may be detected therein by chemical 
 means. The iodide and the bromide of potassium and arsenic 
 are with others to be classed in this category. Others, as iodine, 
 may after their injection into serous cavities be eliminated through 
 the stomach. 
 
 Should the drugs exhibited vary in their strength — as they 
 usually do — they are liable to exert either an irritating or a para- 
 lyzing action on the channels through which they are eliminated. 
 
 The chief efforts at explaining the manner in which patholog- 
 ical conditions follow drugs, have been made through the 
 changes in the skin which have been found to follow the in- 
 ternal administration of some of them. To look for the cause in 
 one direction, as is now and then done, is, however, apt to lead 
 to error. It is certain that these conditions may occur in a 
 variety of ways, and are not due exclusively either to direct ir- 
 ritation of the glands of the skin or of the connective tissue 
 layer, through reflex action, through change in the vessels, or to 
 an influence on the cutaneous nerves. 
 
 In all cases it is the drug as such which is the exciting 
 cause of the changes induced in the skin, and that whether ex- 
 hibited in very large or minimal doses. For it is most character- 
 istic of individuality and the specific disposition which is condi- 
 tioned on it, that influences of what kind soever, which are other- 
 wise inoperative, may manifest themselves by intensifying different 
 changes in individual organs. For this reason the unsupported 
 
32 THE UNTOWARD EFFECTS OF DRUGS. 
 
 hypothesis* that it is not the drug itself, but the quite hypothetical 
 substances which are formed by it in the blood, which, in certain 
 cases, causes the pathological condition of the skin, is to be re- 
 jected. 
 
 The form of a given drug exanthem may not only differ in 
 different persons, but may also vary greatly in the same indi- 
 vidual. The differences here indicated are to be regarded as the 
 expression of individual peculiarities or as dependent on the 
 structure of the skin in different parts of the body. 
 
 The origin of the symptoms which reveal themselves in the 
 organs of special sense as well as in other parts of the body, as 
 a result of the exhibition of certain drugs, is discussed more in 
 detail in the special chapters of this work. 
 
 *Behrend, Berliner Klin. Wochenschrift, 1879, No. 43. 
 
TONICS FERRUM. 33 
 
 Tonics 
 
 FERRUM. 
 
 A variety of untoward effects referable more particularly 
 to the digestive tract, are liable to manifest themselves in the 
 course of the continued use of ferruginous preparations. It is 
 not infrequently noted, in persons having normal digestive 
 powers, that the exhibition of preparations of iron in somewhat 
 increased and prolonged doses, and even the ferruginous waters, 
 is followed by disturbance of 'digestion, diminution of appetite, 
 gastric oppression and vomiting ; and these results are particu- 
 larly liable to follow when the drug is taken on an empty 
 stomach. Defecation is retarded and the stools are blackened 
 by a sulphuret of iron. More recent observations have demon- 
 strated the ferrous salts to be better tolerated than the ferric. 
 Ferrum redactum, the phosphate and the pyrophosphate of iron 
 are said to disturb digestion but slightly. On the other hand 
 the salts with organic acids (lactate, citrate, and acetate of iron) 
 interfere very much with peptonization. 
 
 In very rare cases hemorrhages are said to occur from the 
 mucous membranes. A more common result, according to Trous- 
 seau,* in healthy persons, and particularly in females, is an acne 
 occurring on the face, the breast and back, which runs its 
 course without febrile disturbance. 
 
 The teeth are blackened during the continued use of iron 
 by a coating of the sulphuret of iron. It is necessary for this 
 result that there should be a generation of sulphuretted hydro- 
 gen, either from carious teeth or through decomposition of 
 secretions. The iron, which is held in solution by alkaline 
 secretions of the mouth, is promptly precipitated by the gas. 
 When the teeth are* perfectly sound, blackening may still occur 
 through the ingestion of food or drinks containing tannin, a 
 tannate of iron (ink) being formed. 
 
 ♦Trousseau, Gaz. Medic, de Paris, 1843, No. 12. 
 
34 THE UNTOWARD EFFECTS OF DRUGS. 
 
 The external application of the sesquichloride of iron as a 
 styptic is very often attended by pain in the wound, owing to 
 a defect in the preparation employed. When the iron salt con- 
 tains no free hydrochloric acid, pain is nearly always absent. 
 When pain is caused by a proper preparation, although it is 
 severe it soon ceases. What is true in this regard of the prep- 
 aration in substance is also true of the styptic cotton of com- 
 merce. 
 
 In order to make the sesquichloride of iron more easy of 
 administration and to correct the sharp sour taste, which dilu- 
 tion with water does not overcome, Hager* recommends a mix- 
 ture of the drug with glycerine or syrup, and its dilution im- 
 mediately before taking with cow's milk. By so doing it is 
 claimed that the teeth are not attacked, and that the taste of 
 the iron is covered. 
 
 QUININE. 
 
 It has been claimed that the evil effects which supervene 
 on the exhibition of quinine are due to a saturation of the sys- 
 tem with the drug. It has been established, however, by the 
 frequent occurrence of these accidents after the exhibition of 
 but one medium dose, that there must exist in those who are 
 thus affected a certain susceptibility to this particular action of 
 quinine. It has even been shown by King,f on the strength 
 of an observation of this nature, that this individual predisposi- 
 tion to injurious effects of certain drugs, as in this case of 
 quinine, may be hereditary. 
 
 Organs differing most widely in their nature are influenced 
 by quinine in this manner, and manifest pathological changes. 
 The following symptoms are observed as indicating disturbance 
 which it causes of the central nervous system : headache, deaf- 
 ness, general muscular irritability, with chilliness and a feeling 
 of dizziness, which disappear on the person's assuming the 
 horizontal position. Now and then appear also precordial anx- 
 iety, fainting and threatened collapse. On the other hand, con- 
 ditions of excitation, delirium, etc., are very seldom observed. 
 Should they, for instance, occur after the hypodermic exhibition 
 of the remedy, the fact would indicate the probable presence of 
 
 *Hager, Pharm ic. Centralhalle, 1880, No 46, p. 408. 
 
 tKing, Vierteljahrschr. f. Dermatol, und Syphilis, 1879, p. 370. 
 
TOXICS QUININE. 35 
 
 quinidia in the quinia. Following the hypodermic use of quin- 
 idia, Chirone and Curci observed the occurrence of epileptiform 
 convulsions. Quinidia is much less soluble than quinine and 
 deflects the polarized rays to the right, while quinine turns them 
 to the left. These effects of quinine on the circulatory ap- 
 paratus are observed in a lowering of the heart's action, pallor 
 of the face and coldness of the lips and surface. These symp- 
 toms may occur singly or they may be accompanied by one of 
 the affections which will be considered hereafter, and may last 
 for hours or days. 
 
 The skin of many persons is affected in a peculiar manner 
 by the internal exhibition of even small doses of quinine. The 
 exanthems which are thus caused are distinguished by their 
 variety. Worthy of note as bearing on the explanation of these 
 affections is an observation first made by Chevallier,* and after- 
 wards by other authors, that workmen in the manufacture of 
 quinine are liable, through contact with the drug, to an affec- 
 tion of the skin which manifests itself in a vesicular, pustular 
 or papular eruption on different parts of the body, as on the 
 hands and upper and lower extremities. It follows from this 
 fact that when affections of the skin follow the medicinal use 
 of quinine, these are due solely to the fact that the drug is 
 dispersed in the skin where it causes lesions, their extent being, 
 probably, conditioned on the vascular supply. As more con- 
 firmatory of this view than the declaration of Chevallier, may 
 be mentioned the fact, determined through experiment by H. 
 Munk.f On moistening the electrodes with a solution of 
 quinine in sulphuric acid and passing a current through a part 
 of the body, the skin of this part was noticed, immediately 
 after the interruption of the current, to be anaemic, depressed 
 and dry. In the course of an hour after the passage of the cur- 
 rent the skin thus acted on became so markedly swollen as to 
 be elevated above the surrounding skin, without, however, suf- 
 fering any change of color The swelling subsided in the course 
 of several hours, leaving in its place a hypersemic spot which was 
 dotted with a large number of extravasations of blood of about 
 the size of a pin's head. These extravasations also remained 
 
 *Chevallier, Annal. d'Hygiene et de M^dec. leg. 1851, T. 68, p. 5. 
 tMunk, Archiv, f. Anat. u. Physiolog. 1873, H. 5. 
 
$6 THE UNTOWARD EFFECTS OF DRUGS, 
 
 after the hyperemia had disappeared. Quinine could still be 
 detected in the urine twelve hours after the passage of the 
 current. The passage of the quinine thus gave rise to an 
 erythema which was followed by a purpüra-like eruption. 
 
 A further illustration of the local origin of quinine erup- 
 tion is given by Delioux de Savignac* who observed a "pru- 
 riginous eruption" after he had applied an ointment of quinia 
 sulph. to the skin. 
 
 Analogous eruptions are also caused by the internal admin- 
 istration of quinine. These present themselves according to 
 Grissac,f as : 
 
 i. Purpura. 
 
 2. Roseola. 
 
 3. Scarlatiniform exanthema. 
 
 4. Eczema. 
 
 1. The petechial form was first observed by Vepan.J He 
 reports the case of a lady who took 0.1 gramme (gr. iss) and 
 afterwards 0.15 gramme (gr. ijss) of quinine for neuralgia. 
 Two days afterwards the entire body was covered by purpuric 
 spots which disappeared in the course of nine days but to re- 
 appear after the administration of the drug was resumed. In 
 this case the severity of the eruption was in proportion to the 
 size of the dose, and during its existence there was bleeding 
 of the gums. Gauchet§ also noticed an eruption of this nature 
 in a lady who had previously expectorated blood after taking 
 quinine. The petechia was profusely spread over the entire 
 body ; it disappeared after the suspension of the drug. 
 
 2. Dauboeuf ** has frequently noticed a simple roseola, dif- 
 fering but slightly from that to be next described, in both 
 males and females. It makes its appearance with intense pru- 
 ritus, most frequently after frequent doses of the drug have 
 been exhibited, and in one case it appeared even eight days 
 after the taking of the last dose of the quinine. It soon spreads 
 from its local site, the extremities and buttocks, to the entire 
 body, and usually appears in the form of desseminated patches. 
 
 *Delioux de Savignac, Articl. Quinine, Dictionnaire Encycloped. de Scienc. Medical, 
 1874, p. 188. 
 
 tGrissac, Des Eruptions Quiniques, Paris, 1876, p. 8. 
 jV^pan, Gaz Medic, de Strassb. 1865. 
 SGauchet, Bullet, de Therap., LXXXX. p. 373. 
 **Daubceuf by Gnssac, L. C. p 22. 
 
TONICS QUININE. 37 
 
 The scarlatiniform erythema was first described by English 
 authors. Garraway* observed it to appear simultaneously with 
 oedema of the face. In Hemming'sf case it appeared after the 
 0.06 gramme (grj.) of quinine and was attended by intense 
 itching, a feeling of oppression in the precordial region and a 
 coated tongue, and disappeared by slow desquamation. Skin- 
 nerj observed its appearance in a lady after a dose of 0.06 and 
 0.03 gramme (gr. j — gr. ss). It was attended with shivering and 
 rigor and spread over the whole body and disappeared only 
 after a desquamation which lasted for three months. 
 
 We shall now consider the mixtd form of the quinine exan- 
 thems — a combination of the scarlatiniform eruption and acute 
 eczema. Kobner§ described an eruption of this nature. After 
 the exhibition of 0.22 gramme (3^2 gr.) of the sulphate of 
 quinine the patient, a lady, was attacked with chills, precor- 
 dial anxiety, nausea, vomiting a/d burning beat of the skin, 
 leading to an erroneous diagnosis of scarlatina. When the qui- 
 nine Was repeated the face became slightly swollen and cov- 
 ered with a uniform dark red which spread also over the scalp, 
 ears, neck and extremities. A few spots of normal skin re- 
 mained on the arms. The lower third of the flexor surface of 
 both thighs was normal, but isolated papules of the size of a 
 pea and of a dark red color were scattered over the extensor 
 surface, the intervening surface, however, being normal and its 
 epidermis revealing fine wrinkles. Heusinger** contributes a some- 
 what analogous observation. After the administration of even 
 0.025 gramme (% grain) of quinine to a lady, a nodular ery- 
 thema resembling erythema exsudativa multiforme, appeared on 
 the eyelids, cheeks and a portion of the forehead, with accom- 
 panying headache, fever, nausea, an intense burning sensation, 
 distinct cedematous swelling. At another time in the same 
 patient a dose of 0.1 gramme (ij4 gr.) of quinine only gave 
 rise to some herpetic vesicles on the cheeks, which disap- 
 peared at once in a branny desquamation, on suspension of 
 the drusf. 
 
 *Garraway, British Med. Journal, 1869, H-i P- 3^8. 
 
 tHemming, Eod. loco, p. 533. 
 
 +Skinner, Eod. loc. 1870, I. p. 103. 
 
 §Köbner, Berl. Klin. Wochenschrift, 1877, p. 305. 
 
 **Heusinger, Berl. Klin. Wochenschr. 1877, p. 361. 
 
$8 THE UNTOWARD EFFECTS OF DRUGS. 
 
 The papules on an erythematous surface may be changed into 
 vesicles, and thus cause the eruption to assume a closer re- 
 semblance to eczema. In such event the itching may be ab- 
 sent and the general symptoms be but slightly developed. 
 Thus Denk* noticed in a boy who had taken 0.8 gramme (12 
 grains) of quinine in four days, the appearance of an eruption 
 which was unattended with itching, and which spread over the 
 entire surface, was of a scarlatinous red color, but became pale 
 on pressure, and was dotted throughout with numerous yellow 
 vesicles of the size of a pinhead, distributed chiefly on the 
 neck, in the arm-pits and over the sternum. With the excep- 
 tion of a slight rise in the morning and evening temperature 
 there was no constitutional disturbance. On suspending the 
 drug the vesicles began to break and dry up. The desquama- 
 tion occurred in the form of small scales and large flakes. 
 
 The appearance of an acute eczema may, according to 
 Grissac, be more closely simulated than in the cases just refer- 
 red to, if the numerous vesicles become ruptured and thus 
 unite to form a thick crust. There are, however, no reports of 
 cases of this nature in German literature. 
 
 In order to arrive at a differential diagnosis of the 
 quinine eruption and scarlatina, it is necessary, according to 
 Köbner, to note the course of the temperature and to detect 
 quinine in the urine. In addition one should also be on the 
 lookout for the absence of the scarlatina tongue and of the 
 inflammation of the palate and tonsils, the too slightly increas- 
 ed frequency of the pulse for the stage of scarlatinal efflores- 
 cence, and the onset of the scarlet rash without prodromata. 
 Valuable diagnostic points are the detection of quinine in the 
 urine, either by observing its fluorescence after the latter has 
 been freed of its chloride of sodium (either through precipit- 
 ation with nitrate of mercury) or by the separation of the quin- 
 ine in the form of an iodide by means of a solution of iodine 
 (2 parts iodine, 1 of iodide of potassium and 40 of water). 
 The iodide of quinine is soluble by the aid of heat. 
 
 More unpleasant than any of the symptoms heretofore con- 
 sidered are the disturbances in the organs of special sense 
 which have been observed to follow the exhibition of quinine. 
 
 *Denk, Wiener Med. Wochenschr, 1880, p. 946. 
 
TOXICS — QUININE. 39 
 
 We shall first consider the disturbances of vision, first ac- 
 curately described by A. von Graefe.* Photophobia and even 
 transient amblyopia has been observed to follow small doses. 
 During the continued use of larger doses, graver disturbances of 
 function supervene which may continue for a long time and be 
 with difficulty removed by therapeutic measures. Thus Graefe 
 noted the case of a man, who ih order to break up an in- 
 termittent fever, took quinine in increasing quantities until the 
 dose had reached 0.9 gramme (gi\ xjv.), and until the entire 
 quantity taken had reached upwards of 30 grammes (one 
 ounce). The dose being increased one-third daily, weakness of 
 vision appeared in the right eye, to be followed, in a few- 
 days, by total blindness. The left eye remained sound. An 
 ophthalmoscopic examination three months later revealed noth- 
 ing abnormal, although the quantitative perception of light had 
 failed on the right side. Holding the cause to be a disturb- 
 ance of the intracranial circulation, Graefe abstracted blood 
 from the temple by means of Heurteloup's leech. Following 
 this there was first a gradual return of the quantitative per- 
 ception of light, then a motion of the hand could be 
 detected, and after a time there was a return to the normal 
 condition. In another case, in which 1.8 gramme (gr. xxvij) of 
 quinia sulphate had been taken daily in the same manner for 
 the relief of an intermittent, and in which there was a high 
 degree of bilateral amblyopia, the sight of the left eye was 
 completely restored, spontaneously — but that of the right eye 
 returned only sufficiently to permit the reading of large type. 
 
 Knapp, of New York, has recently examined cases of the 
 untoward effects of quinine on the eye. He found the power 
 of sight diminished in various degrees, and in exceptional cases 
 there was amaurosis with immobility of the pupils. Where 
 there remains a fraction of visual power, a contraction of the 
 field of vision can always be demonstrated. The perceptions 
 of color and light are always diminished. In well marked 
 cases the ophthalmoscopic image has the appearance of an 
 embolus of the retinal arteries, and the red spot in the macula 
 lutea is wanting. The retina does not appear opaque, the 
 papillae are white and flat, and the vessels are highly contracted, 
 
 *Von Graefe, Arch. f. Ophthalmol. Bd. III. 2, p. 396. 
 
40 THE UNTOWARD EFFECTS OF DRUGS. 
 
 in some instances so much so as to leave them scarcely dis- 
 cernible. The diminution in the acuteness of vision continues 
 for some length of time. The prognosis is favorable. 
 
 In the same manner the function of the ear may be sim- 
 ilarly affected to that of the eye, and this disturbance may 
 occur in varying degrees of intensity, either conjointly with that 
 of sight or independently of it. Very frequently — in about 90 
 per cent, of all cases — as the mildest form of the disturbance, 
 only a buzzing or ringing in one or both ears may occur simul- 
 taneously with other nervous disturbances; difficulty of hearing 
 and even deafness may, however, also supervene. These symp- 
 toms, according to Briquet* are in most cases but temporary. As 
 opposed to this statement Baillyf maintains that irremediable 
 deafness may follow the administration of quinine. The cause of 
 these disturbances of hearing is unknown. RoosaJ attributes the 
 effects of quinine on the ear to congestion jn the organ. In an 
 hour after the ingestion of the drug he noticed a slight injection 
 of the vessels of the manubrium mallei and a sensation of 
 increased warmth in • the external ear. Guder, § on the other 
 hand, found in his experiments bearing on the same subject, that 
 the exhibition of one gramme (gr. xv) of the muriate of quinine 
 was followed by a reduction in the temperature of the ear, of 
 0.56 C. within from two to two and a quarter hours. The same 
 dose, and in the same length of time, caused lowered perception 
 of hearing, as tested by the watch and the ordinary tone of voice. 
 Examination of the tympanum failed at any time to reveal hyperae- 
 mia, neither was there any such alteration in the external meatus. 
 So far from this there was at the height of the effect of the drug, 
 rather a lowering of the color of parts naturally red. 
 
 It is further to be noted that a gastro-intestinal catarrh of 
 varying degrees of intensity not infrequently follows the use of 
 quinine. For this reason Binz** calls attention to the danger in 
 fever of giving by the stomach such salts of quinine as are not 
 readily soluble. Quinine in a slightly acidulated solution is 
 readily absorbed and may be given for weeks without ill effects 
 
 *Briquet, Traits Therapeut, de Quinquina et de ses Präparat. Paris, 1853. 
 tBailly, Gazette MeMic. de Paris, 1850, 9. 
 
 JRoosa, Transactions of the American Otological Society, Vol. II, part 1, 1875. 
 §Guder, Experimente über die Chininwirkung. Inaug. Dissert. Berlin, 1880. 
 **Binz, Deutsche Klinik, 1871, 46, p. 409. 
 
TOXICS QUININE. 41 
 
 but when given in the form of pills or powders (and this is 
 particularly so in the case of the slightly soluble sulphate) it is 
 apt to cause irritation of the stomach and bowels, owing, prob- 
 ably, to the deficiency of the acids of the stomach in fever 
 patients. 
 
 It was further noted by Guyochin* that slight irritation of 
 the kidneys and of the mucous lining of the bladder and the 
 urethra may follow the use of quinine, owing probably to the 
 fact that the drug is carried directly to these parts. Faginoiif 
 treated a child in whom there was pain in the urinary passages 
 and a discharge of a few drops of blood on micturition, fol- 
 lowing each administration of quinine. Monneret observed posi- 
 tive haematuria to occur in this manner, and Piorry and Briquet 
 have observed the occurrence of symptoms of cystitis in a very 
 few cases, following the ingestion of quinine. More recently 
 Rivet! nas sported a case in which there occurred spasms of 
 the bladder and haematuria as an effect of an ordinary dose of 
 quinine. 
 
 There is mentioned in the case noted by Gauchet, as above, 
 a symptom which is quite unique in the literature of quinine, 
 viz., haemoptysis. Simon de Ronchard § first noted the occur- 
 rence of several cases of haemoptysis following the administra- 
 tion of quinine in doses of 0.5 gramme (gr. viij) daily. In the 
 persons thus attacked, the lungs and heart were healthy. The 
 haemoptysis promptly ceased with the suspension of the drug, 
 but when it was renewed, blood again appeared in the sputa. 
 It has not yet been determined how this effect of quinine is 
 induced. The investigations of Merat have, however, estab- 
 lished the fact that quinine may be found in the bronchial 
 mucous membrane after the internal exhibition of the drug. 
 
 The symptoms named seldom call for treatment inasmuch 
 as they spontaneously disappear on the suspension of the drug. 
 When the debility which has been referred to is excessive, it will 
 be found necessary to prescribe tonics according to the symp- 
 toms. For the purpose of preventing the head symptoms which 
 
 ♦Guyochin, Absorption, Action Physiologique et TheYapeutiqua de la Quinine. Paris, 
 1872. 
 
 f Faginoli bei Grissac, !. c, p ; 43. 
 
 JRivet, L'Union Medicale, Nov. i, 1881. 
 
 §Simon de Ronchard, Gazette des höpit, Janvier, 1861. 
 
THE UNTOWARD EFFECTS OF DRUGS. 
 
 so frequently attend the employment of quinine, Wade* recom- 
 mends bromhydric acid. Fothergill tested this drug and was able 
 to corroborate its claims. He prescribed, diluted with water, 
 2 — 12 grammes ()4 — 3 fluidrachms) of the acid prepared by 
 precipitating a solution of bromide of potassium, 47 parts, water, 
 350 parts and tartaric acid, 58 parts. Rivet has recommended 
 the subcutaneous administration of morphine as a remedy against 
 the accidents following the use of quinine. 
 
 Lightfootf observed a rapid disappearance of the quinine 
 eruption after the taking of 25 drops of tr. hyoscyamus and 
 alkaline baths. Heusinger (1. c.) powdered the affected portions of 
 the skin with wheat flour. 
 
 SALICYLIC ACID SALICYLATE OF SODIUM. 
 
 Salicylic acid, owing to its liability to be followed by 
 unlooked for action, is to be classed with such drugs as are par- 
 ticularly apt to cause untoward effects. Several of the symp- 
 toms already indicated appear to be tolerably typical concom- 
 itants of the antifebrile virtues of the drug and are thus speci- 
 ally liable to follow its employment. To these symptoms belong 
 several which are yet to be treated of, which are especially 
 referable to the central nervous system. 
 
 The occurrence of other symptoms, such as changes in the 
 skin and functional disturbances of internal organs, is quite rare 
 and is probably due to an idiosyncrasy in the person affected. 
 They have all, however, this feature in common that they 
 readily disappear, leaving no trace of ill effects behind. 
 
 The internal exhibition of salicylic acid causes a repulsive 
 taste, and a burning and grating sensation in the mouth and 
 throat. After its absorption, we may, as noted by Bertagnini, 
 the first experimenter into the physiological properties of this \ 
 drug, and afterwards also observed by Strieker, J have buzzing in 
 the ears, difficulty of hearing and profuse perspiration ; these 
 symptoms do not, however, contraindicate the further employment 
 of the drug. Perspiration supervenes in about two-thirds of the 
 cases, and is sometimes as profuse as that following jaborandi. 
 
 *Wade, Ref. Virchow, Hirsch, Jahresber. 1876. L. p. 400. 
 tLightfoot, Brit. Med. Journal, 1870, L. p. 30. 
 ^Strieker, Bed, Klin. Wochenschr, 1876, No. 8. 
 
TOXICS SALICYLIC ACID. 43 
 
 Patients, and particularly phthisical patients, are very much troubled 
 by it. Other authors have observed more significant disturbances 
 of the nervous system. Thus Riegel* noticed in addition to the 
 symptoms indicated, and following the exhibition of 4-6 grammes 
 (i-i^ drachms), the occurrence of headache, dizziness, and transient 
 delirium; and Schuhmacher, j- in addition to these, observed visual 
 hallucinations which caused considerable anxiety. There may fur- 
 ther occur, according to Riess,J in addition to these psychical 
 disturbances, dimness of vision and a nickering before the eyes. 
 Knapp § noticed diminution of the acuteness of vision and contrac- 
 tion of the retinal vessels of a similar nature though of a less 
 degree, than follows the use of quinine. On the other hand Mül- 
 ler, || observed in a diabetic patient, to whom he had given 15 gram- 
 mes ( I ss) of the salicylate of sodium daily, for nine days, 
 a condition of mental depression with severe headache and 
 mental weakness, and, simultaneously with these, peculiar 
 motor disturbances. The patient complained also of weak- 
 ness in the legs, uncertainty of gait, a paretic inclination of 
 the body to the right side, and notwithstanding the fact that 
 his visual powers were intact, he ran against objects standing in 
 his way These symptoms disappeared within five days after the 
 suspension of the drug, but returned on a repetition of the 
 drug in smaller doses. 
 
 Goltdammer** observed the occurrence of collapse of dif- 
 ferent degrees of intensity in several cases after small doses — 
 5 grammes (gr. lxxv) — of the salicylate of sodium. 
 
 The manner of the occurrence of these symptoms — which 
 bear a certain resemblance to the effects of quinine, — has not, 
 as yet, been investigated. They are probably the expression of 
 a direct impression of the drug upon a certain portion of the 
 brain. 
 
 Of the functional disturbances of internal organs, those 
 which affect the stomach and intestines first demand attention. 
 
 Goltdammer found in a post mortem of a patient suffering 
 
 ♦Riegel, Berl. Klin. W T ochenschr. 1876, p. 182. 
 tSchuhmacher, Deutsche, Med, Wochenschr, 1875, No. 18. 
 JRiess, Berl. Klin. Wochenschr, 1877, p. 29 
 §Knapp, Wien. Medic. Wochenschr. 188 1, p. 1237. 
 I Müller, Berl. Klin, Wochenschr. 1877, p. 29. 
 **Goltdammer, Berl. Klin. Wochenschr. 1876, p. 47. 
 
44 THE UNTOWARD EFFECTS OF DRUGS. 
 
 from acute miliary tuberculosis, to whom twelve grammes ( 3 iij) of 
 salicylic acid had been given, several deep, pea-sized ulcerations 
 on the mucous membrane of * these organs. This is the only 
 observation of this nature on record, and the condition was prob- 
 ably due to hemorrhagic erosion, caused by the irritation of the 
 drug on parts previously changed. As opposed to this is the 
 statement of Riegel (1. c.) that he had never noticed a change 
 in the oesophageal, gastric or intestinal mucous membrane even 
 after doses of from 4 to 6 grammes ( 3 j to 3 jss) of the acid. 
 It is none the less true, however, that there have been cases 
 reported at different times in which the employment of salicylic 
 acid and the salicylate of sodium has been followed by pain in 
 the stomach, vomiting and diarrhoea. Lepine noticed similar symp- 
 toms with collapse after the administration of two doses, at an 
 interval of four hours, of 4 grammes ( 3 j) of salicylic acid. It 
 appears as if the drug is also capable, under certain conditions, 
 although very seldom, of causing irritation of the kidneys. Thus 
 Liirmann* reports a case in which four grammes (3j) of sodium 
 salicylate gave rise to albuminuria, with oedema of both forearms 
 and legs, which disappeared with the suspension of the drug and 
 returned on its being again administered. Müller (1. c.) noticed 
 a diminution in the secretion of urine and albuminuria after 
 larger doses of the drug. Balzf observed, besides albuminuria, 
 haematuria, as a result of the use of salicylic acid and salicylate 
 of soda, and referred the cause directly to inflammation of the 
 parenchyma of the kidneys. 
 
 It yet remains to consider the changes in the skin which 
 have been observed to follow the use of the sodium salicylate, 
 changes which occur in the form of erythema or urticaria or 
 petechiae, and are usually accompanied by intense itching. 
 
 In a case reported by Heinlein,J in which four grammes 
 ( 3 j) of the drug had been given to a patient suffering from 
 articular rheumatism, there supervened, with intolerable itching, a 
 diffused redness of the left side of the face, the lower extremities 
 and the right side of the chest, and also a slight oedema of 
 both eyelids, the upper lips and the lower extremities as far as 
 
 *LUrmann, Berl. Klin. Wochenschr. 1876, p. 477. 
 +Balz Archiv, f. Heilkunde, Vol. XVIII. p. 63. 
 JHeinlein, Aerztl. Intelligenzblatt, April, 1878. 
 
TONICS — RESORCIN. 45 
 
 the middle of the thighs. Within twenty-four hours after the 
 drag had been withdrawn these symptoms had all disappeared. 
 When four grammss ( 3 j) of the salt was given later on, there 
 occurred, accompanied by itching, a disuse erythematous red- 
 ness, while the whole abdomen, and also the lower extremities 
 were covered with diffusely scattered wheals on the reddened 
 base. The wheals disappeared spontaneously in the course of 
 an hour, and the other symptoms on the following day. Leube, 
 also, witnessed an urticaria occurring after a dose of four gram- 
 mes (3j) of the salicylate of soda. Freudenberg* observed a 
 petechial exanthem in a case of marasmus, to whom five gram- 
 mes (gr. lxxv) of the sodium salicylate had been given daily for 
 five days. The very pruritic petechiae, some of which were as 
 large as a fifty cent piece, first appeared on the back, from 
 which they spread the next day over the breast, shoulders, arms, 
 hips and thighs. In the course of eight days the spots became 
 paler and the epidermis was thrown off in great flakes from 
 the diseased parts. After complete recovery five grammes of 
 salicylic acid, given in capsules, was followed by similar results. 
 Ratheryf found in his own case, that after each employment of 
 the salicylate of soda there appeared on his hands and other 
 parts of his body a pemphigus-like eruption. Other authors 
 have also reported the occurrence of herpes labialis. 
 
 RESORCIN. 
 
 This more recent addition to the materia medica produces 
 as do also the other febrifuge drugs, when given in active doses, 
 untoward effects, especially referable to the central nervous sys- 
 tem. LichtheimJ and Brieger § have reported facts pertaining to 
 this point. 
 
 The effects of a dose of 2-3 grammes (gr. xxx to gr. xlv) 
 of resorcin, given either in solution or in substance are manifest 
 in a few minutes, the symptoms being dizziness, buzzing in the 
 ears, and increased frequency of pulse and respiration. The face 
 also becomes flushed and the eyes glisten, the patient being- 
 thrown into a condition simulating intoxication. Frequently 
 
 *Freudenberg, Berl. Klin. Wochenschr. 1878, p. 630. 
 
 tRathery, Gazette des hopit, 18S1. 149 
 
 JLichtheim, Correspondenzblatt f. Schweiz. Aerzte, 1880, 14, 15 Juli. 
 
 §Brieger, Centralbl. f . Med. Wissenschaft, 1880, 37. 
 
40 THE UNTOWARD EFFECTS OF DRUGS. 
 
 there is delirium and accompanying hallucinations. The speech 
 becomes unsteady and slight convulsive twitchings attack the 
 hands. 
 
 Shortly after the ingestion of the drug the surface becomes 
 moist, and in 15 or 20 minutes there occurs a copious perspi- 
 ration. With this there is a reduction of temperature and a dis- 
 appearance of the symptoms of excitation referred to. Brieger 
 noticed the onset of collapse during this latter stage, which 
 became "so great with the defervescence as to demand active stimu- 
 lation. 
 
 The defervescence lasted only a short time. The fever sud- 
 denly reappeared in the course of two or three hours, preceded 
 by a sensation of chilliness and even a decided rigor. 
 
 CHINOLINUM. 
 
 Chinoline, or the tartrate of chinoline, recently recommended 
 as an antiseptic, but more particularly as an antipyretic, has 
 answered to a certain degree the requirements laid on it. It 
 is given in intermittent fever in dozen of one gramme (gr. xv) 
 before the time of the expected paroxysm, and in the form of 
 powder, wafers or the following solution : 
 
 Ijs Chinolini, i gramme (gr. xv.) 
 
 Aq. destillat. 
 
 Syr. rub. idaei aa 50 grammes (3jss.) 
 
 Aq. laurocerasi 2 grammes (3ss.J * 
 
 M. 
 
 It is also employed in whooping cough, but the untoward 
 effects which follow its use, and which it has not yet been found 
 possible to avoid, have militated against its more general employ- 
 ment. 
 
 Pure chinoline has an intensely repugnant odor and a biting, 
 burning taste. The tartrate possesses the same properties though 
 in a modified degree. But the effect on the stomach of both 
 of these preparations is more disagreeable than the properties 
 just mentioned. In the majority of cases, as Lcewy,* among 
 others, has demonstrated, there ensues distressing oppression and 
 severe pain in the stomach, and, in spite of all remedies which 
 may be exhibited to prevent it, vomiting supervenes. This prop- 
 erty would prevent its employment in cases of high fever, sep- 
 
 *L. Lcewy, Wien. Medic. Presse 1881, No. 39. 
 
TONICS STRYCHNIA. 47 
 
 tic diseases, etc., in which there exists great irritability of the 
 stomach, and in which the exhaustion consequent on vomiting 
 must be avoided. 
 
 STRYCHNIA. 
 
 The administration of even medicinal doses of strychnia 
 may, under certain circumstances, be followed by a series of 
 symptoms which differ only in degree from those of actual 
 strychnia poisoning. A dose of 0.005-0.01 gramme (y 1 ^ to ^ 
 gr.) of strychnia may manifest itself in gastric uneasiness, red- 
 ness of the eyes, formication, increased susceptibility to external 
 impressions, heaviness of the feet and stiffness of the limbs. 
 Associated with these symptoms there are unpleasant tension of 
 particular groups of muscles and painful erections. Girl* noticed 
 on several occasions after the repeated internal exhibition of 
 strychnia, the occurrence of periodical cramp-like seizures, which 
 for several weeks assumed a resemblance to the tertian type of 
 intermittent fever, and finally broke up with perspiration. After 
 their subsidence it was possible to arouse them again with 
 strychnia. 
 
 Children are particularly susceptible to the deleterious 
 effects of strychnia, and it is necessary to administer the drug to 
 them with extreme caution. Cases are known in which the 
 hypodermic administration of the drug in medicinal doses, for 
 diphtheritic paralysis, has been followed by a series of grave and 
 indeed fatal symptoms. 
 
 A skin affection resulting from the internal administration 
 of strychnia has also been described. Skinnerf noticed the 
 occurrence of a scarlatiniform eruption in a woman, after a dose 
 of 0.0004 gramme (gr. yfg-), which, however, disappeared with 
 the discontinuance of the drug. 
 
 COLUMBO ROOT. 
 
 Columbo root, which is prescribed as a simple bitter 
 astringent, probably contains as its active principle berberin, 
 together with the crystalline bitter substance columbin. An expe- 
 riment made by Köhler^ on himself with an infusion of 20 
 
 *Girl, Buchner's Repertonum XXXI, 2. 
 tSkinner, British Medical Journal. 1870. I., p. 303. 
 ^Köhler, Handbuch d physiol. Therapeutik, 1876, p. 159. 
 
•• 
 
 48 THE UNTOWARD EFFECTS OF DRUGS. 
 
 grammes to 120 grammes of water admonishes to a certain 
 degree of caution in the administration of this drug. It caused 
 nausea, frequent vomiting, pain in the epigastrium and finally 
 loss of consciousness, after recovery from which he remained in 
 a condition resembling that resulting from a debauch. These 
 symptoms had all disappeared after the lapse of twenty-four 
 hours. With this case before us it would seem advisable, until 
 at least a more accurate pharmacological investigation of the 
 drug has been made, to prescribe it in smaller quantities than is 
 now the custom. It is probable that in small doses only the 
 effects of the bitter principle are secured, while the alkaloid ber- 
 berina manifests its action in larger doses. 
 
 QUASSIA. 
 
 Quassia which is an active poison to the lower forms of 
 insect life, when given in small doses as a stomachic gives rise 
 to no functional disturbance. Its continued use, however, or when 
 given in larger doses, causes in some persons digestive disturb- 
 ances, gastric oppression and nausea, with efforts at vomiting. 
 In addition to these, according to Wibmer,* there occur in 
 children and weakly persons, after larger doses of quassia, dizzi- 
 ness, headache and deafness. Barbier noticed involuntary mus- 
 cular contractions in an irritable woman after an aqueous infu- 
 sion in quassia. 
 
 CHELIDONIUM. 
 
 Celandine, which was formerly regarded as a specific in 
 hepatic affections, is active only when freshly gathered. The 
 herb then contains a yellowish milky juice which is irritant 
 and even blistering to the skin. When given internally in 
 small doses it may excite nausea, or a desire to vomit, and 
 vomiting or diarrhoea, and also headache. Not infrequently also 
 after its internal use there occur papular or vesicular eruptions 
 on different parts of the body and particularly on the face. 
 
 CREASOTE. 
 
 In the long continued use of creasote in diarrhoea there 
 occur, according to Richardson, dryness of the mouth, a burning 
 sensation extending from the pharynx to the stomach, a white 
 
 *Wibmer, Die Wirkungen der Arzneimittel und Gifte, München, 1842, Bd. IV. p. 380. 
 
TONICS — OLEUM TEREBINTHIN.E. 49 
 
 membraniform coating of the tongue and increased frequency of 
 the pulse. In a few cases there occur, also, vomiting and stran- 
 gury, attended by a persistent headache. 
 
 A skin affection has also been observed to follow the exhibi- 
 tion of creasote. M. Bernard* reports the case of a lady in 
 whom, regardless of the form in which he administered the drug, 
 there occurred an eruption with intense pruritus which had the 
 characteristics of urticaria. This disappeared with the suspension 
 of the drug and reappeared when it was renewed. 
 
 Following the external application of this substance in caries 
 of the teeth, should it come in contact with the gums and the 
 tongue, it is apt to cause a swelling of the latter and also a stom- 
 atitis. 
 
 When untoward effects manifest themselves in the course of 
 the internal administration of creasote, the drug must at once be 
 discontinued and such gastric irritation as may have been caused 
 treated, according symptoms, with demulcent drinks. The local 
 effects in the mouth soon disappear, either spontaneously or under 
 antiphlogistic or astringent treatment. 
 
 OLEUM TEREBIXTHINjE. 
 
 The oil of turpentine, prepared by distillation with water 
 from turpentine, the resinous exudate of several varieties of fir, 
 when exhibited either internally or externally in varying doses 
 to certain persons, produces in them a series of untoward effects 
 which are sufficiently troublesome to forbid the repetition of the 
 drug in such cases. 
 
 Following the local application of the drug to the sound 
 skin there occur erythematous changes with a feeling of warmth 
 and pruritus, and sometimes even a vesicular-like eruption of 
 the skin, which rapidly disappear, however, after the withdrawal 
 of the drug. In persons who have employed turpentine for a 
 prolonged period, the skin assumes an eczematous appearance. 
 This eczema has no specific peculiarities, never spreads beyond 
 the seat of its original appearance and disappears with the sus- 
 pension of the drug. It acts very intensely on the surface of 
 wounds and may even give rise to extensive inflammation. The 
 vapor of turpentine may also cause a burning and pruritic 
 
 *M Bernard, Gaz.tte des höpit. 1879, P- J 7°- 
 
THE UNTOWARD EFFECTS OF DRUGS 
 
 erythema, as was exemplified in a case of rheumatism, treated 
 by turpentine vapor baths, after the manner recommeded by 
 Chevandier.* In animals the effects of the drug on the skin 
 are manifested in the shedding of the hair. 
 
 Schlothauerf noticed further the occurrence of profuse saliv 
 ation and stomatitis after a single external application of tur- 
 pentine for the cure of scabies. This evidence of absorption 
 is probably due to reflex excitation of the salivary secretion, 
 through irritation of the mucous lining of the mouth by the 
 turpentine eliminated in the expired air, inasmuch as turpentine 
 taken per orem may also give rise to an increased flow of 
 saliva and reddening of the buccal mucous membrane. 
 
 The internal employment of the oil of turpentine, a well- 
 known method of its employment in a variety of affections, as 
 neuralgia, phosphorus poisoning, and the colic due to gallstones, 
 occasionally gives rise to accidental symptoms which may become 
 intensified to such a degree as to excite grave apprehen- 
 sion. Thus there are occasionally observed as a result of small 
 doses, a burning in the primae viae, the formation of blisters in 
 the mouth, pain in the region of the stomach, colicky diarrhoea 
 or strangury, which usually increase until the urine becomes 
 bloody and of the odor of violets. With this irritation of the 
 kidneys there may be a redness of the urethral mucous mem- 
 brane and also painful erections. 
 
 The repeated exhibition of medicinal doses of the oil of 
 turpentine is not infrequently manifest on the central nervous 
 system, evidence of which is presented in headache, dizziness, 
 mental vacuity. Purkinje J who for three successive mornings 
 took 4 grammes ( 3 i) of this oil, was attacked with sleepiness 
 and could only with great difficulty keep awake ; the intellect 
 and power of motion remained intact. The occurrence of these 
 symptoms is explicable, in so far as Rossbach and Fleischmann § 
 have demonstrated the action of turpentine, in its diminishing the 
 reflex irritability of the central nervous system. Similar manifest- 
 
 *Chevandier, Revue Medico-Chirurg. 1851. 
 
 f Schlothauer, Medic. Zeitung des Vereins für Heilkunde, 25 Juni, 1851. 
 t Purkinje, Ref. in Mitscherlich's Lehrb. der Arzneimittel lehre, B l. II. p. 251. 
 §Rossbach und Fleischmann, Pharmak. Untersuchungen aus dem Würzburger Institut, 
 Bd. III. 
 
TONICS COPAIBA. 5 I 
 
 ations of constitutional effects may result from an extensive 
 external application of the oil of turpentine. 
 
 It is finally to be noted that changes in the skin may ensue 
 on the internal exhibition of turpentine as well as a result of its 
 external application.. According to Berenguier* there may 
 occur after comparatively large doses, a simple, scarlatiniform, 
 wine-colored eruption, spreading by preference over the face and 
 the upper part of the trunk in irregular blotches. Occasionally 
 there appear also on the reddened base a large number of small 
 papular points, which give the surface an eczematous appear- 
 ance. In rare cases the eruption is vesicular in its nature. 
 Brochinf has reported a number of observations, in which there 
 always occurred in certain persons, after the exhibition of tur- 
 pentine, an erythematous or urticaria-like eruption; and this 
 occurred irrespective of the mode of its administration, i. <?., 
 whether it was given pure, in capsules or in solution. The fol- 
 lowing formula is recommended as one which disguises the taste 
 ot turpentine and facilitates its administration: 
 
 Olei terebinthin, 8.0 grammes ( 3 ij). 
 ^Etheris sulph., 3.0 grammes (3 %). 
 Syr. flor. aurant., 30.0 grammes (3" i). 
 Aq. dest, 120.0 grammes ( 3 jv). 
 
 M 
 
 COPAIBA. 
 
 After the employment of the balsam of Copaiba (most fre- 
 quently after the first day and seldom after the eighth) there 
 suddenly occurs, only in certain persons, however, an affection 
 of the skin, first described by Montegre, in 1817. In the 
 majority of such cases only a roseola is at first noticed. The rose- 
 colored, irregular spots may, however, be transformed into true 
 papules projecting above the skin. Occasionally the eruption is 
 papular from the beginning, which, however, according to Bazin,]; 
 does mot present the appearance of the ordinary febrile urticaria. 
 Gubler and Raver have described miliary and scarlatiniform erup- 
 tions, likewise an eczema, as sometimes, though rarely, following 
 the employment of copaiba. The cutaneous change appears by 
 
 *Berenguier, Des eruptions provoquees par l'ingestion des medicaments. Paris, 1874. 
 
 tBrochin, Gaz. des höpit., 1879, Fevr., p. 99. 
 
 $Bazin, Lecons sur les affections cutandes artific. Paris, 1862, p. 184. 
 
52 THE UNTOWARD EFFECTS OF DRUGS. 
 
 preference on the upper and lower extremities, and particularly 
 on the backs of the hands, the knees, around the malleoli, and 
 on the breast, but spreading eventually over the entire body, and 
 is attended with considerable fever. According to Berenguier* 
 the roseola induced by copaiba resembles a papular Syphilide, dif- 
 fering, however, from the latter in its sudden onset, the itching, 
 its predilection for the parts of the body indicated, and a pecu- 
 liar, unpleasant smell of the skin, and particularly through its 
 disappearance on suspension of the drug. 
 
 The eruption is attended by intense itching. The spots or 
 papules are either isolated or in groups. In the latter case 
 they may form patches of considerable extent. The spots dis- 
 appear on pressure and reappear on its removal. Should the 
 drug be suspended on the appearance of the eruption, the lat- 
 ter may disappear without desquamation in a day or two, 
 although owing to individuality on the part of the patient or a 
 long continuance of the drug, from one to three weeks may be 
 necessary for its disappearance. Under the long-continued use 
 of the balsam the eruption may assume a severer form and the 
 deeper tissues may even be involved. 
 
 In referring to a statement of Hardy, f who observed a pem- 
 phigus-like eruption after the employment of copaiba, HebraJ 
 calls attention to the probable fact that in this case it was not 
 pemphigus but urticaria, and that the wheals (quaddeln) of the 
 latter are serous infiltrations of the epidermis which require but 
 to be somewhat aggravated in order to be blisters. 
 
 The balsam of copaiba when employed for a long time and 
 not necessarily in large doses, affects the various mucous mem- 
 branes injuriously. It not infrequently causes loss of appetite, 
 gastric oppression, nausea and vomiting, and still further, accord- 
 ing to Bazin (1. c.) congestion of the conjunctiva and pharynx, 
 and irritation of the kidneys and bladder, to the extent of even 
 causing nephritis and cystitis. 
 
 The manner in which these effects are produced is clear. 
 Balsam of copaiba, like other resinous substances, causes irrita- 
 tion of various degrees of severity, of the mucous membranes, 
 
 *BeVenguier, 1. c, p. 22. 
 
 tHardy, Gazette des hopiteaux, 1869. 
 
 IHebra, Hautkrankheiten, 1., p. 673. 
 
TONICS CUBUB^E (EXT. CUBEBARUM.) 53 
 
 perhaps through the oil of copaiba or copaibic acid which it 
 contains. Its elimination is effected through the lungs and kid- 
 neys, and thus the urinary passages may suffer irritation in 
 proportion to the quantity of the balsam which passes through 
 them. But the balsam may also be excreted through the skin, 
 and thus either it itself or the glands which it contains 
 may be the starting point of an inflammatory action. It 
 has not yet been determined to what extent deviations from 
 the normal vascular distribution or a peculiarity in the 
 glandular elements of the skin are responsible for the effects 
 noted. The fact, however, remains that after the employment 
 of the balsam of copaiba, a peculiar odor, due perhaps to the 
 volatile products of decomposition of the drug, is given off, 
 and that in these cases the effectiveness of the balsam in 
 gonorrhoea is slight. 
 
 It is to be remarked that the urine which is voided after 
 the exhibition of copaiba, gives a precipitate with nitric acid 
 which consists of copaibic acid, and may be easily mistaken for 
 albumen. 
 
 Maestri and Pidoux* report that large doses of the balsam 
 of copaiba occasionally give rise to symptoms of poisoning, 
 among which are paralysis, with tetanoid manifestations. In 
 milder cases there is weakness of the arms and muscles of the 
 face and lowering of general sensibility. 
 
 CUBEB.E (EXT. CUBEBARUM.) 
 
 The employment of cubebs is not, as a rule, attended by 
 untoward effects. In some persons, however, it may cause 
 colicky pains and diarrhoea. 
 
 An eruption is commonly observed only after large doses 
 and in the case of very young persons. It then manifests 
 itself either as an erythema or, more frequently, as a papular 
 eruption, which, as in a case reported by Berenguier (1. a), is 
 diffused over the face, trunk and upper extremities, and which 
 was also abundantly discernible on the lower extremities. The 
 papules are miliary, but unite in many places to form larger eleva- 
 tions on the skin. The eruption occurs without accompanying 
 
 *Maestri u. Pidoux, Ref. Schmidt's Jahrbücher, Bd 97, p. 301. 
 
54 THE UNTOWARD EFFECTS OF DRUGS. 
 
 febrile symptoms or other evidence of disturbance, and disap- 
 pears in the form of bran-like scales in a few days after the 
 suspension of the drug. 
 
 AQUA CALCIS. 
 
 The continued use of limewater through the continued neu- 
 tralization of the acids of the stomach which attends it, not 
 infrequently gives rise to disturbances of digestion and loss of 
 appetite ; vomiting has also been observed to follow such 
 employment of it. There is increase in the urinary secretion dur- 
 ing its use, the stools are usually retarded, and in rare cases 
 here is diarrhoea. 
 
 To obviate these ill effects it has been proposed to substi- 
 tute saccharated lime in doses of 0.5 to 1.0 gramme (gr. viij 
 to xv) in watery solution for the lime water. 
 
 What is true of lime water in this connection is equally 
 applicable to the caibonate of lime. 
 
 SODII NITRAS. 
 
 Löffler* noticed several changes in persons who had taken 
 saltpetre for a length of time, by way of experiment, even 
 though the doses did not exceed the medicinal size. On two 
 occasions there was pain in the intestines and borborygmi. 
 The digestion was generally not disturbed by the drug; but, 
 varying with the quantity of the saltpetre taken, there ensued a 
 feeling of general debility which was manifest on exertion and 
 continued for Several days after the drug had been discontin- 
 ued; disinclination for either bodily or mental action, depression 
 of spirits, fatigue on the slighest exertion, pains in the mus- 
 cles and joints, particularly in the knees, and a persistent 
 inclination to sleep. 
 
 The quantity of urea increases for the first few days fol- 
 lowing the administration of the drug; it then returns to and 
 even falls below the normal quantity. 
 
 *Löffler bei Barth, Teleologische Untersuchungen des Chilisalpeters, Bonn, 1879, P« 5. 
 
ASTRINGENTS ALUMEN. 55 
 
 Astringents. 
 
 A LUMEN, 
 
 Following the frequent administration of alum there 
 appear in some persons gastric disturbances, as loss of appetite, 
 nausea, inclination to vomit and diarrhoea. This effect is due 
 to a direct irritation by the drug, of the mucous lining of the 
 gastro-intestinal tract, and is dependent ,011 the degree of full- 
 ness of the stomach. For should the alum ingested not find a 
 sufficient quantity of albumen or albuminoid substances in the 
 stomach to precipitate it, the mucous membrane of this organ 
 is, in a greater or lesser degree, affected by the drug. The 
 observation of Beginaud, also of Barbier, viz., that the continued 
 use of small doses of alum is prone to induce a cough in per- 
 sons with sensitive bronchi, is also noteworthy. 
 
 BISMUTHI SUBNITRAS. 
 
 (magistekum bismuth.) 
 
 There is scarcely any other drug, the opinions regarding 
 the deleterious or the innocuous nature of which are so con- 
 flicting as are those entertained on the nitrate of the oxide of 
 bismuth. While Monneret,* among others, asserts that the 
 irritating or even poisonous properties which are attributed to 
 this substance are but imaginary, that it may be administered to 
 patients in quantities of from 3 to 6 teaspoonfuls daily with- 
 out inconvenience, and that it can be beneficial only in such 
 doses, there are many competent observers who aver that the 
 subnitrate of bismuth in doses of from two to four grammes 
 ( " ss to I i) may sometimes be attended with baneful untoward 
 
 'Monneret, Central Zeitung, 1849, 43- 
 
56 THE UNTOWARD EFFECTS OF DRUGS. 
 
 effects. The attempt has been made to reconcile these con- 
 tradictions by holding the impurities of the preparation given, 
 and particularly the lead and arsenic which it is said to con- 
 tain, responsible for these untoward effects. As a matter of 
 fact Carnot,* among others, found lead in all the preparations 
 of the subnitrate of bismuth which he examined, in quantities 
 varying from one to ten per cent. Riche,f on the other hand, 
 attributes much less importance to this and maintains that the 
 quantities of lead which he has demonstrated to be present 
 are too insignificant to work any disturbance in the system. 
 BouchutJ would not even have the lead which is contained in 
 the subnitrate of bismuth eliminated, holding, as he does, that 
 it is through this substance that the preparation exerts its cura- 
 tive action in diarrhoea. 
 
 The proportion of arsenic in subnitrate of bismuth is also 
 too small to give rise to the symptoms which are hereafter to 
 be mentioned. 
 
 It then remains but to attribute the ill effects of the bis- 
 muth either to such a temporary condition of the patient as 
 causes an abnormal reaction, or to an improper emplovment of 
 the drug. 
 
 The condition of the individual may have an influence in 
 so far as the presence of undue quantities of acid in the 
 stomach may favor the conversion of the basic subnitrate of 
 bismuth into a corrosive neutral salt; or, if this should be 
 decomposed by water the acid salt may be formed in great quan- 
 tities. These neutral and acid salts are, as Orfila§ demon- 
 strated by his experiments on animals, intense poisons, setting 
 up gastro-enteritis. The same effects would naturally ensue if 
 the basic salt were given simultaneously with acid remedies, or 
 if the patient should take acids after the drug. A readily 
 soluble nitrate of bismuth would thus be formed in the stomach 
 and would be absorbed. 
 
 The untoward effects which are observed to follow the 
 subnitrate of bismuth, are chiefly referable to the stomach and 
 
 *Carnot, Comptes Rend, des sciences de l'Acadamie des sciences. T. LXXXVI., p. 
 718, 1873. 
 
 IRiche, Journ. de Pharm, et Chimie, 1878, 28, p. 147. 
 
 iBouchut, Jahresbuch über Pharmakog. u. Toxikol. von Dragendorff, 1879, p. 268. 
 
 §3rfila, Toxicologic übers, v. Krupp, 1854, II, p. 9. 
 
ASTRINGENTS ACIDUM BORACICUM. 57 
 
 intestines, and are nearly identical with the pathological symp- 
 toms which it is the typical action of the acid salt to excite. 
 Thus Odier* noticed nausea after its use, and Werneckf vomit- 
 ing, colicky pains, and in several cases diarrhoea, while in 
 others there occurred obstinate constipation. With these local 
 symptoms there were associated a sensation of heat, headache, 
 dizziness and general debility. Not infrequently after the exhi- 
 bition of magisterium bismuth there is observed a peculiar dis- 
 coloration of the tongue. According to T. Lawrence Hamilton,;); 
 this is due to a change of the bismuth salt through the sugar formed 
 by the action of the saliva on the starchy food. It is also possible 
 that sulphuretted hydrogen is developed from carious teeth, and 
 that the union of this with the bismuth gives rise to a black or 
 greyish-black sulphuret of bismuth. It is further to be especially 
 noted that the feces after the employment of the subnitrate of 
 bismuth, mostly assume a grayish-black color, and are nearly 
 odorless. It is inferred from this that the bismuth salt is 
 changed in the intestines, in the presence of sulphuretted 
 hydrogen gas, into the sulphide of bismuth, and the gas is thus 
 held fast in combination. The therapeutic indications in the 
 untoward effects named, are a discontinuance of the drug, and 
 the employment, now and then, of calcined magnesia in small 
 doses, or of milk in an emulsion, etc. 
 
 ACIDUM BORACICUM. 
 
 According to the investigations of Binswanger§ boracic acid 
 in medicinal doses is without effect on the human system; 
 should, however, the quantity given be increased to 2 or 4 
 grammes (30 or 60 grains) it may cause a frequent desire to 
 micturate and an increased flow of urine. 
 
 After 8 grammes ( 3 ij) of boracic acid, taken by Bins- 
 wanger in two doses within an hour, there occurred nausea and 
 vomiting, a feeling of pressure and fullness of the stomach, 
 which continued for several hours. 
 
 *Odier, Journ. de Medecin. 1768, T. 68, p. 49. 
 
 tWerneck bei Wibmer, Wirkungen d. Arzneimittel, T. I. p. 418. 
 
 XT. Lawrence Hamilton, British Medical Journal, February, 1881. 
 
 §Binswanger, Pharmakolog. Wirkungen dei Borsäure und des Borax, München. 1847. 
 
58 THE UNTOWARD EFFECTS OF DRUGS. 
 
 Following the external employment of boracic acid as an 
 antiseptic. Molodenkow* has recently reported deleterious 
 untoward and even fatal results. A young woman who suffered 
 from pleurisy and hydrothorax was subjected to thoracentesis 
 without previous chloroformization. The pleural cavity was 
 afterwards washed out with a five per cent, solution of boracic 
 acid, following which distressing vomiting and weakness of the 
 pulse set in. On the following day an erythema appeared on 
 the face and soon extended over the trunk. On the third day 
 the erythema having also spread over the lower extremities, the 
 vomiting having ceased and the mind remaining clear, the 
 patient suddenly died. 
 
 In a second case, after the washing out of a deep abscess in 
 the nates of a young man, of sixteen years of age, there occurred 
 in half an hour vomiting, debility, and a small, scarcely perceptible 
 pulse, and in two days an erythema, first appearing on the face, 
 hiccough and death. The autopsy revealed no cause of the death, 
 which seems to have been due to paralysis of the heart. 
 
 The decided poisonous action of boracic acid in these cases is, 
 perhaps, explained by the experiments of Binswanger, who showed 
 that in the internal exhibition of this drug it is rapidly eliminated 
 by the kidneys, while after its injection into cavities it is less readily 
 absorbed, remains longer in the system and thus exerts its fullest 
 action. 
 
 ARGENTI NITRAS. 
 
 The changes induced by the continued use of silver, either 
 internally or externally, consist of a discoloration of the tissues, 
 due to a deposit in them of the metal. As a result of this 
 accumulation of this foreign substance we may have functional 
 disturbances in the various organs. 
 
 The tissue changes have frequently been made the subject 
 of microscopic investigation. Thus Virchowf examined a piece 
 of the conjunctiva of a man for whose eye the application 
 of a solution of nitrate of silver had been prescribed, 
 but who, through misunderstanding, continued its employment 
 
 *Molodenkow. St. Petersburger Medic. Wochenschrift, No. 42, 188I. 
 tVirchow, Cellular-Pathologic, 1871, p. 250. 
 
ASTRINGENTS ARGENTI NITRAS. 59 
 
 for four months. It had become stained to an intensely blue, 
 nearly black color. A deposit of the silver in the tissue had 
 occurred, "so that the superficial layers of the connective tissue 
 were of a light yellowish-brown color, and a deposit was found 
 in the deep, though in only the fine elastic fibres or corpuscles 
 of this tissue. The basis or intercellular substance remained 
 unaffected. 
 
 That the skin, even when perfectly intact, may afford 
 ingress to the silver is illustrated . by a case, reported by Gam- 
 berini,* of a woman who, in order to dye her hair black, had 
 every two weeks, for two and a half years, applied a pomade 
 containing nitrate of silver. There occurred dyspnoea, palpita- 
 tion, ascites and oedema of the inferior extremities, on the dis- 
 appearance of which the skin assumed a slate-gray to a light- 
 brown color. In addition to palpitation of the heart, irregularity 
 of the pulse has been observed after small doses — 0.005 grammes 
 (gr. ^) of the nitrate of silver. 
 
 The recommendation of the nitrate of silver in epilepsy, 
 tabes dorsalis and similar affections, has through the chroni- 
 city of these affections, and the long continued use of the 
 drug, frequently led to the deposit of silver in the tissues, 
 a condition and its consequences to which the name argyria 
 has been given. The smallest aggregate quantity following which 
 this condition has been noticed, is 30 grammes ( 3 i). The dis- 
 coloration may attack the entire cutaneous covering, equally, or 
 it may be most intense at particular parts, as the face. Cica- 
 trices, the nails and hair may likewise suffer changes of color. 
 
 Functional disturbances generally present themselves in the 
 form of gastritis, although in many cases they are entirely absent. 
 
 As a consequence of the irritation which the drug excites 
 upon the buccal mucous membrane, a stomatitis without saliva- 
 tion may occur, as observed in a case reported by Guipon.f 
 The gums in this case were swollen and of a dark-red color, 
 and presented a violet line on the edges. The incisor teeth 
 were of a slate color, and the mucous lining of the mouth was 
 ' exceedingly sensitive, particularly to heat. 
 
 This affection has more recently been observed by Magitot,J 
 
 *Gamberini, Journal de Medecine de Bruxelles, Decembre, i860. 
 tGuipcn, Bullet, de Therapeutique, 1S66, Vol. 71, p. 86. 
 rfMagitot, Gazette des Höpitaux, 1879, p. 165. 
 
6o THE UNTOWARD EFFECTS OF DRUGS. 
 
 who has described it as "gingivite argentique." In this con- 
 nection he calls attention to the fact that Charcot observed a 
 papular eruption as a result of the continued internal employ- 
 ment of silver, and holds that both affections are due to the 
 Jocal irritative action of the silver. 
 
 Individual organs manifest, as a result of argyria, the fol- 
 lowing changes: 
 
 Neumann* found on examining the skin, that the silver 
 was deposited most abundantly in the papillary layer. A few 
 granules were likewise found in the other layers of the skin, 
 more thickly disposed in the external wall of the hair follicles 
 and sebaceous glands, and in the walls of the sudoriparous fol- 
 licles. The epithelium — reti Malpighi — and the covering of the 
 root sheaths (wurzelscheiden) contained none. 
 
 In the case of a man who had taken nitrate of silver in 
 large doses for epilepsy, Frommannf found at the autopsy an 
 ulcer between the pyloric and cardiac openings. The duo- 
 denum and jejunum were studded with numerous small black 
 bodies, which were crowded most closely together along the sulci 
 of the folds, presenting the appearance of dark, striped pigmen- 
 tation of the mucous membrane. In • the duodenum they took 
 the form of round spots of the size of a cent piece, which were 
 darkest at the centre and becoming lighter towards their mar- 
 gins. The intestinal villi (darmzotten), contained groups of small 
 deep black bodies which were readily soluble in cyanide of potas- 
 sium. 
 
 In the case of a tabetic patient, who in a single year had 
 taken 5,672 pills, containing in the aggregate 34.032 grammes 
 ( § jx) of nitrate of silver, RiemerJ found the capsules of the 
 kidneys gray with numerous dark spots, resembling the Malpi- 
 ghian bodies, and the mucous lining of the pelvis of the kid- 
 neys of a grayish-blue in spots. The changes in the parenchy- 
 ma of the kidneys in argyria, are described by Virchow (1. a), 
 after the appearance, as he found them in a preparation, in a 
 collection in the Pathological Institute at Berlin. In this speci- 
 men there appears in the Malpighian bodies, where the 
 
 »Neumann, Sitzungsberichte d. Gesellschaft Wiener Aerzte, i. März, 1878. 
 
 tFrommann, Virchow's Archiv., Bd. XVII. 
 
 JRiemer, Archiv, d. Heilkunde, 1875, XVI., p. 296 u. 385. 
 
ASTRINGENTS ARGENTI NITRAS. 6l 
 
 transudation of the fluid takes place, a blackish-blue discolor- 
 ation of the entire walls of the vessels, which are contract- 
 ed at this point, and a similar though less pronounced discolor- 
 ation in the connective tissue between the canaliculi. Thus 
 in the whole kidney, with the exception of the parts which 
 are particularly the seat at which eliminination is effected, only 
 those portions are implicated which correspond to the ultimate 
 capillary distribution in the pyramidal substance. 
 
 In addition to portions of the body indicated, Riemer and 
 others have discovered silver in many other and widely differ- 
 ent organs, as the meningeal membranes, the liver, the mesentery, 
 the walls of bloodvessels, the heart, etc. 
 
 Regarding the manner of the absorption and deposit of the 
 metal, opinions differ. Riemer maintains that the pigment 
 as such, is, in the form of reduced silver, absorbed by the 
 walls of the intestines, where it is first stored up, soon how- 
 ever to be carried further by the lymphatics, being partially 
 deposited on the way, but the greater portion being carried 
 into the current of the circulation. It finds its way thence 
 through the walls of the blood vessels, in which a portion of 
 it is deposited, and is finally permanently stored up in the tis- 
 sues. Riemer thus regards the cause of argyria as purely phy- 
 sical, after the same manner as in anthracosis pulmonum and 
 in the tatooing of the skin. He is supported in this view by 
 the later experiments of Huet,* who induced the passage of 
 particles of silver into the tissues by a sort of diapedesis. In 
 this, however, he differs from Frommann, Delioux and others, 
 who hold that it is only possible for the soluble salts of sil- 
 ver to be taken up from the intestinal canal, and that, there- 
 fore, argyria occurs through chemical process, a precipitate tak- 
 ing place in the parts attacked. 
 
 In the differential diagnosis of argyria and Addison's disease, 
 the following points indicated by Gamberini are noteworthy: 
 In the "bronze sickness the color varies between a brown and 
 a black, while in argyria it is of slate-gray, with a tinge of 
 red. On' washing the skin in argyria with a solution of iodine 
 there is a marked change in the color, which change does not 
 occur in the case of the discoloration in Addison's disease." 
 
 *Huet, Journal de 1' Anatomie, 1873, p. 108. 
 
62 THE UNTOWARD EFFECTS OF DRUGS. 
 
 The treatment of argyria may have reference both to the 
 gastric symptoms and to the discoloration of the skin. In 
 regard to the former, existing signs of intestinal irritation must 
 be treated symptomatically. With a view to bringing about a 
 clearing up of the color of the skin, the internal use of the 
 iodide of sodium or the iodide of potassium, so- successful in 
 the hands of Gamberini, and the long continued employment 
 of warm baths should be tried. As a prophylactic measure it 
 is necessary to exercise great care that the silver be not 
 employed for longer than three months, and that the aggregate 
 amount administered do not exceed 15 grammes ( 3 jv.) 
 
 PLUMBI ACETAS. 
 
 When the acknowledged poisonous nature of the acetate 
 of lead, in common with that of the other combinations of 
 this metal, and the extensive exhibition of the same, both 
 internally and externally, in relatively large doses, are taken 
 into consideration, it is singular that deleterious untoward effects 
 are not more frequently observed than is actually the case. 
 The fact must, however, be noted that in those cases of 
 saturnism, which follow the employment of lead in the arts or 
 are due to its presence in the food, the introduction of the 
 metal has generally been going on for a much longer time 
 than is devoted to" its most prolonged exhibition for therapeu- 
 tic purposes, and that the majority of the functional disturb- 
 ances in lead poisoning are excited by the extremely gradual 
 deposit of the minutest particles of lead in the organs, and its 
 later cumulative action. That there are exceptions to this 
 mode of the occurrence of lead poisoning is illustrated by the 
 fact particularly insisted on by Romberg,* that certain persons 
 who have been long subjected to the action of lead have 
 escaped its effects, while others are quickly brought under its 
 influence. - ■ 
 
 Wibmerf collected a few cases in which, probably through 
 causes peculiar to the individual, such as defective elimination 
 through the intestines, kidneys, etc., deleterious untoward effects 
 
 * Romberg, Lehrbuch der Nervenkrankheiten, I., p. 167. 
 tWibmer, 1. c. Bd IV. p. 23» 
 
ASTRINGENTS PLUMBI ACETAS. 6$ 
 
 were observed to follow the exhibition of even medicinal doses 
 of the acetate of lead. Baker* noticed loss of appetite, pain 
 in the stomach, constipation and paralysis of three weeks' dura- 
 tion; one hand, in a man who had for four days, morning 
 and evening, taken 0.06 gramme (gr. j) of the acetate of lead 
 for the relief of haematuria. In another case colicky attacks, 
 which continued during several months, followed the daily 
 exhibition, for but three days, of 0.24 grammes (gr. jv) of the 
 drug. Tanquerel des Planches, f who first thoroughly studied 
 and carefully described the action of lead, cautions against the 
 too free internal exhibition of its preparations, as being very 
 prone to give rise to undesirable symptoms. 
 
 The external application of leao\ in solutions and ointments 
 is also said to have developed unpleasant effects. We shall 
 first note those cases in which discoloration of the skin, of 
 longer or shorter duration, is reported to have followed the 
 employment of the preparations of lead. Thus Foucaud de 
 l'EspagneJ cites the case of a woman who, under the instruc- 
 tions of a physician, employed as an astringent collyrium, a 
 solution of the acetate of lead. Another physician having at 
 the same time ordered her to take sulphur baths for the 
 relief of rheumatism, there occurred a black discoloration of the 
 eyelids, which spread over the cheek bones and was only 
 removed after six days by washes of infusions of aromatic 
 herbs. Berenger-Feraud § contributes a similar observation. In 
 this case the discoloration disappeared only after a duration of 
 thirty months, in spite of all conceivable acid, alkaline and 
 alcoholic washes and cosmetics. 
 
 The application of solutions of lead to the mucous mem- 
 brane and abrasions, appears but rarely to' excite symptoms of 
 lead poisoning. Tanquerel des Planches noticed such a case 
 attending the application of lead-wacer compresses to the eye. 
 Percival || noted the appearance of gastric pains after the 
 repeated application of compresses wet with a solution of ace- 
 
 *Baker, Lond. Med. Transactions, I. and II. 
 
 tTanquerel des Planches, Traite des Maladies de plomb, übers, von Frankenberg IL, 
 
 F- 343- 
 
 ^Foucaud de l'Espagne, Gazette des höpit, 1863, No. 153, p. 611. 
 
 §Berenger-Feraud, Gazette des hopit, 1864, p. 62. 
 
 il Percival, "On the Poison of Lead," 1774, bei Wibmer, Bd. VI., p. 237. 
 
64 THE UNTOWARD EFFECTS OF DRUGS. 
 
 täte of lead to a contused shoulder, the pains disappear- 
 ing with the suspension of the application and reappear- 
 ing with its renewal. The washing of a large ulcer of the 
 leg with lead-water, and the application of a lead plaster also 
 after four days caused a colic, and paralysis of the extremities, 
 which soon disappeared on the discontinuance of the drug. 
 In another case, noticed by Werdmann, a sweetish styptic taste 
 in the mouth and a stiffness of the neck followed the appli- 
 cation of lead-water to an ulcer. In this case also the symp- 
 toms recurred and disappeared with the exhibition and suspen- 
 sion of the drug. 
 
 There is, from a physiological point of view, no room to 
 doubt the possibility of the occurrence of these effects of 
 lead. Inasmuch as it is an established fact, that under cer- 
 tain circumstances lead may be taken into the system through 
 the sound skin, the penetration of the combinations of lead, 
 and particularly the caustic preparations which throw down 
 precipitates with albumen, is intelligible. It is true the 
 quantities thus absorbed are very small, but still they are suffi- 
 cient to give rise after a few applications, to the appearance of 
 the drug in the urine. Why it is that injurious effects so sel- 
 dom ensue on the application of the drug in this manner is 
 not known. Similar individual conditions, however, obtain in the 
 case of the majority of drugs, and they are independent of the 
 manner of their absorption. 
 
 ZINCI OXIDUM» 
 
 The oxide of zinc, in common with all the other combina- 
 tions of the metal, the sulphate alone excepted, which have dur- 
 ing the past few decades been exhibited in affections of the 
 central nervous system, as epilepsy, eclampsia chorea, not infre- 
 quently, like the other metallic salts, manifest undesirable 
 untoward effects, referable mostly to the digestive tract. The 
 doses following which the effects may present themselves may 
 be as small as 0.2 to 0.3 gramme (gr. iij to gr. v). In many 
 persons the symptoms are nausea, disgust, and gastric oppres- 
 sion varying in degree with the individuality of the person and 
 the quantity of food in the stomach, for the irritation of the 
 
ASTRINGENTS CADMII SULPHAS. 65 
 
 gastric mucous membrane is intensified in proportion to the 
 opportunity afforded the zinc salts, either directly or after their 
 solution in the stomach, to form an albuminate on the mucous 
 membrane. Should there be sufficient food present to form an 
 albuminate with all the zinc given, the irritative property of the 
 zinc is almost negatived, inasmuch as the zinc albuminate goes 
 through the regular process of digestion and is taken up into 
 the vascular channels. 
 
 The continued use of small doses of the salts of zinc is to 
 be guarded against, since they are liable, even with the greatest 
 care, to produce ill effects on the different functions. Thus 
 Werneck* found the repeated use of 0.2 gramme (gr. iij) doses 
 of the zinc oxide to produce in his own person, gastric oppres- 
 sion, eructations, slight confusion of thought and later, dizzi- 
 ness and a feeling of bodily exhaustion, and following the fourth 
 dose severe thirst, gastralgia, slight vomiting and a sensation of 
 tension in the limbs. Should the zinc salt reach the intestines, 
 where it may irritate the mucous membrane, diarrhoea is super- 
 added to the above symptoms. Analogous symptoms have been 
 noted by other authors to follow small and long continued 
 doses. It yet remains to be noted that, according to Pareira, 
 the frequent use of medicinal doses of the zinc salts may 
 induce a zinc dycrasia, similar to chronic saturnism, which is char- 
 acterized by obstinate constipation, emaciation and anaemia. 
 
 The symptoms above indicated may certainly be very fre- 
 quently guarded against by administering the zinc salt in sol- 
 uble form, the lactate, for instance, and upon a full stomach. 
 Should the untoward effects have supervened, milk and the white 
 ot eggs may be given, in order that the zinc which may be 
 present may form combinations with them. But special effort 
 must also be made by means of laxatives and diuretics to 
 secure the speedy elimination of the drug from the body. 
 
 CADMII SULPHAS. 
 
 The sulphate of cadmium was employed by Grimaudf as 
 
 *Werneck, Medic. Chirurg. Zeitung 1831, III., p. 317; ref. bei Wibmer 1. c. Bd. V., 
 p. 469. 
 
 tGrimaud, Gazette Medical de Paris, 1851. 
 
66 THE UNTOWARD EFFECTS OF DRUGS, 
 
 an internal remedy in syphilis, chronic rheumatism, etc. It irri- 
 tates to a much higher degree than the zinc salts, the stomach 
 and the intestinal canal, such irritation being, however, only of 
 a transitory nature. Burdach observed after 0.06 gramme (grj) 
 salivation, colic, and hypercatharsis with tenesmus. 
 
 An ointment of the cadmium sulphate produced, according 
 to Grimaud, a pustular eruption similar to that caused by tar- 
 tar emetic. 
 
 BARII CHLORIDUM. 
 
 The chloride of barium which was formerly, on the recom- 
 mendation of Hufeland,* regarded as a specific in the various 
 forms of scrofula, causes sometimes in certain persons and in quan- 
 tities not exceeding the maximum dose (0.12 [grij], the amount 
 daily ingested not exceeding 1.5 gramme [grxxij] ), functional 
 disturbances in organs of the most diverse character. Accord- 
 ing to Lisfranc,f the poisonous action of the barium chloride 
 varies with the climate, inhabitants of southern latitudes toler- 
 ating decidedly larger doses than those living at the north. 
 
 The disturbance of the stomach and bowels are manifest- 
 ed in the nausea, and even vomiting, loss of appetite, colicky 
 pains, oppression in the epigastrium and diarrhcea. Catarrhal 
 irritation of the conjunctiva, the nasal and respiratory mucous 
 membrane — the latter perhaps extending from the pharynx — has, 
 in a few instances, been observed to follow the employment of 
 baryta. 
 
 The prolonged use of medicinal doses may, as Hufeland 
 has observed, intensify the effects already detailed until symp- 
 toms of well-marked gastro-enteritis may supervene, and in 
 addition to this symptoms referable to the central nervous sys- 
 tem, as dizziness, great anxiety, faintness, muscular weakness, 
 trembling and even convulsions. KohlJ observed in one case 
 in which the barium chloride had been administered for twenty 
 four days, salivation, swelling of the salivary glands, a foul 
 odor of the breath and loosening of the teeth. 
 
 It is not improbable that this aggravation of the symptoms 
 
 *Hufeland, Ueber die Natur, Kenntniss und Heilart der Scrofelkrankheit, Berlin, 1819. 
 tLisfranc bei Bernatzik, Encyclopaedic der ges. Heilkunde, 1880, Bd. II., p. 15. 
 $Kohl bei Husemann, Toxicologic, p. 945. 
 
ASTRINGENTS ACIDUM TANNICUM. 67 
 
 by the prolonged use of baryta is due to a cumulative action 
 of the drug, in consequence of its tardy elimination by the 
 urine and faeces. This view is supported by the fact 
 that a demonstrable quantity of the barium chloride is trans- 
 formed in the body into the sulphate, which latter being a sub- 
 stance which is dissolved with difficulty, is deposited at the 
 place at which the change is effected, whence it is slowly elim- 
 inated from the system. In this manner it is possible for an 
 intense activity of the baryta to manifest itself, and one which 
 may continue for a long time after the administration of the 
 drug has been suspended. 
 
 These facts explained an observation of Schwilgue,* who 
 found that when he gave minute doses of baryta, the irritation 
 of the various organs was aggravated after the suspension of 
 the drug, and continued for at least seven weeks thereafter. 
 
 The treatment of the symptoms mentioned consists in the 
 first place in the suspension of the drug. The gastric symp- 
 toms demand such agents as are calculated to allay the inflam- 
 mation. With a view to facilitating the elimination of the baryta 
 diuretics are to be recommended. The employment of a direct 
 antidote, such as the sulphate of sodium or magnesium is indi- 
 cated in only very severe cases. 
 
 ACIDUM TANNICUM. 
 
 The susceptibility to the action of tannic acid varies with 
 the individual. Thus Tully, who for a week took 0.6 grammes 
 (gr. x) of tannin daily, experienced nothing further than slight 
 nausea and anorexia, while Hennig,f after taking but 0.2 
 grammes (gr. iij), experienced pain in the stomach and bowels, 
 a coated tongue, eructation, thirst, tenesmus and an aggravation 
 of a habitual hemorrhoidal congestion. 
 
 Roller]; observed after a large dose of tannin, taken for 
 the relief of a diarrhoea, pain in the stomach and abdomen, 
 violent emesis and a constipation which continued for fourteen 
 days with slight fever. After the constipation was relived the 
 
 *Sehwilg-ue, Matiere Medicale, T. L, p. 409. 
 
 •fHennig, Archiv, f. physiol. Heilkunde, Bd. XII., 1853. 
 
 ^Roller, Wiener Medic. Wochenschrift, 1865, 97. 
 
68 THE UNTOWARD EFFECTS OF DRUGS. 
 
 stools were for a time mixed with blood and pus. This was 
 probably due to a caustic action of the tannin on the gastric 
 intestinal nerve. 
 
 In order to guard against such symptoms with a certainty, 
 and to permit of the prolonged employment of tannin, L. Lewin* 
 recommends the administration of either the albuminate of tan- 
 nin or an alkaline solution of tannin. The first is readily pre- 
 pared by dissolving the quantity of tannin ordered in a little 
 water, precipitating it with a solution of albumen, and then 
 adding an excess of albumen until the albuminate thus formed is 
 dissolved. For a solution of 2 grammes (gr. xxx) of tannin in 
 100 ( J iij) grammes of water, the white of one egg dissolved 
 in 100 ccm ( § iij) of water, and then filtered, is sufficient. The 
 alkaline solution of tannin may be prepared by adding to the 
 solution of the desired quantity of tannin in water, carbonate of 
 sodium, until the reaction becomes feebly alkaline, or by the 
 addition of albumen to it, and by adding the carbonate of sodium 
 until the abuminate of tannin again dissolves. These solutions 
 may be given as follows: 
 
 (1). Tannin albuminate: 
 
 Ifc Solut. acid, tannic, 2 %, 100 grammes (5 iij). 
 
 Adde agitando. 
 
 Sol. Albumin, ovi 100 grammes ( 5 iij). 
 M 
 
 This solution has a milky appearance, a very slightly astrin- 
 gent taste and is well borne by even small children. Should more 
 tannin than 2:100 be desired, the proportion of albumen must also 
 be increased. 
 
 (2). Tannate of Soda : 
 
 IJ Solut. acid, tannic i.o — 5.0 grammes (gr. xv to gr. lxxv) to 150.0 grammes ( § v). 
 Adde solut. sodii bicarb, q. s., ad react, alkalin. 
 
 I 
 
 In this formula the tannin is most readily absorbed. This 
 very slightly alkaline solution must be kept in a well stoppered bot- 
 tle and employed in from one to two days, inasmuch as it is changed 
 under the influence of air and light, into a light-brown, greenish- 
 brown or dark-green color, by the products of , oxidation which are 
 formed in it. 
 
 *L. Lewin, Untersuchungen über Wirkung und Verhalten des Tannins im Thier körper 
 
 Virchow's Archiv, Bd. 81, r88o. 
 
ASTRINGENTS ERGOTINUM. 69 
 
 Alkaline tannin albuminate : 
 
 B Acid, tannic 2.0—5.0 grammes ( 3 ss to 3 ]%). 
 
 Aq. dest. 100.0 grammes ( I iij). 
 
 Adde agitando. 
 
 Album, ovi unus. 
 
 Sodii bicarb, solut. q. s. et fiat solutio limpida. 
 M 
 
 This solution unites in itself the tannin albuminate and the 
 tannate of sodium. It is best adapted to cases requiring the pro- 
 longed employment of tannin. It must be freshly prepared as it 
 does not keep for more than two days. 
 
 ERGOTINUM. 
 
 The extractum secale cornuti of Wiggers, as does also that 
 of Boujeau, produces, now and then, in medicinal doses — 0.2 to 
 0.4 gramme (gr. iij to gr. vj) — sickening taste, irritation of the 
 throat, increased secretion of saliva, nausea, burning in the 
 stomach, abdominal pains, eructations, vomiting and diarrhoea. 
 Associated with certain of these symptoms we may have confu- 
 sion of thought, head ache or sensations of chilliness, dizziness, 
 dilatation of the pupils and also general debility, uncertainty of 
 gait and irregularity of the pulse. Apart from the idiosyncrasy 
 of the patient, the differences in the action of this drug are 
 probably traceable to the variability in the chemical constitu- 
 tion of the preparations employed. 
 
 Following the hypodermic employment of ergotin, first 
 recommended by von Langenbeck* (after the following formula: 
 Ext. sec. corn. Boujeau 2.5 gramme [gr. Ix], spts vini et gly- 
 cerin« 7.5 [3 ij] ), a series of undesirable untoward effects 
 were observed. Von Langenbeck noticed after an injection of 
 0.3 gramme (gr. v.) a glimmering before the eyes and pain 
 in the shoulder. Eulenburgf noticed dizziness and vomiting 
 under similiar conditions. 
 
 The general symptoms were more threatening in a case 
 reported by Rezek,J in which 0.04 gramme (gr. f) of ergotin had 
 been injected. Five minutes after this injection the patient 
 was seized with several general convulsions, the pupils became 
 
 ♦Langenbeck, Berl. Klin, Wochenschr, 1869, p- 117. 
 
 •fEulenburg, Die hypodermat. Injection der Arzneimittel, Berlin, 1875, P« 2 40« 
 ref. bei. Eulenburg, 1. c, p. 244. 
 
yo THE UNTOWARD EFFECTS OF DRUGS. 
 
 dilated, the eyeballs rolled, loss of consciousness supervened, 
 the skin became cool and the pulse disappeared. These symp- 
 toms subsided under cold douches and the internal adminis- 
 tration of ether. Phillipi noticed yawning, labored breathing, 
 dilatation of the pupils, smallness of the pulse, efforts at vomiting 
 and incoherent speech, in a lady to whom hypodermic injections of 
 0.3 grammes (gr. v) doses of dialyzed ergotin were administered 
 for menorrhagia, the symptoms supervening in from 30 to 40 
 minutes after each injection. This condition lasted for one or two 
 hours and was relieved by counter-irritation and the exhibition of 
 analeptics. It was a peculiar fact that the exhibition of ergotin to 
 this lady in the form of pills or suppositories, caused no such 
 untoward effects. 
 
 Hildebrandt* observed symptoms which were milder. Fol- 
 lowing six injections in the case of a female, the patient 
 became dizzy and unsteady of gait ; spasmodic contractions of 
 the flexors of the upper and the lower extremities, nausea and 
 constriction of the chest also occurred. The symptoms disap- 
 peared with the suspension of the drug to return with its 
 resumption. 
 
 Of more frequent occurrence than these general systemic 
 disturbances are the symptoms, of greater or lesser intensity of 
 localized reaction. This is most marked after each hypoder- 
 mic injection at the point of penetration, around which there 
 occurs a painful nodular infiltration which does not go on to 
 suppuration. Hildebrandt,* who employed the plan of injecting 
 ergotin for the relief of fibro-myoma of the uterus, believed 
 that the pain which thus ensues is due to the presence of 
 alcohol in von Langenbeck's solution, which is employed. He 
 employed, on account of this a solution of ext. secale cornut. 
 aq. 3.0 grammes (gr. xlv) to glycerine and water, of each 7.5 
 grammes (3ij), following which he observed less pain, although 
 there also remained persistent nodules of the skin, which were 
 somewhat sensitive. 
 
 Bengelsdorfff saw also as a result of injections of ergotin, 
 after Hildebrandt's formula — the ergotin in which is not 
 fuliy dissolved but remains principally in suspension — a fre- 
 
 *Hildebrandt, Berl. Klin. Wochenschr., 1872, p. 298. 
 'rBen^elsdorff, Berl. Klia. Wochenschrift, 1874, p. 21. 
 
ASTRINGENTS FOLIA SALVIA. yjr 
 
 quently decidedly painful and not infrequently positively phleg- 
 monous, non-suppurating inflammation, encircling to a greater 
 or less circumference the point of injection. Accompanying 
 this there was usually a hard, nodular swelling, varying in size 
 with the size of the injection, which frequently remained for 
 eight days and over. The nodules could not be prevented 
 either by deep insertion of the cannula or by friction. 
 
 FOLIA SALVIA. 
 
 The popular domestic remedy, sage leaves, occasionally 
 employed internally in the form of an infusion, as an astringent, 
 may under certain circumstances, as Pidoux realized in his own 
 experience, give rise to unpleasant symptoms. This observer 
 experienced, after taking a cold infusion, a profuse perspira- 
 tion, which continued for several hours, a bitter taste, a dry- 
 ness of the mouth and throat, constipation and increased fre- 
 quency of the pulse. These symptoms show the effect to be 
 due to a joint action of the tannin and ethereal oil contained 
 in the plant. 
 
 PIX LIQUIDA. 
 
 Tar, which, in the form of tar-water, was formerly exten- 
 sively administered as an internal remedy in skin diseases, and 
 also in bronchial affections, is now most frequently employed 
 externally, either in its pure state as an embrocation in ecze- 
 ma, or, in the form of tar-water, as an inhalation. In either 
 form it may, should any very considerable quantity of its active 
 principles be absorbed, give rise to results at once not contem- 
 plated and deleterious. These may be either generalized or 
 local in their nature. 
 
 The systemic effects manifest themselves as the result of 
 smaller quantities taken, in nausea, and an inclination to vomit, 
 while larger quantities give rise to headache, a sensation of 
 dizziness, and vomiting or diarrhoea with abdominal pains. 
 
 The local symptoms consist of an inflammatory irritation of 
 the sound skin, an irritation which is intensified when ths 
 skin is altered by disease, and which is perhaps due to the 
 carbolic acid or creasote, or perhaps to the empyreumatic 
 
72 THE UNTOWARD EFFECTS OF DRUGS. 
 
 ingredients which are contained in the tar. As a result of this 
 local irritation there occurs, according to Hebra* an acne of 
 a hard, red, bullet-like nature, which may last as long as the 
 influence of the tar continues. After the acne has once 
 developed it yields very slowly, requiring an average of from two 
 to four weeks for its involution, when, however, it disappears 
 without any remnant of scars or pigmented spots. Hebra's 
 modification of Wilkinson's tar and sulphur ointment (sulph. 
 prsecip., picis liquidae, aa 180 parts; cretae albae, 120 parts; 
 saponis dornest., adipis, aa 500 parts), for scabies is liable to 
 excite eczema, either by being spread over the sound skin, or 
 by reason of the hypersensitiveness of some persons to oint- 
 ments. 
 
 Urine voided after inunction with tar often shows changes 
 which are probably due to the carbolic acid contained in the 
 tar, which is thus shown to have been taken up into the cir- 
 culation. Pettersf has found the urine in such cases to be of 
 a deep blackish-brown, and emitting the peculiar odor of tar. 
 On distilling the urine with sulphuric acid, he obtained, in 
 the distillate, besides carbolic acid, certain heavy, dark-brown 
 oily drops resembling those of creasote. As bearing on this 
 fact it should be mentioned that after the taking of carbolic 
 acid, the dark urine which is occasionally voided contains hydro- 
 chinon, which is a product of the oxidation of carbolic acid. 
 
 As a point of diagnostic value may be mentioned the 
 observation of Jacubasch, that after inunction with a tar oint- 
 ment (tar 1 part, vaseline, 10 parts) in eczema, albumen was 
 distinctly present in the urine, which disappeared with the sus- 
 pension of the remedy, again to appear with its renewal. 
 
 OLEUM JUNIPERI EMPYREUMATICUM OIL OF CADE. 
 
 The oil of cade, the product of the dry distillation of 
 the juniperus oxycedrus, not infrequently, by its external 
 application, excites an inflammatory action. KleinhausJ who 
 applied the undiluted oil, after the usual method, directly to 
 
 *Hebra, Lehrbuch der Hautkrankheiten, I., p. 594. 
 tPetters, Präger Viertel jahrschr., 1855, Jahrg. XII., Bd. 3. 
 JKleinhaus, Aügesz. Medic. GcEtraizeit., 1863, No. 24, p. 185. 
 
ASTRINGENTS OLEUM JUNIPERI EMPYREUMAT1CUM. 73 
 
 acute or chronic eczematous or impetiginous surfaces, observed 
 that when the skin was even only partially inflamed, a pretty 
 well defined swelling and redness with severe pain was devel- 
 oped as an effect of the oil, and that the hair follicles 
 shortly afterwards appeared on the skin as nodules of the size 
 of hempseed, an affection which is perfectly identical with tar 
 acne. 
 
 Bazin observed in patients who had employed the inunc- 
 tion of oil of cade in psoriasis, an eruption of isolated or 
 grouped papules, which were tolerably large, slightly confluent 
 and hard, with an areola, particularly on such parts of the 
 body as are well covered with hair. They were located on 
 the skin with broad nodular bases, and terminated in a point 
 and sometimes in a vesicle. At the point there was always found 
 a black spot, which was due to the presence of a hair. These 
 papules hardly ever went on to suppuration, and even when 
 scratched pus formed only at the points. The seat of the affection 
 is in the hair follicles. Bazin gave to it the name Cade-sycosis 
 (sycosis cadi que). 
 
 In many cases, according to Kleinhaus, the swelling and 
 inflammation spread from the point of original application over a con- 
 siderable area, when they may give the appearance of an erysipela- 
 tous dermatitis ; the lymphatic vessels and glands may even become 
 involved in the inflammatory process. 
 
 Water dressings and soothing ointments are sufficient, in con- 
 nection with the suspension of the application, to allay the slighter 
 forms of this irritation first noted. 
 
 For the relief of the pain in the variety characterized by wide- 
 spread dermatitis, warm baths are recommended, the patient 
 remaining in them for from half an hour to an hour at a time ; opiates 
 may also be given internally, in small doses. Kirchheim* has 
 reported an observation which shows how, in consequence of exten- 
 sive painting with tar, severe symptoms may be developed in many 
 individuals. A soldier who suffered from eczema squamosum, was 
 painted with tar on the extensor side of all extremities, once a day 
 for three days. On the fourth day there ensued vomiting, head- 
 ache, want of appetite and pain in passing urine. Then followed 
 
 *Kirchheim, Berlin Klinische Wochenschr., 1872, No. 19, p, 224. 
 
74 THE UNTOWARD EFFECTS OF DRUGS. 
 
 watery exudations from the skin, presence of albumen in the urine, 
 pains in the renal region, and, finally, anasarca and oedema of the 
 lungs. The latter was cured. The other symptoms, which proved 
 to be those of morbus Brightii, complicated with gastric catarrh, 
 still continued for a relatively long period, and the oedema and the 
 albiiminaria disappeared only slowly. 
 
 An untoward effect of oil of cade, of rather secondary import- 
 ance, is the brown coloring of the skin which it is difficult to get rid 
 of. To obviate this the oil may be given in form of soap. For this 
 purpose the following may be prescribed : Butyr. cacao. 12.0, Ol. 
 cadini 9.0, Ol. lini, Lig. ammon. caustici. ää 4.0. Of this 4 to 10 grm., 
 according to the size of the affected part, may be rubbed in. This 
 soap may be easily washed off with water. 
 
 ACIDA. 
 
 The dilute, inorganic acids, as sulphuric, hydrochloric, phos- 
 phoric, nitric, and the fruit acids — citric, tartaric, etc. — cause by 
 their long continued employment, disturbances of digestion. The 
 appetite fails, the tongue becomes coated, the teeth ache, gastric 
 oppression and eructations supervene, and occasionally there is 
 salivation and diarrhoea. 
 
 Attending the prolonged use of dilute nitric acid there frequent- 
 ly occur, according to Mitscherlich*, erosions of the gums and 
 tongue, the gums bleeding very readily, and the teeth becoming 
 loose — symptoms which must be regarded as due to the local 
 action of the acid. 
 
 ACIDUM CARBOLICUM. 
 
 The fact that in some persons the exhibition of carbolic acid 
 even in medicinal doses is capable of causing general nervous dis- 
 turbances, has been familiar since the drug was first employed. 
 Declatf observed as a result of its use, a slight headache which lasted 
 for from 5 to 15 minutes, spreading over the entire head and return- 
 ing with each repetition of the drug, being most intense in the 
 frontal region in some persons, and in others being more severe in 
 the occipital. Neumann noticed heaviness and fullness (eingenom- 
 
 *Mitscherlich, Lehrb. d Arzneimittellehre, Bd. Ill, p. 81. 
 fDeclat, Traite de l'Acide ph<2nique, Paris, 1854. 
 
ASTRINGENTS ACIDUM CARBOLICUM. 75 
 
 mensein) of the head, weakness of the legs, dizziness, the appearance 
 of rings before the eyes, a sensation as of crawling insects and 
 profuse sweating, to follow the administration of the acid in the pill 
 form. 
 
 It is only in later years that the profession have 
 become aware of the fact that under certain circumstances 
 exceedingly deleterious and even fatal consequences may follow 
 the application of carbolic acid to wounds. Observers 
 are almost unanimously of the opinion that idiosyncrasy 
 on the part of the patient enters as a factor in such 
 cases. The nature and extent of this idiosyncrasy are unknown but 
 •that it is the chief if not the sole influence in the causation of these 
 untoward effects, there is no doubt. 
 
 Busch,* therefore, classes carbolic acid with those drugs which, 
 while they are valuable in medicinal doses, are poisonous to certain 
 persons, the reason for whose sensitiveness is not yet known, when 
 taken in quantities which innumerable other persons may take with- 
 out injury. 
 
 The absorption of carbolic acid may take place under any 
 method of its administration. After the application of the acid 
 either by frictions to the sound skin or by keeping it in contact with 
 the surface of a wound or mucous membranes, it may be detected in 
 the tissues, in the blood and in the secretions and excretions. 
 Through either of these modes of application the condition to wmich 
 the name of "carbolism" has been given may be induced, and by 
 which is understood the abnormal action of carbolic acid induced by 
 one or more doses of the drug. 
 
 Formerly the passage of brown or greenish brown urine, or of 
 urine which, though light when voided, became of a blackish brown 
 or deep black color when exposed to the air, was regarded as the 
 most reliable criterion of carbolism. Bill held that the carbolic 
 acid in the animal body is transformed into chinone and that this 
 imparts to the urine the black color. More recently, however, the 
 cause of the discoloration has been explained by Baumann and 
 Preusse.f They showed by analysis of such carbolized urine that 
 it contained hydrochinon, in the form of hydrochinon sulphuric acid, 
 
 *Busch, Berlin. Klin. Wochenschrift, 1880, p. 304. 
 
 tBaumann und Preusse, Archiv, f. Anatomie, u. Physiologie, 1879, p. 245. 
 
76 THE UNTOWARD EFFECTS OF DRUGS. 
 
 in addition to this coloring matter. According to this view, a not 
 inappreciable amount of the carbolic acid introduced into the 
 body is converted, by oxidation, into hydrochinon. A portion 
 of this is by further oxidation changed in the system into 
 indefinite coloring matter which is excreted by the urine to 
 which it imparts its color, but the major portion appears in 
 the urine as hydrochinon sulphuric acid. The dark discoloration 
 which in many samples of urine occurs only on standing, is caused 
 by the splitting up of the eliminated hydroch. and the freeing in 
 this manner of the hydrochinon, which, under the influence of the 
 atmosphere, is oxidized into colored compounds. It follows from 
 this that the greater the alkalinity of the urine the more rapidly 
 does the change take place. 
 
 It has been established through accurate observations that this 
 carbolized urine is not always pathognomonic of deleterious unto- 
 ward action of the drug ; it is more frequently the case that a num- 
 ber of but slightly characteristic but dangerous symptoms combine 
 to constitute carbolism and to determine a fatal result. Küster,* 
 who demonstrated the poisonous properties of carbolic acid, particu- 
 larly in antiseptic treatment of wounds, indicated as the reason why 
 so few fatal results of the use of the drug are reported the fact that 
 the uncertainty of the symptomatology has permitted the accidents to 
 be classed as shock, collapse, etc. He observed a fatal termination in 
 four or five of such cases, He mentions general debility and exist- 
 ing disease as predisposing to the occurrence of deleterious action 
 of carbolic acid. Von Langenbeckf noticed a severe case of carbolic 
 acid intoxication in a boy, abscesses in whom had been treated with 
 a carbolic paste ; in two other cases death followed the employment 
 of the "dry carbolated dressing" of slight operations. RoseJ also 
 reported a case in which the application of carbolized cotton, which 
 was moist and smelt very strongly of carbolic acid, was followed by 
 gangrene of a finger, a wound in which had previously been healing 
 kindly. 
 
 A case accurately observed by Busch (1. c.) may be mentioned 
 here as characteristic of the symptomatology of carbolism: A boy 
 suffering from an abscess under the trochanter was operated on for 
 
 *Küster, Berl. Klin. Wochenschr. 1878, No. 48. 
 
 tLangenbeck, eo 1. loco. 1878, No. 48. 
 
 ariose, Verhandlungen d. Gesellschaft d. Aerzte in Zuri:h, 19 Dec, 1874. 
 
ASTRINGENTS ACIDUM CARBOLICUM. 77 
 
 its relief. During the few minutes consumed by the operation he 
 was kept under a two-per-ceiTc. carbolic spray, and the wound was 
 afterwards dressed with carbolic gauze. During the day following 
 the operation he was seized with vomiting, which was attributed to 
 the chloroform which had been employed. On the following morn- 
 ing the bandages were removed under the carbolic spray ; during 
 the day there was nausea, and in the evening there were symptoms 
 of collapse and carbolic acid was detected in the urine. The pulse 
 became small and frequent and the temperature sank to 35.5°C. 
 The frequent vomiting made it impossible to administer remedies by 
 the stomach, and in spite of the hypodermic and external application 
 of analeptics, the boy died fifty hours after the operation. 
 
 Lücke* noticed nephritis as one of the local effects of carbolic 
 acid; it disappeared, however, with the suspension of the drug. E. 
 Wagnerf investigated more accurately the changes in the kidneys. 
 He applied carbolic acid to a case of gangrene of the leg and on 
 the following day detected the drug in the urine. This latter con- 
 tained numerous casts of medium width, and chiefly hyaline, inter- 
 spersed with a few fatty and red blood corpuscles, or renal epithe- 
 lia. A post mortem. microscopical examination of the kidneys 
 showed the uriniferous tubules to be dilated, their epithelia large, 
 projecting far into their cavities and fatty, while the cavities 
 contained numerous lumps of protoplasm and jagged glistening- 
 bodies. 
 
 In our opinion the influence of the spray has not been suffi- 
 ciently regarded in the discussion of the question of the absorption 
 of carbolic acid in the antiseptic treatment of wounds by means of 
 carbolic acid. OlshausenJ maintains that absorption is more apt to 
 occur by the skin during the first carbolic acid dressing, and Lan- 
 genbuch] holds that the liability to absorption through this channel, 
 as compared with that which takes place from wounds, is under- 
 estimated, and believes that less is absorbed through the cleansing 
 of wounded surfaces than is taken up by the normal skin. As facili- 
 tating absorption he mentions the soaping and shaving and scraping 
 
 *Lücke, ßerl. Klin. Wochenschr., 1878, p. 248. 
 t'A" agner, Deutches Archiv, f. Klin. Medicin, i83o, p. 
 JOlshausen, Berl. Klin. Wochenschr., 1878, p. 248. 
 Langenbuch, eod. loc, 1878, p. 414. 
 
7& THE UNTOWARD EFFECTS OF DRUGS. 
 
 of the skin, through which the sweat glands are laid open, as well as 
 the positive bathing of the skin with the carbolic spray. 
 
 The latter operates also in still another manner. It has been 
 demonstrated by Röhrig* that finely pulverized watery solutions of 
 substances are absorbed by the skin, which does not happen when 
 the solution is simply laid upon it. The experiments bearing on 
 this matter, performed under every conceivable precaution show- 
 ed that when watery solutions of, for instance, the iodide and 
 the ferrocyanide of potassium were applied to the skin in the form 
 of spray, these substances made their appearance in the urine. It 
 was also found possible to stupefy and to partially paralyze animals 
 by solutions of morphia and woorara applied in the same 
 manner, thus showing that substances may be introduced 
 into the system, through the skin, more readily and in 
 larger quantities when applied by means of an atomizer than 
 when simply laid in contact with it. The opinion that a very large 
 percentage of the carbolic acid in the carbolic spray is taken up by 
 the skin, and particularly through the sweat glands, is thus fully jus- 
 tified. It also clearly follows that children, in whom the powers of 
 resistance are naturally weak, are, under these circumstances, much 
 more liable to carbolic poisoning than adults ; the surface of the 
 wound acted on by the spray bearing also in their case a 
 much larger proportion to the surface of the body, a proportionately 
 larger quantity of the carbolic acid is, cetczris paribus, taken into the 
 system. The deleterious predisposing influence of soaping, brush- 
 ing and shaving — manipulations also condemned by Lister — to 
 untoward effects must, however, not be underestimated. 
 
 It clearly follows from what has been said that the introduction 
 of carbolic acid into cavities lined with mucous membrane may be 
 followed by carbolic poisoning. The administration of enemata con- 
 taining carbolic acid, and the irrigation of the uterus and the vagina 
 with the drug, are to be particularly considered in this connection. 
 Thus Praetoriusf observed buzzing, in the ears, dizziness, weakness, 
 and attacks of fainting in a woman in whom the rectum was 
 washed out with a dilute solution of carbolic acid, these symp- 
 toms supervening after a third of the following solution had been 
 
 *Röhrig, Physiologie der Haut, 1878, p. 116. 
 tPraetonus, Berl. Klin. Wochenschr, 1879. p. 214. 
 
ASTRINGENTS THYMOL. 79 
 
 given : % litre ( 3 viij) of a one per cent solution in }s litre ( 5 x) of 
 warm water. Kottmeyer* reports symptoms quite similar after the 
 employment of an enema of a half per cent solution of carbolic acid 
 in a lad suffering from oxyurides. 
 
 Olshausen (1. c.) noticed symptoms of profound intoxication 
 after irrigation of the uterus, and Löhleinf observed, after two 
 days, symptoms of poisoning in puerperal women, in whom 
 vaginal and uterine injections were employed. Finally, Edwards]; 
 saw hiccup, nausea, chills, and anasarca, with diminution or sup- 
 pression of urine, delirium and death, following the introduction of 
 cotton tampons saturated with carbolic acid into the vagina. He 
 attributes these symptoms to an acute nephritis and consequent urae- 
 mia, caused by carbolic acid. 
 
 The treatment of carbolism is to be varied with the manner of 
 the introduction of the acid into the system. A directly antidotal 
 procedure is usually without effect. Husemann and Ummethum 
 recommend saccharated lime (Calcaria saccharata) as an antidote, 
 the lime uniting with the acid to form an insoluble and compara- 
 tively innocuous compound. The sulphate of sodium, also, it is 
 claimed, is antidotal through its union with the carbolic acid to 
 form a non-poisonous phenol sulphate. 
 
 Should the drug have been introduced in an enema and only a 
 short time have elapsed between such introduction and the employ- 
 ment of means of relief, irrigation of the bowel is to be commended 
 as the first procedure. In the case of carbolism, as it is commonly 
 observed, and due to absorption of the acid through the skin and 
 the surface of wounds prompt symptomatic treatment of the general 
 symptoms is indicated. The internal or hypodermic exhibition of 
 excitants, energetic irritation of the skin by sinapisms and friction, 
 and the fardaic current will be found valuable aids to this end. To 
 combat the vomiting, small oieces of ice and vegetable astringents 
 should be given. 
 
 THYMOL. 
 
 Thymol, contrary to carbolic acid, combines with its exceed- 
 ingly antiseptic and antifermentative properties, which were first 
 
 *Kottmeyer, eod. Ice. 1879, p. 501. 
 
 tLohlein, eod. loc. 187S. p. 25. 
 
 ^Edwards, Virchow, Hirsch's Jahresber, 1869, I., p, 349. 
 
8o THE UNTOWARD EFFECTS OF DRUGS. 
 
 demonstrated by the experiments of L. Lewin,* and which are by no 
 means sufficiently appreciated, perfect safety in its internal and 
 external use. Although it is used extensively for dressing of wounds, 
 syringing of serous cavities and abscesses, etc., no i?ijurious effect 
 upon the /mictions of the body has ever been observed. 
 
 After the internal administration of a solution of i gramme (gr. 
 xv) of thymol to 1,000 gramme (i quart) of water, a burning sensa- 
 tion in the mouth and gastric region is observed as an untoward 
 effect. Should the drug, however, be taken in substance or pills in 
 large doses of i to 1.5 grammes (gr. xv to gr xxiij) within 24 hours, 
 the burning in the epigastric region increases; the latter itself 
 becomes tender on pressure and finally the burning sensation devel- 
 opes into pain, which may last several days after the drug has been 
 discontinued. According to Bälzf, perspiration is sometimes 
 observed and occasionally a transient buzzing of the ears and partial 
 deafness. After doses of 2 to 3 grammes (gr. xxx to gr. xlv.) which 
 produce a decrease of temperature of 2 C. (3-6 F.) Balz observed, 
 in rare cases, dizziness and delirium. 
 
 *L. Lewin Das Thymol ein Antisepricum und Antifermentativum, Virchow's Archiv. 
 Bd. 65. 
 
 iQ'dlz Archiv der Heilkunde, 1877, p. 344. 
 
ALTERATIVES HYDRARGYRUM. 
 
 Alteratives. 
 
 HYDRARGYRUM. 
 
 Among the drugs which, through their extensive therapeutic 
 application, are frequently productive of symptoms annoying to the 
 physician, and still more so to the patient, mercury occupies a 
 leading position. The affections which follow its internal and 
 external administration are varied in their character. They com- 
 prise structural lesions of the skin and mucous membranes, as well 
 as purely functional disturbances of various organs not traceable to 
 any appreciable organic change, e. g., of the salivary glands and 
 parts controlled by the peripheral and central nervous systems. 
 This condition has been enominated " hydrargyrosis ' or mercu- 
 rialism. 
 
 To obviate the numerous external inconveniences as well as the 
 directly deleterious untoward effects, so frequently traceable to the 
 traditional modes of the application of mercury, several new methods 
 have of late years, and especially in the treatment of syphilis, been 
 devised for the administration of, mercury. The inunction of mer- 
 curial ointment, which was formerly applied in alarming doses — even 
 to 500 grammes ( 5 xvj) daily — is still productive of the greatest 
 number of undesirable untoward effects, perhaps because of the fact 
 that the quantities of mercury taken into the system through this 
 means, are too small to destroy the syphilitic virus in a short time, or 
 because the quantities absorbed through its long continued use, are, 
 though small, sufficiently large to cause injurious effects in persons 
 predisposed to the action of the drug. 
 
 The prolonged use of calomel is also, as has been demonstrated 
 by Radziejewski,* sometimes accompanied by undesirable results, 
 through its retention in the caecum, where, by prolonged contact 
 with the chlorides of sodium and ammonium, it is changed into cor- 
 rosive sublimate and thus causes erosion and ulceration. 
 
 For this reason the plan of treating syphilis by hypodermic 
 
 *R.adzijjewski 1 Archiv, für Anatomie und Physiologie, 1870, p. 22, 
 
82 THE UNTOWAÜD EFFECTS OF DRUGS. 
 
 injections of the bichloride of mercury, as introduced by G. Lewin,* 
 and in which almost all the mercury is taken into the circulation 
 may be regarded as a veritable advance, though even in this manner 
 of applying it untoward effects are occasionally noted. More recently 
 two other combinations of mercury have been recommended by 
 Bambergerf with a view to obviating the local irritation which so 
 frequently follows the hypodermic employment of the corrosive sub- 
 limate. One of these is a solution of the albuminate of mercury, 
 prepared by combining ioo ccm. ( 5 iij) of a filtered solution of albu- 
 men (1 volume white of egg to 3 or 4 of water) 60 ccm. ( 3 ij) each 
 of a five per cent, solution of corrosive sublimate and a twenty 
 per cent, solution of common salt, and 80 ccm. ( 5 ijss) of 
 distilled water. One ccm. of this solution, which becomes clear on 
 standing two days, and filtering, contains 0.01 (gr. }i) of bichloride 
 of mercury in combination with albumen. This solution causes no 
 local irritation. 
 
 This author recommends even more highly a solution of pep- 
 tonized mercury, prepared in the following manner: One gramme 
 (15 gr.) of soluble, commercial peptone is dissolved in 50 grammes 
 ( 3 iss) of water and the solution filtered. To the filtrate add 20 
 ccm. ( 3 v) of a 5 per cent, solution of corrosive sublimate, and to 
 dissolve the resulting precipitate 15 to 16 ccm. ( 3 ss) of a 20 per 
 cent, solution of common salt. Sufficient water is added to the 
 resulting solution to make 100 ccm. ( 3 iij), which after standing for 
 several days is filtered. Each ccm. of the solution contains 0.01 
 gramme (gr. T /e) of mercury in the form of the peptone combination. 
 The elimination of the mercury by the kidneys is said to be very 
 prompt when this fluid is given hypodermically. The chief value is, 
 however, ascribable to the method, the cure being more promptly 
 effected through it and the system is thus kept under the influence 
 of mercury for but a limited time. 
 
 We shall open our consideration of the untoward effects of mer- 
 cury with a description of the 
 
 Changes in the Skin. — The affections which manifest themselves 
 in the skin after the exhibition of mercury, in many persons, are ery- 
 thema and eczema (eczema mercuriale). The latter was first noticed 
 
 *G. Lewin, Die Behandlung der Syphilis mit subcutaner Sublimatinjection, Berlin, 1869. 
 tBamberger, Wiener medic. Wochenschrift, 1876, No. 11 u. No. 4, p. 1074. 
 
ALTERATIVES HYDRARGYRUM. 8$ 
 
 by Benjamin Bell* and Pearson, while Alleyf was the first to accu- 
 rately describe these affections, and to apply to them the name 
 hydrargyria. Hebra,J and Kussmaul || also, failed to recognize in it 
 any characteristic peculiarity of either course or symptoms, and 
 regarded it as identical with ordinary eczema, while Bouchardat 
 regards it as a disease sui generis 
 
 According to older authors mercurial eczema, which 
 ordinarily occurs after the external application of mercury, 
 may also follow its internal exhibition. Thus Alley (1. c.) 
 noticed it in an adult as a result of 0.12 gramme (gr. ij) 
 of calomel, and in a girl as a result of 0.18 gramme (gr. 
 iij) of the drug. Ascherson observed it in a young man after 
 the injection of 0.24 gramme (gr. jv). More recently Fournier 
 reported an exanthematous eruption, and Engelmann§ described a 
 case in which after the injection of 0.45 gramme (gr. viij) of calo- 
 mels, in doses of 0.15 gramme (gr. ijss), and two hours after the last 
 dose, an erythema on the head, with symptoms of fever, swelling of 
 the face, etc., began to develop. The eruption spread, in the course 
 of a single night, over the whole body and was attended by a sensa- 
 tion of intense burning, itching and great debility. After four days 
 it subsided and the skin of the face and breast peeled off in large 
 flakes, as in scarlatina. The appetite and strength were restored 
 very slowly. This same person declared that he had frequently 
 before had the same symptoms after the internal administration of 
 mercury. 
 
 Hebra, on the other hand, declares against the possibility of 
 such a development of the exanthema, regardless of the preparation 
 of mercury which may have been employed. It is, at most, very 
 seldom met with and appears only in virtue of individual predispose 
 tion. 
 
 This eruption, however, not infrequently appears after the 
 shorter or longer external exhibition of mercury, and especially after 
 the inunction of blue ointment. In some it appears as axonsequence 
 of minute doses of the drug, while in others it does not occur after 
 
 *B. Bell, Treatise on Gonorrhoea virulenta and Lues venerea, IL, p. 228. 
 t Alley, Observations on the Hydrargyria or that vesicular Disease arising from the exhi- 
 bition of Mercury. Dublin, 1804. 
 
 $Hebra, Hautkrankheiten I., p. 452. 
 
 HKussmau',, Untersuchungen über den constitutionellen Mercuriahsmus, Wurzburg, 1861. 
 
 §Engelmarn, Berlin. Klin. Wochenschr, 1870, p. 647. 
 
84 THE UNTOWARD EFFECTS OF DRUGS. 
 
 even large doses and their long continued employment. Alley found 
 it to occur with twice the frequency in men as in women, which fact 
 he accounts for by the additional fact that men find the necessity of 
 employing of blue ointment much more frequent than obtains in the 
 case of women. 
 
 Hebra defines eczema mercuriale as a disease of the skin char- 
 acterized by a multitude of red tubercles, vesicles, or small pustules 
 which are very thickly disposed. Alley distinguishes three forms of 
 eczema which he classifies, according to the severity of the attack 
 and the mode of their development, as follows: 1, Hydrargyria mitis; 
 2, Hydrargyria febrilis; and 3, Hydrargyria maligna. Such a differ- 
 entiation is, however, very arbitrary, inasmuch as the three forms are 
 identical in all essential particulars. 
 
 The exanthem sometimes occurs after but one, though more 
 frequently after several applications of the blue ointment, ■ and is 
 •attended by intense itching and burning, its seat being most frequent- 
 ly in the inner surface of the thighs, on the scrotum or vulva, and 
 thighs, being seldom found on the upper extremities, back or face. 
 In many persons the eruption is attended from its beginning to its 
 disappearance with fever, headache, sleeplessness and gastric dis- 
 turbances. The parts of the skin affected are covered with dark red 
 spots of different sizes, and disappearing readily on pressure, which 
 soon become confluent over a large surface, on which appear numer- 
 ous vesicles of the size of a pin head, seldom larger, containing a 
 fluid which is at first clear but later becomes opaque; these vesicles 
 may either burst or dry up. Usually, after four or five days, the 
 eruption, which sometimes resembles that of measles and again that 
 of scarlatina, grows pale and the epidermis peels off either in branny 
 scales or in larger flakes. Recovery is usually complete after from 
 eight to fourteen days. 
 
 In some cases the patient suffers more severely, the whole body 
 or large areas of it being affected with the eruption. In these cases, 
 too, the fever runs high, and there is angina of the fauces; the 
 numerous pustules either bursting spontaneously or having been 
 scratched open, emit their irritating and ill-smelling contents which 
 further aggravate the trouble, causing painful excoriation and swell- 
 ing of the denuded skin and the formation of crusts. In such 
 aggravated cases of eczema there is a repeated desquamation of the 
 epidermis, and also, though rarely, a falling of the hair. The latter 
 
ALTERATIVES HYDRARGYRUM. 85 
 
 fact is especially noteworthy, inasmuch as it is the only symptom 
 referable to the skin, which is observable in animals which have 
 been subjected to the long continued action of mercury. 
 
 In addition to these affections of the skin, mercury is also said, 
 in very many cases, to cause by its external application gangrenous 
 ulcers, and even to give rise to gangrene. We must, however, con- 
 cur with Gwalter* that such an effect of mercury has not beer 
 satisfactorily proven. 
 
 Regarding the manner of the development of the mercurial 
 exanthem, as a result of the inunction with blue ointment, nothing 
 is definitely known. There are two possible methods of its occur- 
 rence, both being dependent on our conception of the manner in 
 which absorption takes place. According to one theory the mercury 
 applied by inunction is vaporized by the heat of the body, in which 
 form it finds its way into the lungs and thence into the various parts 
 of the body. Assuming this to be true, the affections of the skin 
 which have been described can only occur secondarily, the drug 
 being first taken into the circulation and there transformed into 
 the bichloride or oxide of mercury. Should we, however, commit our- 
 selves to the theory that the rubbing of mercury with fat converts 
 it into an oleate, and that it is absorbed as such by the skin, 
 we must believe that the eruption is due to the direct irrita- 
 tion of the drug. This irritation unduly prolonged may lead 
 to a hyperemia of the capillaries of the skin, with swelling of 
 the epidermis and sebaceous glands, and give rise, as a result, to 
 exudation, tubercles and vesicles. The latter is probably the usual, 
 if not the only manner in which the skin disease is developed. This 
 is the more acceptable view, since the oleic acid combinations with 
 mercury, as, for instance, the corrosive sublimate, may produce their 
 corrosive effects in this manner. On the other hand the rapid 
 introduction of the preparations of mercury, even of the corro ve 
 sublimate, into the circulation, as by hypodermic injection, does not 
 give rise to either erythema or eczema. It appears from this that 
 for the occurrence of the latter symptoms it is necessary that a solu- 
 ble salt of mercury should act on the different layers of the skin, as 
 is the case under frequent applications of blue ointment, which con- 
 tains combinations of mercury with a fatty acid. This theory does 
 
 F Gwalter, Ein Fall von Quecksilber Vergiftung. Inaug.-Dissertation Zürich, 1877. 
 
86 THE UNTOWARD EFFECTS OF DRUGS. 
 
 not, however, exclude the possibility of the occurrence of changes in 
 the skin through the internal exhibition of mercury, as seems likely 
 in view of later observations. 
 
 As an argument against the view of the specificity of the affec- 
 tions of the skin following the application, advanced by the anti- 
 mercurialists, so-called, it is sufficient, without entering into subtle 
 deductions, to direct attention to the numerous cutaneous eruptions 
 referred to in this work, produced by substances of the most hetero- 
 geneous nature. These reveal a most complete analogy among 
 themselves, and the only specificity which they have in common is a 
 direct or reflex action on the skin. 
 
 The treatment of mercurial eczema consists in the immediate 
 suspension of the drug, and the local application of emollients, as 
 oil, ointments, or vaseline. 
 
 The second untoward effect of the employment of mercury, 
 which calls for notice is the salivation or stomatitis which occurs 
 in from 30 to 40 per cent, of all cases. In most cases in from 24 to 
 48 hours, and in rare cases in two or three hours, after the internal 
 exhibition or external application of mercurial preparations in med- 
 icinal quantities salivation sets in, either alone or accompanied by 
 redness, swelling, loosening and tenderness of the gums. Salivation 
 may also precede the latter symptoms and may be so excessive as to 
 amount to as much as five kilos (five quarts) during twenty-four 
 hours, and continuing during the night, may deprive the patient of 
 his sleep. It lasts generally from three to ten days, but may con- 
 tinue longer, and is attended by an offensive odor from the mouth 
 and a subjective metallic taste. There is nothing characteristic in 
 the saliva itself. Its specific gravity may rise to 1059 at the onset 
 of the salivation, but falls later on. After a certain time it develops 
 an offensive odor, is strongly alkaline in its reaction and acts as an 
 irritant on the part over which it flows. The gums, the mucous 
 lining of the cheeks and palate, the tongue, the soft palate and the 
 tonsils undergo changes in degrees varying with the individuality of 
 the patient, the duration of the exhibition of the mercury and the 
 quantity administered. The changes may embrace all the stages 
 from a simple hyperaemia to ulceration and necrosis of the tissue. 
 
 In the milder degrees of mercurial stomatitis the margins of 
 the gums, which bleed very readily, are covered with a yellowish, 
 slimy substance which emits a foul odor. The teeth may become 
 
ALTERATIVES HYDRARGYRUM. 
 
 loose and the ulcers, which in the more aggravated forms manifest 
 a disposition to spread both in depth and breadth, have generally 
 even, dentated margins, and are covered at the bottom with a thin 
 yellowish secretion. Not infrequently a swelling of the lymphatic 
 glands of the neck is also observed. 
 
 The subjective general disturbances are very serious, even in 
 the milder attacks of mercurial salivation. Sleep is prevented by 
 the constant necessity of either expectorating the saliva or swallow- 
 ing it. In addition to this there is the pain caused by the contact 
 of the food with the inflamed or ulcerated parts. The swelling of 
 the tongue, which is not an infrequent occurrence, interferes with 
 articulation, all of which taken in connection with the febrile con- 
 dition frequently present, the anorexia, headache and bodily weak- 
 ness make the condition of the patient a very tormenting one. 
 After this condition has existed for several days, the drug having 
 been suspended in the meantime, the salivation begins to diminish 
 in quantity and the morbid changes which have been caused in the 
 mucous lining of the mouth begin to improve, and existing ulcers 
 begin to heal, leaving, when the process is complete, radiate 
 cicatrices. In cases in which the destruction of tissue has been 
 excessive, several weeks and even months are required for complete 
 restitution. 
 
 There are two circumstances which observation has shown to pre- 
 dispose to the occurrence of affections of the mouth, and particu- 
 larly salivation, in mercurialization, viz.: i, Uncleanliness of the 
 mouth, and 2, a weak, anaemic constitution or serious antecedent 
 disease. 
 
 The changes above indicated may also be excited by the hypo- 
 dermic administration of mercury. This circumstance, taken in con- 
 nection with the fact that mercury may be detected in the saliva, 
 probably as an organic compound, proves that the drug is eliminated 
 through the salivary glands, regardless of the manner of its adminis- 
 tration. It is in this way that salivation and changes of the tissue in 
 the cavity of the mouth are explained, since it must be conceded that 
 the immense quantities of saliva which are secreted are due to either 
 the direct irritating action of the mercury on the parotid and sub- 
 maxillary glands, or to reflex nervous excitation of them, and fur- 
 thermore that the saliva thus secreted, if it contain sufficient mer- 
 cury, must, if its action on the tissue be sufficiently prolonged, 
 
THE UNTOWARD EFFECTS OF DRUGS, 
 
 inflame or erode those parts of the buccal cavity which it bathes. 
 It is to be observed that early infancy presents a certain immu-- 
 nity against the production of salivation in consequence of the 
 administration of calomel. The reason for this immunity lies pro- 
 bably in the absence of chloride of sodium from the food (milk) 
 which nurslings receive. A transformation of calomel into corrosive 
 sublimate may thus either not take place at all or to a very slight 
 degree. The susceptibility of this age, even to vapors of mercury, 
 is exceedingly small. Grapin* reports that a woman, who, with her 
 14 months old child, was constantly exposed to mercury vapors, 
 became sick with a severe stomatitis, whilst the child, though it was 
 nursed by its mother, remained healthy. Oesterlen demonstrated 
 by experiments, that young cats, which were treated with mercurial 
 ointment, acquired neither salivation nor stomatitis. 
 
 The treatment of the mercurial affections of the mouth must, in 
 the first place, be prophylactic. To this end it is necessary that 
 patients should keep their teeth clean, and especially that they should 
 remove from carious cavities the products of decomposition. Inas- 
 much as the poorly nourished have a special predisposition to these 
 affections, care must be taken to secure proper nutrition. After the 
 suspension of the mercury the exhibition of potassium chlorate, first 
 recommended by Herpin, still occupies the first place among both 
 prophylactic and curative measures. It affects most rapidly and 
 most effectively the morbid processes in the mouth. It is given in a 
 2 to 3 per cent solution, employed as a mouth-wash and gargle, and 
 also in quantities of from two to three grammes (gr. xxx to gr. xlv.), 
 daily, internally. In cases of uncomplicated salivation an astrin- 
 gent wash (tannin, gr. xv to gr. xlv, in water 3 jvss), is beneficial. 
 Alum in solution (one to one and a-half per cent,), may also be 
 employed in addition to the potassium chlorate, as a moüth-wash. 
 When inunction is being employed, Siegmund recommended the 
 application of tar to the gums, both as a preventive and curative meas- 
 ure in stomatitis mercurialis. When the gums bleed easily they may 
 with benefit be painted with tr. myrrhae, with equal parts of tr. 
 myrrhae and tr. kino, or with tr. kranierise. The latter substances 
 may also be employed to cleanse foul ulcers of the mouth when it is 
 preferable not to employ disinfectants, distinctively such as carbolic 
 
 *Grapin, Archives, gener., 1845, iv. p. 331. 
 
ALTER A.TIVES HYDRARGYRUM. 8 
 
 acid in strength of 0.5 — 1.0 to 150 of water, or thymol 0.5 to 500 of 
 water. 
 
 The untoward effects of mercury hitherto described are by far 
 the most frequent of occurrence, and may succeed large and medium 
 doses as well as small doses. Notwithstanding the fact that their 
 duration is short they are classed with that collection of symptoms 
 to which the term mercurialism has been attached. They merely 
 indicate that mercury has been absorbed, that it is circulating in 
 the system and that it is causing certain functional or anatomical 
 changes on either its channel of entrance or exit. True constitu- 
 tional hydrargyrosis or mercurialism, however, that is the condi- 
 tion of disturbed nutrition, sensation and even motion which seri- 
 ously interferes with the economy of the system, and which most 
 frequently follows the prolonged use of small closes, does not disap- 
 pear so readily; it is due, probably, to elimination and deposit of 
 the metal in the different organs. These symptoms obtain in their 
 most characteristic form among workmen, who employ mercury 
 regularly in their business, and are described in a classic manner by 
 Kussmaul (1. c.) They occur less frequently as a result of the 
 medicinal employment of the metal, and in the following considera- 
 tion of the subject only such effects will be treated of as are indis- 
 putable, and no mention will be made of the exaggerated charges 
 which have been urged by the opponents of the drug. 
 
 The disturbances of nutrition are always associated with changes 
 in the general condition and are almost wholly provoked by direct 
 effect of the mercury on the alimentary canal or its secretory glands, 
 and not, as was formerly held, through some mysterious power it pos- 
 sesses of causing the organs to melt and the blood to decrease.. 
 There are several facts to prove that the stomach and intestines are. 
 affected. 
 
 G. Lewin (1. c.) observed symptoms of gastro-enteritis, pain and 
 a burning sensation in the region of the stomach, especially on pres- 
 sure, and diarrhceaic stools frequently tinged with blood as a result 
 of the subcutaneous injection of mercury, and more particularly when 
 the ordinary dose had been exceeded. Together with these symp- 
 toms the general condition of the patients was bad, they being pale, 
 complaining of weakness, suffering from debility and having their 
 sleep disturbed by frightful dreams. This effect on the intestinal 
 
90 THE UNTOWARD EFFECTS OF DRUGS. 
 
 tract is explained in the belief that the metal is eliminated through 
 this channel even after hypodermic exhibition of the drug. 
 
 Corroborative of the changes above indicated, as affecting the 
 alimentary canal, might be adduced the experiments on animals as 
 well as the post mortem appearances in man, revealing evidences of 
 catarrh in its various stages, and even ulcerations, especially of the 
 ileum and caecum. The anorexia, emaciation, emesis, gastric and 
 abdominal pains and decline of bodily health, frequently observed 
 in those who have been subjected to a prolonged course of small 
 doses of mercury, are explicable in the same manner. This explana- 
 tion is especially satisfactory when it is remembered that the elimina- 
 tion of the metal, together with the tangible anatomical changes in 
 the stomach and intestines above noted, causes an impairment of 
 the activity of the digestive juices. In consequence of the gradual 
 decrease or loss of appetite we find that such persons not only take 
 a smaller quantity of food, but that that which they do take is 
 assimilated much more slowly coincidently with the onset of a 
 catarrhal condition of the intestines. Under certain conditions this 
 assimilation is so slow that the nutritive processes are kept up at the 
 expense of the body itself. 
 
 This conception of the matter is well sustained by the result of 
 investigations of tissue metamorphosis by Von Boeck, in a syphilitic 
 who had been treated by means of inunctions of mercurial ointment. 
 He discovered no change in the decomposition of the albumen dur- 
 ing the treatment. In this case, however, the operation of the mer- 
 cury was continued only sixteen days — a period which is generally 
 too short for the appearance of changes, of the nature of that 
 described, in the digestive tract. It is necessary — and this is particu- 
 larly to be borne in mind — for the occurrence of disturbances of 
 nutrition, that there should either be a predisposition on the part of 
 the patient or a prolonged action of mercury on the digestive tract. 
 
 As an accompaniment of disturbances of nutrition, and seldom 
 appearing alone, there is a change in the urine which is an index to 
 the condition of the kidneys. It not infrequently contains albumen 
 although in but insignificant amount. Inasmuch as the kidneys, as 
 has been demonstrated, are the channel through which a portion of 
 the mercury is eliminated, the cause of the presence of the albumen 
 is probably traceable to the irritation of the drug on the uriniferous 
 tubules. The view that this albumen does not originate in structural 
 
ALTERATIVES HYDRARGYRUM. 
 
 changes in the kidneys but is really the mercury which is thus elimi- 
 nated in the form of an albuminate, is not supportable, the fact being 
 that albumen is seldom found in the urine of persons under mer- 
 curial treatment, while the drug itself is constantly present. 
 Albumen, however, appears when the drug is given in poisonous 
 doses, and then also substantial changes in the urinary tract are 
 demonstrable. Sugar has also, in addition to albumen, been found 
 in the urine after the use of mercury. This was proven by the 
 experiments of Saikowski* and Rosenbachf on animals. In this 
 regard mercury bears a certain analogy to other poisonous sub- 
 stances as morphia, carbonic oxide, etc. 
 
 The therapy of the general disturbances of nutrition consists 
 in the removal of the deleterious agent and in a suitable dietary. 
 Besides this improvement in the hygienic condition of the patient, 
 appropriate non-irritating food must be given, with a view to correct- 
 ing the possible changes in the alimentary canal, and eliminating the 
 drug as rapidly and completely as possible from the body. The 
 latter may be effected by inducing active diuresis, by means of 
 vapor and sulphur baths, but particularly, as recommended by 
 Melsens,J by means of iodide of potassium, after the employment of 
 Avhich larger quantities of mercury are discharged through the 
 kidneys than under ordinary circumstances. 
 
 The disturbances of nutrition and of the general condition 
 described, as has been observed to be the case in chronic poisoning 
 by other active metals, are frequently but the precursors of func- 
 tional disturbances in the general nervous system. Occasionally 
 some of the latter also appear during the course of the ordinary 
 treatment by inunction. 
 
 The disturbances of sensation are evident not only in an altera- 
 tion of certain physical attributes and affections, but also as demon- 
 strable peripheric functional changes in the organs of special sense, 
 as those of the sense of touch and pain, etc. The individuality of 
 the person attacked plays an important part in this matter ; in some 
 persons we find nervous affections of a centric nature and of greater 
 or lesser degrees of severity, while in others the disturbance mani- 
 fests itself in the form of either peripheral anaesthesia or hyperaes- 
 
 * Saikowski, Virchow's Archiv. Bd. xxvii., p. 346. 
 
 t Rosenbach, Zeitschrift f. naturw. Medicin. 3. Reibe, xxxiii. 
 
 % Melsens, Annal. de Physique et de chimie, III. S., T. 26. 
 
92 THE UNTOWARD EFFECTS OF DRUGS. 
 
 thesia. The following central disturbances have been observed to 
 'follow the hypodermic injection of mercury: A condition of physi- 
 cal erethism, manifesting itself in a bad temper or increased 
 irritability, or diffidence or bashfulness. These manifestations are 
 associated with pallor of the countenance, asthmatic respiration, 
 and even irregularity of the heart's action and great debility. 
 These were first noted by Pearson after mercurial inunctions, and 
 have been also noted by G. Lewin in individual cases. Bauer* and 
 Kussmaul observed the most marked cases among the workmen 
 engaged in the manufacture of mirrors. Kussmaul maintains that 
 these symptoms are especially characteristic of the action of mer- 
 cury. Their continuance may result in sleeplessness and other 
 disturbances of the sensation due to increased excitability of the 
 brain, especially of the cortical layer of the cerebrum, such as 
 hallucinations and even delirium, which, however, are but temporary 
 and cannot properly be classified as independent forms of disease. 
 There frequently appears pain in the joints, in the face and 
 teeth, or, the converse of this, viz., paralysis of sensibility, may 
 supervene, manifesting itself as veritable anaesthesia and analgesia. 
 
 In addition to these changes in the sphere of sensation there 
 are other mercurial affections which manifest themselves as disturb- 
 ances of motion. These are most frequently observed in the tremor 
 mercurialis, which appears most frequently in the chronic form of 
 mercurialism, but may come on paroxysmally. At first only the 
 arms and hands are attacked, but in cases of the long continued 
 action of the drug the lower extremities and the muscles of the trunk 
 also suffer. An examination of the muscles thus affected with refer- 
 ence to their electric excitability shows them to be normal, though 
 they may be reduced to a condition of great debility. In this regard 
 as also in the absence of paralysis this mercurial affection of the 
 muscles differs from that which occurs as a result of lead poisoning. 
 
 A sensation of dizziness which not unfrequently supervenes on 
 the hypodermic and even epidermic administration of mercury would 
 seem to imply a simultaneous disturbance of sensation and motion. 
 In some of his patients to whom he had administered hypodermic 
 injections of maximal quantities of mercury, G. Lewin observed 
 marked debility and attacks of dizziness so severe as to necessitate 
 
 *Bauer, Ueber Mercurialismus Inaugural Dissertat. Erlangen, i860. 
 
ALTERATIVES HYDRARGYRUM. 93 
 
 the patients laying hold on something for support in order to 
 prevent their falling. These vertiginous seizures with the symp- 
 toms of faintness, continued even after the patients were put to bed. 
 The identity of these symptoms following the hypodermic injection 
 of large doses of corrosive sublimate with the attacks of dizziness 
 supervening on the long continued use of mercury, and which were 
 formerly termed eclampsia mercurialis, is complete. 
 
 The symptoms, which are referable to the central nervous sys- 
 tem are undoubtedly due to a direct influence of the mercury, which 
 Kussmaul has denominated a brain poison, on the parts affected 
 and in such a manner that the more transient symptoms manifest 
 themselves in cases in which the drug is merely suspended in the 
 circulation, while those of a chronic nature are due to a deposit of 
 the mercury in the nerve centres and in the sensory and motor 
 tracts. As supporting the latter statement we would refer to the 
 observations of Pickel,* who, through dry distillation of the brain 
 of a patient who had been subjected to prolonged mercurial treat- 
 ment, was able to demonstrate the presence of the metal. Laudererf 
 made a similar demonstration in the case of a person who had been 
 poisoned by mercury. There is, up to the present time, an absence 
 of investigation with a view to determine the extent to which the 
 metal thus effects a deposit in the spinal cord, and the peripheral 
 distribution of the nerves. It must be conceded that the tran- 
 sient as well as the permanent changes induced by mercury are 
 primarily due to changes of a chemical nature in the central and 
 peripheral nervous tissue, although the changes may not be demon- 
 strable under the microscope. Microscopical examination of these 
 parts after the exhibition of mercury has, as yet, been productive of 
 but insignificant results. Pleisch and Koch, respectively, found a 
 darker color of the gray and white substance. 
 
 The prognosis of these affections, and particularly of tremor 
 mercurialis, is dependent on the duration of their continuance. It 
 may be favorable when this continuance has been of short duration, 
 but it is doubtful, if not positively unfavorable, if the affection has 
 continued for any considerable length* of time. 
 
 The therapy must be conducted on the same general principles 
 that obtain in the treatment of general disturbances of nutrition. 
 
 *Pickel, Büchner, Toxicologic, 1822, p. 433. 
 
 tLauderer, Buchner's Repertor. III. Reihe, Bd. 25, p. 248. 
 
94 THE UNTOWARD EFFECTS OF DRUGS 
 
 and must be directed to the removal of the mercurial influence, and 
 to the most complete elimination of the metal from the system. In 
 addition to this cold frictions, douches and sea-baths, and in the 
 condition of erethism, the use of nervines are indicated. The elec- 
 tric current might be tried in conditions of anaesthesia and anal- 
 gesia. 
 
 ACIDUM ARSENIOSUM. 
 
 The similarity of the physiological action of the various com- 
 pounds of arsenic extends to the untoward effects which attend the 
 single or repeated exhibition of the drug. We shall, therefore, con- 
 sider only the arsenious acid, which may be regarded as the typical 
 preparation of arsenic. 
 
 Binz and Schulz* have recently shown that when arsenic acid 
 is digested for several hours at a temperature of 38 ° C, 
 with fresh fibrin, fresh brain substance, white of egg or 
 pancreas, it appears in the dialysate as arsenious acid. 
 They also demonstrated the presence of arsenious acid in the 
 fluid contents of the intestines in animals after the exhibition of 
 arsenic acid, and, vice versa, the presence of arsenic acid after 
 arsenious acid had been introduced. According to these observers 
 the processes of oxidation and reduction take place in the glands, in 
 the protoplasm of the nerve centres and in all other cells in which 
 the conditions for the development of such action obtain. Through 
 this continual exchange of nascent oxygen in the molecules of living 
 albumen the oxidation of the living cells is more active than obtains 
 in the case of normal tissue change, and it is upon this local 
 increased oxidation that all the phenomena of the effects of arsenic 
 depend. 
 
 This explanation, also renders more comprehensible a 
 portion of those phenomena which appear as a result of the internal 
 or external exhibition of arsenic, and which lie beyond the domain 
 of physiological action. It is especially applicable as an explanation 
 of the influence which is exerted on the skin of both man and 
 animals by the internal administration or external application of the 
 drug. The ancient physicians were even familiar with this modus 
 operandi of mercury. Thus Paulus Aeginetaf writes: "Arsenici vis 
 
 *iJinz <*n j Schulz, Archiv für experimentelle Pathologie und Pharmakologie, Bd. XL, p. 200. 
 +Paulus Acgincta, Opera ed J. Guinterius, Lugüuni, 1551, p. 479. 
 
ALTERATIVES — ACIDUM ARSENIOSUM. 95 
 
 est caustica, utuntur eo in pilis abolendis, quod si diutius adhaesertt 
 etiam cutem ipsam attingit." The application of arsenic to the 
 healthy skin, either in a watery solution, or as an ointment or paste, 
 and maintained in contact for some time, gives rise to an inflam- 
 matory action, attended by a stinging or burning pain and a slight 
 fever, and vesicles or pustules may develop on the reddened surface 
 without the appearance of any symptoms of general absorption. 
 Should the inflammation, however, become aggravated there may 
 set in, according to Falck,* an erysipelatous swelling upon which 
 may appear a discolored sanguinolent eruption which may mark 
 the beginning of general poisoning, after the same manner, as will 
 presently be described, that these also appear as a result of the 
 internal exhibition of the drug. The same results follow the applica- 
 tion of the drug to the surface of wounds. The hair generally falls 
 out on affected parts. The exanthemata heal through the shedding 
 of the epidermis of the inflamed surface, in the form of large flakes. 
 
 Changes of different kinds, but of an analogous nature, have 
 been observed to follow the internal exhibition of arsenic in ordinary 
 medicinal doses, and especially when given in the form of Fowler's 
 solution. The variety which these changes may assume is manifest 
 in the, it must be confessed, somewhat homoeopathic description of 
 Imbert-Gourbeyre:f 
 
 " Eruptions petechiales ou ecchymoses eruptions papuleuses' 
 ortiees, vesiculeuses, erysipelateuses, pustuleuses .... telles- 
 sont les principales formes de l'arsenic, exanthematogene dans ses 
 manifestations a la peau." According to this, individual authors vary 
 in their descriptions of arsenical eruptions. Thus MacnalJ reports 
 an eruption resembling that of measles in a case to which he had for 
 only three days given 0.18 gramme (gtt. iij) of Fowler's solution. 
 Pareira observed, in a gouty patient for whom he had prescribed 0.01 
 gramme (gr. }£) of the arseniate of potash daily, on third day and 
 after a restless night with headache and a sensation of increased 
 warmth of skin, a very red eruption of the face, neck, the upper 
 part of the trunk and flexor surfaces of the joints and like- 
 wise an ©edematous condition of the eyelids. The eruption 
 
 * Falck, Dxe klinisch wicnügen Intoxicationen. Virchow's Pathologie und Therapie, Bd. 
 
 I-, p-254- 
 
 t I nbert-Gourbeyre, Gazette, medic, de Paris. 1862, p. 227, und Etude sur quelques symp 
 tomes de 1'arsetnc. Pars, 1862. 
 
 X Macnal, Mecical Times and Gazette, 1868. 
 
<)6 THE UNTOWARD EFFECTS OF DRUGS. 
 
 disappeared between the second and fifth day, while desqua- 
 mation in the form of flakes continued for nearly two months. 
 The administration of arsenic after all these symptoms had disap- 
 peared aroused them again, when they were also accompanied by 
 salivation. The eruption, according to Imbert-Gourbeyre, appears 
 by preference on the neck, face and genitals, but likewise on the 
 hands. The papules which constitute the eruption are of the size of 
 a pin's head, at first distinct in groups but later becoming united 
 and forming patches of the size of a lentil or larger. He also, like 
 Pareira, describes the eruption as lasting from six to eight days, but 
 observed only a branlike desquamation of the epidermis. 
 
 The minuteness of the dose which is sufficient to cause an 
 eruption is exemplified in a case reported by Bazin,* in which 
 erythematous pustules were developed after the exhibition during 
 fifteen days of 0.05 gramme (gr. -|) of arsenic. 
 
 A report by Wyssf of the case of a boy in whom he noted an 
 area Celsi (porrigo decalvans) after the prolonged internal use of 
 arsenic is of interest in this connection. He makes use of this 
 observation to establish the view that this affection is due to a dis- 
 turbance of nutrition in the hair follicles and not, as has recently 
 been maintained, to the development of a fungus. 
 
 A contemplation of the effect of arsenic on the skin, as here 
 detailed, must confirm one in the view that the changes which are 
 induced by the internal and the external exhibition of arsenic are 
 identical. In such case there must, therefore, after the internal 
 administration of arsenic in many persons, be a permeation of the 
 skin and also a partial elimination of it through this organ. This 
 is in fact the case, as has been demonstrated by various authors. 
 
 Chatin J succeeded in demonstrating the presence of arsenic in 
 the contents of a blister which was raised by cantharides on a person 
 who had been poisoned by arsenic. Barella|| established the fact 
 of direct elimination of arsenic through the sweat glands, partic- 
 ularly when the skin acted vicariously for the kidneys, while Ber- 
 geron and Lemattre § showed that the arsenious acid combinations 
 with the alkalies may be eliminated with the perspiration, but that 
 
 *Bazm, Lecons sur les affections cutan^es artificielles. Paris, 1862, p. 196. 
 
 f Wyss, Archiv für Heilkunde, Bd. xi, 1870, p. 17. 
 
 :tChatin, Journ. de Chimie Medicale, 1848, p. 328. 
 
 HBarella, Journ. de Mödicine de Bruxelles Juillet, 1863. 
 
 §Bergeron and Lemattre, Archive gener. de Medecine, 1804, vol. ii, p. 173. 
 
ALTERATIVES ACIDUM ARSENIOSUM. 97 
 
 the combination of this acid with iron is so split up in the system 
 that the iron is given off in the urine, the arsenic appearing as an 
 arsenite of potassium in the perspiration. 
 
 In the light of these facts we are constrained to regard the 
 affections of the skin which we have considered, as due to the direct 
 local effect of the arsenic, and that regardless of the manner of the 
 exhibition of the drug, and we must, furthermore, with Binz and 
 Schulz, seek their causation in an increased local combustion in the 
 living cells. 
 
 Inasmuch as the arsenical eruption, as has been remarked, dis- 
 appears spontaneously in several days, any medical means for its 
 relief are scarcely called for. In cases in which the dermatitis has 
 spread at all extensively or has assumed a malignant character, it 
 will be found necessary, in addition to the administration of diu- 
 retics with a view to eliminating the drug through the kidneys, to 
 resort to local antiphlogistic applications, and, in the event of the 
 presence of the products of decomposition to apply antiseptics. 
 
 The internal employment of arsenic for a longer or shorter 
 period is, conditioned on the individuality of the patient, more 
 frequently followed by irritation of the mucous membrane of the 
 mouth, throat and stomach, and consequent digestive disturbances, 
 than by the symptoms detailed in the foregoing. The tongue under 
 such circumstances is heavily coated, and there appears a disagree- 
 able burning in the mouth, thirst, oppression in the region of the 
 stomach, anorexia, belching and even vomiting. The mouth affec- 
 tion may assume the form of either angina or stomatitis. Very 
 small doses of arsenic are also not infrequently productive of pro- 
 fuse salivation. Harles* was the first to note this fact, which he 
 did in the following language: " Diutius continuato arsenici usu 
 satis parco excitatur haud ita raro salivas aliquanto largior secretio, 
 sive ptyalismi levior species." More recently Imbert-Gourbeyre, 
 Trousseau and Morgantif have, among others, reported similar 
 effects. 
 
 This irritation of the mucous membrane of the mouth not in- 
 frequently extends to the respiratory passages, and we then have a 
 dry cough, bronchitis and hoarseness. 
 
 *Harles, De usu arsenici, Norimbergae, 1811, p. 301. 
 tMorganti, Gaz, Medic, de Paris, 1852. 
 
98 THE UNTOWARD EFFECTS OF DRUGS. 
 
 Should the nasal mucous membrane be attacked we have a 
 burning sensation in the nose, coryza, a dry catarrh, or in rare 
 cases, as was first noted by Heim,* epistaxis. Should the mucous 
 membrane of the nose, the tear ducts and the conjunctiva become 
 involved through an extension of the catarrhal process (and this 
 happens quite frequently) we have lachrymation, photophobia, 
 amblyopia, swelling of the eyelids and the other, including the 
 objective, symptoms of conjunctivitis. An icteric discoloration of 
 the sclerotic — a quite common symptom in xanthopia from arsenical 
 poisoning — is very seldom observed. 
 
 In some persons headache, buzzing in the ears and dizziness 
 occur as evidences of nervous disturbance. 
 
 It remains to be mentioned in conclusion, that certain French 
 authors, as Charcotf and DevergieJ have advanced the statement 
 that anaphrodisia not infrequently occurs as a result of the use of 
 Fowler's solution. This suspension of sexual instinct disappears on 
 the discontinuance of the drug. 
 
 The treatment of the symptoms detailed consists in a prompt 
 suspension of the drug and the administration of demulcents to the 
 mucous membranes affected. Inasmuch as all of the pathological 
 processes disappear in a short time after the discontinuance of the 
 drug, it is scarcely necessary to institute any antidotal treatment, 
 such as the exhibition of hydrated magnesia or the hydrated sesqui- 
 oxide of iron. 
 
 It is necessary, from a prophylactic point of view, that arsenic 
 should not be given on an empty stomach, that the ordinary doses 
 be not too rapidly increased, and, above all, that the use of drug 
 should not be too long continued. 
 
 AURI CHLORIDUM. AURI ET SODII CHLORIDUM. 
 
 The chloride of gold, as also the officinal chloride of gold and 
 sodium which was much employed and highly praised as a specific 
 in syphilis ||, very frequently, according to the observations of 
 Chrestien,§ and in doses of even 0.003-0.006 (gr. -fa to gr. ^), gives 
 
 *Heira, Vermischte Schriften, 1836, p. 302. 
 
 ^Charcot, Bullet, de Therapeut, lxvi., p. 529. 
 
 JDevergie, Eod. loc. lxvii., p. 175. 
 
 ILrgrand, Bulletin de Therapeatique, De"cembre, 1846. 
 
 §Chrestien, De la methode iatraleptique Ilieme ödit. Pans, 1803. 
 
ALTERATIVES PHOSPHORUS. 
 
 99 
 
 rise to a feeling of heat and burning in the skin, gastric disturb- 
 ances, colic and diarrhoea. The chloride of gold and sodium 
 causes, even in doses which are below the standard maximum dose, 
 according to Wibmer, headache, sleeplessness, dryness of the mouth, 
 a feeling of oppression in the region of the stomach and diarrhoea. 
 Others have noted in increased flow of urine, salivation and 
 increased sexual power, as a result of the use of this drug. 
 
 The gastric disturbances referred to are explained in the gold 
 salts and by the ready solubility of the double compounds of the 
 chlorides of gold and sodium in the alkaline chlorides. They mani- 
 fest the closest similarity to the disturbances observed as effects of 
 other powerful metals, and are due to the irritation of the tissues, 
 the mucous membranes of the primae viae more particularly, by the 
 by the ingested drug. 
 
 PHOSPHORUS. 
 
 Even a single small dose (0.002 gramme [gr. ^L] ) of phosphorus 
 is capable of causing in some persons, who, for personal reasons, can- 
 not tolerate the drug, nausea and vomiting, with a feeling of oppres- 
 sion or pain in the region of the stomach, diarrhoea attended 
 with tenesmus, and in rare cases jaundice which may last, it is 
 said, for weeks and even months. The variability in the opera- 
 tion of this drug is, perhaps, due in some cases also, to the 
 manner of its exhibition, inasmuch as phosphorus taken in 
 the form of pill or in oil remains longer in the stomach than 
 when it is given in a menstruum, which facilitates its absorption, as 
 chloroform, etc., and this long continuance of the absorptive process 
 predisposes to the irritation of parts with which the drug lies in 
 contact. Through an avoidance of this cause of irritation, by dis- 
 solving the drug in a solution of chloroform and administering it in 
 capsules, Dujardin-Beaumetz* was enabled to employ it uninterrupt- 
 edly for from eight toten days, and in doses of from 0.003-0.004 
 gramme (gr. ^-gr. tV)> b3fore an y symptoms of digestive disturb- 
 ance developed, and such symptoms as then ensued disappeared 
 with the temporary suspension of the drug or the diminution of its 
 dose. Felix, f who treated methodically certain pulmonary affections, 
 
 * Dujardin-Beaumetz, Wiener Medicinbche Wochenschrift, i86S,p. 767. 
 
 tFelix, De Taction physiologique et therapeutique du Phosphor pur. Bruxelles, 1881, p. 91 
 
IOO THE UNTOWARD EFFECTS OF DRUGS. 
 
 as emphysema, tuberculosis, etc., with phosphorus, cautions against 
 the employment of excessive doses. The commencing dose, accord- 
 ing to him, should be 0.0005 grammes (gr. ^fa) and gradually in- 
 creased to 0.003 gramme (gr. -J-). He recommends the emulsion 
 
 and the pill, made with a combination, in each dose, of 0.01 0.02 
 
 gramme (gr. -J. to gr. 1) of muriate of morphia, as the more eligible 
 forms of administration. Should untoward effects occur in spite of 
 these precautions, the milk of magnesia (carbonate of magnesia 
 given in gum-water) should be given as an aperient. Small doses 
 of bismuth subnit. with opium may be given for the gastric pains. 
 
 IODINIUM. 
 
 In consequence of the extraordinary curative powers of iodine 
 and its compounds, and on account of its peculiarly wide range of 
 therapeutic application, the attention of physicians was, even at an 
 early day (1820), called to certain changes in the body which occa- 
 sionally occur as a result of the exhibition of the drug. It was, it 
 is true, a considerable time before these were recognized as the 
 untoward effects of iodine, and the controversies as to the existence 
 of such a thing as an " iodine disease," or " iodism," or whether the 
 symptoms are traceable to other causes, fill many a page of the 
 literature on pharmacology. Goitre, in particular, among other 
 diseases, was formerly subjected to internal and external treatment 
 with iodine, and consequently the abnormal effects of the drug were 
 frequently observed in connection with this affection. As a result 
 of this fact there was no lack of authors* who denied the occurrence 
 of such effects of the drug when it was given for other affections, 
 and also attributed the symptoms which occur during the iodine 
 treatment of goitre, to " the absorption of the organic substances 
 present in the goitre." But the occurrence of iodism was also com- 
 batted on more common sense grounds. Thus Hjaltelinf instanced 
 the fact that the inhabitants of Iceland, particularly those living on 
 the coast, employ as a principal article of diet the algae, belonging to 
 the class of laminaria, which are so rich in iodine as to cause them 
 to constitute a source from which the drug is manufactured. Many 
 
 * Roser, Ueber die SD^en. Jodkrankheit, richtiger Krankheit der vertriebenen Kröpfe 
 Würtemb. Medic. Correspondenzbl. 1844, No. 31, und Arch. f. physiol. Heilkunde, Bd. VII. 
 1848, p. 74. 
 
 t Hjaltelin, Allgem. Medic. Centralzeitung, 1853, p. 745. 
 
ALTERATIVES IODINIUM. IOI 
 
 persons consume as a diet from 200 to 250 kilos (437 to 457 lbs.) 
 of these dried plants annually. Since 50 kilos of these algae yield 
 at least 250 grammes ( 3 viij) of iodine, these people consume an 
 aggregate of from one to one-and-a-quarter kilo (2t to 2}4 lbs.) of 
 iodine, equal to about 1% kilo (3% lbs.) of iodide of potassium, 
 annually. In spite of this large consumption of iodine, Hjaltelin 
 was unable to discover any symptoms of iodism. But although the 
 inference from these facts is clear, they should not be accepted as 
 conclusive, for, not to mention the fact that the proportion of iodine 
 contained in the algae as here stated is five times greater than it 
 really is, it must be remembered that, as in the case with other veg- 
 etables, only a small proportion of them is taken up by the fluids of 
 the system, much the largest portion being discharged with the 
 faeces as refuse. It will thus be seen that these coast dwellers appro- 
 priate only a very minute proportion of the iodine, which is very 
 firmly incorporated in the plants. It would lead us too far to 
 recount at this place, all the other objections which have been raised 
 in this connection. It is now a well established fact that iodine and 
 its salts, by its single or repeated internal or external administration, 
 in doses of different size, are capable of causing changes in various 
 organs, or in the general system, but only in those who are pecu_ 
 iiarly susceptible to its influence. 
 
 The external application of only such preparations of iodine 
 as contain the iodine in a free state, is productive of deleterious 
 untoward symptoms. Preparations of this nature are such oint- 
 ments of iodide of potassium as have turned yellow, Lugol's solution 
 or the 
 
 Tincture of Iodine. The physiological local action of the 
 tincture of iodine upon the healthy skin, the mucous membranes, 
 and serous cavities is familiar. It is identical with that of iodine 
 vapor. The sound skin is reddened by the irritation which it 
 causes, and there is a feeling of heat which developes into a burn- 
 ing and pricking sensation; at first it becomes yellow but under 
 repeated applications the color becomes of a dark brownish red, 
 when it dries up and becomes wrinkled and eventually peels off in 
 flakes. Associated with this normal effect there are, not infre- 
 quently, incidental symptoms either in the immediate seat of applica- 
 tion or at some remote part, such symptoms taking the form of an 
 exanthematous affection, resembling measles, or of a papular, pus- 
 
I02 THE UNTOWARD EFFECTS OF DRUGS. 
 
 tular or even vesicular nature which soon heals, with desquamation, 
 on suspension of the drug. Thus A. Simon and Regnard* among 
 others observed after the inunction of tinea capitis in children 
 with a mixture of iodine and glycerine, the appearance of an exten- 
 sive papular eruption on the face and other parts of the body. This 
 observation is verified by Badin.f He could never cause albu- 
 minuria in adults by painting the skin with iodine, while its applica- 
 tion to a normal surface .no larger than can be covered by the 
 hand, has excited this affection in children eight or nine years of 
 age. He assigns the cause of this difference in effect to an 
 increased facility of absorption in the skin of infants. This increase 
 of absorptive power permits of the entrance of iodine as such into 
 the circulation, while in adults, in whom it is absorbed more slowly, 
 it enters the system in the form of the iodide of potassium or 
 sodium. This explanation is, however, not satisfactory in view of 
 the disturbances, which will be described below, which the iodide of 
 potassium induces in the urinary organs. In addition to this an 
 observation of JacubaschJ must be adduced as evidence against this 
 limitation of the appearance of albuminuria. He noted the appear- 
 ance of albumen in the urine, not only in children after painting 
 them with iodine (for the relief of psoriasis, swelling of the glands, 
 etc.), but also in a girl twenty-five years of age to whom an exten- 
 sive application of the tincture of iodine had been made for the 
 relief of an abdominal enlargement. The albuminuria appeared 
 and disappeared in this case with the application and suspension 
 of the drug. Zesas§ reports a still more remarkable case, which 
 occurred in a patient forty-one years of age, and in which albumen 
 was observed in the urine after four applications of iodine to an 
 inflamed knee. This disappeared with a discontinuance of the 
 iodine, but returned again after the drug had been reapplied for 
 three days. 
 
 It is self-evident that the local effects of this drug on such 
 portions of the skin as are deprived of their epidermis, and on the 
 mucous membranes and the surface of wounds, must be more 
 intense, as must also be the local changes and subjective symptoms 
 
 *Simon u. Regnard, Gaz. Medic, de Paris, 1874, p. 262. 
 
 iBadin, De l'albuminurie consecutive aux applications de teinture d'iodechez l'ent, fan 
 Paris, 1876. 
 
 $Jacubasch, Charite^Annalen Jabrg. vi, 1881. 
 §Zesas, Wien. Medicin. Wochenschr. No. 18, 1882. 
 
ALTERATIVES IODINIUM. 
 
 thus induced. The pain which results from the irritation, which 
 may even amount to cauterization, although very transitory in its 
 nature, is nevertheless very severe. The iodine coagulates existing 
 secretions of wounded surfaces and serous cavities, through direct 
 combination with the albumen or albuminoid substances which 
 they contain, and may thus excite active inflammation with conse- 
 quent exudation or suppuration. In such event eruptions may also 
 appear on remote parts of the body. This circumstance proves the 
 fact that iodine may be absorbed from the place of its application, 
 and after its absorption act on the skin. 
 
 But absorption after its external application manifests itself in 
 another and still more unpleasant manner, viz., by the appearance 
 of more remote effects on certain organs and their functions, as also 
 through a series of general constitutional symptoms. These are, 
 therefore, in a measure identical with the symptoms which frequently 
 present after the internal exhibition of the compounds of iodine. 
 Simon and Regnard (1. c.) saw coryza and epistaxis occur, in addi- 
 tion to the papular eruption already mentioned, as results of the 
 inunction of iodine. They, moreover, also observed in fourteen 
 cases four cases of albuminuria in connection with the presence of 
 iodine in the urine. The albumen disappeared and reappeared with 
 the suspension and renewal of the drug. Buckell* reports the 
 case of a lady in whom a very light application of the tinc- 
 ture of iodine to a tumor occurring between the thoracic and 
 cervical vertebra, was followed by pain and a feeling of oppression 
 in the epigastric region, with trembling, weakness, profuse perspira- 
 tion, dribbling of urine and inability to maintain the erect posture. 
 The administration of analeptics and the application of warmth to 
 the epigastrium caused the symptoms to disappear after several days. 
 Neiatonf injected two syringefuls of a dilute solution of iodide of 
 potassium into a cold abscess, after having emptied it of its con- 
 tents. In two hours there occurred disturbance of vision, vomiting, 
 a ttiread-like pulse, swelling of the upper eyelids, pain in the larynx, 
 and on the following day aphonia, a croupous cough and prostra- 
 tion. Under the application of ice, sinapisms to the extremities, 
 vesicants to both sides of the neck, and laxative pills, these symp- 
 
 * Buckell, The Lancet, i. Febr. 1843. 
 
 tNelaton, L'abeille M&iicale, 15 Novembre, 1853. 
 
I04 THE UNTOWARD EFFECTS OF DRUGS. 
 
 toms disappeared after three days. Fonssagrives* observed a 
 similar case. In two hours after the injection of a small quantity of 
 a solution of half the strength of the officinal tincture, into a tunica 
 vaginalis traumatically inflamed — its fluid contents having beer 
 previously evacuate^ — he observed a swelling of the scrotum 
 accompanied by considerable fever. Against the following day 
 there had developed, irritation of the bronchi, a nasal catarrh, red- 
 dening of the eyes, oedema of the epiglottis and salivation. The 
 fever continued- for five days. The more or less prolonged internal 
 exhibition of iodine in medicinal doses gives rise to a greater 
 variety of untoward effects than the more acute symptoms which 
 result from the external application of the drug. Inasmuch as the 
 iodide of potassium is much the more frequently employed when it 
 : s desired to secure the effects of iodine on the system, we shall con- 
 sider it in lieu of all the other compounds of iodine. 
 
 POTASS] [ IODIDUM. 
 
 The first comprehensive treatise on the subject of " iodism " 
 was prepared by Rilliet.f He differentiated three forms of the 
 affection. The first, according to his opinion, occurs in all persons 
 and at all ages after large doses, and is due to irritation of the 
 gastro-intestinal tract by the iodine. The second is conditioned on 
 a certain predisposition in individual organs, and manifests itself in 
 the gradual appearance of slight nervous disturbances and anomalies 
 of secretion of various mucous membranes and in affections of the 
 skin. The third form is known as iodine cachexia or constitutional 
 iodism. It embraces a series of general constitutional disturbances 
 and disturbances of the nutritive functions, and appears as a 
 result of the prolonged use of minimal doses of the drug. 
 Practical observation has, however, shown that such a dog- 
 matic division is not possible, inasmuch as sometimes one and 
 sometimes another group of symptoms present, and small 
 doses may arouse untoward action in one person which can 
 be made to appear in others only as a result of large doses, 
 and vice- versa. It may be stated, therefore, that sometimes one 
 organ and sometimes another is disturbed in its functions or 
 
 * Fonssagrives, L'Union Medicale, i860, No. 7.1. 
 tRiiliet, Bullet, de l'Academic de Medec, iC6a, p. 382. 
 
ALTERATIVES POTASS1I IODIDUM. I05 
 
 suffers material changes through the action of iodine, and that the 
 cause of these disturbances is unknown. We are not able, however, 
 to deduce from this any rule, the conditions necessary to the 
 development of these affections being unknown. We must, there- 
 fore, be 'content to consider the variable symptoms of the effects of 
 iodine on separate organs in their details. Similar conditions 
 supervene on the ingestion of the iodine combinations, notably the 
 iodide of potassium, a fact which M. Rosenthal* demonstrated by 
 means of experiments on himself, administering the drug by means 
 of enema. Absorption takes place rapidly from the mucous lining 
 of the intestines even when the drug is given in a diluted solution. 
 
 Following the ingestion of the iodide of potassium many per- 
 sons, and particularly in the morning after waking, experience an 
 astringent, metallic, bitter taste on the tongue. This may be made 
 to promptly disappear, according to Laroche, f by rinsing the mouth 
 with cold water to which a tabiespoonful of Spiritus cochleariae 
 has been added. In addition to this there is observed, in 
 particularly sensitive persons, as an effect of small doses, scratch- 
 ing and burning and a sensation of dryness in the throat, and a 
 sense of constriction of the pharynx. In rare cases an impairment 
 of the ability to swallow has also been observed. The sensation of 
 burning may extend from the throat along the sternum to the region 
 of the stomach. Associated with this there is frequently increase in 
 the secretion of saliva, in consequence of the peculiar property of 
 the iodide of potassium to increase the secretion of nearly all the 
 glands. 
 
 Although the functions of the stomach are not affected by one 
 or more small or moderately large doses of the potassic iodide, the 
 appetite being sometimes even stimulated thereby to a degree of 
 intense hunger, nausea and vomiting are nevertheless occasionally 
 excited in persons having a pronounced aversion to the drug, while 
 in others, as observed by Ricord,]; there is a pain referable to the 
 fundus of the stomach, which is increased by pressure, but which 
 has no influence on the digestion. Rabuteau ascribes this pheno- 
 menon to an adulteration of the potassic iodide (KI) with the 
 potassic iodate (KI0 3 ). In this case, according to this author. 
 
 *Rosenthal, Sitzungsbericht der Wiener Akademie, Band XLVI, Abth. II. 
 ^Laroche, Canstatt's Jahresbericht f. d. ges. Medicia, 1844, iv., p. 195. 
 ^Ricord, Bulletin Generale de Therapeut . , 1842, p. 161. 
 
Io6 THE UNTOWARD EFFECTS OF DRUGS. 
 
 iodine is set free through the influence of the acids of the stomach, 
 and thus attacks the mucous membranes. Though this hypothesis 
 is not strictly tenable, these symptoms being also sometimes 
 observed after the exhibition of pure iodide of potassium, it is never- 
 theless possible that in some persons the freed iodine conduces to 
 the development of the symptoms as above. In view of this possi- 
 bility, the iodide of potassium should be tested for the iodate, in the 
 manner to be hereafter described, as soon as there exists any doubt 
 as to the purity of the drug. 
 
 Disturbances of digestion supervene only after large and long- 
 continued doses of the iodide of potassium. 
 
 On the other hand, the irritative effects of the drug on the 
 mucous membrane of the air passages develop so readily, that the 
 majority of those who take it suffer from them to a greater or lesser 
 degree. This irritation extends, in the first place, to the mucous 
 membrane of the nose, but often simultaneously attacks the mucous 
 lining of the larynx, bronchi and their divisions. 
 
 Since this effect on the nose was first observed, the name 
 "iodine catarrh" has been attached to it. It manifests itself in 
 inflammation, of varying degrees of intensity, of the mucous mem- 
 brane of the nose, and may spread over the whole extension of this 
 membrane, involving the posterior nares, frontal sinuses and antrums 
 of Highmore. The mucous membrane of the nose becomes soft and 
 spongy, and secretes quite freely, and the subjective symptoms, 
 which often begin with a burning sensation in the nose, take the 
 form in their further course, of a sensation of oppression, occlusion, 
 sneezing, etc. Should the regio olfactoria be most decidedly 
 affected, loss of the sense of smell may ensue. The affection disap- 
 pears shortly after the suspension of the drug. 
 
 In the description of the acute pathological symptoms caused 
 by the external application of iodine, the occurrence of oedema of 
 the glottis has already been referred to. The tendency of the com- 
 pounds of iodine to produce catarrhal effects on the mucous mem- 
 branes, makes it probable that oedema of the glottis is traceable to 
 an acute swelling of the mucous membrane of those parts, with con- 
 sequent infiltration of the submucous connective tissue. The irrita- 
 tion of the mucous membranes of the lower air passages, superven- 
 ing in many persons on small doses of the iodide of potassium, may 
 also be adduced in support of this view. Thus Ricord (1. c.) often 
 
ALTERATIVES POTASSII lODIDUM. 107 
 
 observed a bronchitis, which was demonstrable on physical examin- 
 ation, accompanied by labored respiration, cough, with asthmatic 
 breathing, pain in the chest, and quite free expectoration, which, 
 however, never became^purulent. Some authors* have, without suf- 
 ficient warrant, classified these difficulties of breathing as " iodine 
 asthma," after a manner analogous to the classification which was 
 formerly made of the disturbances of respiration following the 
 employment of lead, mercury, and other heavy metals. But even true 
 oedema of the glottis may be caused by medicinal doses of iodide of 
 potassium, as has been demonstrated by Petitjean,f although only in 
 those who had been suffering from laryngeal affections previous to 
 the treatment with iodide of potassium. In -case of a person 
 deceased in consequence of such oedema of the glottis, small ulcera- 
 tions were found in the larynx, as well as oedema of the epiglottis. 
 That existing lesions may become aggravated in this manner is shown 
 by a case reported by Rodet, \ in which a man, in whom tuber- 
 culosis was suspected, had more or less copious hemorrhage after 
 each dose of the iodide of potassium. 
 
 By the transmission of the catarrhal irritation to the vocal 
 cords phonation may even be interfered with, in very rare cases, 
 without the existence of deeper lesions. 
 
 Pathological changes of a nature analogous to those occurring 
 in the mucous membranes, already referred to, may quite frequently 
 appear in the eyes and their appendages, after the use of the potas- 
 sic iodide. These seldom appear alone, occurring most frequently 
 in an acute form in one or both eyes in connection with the iodine 
 catarrh, or bronchial catarrh of similar origin, and manifest them- 
 selves also simultaneously, partially in catarrhal irritation of the 
 connective tissue as well as of the lining of the lachrymal sac and 
 duct. The vessels of the conjunctiva palpebrarum and conjunctiva 
 sclerae are greatly injected, the mucous membrane is itself swollen 
 and loosened, there is lachrymation but only occasionally photo- 
 phobia. On the other hand Chemosis and oedema of the eyelids 
 now and then occur. The subjective symptoms vary with the 
 degree of the affection. The patient usually complains of burning 
 
 *Santlus, Deutsche Klinik, 1856, p. 18. 
 
 tPetitjean, Accidents du cote de la peau et des mucueuses detet mint'-.; p r l'administration 
 de l'jodure de Potassium, Paris, 1879, P- 2 9- 
 
 JRodet, Gazette M^dicalede Paris, 1847, P- 94 6 - 
 
Io8 • THE UNTOWARD EFFECTS OF DRUGS. 
 
 and itching and of the sensation of a foreign substance in the eye. 
 In some there is also a painful sensation of pressure in the supraor- 
 bital region at the foramen of exit of the supraorbital nerve. 
 
 These untoward effects of the potassic iodide may, according 
 to the specific disposition of the individual, supervene after the 
 exhibition of one or repeated doses. They most frequently appear 
 after the repeated use of small doses, and disappear spontaneously 
 in a few days after suspension of the drug, and without leaving any 
 after-effects; their disappearance is facilitated by the application of 
 compresses wet with slightly astringent lotions. Cases in which the 
 symptoms, as above described, have come under observation after 
 the use of only 0.5 gramme (gr. vijss) of the iodide of potassium 
 have frequently been reported. Thus Mecklenburg,* among others, 
 observed in the course of a few hours after the exhibition of 0.5 
 gramme of the drug, violent pain in the eyes, profuse lachrymation, 
 a burning sensation in the nose and throat, and a swelling and livid 
 discoloration of the upper eyelids and especially in the tarsal region. 
 After the expiration of twenty-four hours these symptoms disap- 
 peared. The renewed administration of only 0.25 gramme (gr. jv) 
 of the drug caused the same symptoms, with the exception of the 
 swelling of the eyelids, to reappear within four hours. 
 
 Besides these more external symptoms there occurs, though very 
 rarely, as a result of the use of the potassic iodide, a lessening of 
 the power of accommodation, decrease in the acuteness of vision, 
 and, in short, the symptoms of presbyopia. Corlieuf reports a case 
 of this nature, in which, besides other abnormal effects of iodine, 
 presbyopia with dilatation of the pupils and a suddenly occurring 
 hypermetropia were observed. These symptoms disappeared in a 
 few days after the discontinuance of the iodine. DorvalJ 
 observed diplopia and weakness of vision, and Brera, § dullness 
 of vision and orbital pain. Which of these possible factors has 
 been active in the causation of these functional disturbances, has 
 not, as yet, been determined. 
 
 The symptoms of irritation of the skin mentioned above, and 
 their effects on more remote parts of the body after the external use 
 
 *Mecklenburg, Berl Klin. Wochenschr., i860, p. 262. 
 tCorlieu, Gazette des Hopitaux, Juin, 1856. 
 *$Dorval, Eod. loco, 
 §Brera, Eod. loco. 
 
ALTERATIVES POTASSII IODIDUM. 109 
 
 of the iodide of potassium, make their appearance also in many per- 
 sons, under the most diverse conditions of its internal administration 
 as regards the dose of the drug and the duration of its continuance, 
 with this distinction that there is a greater variety in the eruptions 
 thus caused. The especial untoward action of the iodide of potas- 
 sium has been known since the drug was first introduced into the 
 materia medica, and innumerable references to it are contained in 
 literature. As a general result the fact is established that the iodide 
 of potassium may often produce cutaneous eruptions, with or with- 
 out fever, from the simple erythematous to the petechial form, which 
 may occur either alone or accompanied by other abnormal effects of 
 iodine and which disappear, as a rule, soon after the suspension of 
 the drug. 
 
 These eruptions are divisible, according to Fischer,* into four 
 principal forms. 
 
 I. The Erythematous Form. — The skin, especially that of the 
 forearms, but also of the face, is diffusely reddened or in circum- 
 scribed spots, and its temperature is elevated. With the discontinu- 
 ance of the drug this symptom disappears after a few hours, but 
 under its continued use the exanthem may develop into the most 
 common form, viz.: 
 
 II. The Urticaria-like Form. — This occurs especially on ihe 
 lower part of the trunk and extremities, but also on the other parts 
 of the body. It appears as intensely red wheals which are slightly 
 elevated, surrounded by an areola and gathered in groups, differing 
 from true urticaria only in their higher color, being commonly 
 described as of a pink-red color and turning pale under pressure. 
 They disappear, without desquamation, on the discontinuance of 
 the iodine. 
 
 III. The Nodulo-pustular Form. — This form is seldom 
 observed, occurring most frequently in scrofulous subjects and 
 usually on the upper part of the body. A deep-red, pruritic spot is 
 formed, and is transformed through exudation into a papule or a 
 bluish-red nodule, with or without an areola. This may persist, but 
 as a rule, a colored vesicle filled with a clear fluid, or a pustule,, 
 which may either break or dry up, is developed on the top of it 
 while the papule slowly disappears with desquamation after discon- 
 
 : Fischer, Wien. Medic. Wochenschr., 1859, No. 29, p. 470. 
 
IIO THE UNTOWARD EFFECTS OF DRUGS. 
 
 tinuing the use of the iodide of potassium, often leaving behind a 
 bluish-red or marble-colored pigmentation of the skin. 
 
 As intermediate forms small blisters, acne-like pustules (iodine 
 acne) and even furuncles are observed. Thus Brshesinsky* saw 
 large furuncles surrounded by severe inflammation develop on the 
 breast and between the shoulder blades in the case of a woman who 
 took thirty drops of the tincture of iodine three times a day. Under 
 the application of warm fomentations these furuncles fell off as 
 nodes, leaving large ulcers behind. 
 
 IV. The Fczematous Form. — This is a very rare variety, and 
 attacks chiefly the hairy scalp, and in the neighborhood of the 
 scrotum. The differential diagnosis between this and syphilitic 
 eruptions is not difficult, particularly as the form disappears very 
 quickly on discontinuance of the drug. 
 
 For the sake of completeness a form more recently observed 
 may be added : 
 
 V. The Petechial Form. — Fournierf describes this form, which 
 he calls purpura jodina (Jodisme petechiale), as a very rare affec- 
 tion. He noticed that the eruption, which has also been men- 
 tioned by Ricord, occurs during the first three days of the exhibition 
 of the iodide of potassium, less frequently between the third and the 
 sixth day. In some cases it appeared simultaneously with the exhi- 
 bition of iodine, and in one patient a new eruption appeared with 
 each increase of the dose. It was confined in each to the legs, (occur- 
 ring only once in the trunk), and appeared more profusely on the 
 extensor than on the flexor surfaces. It never appeared on the 
 knees or on the feet. Usually as many as a hundred discrete patches 
 occur on each leg. The eruption is miliary, the spots being mostly 
 of the size of a pin's head, seldom reaching that of a lentil, and 
 accompanied by no constitutional disturbance. It attains its perfect 
 development within two or three days, and continues at the longest 
 for from two to three weeks, when it disappears. PetitjeanJ con- 
 firms these reports in the main, but describes a case in which the 
 eruption appeared also on the dorsal surface of the foot. 
 
 Auspitz § also observed a similar eruption in a patient who had 
 
 *Brshe3insky, Canstatt's Jahresber. f. d. ges. Medicin, 1843, iv., p. 32. 
 
 tFournier, Revue Mens, de Medecine, 1877, p. 653. — Vierteljahrschr. f. Dermatologie u. 
 Syphilis. 1878, p, 294. 
 
 ^Petitjean, 1. c , p. 35. 
 
 §Auspitz, Vierteljahrschf. Dermatolog, u. Syphilis, 1878, p. 204. 
 
ALTERATIVES POTASSII IOJJIDUM. 
 
 taken 25 pills of iodide of potassium of 0.2 gramme (gr. iij) each, or 
 a total quantity of 5.0 grammes (gr. lxxv). 
 
 The occurrence of the untoward effects of the potassic iodide 
 finds its most satisfactory explanation in the hypothesis that the 
 drug, or the products of its decomposition, exerts a direct influence 
 through the circulation on the respective parts. The theory of " the 
 saturation of the system with the iodide of potassium," of which the 
 symptoms detailed were regarded as the expression, and which was 
 formerly accepted by most of the authors, is manifestly obscure and 
 indefinite, and is so plainly refuted by the fact that these symptoms 
 appear after even very small doses, that any further discussion of it 
 maybe dispensed with. In addition to this chemical analysis points 
 also to the local origin of the affection. 
 
 It has long been known that iodine may be detected in the 
 secretions, as the urine, saliva, sweat, milk and tears, shortly after 
 the exhibition of the iodide of potassium. Adamkiewicz* assigns 
 the cause of the iodine acne to the influence of the iodide on the 
 sebaceous glands. According to this author the ingested iodide 
 combining with the nitrate of ammonia present in the stagnant 
 secretions of the skin, sets free the iodine, which may act as an irri- 
 tant on the glands and the tissue adjacent and in this manner give 
 rise to the affection. That the iodine eliminated with the sweat 
 does not cause this affection is evident from the well-known fact 
 that iodine acne does not attack the palms of the hands or 
 the soles of the feet. Buchheim declares that the iodine erup- 
 tion is due to the action of ozone on the iodide of potassium 
 eliminated with the perspiration, the iodine being thus set 
 free That the drug selects these unwonted avenues of escape 
 instead of being eliminated through the ordinary channels may 
 be particularly due to individual peculiarities, or partially also 
 to the fact that the urinary apparatus may be functionally less active, 
 the inactivity, however, being still within physiological limits, as in 
 the summer for instance, or it may be actually diseased. 
 
 Johnsonf observed the appearance of a pustular iodine exanthem 
 in many cases of Bright's disease as a result of small doses of iodide 
 of potassium, and RoseJ was able to detect iodine in the matter 
 
 * Adamkiewicz, Chant-e Annalen, iii., 1876. 
 tJohnsco, British Medical Journal, Jan., 185g. 
 JRose, Virchow's Archiv, Bd. 35, 1864, p. 32. 
 
112 THE UNTOWARD EFFECTS OF DRUGS. 
 
 vomited shortly after the injection of preparations of iodine into an 
 ovarian cyst.' In the latter instance the drug found its way into the 
 stomach probably on account of a partial suppression of the urinary 
 secretion. 
 
 The observation of Simon and Regnard (1. c.) that albuminu- 
 ria is sometimes caused by an external application of iodine, shows 
 that the drug may exert a direct influence upon the urinary pass- 
 ages. The potassic iodide is said to have a similar effect on 
 some persons: Rodet (1. c.) and Petitjean (1. c.) report cases in 
 which vesical tenesmus, dysuria, retention of the urine, and even 
 haematuria followed the employment of this salt. 
 
 The old and common experience that iodine effects a reduction 
 of hyperplastic glandular tissue, finds a physiological counterpart 
 in the effect of the prolonged employment of medicinal doses of 
 the iodide of potassium on the testicles, ovaries and mammae. 
 Many authors claim to have observed, under such conditions, vari- 
 ous degrees of atrophy of organs, which were previously in a 
 normal condition. It is probable that the direct localized action of 
 the iodide, or the iodine in its composition, plays an important 
 part in the causation of these effects. 
 
 As regards the genital system, an increased excitability of the 
 sexual appetite, spermatorrhoea, and, in women, a greater profusion 
 of the menses, are said not infrequently to follow the protracted 
 employment of the iodide of potassium. 
 
 Mention must lastly be made of the disturbances of the gen- 
 eral nervous system and of nutrition — that group of symptoms 
 called by Rilliet " constitutional iodism," which follow, in many per- 
 sons, the employment of iodine. According to this author, even 
 minimal doses of the iodide of potassium, if long continued, are 
 capable of producing this condition. The patients present a pecu- 
 liar cachectic discoloration of the skin, and, in spite of the fact 
 that the appetite is usually good, there may be considerable emacia- 
 tion. This emaciation is apparent in the face, around the hips, 
 breast and testicles, and is accompanied by a sensation of faintness 
 and bodily weakness. In addition to these a series of nervous dis- 
 turbances may supervene, as anxiety, restlessness, a kind of 
 oppression called by French authors "ivresse iodique," disturbances 
 of hearing, lancinating pains in the extremities, a slight jerking of 
 the tendons, and nervous palpitation of the heart. 
 
ALTERATIVES BROMINUM. 
 
 Though the facts thus far reported prove that the iodide of 
 potassium often fails of its normal effects, causing in their stead 
 untoward effects in the most varied organs, it would nevertheless 
 be carrying the objection to its use too far to limit its use to but a 
 few affections, as proposed by Rodet, inasmuch as these phenomena 
 occur in only a limited number of cases, and are, in the main, of a 
 transitory nature. 
 
 This fact does not, however, remove the necessity for caution 
 in the administration of the iodide of potassium, and, especially in 
 diseases of the throat and kidneys, and the suspension of the drug 
 on the appearance of the first symptoms of untoward effects. 
 Should disturbances of the intestinal tract, as vomiting, 
 diarrhoea, etc., supervene immediately or in a short time after the 
 exhibition of the drug, it would be well to examine the solution of 
 the iodide of potassium with reference to its purity, for which pur- 
 pose muriatic or sulphuric acid should be added to it. In the 
 presence of the iodate of potassium a reduction takes place and 
 iodine is set free. 
 
 BROMINUM. 
 
 Owing to the unpleasant physical properties of bromine the 
 drug has not met with much favor as a therapeutic agent. It is, 
 however, sometimes employed in aqueous solution in inhalations, 
 and also in gargles, in infectious diseases. In addition to this it 
 may be employed in the purification of dwelling apartments which 
 are suspected of being infected. Recently the method devised by 
 Frank, viz., the incorporation of the bromine in a solid substance 
 has been resorted to. Pieces or sticks of infusorial earth, a very 
 porous substance, capable of absorbing a large quantity of fluid, 
 and of low specific gravity, are impregnated with liquid bromine. 
 It requires seven times its volume of bromine to completely saturate 
 it, and when placed in an air-tight vessel the saturation is preserved. 
 The pieces are so dry as to permit of their being handled with the 
 naked hand. In the presence of atmospheric air this porous sub- 
 stance gives off the bromine completely, in the form of vapor. 
 According to Wernich* the entire cubic contents of a room may be 
 rendered innocuous as regards the disease germs which it may con- 
 tain, by evaporating in it 4 grammes ( 3 j ) of bromine, after the 
 
 *Weroich Centralbl. für die Medic. Wissens. h. No. n, 1882. 
 
114 THE UNTOWARD EFFECTS OF DRUGS. 
 
 manner indicated, for each cubic meter (ij cubic yards) of the con- 
 tents of the room. Owing to the great weight of bromine vapor — 
 it being five-and-a-half times as heavy as atmospheric air — and the 
 facility with which it is condensed, it is especially adapted to the 
 disinfection of spaces which are difficult of access, as for instance, 
 the holds of ships, casemates, vaults, etc. This method is certainly 
 to be preferred to all others when it is possible to com- 
 pletely close up a room and prevent its use for a length of 
 time. These conditions are necessary inasmuch as the bromine 
 which in liquid form is a caustic to the skin and mucous mem- 
 brane, is also an irritant when in the form of gas it comes in 
 contact with the mucous membrane, exciting a condition which may 
 vary from a slight degree of redness to one of violent inflammation. 
 It is because of this property of the drug that one frequently 
 observes conjunctivitis, coryza, salivation, a feeling of suffocation 
 and slight bronchitis, with cough, in those who have inhaled bromine, 
 either for therapeutic purposes or accidentally in rooms filled with its 
 vapor. 
 
 The internal employment of bromine-water also frequently 
 gives rise to catarrh, lachrymation, bronchial catarrh, salivation and 
 diarrhoea. Glover,* in experiments on himself with this substance, 
 observed only occasional gastric pains, though larger doses gave 
 rise to nausea, a burning in the mouth, gastric oppression, etc. 
 Other authors have shown by experiment that taken in small doses, 
 for some time, bromine water exerts a depressing influence on the 
 central nervous system, causing formication, a disposition to sleep, 
 apathy, mental confusion, and a weakness of the reasoning power 
 and memory. These symptoms disappeared on the suspension of 
 the drug. 
 
 POTASSII BROMIDUM. 
 
 In contrast with the comparatively few and slight affections 
 which arise from the use of bromine, may be placed a series of 
 untoward effects following the internal employment of the bromides, 
 and especially of the bromide of potassium, and what is true of this 
 salt in this respect is also true of the sodium and ammonium salt. 
 These effects evince in a general way a certain similarity to those 
 
 *Giover, Edinb. Medic, and Surg. Journal, 1842, p. 120. 
 
ALTERATIVES POTASSII BROMINUM. 1 1 5 
 
 caused by the iodide of potassium, but do not present such a varie- 
 ty, and when once developed are more persistent. The mucous 
 membranes are more frequently attacked, though in a milder 
 degree than by the iodide of potassium ; but, on the other hand, 
 the effect in many cases on the integument, and more particu- 
 larly on the central nervous system, exceeds in intensity and dura- 
 tion the effect of iodine. 
 
 The fact already noted of iodide of potassium, viz., that the 
 occurrence of abnormal symptoms following its use is very much con- 
 ditioned on the individuality of the person in whom they appear, is 
 equally true of the bromide of potassium. For while these symp- 
 toms appear in many persons as a result of single or repeated small 
 doses, there are others whose tolerance of the drug permits of their 
 taking even poisonous quantities. As an illustration of this lack of 
 susceptibility may be mentioned a characteristic case reported by 
 Schweig,* in which 31 grammes ( 3 j) of the bromide of potassium 
 was taken in seven hours without the least manifestation of reaction, 
 and 93 grammes ( 5 iij) taken in the course of 48 hours caused only 
 a diminution in the quantity of urine excreted, salivation and sleep. 
 Arthand reports also fourteen cases in which the daily exhibition of 
 from 10 to 12 grammes ( 3 ijssto 3 iij) caused no cutaneous disease. 
 
 In a short time after its administration the bromide of potassium 
 gives rise to a salty, and, according to some, bitter aftertaste ; some- 
 times there is also an increased secretion of saliva, traceable to an 
 irritation of the mucous membrane of the mouth, and a reflex action 
 on the salivary glands. In sensitive persons it causes a burning sen- 
 sation in the throat, and sometimes a slight nausea and eructation, 
 and when given on an empty stomach it occasionally causes pain in 
 that organ, or a feeling of gastric oppression, warmth or fullness. 
 Actual gastric catarrh following its employment is a rare occurrence 
 unless the drug is given improperly or on an empty stomach. Occa- 
 sionally eructation and vomiting are observed in some patients 
 shortly after a dose of the drug; diarrhoea seldom occurs. On the 
 other hand, as was first pointed out by Hutte,f the prolonged use of 
 small doses, or larger quantities taken for a shorter time, occasions a 
 blunting of the sensibility as well as of the reflex action of the soft 
 palate, the root of the tongue, and the posterior wall of 
 
 *Schweig, Virchow-Hirsch's Jahresber, 1876, p. 401 
 tHütte, Gazette Medicale de Paris, 1850, Juin 28. 
 
Il6 THE UNTOWARD EFFECTS OF DRUGS. 
 
 the pharynx. Gatumeau* noticed such complete analgesia after 
 3 grammes (gr. xlv) of the drug that irritation of the pharynx and 
 epiglottis and of the posterior wall of the pharynx excited 
 no reflex efforts at deglutition. Kroszj- noticed on himself after 
 large doses of the bromide of potassium such a diminution of reflex 
 excitability in the parts indicated, that it was impossible to evoke 
 reflex nausea by irritating the palate. The depression of the sensi- 
 bility of the respiratory mucous membrane is not less marked. This 
 fact must be borne in mind in connection with the bronchial catarrh 
 with profuse secretion which not infrequently attends the 
 prolonged employment of this drug, particularly in the treatment 
 of epilepsy, mania, etc, StilleJ pointed out the possibility of 
 the occurrence of dangerous and even fatal catarrh in the course of 
 the prolonged employment of the bromide of potassium, through 
 the prevention, by the diminution of the reflex excitability of the 
 respiratory tract, of the fits of coughing which may be necessary to 
 remove accumulated mucus. As Höring § found to be the fact in his 
 own case, the bronchial catarrh is sometimes attended with pain in 
 the larynx, paroxysms of coughing and hoarseness. According to 
 older authors || haemoptysis, which, however, disappears on the sus- 
 pension of the drug, is said to occur in many who are subjected to 
 its influence. No confirmation of this statement is, however, to be 
 found in recent literature. As more recently remarked by Veiel,** . 
 a concomitant symptom to those mentioned, of the effects of the 
 potassic bromide, is a foetid odor of the breath. This cannot be 
 due, as in the case of mercury, to any morbid changes in the mouth, 
 inasmuch as the changes in the mouth wrought by this salt are 
 insufficient. It is probable that the bromine in the salt suffers a 
 temporary separation from the potassium in the body and that it is 
 partially eliminated through the lungs, thus imparting the odor to 
 the breath. It must not be inferred from this, however, that it is the 
 bromine, as such, which excites the catarrhal changes in the mucous 
 membranes, for although a small per centage of it may escape from 
 
 *G tumeau, These Montpellier, 1869. 
 
 fKrosz, Archiv für experiment. Pathologie u. Pharmacologic, Bd. vi, p. 15. 
 ifStilld, Virchow-Hirsch's Jahresber. 1878, L, p. 3C4. 
 
 §Köring Ueber die Wirkung des Broms und seiner Präparate auf den thierischen Organis- 
 mus, Tübingen, 1838. 
 
 DCanstatt's Jahresbericht für die ges. Medicin, 1843, IV., p. 31. 
 ** Veiel, Viertel jahrschr. f. Dermatol, u. Syphil., 1875, p. 17. 
 
ALTERATIVES — POTASSII BROMIDUM. 117 
 
 the body in the form of a vapor, the greater part immediately on its 
 separation from the potassium finds a sufficiency of the metallic alka- 
 lies to enable it to exert its action on the various mucous membranes 
 in the form of a bromide. 
 
 Among the mucous membranes which may be attacked are 
 those of the nose and eyes, as is evidenced by the occasional 
 occurrence of coryza, conjunctivitis, lachrymation, etc., as a 
 result of the employment of the bromide of potassium. The 
 functions of the visual apparatus are but slightly affected. Dilata- 
 tion of the pupil is an almost constant effect of repeated doses of 
 the bromide of potassium. Laborde* observed in several cases, 
 within one or two hours after the exhibition of the drug, cloudiness 
 of vision, and in some instances anesthesia of the scleral conjunc- 
 tiva. Hutte (1. c.) declared that myopia, amblyopia, and diplopia 
 may be caused by the drug. Martin Damourette and Pelvetf 
 affirm the latter fact, while Nicol and Mossop are said to have 
 observed, in addition to this, dilatation of the retinal blood vessels. 
 In opposition to these claims may be placed the experiments of 
 KroszJ on himself and others, which always gave negative results as 
 regards these pathological symptoms. 
 
 The bromide of potassium has been demonstrated to be 
 capable of causing a wide range of affections of the genito-uri- 
 nary organs. In addition to a positive increase in the secretion of 
 urine, there is in some persons dysuria, a constant feeling of full- 
 ness of the bladder and a diminution of the sensibility of the 
 urethral and vaginal mucous membranes. Rabuteau § declares that 
 the prolonged use of the drug causes a diminution of the sexual 
 appetite. Thielmann || had previously utilized this property of the 
 drug by prescribing it as an antaphrodisiac, in doses of 0.18 gramme 
 (gr. iij). Laborde (1. c.) on the contrary declares that he found it in 
 his own case, and after a single large dose, to cause sexual excite- 
 ment, erections and pollutions. Voisin** reports the same effect 
 as occurring, though rarely, as a result of ordinary doses. A dimin- 
 ution of the catamenia is said to occasionally occur in women. 
 
 *Laborde, Gazette Medicale de Paris, 1869. 
 
 tM. Damourette et Pelvet, Bullet, de Therapie, lxxiii., 1867, p. 241. 
 JKrosz, 1. c. p. 21. 
 
 §Rabuteau, Gazette Medicale de Paris, 1869, p. 312. 
 Thielmann, Medicin. Zeitung f. Russland, 1854. 
 **Voisin, Bulletin Generale de Therapeutique, LXXX1II, 1867, p. 241. 
 
Il8 THE UNTOWARD EFFECTS OF DRUGS. 
 
 The irritating action of the bromide of potassium on the skin 
 denuded of its epithelium, and on the mucous membrane, manifests 
 itself also in the frequent occurrence, in many cases, of a variety 
 of cutaneous eruptions after its internal administration. These 
 have long been recognized, and have been collectively designated 
 as "bromine acne," although they belong to a different classification 
 in dermatology. 
 
 Berenguier* observed them as occurring in fifty-three per cent, 
 of all cases treated by the bromide of potassium, Clark and 
 Amoryf in sixty-six per cent., and Voisin in seventy-five per 
 cent. Several authors, as Bedford Brown, J noted their occurrence 
 accompanied by local or general elevation of temperature, while 
 Veiel (1. c.) emphasizes the fact of the gradual and non-febrile 
 occurrence of the acne-like efflorescence; Voisin observed the occur- 
 rence of fever in only one case of general bromine acne. Falret§ 
 declares that he has always observed the occurrence of an eruption 
 after the exhibition of 4 grammes ( 3 j) of the salt. It is, however, 
 an established fact that it may be developed after much smaller 
 doses. Children are, as a rule, more liable to be attacked by it. 
 
 The bromine eruptions which present themselves are differently 
 described by different authors. They are, however, for the great 
 part traceable to morbid changes in the sebaceous glands and their 
 results, and since the different stages of the development of these 
 affections are present at the same time — in the progressive and 
 retrogressive metamorphosis of the affection — in one and the same 
 person, they closely resemble the various dermatoses. 
 
 Voisin (1. c.) has classified all the changes of the skin which 
 occur as a result of the use of bromine. But in view of other and 
 more recent observations his classification may be advantageously 
 increased to make room for the addition of several varieties. 
 The following may, therefore, be regarded as embracing all the 
 changes of the skin due to this cause. There appear, during the 
 internal administration of bromide of potassium in certain persons, 
 according to their specific predisposition and independently of sex 
 and the systemic condition as regards health, at various times and 
 after the most various doses, various affections of the skin, as: 
 
 *Berenguier, Des eruptions provoquees par Fingestion des Medicaments, Paris, 1874, p. 4. 
 tClark u. Amory, Virchow-Hirsch's Jahresber., 1872. 
 ^Bedford Brown, Virchow-Hirsch's Jahresber., 1873, p. 358. 
 §Falret, Annales Medico-psychologiques, 1871. 
 
ALTERATIVES POTASSII BROMIDUM. 119 
 
 i. The Erythematous Form. This was regarded by Veiel 
 (1. c.) as the sole untoward symptom of the action of the drug; and 
 he maintained that it was attended by fever and occurred only on 
 the lower extremities over which it was diffusely spread. The 
 eruption was very painful. Brown (1. c.) also describes this form of 
 eruption as an expression of the action of the bromide of potassium. 
 He saw the development of rubeola in children under similar 
 conditions. 
 
 2. Acne. — This is by far the most common form of eruption 
 following the exhibition of the bromide of potassium. According 
 to Veiel a thickened skin, which owing to the secretion of sebum 
 has an unctuous feel, or an integument on which there are come- 
 dones or pre-existing acne, is peculiarly predisposed to the occur- 
 rence of this form of eruption. It appears, under various modifica- - 
 tions, which present a complete analogy, as regards their seat and 
 appearance, to ordinary acne. The first step in its development is 
 generally an erythematous change in the skin, attended by a prick- 
 ing and burning sensation. It is convenient to make a subdivision 
 of this form into two varieties: 
 
 a. Acne Punctata. — This usually precedes the pustular form. 
 It is characterized by the appearance of red elevations of the size of 
 millet seed or peas, on a more or less indurated base with an areola, 
 and attacks by preference the face, eyebows, hairy portion of the 
 scalp, being more rarely situated in the breast and back, and almost 
 never on the lower extremities. Veiel found that most of the 
 nodules were pierced by hairs. After a longer or shorter duration 
 this form may disappear with desquamation, or pass into 
 
 b. Acne Pustulosa. — This may be regarded either as a disin- 
 tegration of the nodules or as an independent variety. The pustules 
 are at first of the size of a pin's head, of a yellowish-white color, 
 surrounded by an areola, becoming larger later on, and, according 
 to Voisin, assuming even the form of ecthyma pustules. After a 
 few days or weeks the pustule discharges its contents, and there 
 remains in its place a solid nodule or a red spot. The number of 
 these pustules varies. The whole face is occasionally covered and 
 disfigured by the densely disposed points of efflorescence. The 
 pustules persist from days to months, and should the drug not be 
 discontinued they may persist for years. Ordinarily they disappear 
 in from one to three weeks after the drug has been suspended. 
 
I20 THE UNTOWARD EFFECTS OF DRUGS. 
 
 Voisin (1. c.) noticed also that the number of the pustules was 
 increased and diminished with the increase and diminution of the 
 quantity of the bromide taken. After healing they frequently leave 
 behind slightly depressed, irregularly round cicatrices or red spots. 
 This pustular variety selects the same location for its appearance 
 as does the papular variety above considered. In some cases the 
 pustules become confluent, and on the scalp they are usually covered 
 with crusts. Veiel examined the pus of the acne with negative 
 results for bromine, being able to discover it only in the urine. 
 Guttmann,* on the contrary, was able to demonstrate the presence 
 of bromine in the secretion of the pustules in a man in whom 
 pustular acne had supervened on the employment of the potassic 
 bromide for a year, the drug at first having been given in quantities 
 'of 4 grammes ( 3 j) a day, and afterward increased to 12 grammes 
 (3 iij). His method was the usual one, of separating the bromine 
 from the potassium by added chlorine water to the diluted and 
 filtered pus, and then extracting the bromine by means of chloro- 
 form. 
 
 3. The Urticarious Form. — This variety was several times 
 observed by Veiel. It appeared only on the lower extremities, and 
 on erythematous surfaces, in the form of wheal-like elevations of 
 from a quarter to a half inch in diameter, very sensitive, and 
 changed, by degrees into a wart-like excrescence which went 
 on to ulceration. The ulcer thus formed was deep and ill-condi- 
 tioned, and disappeared as soon as the bromide was discontinued. 
 This variety is, doubtless, identical with the tumor-like 
 variety described by Voisin, which, according to this description, is 
 of the form of oval-shaped tumors or elevations, from 2 to 5 ctm. (a 
 half an inch to two inches) in diameter, of a rose or cherry color, 
 with indurated base. They appear exclusively on the lower extremi- 
 ties, and particularly on the calves of the legs, and are covered with 
 small yellowish prominences, which, on closer examination prove to 
 be agminated, acne-like pustules, from which cream-like contents 
 exude, either spontaneously or on puncture. They arc very painful 
 when touched, and may, should the drug not be discontinued, 
 be changed into foul, atonic ulcers, which may continue for from 
 three to four months, but which disappear in two or three days after 
 the suspension of the bromide of potassium treatment. 
 
 *Guttmann, Virchow's Archiv., Bd. 74, p. 540. 
 
ALTERATIVES POTASSII BROMIDUM. 
 
 Neumann* noticed a similar affection. He established the fact 
 that these tumors are caused by an inflammation of the glands of the 
 skin, accompanied by an increase of their cellular elements, and a 
 consecutive hypertrophy of the cells in the cutaneous tissue, besides 
 also an enlargement of the papillae of the skin. The hair follicles 
 are enlarged, and assume the form of long tubes or globular sacs, 
 filled with pus, epithelial cells and masses of smegna. 
 
 4. Erythema A T odosum. — In two out of ninety-six cases treated 
 with the bromide of potassium, Voisin observed, on the upper and 
 lower extremities as also on the trunk, slightly elevated patches of 
 different forms, some with smooth margins, and some with irregular 
 outlines. They were from 4 mm. (one-fifth inch) to 6 ctm. (two 
 inches) in diameter, of a dark red color in the centre, and lighter 
 toward the periphery. They arise and disappear very quickly, and, 
 as regards form, color and induration of the base, they are identical 
 with erythema nodosum; while in their reappearance after being 
 rubbed they resemble urticaria. 
 
 Veiel reports his observation of such cases of erythema nodo- 
 sum, but that it was always confined to the lower extremities. 
 Smith f saw also after larger doses of the bromide of potassium, 
 large, slightly elevated patches of the size of a fifty-cent piece, of a 
 purplish color, and having their seat on both arms. They bled very 
 readily, were of an indolent character, and disappeared after the dis- 
 continuance of the drug. 
 
 5. The Vesicular Form. — Voisin observed in a single case the 
 appearance of a weeping eczema on the thighs after the bromide of 
 potassium had been administered for over a year. The observa- 
 tion stands unsupported in the literature of the subject. 
 
 6. The Furuncular Form. — The coincidence of the occur- 
 rence of furuncles with the employment of the bromide of potas- 
 sium, has been noted by so many authors that there can be no doubt 
 that the two stand in the relation of effect and cause. Voisin, 
 Smith and Neumann observed the furuncles in various degrees of 
 development and on different parts of the body. The latter of 
 these observers saw them on the hairy portions of the face, and on 
 the forehead and neck. 
 
 It must be mentioned in conclusion that Veiel (1. c ) noticed 
 
 *Neumann, Wiener Medic. Wochenschr, 1878, p. 124. 
 tSmith, Virchow-Hirsch's Jahresbericht, 1879, p. 3 8 4- 
 
THE UNTOWARD EFFECTS OF DRUGS. 
 
 the appearance of numerous warts on the face and legs of a lad, in 
 a short time after he had commenced the use of the bromide of 
 potassium. 
 
 There is a variety of opinion as to the manner in which the 
 various affections of the skin which have been described, occur 
 after the employment of the bromine salt. While Clarke and 
 Amory regard the bromine acne as a trophic neurosis, and not as 
 dependent on the elimination of the bromide of potassium, and 
 while Veiel also, having failed to discover any bromine in the acne 
 pustules, does not regard the eruption as clue to a local irritation of 
 the sebaceous glands, Martin, Damourette and Pelvet attribute the 
 cause of the affection to the action of the drug on the skin, through 
 which channel it is eliminated. The fact that Guttmann demon- 
 strated the presence of the potassic bromide in the con- 
 tents of acne pustules changes the a priori probability that 
 the salt may be eliminated through the skin into a certain- 
 ty. We find in this fact, on the one hand, an analogy estab- 
 lished between similar eruptions excited by the iodine salts, 
 and on the other hand, a confirmation of the view that it is 
 the bromine and not the potassium of the salt, as has been declared 
 by some authors, which is the cause of the disturbance. In support 
 of this assertion the fact may be adduced that other combinations of 
 bromine are followed by a similar effect. Thus Gowers* showed 
 that similar eruptions follow the use of the bromide of ammonium, 
 and Starkf reports that in seventy-five per cent, of all the cases of 
 epilepsy treated with the bromide of sodium acne appeared, and 
 that it was of longer duration and much more frequently went on to 
 suppuration. In no instance did he observe an affection of the skin 
 as a result of the administration of the chlorate of potassium. 
 
 The leading indication in the treatment of these affections is 
 the suspension of the drug. Gowers (1. c.) employed Fowler's solu- 
 tion in the treatment of the acne. The daily administration of five 
 drops of this preparation was sufficient to cause a disappearance of 
 the acne pustules in fourteen days. That this result is due to the 
 medicine is, however, simply imaginary, inasmuch as experience has 
 shown that the affection may disappear within that time without a 
 
 *Gowers, Lancet, 1878, p. 866. 
 
 + Stark, Zeitschr. f. Psychiatrie xxxii., p. 1482 
 
ALTERATIVES POTASSII BROMIDUM. 123 
 
 resort to therapeutic measures. Prowse* employed for the same 
 purpose a solution of one part of salicylic acid in thirty of water. 
 
 In contrast with the quite transitory untoward effects of the 
 bromide of potassium which have heretofore been considered, we 
 find a group of symptoms referable to a series of functional dis- 
 turbances of the central and peripheral nervous system, which may 
 be associated with the disturbances already described, which fre- 
 quently continue after the suspension of the drug, and which leads 
 to a permanent impairment of the health of the person affected. This 
 condition is bromism, so-called. 
 
 Voisin makes a distinction between a chronic and an acute 
 bromism and bromine-cachexia. There is usually a violent frontal 
 headache in all forms of the affection, a symptom which is also 
 occasionally observed as a result of the use of the bromide of potas- 
 sium without the occurrence of bromism; a bronchial catarrh and a 
 cough may also supervene as complications. Acute bromism may 
 develop suddenly, even after years of tolerance of the potassic 
 bromide and manifests itself in a staggering gait, mental apathy, 
 lustreless eyes, somnolence, etc. While that form which developes 
 slowly is characterized by a faded complexion, dryness of the 
 mouth, a foul breath, emaciation, diarrhoea, a loss of the normal 
 carriage of the body, trembling of the hands, weakness of memory 
 and a loss of will power. It may, furthermore, manifest itself in 
 symptoms referable to disturbance of the cerebro-spinal system, 
 as delirium and hallucinations, and in disturbances of the 
 centres of sensation and motion. According to Voisin (1. c.) 
 the bromine cachexia sets in with loss of appetite, emaciation, and 
 somnolence, and the resulting condition of weakness leads to the 
 formation of carbuncles, and pneumonia, which may prove fatal, 
 should the employment of the bromide of potassium be persevered 
 in. 
 
 Though this classification is open to the objection of being too 
 dogmatic, the fact is still established that all the symptoms which 
 have been detailed may supervene, in the most varied modifications, 
 on the employment of the bromide of potassium. The question as 
 to which of the constituents of this salt these peculiar effects are 
 attributable, has also been variously answered at different times. It 
 
 *Prowse, British Medical Journal, July 24, 1880. 
 
124 THE UNTOWARD EFFECTS OF DRUGS. 
 
 may, however, now be accepted as a certainty that they are due to a 
 combined action of the bromine and the potassium. Stark (I. c.) 
 showed in his series of very careful observations that patients 
 treated with the chlorate of potassium manifested symptoms of 
 cerebral disturbance, such as confusion of ideas, a lessening of the 
 reflex excitability of the pharynx, uncertainty of gait, etc. Krosz 
 (1. c.) ascribes the cause of bromism to the bromine exclusively, in 
 so far as it involves the cerebral and nervous elements, and charges 
 the anaemia and motor disturbances to the potassium. 
 
 The treatment of bromism consists in a withdrawal of the drug, 
 means for the acceleration of its elimination and an appropriate 
 diet. The physical strength of the patient must be improved, and 
 a change of residence must be advised as a means for the relief of 
 the psychical symptoms. The kidneys are to be stimulated to 
 facilitate the elimination of the bromide of potassium, inasmuch as 
 they are the usual channels for the escape of the halogen salts; 
 diuretics are, therefore, indicated. 
 
 POTASSII CHLORAS. 
 
 Jacobi* has more recently called attention to the dangers which 
 may attend the exhibition of large doses of the chlorate of potas- 
 sium, and has reported a number of observations of dangerous 
 transitory symptoms and even fatal effects as resulting from such 
 employment of it. These reports have been confirmed by the 
 observations of Marchand, f Baginsky,J Hofmeier§ and Weg- 
 scheider.|| On the basis of these facts Marchand declares 
 that the chlorate of potassium should be entirely rejected in 
 practice, and particularly in the treatment of children. It 
 must be said, however, that the cases which he adduces in 
 support of this declaration have been shown by Küster** not 
 to be impervious to criticism in the matter of diagnosis. But 
 should all drugs, which, when given in improper quantities, or even 
 
 *Jacobi, Gerhardt's Handbuch der Kinderkrankheiten, ii., p. 764 and The Medical 
 Record, 1879, iii., 112. 
 
 tMarchand, Virchow's Archiv., Bd. 77, p. 456. 
 
 JBaginsky, Arch. f. Kinderheilkunde, nach einen Vortrage vom 10 November, 1878. 
 
 §Hofmeier, Deutsche Medicin. Wochenschr., 1880, Nos. 38 and 39. 
 
 RWegscheider, eod. loc, No. 40. 
 
 **Küster, Berlin. Klin. Wochenschr., 1880, No. 40. 
 
ALTERATIVES POTASSII CHLORAS. I 25 
 
 when given in their ordinary doses, occasionally give rise to 
 unpleasant symptoms, be thus discarded, the materia medica would 
 soon be reduced to the minimum of ingredients. In place of being 
 thus ready to discard a drug, it would be well to first determine the 
 exact doses suitable for different ages, and to determine as nearly as 
 possible, the conditions of the system which perhaps predispose to 
 those unpleasant symptoms. 
 
 The fact that over-doses of the chlorate of potassium are liable 
 to cause fatal poisoning has been recognized ever since Lacombe* 
 published a case of this nature. Isambert,f who employed the drug 
 for several days, during which he increased the daily amount from 
 S to 20 grammes ( 3 ij to 3 v), noticed as a result, greenish colored 
 stools and increased discharge of urine, with accompanying pres- 
 sure and pain in the region of the kidneys. He could detect the 
 salt in the urine within ten minutes after its exhibition, and the 
 elimination continued for one or two days. PodcopaenJ demon- 
 strated the poisonous action of the chlorate of potassium on dogs by 
 injecting it subcutaneously. 
 
 The cases of poisoning reported by the authors cited present a 
 series of symptoms rivalling in their defmiteness and threatening 
 nature those which follow the most active poisons. These symp- 
 toms are a continuous choking sensation and persistent vomiting, 
 an icteric discoloration of the skin, pain in the stomach and in the 
 region of the kidneys, epistaxis, diminution in the quantity of urine 
 or anuria, which may last for a day or a day and a half, hematuria 
 and albuminuria. These symptoms may be attended with insom- 
 nia, alternating sensations of cold and heat, without, however, 
 demonstrable fever, a small, rapid pulse, violent hiccough, coma and 
 death. In the case reported by Wegscheider there appeared on the 
 seventh day of the poisoning an eruption of defined red spots, of 
 the size of a bean, and not elevated, and becoming temporarily pale 
 under pressure, at first confined to the arms and forehead but after- 
 wards spreading over the entire body and becoming larger and of 
 a copper color. 
 
 As opposed to these observations there may, however, be 
 
 *Lacombe, Journ. de Medecine de Bruxelles, 1856. 
 
 tlsambert, Etudes chimiques, physiologiques et cliniques sur l'emploi Therap. de Clor, de 
 Potasse, Paris, 1856. 
 
 ^Podcopaen, Virchow's Archiv. Bd. XXXIII. p. 505. 1865. 
 
I2Ö THE UNTOWARD EFFECTS OF DRUGS. 
 
 mentioned the fact that there had, previous to the record of them, 
 been no case mentioned in the literature of the subject in which the 
 exhibition of the chlorate of potassium, in medicinal doses, had been 
 followed by other deleterious untoward effects than some disturb- 
 ance of digestion. In speaking of medicinal doses we have in 
 mind those given by Falck:* 0.1-0.5 gramme (gr. jss to gr. viij) 
 per dose, or 5 grammes (gr. lxxv) during the course of the day, or 
 those laid down by Jacobi (I.e.): for a child of from one to three 
 years 1-2 grammes (gr. xv to gr. xxx) daily, and for adults 6-8 
 grammes ( 3 jss to 3 ij) a day. 
 
 It is, of course, understood that we eliminate from this connec- 
 tion those cases in which it is impossible to determine to a certainty 
 whether the symptoms, or fatal issue, are due to the chlorate or to 
 existing diphtheria for which the drug has been given. As soon as 
 the amount of the drug exhibited exceeds the quantity ordinarily 
 prescribed a list of deleterious effects may supervene, as 
 Marchand has noted in his second observation: A boy of three 
 or four years, who during the course of the day had taken 10 
 grammes ( 3 ijss) of the chlorate of potassium for a stomatitis, 
 became soporose, and was afterwards attacked with diarrhoea and 
 vomiting. These symptoms were followed by delirium, epistaxis, 
 hsematuria and albuminuria, the urine also depositing a granular 
 brownish sediment. It was fully two weeks before the normal 
 condition was restored. 
 
 The treatment of such accidents can at best be but symp- 
 tomatic. The stomach must be emptied of its poisonous con- 
 tents, the vomiting allayed by pellets of ice, champagne, etc., and 
 the kidneys soothed by means of demulcent drinks: these are the 
 remedial measures to be resorted to. 
 
 POTASSIUM CHLORIDUM. 
 
 The chloride of potassium, regarded by Sanderf as of equal 
 value with the potassic bromide, is claimed by him to possess the 
 advantage of not being followed in its exhibition by untoward 
 effects. Neither of these statements have, however, been borne out 
 
 * Falck, Uebersicht der Normalgaben der Arzneimittel, Marburg, 1875, p. 10. 
 ISander, Centralbl. f. d. Medicin. Wissenschaften. 1868, No. 52. 
 
ALTERATIVES POTASSIUM CHLORIDUM. 12/ 
 
 by farther experiments. Thus Starck,* as has already been indi- 
 cated, found that the chloride of potassium exerted no influence 
 whatever in epileptic seizures, but that it, on the contrary, caused 
 in individual cases a series of deleterious untoward effects similar 
 to those aroused by the bromide given in medicinal quantities. 
 These consisted of a slight degree of mental confusion, drowsiness, 
 torpidity, pain in the limbs, diminished power of motion, difficulty 
 of speech, lessening of the appetite, and in one case a complete 
 suspension of the reflex irritability of the pharynx. During the 
 manifestation of these symptoms the pulse diminished perceptibly 
 in frequency. 
 
 POTASSIUM SULPHIDUM. 
 
 The external application of the alkaline sulphides, and particu- 
 larly the sulphide of potassium, in the form of ointments, lotions 
 and baths, may in certain persons, and particularly in such as are 
 predisposed, not infrequently give rise to an irritation, the intensity 
 of which is in indirect proportion to the quantity of the salt 
 employed. 
 
 According to Bazinf there appears on a reddened base, and 
 attended by intense pain, small, confluent vesicles, which become 
 filled with purulent or serous fluid, and surrounded by an areola of 
 two or three times the extent of their diameter. The affection dis- 
 appears in the course of a few days. 
 
 But more serious symptoms may manifest themselves as a result 
 of inunctions with the sulphide of potassium. Thus Bazin saw after 
 four or five applications of a solution of 4 grammes ( 3 j) of this 
 salt in 30 grammes ( 3 j) of water, to the lumbar region, an intense 
 phlegmonous inflammation, with the formation of pustules and 
 abscesses. A peculiarity in this case was the fact that there was but 
 a very moderate degree of inflammation on the thighs and buttocks, 
 to which the lotion had also been applied. 
 
 *Starck, Zeitschr. f. Psychiatrie xxxii., p. 15Q. 
 
 tBazin, Lecons sur les affections cutanees artificielles, Paris, 1862, p. no. 
 
128 THE UNTOWARD EFFECTS OF DRUGS. 
 
 Excitants. 
 
 CAMPHORA. 
 
 Camphor taken into the mouth gives rise to a biting and after- 
 wards burning taste, which is followed by a feeling of cold extending 
 into the stomach. If kept for some time in the mouth it occasions 
 symptoms of local irritation of the mucous membrane, pain, swelling, 
 etc. The painful irritative action of the drug is also manifest when 
 it is applied to abraded surfaces. 
 
 The effects noticeable after the internal exhibition of camphor 
 in medicinal doses vary, according to Jörg,* with the individuality 
 of the person affected. While 0.3 — 0.5 gramme (gr. v. to gr. viij.) 
 occasions no perceptible abnormal sensation in some, from 0.03 — 
 0.06 gramme (gr. ss. to gr. j.) will give rise in others to headache, 
 dizziness, slight mental confusion, flushing of the face, with dryness 
 of the mouth and thirst. 
 
 The alcoholic solution of camphor is said to be more energetic 
 in its action than the drug in substance. Purkinjef noticed in his 
 own case after doses of upwards of 0.5 gramme (gr. vijss.) an agree- 
 able excitement and enlivenment, resembling alcoholic intoxication, 
 and a slight prickling sensation in the skin. 
 
 While these symptoms for the most part rapidly disappear, 
 without any unpleasant sequelae, the symptoms which follow enemata 
 containing camphor are not infrequently more threatening and per- 
 sistent, demanding therapeutic interference. In such cases there 
 occur vomiting, the egesta smelling of the drug, strangury, heat, 
 clammy perspiration, also having the odor of camphor, increased 
 frequency of pulse, and exaltation of spirits which may even develop 
 into delirium. 
 
 In such cases enemata of senna and sulphate of sodium, 
 sinapisms to the nape of the neck and body, or cold compresses or 
 cold douches to the head, are indicated by way of treatment. 
 
 *Jörg, Materialien zu einer Arzneimittellehre, Jena, 1827, p. 330. 
 f Purkinje, Neue Breslauer Samml., 1829, i., p. 428. 
 
EXCITANTS MOSCHUS. I 29 
 
 MOSCHUS. 
 
 The statements regarding the untoward effects following the 
 use of musk are somewhat contradictory. Jörg* noticed in those 
 on whom he experimented that doses of 0.06-0.25 gramme (gr. j to 
 gr. jv) were followed by slight headache, particularly in the frontal 
 region, mental confusion, dizziness and a sense of pressure in the 
 eye sockets. As touching the digestive tract, Jörg, in his own case, 
 experienced gastric oppression, eructations with a permeating odor 
 of musk following 0.18 gramme (gr. iij) of the drug, and others 
 noticed a burning and dryness of the throat. On the other hand 
 Trousseau and Pidouxf experienced, after similar doses, only a pecu- 
 liar warmth of the stomach and abdomen, which was followed by a 
 pronounced sensation of hunger. Later they experienced also pain 
 in the frontal and occipital regions, dizziness and an excitement of 
 the sexual organs. 
 
 According to other observations of MitscherlichJ small doses of 
 musk may occasionally give rise to vomiting without digestive dis- 
 turbance, a peculiarity probably traceable to an inherent aversion to 
 the drug. Diarrhoea has also been observed to follow the exhibition 
 of musk. 
 
 RADIX VALERIANAE. 
 
 The root of valerian, very generally regarded as comparatively 
 inert, may, according to Jörg (1. c), even in small doses, excite 
 unpleasant symptoms in some persons. He occasionally observed 
 the following symptoms, occurring either singly or combined, as 
 effects of from 4 to 8 grammes ( 3 j to 3 ij) of an infusion of the 
 root : a scraping sensation in the throat, eructation, nausea, head- 
 ache, particularly in frontal and parietal regions ; a feeling of con- 
 striction of the throat, borborygmi, diarrhoea, colicky pains and 
 anorexia. 
 
 Barbier § noted hallucinations of sight in a person who was 
 being treated with valerian. 
 
 *Jörg, 1. c, p. 285. 
 
 tTrousseau et Pidoux, Traite de Therap. Illieme edit, II., p. 193. 
 JMitscherlich, Lehrbuch der Arzneimittellehre, Berlin, 1849, Bd. II., p. 369. 
 §Barbier, Matiere Medic. 1824, II., p. 83. 
 
I30 THE UNTOWARD EFFECTS OF DRUGS. 
 
 FLORES ARNIC^E TINCTURA ARNICiE. 
 
 Arnica, even in small doses and regardless of the manner of its 
 employment, may cause disagreeable effects in some persons. An 
 infusion of 0.3 to 1.0 gramme (gr. v to gr. xv) in 120 grammes 
 ( S J v ) °f water, not infrequently causes a burning and scratching 
 sensation in the mouth and throat, pains in the stomach, eructations, 
 a cutting pain in the abdomen, and occasionally also tenesmus and 
 diarrhoea. Later an oppressive headache, mental confusion, dizzi- 
 ness and restless sleep ensue. 
 
 More recently Wilkinghoff* has shown that the active principle 
 of arnica may become weaker and finally become inert with age. 
 This fact offers an explanation of the diversity of action which 
 attends the drug. 
 
 It appears that the symptoms mentioned as referable to the 
 primae viae, are due to a local irritative action of the drug, and that 
 the nervous disturbances are of a reflex nature. In support of this 
 view may be adduced the fact that the application of the tincture of 
 arnica to the sound skin, causes, according to the activity of the 
 preparation employed, either itching and burning and shortly after 
 a reddening of the affected parts, or miliary or linseed sized pus- 
 tules, or even distinct bullae, may appear on the reddened base. 
 These changes are attended by decided constitutional symptoms. 
 
 Wilkinghoff, Medicin. Beiträge zur Kenntniss der Arnica montana. Inaug.- Dissert. Bonn, 
 
NARCOTICS — -OPIUM. IZL 
 
 Narcotics. 
 
 OPIUM. 
 
 There is scarcely any other medicinal substance, the abnormal 
 action of which is so largely dependent on the individual conditions 
 of the patient, as is the case with opium. Among these conditions 
 are the age and sex of the person, the nature of the disease, and, 
 according to Charvet,* even the climate and race; in short, that 
 peculiar susceptibility to the particular action of a certain drug, 
 which is dependent on certain physical properties which it is difficult 
 to define in a given case. 
 
 Regarding the matter of age it is to be noted that in many 
 children deleterious and even fatal effects may readily follow the ex- 
 hibition of opium. The recognition of this fact has caused it hereto- 
 fore to be regarded as an axiom that opiates should be given in very 
 small and definite doses in such cases. More recently, this teaching 
 has been largely ignored, the dangers which have been said to result 
 from the use of the drug being regarded either as overdrawn or 
 absolutely without foundation. The numerous accidents, however, 
 which are recorded in the literature of the subject, and in spite of 
 small and even minimal doses of opium, serve as a good basis for 
 this warning and argue for great circumspection in the employment 
 of the drug. Thus Sobotka,f among others, reports several cases in 
 which serious toxic symptoms supervened on the exhibition of almost 
 minimal doses of opium and in one case even death ensued on the 
 administration of a tablespoonful of a mixture of 180 grammes ( 3 vj) 
 containing 3 drops of laudanum and 15 grammes ( 3 ss) of syrup 
 of poppies. Edwards]; and Smith § also, saw fatal effects follow 
 even still smaller doses — 0,0003 to 0.0006 gramme (gr. 2 ±^ to gr. 
 j-Ju). A larger number of similar observations have been collected 
 by Taylor. J 
 
 *Charvet, Die Wirkung des Opiums auf die Thier. Oeconomie. Leipzig, 1827. 
 
 +Sobotka, Journal f. Kinderkrankheiten, Decemb., 1845. 
 
 ^Edwards, Ref. bei Taylor die Gifte. 
 
 §Smith, Medical Times and Gazette, 1854, April 15, p. 386. 
 
 ÜTaylor, Die Gifte, übersetzt von Seydeler, Coin, 1863. Bd. III., p. 31. 
 
I32 THE UNTOWARD EFFECTS OF DRUGS. 
 
 Owing to their greater susceptibility to irritation women are, 
 cseteris paribus, more apt than men to suffer from the abnormal 
 action of the drug. Gastric disturbances and existing hypersemia of 
 the brain are, furthermore, conditions which predispose to these 
 deleterious untoward effects. But constitutional bodily conditions 
 are preeminently capable, in all persons, of modifying the normal 
 action of opium or of exciting unwonted symptoms. 
 
 The untoward effects noted up to this time may manifest them- 
 selves regardless of the form in which the drug is given. They 
 appear, however, to be most apt to occur after enemata, inasmuch 
 as there are numerous cases on record, in which very minute doses 
 of opium given in this form, were followed by threatening symptoms 
 and even death. Whether, as maintained by Dupuytren,* absorption 
 of opium is more rapid and complete from the intestines than from 
 the stomach, thus facilitating a more complete action of the drug, 
 has not yet been determined by experimentation. 
 
 We shall first consider the central nervous system as the seat of 
 action of opium. There not infrequently occur in certain individ- 
 uals after doses of 0.015 to 0.05 gramme (gr. J- to gr. -§-) intense 
 mental confusion, vertigo and headache, lasting for several 
 hours and even days, being sometimes referable to the frontal 
 region and sometimes to the occipital. These symptoms were 
 familiar to the ancient physicians, such as Scribonius, Largus 
 and others. Tralles,f who reports an observation of this 
 nature in a man, says regarding it in rather unclassical Latin: 
 ". . . per multos dies ponderosissimum caput circumgestasse." 
 Convulsions are also said to have been observed as an effect of 
 medicinal doses of opium. Larger doses, which, however, fall short 
 of the maximum amount, are furthermore asserted to have caused 
 buzzing and ringing in the ears, confusion of ideas, dimness of 
 vision, disturbances of hearing, and partial or complete unconscious- 
 ness. The motor tract may be affected in a similar manner, and, as 
 stated by AlbersJ, twitching of the tendons, particularly of the exten- 
 sor muscles, tremor of the hands, jerking, a sort of paralytic weak- 
 ness of the lower extremities and even temporary paralysis have 
 been observed. Occurring either simultaneously with these symp- 
 
 * Dupuytren Lecons de Clinique Chirurgie. Paris, 1832, 1, p. 187. 
 tTralles, Usus Opii salubris et noxius, Vratislav, 1774. 
 tAlbers, Virchow's Archiv, Bd. 26, p. 225. 
 
NARCOTICS — OPIUM. 133 
 
 toms or independently of them, disturbances of the digestive 
 apparatus may also present as effects of the action of opium. The 
 mouth and the throat become dry, nausea and vomiting occur and 
 the appetite fails. The latter, however, occurs most frequently only 
 as a result of the repeated exhibition of the drug. 
 
 The changes which occasionally take place in the skin as a 
 result of the use of opium, merit a special consideration. Aside 
 from the very profuse diaphoresis which sometimes occurs, the face 
 becomes turgid and highly reddened, while the rest of the integu- 
 ment is hot to the touch. In such cases tormenting itching without 
 eruption may also occur. This " pruritus opii " was noted by 
 Dioscorides,* Paulus Aegineta,f and other writers also in the last 
 century, and described as an annoying and unbearable affection. 
 
 In rare cases an eruption occuring with or without itching has 
 been observed to appear as a result of the medicinal use of opium. 
 Trallesj; was the first to describe this eruption. According to his 
 view there exists a certain relation between it and the sweating 
 which appears synchronously with it. The occurrence of sweating is 
 however, not a condition of the occurrence of the eruption. 
 Duclos § makes especial note of the fact that it may occur without 
 diaphoresis. 
 
 The opium eruption generally occurs in the form of small red 
 isolated spots, which resemble roseola in their general character. 
 According to an observation made by Rieken || these spots may 
 spread over the whole body and thus present a scarlatiniform ap- 
 pearance. Even the mucous membrane of the mouth and throat 
 may, according to him, be attacked with this " erythematous inflam- 
 mation." He saw such an eruption in a man after each internal 
 exhibition of opium, and even though it was merely employed in 
 ointments and collyria containing it. These erythematous spots, 
 according to Berenguier,** occur on the face, neck, arms and breast 
 shortly after the exhibition of opium and disappear without leaving 
 a trace behind. Behrend*** has also more recently observed an 
 
 *Dioscorides, De noxiis venenis. Cap. xxiii. Venetiis, 1516, p. 124. 
 tPaulus Aegineta, Opera. Lugduni, 1551. Lib. v. Cap. XLIII. p. 355. 
 JTralles, 1. c. p. 137 und 138. 
 
 §Duclos, Journ. de Medec. Septembre, Novembre, 1846, Ref. in Schmidt's Jahrbücher, 
 Bd. 64, 1849, P- 74- 
 
 URieken, Schmidt's Jahrbücher, Bd. cvii., p. 22. 
 
 **Bereguiner, Des eruptions provoquees par l'ingestion des medicaments. Paiis, 1874. 
 
 ***Behrend, Berliner Klin. Wochenschrift, 1879, P- 626 - 
 
134 THE UNTOWARD EFFECTS OF DRUGS. 
 
 opium exanthem. This occurred after the exhibition of a powder 
 composed of 0.015 gramme (gr. x /^) of opium and 0.5 gramme 
 (gr. vijss) of sugar, and was attended by intolerable itching. On the 
 chest it extended from the clavicles to the lower end of the sternum, 
 and appeared also on the inner surface of the arms, on the flexor 
 surfaces of the forearms and the wrists, on the thighs, from the 
 location of the adductors to the popliteal spaces, and on the posterior 
 and inner surfaces of the legs, terminating at the ankles in a stripe of 
 livid discoloration of about three fingers in breadth. It appeared 
 as a pale scarlatina-like red, which spread to the surrounding 
 healthy skin, and was seen, on closer examination to consist of 
 closely disposed papules of the size of a pin's head. Several days 
 after the disappearance of the eruption a fine bran-like desquamation 
 of the epidermis ensued. 
 
 Brand* also observed an eruption which occurred with intense 
 itching and fever, and appeared on the trunk and flexor surfaces. 
 It consisted of innumerable small points which gave it the appear- 
 ance of diffused redness. In this case and in one of a similar nature, 
 desquamation supervened after a week and continued for upwards of 
 ten days, shedding flakes of various sizes. 
 
 The manner of the occurrence of this eruption is probably the 
 same as that in which eruptions occur in connection with other med- 
 icines. We may in addition, in this case, regard as a cause, a direct 
 action of the drug on the parts of the skin attacked or on the trophic 
 nerves. This hypothesis enables us at least to form an opinion as 
 to the most direct cause of this affection, even though we are unable 
 to explain by means of it, how it is that only certain persons and only 
 certain portions of the bodies of these are attacked. Notwithstand- 
 ing the statement made by Behrend (1. c.) in his description of the case 
 mentioned, that the occurrence of the opium eruption in consequence 
 of a partial elimination of the drug through the skin, or even through 
 its presence in the cutaneous vessels, is to be excluded " with abso- 
 lute certainty," we cannot by any means so concede it, inasmuch as 
 a similar elimination has been demonstrated and is known to occur 
 in the case of other drugs. His claim that the eruptions following 
 the use of opium and other drugs are due to a change induced by 
 them in the blood, would, even were it true, be conditioned at least 
 on a localized action of the dyscrasic blood on the skin. 
 
 : Brand, Berliner Klin. Wochenschr, 1879, p. 718. 
 
NARCOTICS MORPHIA. 
 
 In the matter of the treatment of the untoward effects of opium, 
 the suspension of the drug is usually followed by a spontaneous 
 recovery. Should very threatening symptoms, such as coma, etc., 
 occur, external irritation, stimulants, ice compresses, cold baths, sin- 
 apisms, etc., are to be resorted to. According to Da Costa* the 
 bromide of potassium is a preventive of the untoward effects of 
 opium and particularly of the faintness, headache, dizziness and 
 nausea, besides lessening also the pruritus of the skin, when taken in 
 doses of 2 to 3.5 grammes ( 3 ss to 3 j) several hours before the 
 
 exhibition of the opium. 
 
 MORPHIA. 
 
 What has been declared of the action of opium is equally appli- 
 cable to that of its most active constituent, morphia, and its salts. 
 Headache, stupor and particularly nausea and vomiting — the appe- 
 tite not being impaired— have been observed to follow its use. 
 Thus Billrothf observed in the case of a lady that small doses — 
 0.007 an d even 0.003 gramme (gr J- — gr ^V were followed by such 
 a feeling of anxiety, nausea and vomiting, that in spite of intense 
 pain, she refused to take the drug. 
 
 Laborde accounts for the vomiting on the supposition that the 
 morphia is of bad quality, having been partially transformed, by 
 keeping, into apomorphia. There has, however, been no exact 
 chemical investigation made on this subject. Bally.]; observed gastric 
 pains occurring, especially in women, in addition to vomiting, as a 
 result of the use of morphia. They disappeared simultaneously 
 with the suspension of the drug. He also occasionally observed 
 colicky pains referable to the region of the umbilicus. Brochin 8 
 has reported a case in which the " idiosyncrasy " against morphia 
 was so great, that 0.0025 gramme (gr ^K) of. the drug administered 
 hypodermically caused irregularity of respiration, momentary sus- 
 pension of the heart beat and profound narcosis. 
 
 WernichJ has called attention to the occurrence of paresthesia 
 of the sense of taste after the employment of morphine^ which, ac- 
 
 *DaCosta, Virchow-Hirsch's Jahresbericht, 1871, I., p. 307. 
 tBillroth, Wiener Medicin. Wochenschrift 1868, p. 763. 
 $Bally. Mem. de l'academ royale de Medic I. 99. 182S. 
 §Brochin, Gazette des Höpit, 1877, p. 226. 
 JWernich, Archiv, f. Psychiatrie, Bd. II., p. 174. 
 
136 THE UNTOWARD EFFECTS OF DRUGS. 
 
 cording to his observation, is particularly prone to supervene in 
 patients who are much reduced, and in persons, otherwise healthy, 
 who have suffered from prolonged inanition. These effects are 
 probably due to a central excitation of a similar nature to that in- 
 duced by santonin. The persons thus attacked complain, shortly 
 after the injection, of an intensely bitter or sour taste, which, for the 
 most part, ceases with the cessation of the action of the morphia. 
 
 The occasional untoward action of morphia on the eyes has 
 been minutely described by v. Graefe.* It reveals itself, particularly 
 in very irritable persons, in spasm of accommodation, which super- 
 venes on the excitation wrought by the drug on the ciliary muscle. 
 The focal point is brought so near that the range of accommodation 
 is very much contracted, and myopia is the result. Sommerfrodt 
 observed a spasm of accommodation, lasting only half a minute, to 
 occur in an analogous manner after the subcutaneous administra- 
 tion of 0.0 1 gramme (gr. 1) of morphia. The outlines of the faces 
 and heads of those standing by the bed seemed to the patient to sud- 
 denly coalesce, so that he was unable to recognize any one. While, 
 according to Graefe, this condition supervenes mostly in from half 
 to three-quarters of an hour after the injection, it appeared in this 
 case directly after it. 
 
 The use of morphia may also cause changes in the skin, as evi- 
 denced by the pruritus and exanthematous eruptions which follow. 
 Thus Apolantf saw an urticaria-like eruption occur in a man who 
 took several doses of twelve to fifteen drops of a solution of 0.08 
 grammes (gr. j-J-.) of muriate of morphia in 10.0 grammes ( 3 ijss) of 
 bitter almond water. The patient, without knowing the ingredients 
 of the prescription, attributed the eruption to morphia, from the fact 
 that he had observed his susceptibility to this untoward effect of the 
 drug on a previous occasion. The eyelids became swollen, the whole 
 face cedematous, and the hands and other parts of the body covered 
 with red, wheal-like elevations. Desquamation set in after five days, 
 following which whole pieces of epidermis could be pulled off. 
 
 The peculiar untoward effects of morphia mentioned are to be 
 distinguished from the symptoms which certainly and frequently 
 occur, although the manner of the occurrence is not clear, after the 
 subcutaneous injection of the drug when the canula is accidentally 
 
 *v. Graefe, Archiv f. Ophthalmologie, Bd. IX., 2, p. 62. 
 tApolant, Berliner Klin. Wochenschrift 1877, p. 361. 
 
NARCOTICS OPIUM EATING AND THE MORPHIA HABIT. I37 
 
 introduced into a vein, thus making a direct intravenous injection, 
 Under such circumstances there occur, as Chouppe* has stated, 
 flushing of the face, heaviness of the head, confusion of ideas, 
 increased frequency of the pulse, up to ioo beats, a feeling 
 of anxiety and cold perspiration. These symptoms disappear 
 in a few minutes, and may be prevented by a slight 
 withdrawal of the canula after it has been introduced, 
 or by first introducing the canula, and injecting the fluid only after 
 any bleeding which may occur from the puncture has ceased. 
 
 Disagreeable effects have quite frequently been observed when 
 opaque solutions of morphia, due to fungi, have been used for sub- 
 cutaneous injections. Thus Dumasf reports a case in which, after 
 the injection of the opaque precipitate of a solution of morphia, a 
 phlegmonous erysipelas of the abdominal walls was developed. At 
 the site of the injection there was a hard nucleus which soon 
 developed into an intensely red swelling, which included almost the 
 fourth part of the abdomen. A putrid liquid w T as evacuated by 
 incision. There appeared inflammation and scaly desquamation of 
 the subcutaneous areolar tissue with violent symptoms. Under 
 antiseptic treatment, and after several incisions had been made, the 
 patient recovered. Dumas recommends the boiling of the solution 
 before each injection. 
 
 According to the investigations of HambergJ a solution of the 
 sulphate of morphia keeps longer, and is less inclined to decompo- 
 sition and to the formation of mycelia than a solution of the 
 muriate of morphia. 
 
 As a conclusion to this subject we shall notice the pathological 
 condition which has frequently and thoroughly been discussed in 
 recent literature, as following the habitual use of opium or morphia. 
 
 OPIUM EATING AND THE MORPHIA HABIT. 
 
 The symptoms which develop as a result of the continuous em- 
 ployment of opium in increasing doses, are of the same nature as 
 those which attend the internal or hypodermic exhibition of morphia. 
 The quantities which can be taken by some persons for a long time 
 
 : Chouppe, Gazette hebdomd de Medecine et de Chirurg. Mars, 1876, p. 162. 
 Dumas, Bullet, gener de Therap. 30 Juin, i83i. 
 :Haruberg, Pharmaceut. Zeitung No. 49, 1881. 
 
I^S THE UNTOWARD EFFECTS OF DRUGS. 
 
 without injurious effect are enormous, when we recall the smallness 
 of the dose ordinarily required to give rise to grave and even fatal 
 symptoms. Were it not for the fact that we are obliged, through 
 indubitable evidence, to believe the reports of the enormous amounts 
 which are said to have been given, we should give the reports of such 
 quantities but little credence. Toleration for doses, which, under 
 other circumstances would certainly be fatal, is conditioned on habit- 
 uation to the action of the poison, and can only be established by 
 commencing with small doses and gradually increasing them. There 
 is nothing to oppose the view that the cell groups whose functions 
 are especially involved are at first only temporarily changed by the 
 opium, then losing their energy through the continuous chemical or 
 physical influence exerted on them, they demand an increasing 
 strength in the irritant to arouse the same functional capacity which 
 previously obtained, and are thus at the same time protected against 
 the danger of poisonous action on the part of the drug given. 
 Finally, however, a point must be reached at which the quantities 
 given are no longer sufficient to arouse or to inhibit certain organic 
 functions, and when a further increase of the dose induces such 
 deep-seated changes in the organ itself, or,, through reflex or sympa- 
 thetic action in other organs, that the symptoms of poisoning and 
 its consequences supervene. 
 
 These conditions may be developed through the repeated thera- 
 peutic employment of opium or morphia. The patient who has come 
 to understand the anodyne effect of these drugs resorts to them 
 when opportunity offers, for relief in conditions of such slight indis- 
 position as would be borne by another without seeking medical aid. 
 Herein lies the first step on the track which leads inevitably to the 
 pernicious use of these narcotics. For when the unpleasant bodily 
 conditions which furnish an excuse for the taking of the drug are 
 wanting, there appear first, psychical emotions, as worry and anx- 
 iety, which are superseded by slight mental disturbances, anger, 
 vexation, etc., happy forgetfulness to which, or a pleasant alienation 
 of consciousness lasting for hours, is secured by suitable doses of 
 the opiate. And should these inducements fail, the constantly in- 
 creasing indisposition to work, the neglect of social and domestic 
 duties, and the other manifold changes in the emotional nature as 
 well as in the bodily functions, furnish an excuse for a further 
 
NARCOTICS OPIUM EATING AND THE MORPHIA HABIT. 1 39 
 
 increase of the dose, until a bodily and spiritual marasmus, or a nat- 
 ural or violent death closes the deplorable scene. 
 
 Before the more promptly and powerfully operative morphine 
 came into the extensive employment which now obtains, the phases 
 of the abuse of narcotics, above described, were observed either sin- 
 gly or collectively in the effects of opium. Flemming* gives a graphic 
 description of the moral condition and bodily tortures of the opium 
 eater. He shows how such persons can only be induced by. strat- 
 egy to acknowledge their vice, how they have become lost to all 
 sense of shame, and how social and family ties are severed by this 
 passion. In the advanced stages of this condition there are mental 
 depression or exaltation, childish impatience, inability to think or to 
 fix the attention on a certain object, a want of interest in the daily 
 occurrences of life, as also a beclouding of the memory and judg- 
 ment. Simultaneously with these, bodily sufferings manifest them- 
 selves, such as sleeplessness, a gnawing pain in the region of the 
 stomach, anorexia, chilliness with sweating, and not infrequently 
 disturbances of the sexual function. 
 
 Morphia taken internally gives rise to the same symptoms. In 
 a case reported by Samterf the morphia habit was continued for 
 three years, during which in a period of about 323 days, upwards of 
 79.5 grammes ( 3 ij ss) were taken. EderJ reports still larger doses. 
 In the case observed by him the patient took laudanum for six 
 years in increasing doses up to 30 grammes ( f j) per day, for 
 eighteen months pure opium, commencing with 1 gramme (gr. xv) 
 and increasing to 9 grammes ( 3 ijx)> daily ; and for eighteen months 
 morphine in commencing quantities of 0.4 gramme (gr. vj), which 
 were later increased to 2.6 gramme (3ij) a day. 
 
 The introduction of the hypodermic use of morphia and the 
 practice of intrusting the syringe to the patient to be used either 
 personally by himself or by his attendants, has undoubtedly done 
 much to cause the spread of the morphine habit, although we are 
 not yet quite justified in saying with Bouchardat,§ " que le mor- 
 phinisme fait ä Berlin de tels progres qu'il y a des maisons de sante 
 speciales pour en recueillir les victimes." 
 
 *Flemming-, British Medic. Journal, February 51, 1868, p. 177. 
 
 tSamter, Deutsche Klinik, 1864, 16, 17. 
 
 *Eder, Oestreichische Zeitschrift f. pr. Heilkunde, 1864, No. 33. 
 
 §Bouchardat, Annuaire de Therapeut, de Matiere me\iic. Paris, 1.879, P- *3« 
 
140 THE UNTOWARD EFFECTS OF DRUGS. 
 
 Observations bearing on this subject have been of increasing- 
 frequency of late years. Mattison,* in America, has called attention 
 to the abuse of morphia which obtains in that country. Lährf and 
 FiedlerJ were the first to raise their voices against the spread of this 
 vice in Germany, which they attributed in part to the medical pro- 
 fession. Coincidently with Fiedler, L. Lewin § reported a case of 
 the morphia habit. More recently Levinstein, || basing his remarks 
 on extensive observations, has treated the subject most thoroughly, 
 and following him Burkart** reported his observations. 
 
 In all cases there is an equal and gradual decline of the 
 psychical life, and further a series of bodily ailments, such as we 
 have indicated as pertaining to the action of opium and to the un- 
 toward effects of morphia. As less frequent symptoms there appear 
 in some cases slight transient albuminuria and also glycosuria, in a 
 similar manner to their occurrence in other conditions of chronic 
 intoxication. The morphia habit should be regarded as such a 
 condition, and we cannot share the opinion of those who regard 
 either the individual groups of symptoms or the entirety of the 
 pathological appearances which present, as diseases in themselves. 
 For the arsenic habit, alcoholism, and the group of saturnine affec- 
 tions and other states in which the mental and bodily conditions are 
 equally extensively affected, may be regarded, from a clinical 
 standpoint, as intoxications which have only received such a special- 
 impress through the secondary phenomena due to the long continu- 
 ance of the condition, as have made the pathological aspect some- 
 what complex. 
 
 The therapy of opium-eating and the morphia-habit consists, 
 naturally, in the withdrawal of the drugs. Regarding the manner of 
 this withdrawal, i. <?., whether it shall be sudden or gradual, there is 
 a diversity of opinion. This question, as it applies to pure opium, 
 was discussed before the morphia-habit was known. Christison first 
 enforced the sudden withdrawal of the narcotic in 1850. According 
 to Flemming (1. c.) the mental and bodily sufferings of the patient 
 are aggravated by this method; he becomes sleepless, irritable,. 
 
 *Mattison, Schmidt's Jahrbücher, 1875, No. 1, p. 21. 
 
 1 Lahr, Zeitschrift f. Psychiatrie 1872, H. 3. 
 
 ^Fiedler, Deutsche Zeitschr. f. pr. Medicin 1874, No. 27. 
 
 §L. Lewin, Eod. loco 1874, No. 28. 
 
 IILevinstein, Die Morphiumsucht, Berlin, 1876 und Berl. Klin. Wochenschrift 1875, No. 48. 
 
 **Burkart, Die chron. Morphium Vergiftung-, etc., Bonn, 1877. 
 
NARCOTICS CANNABIS INDICA. I4I 
 
 anxious, despondent and begs and importunes for opium. In con- 
 nection with this condition there are thirst, neuralgic pains, diar- 
 rhoea, sweats, chills, etc. But a sudden withdrawal of the drug tests 
 the physical and moral powers of the patient less severely than a 
 gradual diminution, for after each dose let it be ever so small, there 
 is an unpleasant reaction. In recent times both methods have also 
 been advocated for the withdrawal of morphia. In the course of 
 withdrawal should the patient be perfectly isolated and have no 
 opportunity of recourse to morphia, conditions of collapse are of 
 quite frequent occurrence, and to combat this it is necessary to 
 resort to analeptics, otherwise a fatal issue may easily ensue. The 
 state of excitability which occurs shortly after the withdrawal of the 
 morphia is equally to be feared, inasmuch as suicide in this condi- 
 tion is not an uncommon occurrence. The only means of determin- 
 ing whether morphia has been secretly administered during the 
 period of withdrawal is furnished by a study of the subjective con- 
 dition of the patient. Should this be very good there is in the fact 
 room for suspicion. The demonstration of the alkaloid in the 
 urine is generally an unreliable test, from the fact, as established by 
 Landsberg,* that the drug is very readily decomposed in the 
 blood. 
 
 Only a very small proportion of these patients succeed in 
 really and permanently weaning themselves from the morphine. By 
 far the largest number of them fall again into the old vice shortly 
 after the withdrawal of the drug. The exhibition of substitutes for 
 the morphia, such as cannabis indica, hyoscyamus, etc., has been 
 attended by no results. So also is the use of atropia, valerianate of 
 zinc, quinine and the bromide of potassium, as symptomatic remedies, 
 not indicated, inasmuch as the temporary relief of one or another 
 pathological condition, the cause not being removed, is quite use- 
 less. 
 
 CANNABIS INDICA. 
 
 EXTRACT CANNABIS INDIC/E. TR. CANNABIS INDICiE. 
 
 There occur, dependent on the strength of the preparation and 
 the individuality of the patient, after the exhibition of the prepara- 
 tions of hemp, untoward effects of varying degrees of intensity, which 
 
 *Landsberg-, Pflüger's Archiv, Bd. xxiii., 1880, p. 432, 
 
142 THE UNTOWARD EFFECTS OF DRUGS. 
 
 differ from the symptoms following the use of opium in being of 
 relatively rare occurrence, in being transitory in their action and in 
 leaving no unpleasant sequelae. The facts pertaining to this subject 
 have been recorded by Schroff.* He usually observed in those on 
 whom he experimented, a blunting of the sense of touch with a sen- 
 sation in the lower extremities as if asleep, vertigo, visual delusions 
 and slight delirium. Husemannf noticed as a result of an experi- 
 ment on himself, an alarming state of hilarity, while on another 
 occasion his spirits were depressed and sorrowful, a condition with 
 which the hallucinations and illusions which he experienced were 
 fully in keeping. 
 
 CAFFEINUM. 
 
 Caffeine, so largely employed as a remedy in migraine, seems 
 to produce different effects in different persons. HusemannJ noticed 
 after only 0.24 gramme (gr. jv.) severe determination of blood to 
 the head and embarrassment of respiration, while Albers§ experi- 
 enced no result after 0.18 — 0.3 gramme (gr. iij — gr. v) of the citrate 
 of caffeine. Frerichs, who took two grammes (gr. xxx.) of the pure 
 caffeine, felt only a slight sensation of cerebral congestion and 
 vomited but once. 
 
 FOLIA HYOSGYAMI. 
 
 EXTR. HYOSCYAMI. 
 
 The untoward effects following the employment of the prepara- 
 tions of hyoscyamus have very much in common with those excited 
 by belladonna. The affections of the skin are particularly promi- 
 nent, amounting in many persons to an erythema. Thus Cabot |[ 
 reports the case of a man who took tr. hyoscyamus to relieve a pain 
 in the abdomen. In a short time his nose began to swell, and a 
 slight swelling, accompanied by itching and a burning sensation, 
 spread over his whole body. The face became red and shining, 
 and this redness spread to the line of the umbilicus, below which 
 
 *V. Schroff, Lehrbuch der Pharmakologie, 1855, p. 536. 
 
 tHusemann, Handbuch der Toxikologie, 1862, p. 430. 
 
 JHusemann, 1. c, p. 544. 
 
 §Albers, Deutsche Klinik, 1853, 34. 
 
 iCabot, American Journal of the Medical Sciences, October, 1851. 
 
NARCOTICS HYOSCYAMIN. 143 
 
 there appeared only separate red spots. This erythema began to 
 fade in the course of an hour and a half, and almost entirely disap- 
 peared in a day. Bessieres* observed in a lady who had frequently 
 taken vaginal injections of a decoction of hyoscyamus, an erythema 
 of the face after an enema of the same material. Picardf also 
 reports the case of a woman in whom there occurred an erythema of 
 the face after the use of enema containing a medicinal dose of 
 hyoscyamus. 
 
 GoldingJ saw several occurrences of a pustular eruption follow- 
 ing the internal exhibition of small doses of hyoscyamus. 
 
 Functional disturbances of other organs may occur simultane- 
 ously with this affection, such as excessive dilatation of the pupils, 
 dizziness, weakness and collapse. Paralytic conditions of the upper 
 and lower extremities have also occasionally been observed. The 
 continued use of the drug is further said to give rise to swelling of 
 the parotids, salivation and catarrh of the nasal mucous membrane. 
 
 Therapeutic measures are only demanded for the weakness 
 which occurs, and consists in the exhibition of stimulants. 
 
 HYOSCYAMIN. 
 
 HYOSCIN. 
 
 The alkaloid of henbane has recently been introduced into 
 psychiatty, for its simple sedative properties, its mode of adminis- 
 tration being partially internally and partially hypodermically. 
 The untoward effects of the drug have thus become more familiar 
 than formerly. Some of these untoward effects may be due to the 
 bad quality of the drug or to a defective preparation of it. But 
 the purest, crystallized hyoscyamin may also, in some persons, give 
 rise to them. 
 
 Empis § gave pills containing 0.005 gramme (gr. 1-12) of hyos- 
 cyamin to a patient who had previously employed large doses of 
 hyoscyamus. The first dose excited a condition of irritability, the 
 
 *Bessieres, Abeille Medicale, November, 1853. 
 
 tPicard, Ref. bei FodeVe, Traitö de Medec. legale et d' hygiene publ. T. IV., p. 25. 
 $Goldiagf bei Wibmer, Wirkungen d. Arzneimittel und Gifte. München, 1842, Bd. Ill, p. 
 149. 
 
 §Empis, Gazette des Löpit. 1879, p. 949. 
 
144 THE UNTOWARD EFFECTS OF DRUGS. 
 
 patient (a female) becoming as if intoxicated, the blood rushing to 
 her head, and vomiting supervening. The second pill, given the 
 next day, caused a return of the uneasy symptoms, the speech 
 became difficult and swallowing impossible, and a delirium, similar 
 to that caused by alcohol, occurred ; respiration became laborious, 
 the pupils dilated and in addition to these there were symptoms of 
 clonic convulsions. This condition lasted for three hours and 
 demanded the exhibition of analeptics. 
 
 According to the observations of Reinhard,* also, the prolonged 
 employment of hyoscyamin gives rise to undesirable symptoms. He 
 administered to an insane person subcutaneous injections (0.05 
 gramme [gr. 5-6] in 5.0 gramme [ 3 j ] of water), and observed as a 
 result a decrease of nutrition, a sickly aspect, and frequently the 
 occurrence of boils. 
 
 Hyoscin, the alkaloid prepared by Ladenburg from amorphous 
 hyoscyamin, of which there is a crystallizable hydriodate, also gives 
 rise, during its therapeutic employment, to untoward effects similar 
 to those induced by atropia. Edlefsen and Illing,f and GnauckJ 
 also, assert that there is great variability in the individual suscepti- 
 bility to the drug. Some persons cannot tolerate even 0.0001 
 gramme (gr. 1-600) of hyoscin, while in others the subcutaneous 
 injection of 0.0025 gramme (gr. 1-25) gives rise to no particularly 
 untoward effects. Of the latter a feeling of oppression, and be- 
 numbed sensation, especially in the frontal region, of the head, and 
 pressure over the eyes, were noticeable. Following these there is 
 usually thirst, dryness of the throat, nausea, trembling, a sensation of 
 heat and labored breathing. In addition to these there are also a 
 sensation of dizziness, numbness, intoxication and a staggering gait. 
 This condition may disappear in the course of an hour, leaving 
 nothing beyond a disagreeable sensation in the head. Should the 
 condition, however, be aggravated, there occurs a delirium of the 
 nature of that caused by the use of atropia. 
 
 *Reinhard, Archiv f. Psychiatrie, XI., p. 391. 
 
 tE,lefsen u. Illing, Cer.tralbl. f. die Med. Wissenschaft, 1881, No. 23, 
 
 $Gnauck, Eod. loc. No. 45, 1881. 
 
NARCOTICS ATROPIA. 145 
 
 ATROPIA. 
 
 ATROPIA SULPHAS. 
 
 The external employment of normal doses of atropia in eye 
 practice, is, in addition to its physiological mydriatic action, attended, 
 in some persons, by abnormal local and general symptoms of its 
 absorption. 
 
 As regards the local symptoms, Von Graefe* observed that the 
 mydriatic, at first non-irritating, cannot be long borne by certain per- 
 sons. There occurs, as a result of the repeated action of the drug, an 
 anatomical change, which affects the normal susceptibility of the con- 
 junctiva to the further influence of medicine. There thus occur 
 blepharo-conjunctival irritation, lachrymation, oedema of the lids and 
 even an erythematous eruption, after each fresh instillation of atropia, 
 when the conjunctiva has once become saturated with the drug. 
 This antipathy of the conjunctiva sometimes continues for months 
 after the suspension of the drug, the mucous membrane the while 
 being to all appearances perfectly normal. In some of the more 
 developed cases there appears a peculiar form of granulations, 
 resembling the usual vesicular lymph follicles of the lower lid and 
 distinguishable from them by the consistency and yellowish color of 
 their contents, and the diminished vascular supply of the mucous 
 membrane. As a means of permitting the renewed employment of 
 atropia, Graefef recommends the intermittent use of solutions of the 
 acetate of lead or the nitrate of silver. 
 
 HillerJ traces this "atropia-conjunctivitis" to the action of 
 fungi, especially the thread-like fungi, which are very frequently 
 formed in solutions of atropia. 
 
 According to the investigations of Krcemer, § who noticed 
 almost typical irritation of the conjunctiva immediately after the 
 instillation of a solution of atropia thus changed, such solution may 
 be rendered perfectly clear, and kept so by boiling and the addition 
 of boracic acid (4 parts to 100 of water) and carbolic acid (1 part 
 to 1000 of water). 
 
 *A. V. Graefe. Archiv f. Ophthalmol., Bd. I, 2., p. 242 und Bd. X, 2, p. 200. 
 
 tGraefe, Eod. loco Bd. II. 
 
 $Hffler, Zeitschr. f. Klin. Medic. Bd. iii, Heft 1. 
 
 §Krcemer, Correspondenzbl. f. schweLz. Aerzte, 1881, No. 19. 
 
I46 THE UNTOWARD EFFECTS OF DRUGS. 
 
 In addition to these local changes Graefe observed as a result of 
 the use of atropine, particularly in syphilitic iritis, an occasional per- 
 manent dilatation of the pupil. 
 
 The symptoms of the absorption of atropia, following its appli- 
 cation to the eye, point to an action of the drug on the central 
 nervous system, such as otherwise occurs only as a result of poison- 
 ing by the drug. These are on the whole but very seldom observed 
 either after instillation of the drug into the eye, or the use of eye 
 washes containing it, and are not due to the amount absorbed from 
 the eye, but rather to that which finds its way through the tear ducts 
 into the throat and stomach. The susceptibility to atropia is, there- 
 fore, thus directly proportioned to the patency of the tear ducts. In 
 evidence of this fact may be adduced the circumstance noted by R. 
 Liebreich* that the prolonged use of collyria containing the largest 
 doses, by patients suffering from impermeable tear-ducts, gives rise to 
 no constitutional symptoms. According to observations by Chassaig- 
 nac three or four drops of a solution of 0.06 gramme (gr. j) in 10 
 grammes ( 3 ijss) of water, instilled into the eye in a case of double 
 cataract with adhesions of the iris to the lens capsule, caused dizzi- 
 ness in half an hour, and later turgescence of the face, a scratching 
 sensation in the throat and mental hallucination, which disappeared, 
 spontaneously, three or four days later. Labordef saw it produce 
 in adults mental confusion and delirium, while Galezowski noticed 
 symptoms of convulsions only in children. 
 
 The statements of Laborde are corroborated in an interesting 
 manner by the contribution by Kowalewski J of the report of a^, case 
 in which a man into whose eye an unusually large quantity of atro- 
 pia had been instilled, became very much excited, and experienced 
 also hallucinations of sight, hearing and feeling, which hallucinations 
 the patient described as the embodiment of abstract conceptions. 
 On the fifth day there appeared also a dryness of the mouth, spasm 
 of the pharynx, etc., from which it took ten days to completely 
 recover. 
 
 An observation of von Grsefe § merits especial mention, viz., 
 that not unfrequently there occur as a result of the continued use of 
 
 *R. Liebreich, Berliner Klin. Wochenschrift, 1864, p. 457. 
 •j-Laborde, Gazette Medicale de Paris, 1878, p. 606. 
 JKowalewski, Allgemeine Zeitschr. f. Psychiatrie, Bd. 36. Heft 4. 
 §v. Graefe. Archiv f. Ophthalmologie, Bd. IX., 1864. 
 
NARCOTICS ATROPIA. I47 
 
 collyria of atropia, symptoms which may be regarded as of erethistic 
 debility and suspension of assimilation. This is a condition which 
 it is difficult to distinguish and to assign its true cause, owing to the 
 absence of the other symptoms of the action of atropia. 
 
 An analogous condition to this is furnished by experiments 
 which Rossbach and von Anrep conducted on dogs. The animals 
 become habituated to the drug, but also become emaciated, debili- 
 tated, and lose their energy, spirits and appetite. In spite, however, 
 of the habituation, each new dose of the drug causes acceleration of 
 pulse and mydriasis. 
 
 It is not necessary to indicate curative measures for these affec- 
 tions, inasmuch as the symptoms detailed usually disappear shortly 
 after the suspension of the drug. When they are unusually severe, 
 small doses (0.005 to °- 01 gramme [gr. T V to -J-] ) of morphia may be 
 given, but prophylactic measures are to be preferred. According to 
 R. Liebreich (1. c), patients should be recommended to bend their 
 heads forward during the instillation of the atropia, in order to pre- 
 vent them from swallowing the tears or the solution which escape 
 from the eyes, to frequently blow their nose, and to gargle or to 
 press the eyelid so that the tear duct may be drawn downward. 
 Inasmuch as this plan, owing to the recumbent position, awkward- 
 ness, etc., of the patient, does not always succeed, Liebreich seizes the 
 edge of the lid with a pair of small pincers, of the nature of a serre- 
 fine, so as to produce a certain degree of ectropion, thus directing 
 the punctum lachrymale downwards and outwards. It is usually 
 sufficient to only treat the lower lid in this manner, but when large 
 doses are employed, or in the case of susceptible persons, the upper 
 lid must be similarly treated. 
 
 The internal exhibition of atropia is less frequently followed by 
 untoward effects. When such do appear they are usually confined 
 to dryness of the mouth, a raw sensation in the throat, slight fullness 
 of the head, the appearance of rings before the eyes, and sometimes 
 also diplopia and flushing of the face. It is only as a result of large 
 doses that threatening symptoms supervene, referable to the circu- 
 latory system, the motor and psychical spheres and sensations. 
 
 Occasionally after the use of small medicinal doses there arises 
 an affection of the skin. Thus Lusanna* reports a case in which the 
 
 *Lusanna, L'Union M^dicale, 1854. 
 
THE UNTOWARD EFFECTS OF DRUGS. 
 
 skin presented an intensely red color, as if it had been exposed to 
 the intense heat of the sun, in fifteen minutes after a small dose of 
 atropia. This erythema lasted from half an hour to an hour, and 
 appeared after each exhibition of the drug. 
 
 HOMATROPIN. 
 
 Homatropin, the product of the action of hydrochloric acid in 
 atropin, was used both in this form and as the bromhydrate of 
 homatropia, as a mydriatic and also as a remedy against night 
 sweats of phthisis, by Bertheau* and Fronmüller, j- Its general 
 properties are similar to those of atropia, from which it differs, how- 
 ever, in that it requires larger quantities to cause poisonous effects 
 and that these effects disappear more quickly. 
 
 The following untoward effects have been observed to occur as 
 a result of the internal exhibition or subcutaneous introduction of 
 0.02 — o.i gramme (gr. -J- to gr. jss) of this substance: weakness 
 and uncertainty of gait, vertigo, a feeling of fatigue, irritation of 
 the throat, difficulty of deglutition, excited babbling and fullness 
 of the head. 
 
 BELLADONNA 
 
 FOLIA RADIX EXTRACTUM UNGT. BELLADONNA. 
 
 Various authors have noticed an eruption after the external and in- 
 ternal exhibition of belladonna, which, like most medicinal eruptions, 
 is of a very transient nature. This skin affection is sometimes general 
 and sometimes localized, and appears, according to Guerard,J even 
 after small doses, especially in small children. It generally takes 
 the form of extensive erythematous spots, or a scarlatinal exanthem. 
 The spots disappear on pressure, but return when it is removed. 
 They appear chiefly on the face and neck, are unattended by itching, 
 and soon disappear. The eruption may appear very shortly after 
 the exhibition of the drug and may pass through its several stages 
 of development, from the most pronounced redness to paleness, 
 
 *Beriheau, Berl. Klin. Wochenschrift, 1880, No. 41. 
 
 tFronmüller, Memorabüien, i£8o, No. 7, und 1882 Heft I. 
 
 ^Guörard, Des Eruptions mddicamenteses pathogänetiques, Paris, 1862, p. 26. 
 
NARCOTICS DUBOISINUM. 149 
 
 in a few hours. In some cases, as if to complete the resemblance 
 to scarlatina, there is also redness and pain in the throat. There is 
 neither fever nor desquamation. 
 
 Traube* declares, from his own experience, that a similar exan- 
 them may follow the use of belladonna. Berenguierf observed a 
 diffuse scarlatinal redness following the use of a belladonna mix- 
 ture, which lasted for eight hours and then suddenly disappeared. 
 
 Wilson^ noticed the appearance of a sclarlatiniform exanthem 
 which disappeared in the course of three or four days without des- 
 quamation, in two lying-in women, for the swelling of whose mam- 
 mary glands he had used a belladonna liniment for several days. 
 Köbner, also, found a noticeable hyperemia, particularly on the 
 face, after the employment of a vaginal suppository containing ex- 
 tract of belladonna. 
 
 Bader § observed grave symptoms as a result of the employment 
 of a vaginal suppository compound of cacao butter, and containing 
 0.2 grammes (gr. iij) of extract of belladonna. In five hours the 
 face of the patient became of a scarlet red color, with cold cheeks, 
 pulse 160, cool surface, dilated pupils and irritation of the throat, 
 the general condition, however, remaining unimpaired. These 
 threatening symptoms rapidly disappeared under the use of a hypo- 
 dermic injection of 0.03 gramme (gr. -fa) of morphia and the 
 administration of champagne. 
 
 It follows, as a matter of course, that belladonna may also, 
 through its internal and external exhibition, give rise to the abnor- 
 mal somatic symptoms identical with those specified as following 
 the employment of atropia. Two cases observed by Golden || in 
 which the employment of belladonna ointment to the breast caused 
 a suppression of the secretion of milk, are worthy of note in this 
 connection. 
 
 DUBOISINUM. 
 
 Duboisia is a yellow alkaloid, in the form of an extract, pro- 
 cured from an Australian plant belonging to the solanaceae, the. 
 
 ♦Traube, Beiträge zur Pathologie und Physiologie, Berlin, 1871, IL, Abth. 1 p. 163. 
 
 tBercr.guicr, l.c.,p. 3 i. 
 
 JWilson, Virchow, Kirsch's Jahresbericht f. d. ges. Mediein, 1872, L, p. 380. 
 
 §Bader, Corrccpondcnzbl. f. Schweiz. Aerzte, 1 Octob., 1S81. 
 
 ÜGolden, Lancet, 1856, No. 6. 
 
150 THE UNTOWARD EFFECTS OF DRUGS. 
 
 duboisia myoporoides. It was prepared by Gerrard and simultane- 
 ously by Petit, in 1878. It is slightly soluble (1:120) in water, but 
 readily soluble in alcohol, chloroform, etc. The watery solution 
 has a slightly alkaline reaction. Its sulphuric acid compound is 
 crystalline. 
 
 The principal effect of duboisia is to cause dilatation of the 
 pupils, in which property it has been found by some experimenters 
 to equal, and to even excel atropia. It is said, as affirmed by Wecker, 
 to be less irritant to the conjunctiva than atropia. The hypodermic 
 injection of 0.001 gramme (gr. -J^) in watery solution prevents or 
 diminishes the colliquative night sweats of phthisis. 
 
 Gubler, on the other hand, observed after the hypodermic in- 
 jection of 0.0005 gramme (gr. y^-) of this substance, dryness of the 
 throat and disturbances of sight, and after 0.00 1 gramme (gr. g^) 
 thirst, increased frequency of the pulse, redness of the skin and 
 occasionally collapse. Sidney Ringer found that the subcutaneous 
 injection of three drops of a solution of one part of extract of 
 duboisia in four of water, given during the height of the action of 
 Pilocarpin, caused dryness of the skin in seven minutes, and in ten 
 minutes a sufficient degree of dryness of the mouth to cause the 
 patient to complain of it. 
 
 Untoward effects have also been already observed to follow ths 
 application of duboisia to the eye. Thus Davidson* reports 
 eight cases in which the instillation of duboisia was fol- 
 lowed by pathological symptoms of varying degrees of intensity, 
 such as vertigo, restlessness and excitement, which developed even 
 into violent delirium. In several cases dryness of the throat was 
 also observed. Schölerf employed a watery solution of 0.05:5.0 
 without observing any symptoms of general intoxication. On the 
 other hand he observed a well-defined follicular conjunctivitis in 
 three or four cases after the application of the drug, and in two or 
 three cases the instillation was followed by pain, redness of the 
 conjunctivae and immobility of the pupils. 
 
 ^Davidson, Lancet. September 6, 187g. 
 
 tSchöler, Jahresbericht übres. Augen-Klink für 1878, Berlin, 1879. 
 
NARCOTICS AC02WTINUM. 1^1 
 
 ACONITINUM. 
 
 TTJ*BERA EXTRACT. TR. ACONITI. 
 
 The effects of various preparations of aconitia prove that 
 action of the same is modified by the method of preparing the 
 alkaloid. While the German aconitia is not particularly poison- 
 ous, as compared with other poisonous substances, such properties 
 are claimed by nearly every English experimenter for their 
 domestic aconitia (Morson's Napellin or pure aconitine), which is 
 probably prepared from the aconitum ferox, by a secret process. 
 
 While the maximum doses of the German aconitia, according 
 to the German pharmacopoeia, is 0.004 gramme (gr. ■£%), Pereira* ob- 
 served symptoms which are well nigh fatal, to follow 0.0015 gramme 
 (gr. _l_) of the English aconitia. Notwithstanding the fact that 
 the individuality of the person taking this active drug plays an 
 important part in determining its action, the difference in the modes 
 of action of the two varieties, as pointed out by Schroff, is too great 
 to be left out of the question in determining the cause of the 
 deleterious untoward action of the drug. Various degrees of such 
 action have, however, been observed to follow each of the two 
 varieties. 
 
 The English aconitia is said by Pereira to provoke heat and 
 itching of the surface of the body, even when given in very minute 
 doses. Turnbullf observed, after its external application, a prick- 
 ing sensation on the part to which it was applied, and Schroff]; 
 found that a dilute alcoholic solution of this preparation applied to 
 the forearm caused formication and pricking, without the evidence 
 of any inflammatory change. 
 
 Cases of poisoning occurring as a result of the employment of 
 the English instead of the German aconitin, are frequently recorded 
 in literature. The English preparation should, in our opinion, be 
 entirely discarded for internal use. 
 
 The German aconitia and other pharmaceutical preparation? 
 
 *Pereira, Refer, bei Husemann, Pflanzenstoffe, 1871, p. 226. 
 
 tTurnbuli, On the Preparations and Medical Employment of Aconitina. London, 1835. 
 
 ^Schroff, Journal für Pharmako dynamik, Toxikologie und Therapie, Bd. I., 1857, p. 365. 
 
152 THE UNTOWARD EFFECTS OF DRUGS. 
 
 made out of the wolfsbane, cause, as Dworzak and Heinrich* 
 experienced in their own persons, a biting, burning sensation of 
 the tongue and lips, and salivation. An eruption of whitish vesi- 
 cles has also been occasionally seen on these parts. There further 
 not unfrequently occur a vague drawing sensation in the face, 
 which may develop into a persistent pain, confined to the distribu- 
 tion of the trigeminus nerve, and be accompanied by a very annoying 
 pricking sensation, occurring particularly on the chin and cheeks, 
 but appearing also on the trunk and extremities. The mucous 
 lining of the stomach and intestines is also irritated by this drug. 
 Nausea, and even vomiting and borborygmi may occur. The 
 frequency of the pulse is very markedly reduced. The continued 
 use of the aconite gives rise to more remote effects, as headache, a 
 greater or lesser degree of fullness of the head, buzzing in the ears, 
 and general weakness — symptoms which disappear shortly after 
 the suspension of the drug. 
 
 Although the exhibition of medicinal doses of the German and 
 the other preparations of aconitia, does not generally cause an ap- 
 prehension of symptoms threatening to life, pre-existing weakness 
 of the heart's action, or other causes predisposing to the more 
 intense action of the drug, may render the employment of direct 
 therapeutic measures necessary. Contrary to the view formally 
 entertained regarding its ill effects, L. Lewinf has shown that aco- 
 nitia belongs to that class of cardiac poisons whose fatal action 
 may be long postponed, and even entirely obviated, by prolonged 
 artificial respiration. Artificial respiration must, therefore, be re- 
 sorted to as soon as symptoms of dyspnoea and anomalies of the 
 heart's action (irregularity, intermittency, etc.,) manifest them- 
 selves. In addition to this, and also in the slighter manifestations 
 of the action of aconitia, the ordinary stimulants and diuretics may 
 be employed to assist in the more rapid elimination of the drug. 
 There is no direct antidote to aconitia known. 
 
 *Dworzak u. Heinrich, Präger Vierteljahrschrift, Bd. 42, p. 153 ff. 
 
 +L. Lewin, Experimentelle Untersuchungen über die Wirkung d. Aconitin auf das Herz, 
 Berlin, 1875. 
 
NARCOTICS VERATRINÜM. T53 
 
 VERATRINUM. 
 
 RHIZOMA TR. VERATRI. 
 
 That the alkaloid derived from the leaves of the white helle- 
 bore, as well as from the root of the plant, when given for 
 therapeutic effect is not infrequently followed by a few pathological 
 symptoms, is a fact which was familiar to the ancients and the 
 physicians of the middle ages. These symptoms may supervene, 
 in a greater or lesser degree of intensity, from any form in which 
 the drug is administered. 
 
 A mere trace of the powder, which may be accidentally brought 
 in contact with the nasal mucous membrane, causes violent and 
 persistent sneezing, and may even give rise to profuse epistaxis. 
 The conjunctiva is also violently affected when veratria, in the form 
 of either an ointment or solution, is applied to it. The symptoms 
 following the quite extensive external employment of this drug- 
 in neuralgia of the various nerve trunks, has furnished an 
 opportunity for the careful study of its effects. An oint- 
 ment of 0.6 — 1.0 gramme (gr. jx to gr. xv) of veratria to 30 
 grammes ( 5 j) of lard, excites in a short time, not only at 
 the seat of application but also in remote parts of the body, 
 a sensation of pricking and increased heat. According to Reiche* 
 this sensation gradually increases to burning, and through longer 
 continuance of the application, a feeling of restlessness and anxiety 
 supervenes. These symptoms may become permanent should the 
 further employment of the veratria not be withheld, and the patient 
 thus be deprived of sleep. Occasionally, also, a pruritic petechial 
 or other vesicular eruption, which soon disappears with the discon- 
 tinuance of the drug, has been observed on various parts of the 
 body. The untoward effects may be more intense as a result of the 
 internal exhibition of the drug. Veratria, owing to its property of 
 lowering the frequency of the pulse and blood pressure, and reduc- 
 ing the temperature and the frequency of respiration, has been and 
 is still employed in febrile affections, and particularly in pneumonia. 
 In such cases it is given in doses of 0.003-0.0005 gramme (gr. ^ 
 to gr. yl^) and even more than the maximal dose of 0.0 1 gramme 
 
 : Reiche, Medic. Zeitung d. Vereins f. Heilkunde, 1839, 23. 
 
154 THE UNTOWARD EFFECTS OF DRUGS. 
 
 (gr. i). But even small normal doses usually excite dryness of the 
 mouth, burning in the throat, difficult deglutition, nausea, choking, 
 and vomiting, and occasionally also salivation, colicky pains and diar- 
 rhoea, in which the discharges may be tinged with blood. Children, 
 as stated by Forcke,* frequently vomit after the first dose, but 
 adults rarely. 
 
 During the continued employment of medicinal doses a prick- 
 ling or burning sensation occurs in remote parts of the body and 
 particularly in the extremities. In many persons there occur vertigo 
 and dimness of vision, and also a trembling and uncertainty of 
 motion. In others completely developed collapse may ensue. Cer- 
 ebral symptoms not unfrequently occur as a result of the employ- 
 ment of tr. veratr. virid. Thus Fleischmannf reports the case of a 
 boy in whom dryness of the throat, great thirst and later temporary 
 convulsive movements of the hands and fingers, raving and slight 
 delirium, occurred after the exhibition of teaspoonful doses hourly 
 of the following mixture ; tr. veratri virid. gtt vj, mucilage 60.0 
 grammes ( § ij). 
 
 Forcke observed a pustular eruption on the face, and particu- 
 larly around the mouth, in several cases. 
 
 EulenburgJ noticed the formation of an abscess in one instance, 
 after the hypodermic injection of an alcoholic solution of 0.0012- 
 0.0015 gramme (gr. -gL- to gr. ^), and usually after such an injection 
 there occurred a slight and occasionally spotted redness and swell- 
 ing around the point of entrance of the needle. The sensation of 
 burning continued for several hours after the injection. Hiffelsheim 
 also declares that pain and erythema occur as a result of the hypo- 
 dermic administration of veratria. Sometimes the toxic symptoms 
 develop into prostration. 
 
 The therapeutics of the untoward effects indicated, consist in 
 the immediate discontinuance of the drug and the exhibition of 
 analeptics, and particularly the liquor ammonii anisatus, in from 5 to 
 15 drop doses,§ or, according to Reiche (1. a), black coffee with 
 lemon juice. The drug must never, according to Troetscher,| be 
 given during existing catarrh of the stomach. 
 
 *Forcke, Physiologisch— therapeutische Untersuchungen üb. d. Veratrin. Hannover, 1837 
 tFleischmann, Prager medic. Wochenschrift 1876, No. 10. 
 :fEulenburg, Die hypodermatischen Injectionen, Berlin, 1875, p. 278. 
 §Husemann, Pflanzenstoffe, Berlin, 1871, p. 510. 
 {Troetscher, Wiener Medicin. Halle, 1863, P- 487- 
 
NARCOTICS EXTRACTUM FAK.t CALABARIC^E. 155 
 
 EXTRACTUM FAB^E CALABARIC^E 
 
 ESERIN S. PHYSOSTIGMiy. 
 
 The untoward effects which manifest themselves in connection 
 with the external application of the calabar bean to the eye, have 
 been clearly demonstrated by the classic experiments of A. v. 
 Graefe.* According to him this drug penetrates the cornea and 
 being dissolved in the fluids of the eye, exerts its influence directly 
 on the iris and ciliary muscle. He found that immediately after the 
 instillation of a solution of the alcoholic extract in glycerine, there 
 ensued a biting sensation in the conjunctival sac and a correspond- 
 ing reflex action on the orbicularis muscle, and the lachrymal secre- 
 tion, the intensity of these effects varying with the individuality of 
 the person and the strength of the solution. Following this, when 
 the contraction of the pupil and the accommodative changes set in, 
 a painful sensation of contraction, partially along the equator of the 
 globe and partially in front of it in the region of the ciliary body, is 
 complained of. Others refer to a nervous contractile pain in the 
 entire eye ball, which spreads, after the manner of the ciliary neu- 
 rosis, along the course of the supraorbital nerve, assuming the 
 nature of migraine on the corresponding side of the head. Graefe 
 leaves it undecided whether this pain is most dependent on spasm 
 of the tensor or sphincter. 
 
 He made no observation touching more remote effects. Should 
 such have occurred they would, most naturally, have been ascribed 
 to the passage of the drug along the tear ducts. 
 
 Following the internal exhibition of small doses of the extract 
 of calabar bean, as they are employed in neuralgia, tetanus, epilepsy, 
 and also in atropia and strychnia poisoning, Fraserf observed an 
 intense pain in the epigastrium, as well as vertigo, and weakness of 
 the muscles of the extremities, and weakening and irregularity of 
 the heart's action. The latter symptom may take on the nature 
 of paralysis, but is, however, of but short duration. 
 
 LevenJ; noticed nausea and general uneasiness as a result of 
 small doses of physostigmin. 
 
 *A. v. Graefe, Archiv f. Ophthalmologie, Bd. ix., 1865, III., p. 87. 
 tFraser, Transactions of the Royal soc. of Edinburgh. XXIV., 1867, 73. 
 + Leven. Journ. de Pharmac. et Chimie, I, 70. 
 
156 THE UNTOWARD EFFECTS OF DRUGS. 
 
 AMYGDALAE AMAR^, 
 
 AQUA AMYGDAL. AMARARUM. AQ. LAUROCERASI. 
 
 Bitter almonds are said by Stille* occasionally when given in 
 medicinal doses to cause a copious urticarious eruption. Gregory 
 also observed a similar eruption on himself after eating a bitter 
 almond. This effect is traceable to the presence of hydrocyanic 
 acid in the almond. This is corroborated by the fact that water 
 containing hydrocyanic acid, such as bitter almond water and 
 cherry laurel water, also give rise to similar untoward effects. 
 
 Small doses (10 drops) of cherry laurel water may give rise to 
 irritation of the throat and an increased flow of saliva. Should this 
 quantity be somewhat exceeded, as so often happens in practice, or 
 should small doses be frequently repeated, there occur, according to 
 Coullon,f nausea, vomiting, vertigo and headache. In connection 
 with the sensation of dizziness, there may also occur buzzing of the 
 ears, labored breathing, and great depression. 
 
 In view of this fact, and of the additional fact of the dissimilar 
 strength of waters containing hydrocyanic acid as well as of the 
 varying degree of individual susceptibility to the action of the same, 
 Köhler, J very properly cautions against the usually reckless admin- 
 istration of this drug as an antispasmodic. Trousseau and Pidoux 
 most correctly indicate its value when they say that it is often dan- 
 gerous, nearly always useless, and exceedingly rarely curative. 
 
 SEMEN COLCHICI. 
 
 TINCTURA VINUM COLCHICI. 
 
 The efficacy of the preparations of Colchicum is dependent on the 
 percentage of colchicin which they contain. This, however, varies 
 with the season of the year during which the drug is gathered. 
 
 »Stille, Therapeutics and Materia Medica. Philadelphia, 1874, I., p. 175. 
 
 tCoullon, Rechercheset considerations medic, sur l'acide hydrocyanique Paris, 
 
 1819. 
 
 $Köhler, Handbuch der physiolog. Therapeutik, Göttingen, 1876, p. 1 33. 
 
NARCOTICS SEMEN COLCHICI. 157 
 
 According to Aschoff and Bley* the Colchicum root contains the 
 largest percentage of colchicin in July and August. It is not 
 impossible that this circumstance is responsible for the abnormal 
 symptoms which appear after the therapeutic employment of Col- 
 chicum gathered in the autumn. 
 
 Small doses (0.1-0.3 gramme [gr. jss to gr. jvss]) of the seeds 
 have been often observed to cause burning in the throat and 
 stomach, ptyalism, distressing nausea, and serous diarrhoea with 
 tenesmus. Some or all of these symptoms sometimes appear only 
 after the prolonged use of the drug, but occasionally also occur 
 soon after its exhibition. There are not infrequently, though with 
 greater inconstancy, associated with the symptoms named, fullness 
 of the head, headache and vertigo. The secretion of urine may 
 also be attended with pain. 
 
 The symptoms referable to the gastro-intestinal canal are due 
 to the local irritation of the drug. In support of this view are the 
 established toxic effects of large doses of the drug on man and 
 beast, viz., intense inflammatory changes in the mucous membrane 
 of these organs. 
 
 The untoward effects described most frequently occur after the 
 use of the wine of Colchicum seeds, the prescribed dose of which 
 (2 grammes [ 3 ss] per dose, or 6 grammes [ 3 jss] per diem) is cer- 
 tainly excessive, should the wine have been prepared from the fresh, 
 active plant. 
 
 The action of officinal colchicin, of the Phar. Austrica, which 
 is readily soluble in water, has been observed on man, by Schroff. f 
 After the exhibition of 0.0 1 gramme (gr. -J-) of this principle, there 
 was at first a bitter and afterwards irritating taste, which was soon 
 followed by eructation, nausea, retching and salivation. After 0.02 
 gramme (gr. -J-) there occurred in addition to these symptoms, 
 vomiting and diarrhoea with tenesmus, and later chills and sleep- 
 lessness. 
 
 In the subcutaneous application of colchicin as recommeded by 
 Badia, and later by Heyfelder, J in rheumatic affections, the drug 
 produced an intense burning and itching on the seat of the injection, 
 which usually lasted only half an hour, but often longer. In one- 
 
 *Aschoff und Bley, Archiv d. Pharmacie, Januar, 1857. 
 tSchroff, Oesterreichische Zeitschr. f. pr. Heilkunde 1856, II., 22. 
 JHeyfelder, Berl. Klin. Wochenschrift No. 15, 2877. 
 
158 THE UNTOWARD EFFECTS OF DRUGS. 
 
 third of all cases there occurred a local inflammation of the skin, 
 with slight swelling and tenderness on pressure. In view of this 
 peculiarity of the colchicin, it is advisable not to employ it during 
 high febrile disturbance, or to apply it to inflamed parts; in the 
 latter condition, if employed at all, it should be applied only at some 
 distance from the seat of the inflammation. In a very sensitive 
 person, slight dysuria was several times observed after this medica- 
 tion. 
 
 FOLIA DIGITALIS. 
 
 EXTRACTUM TINCTURA UNGUENTUM DIGITALIS. 
 
 Digitalis shares with only a few other drugs the property, which 
 is perhaps due to its abnormally slow elimination by the kidneys, 
 of continuing its action in the body during a relatively long period, 
 and, therefore, of giving rise, through the continued administration 
 of repeated doses, to cumulative action. The latter may under 
 certain circumstances give rise to threatening appearances and even 
 to symptoms of positive poisoning. Among the latter are the 
 following: headache, dryness in the throat, nausea, choking,x and, in 
 well marked cases, buzzing in the ears, disturbances of vision, man- 
 ifesting themselves in muscae volitantes, amblyopia or diplopia, and 
 later in dizziness, fainting, vomiting, diarrhoea, sleeplessness, a thread- 
 like, scarcely perceptible, irregular pulse, and a quite distinct fall in 
 the temperature of the body, due to lowering of the activity of the 
 circulation. A headache was particularly observed to occur after 
 0.03-0.09 gramme (gr. ss to gr. jss) of the drug. In some persons 
 0.15 gramme (gtt. iij) of the tincture of digitalis is sufficient to 
 arouse the symptoms mentioned. 
 
 In the absence of any known direct antidote to digitalis, treat- 
 ment of these effects must be symptomatic, as the exhibition of 
 stimulants, counter-irritants, etc. In view of the property indicated, 
 through which death may suddenly occur as a consequence of 
 cardiac paralysis, prophylactic measures must receive especial atten- 
 tion, especially when the drug is to be administered for some time, 
 and its use must be suspended on the first appearance of abnormal 
 subjective symptoms. 
 
 In the opinion of Durosiez, some of the unexpectedly fatal cases 
 
NARCOTICS FOLIA DIGITALIS. 159 
 
 of inflammation, occurring during a course of treatment with strong 
 infusion of digitalis, are traceable to the poisonous action of the 
 drug. 
 
 An observation of Traube's* regarding the occurrence of a skin 
 affection after the employment of digitalis, should be mentioned as 
 something which seldom happens. In a case of pericarditis and 
 pleuritis the patient was given between the fourth and the sixth 
 days of his sickness 3.75 grammes (gr. Ivj) of digitalis in infusion. 
 In four days after the last dose there appeared, the body being of 
 normal temperature, an erysipelatous affection of the face which, five 
 days later, resulted in an excessive flake-like desquamation. In a 
 second case, of pleuropneumonia, 4.08 grammes (gr. lxj) of digitalis 
 were given in an infusion in five days. Four days after the last 
 dose of digitalis the patient, who up to that time had been free from 
 fever, experienced an exacerbation of fever, and on the fifth day 
 there appeared on the trunk, the supinator surfaces of the forearm 
 and back of the hands, a papular eruption, consisting of quite promi- 
 nent, carmine-red spherical spots, the color of which disappeared on 
 pressure, the majority of them uniting in confluent patches over the 
 surface of the skin. On the following day desquamation in 
 quite large flakes occurred on the face, while new eruptions were 
 observed on the arms and neck. In still four days the eruption had 
 almost entirely disappeared, and it was only in the course of a 
 typhoid affection which subsequently developed, that desquamation 
 ©f the trunk and extremities took place in large flakes. 
 
 Schuchardtf observed a similar eruption in a robust young man, 
 spreading over his entire body, after he had taken digitalis for some 
 time for the relief of endocarditis. This same person, having re- 
 sumed the medicine a year later, was attacked with the same eruption 
 and of equal intensity. 
 
 It is, perhaps, not unimportant, for a proper understanding of 
 the manner of the occurrence of this affection, to instance the fact 
 that the officinal digitalis ointment (ext. digitalis 1 part, unguent, 
 ceras 9 parts), but in a greater degree a salve prepared with lard 
 and fresh digitalis leaves, may, when several times rubbed into the 
 skin, excite a slight inflammation and papular eruption Its appli- 
 
 *Traube, Charite-Annalen, Jahrg. I., p. 622 u. Jahrg. II., p. 19. Beiträge zur ü athoIogie s 
 &■ IL, i. Abth. , p. 130, 156, 164. 
 
 tSchuchardt, Handbuch der Arzneimittellehre, Braunschweig, 1858, p. 553. 
 
IÖO THE UNTOWARD EFFECTS OF DRUGS. 
 
 cation to skin deprived of its epidermis excites, as a matter of 
 course, a more violent inflammation. It is, therefore, conceivable 
 that in connection with a certain individual disposition the accumu- 
 lation of a large quantity of the active principle of the digitalis in 
 the circulation, may excite the same irritative effect on the skin as 
 the external application of the drug. This explanation accounts for 
 the circumstance, noted in cases reported by Traube, that the 
 exanthem first appeared after the use of the digitalis had been sus- 
 pended. 
 
 The following statement of Reil* is worthy of note: cumulative 
 effects are very seldom noticed after the employment of digitalin, be- 
 cause there appear as harbingers of intolerance of the drug, a sensa- 
 tion of weakness in the epigastrium, an inclination to vomit, exhaus- 
 tion, dimness of vision and heaviness of the head, which admonish to 
 a discontinuance of the drug. 
 
 CHLORALUM HYDRATUM— CRYSTALLISATUM. 
 
 The occurrence of untoward effects after the internal exhibition 
 of chloral hydrate, is, in view of the very extensive employment of 
 this drug, not very frequent. This is the more to be wondered at 
 because of the fact noted by Richardsonf that its habitual use as 
 particularly noted in England and America, even in "chloral 
 drinkers," causes no habituation to the effects of the drug, and gives 
 rise to no deleterious consequences so long as the standard doses 
 are not exceeded. Other observers have confirmed these observa- 
 tions on the basis of reports from insane asylums, from which he also 
 established the fact that the employment of a pure preparation for 
 its hypnotic action for even a prolonged period, neither necessitates 
 any increase of dose, nor produces any unpleasant effects as is the 
 case with opium and its alkaloids. The use of impure preparations 
 of chloral, however, in consequence of the formation of deleterious, 
 chlorinated substances and increasingly acid reaction, gives rise 
 to perverse therapeutic effects. 
 
 The bad quality which is usually peculiar to those preparations 
 which are not well crystallized, is probably one of the causes of fatal 
 effects which are reported in literature as following one or more 
 
 *Reil, Materia. Medica d:r reinen Pflanzenstoffe, Berlin, 1357, p. 155. 
 •{•Richardson, Medical Times and Gazette, February, 1871. 
 
NARCOTICS CHLORALUM HYDRATUM. l6l 
 
 medicinal doses. It is a notable fact, in this connection, that during 
 the first years of the employment of chloral, many of such cases 
 were reported, while on the other hand with the more perfect means 
 of manufacture of recent times, such accidents are very rarely de- 
 scribed. Should such cases so occur they are in the first place 
 ascribed to the impurities of the preparation, inasmuch as we 
 are familiar with several organic combinations with chlorine which, 
 even when given in small doses, are capable of deleterious effects. 
 At the same time individual predisposition to the occurrence of 
 such symptoms also plays an important role, and the condition 
 of the absorptive organs is particularly to be taken into considera- 
 tion. 
 
 It is a noteworthy characteristic of the fatal cases reported by 
 various authors as resulting from chloral hydrate, that these almost 
 always follow the exhibition of the drug immediately or at a very 
 short interval, and usually in cases in which there is much anxiety. 
 Nötel,* among others, reports such accidents after the exhibition of 
 4 grammes ( 3 j) of chloral, Jolly, f in two insane persons after 5 
 grammes (gr. lxxv) each, Marsh, J in four persons, the majority of 
 whom were drunkards, after 3 grammes (gr. xlv), and Fürstner § in 
 a girl after but two grammes (gr. xxx). The autopsies, as published, 
 furnished no insight into the causes of death. 
 
 In rare cases, according tc KirnJ there occur disturbances of 
 respiration, which may increase from a sense of fear, anxiety and 
 shortness of breath, to attacks of dyspnoea and even asphyxia. So 
 also Shaw** observed spasmodic breathing and irregular action of 
 the heart after about one gramme (gr. xv) of chloral. The mucous 
 lining of the air-passages, according to Marsh, suffers change 
 after an ordinary dose of chloral, as evidenced by the bronchitis 
 which he observed. 
 
 Much more frequent than the symptoms mentioned is the 
 irritation of the conjunctiva which follows one or more doses of 
 chloral. Redness and swelling of the conjunctiva are noticed, 
 which, however, disappear shortly after the discontinuance of the 
 
 *Nötel, Virchow-Hirsch's Jahresbericht f.d. ges. Medicin, 1872, II., p. 
 
 tJoll}'-, Bair. ärztl. Intelligenzblatt, 1^72, No, 13, 14. 
 
 $Marsh, Virchow-Hirsch's Jahresb., 1875, 1., p. 479. 
 
 §Fürstner, Archiv, f. Psychiatrie, Bd. VI., 1876, p. 344. 
 
 IKirn, Allgem. Zeitschr. f. Psychiatrie, 1872, p. 316. 
 
 **Shaw, Virchow-Hirsch's Jahresber., 1871, 1., p. 334. 
 
IÖ2 THE UNTOWARD EFFECTS OF DRUGS. 
 
 drug. Steinheim* reports the case of a lady whom he treated for 
 asthmatic attacks, who experienced a severe disturbance of vision on 
 each of three occasions after the employment of chloral. It mani- 
 fested itself as dimness of vision or complete blindness. 
 
 The " chloral rash " described by Schulef which manifests 
 itself in flashes of heat, and congestion of the head with injection of 
 the conjunctivae, occurs only when the chloral is followed by a 
 draught of an alcoholic beverage. 
 
 CurschmannJ reports, among other untoward effects, swelling of 
 the epiglottis and false vocal cords, and Reimer§ the occurrence of 
 bed sores. The aetiological connection of the latter symptom with 
 the use of chloral is, however, as yet, doubtful. According to 
 Reimer, the bed sore resulting from chloral differs from the ordi- 
 nary variety due to long continued pressure, in the fact that it 
 occurs after very light external pressure, and that it may occur, 
 develop and spread deep into the subcutaneous tissue, the epider- 
 mis and cutis remaining intact. 
 
 Quite peculiar cases are reported in the literature of chloral, in 
 which icterus is said to have resulted from the use of the drug. 
 Thus Wernich|| reports four observations in which an existing jaun- 
 dice became intensified after the use of chloral, and also the case of 
 a tippler in whom four grammes ( 3 j) of chloral hydrate excited a 
 fresh attack of icterus. Arndt** also observed the appearance of 
 jaundice in a paralytic after he had employed the drug for fourteen 
 days, it passing off with the suspension of the drug and recurring 
 with its renewal. The opinion of Gellhornff that an atrophied 
 condition of the liver of a quite peculiar nature, may, among other 
 affections, occur as an expression of the idiosyncratic action of 
 chloral, is somewhat hypothetical. This observation is the 
 only one of the kind recorded. In addition to the symptoms 
 which have been recorded, there have been observed in some per- 
 sons either polymorphous or simple eruptions, following either 
 immediately after the exhibition of variable doses of chloral, or 
 
 *Steinheim, Berliner, Klin. Wochenschr. 1875, P- 77- 
 
 tSchüle, Zeitschrift f. Psychiatrie, Bd. 28, p. 4. 
 
 JCurschmann, Deutsches Archiv f. Kl. Median. Bd. VIII, p. 151 
 
 §Reimer, Zeitschr. f. Psychiatrie. Bd. 28. p. 316. 
 
 JWernich, Deutsches Archiv, f. Klin. Medic, Bd. XII., p. 32. 
 
 **Arndt, Archiv, f. Psychiatrie, Bd. III, Heft 3. 
 
 ttGellhorn. Zeitschrift f. Psychiatrie, Bd. 28, p. 625. 
 
NARCOTICS CHLORALUM HYDRATUM. 163 
 
 occurring some time after. These may be classified as the erythe- 
 matous, urticarious and the eczematous varieties. 
 
 1. The erythematous form is relatively the most common. There 
 is usually observed on the face and neck an eruption of the nature 
 of a diffuse hyperemia. On the other parts of the body, the trunk 
 and extremities, the erythema generally occurs in the form of irregu- 
 larly outlined, roseola-like or dark red spots, bearing a striking 
 resemblance to purpura. According to Schule (1. c.) it appears to 
 follow, by preference, the course of the nerve trunks. It disappears 
 with the suspension of the drug. Brown* observed in one case an 
 inflammatory redness which spread uniformly over the whole body, 
 while Husband, f in the case of a female patient who took two doses 
 of 1.3 gramme (gr. xx) each, daily for eight days, and two doses of 
 2 grammes (gr. xxx) each, for five days, observed a scarlatiniform 
 eruption, occurring with high fever and hyperesthesia of the skin, 
 and being followed after its subsidence by abundant desquamation. 
 Köbner also reports a case in which there occurred, after the pro- 
 longed employment of chloral, not a simple hyperaemic redness, but 
 an erythema exsudativum which spread over nearly the whole sur- 
 face of the body. It was quite scarlatiniform in its appearance, dif- 
 fering only in the fact that the skin was more swollen and infiltrated. 
 The eruption burned and itched, and disappeared with desquama- 
 tion, the use of chloral being continued, only after four or five 
 weeks. 
 
 2. The urticarious form has been observed by GauchetJ and 
 Chapman § among others. The latter observed its occurrence in a 
 lady who had taken a gramme (gr. xv) of chloral each evening for 
 fourteen days. After this time there occurred an erythema which 
 disappeared with the suspension of the drug, and when it was again 
 given, two days later, rapidly covered the skin of the entire body 
 with wheals, which were the seat of a sensation of heat; simultane- 
 ously with this was hyper-secretion of the conjunctivae. Those erup- 
 tions, which have been classed as papular and which occur 
 under the same conditions, must be classed with this urticaria-like 
 form. Thus Arndt (1. c.) observed a papular eruption which occur- 
 
 *Brown, Lancet, 1871, Vol. I., p. 440. 
 
 fHusband, Eod. loco., 1871, No. 25. 
 
 JGauchet, Bulletin gener. de Therapeut. 1871, p. 420. 
 
 gChapman, Lancet, 1871. 
 
164 THE UNTOWARD EFFECTS OF DRUGS. 
 
 red after chloral had been used for eight days, appearing first on the 
 extensor surfaces of the upper extremities, but spreading, later, over 
 the whole body. This appeared and disappeared with the use and 
 disuse of the drug. Kirn (1. c.) observed a similar eruption which 
 was confined to the arms. 
 
 3. Under the continued use of chloral the nodules may develop 
 into vesicles with serous or purulent contents, and these, when they 
 burst, present a complete resemblance to eczema. This, however, 
 happens very rarely, and the only case recorded seems to be that 
 observed by Kirn, and even this is not a pure case, inasmuch as dur- 
 ing the existence of the exanthem, quinia, a drug which is itself 
 capable of giving rise to a variety of dermatoses, was given hypo- 
 dermically. In a robust person, suffering from puerperal mania 
 there appeared on the ninth day of the exhibition of chloral, with 
 febrile disturbance, an exanthem, with simultaneous swelling of the 
 face, cheeks, eyelids and ears. It disappeared after a time, and re- 
 aopeared on the renewal of the chloral, when the skin presented, 
 in a very variable manner, sometimes an impetiginous, sometimes a 
 weep ng, and again a squamous form of eczema and ichthyosis, in 
 which the desquamation was not confined to a short period, as is the 
 case with the acute exanthemata, but continued for many weeks, 
 large flakes of epidermis being shed from all parts of the body. At 
 a later stage of the affection the disturbances of the skin manifested 
 themselves in a distinct falling of the hair, and a gradual shedding 
 of the nails of the upper and lower extremities. 
 
 Schule and others have ascribed as the direct cause of the skin 
 disease a paralysis of the vaso-motor nerves by the chloral. Efforts 
 have not been wanting, as in the case of other drugs, to explain the 
 occurrence of these untoward effects of chloral. Those authors who 
 have undertaken such explanation, regard the untoward effects as 
 due to a chronic poisoning of the blood, and maintain that they can- 
 not be developed until the body has become saturated with the drug. 
 According to this view chloral must possess a cumulative action 
 similar to that which obtains in the case of digitalis. This view will, 
 however, on closer consideration of the existing conditions, be found 
 to be untenable. By a blood poisoning we understand a chemical 
 or physical change of such a nature in the constituents of the blood 
 that they are no longer in a condition which fits them for a proper 
 discharge of their normal functions. In this sense of the term one 
 
NARCOTICS CHLORALUM HYDRA TUM. 1 65 
 
 may regard as blood poisoning that condition induced by the inhal- 
 ation of carbonic oxide or sulphuretted hydrogen, by the ingestion 
 of too large doses of chlorate of potassium, or the introduction of 
 other heterogeneous substances into the circulation. But in all these 
 cases there occur changes in the blood whose existence may be 
 demonstrated either by the spectroscope or the microscope, or even 
 by simple unaided inspection. In the case of chloral, however, 
 none of these methods have as yet been able to detect any evidences 
 of such action, and we are, therefore, not justifiable in admitting the 
 claim of blood poisoning. There can also be no definite standard 
 fixed for such saturation of the system with chloral as shall give rise 
 to the untoward effects indicated, inasmuch as these occur in some 
 instances even after but a single small dose. On the other hand, if 
 such a degree of saturation should be reached, the cumulative action 
 of chloral would occur at the same time, and this would suffice to 
 ensure the sedative and hypnotic effects of the drug without the 
 necessity of its further administration. That this is not the case 
 needs scarcely to be mentioned. There must, therefore, be other 
 conditions for the occurrence of the symptoms named. They are 
 most effectually explained by the general facts as detailed in the 
 introduction to this work. It is probable that the chloral, or the 
 products of its decomposition, which find their way into various 
 organs, exert on some persons, perhaps either because of abnormal 
 vascular supply or other individual property, a direct irritating or 
 paralytic effect. This continues as long as the products remain in 
 the system. Bodily conditions which either prevent or cause a 
 retardation of elimination of the products of waste, may also favor 
 its occurrence. 
 
 No particular therapy is necessary for the relief of the effects of 
 chioral as described, inasmuch as they disappear spontaneously with 
 the suspension of the drug. In the case also of the fever which 
 usually attends the chloral eruption, there is no therapeutic interfer- 
 ence demanded, as, according to Schule, neither quinine nor cold 
 baths are followed by material benefit. It should also be mentioned 
 in this connection, that quinine is apt to induce a variety of com- 
 plications in those in whom there is a predisposition to the occur- 
 rence of drug eruptions, and that it is, therefore, better to entirely 
 abstain from its employment. 
 
66 
 
 THE UNTOWARD EFFECTS OF DRUGS. 
 
 CHLOROFORMUM. 
 
 Soon after the introduction of chloroform into medical practice, 
 and in the midst of its progress through the civilized world, cases 
 became known in which the narcotized persons never awoke. If in 
 the beginning of the employment of this drug fatal cases were not 
 reported, because of a suspicion on the part* of the physician in 
 attendance that he was himself personally responsible for the mis- 
 fortune, the increasing number of such accidents soon made it prob- 
 able that there must be certain conditions which are to be regarded 
 as causes of the so-called " chloroform deaths." These conditions 
 are even yet, in spite of the large number of the most careful clinical 
 and experimental observations, not determined with any degree of 
 certainty. On the other hand the symptomatic appearances which 
 precede or accompany death from chloroform have been closely 
 observed and described. 
 
 In a small proportion of the fatal cases of chloroform narcosis, 
 death occurs without any warning prodromal symptoms. In such 
 cases the pulse ceases suddenly, during complete or incomplete 
 narcosis, respiration ceases in. one or two minutes, the face becomes 
 pallid, the pupils dilate and death ensues. Generally, however, the 
 warning is given of a disastrous result of a narcosis by one or more 
 premonitory symptoms. There occur persistent vomiting, decided 
 pallor of the face, labored and occasionally stertorous, ringing 
 respiration, extreme mydriasis, failure to excite reflex action through 
 irritation of the conjunctiva of the globe, spasmodic muscular move- 
 ments, a certain muscular rigidity, and a small, scarcely perceptible 
 pulse, which, in spite of the contractions of the heart, entirely disap- 
 pears. Respiration ceases either simultaneously with or before the 
 stoppage of the pulse, or it may continue after the pulse ceases. In 
 the former case death must be attributed to asphyxia, in the latter to 
 syncope. Billroth* observed in a case of death from chloroform 
 during convulsions, that the haemorrhage from a wounded finger 
 ceased just before the event. 
 
 Kappelerf has collected with great care the statistics of death 
 occurring from chloroform in so far as these have been published > 
 He reports 101 fatal cases, of which 78 were in males and 23 in 
 
 ^Billroth, Wiener Medic. Wochenschr. 1866, No. 46. 
 
 tKappeler, Anaesthetika. Deutsche Chirurgie von Billroth und Lücke, Lief. 20, p. 100 uff. 
 
narcotics — chloroformüm:. 167 
 
 females. The most fatal was between the ages of 46 and 60, 24.7 
 per cent, of the deaths occurring in patients between those years. 
 The next most fatal age was from 31 to 45, between which years the 
 deaths were 20.7 per cent., while in only one fatal case was the 
 patient over sixty and in one also under two years of age. Death 
 occurred before complete anesthetization in 43 cases, and during 
 complete narcosis in 47. In 11 cases there is no statement on this 
 point. In 56 fatal cases of anaesthesia the chloroform was inhaled 
 from a cloth or lint, in five cases from Esmarch's "chloroform 
 basket," and in an equal number of cases from Clover's inhalation 
 apparatus. The quantity of chloroform employed varied in 46 cases 
 between 20 drops and 30 to 60 grammes ( 3 j to f ij), the average 
 quantity being 11.1 gramme ( 3 ij f). Of 20 cases, regarding which 
 the facts are given, death occurred in 10 within from six to fifteen 
 minutes, and in five after from one to three minutes. 
 
 The anatomo-pathological changes hitherto detected afford, 
 because of their inconstant and general nature, no clear insight to the 
 immediate cause of death. The experiments of the English Chloro- 
 form Committee, which were conducted chiefly on dogs, revealed 
 many similar facts to those observed in the autopsies of patients 
 dying from chloroform, viz.: a great fullness of the cavities of the 
 heart with blood, those of the right side being more distended than 
 those of the left. In several cases there were found, as Langenbeck 
 among others as early as 1848 declared there might be, gas bubbles 
 in the veins of those dying from the effects of chloroform. This 
 fact led some French investigators to attribute death from chloro- 
 form to the development of chloroform vapors in the veins, or to 
 embolism in the pulmonary capillaries from this cause. More re- 
 cently renewed observations on the accumulation of gas has led to 
 experimental investigation of this phenomenon. V. Recklinghausen, 
 in three fatal cases of chloroform poisoning, in which breathing con- 
 tinued for some time after cessation of the pulse, found gas bubbles 
 in the larger venous trunks and the heart, in spite of the fact that 
 there was no discoverable trace of decay or decomposition in the 
 body. Sonnenburg* was able, in the experiments which he under- 
 took on animals on the strength of this observation, to develop a 
 gas, which he showed to be nitrogen, in the vessels, but was unable 
 
 5 Sonnen ->u •;. Tageblatt der Naturforscher-Versammlung- zu Baden-Raden, 1S79, P> 2 9- 
 
l68 THE UNTOWARD EFFECTS OF DRUGS. 
 
 to determine the precise conditions and properties necessary to the 
 occurrence of this formation. One may, in his opinion, regard it 
 either as the mechanical separation of the nitrogen, or as the libera- 
 tion of the same, through peculiar pressure, in the vessels and in the 
 presence of chloroform. 
 
 This demonstration of the liberation of a gas in the vessels after 
 the inhalation of chloroform, is, when considered from a general 
 toxicological point of view, highly important. It, however, brings 
 us no nearer a knowledge of how it is that in rare cases death occurs 
 from chloroform narcosis, in spite of the greatest care and watchful- 
 ness, while on the other hand other patients may be anaesthetized 
 with the same chloroform and perhaps very carelessly, without the 
 occurrence of any ill effects. As might have been naturally ex- 
 pected there have been, in the course of time, a great variety of 
 circumstances alleged as causes of the bad or fatal, results of chloro- 
 form narcosis. We have, however, not as yet been in a position to 
 regard any one or more of them as the general or sole etiological 
 factor. It is thus impossible to concede the truth of such a positive 
 statement as the following, first made by Sedillot* and later by 
 Yvonneauj: "le chloroforme pur et bien employe ne tue jamais," 
 inasmuch as there are probably other factors which, under certain 
 circumstances, may determine the ill results of the anaesthesia. 
 
 The many conditions which have hitherto been held responsible 
 for death from chloroform, may be arranged under three heads, as 
 follows: | 
 
 i. The quality of the chloroform. 
 
 2. The manner of its administration. 
 
 3. The mental and physical condition of the patient. 
 
 i. The bad quality of the chloroform is usually regarded as the 
 chief factor in the causation of ill effects or death from its employ- 
 ment. It is a familiar fact that chloroform may, either through 
 design or accident, be adulterated in many ways. The former con- 
 sists in the addition of alcohol or ether, and the latter may be the 
 result of the method employed in the manufacture of the drug or of 
 the spontaneous decomposition of the chloroform by the action of 
 light. The impurities which occur in the manufacture of chloro- 
 form consist chiefly either of a mixture of acetyl and its chlorine 
 
 *Se*dillot, Gazette de Strassbourg, 7851, 7., 11. 
 fYvonneau, De l'emploi du Chloroforme, Paris, 1853. 
 
NARCOTICS — CHLOROFORMUM. 169 
 
 derivatives or fusel oil. These may be detected by the occurrence 
 of a black or red color on the addition to chloroform containing them, 
 of concentrated sulphuric acid. The products of the spontaneous 
 decomposition of chloroform may be: free chlorine (detected by the 
 appearance of a red color when such chloroform is dropped into a 
 dilute solution of the iodide of potassium), hydrochloric acid (the 
 chloroform containing it becoming cloudy on the addition of nitrate 
 of silver), and hypochlorous acid (the presence of which is detected 
 by the bleaching of blue litmus paper when dipped in chloroform). 
 In addition to these there may also be found higher chlorine com- 
 pounds, as for instance, ethene chloride (Dutch liquid), ethyl 
 chloride, tetrachloride of ethene, ethidene chloride, trichlorethane, 
 tetrachlorethane, chlorallyl, amyl chloride, and aldehyde and amy- 
 lene. 
 
 All these impurities of an organic nature, the majority of which 
 may be demonstrated by qualitative analysis, usually betray their 
 presence by the change in the specific gravity and the boiling 
 point of chloroform. Officinal chloroform has a sp. gr. of 
 1.496; absolutely pure chloroform at i5°C. (59°F.) a sp. gr. of 
 1.502; at i7.5°C. (64°F.) a sp. gr. of 1.497; and at 2o°C. (68°F.) a sp. 
 gr. of 1.493. The presence of 0.5 per cent, of alcohol reduces the 
 sp. gr. to 1.493 at I 5°C (59°F.) and 1 per cent, to 1.485. In the 
 san d manner ether, ethene chloride and amylene reduce the specific 
 gravity, while tetrachlorethene, tetrachlorethane and trichlorethane 
 raise it. The boiling point of officinal chloroform is between 6i° 
 and 62°C. (i43°F.). It is lowered by ethylic chloride, ether and 
 amylene, and raised by alcohol, ethylenic chloride and the rest of 
 the higher chlorine compounds mentioned above. Chloroform pre- 
 pared from chloral and also the English chloroform, both of which 
 are said to undergo no decomposition, have a specific gravity of less 
 than 1.49. 
 
 Nearly all of the higher compounds with chlorine which have 
 been mentioned, cause untoward effects when inhaled, and are quite 
 capable of causing accidents when administered in the presence of 
 certain predisposing bodily conditions. While it is true that these 
 by-products have, heretofore, been discovered in but a few of the 
 cases which have been recorded, it appears that as a rule no very 
 accurate investigation of them has been made. The observation 
 
170 THE UNTOWARD EFFECTS OF DRUGS. 
 
 of Bartscher* on the difference between the action on man of pure 
 chloroform and that containing foreign chlorinated products, is 
 worthy of notice. While he was able to very readily procure nar- 
 cosis with fresh chloroform, a sample which had stood for several 
 weeks caused a series of evil effects both during the narcosis and in 
 the course of the next twenty-four hours. The changes which the 
 chloroform suffered in standing were first manifest in the loss of the 
 somewhat pleasant sweetish taste and by its causing a burning sen- 
 sation in the nose and throat which gradually developed into a feel- 
 ing of unpleasant irritation. In such cases the presence of hydro- 
 chloric acid, alcohol and ethene chloride could always be demon- 
 strated. The deleterious untoward effects disappeared with the 
 use of rectified chloroform. Berghmannf found in a sample of 
 chloroform from the employment of which death occurred before 
 full anaesthesia was secured, small quantities of chloride of allyl. In 
 another case reported by Hüter,;); in which death occurred during 
 complete anaesthesia, only a third of the chloroform administered 
 was distilled over at the proper temperature (62 Cels. [i43-|°F.]). 
 The remainder boiled only at 70 and 75° Cels. (158 and i67°F.), 
 and even at 8o° Cels. (r76°F.), there was a not inconsiderable residue. 
 Neither hydrochloric acid nor free chlorine was among its contents. 
 It seemed to have been prepared from impure alcohol, and contained 
 chlorinated products. From the occurrence of effects of this nature 
 one cannot but regard the bad quality of chloroform as an important 
 factor in the causation of death, especially when the patient was 
 robust and suffering from no pre-existing disease. In order to 
 ensure certain security against effects such as reported, the custom 
 of Huter to administer only such chloroform whose boiling point 
 has been determined, is to be recommended. 
 
 2. The improper manner of its administration, that is, the in- 
 halation of chloroform without a proper admixture of atmospheric 
 air, is much more certain than impure chloroform to cause threaten- 
 ing symptoms or death. In England, particularly, the greatest im- 
 portance is attached to this factor in the causation of death from 
 chloroform. Thus the English Chloroform Committee § gave ex- 
 pression to the opinion that those cases in which death occurs 
 
 *Bartscher, Berl. Klin. Wochenschr., 1866, p. 325. 
 tBerghmann, Ref. by Kappeler, 1. c, p. 88. 
 JHUter, Berl. Klin, Wochenschr., 1866, No. 30. 
 §Medico-Chirurg\ Transact, xlvii., 1864, p. 323. 
 
NARCOTICS CHLOROFORM U.M. i;i 
 
 before the stage of anaesthesia as well as those in which death 
 occurs from syncope before the beginning of the stage of excitement, 
 are due to the sudden inhalation of too concentrated vapors of 
 chloroform. Holmgreen* has more recently succeeded in showing, 
 by experiment, that the retardation or suspension of the heart beat 
 from the inhalation of a too concentrated condition of the chloro- 
 form vapors at the beginning of narcotization, results from a reflex 
 influence from the branches of the trigeminus distributed to the 
 nasal and pharyngeal mucous membrane on the vagus. Should 
 these parts be protected from contact with the chloroform vapors, 
 as may be done by administering them through a tracheal canula, 
 these disturbances of respiration and the pulse, as the Chloroform 
 Committee found, do not appear. Lallemand, also, and Perrinf 
 and Duroy, observed the speedy occurrence of death in animals 
 which inhaled the too concentrated chloroform vapors. A mixture 
 of 4 parts of chloroform with ioo parts of atmospheric air was 
 found by them to be innocuous, while one of 8:100 was deadly in 
 its effects. In order to obviate the danger of too concentrated 
 chloroform vapors, the Chloroform Committee laid down the follow- 
 ing mixture as the standard of strength for inhalation: chloroform 
 3^ parts to 100 parts of atmospheric air, and as the maximum a 
 mixture of chloroform 4^ parts with 100 of air. 
 
 For the preparation of this or similar mixtures Clover and 
 others have devised various apparatuses. These are, however, too 
 complicated and furnish a no more certain protection against the 
 dangers of chloroform, which lie in the concentration, than the 
 ordinary chloroform basket in the hands of a competent person. 
 The dangers which are due to concentration may with cer- 
 tainty be avoided by giving the chloroform gradually, beginning with 
 small quantities and allowing a free admission of fresh atmospheric 
 air to the air passages. 
 
 P. Bertj; traces nearly all of the dangers which attend anes- 
 thetization by chloroform, to the methods of its administration 
 which have heretofore been in vogue. He calls the interval between 
 the anaesthetizing and the fatal dose, the "turning zone" 
 
 '■"Holmgreen, Virchow-Hirsch's Jahresbericht 1867, I., p. 450. 
 
 tLallemand, Perrin, Duroy, Du role de i'al cooj. et des anesthesiques dans Torganisme 
 Paris, i36o. 
 
 JP. Bert, Communication sur les Anesthesiques, Bullet, de l'Academ. de Medec. 
 Nov. 1881. 
 
172 THE UNTOWARD EFFECTS OF DRUGS. 
 
 (wendezone, zone maniable), that is the time when it still lays in the 
 power of the surgeon either to restore the patient to a conscious- 
 ness of pain or to permit him to die. As regards 
 the limits of this zone, he found that the fatal dose is always 
 double that required to produce anaesthesia. According to this 
 the inhalation of the anaesthetic is most dangerous the limits of 
 whose " Zone maniable" is most contracted. In the pernicious method 
 of anaesthetization heretofore employed the patient inhales alternately 
 a mixture of the anaesthetic and atmospheric air which depends for 
 its proportions on the absorptive power of the basket or compress, 
 and the distance between the apparatus and the respiratory organs. 
 This mixture is sometimes in less than anaesthetic proportions and 
 sometimes in the " wendezone," and may also approach the fatal 
 dose or even reach it. Should the inhaling apparatus be removed 
 on the appearance of threatening symptoms, the composition of the 
 mixture in the lungs is forthwith changed at the next inspiration, 
 but it is not always possible to avert the fatal issue. 
 
 According to P. Bert the activity of the chloroform inhaled does 
 not depend on the actual amount taken, but rather in the proportion 
 in which it exists in the atmosphere inspired. He, therefore, re- 
 gards the methods of inducing anaesthesia heretofore employed as 
 incorrect, and proposes to have the anaesthetic inhaled through a 
 small mask and a tube from a zinc box holding from 200 to 300 
 liters (50 to 80 gallons) and in which definite proportions of atmos- 
 pheric air have been mixed with the anaesthetic in the form of vapor 
 or gas. In this manner every danger may be obviated, and even 
 the watching of the pulse and respiration rendered unnecessary. 
 
 It is very manifest from this that P. Bert leaves entirely out of 
 consideration the powerful influence of individuality which may cer- 
 tainly be sufficient to induce unfavorable action in some persons. 
 
 3. The mental and physical condition of the patient is a much 
 more important factor in the causation of dangerous symptoms dur- 
 ing anaesthetization by chloroform than both of the factors already 
 mentioned. But we are not any more justified in regarding the bad 
 quality of the chloroform or its improper administration, as the only 
 cause of all the deaths from chloroform, or of its untoward effects, 
 even, than we are in holding that any of the conditions about to be 
 mentioned is the exclusive factor in the causation of the perverse 
 action of the drug. The several authors have held the following 
 
NARCOTICS CHLOROFORMUM. 173 
 
 conditions, pertaining to the mental and physical spheres, responsible 
 for such action : 
 
 a. The idiosyncrasy against chloroform. 
 
 Clemens,* Billroth, f and Denönvilliers.J The latter, par- 
 ticularly, declares that the death from chloroform which 
 occurs with lightning rapidity after a few inhalations of the 
 drug, is due to idiosyncrasy. He cites as analogous 
 occurrences the specific action of other drugs, as iodide of 
 potassium, etc., upon certain persons. Clemens claims to have fre- 
 quently met this chloroform idiosyncrasy. It manifests itself in 
 persons who submit to the use of chloroform through an earnest 
 desire for a painless operation, but who, after the first inhalation 
 spring up declaring that they had rather undergo the operation 
 without the anaesthetic. Denonvilliers is of the opinion that the 
 peculiar susceptibility to the toxic effects of chloroform which exists 
 in some persons is but temporary, inasmuch as patients who some 
 time before have borne the drug very kindly during a first opera- 
 tion have succumbed at its second administration. An attempt was 
 already made in the introduction to this work to furnish a founda- 
 tion for a conception of the term "idiosyncrasy" — a term in itself 
 without significance. If we conceive it to refer to a certain physi- 
 cal condition, which is either congenital and consisting of a falling 
 short of the normal standard of the structure or an improper arrange- 
 ment of the different parts of the body, or is but temporary and a 
 consequence of functional disturbances in individual organs, we 
 are able to explain the deviation from the normal action of chloro- 
 form, as, for example, the ready occurrence of reflex stoppage of 
 the heart beat, the occurrence of eruptions or of vomiting in given 
 cases. 
 
 b. Psychical depression. 
 
 According to the views of the English Chloroform Committee, 
 such persons as are under the influence of any emotion, whether it 
 be fear, fright or care, etc., are peculiarly liable to succumb to the 
 action of chloroform. The same is true of persons who have 
 suffered injury from the action of any sudden external force, or, in 
 other words, are suffering from that complexity of symptoms known 
 
 *Clemens, Archiv, f. Heilkunde, 1854, p. 500. 
 
 tBillroth, Wiener Medic. Wochenschr. 1868, No. 47. 
 
 ^Denonvilliers, Bulletin de 1' Academie de Medec, Juin. Juillet, 1857, T. xxiL 
 
174 THE UNTOWARD EFFECTS OF DRUGS. 
 
 as " shock," manifesting itself in mental apathy or unconscious- 
 ness, feebleness of the pulse, pallor of countenance, etc. 
 
 c. Bodily weakness. 
 
 It matters little whether this condition be the result of pro- 
 longed suffering, direct loss of blood, or venereal excesses. Paget,* 
 in the case of a girl of dissolute habits, who died after the first few 
 inhalations of chloroform, which was being given for the removal 
 of a carcinoma of the vagina, attributed the death to the debilitated 
 bodily condition resulting from her dissolute life. In confirmation 
 of these observations are Clemens'f experiments on dogs, rabbits, 
 guinea pigs, and also on large insects, which resulted in showing 
 that those in which there had been previous immoderate sexual 
 indulgence were more readily destroyed by chloroform and with 
 smaller doses than those which had not been thus indulged. 
 
 d. Cardiac affections, a fid especially fatty degeneration. 
 
 A fatty condition of the heart, notwithstanding the negative re- 
 sults of an investigation in this direction by Kidd,J in persons who 
 died during chloroform narcosis, must be regarded as an important 
 factor in the causation of death under such circumstances. Sansom § 
 found it to exist in eighteen out of fifty-six such cases, and in the 
 sixty autopsies tabulated by Kappeler|| in sixteen there were various 
 degrees of fatty degeneration of the heart. Regardless of this large 
 percentage Kappeler holds a fatty heart to be relatively rather than 
 absolutely dangerous, inasmuch as on the one hand some of those in 
 whom this condition was found had previously taken chloroform 
 without bad effects, and on the other hand he had never seen any 
 symptoms of disturbance from the action of chloroform in amputa- 
 tions for senile gangrene, a condition in which atrophy and fatty 
 degeneration of the heart are very common. This limitation of 
 fatty degeneration of the heart to a sphere of but relative impor- 
 tance as a source of danger, is entirely proper, inasmuch as the 
 very frequent occurrence of this condition, in slight degrees, would 
 be liable, in an investigation of the causation of deaths from 
 chloroform, to direct attention in wrong channels and lead to 
 erroneous deductions. 
 
 * Paget, Lancet, October, 1853. 
 
 tClemens, 1. c, p. 504. 
 
 $Kidd, British Medical Journal, 1862, Jan. 25, May 24. 
 
 §Sansom, Chloroform, its action and administration, London, i£ 
 
 JKappeler, 1. c, p. 121. 
 
NARCOTICS CHLOROFORMUM. 175 
 
 e. Chronic alcoholism. 
 
 It has not yet been determined how it is that inebriates present 
 such abnormal reactions to the inhalation of chloroform as are so 
 often noticeable in the operating room. Such individuals not only 
 require much larger quantities of chloroform to bring about complete 
 anaesthesia than are required in normal persons, but there also 
 occur in them a high degree of excitation, manifesting itself in ex- 
 cessive muscular activity, shrieking and struggling and in uncon- 
 scious attempts to leave the operating table. In the condition of 
 relaxation which follows this stage of excitement there not infre- 
 quently occurs a state of collapse with stertorous breathing which 
 may readily lead to a fatal issue. It is very natural to attribute these 
 symptoms to the combined action of the alcohol and the chloroform, 
 and attempts have been made to discover this action in different 
 directions. Lefort is of the opinion that the organism weakened by 
 the action of alcohol is unable to tolerate the chloroform, an ex- 
 planation which is little more than a statement of the fact. Accord- 
 ing to Scheincsson* chloroform operates both to prevent the pro- 
 duction of heat and to retard the bio-chemical processes in the body. 
 Alcohol operates in the same way, and thus inebriates, through a 
 combination of the action of these two agents, are more liable to un- 
 pleasant untoward symptoms and even to deleterious consequences. 
 It is, however, difficult to understand how causes — a lowering of 
 the temperature and a retardation of the chemical processes in the 
 body — could operate in so short a time as intervenes between the 
 commencement of narcosis and the beginning of sleep, to exert such 
 excessive action. It would appear to be more natural to suppose 
 that the material changes in the central nervous system in chronic 
 alcoholism manifest themselves only in a higher degree and in a 
 more deleterious manner in functional disturbances, than is the case 
 in the ordinary excesses in alcoholic beverages. According to this 
 view the collective abnormal symptoms are of either central or reflex 
 origin. 
 
 According to the statistics collected from various authors the 
 percentage of deaths from chloroform occurring among inebriates, 
 varies from 10 to 13. 
 
 *Scheinesson, Untersuchungen über den Einfluss des Chloroforms auf die 
 Wärmeverhältnisse dir Organe und den Blutkreislauf. Dorpat, 1868 und- Archiv der 
 Heilkunde, Bd. X., 1869. 
 
I76 THE UNTOWARD EFFECTS OF DRUGS. 
 
 We have discussed in the foregoing the causes which, either 
 singly or combined, result in death from chloroform, and have 
 pointed out the symptoms under which it occurs. Fortunately, such 
 deaths are relatively few — occurring about once in three thousand 
 cases — and it is probable that by a closer investigation into the 
 causation, a more favorable showing than this would appear. Doubt- 
 less the death rate would also be still further reduced through a cor- 
 rect knowledge of and attentive regard for the milder accidents 
 which are observed in the majority of the cases of the administration 
 of chloroform, and which, as was remarked at the beginning of this 
 article, not infrequently precede death from chloroform. 
 
 To these occurrences belong the tonic spasm of the muscles 
 concerned in mastication and the posterior muscles of the tongue, 
 which frequently occurs during the stage of excitement. The 
 tongue is thus drawn spasmodically backwards by means of the 
 stylo-glossal and stylo-pharyngeal muscles, and presses down the 
 epiglottis. In this manner there is caused a mechanical closure of 
 the entrance to the glottis, which, if relief be not at once afforded, 
 results in mechanical suffocation, with cyanosis of the lips, exoph- 
 thalmus, etc. 
 
 Another unpleasant untoward effect is the vomiting which may 
 occur at any stage of the action of chloroform. This nearly always 
 occurs when the stomach is full, and may be so persistent as to con- 
 tinue for even twenty-four hours after recovery from the anaesthesia, 
 and is usually accompanied by thirst, headache and mental depres- 
 sion. The entrance of the contents of the stomach into the air pas- 
 sages seldom occurs under such circumstances, inasmuch as the 
 patient usually awakes at the commencement of vomiting. In the 
 10 1 cases of death collected by Kappeler, death occurred from suffo- 
 cation in this manner in only two. 
 
 In rare cases jaundice and the discharge of the coloring matter 
 of the bile in the urine have been observed as a result of the inhala- 
 tion of chloroform. 
 
 The greatest attention is, however, demanded by the symptoms 
 referable to the organs of respiration and circulation. As has al- 
 ready been stated, reflex apncea may occur after the first few inhala- 
 tions of the chloroform. There suddenly occur in such cases one 
 or more pauses of greater or shorter length in respiration, or the 
 inspirations become shallower and slower, or, finally, after a long, 
 
NARCOTICS CHLOROFORMUM. 1 77 
 
 jerking expiration, inspiration is entirely suspended. These 
 conditions either spontaneously disappear or are readily relieved 
 by skilled assistance. In the same manner irregularity or 
 complete stoppage of the pulse, and pallor of the face, may also 
 occur. These symptoms may also disappear spontaneously. In 
 contrast with these is that group of symptoms which present under 
 the name of chloroform syncope, in which the radial pulse sudden- 
 ly disappears, the heart sounds become scarcely audible, the face 
 assumes the appearance of death and respiration ceases. It is only 
 in the rarest cases that restoration is possible under such circum- 
 stances. 
 
 Richet* noted another untoward effect of chloroform which is 
 remarkable, however, only from a pathological point of view. Dur- 
 ing a normal narcosis there appeared an eruption of dark-red spots 
 which spread over the whole body and which had the appearance of 
 purpura haemorrhagica, disappearing, however, under pressure of 
 the finger. 
 
 The untoward effects of the external application of chloroform 
 to the sound skin or mucous membrane, are of an interest quite 
 equal to those following its inhalation. Following the rubbing in of 
 chloroform upon the sound epidermis there occurs a smarting red- 
 ness, and not infrequently there appears an urticaria-like eruption or 
 an eczematous change of the skin, while vesicles may also result 
 from its long-continued use. Applied to certain sensitive portions 
 of the skin, as, for instance, the scrotum, chloroform causes such 
 severe and persistent pain that the patient usually objects to its re- 
 newal. For this reason the method of treating orchitis recommend- 
 ed by Bouisson,f viz., the application of compresses wet with chloro- 
 form, is objectionable. 
 
 Chloroform applied to wounds and mucous membranes causes 
 irritation of disproportionate intensity. When during anaesthesia it 
 drops from the chloroform basket on the lips, it sometimes either 
 produces fissures of the lips, or the mucous membrane is shed in 
 pieces. 
 
 The treatment of chloroform accidents. — The disturbances of 
 respiration and circulation are the first to demand energetic treat- 
 ment. The mechanical closure of the glottis by the spontaneous 
 
 *Richet, Journal de la Societe des Scienc. Medic, de Bruxelles, 185 1. 
 tBouisson, Annales des maladies de la peau Janvier, 1851. 
 
178 THE UNTOWARD EFFECTS OF DRUGS. 
 
 falling back of the tongue or by spasmodic contraction of the 
 posterior muscles of the tongue, is overcome by opening the mouth, 
 if need be by means' of Heister's speculum, and by forcibly drawing 
 the tongue forward by means of a tongue forceps or a loop of 
 thread, and cleansing the mouth of mucus. In many cases the em- 
 barrassment to the entrance of air may be overcome by the 
 more simple manipulation of the lower jaw, after the method 
 described by Heiberg.* This is best accomplished by the 
 operator's standing behind the recumbent patient, placing both 
 thumbs on the symphysis of the lower jaw, pressing the second 
 joint of the bent index finger behind the posterior borders of the 
 ascending rami of the jaw, thus holding the entire bone firmly be- 
 tween his hands and then drawing it forcibly forward. To accom- 
 plish the same object, Kappeler, standing before the patient, places 
 his thumbs close beside his nose on the anterior border of the upper 
 jaw and with the hooked index fingers, formed by bending the 
 distal phalanges, placed behind the angles of the lower jaw, draws 
 the bone forward. By this means both the tongue and the os 
 hyoides are drawn forward and the epiglottis, which is drawn with 
 them, is raised up. 
 
 If, notwithstanding the fact of unobstructed entrance of air in- 
 to the lungs, disturbances of the respiration and circulation super- 
 vene, with simultaneous change in the color of the patient's face, 
 the chloroform should be forthwith discontinued and a free supply 
 of fresh air provided, and should anaesthesia not be complete, as 
 evinced by response through reflex movements to external irritation, 
 the cold water douche or the injection of cold water into the nasal 
 cavities, and the use of irritant inhalations, as of ammonia, 
 carbonate of ammonia, etc., should be resorted to. As Billroth,! 
 however, very truly declares, no time should be wasted in these 
 measures in complete anaesthesia. They are of no service under 
 such conditions and resort must at once be had to artificial respira- 
 tion. 
 
 A number of methods of effecting artificial respiration have 
 been proposed: 
 
 1. Direct inflation from mouth to mouth, in which method ex- 
 piration is assisted by compression of the lower portion of the thorax, 
 
 *Heiberg, Berliner Klin. Wochenschr., 1874, p. 449. 
 1 Billroth, Wien. Medic. Wochenschr., 1868, p. 795. 
 
NARCOTICS CHLOROFORMUM. 179 
 
 and for the completion of which the nostrils must be closed. In this 
 method, as Billroth has observed, a portion of the air blown in finds 
 its way into the stomach. 
 
 2. Inflation by means of a bellows. Plouviez* introduced the 
 nozzle of a bellows into one nostril or into the throat, and suddenly 
 expressed a current of air into the lungs. At the same time the 
 breast and the abdomen were alternately compressed. 
 
 3. Inflation through a laryngeal catheter. Should it be im- 
 possible, owing to spasm of the posterior lingual muscles and the 
 upper pharyngeal muscles, to introduce the catheter, tracheotomy 
 will be necessary and air introduced through the tracheal canula by 
 the mouth or bellows. 
 
 4. Marshall Hall's method, in which the patient is regularly 
 several times a minute turned on his back and on his side, pressure 
 being made on the back at each turn. 
 
 5. Galvanization of the phrenic. The moistened positive 
 electrode of a constant battery or interrupted induction apparatus, 
 is placed over the phrenic nerve in the neck, over the scalenus muscle, 
 and the negative electrode over the precordial region under the 
 border of the ribs, or both poles are placed on the neck, one on each 
 side, at the outer border of the sterno-cleido-mastoid muscles. 
 
 6. Allowing the head of the patient to hang down, according 
 to Nelaton, or suspending him by his feet, after the method success- 
 fully adopted by Spoererf in one case. 
 
 7. Acupuncture or electro-puncture of the heart. This was 
 resorted to by Hüter,]; as a dernier ressort, but without success in 
 a case of arrest of the heart-beat. He plunged one needle two 
 inches in length into the fourth intercostal space at the edge of the 
 sternum, to the depth of three quarters of an inch to an inch, and a 
 second nearer the nipple and somewhat lower down. 
 
 The occurrence of one or several fits of vomiting during 
 anaesthesia, or on awaking from it, seldom demands therapeutic in- 
 terference. Should it, however, become more frequent, small pieces 
 of ice or champagne should be given. Usually the application of 
 cold compresses over the stomach suffices to allay it. 
 
 *Plouviez, Journal de la Soc. des Sciences medic, de Bruxelles, 1857, p. 14. 
 tSpoerer, Petersburger Medic. Zeitschrift, 1866, p. 1 10. 
 JHüter, Berliner Klin. Wochenschr., 1865, p. 486. 
 
l8o THE UNTOWARD EFFECTS OF DRUGS. 
 
 IODOFORMUM. 
 
 Aside from the odor due to its elimination, there have as yet 
 been no untoward effects observed from the employment of iodo- 
 form, other than such as are referable to the central action of the 
 drug. After the anaesthetic or hypnotic action of this drug had 
 been indicated by Italian authors, Binz* showed that the effect was 
 due to a liberation of iodine in the system. " As a yeast-cell when 
 touched by iodine no longer decomposes sugar, and a white corpus- 
 cle no longer throws out processes, so is the peculiar function of a 
 brain cell under such circumstances held in abeyance; it is no 
 longer susceptible to external impressions, and ceases to generate 
 impulses for its centrifugal processes. Itsleeps, should the effect 
 caused by the iodine be reparable; should the structure be destroyed 
 by the iodine, it dies." 
 
 An illustration of the correctness of this deduction is afforded 
 by several cases reported by Oberlsender,-)- among others, in which 
 untoward effects of a central nature followed the employment of 
 iodoform. A female affected with gummy tumors took 42 grammes 
 ( 3 xss) of iodoform, in the form of pills, in the course of 80 days. 
 There occurred at the end of this time vertigo, a sensation of weak- 
 ness and double vision. These symptoms continued two and a half 
 days. In spite of the suspension of the pills, she began to vomit 
 and fell into a deep sleep, from which she was aroused only with 
 difficulty. For several days this sleepiness alternated with excite- 
 ment, incoherence of speech, a feeling of anxiety and twitching of 
 the muscles of the face and trunk. It was not before the twelfth 
 day after the onset of these symptoms that she could stand alone 
 and walk a short distance. 
 
 The second case was that of a person who had taken five 
 grammes (gr. lxxv) of iodoform, in pills, in the course of seven days, 
 for ulceration of the throat. Somnolence supervened, the gait 
 became difficult and uncertain, and there was headache over the 
 entire circumference of the head. After this condition had lasted 
 for a day, there set in a comatose condition, which lasted for five 
 
 *ßinz, Archiv, f. Experimen. Pathologie u. Pharmakologie. Bd. viii., p. 310, u. Bd. viii., 
 p. 159. 
 
 tDeutsche Zeitschrift f. pr. Medicin, 1878, No. 37. Refer, in Archiv f. Dermatologie u. 
 Syphilis, 1879, p. 372. 
 
NARCOTICS IODOFORMUM. 
 
 days, the patient responding promptly, however, to external irrita- 
 tion and making motion as if warding it off, and swallowing 
 nourishment. The urine showed a distinct iodine reaction. It 
 was not until after fourteen days after the appearance of these 
 symptoms that the patient could be pronounced cured. The 
 liability of confounding these cases with cerebral syphilis is slight, 
 inasmuch as there is no improvement in the latter from the expectant 
 plan of treatment. 
 
 Connected with the extensive employment of iodoform in 
 antiseptic dressing, as also as a specific in localized tuberculous 
 processes as it is now employed in surgery, a series of unto- 
 ward effects, at times dangerous and even fatal, have been noted. 
 The majority of these are traceable to the injudicious use of 
 the drug. Large cavities of wounds, joints, etc., have been and are 
 still, packed with this substance and even from ioo to 200 grammes 
 ( 3 iij to 3 vj) has been introduced into the cavity of the abdomen. 
 It is not to be wondered at that the deleterious action of iodine 
 should thus be manifest in the most varied organs and systems. In 
 some cases the temperature is raised to 41 C. (105. 8° F.), the pulse 
 to 150 per minute, vomiting occurs, the appetite is diminished, the 
 patients b'ecome languid, complain of dizziness, mental confusion, 
 are incapable of either mental or physical exertion and usually fall 
 into a lethargic condition. Following this condition, according to 
 Henry,* paralysis of the sphincters, disturbances of speech and 
 finally death may suddenly occur. Should even a certain degree of 
 toleration have been secured through several weeks' use of the drug, 
 death may occur with mental clearness but with aseptic fever, 
 even should the use of the drug in the meantime have been discon- 
 tinued. 
 
 The most disturbing, and through their relative frequency and 
 the suddenness of their onset, the most dangerous forms of intoxi- 
 cation, are, as Schedef has declared, on the basis of his own obser- 
 vations, are the disturbances of the cerebral functions, whether 
 these are due to acute meningitis or to actual mental disease (melan- 
 cholia, great depression of spirits, etc.), which occur, and which, even 
 when the iodoform has been discontinued, may lead to a fatal issue. 
 
 These results, as L. LewinJ has declared, compel us to look to 
 
 *Henry, Deutsche Medic. Wochenschrift, No. 34, 1881. 
 
 tSchede, Centralbl. f. Chirurgie, No. 3. 1882. 
 
 iL. Lewin, Berl. Klin, Wochenschrift. No. 42, 1882. 
 
182 THE UNTOWARD EFFECTS OF DRUGS. 
 
 other causes than the doses in which the drug has been employed, 
 and above all to have a regard for the individuality of the patient. 
 
 The desired therapeutic end may be secured by much smaller 
 and non-toxic doses by insufflating the drug in a finely powdered 
 condition into the cavity of wounds, or by dusting it on wounded 
 surfaces. In the case of existing fistulae iodoform pencils may be 
 introduced for their antiseptic effect, and in situations to which it 
 is impossible to apply the solid substance, the iodoform may be ap- 
 plied by means of volatilization with steam. In cases in which un- 
 toward effects occur even in connection with these means of the ad- 
 ministration of the drug, the cause must be referred to the idiosyn- 
 crasy of the individual. This idiosyncrasy seems to be peculiarly 
 marked in the case of females. 
 
 The exhibition of large quantities of iodoform may, as observed 
 by Falkson,* cause the drug to play the part of a foreign body; 
 it may become incorporated with the newly formed connective tissue 
 in which it may remain encapsuled after the subsidence of the 
 healing process. In such cases, however, it generally gives rise to 
 an iodoform abscess, showing itself in a circumscribed swelling, with 
 pain on pressure and redness of skin. An incision causes the expul- 
 sion of pure iodoform, with occasional slight admixture with mucus. 
 The exhibition of iodoform in the form of crystals! is particularly 
 favorable to the formation of such abscesses/ 
 
 METHYLENI BICHLORIDUM. 
 
 Since 1867, when Richardson first recommended the bichloride 
 of methylene, or chloromethyl, as an anaesthetic, this drug has been 
 extensively employed, it being said to be preferable to chloroform 
 in that its use is attended with less danger and is accompanied by 
 but slight untoward effects. It has, however, been established in 
 course of time that this substance has no special advantages over 
 chloroform and is scarcely less dangerous. Holländer,! who 
 employed it in the extraction of teeth, found it necessary in one 
 case to administer nearly 30 grammes ( 3'j) to destroy sensation, 
 after which he observed a state of excitement, severe fits of vomit- 
 ing, and a condition of confusion of the head which continued for 
 
 *Falkson, Archiv, fur Chirurgie Bd. X. 
 
 tHolländer, Berliner Klin. Wochenschrift, 1867, p. 49. 
 
NARCOTICS ETHYLIDEXI BICHLORIDUM, 183 
 
 upwards of an hour after the cessation of anaesthesia. Hegar and 
 Kaltenbach* noticed asphyxia after the inhalation of the bichloride 
 of methylene, and when the drug was administered by means of the 
 wire basket instead of Junker's apparatus, it caused excoriation of 
 the lips and cheeks. 
 
 But in addition to these slighter accidents, fatal consequences 
 have followed the exhibition of the drug. These occur either sud- 
 denly, without disturbance of respiration or change in the color of 
 the face, or the breathing becomes gasping, the pulse at the wrist 
 small and fluttering, the color of the face pale ,or livid, and death 
 occurs with complete arrest of the pulse and no convulsions. It 
 should be mentioned here that a more recent examination of a prepa- 
 ration known as bichloride of methylene, imported from England, 
 shows it to present nothing in common, except the name, with the 
 methylene chloride; that it consists much more largely of chloro- 
 form, which may, by the addition of alcohol, be brought to nearly the 
 specific gravity of the methylene bichloride. 
 
 ETHYLIDEXI BICHLORIDUM. 
 
 The chloride of ethylidene, recommended as an anaesthetic 
 and occasionally employed clinically for this purpose, is a fluid 
 which boils at 6o° C. (140 F.) and produces prompt and easy 
 anaesthesia with regularity of the pulse and respiration. The occur- 
 rence of a death during anaesthesia induced by this agent, has, 
 however, prevented its further trial. 
 
 ETHER SULPHURICUS. 
 
 Sulphuric ether, like chloroform, causes by its inhalation, a 
 series of accidents which are either of a transitory nature or may be 
 attended with fatal consequences. The transitory symptoms are 
 associated with persistent vomiting, which occurs not only during 
 the anaesthesia but continues also after the operation, to be followed 
 by explosive coughing. The latter occurs, probably, in consequence 
 of the accumulation of saliva in the air passages, due to the 
 
 ? Hegar u. Kaltenbach, Operative Gynaekologie, 1874, p. 25. 
 
184 THE UNTOWARD EFFECTS OF DRUGS. 
 
 increased salivation which always occurs during the anesthetiza- 
 tion. 
 
 The threatening symptoms are referable to the respiration and 
 the circulation. Pallor or cyanosis of the face occur, the respiration 
 at the same time becoming irregular or ceasing entirely, and the 
 pulse becoming small and finally imperceptible. Cases are reported 
 in which artificial respiration, drawing forward the tongue, etc., 
 were successful in effecting restoration even after this threatening 
 condition had set in. Should, however, the mechanico-therapeu- 
 tical means against these disturbances not be at once resorted to, 
 death occurs suddenly, the respiration and pulse ceasing simul- 
 taneously, or the latter outlasting the former for several minutes. 
 In the majority of cases reported by English authors, death occurred 
 without any premonitory symptoms. In a few there occurred violent 
 muscular excitement, cyanosis or turgescence of the face, dilatation 
 of the pupil or labored breathing. Only one fatal accident has oc- 
 curred in each 30,000 ansesthetizations by ether. 
 
 The rules governing the procedure against these accidents are 
 the same as those which are to be observed in chloroform syncope. 
 As a prophylactic measure the head must be raised so as not to 
 afford the saliva an opportunity to flow into the air passages. 
 Regard must also be had, as in the case of chloroform, to the degree 
 of concentration of the vapor, and that the preparation employed be 
 perfectly pure. 
 
 The habitual use of ether, as was noted in the case of a 
 so-called "ether-breather," observed by Ewald,* gives rise to 
 general lassitude, weakness, muscular tremor, and a peculiar, disa- 
 greeable odor of the body. 
 
 AMYLI NITRITUM. 
 
 The amyl nitrite, a product of the action of nitric acid on 
 amylic alcohol, was held during the first years of its employment, 
 providing it contained no deleterious by-products, such as hydro- 
 cyanic acid and nitric acid, to be a harmless substance, productive 
 of no disturbing symptoms. Later, however, untoward effects 
 referable to the functions of various organs have been frequently 
 
 *Ewald, Berliner Klin. Wochenschrift, 1875, p. 1; 
 
NARCOTICS AMYLI NITRIUM. 185 
 
 observed to follow its use. The occurrence of these is dependent 
 on the individuality of the person, but may also occasionally occur 
 in those who are accustomed to the inhalation of the drug. 
 
 Of the special organs of sense that of sight is most frequently 
 affected by its use. The subjective sensations of color which it pro- 
 duces are not, as Schrceter* found in several patients, alike in all 
 cases, being only occasionally very distinct in many, and not exactly 
 alike at ea^h inhalation. They consist in their typical form, accord- 
 ing to Pick, \ of the appearance of an intensely yellow halo around 
 any fixed point upon a bright background. The yellow circle is 
 again surrounded by a bluish violet border. This symptom is prob- 
 ably nothing more than the projection of the macula lutea, and 
 the bluish-violet border its complementary color. The patients 
 treated by Sander, J with the nitrite of amyl, declared of their own 
 accord, that everything seemed yellow to them for some time. It 
 could not be accurately determined in these cases whether this was 
 owing to the yellow color of the portion of the field of vision corre- 
 sponding to the macula lutea. This yellow vision disappears only 
 after some minutes, gradually becoming paler. Schrceter noticed 
 also an impairment of the acuteness of vision. Patients who had 
 inhaled the amyl nitrite for some time found it impossible, for 
 instance, to distinguish clearly the figures of a large clock, they 
 having a blurred appearance. Normal acuteness of vision returned 
 with the suspension of the drug. 
 
 Abnormal effects on the central nervous system have been but 
 rarely observed. Veyrieres § observed in his own case, after the con- 
 tinued inhalation of the drug, vertigo and stupor lasting from six to 
 eight minutes and followed by headache of two hours' duration. In 
 some cases of mental aberration Schrceter noted delirium of the 
 senses, or increase or diminution of the same, during the inhalation 
 of the drug, and Bourneville|| has reported similar cases. He ob- 
 served the occurrence of violent headache, vertiginous feeling, and, 
 in hysterical persons, illusions of sight in connection with the yel- 
 low vision, as results of the employment of the nitrite of amyl. 
 
 Following the inhalation of this agent, and to a certain degree 
 
 *Schroter, Zeitschrift f. Psychiatrie, Bd. 32, 5, p. 527. 
 
 tPick, Centralbl. f. die Medic. Wissenschr. , 1873, p. 866. 
 
 ^Sander, Medicin, psycholog. Gesellsch. zu Berlin, Sitzung vom 4, December, 1874. 
 
 §Veyrieres, Virchow-Hirsch's Jahresbericht, 1875, *•> P- 481. 
 
 IBourneville, Gazette Medicale de Paris, 1876, No. 13. 
 
l86 THE UNTOWARD EFFECTS OF DRUGS. 
 
 occurring as an after-effect, Sander observed sudden profound col- 
 lapse characterized by fainting, falling, pallor of countenance, a 
 small pulse and a cold, clammy sweat. Samelsohn* also describes 
 a case in which a patient, while under the full effects of the nitrite 
 of amyl, drew a few deep spasmodic breaths, became chilly and was 
 covered with a cold sweat; the pulse became small and thready and 
 extraordinarily slow, and while consciousness was impaired it was 
 still retained. Urbantschitschf, too, notes the fact that in some 
 cases the inhalation of even two drops of the nitrite of amyl may 
 cause collapse, with paresis or serious vertigo and embarrassment of 
 respiration. 
 
 In connection with the other untoward effects the statement of 
 Bourneville is noteworthy, that following the inhalation of the nitrite 
 of amyl there frequently occur trembling of the lips and difficulty of 
 chewing. Urbantschisch observed after its use dryness of the mouth, 
 which lasted for from twelve to twenty-four hours. Occasionally 
 there first occur, instead of redness of the face, palpitation of the 
 heart, pressure in the head and ears and irritation of the throat. 
 Veyrieres also observed the latter symptom, while Ladendorf| 
 noticed on two occasions, during a four weeks' course of the amyl 
 nitrite, the occurrence of a violent, dry spasmodic cough. Some 
 other authors have also reported distressing nausea and vomiting as 
 results of the repeated inhalation of the drug. 
 
 In using the nitrite of amyl care must be taken that the prepara- 
 tion employed does not present an acid reaction. Unless a few 
 small pieces of burnt chloride of calcium or a little magnesia 
 have been added to it, a preparation of amyl nitrite, origin- 
 ally neutral, may undergo decomposition and generate nitric acid on 
 standing a length of time. Hydrocyanic acid is easily detected by 
 shaking the nitrite of amyl with water, and testing the latter for 
 Prussian blue. 
 
 *Samelsohn, Berliner Klin. Wochenschrift, 1875, p. 349. 
 tUrbantschitsch, Wiener Medic. Presse, 1877, 8 u. ff. 
 JLadendorf, Berliner Klin. Wochenschrift, 1874, p. 539. 
 
EVACUANTS PURGATIVES. 1 87 
 
 EVACUANTS, 
 
 I.—PURGATIVES. 
 
 OLEUM RICINI. 
 
 In many persons there is an unconquerable repugnance to castor 
 oil, and when the oil is taken by such it frequently causes nausea 
 and vomiting. The latter occurs also should the oil have lost its 
 freshness and free fatty acids have formed in it. As means of dis- 
 guising the disagreeable, peculiar fatty taste of castor oil and to 
 render it more palatable, numerous vehicles, such as wine, brandy, 
 milk and coffee, have been commended. Starke* recommended to 
 this end that the oil be converted into a thick, dough-like paste, 
 with sugar (1:3) or compound liquoric powder (1:3), and then incor- 
 porating this with powdered cinnamon or some other corrective. 
 
 ALOE. 
 
 As an accompaniment of the special action of aloe, viz., ordinarily 
 soluble, non-watery stools with moderate griping, there not infre- 
 quently occur, in addition to a sensation of warmth and pressure in 
 the region of the stomach and frequent eructations, a congestive con- 
 dition of other abdominal organs, as the kidneys and uterus. 
 Through such action pre-existing haemorrhages, chiefly of the latter 
 organ, may be aggravated to a threatening degree. Larger doses 
 of aloes, given either in substance or in the form of extract, are also 
 said to have been abortifacient. Women under such conditions 
 complain of pain in the region of the kidneys and uterus, and of a 
 feeling of weight in the pelvis. 
 
 Should an aloetic preparation be employed for a length of time, 
 there occurs, in consequence of the persistent congestion of the de- 
 scending colon and rectum, dilatation of the haemorrhoidal veins 
 
 *Starke, Berliner Klin. Wochenschr, 1879, p. 232. 
 
THE UNTOWARD EFFECTS OF DRUGS. 
 
 which may eventually give rise to hemorrhoidal tumors. It is 
 however, doubtful, in view of the numerous other uncontroll- 
 able conditions which give rise to this affection, whether the state- 
 ment made by Fallopius* be true, that out of a hundred persons who 
 make habitual use of aloes ninety are attacked by haemorrhoids. 
 Elderly, and weakly young persons manifest a special predisposition 
 to such action of aloes. 
 
 FRUCTUS COLOCYNTHIDIS. 
 
 Colocynth belongs to the drastic purgatives, which probably 
 exert their effects through a direct irritation of the mucous mem- 
 brane of the intestines. For this reason, and particularly when the 
 digestive tract is in an irritated condition, the stools caused by colo- 
 cynth are accompanied by severe pain and tenesmus, and may even 
 be mixed with blood. 
 
 TUBERA JALAP^E. 
 
 Like most other resins and substances containing resins, 
 which owe their purgative action to direct irritation of the intes- 
 tinal tract, jalap root, which is operative only in the presence 
 of bile or biliary salts, usually causes abdominal pains and bor- 
 borygmi. Nausea occasionally manifests itself as an evidence of 
 gastric irritation, and vomiting may also occur. Large and fre- 
 quently repeated doses may give rise to catarrhal inflammation of 
 the gastro-intestinal mucous membrane. 
 
 GAMBOGIA. 
 
 ' While small doses of gamboge ordinarily give rise to no pecu- 
 liar untoward effects, there still occur in some persons, even after 
 o.i — 0.2 gramme (gr jss — gr iij) abdominal pains, vomiting and 
 distinct increase in the quantity of urine. 
 
 HERBA GRATIOL^E. 
 
 Gratiola, formerly extensively employed as a purgative, causes 
 
 *FalIopius, Opera omnia. De Medicam. purg. simpl. Francofurti, 1600. 
 
EVACUANTS — PURGATIVES. 189 
 
 according to numerous old writings on the subject, even in doses of 
 0.5 — 1.0 gramme (gr viiss — gr xv), given even in the form of powder 
 or decoction, instead of purgation, nausea and vomiting, or, in addi- 
 tion to these, salivation, burning in the urinary tract, anorexia, and, 
 as Bouvier* observed in the case of a woman in whom it was admin- 
 istered in an enema, nymphomania. Probably the age of the 
 drug, and its percentage of gratiosolin, the active principle of 
 gratiola, have much to do in determining the occurrence of the 
 symptoms named. 
 
 FLORES SULPHURIS. 
 
 Sulphur, which nas been extensively prescribea, in its various 
 chemical combinations, as a purgative in thoracic affections and in 
 chronic metallic poisoning, may, particularly when the digestive 
 tract is not intact, readily excite gastric and intestinal irritation and 
 digestive disturbances. In the presence of the alkaline intestinal 
 juice it is partially transformed into an alkaline sulphate, and as 
 this is decomposed by the carbonic acid of the blood and the tissues 
 into absorbable sulphuretted hydrogen gas, the skin and the expired 
 air usually smell of this gas. In larger doses this drug may, accord- 
 ing to Wibmer,f give rise to a miliary eruption. 
 
 During the external application of sulphur ointment there 
 occurs, in some persons, an artificial eczema, which soon disappears 
 with the suspension of the drug. 
 
 OLEUM TIGLII. 
 
 Croton oil, when administered internally, frequently gives rise, 
 in different degrees in different persons and in addition to its drastic 
 purgative action, to an irritative, burning taste in the mouth, dryness 
 and burning in the throat, eructations, nausea and colicky pains in 
 different parts of the abdomen. 
 
 As a derivative, applied externally to the skin, there occurs after 
 one or two applications, an erythema accompanied by itching and 
 pain and slight fever, and upon this there appear, sometimes dis- 
 crete and sometimes confluent, hard vesicles with serous contents, 
 which in a day or two become purulent — and then burst, or there 
 
 *Bouvier, Gazette de Sante Aoüt. 1816. 
 tWibmer, Wirkungen der Arzneimittel, V., p. 276. 
 
190 THE UNTOWARD EFFECTS OF DRUGS. 
 
 appear at once a large number of maturated pustules upon which 
 crusts form within twenty-four hours. There not infrequently 
 occur, secondarily, particularly on the scrotum, according to Wib- 
 mer*, herpetic eruptions, due, perhaps, to accidental contact of the 
 oil, but perhaps also to its positive absorption. The former is the 
 more likely, inasmuch as such eruptions have never been observed 
 as a result of the internal exhibition of the drug. Tartar emetic, 
 after whose external application similar secondary eruptions have 
 also been observed on the genitals, differs from croton oil in that 
 when given internally it may also give rise to these exanthems. 
 Experiments on animals have shown that the external application 
 of croton oil causes albuminuria, and that too without regard to the 
 painful eczema, and without the causation of any appreciable in- 
 flammatory change in the kidneys. The possibility of such changes 
 in the urine of human beings has not, as yet, been recognized. 
 
 According to Tangenbeck, f the endermic introduction of 
 croton oil gives rise to phlegmonous inflammation and suppuration. 
 
 The above-mentioned skin affections disappear with slight 
 desquamation in from three to eight days after the suspension of 
 the drug, leaving only a pale vellow discoloration at the seat of the 
 affection. 
 
 II.— EMETICS. 
 
 ANTIMONII ET POTASSII TARTRATIS. 
 
 It is known that the external application of tartar emetic, either 
 in solution or ointment, causes both eczema (papules, vesicles, 
 oedema) around the orifices of the glands, as well as extensive pus- 
 tular disease (ecthyma antimoniale) of the skin. The derivative 
 method of treatment, to which end tartar emetic is still occasionally 
 employed, causes intense pain to the patient. Usually only a simple 
 inflammatory irritation is aimed at, but instead of this there is apt 
 to occur extensive destruction of tissue. Particularly in the appli- 
 cation of the so-called " pox salve" to the head to combat certain 
 mental diseases, such as dementia paralytica, there readily occur 
 deep, excavated ulcers, with occasional exfoliation of bone at the 
 
 *Wibmer, 1. c. I., p. 215. 
 
 tM. Langenbeck, Die Impfung der Arzneikörper, Hannover, 1856, p. 84. 
 
EVACUANTS EMETICS. IQI 
 
 bottom of the lesion. Among the older reports bearing on this 
 subject, should be mentioned that by Jacobi*, who, in the year 1819, 
 witnessed in several persons whose entire scalps had been anointed 
 with tartar emetic ointment, perforation of both lamellae of the 
 parietal bones, resulting from necrosis following the inunction. In 
 view of such facts it is certainly not superfluous to mention that 
 Hebra long since denounced such treatment as a " useless, injurious 
 procedure, and occasionally even dangerous to life." 
 
 The internal administration of tartarized antimony as an 
 emetic, either alone or in combination with ipecacuanha, as also the 
 employment of other preparations of antimony, is sometimes fol- 
 lowed, especially in children, by a condition resembling collapse, owing 
 to the very pronounced property of antimony in causing a lowering 
 of the frequency and force of the heart beat. It is recommended, 
 for these reasons, that analeptics, such as wine, coffee, etc., be given 
 after each emetic action of the drug. All those dangerous symp- 
 toms and even fatal results which have been reported as following 
 the longer or shorter administration of the drug, even in small 
 doses and to adults, are referable to the same cause. Doubtless the 
 individuality of the patient plays an important part in such cases. 
 Thus Falotf reports three cases in which, after from one to three 
 small doses of tartar emetic, there occurred, in addition to 
 vomiting, delirium and spasms, such prostration of the 
 vital powers that life was saved only through the energetic 
 use of stimulants. Beau J made an observation which was 
 quite analogous, two fatal cases occurring after the exhibition 
 of small doses of antimony. In these cases also the symptoms from 
 the first were those of pronounced debility — a very small pulse, gen- 
 eral cyanosis and emaciation of the face. The prostration increasing 
 and the extremities being cold, death ensued. Although tartar 
 emetic is now no longer as extensively employed as formerly, it 
 is employed with sufficient frequency as an emetic and expectorant 
 to justify this reference to the possibility of deleterious consequences 
 from its use. 
 
 Its exhibition should be strictly interdicted in persons suffering 
 
 *Jacobi, Damerow's Zeitschrift f. Psychiatrie, Bd. XI., p. 369, Ref. bei Schuchard« Arznei- 
 mittellehre, Braunschwe ; g-, 1858, p. 226. 
 tFalot, Union Medicale 1852, p. 245. 
 JBeau. Bulletin de Therapeutique, Sept. 1856. 
 
192 THE UNTOWARD EFFECTS OF DRUGS. 
 
 from the slightest pathological condition, such as catarrh, etc., of 
 the intestinal tract, inasmuch as either its external or internal 
 administration in such cases always excites inflammatory irritation 
 and even deeper lesions of the mucous membrane of the stomach 
 and intestines. This disturbance, after the external application of 
 the drug, occurs, as demonstrated by Radziejewski,* through the 
 elimination of the metal through the stomach and intestines. This 
 inflammatory irritation is also, doubtless, the cause of the vomiting. 
 This is induced by reflex irritation of that part of the central appa- 
 ratus which controls the act of vomiting. Occasionally excessive 
 vomiting occurs. 
 
 The caustic action of tartar emetic, as also that of other com- 
 binations of antimony, Kermes mineral, for instance, occasionally 
 manifests itself, during the internal exhibition of medicinal doses, 
 in pustules and vesicles in the mouth, throat, oesophagus and even 
 in the larynx. Lsennecf held these symptoms to be secondary and 
 due to a saturation of the body with the drug. Falck,| on the other 
 hand, declared this action to be purely local and due to the exhibition 
 of the drug in solution, no instance of any of the changes mentioned 
 having ever been observed to follow its administration in pill form. 
 Although we may not be able to admit the hypothesis of the saturation 
 of the system with tartar emetic, we must, nevertheless, concede the 
 possibility of the secondary occurrence of the changes mentioned as 
 an effect of the antimony circulating in the blood, and particularly 
 so because of the fact that affections of the skin and mucous mem- 
 brane have been seen in parts with which, primarily, the drug never 
 came in contact. Thus it has been established, through numerous 
 observations, that not infrequently, and without the drug's having 
 been conveyed by the fingers from the original seat of application, 
 that secondary pustular eruptions occur, particularly on the genitals 
 and inner surfaces of the thighs, several weeks after the inunction. In 
 addition to this there have been many cases reported in which pus- 
 tular eruptions have occurred by preference on the parts mentioned, 
 and also on other parts, after the internal exhibition of tartarized 
 antimony. Thus Imbert-Gourbeyre § adduces an observation of 
 
 *Radziejewski, Archiv f. Anatomie u. Physiologie 1871, p. 472. 
 tLaennec, Gazette des hopitaux 1853, No. 6. 
 
 jFa^ck, Canstatt's Jahresbericht über die gesammte Medicin 1853, V., p. 148. 
 §Imbert-Gourbeyre, Gazette Mddicale de Paris 1861, pp. 3, 17 u. ff. 
 
EVACUANTS — EMETICS. 19; 
 
 Gohlius'* in which, after a large dose of antimony, there occurred 
 a red eruption over the entire body. Bceck-r also saw a similar 
 occurrence after the administration of 0.6 gramme (gr. jx) of tartar 
 emetic during 36 hours, and HelbertJ reports a similar case. In 
 explanation of this phenomenon, there are, as Hermann pointed out, 
 two possibilities. Its cause must reside either in an inflammatory 
 irritation acting on the peripheral nerves, and thus exciting reflex 
 inflammatory changes in the vessels, or in a direct action on the 
 vessels themselves. Engorgement of the capillaries of the skin and 
 exudation thus occur, and finally the formation of pustules. It is 
 also possible, however, for the glandular organs of the skin to suffer 
 inflammatory change through the direct action of the drug. 
 
 The slightest forms of antimonial eruption demand no thera- 
 peutic interference. Extensive ulcerations are to be treated on the 
 general principles governing the treatment of wounds. The gastric 
 disturbances demand treatment, particularly should there be oppres- 
 sion and pain in the region of the stomach, and should but a short 
 time have intervened between the exhibition of the antimony and 
 the occurrence of these symptoms. To this end the stomach should 
 be washed out, opiates or other narcotics, in small quantities, being 
 added to the fluid employed. Should there be excessive vomiting, 
 the vegetable astringents, tannin, decoction of cinchona, etc., should 
 be resorted to, inasmuch as in such Cases antimony is probably pres- 
 ent in the stomach, and this forms such combinations with the drugs 
 named as are either but slightly soluble or entirelv insoluble. 
 
 RADIX IPECACUANHA. 
 
 Ipecac, now but seldom applied internally for its irritant effect 
 on the skin, causes, as noted by Bazin, § when applied in the form of 
 an ointment (1: 2 of lard), after the second or fourth inunction, a 
 papular eruption — without disturbing the underlying corium. At 
 first there is a diffuse redness with burning, and upon this there 
 appear slight elevations. The number and size of these latter 
 increase, with intense itching, while the intervening skin may regain 
 
 *Gohlius. Medicin. practic, clinic, et forensis. Lipsiae, 1735. 
 
 tBoeck, Preussische Vereinszeitung 1843, No 8. 
 
 $Helbert, De exanthemat. arte factis, Göttingen, 1844. 
 
 §Bazin, Lecons sur les affections cutanees artificielles, Paris, 1862, p. 106. 
 
194 THE UNTOWARD EFFECTS OF DRUGS. 
 
 its normal appearance. They finally become quite large and red, 
 remain distinct, and disappear under pressure of the finger. After 
 suspension of the inunction the eruption begins to disappear after a 
 time — from one to two weeks — without desquamation or leaving any 
 scars. The pruritus continues until complete disappearance of the 
 eruption. According to Delioux* an ipecac ointment may give rise 
 to pustules with depressed centres, like those caused by tartar 
 emetic, with this difference, however, that it leaves no scars like 
 the eruption caused by the latter. 
 
 The repeated internal administration of small doses of ipecac 
 may, through the local action of the drug, give rise to gastric and 
 intestinal catarrh, with its natural consequences, anorexia and diar- 
 rhoea. The latter occurs most frequently when vomiting is not 
 excited. The passages are then less abundant, usually mucous or 
 bilious and slimy, and frequently tinged with blood. According to 
 Arnold f ipecac not infrequently manifests differences in its effects. 
 Occasionally vomiting follows 0.6 gramme (gr. jx), while in other 
 cases 2.4 grammes (gr. xxxvj) causes no such action. The cause of 
 the difference resides partially in the individuality of the patient, 
 partially in the activity, the origin and the age of the root. Emetin, 
 the alkaloid of ipecac, is more uniform in its action, but it, also, is 
 not free from untoward effects. 
 
 III.— DIURETICS. 
 
 BULBUS SCILLAE. 
 
 Squill and its active principle, scillitin, in addition to their 
 diuretic property, occasionally in small medicinal doses give rise 
 to nausea, and should it be given in such small doses for 
 any considerable length of time, as in dropsical conditions, vomit- 
 ing and a serous diarrhoea with griping may supervene. Inas- 
 much as it fails of its diuretic action after a time, the doses are 
 usually enlarged. Following such increase the symptoms as de- 
 scribed may become aggravated, and irritation and burning of the 
 throat, colicky pains, pain on voiding urine and bloody urine may 
 
 *Delioux, Gazette de Paris 1852, No. 6 u. ff. 
 
 tArnold, Das Erbrechen und die Wirkung der Brechmittel, Stuttgart, 1840. 
 
EVACUANTS EXPECTORANTS. 195 
 
 occur. These symptoms are the expression of a local irritant action 
 of the drug on the portions of the mucous membrane with which it 
 comes in contact. As a reflex action from the stomach a diminution 
 in the frequency of the pulse is observed. 
 
 RADIX SARSAPARILLE. 
 
 Following the exhibition of large doses of sarsaparilla root, 
 gastric uneasiness, nausea, inclination to vomit, anorexia and general 
 debility are frequently observed. These symptoms are identical 
 with those which have been noticed after the therapeutical employ- 
 ment of smilacin, the active principle of the root. 
 
 FOLIA TOXICODENDRI. 
 
 The officinal fresh leaves of poison-sumach contain a yellowish- 
 brown milky juice, which is also found in the tincture of the rhus 
 toxicodendron. This drug has been but seldom employed in recent 
 times. It is, however, still necessary to mention the fact that the 
 fresh leaves, as also the tincture, when given in doses within the 
 maximum limit, may cause in certain persons pain, gastro-enteric 
 symptoms, as also vertigo, deafness, delirium, anaesthesia and a 
 paralytic condition. In addition to these there occur after the ex- 
 ternal application of the fresh leaves or the extract, violent itching, 
 an erysipelatous redness and swelling of the skin, and also a vesi- 
 cular, rubeola-like, intensely itching eruption, which disappears only 
 after several days, with desquamation. The same symptoms are said 
 to be caused by the emanations of the living pjant. 
 
 IV.— EXPECTORANTS. 
 
 AMMONII CHLORIDUM. 
 
 Small doses of sal ammoniac introduced into the stomach cause 
 no symptoms of disturbance. The prolonged use of doses of i to 2 
 grammes (gr. xv. to gr. xxx.) may, however, cause derangements of 
 digestion and loss of appetite. The daily administration of quanti- 
 
196 THE UNTOWARD EFFECTS OF DRUGS. 
 
 ties of 4 to 8 grammes ( 3 j. to 3 ij.) was observed by Jacquot* to 
 cause, in addition to nausea and vomiting, diarrhoea and colic. It 
 seems that the occurrence of these untoward effects is dependent on 
 individual circumstances. The continued use of the drug in 
 moderate doses usually gives rise to constipation, which is due to an 
 atonic condition of the intestines. 
 
 ANTIMONII SULPHURETUM. 
 
 Owing to its insolubility in water and dilute acids the sulphuret 
 of antimony, favorably regarded as an expectorant and resolvent, is 
 not absorbed from the stomach. As was demonstrated by the ex- 
 periments of L. Lewin,* it is, however, partially soluble in the alka- 
 line juices of the intestines, and may thus, as practical experience 
 teaches, give rise to the full effects of antimony, as manifested by 
 the occurrence of vomiting and diarrhoea. The intensity of these 
 untoward effects is dependent on the quantity of the drug dissolved 
 in the intestines. It varies, however, with the degree of fullness of 
 the stomach, as when the stomach is full the free drug which is not 
 absorbed is carried with the contents into the intestines, and thence 
 discharged with the faeces. According to this the untoward effects 
 are most intense when the stomach contains the least food. 
 
 RADIX SENEG^E. 
 
 The older literature contains isolated statements regarding the 
 untoward effects following the use of senega. Thus in individual 
 cases doses of 1 to 1.5 gramme (gr. xv. to gr. xxiii.) are said to have 
 caused irritation and burning in the throat, salivation, gastric op- 
 pression, nausea and vomiting, and loss of appetite. These symp- 
 toms were followed by colicky pains and diarrhceic discharges. 
 More recently attention has been called to the fact that occasionally 
 a drug is sold as senega by reputable trade houses, which neither 
 produces the effects of senega nor is botanically identical with it. 
 
 *Jacquot, Schuchardt's Arzneimittellehre, Braunschweig, 1858, p. 390. 
 *L. Lewin, Virchow's Archiv. Bd. 74. 
 
EVACUANTS ANTIPARASITICA. I97 
 
 V.— ANTIPARASITIC.^. 
 
 BALSAMUM PERUVIANUM. 
 
 In contrast with other balsamics Peruvian balsam has hereto- 
 fore been seldom reported to cause untoward results. Recently, 
 however, Mcegling* has reported the occurrence of an urticaria 
 which lasted for four days, as the result of a single inunction with 
 the balsam of Peru. Having one evening anointed himself on the 
 arms, shoulders and breast, with about 8 grammes ( 3 ij.) of the 
 balsam, for the cure of scabies, he was attacked with heat and un- 
 easiness and also a burning sensation in the lungs with fits of cough- 
 ing. On the following morning there appeared on the inner surface 
 of the knee and on the shoulders a redness of the skin in patches, 
 accompanied by intense pruritus. The itching disappeared during 
 the course of the day, but reappeared towards evening. It appeared 
 in closely disposed wheals situated on the thighs, sides of the 
 abdomen, arms and shoulders. Simultaneously he experienced 
 chills and nausea, without elevation of temperature. It was only 
 after two days and following occasional inunctions of lard, with relief 
 of the local and constitutional symptoms, and after the urticaria had 
 in turn also attacked the face, neck, back, forearms, legs and dorsal 
 surface of the feet, that Mcegling relieved himself by means of a bath, 
 and by removing a woolen undershirt which he had worn for four 
 days. 
 
 The congestion of the lungs may, according to Mcegling, have 
 been due cither to absorption of the drug by these organs, or, seeing 
 that he had been suffering for some time from bronchitis and 
 haemoptysis, it may have been the expression of a deleterious action 
 on the place of least resistance." 
 
 Less extensive eczematous eruptions of the skin are occasionally 
 observed as results of a local irritant action of the Peruvian balsam 
 — perhaps only when an inferior quality is applied — on parts to 
 which it has been applied for the relief of scabies. Such an erup- 
 tion may cause the disease to be suspected long after the itch-mites 
 have been destroved. 
 
 *Moegling, Berliner.Kltn. Wochenschr., 1880, p. 557 
 
198 THE UNTOWARD EFFECTS OF DRUGS. 
 
 STYRAX LIQUIDUS. 
 
 Unna* observed albuminuria in patient suffering from scabies, 
 and being treated with ' styrax ointments (styrax, rapeseed oil, 
 of each 10 parts, and spirit 1 part). It occurred in nine out 
 of 124 patients thus treated. A relatively large quantity of albumen 
 quickly appeared and as quickly disappeared. Unna maintains 
 that the tolerably large amount of balsamic substance which is 
 absorbed by the skin is the cause of the albuminuria. The passage 
 of substances of higher atomic weight through the walls of the 
 renal capillaries is said to make them capable also of allowing 
 albumen to pass through. 
 
 RHIZOMA FILICIS. 
 
 Ext. Filicis Maris JEthereum. 
 
 The root of the male fern, or its extract, administered in extra- 
 ordinarily large doses for the expulsion of the tapeworm, has a dis- 
 agreeable, irritating taste and occasionally gives rise to gastric pains, 
 nausea, vomiting, diarrhcea and abdominal pains. It is to be sus- 
 pected that the uncertain strength of the preparations employed is 
 responsible for these symptoms. 
 
 CORTEX RADICIS GRANATI. 
 
 The administration of pomegranate root bark in doses such as 
 are ordinarily exhibited for the expulsion of tapeworm, and par- 
 ticularly when the intervals between the doses are too short, is 
 frequently productive of nausea, vomiting, abdominal pains and 
 diarrhoea. Not infrequently there also occur vertigo, a feeling of 
 weakness and occasionally trembling of the limbs. In weakly per- 
 sons the continued vomiting may result fatally. The vomiting is, 
 however, peculiarly obstinate when the pomegranate root bark has 
 been given in immoderate doses, of say 300 grammes ( § j x ss) as re- 
 commended by Bettelheim. Such doses are never permissible. Ac- 
 cording to Merat, the bark is also a diuretic. These symptoms soon 
 
 *Unna, Virchow's Archiv, Bd. 74. 
 
EVACUANTS ANTIPARASITIC A. 
 
 I 9 9 
 
 disappear with the suspension of the drug. These different effects 
 are dependent on the age of the preparation, the fresh root alone 
 having any curative effect. In the use of a reliable preparation the 
 necessary doses are smaller, and inasmuch as the effects soon follow 
 the untoward effects are also of less frequent occurrence and of 
 shorter duration. 
 
 SANTONINUM. 
 
 Semen Cince. 
 
 Wormseed, as well as the santonin derived from it, almost 
 always, when given in medicinal doses, gives rise to undesirable 
 effects. 
 
 Neither santonin, which is insoluble in water, nor its soluble 
 salt with soda gives a red color when mixed with alkalies. This 
 occurs, however, when the drug is dissolved in alcohol and then 
 precipitated with alkalies. Santonin undergoes similar changes in 
 the human body to those produced on it by alcohol. After it has 
 been taken in any form and in small doses (0.2 gramme [gr. iij] 
 or more) after from two to three hours, the voided urine presents 
 a yellow color, as if curcuma or chrysophanic acid had been added 
 to it. White paper or linen soaked in it shows when dried, yellow 
 spots, a fact first pointed out by Martin.* The addition to such 
 urine of alkalies, such a soda-lye, ammonia, an alkaline carbonate, 
 etc., causes as cherry-red color. The red color disappears spon- 
 taneously after from 30 to 36 hours, in contrast with the urine 
 voided after the employment of rhubarb, the red color produced in 
 which by alkalies, according to J. Munk,f is permanent. Further 
 differences are noted by this author, the red discoloration of rhu- 
 barb urine disappearing under the action of reducing agents (zinc 
 dust, sodium amalgam), while that of santonine urine resists these; 
 baryta and lime water, also, added to the rhubarb urine throw down 
 the chrysophanic acid with the precipitate, the red color of which is 
 not removed by washing, while in alkaline santonine urine the pig- 
 ment remains in solution under the same treatment. 
 
 Santonine urine, as opportunely discovered by L. Lewin, 
 deflects the plane of polarization to the left. The changes which 
 
 *Martin, Buchner's N. Repert. f. Pharmacie, Bd. ii , 1853, H. 
 tj. Munk, Virchow's Archiv, 1878, p. 136. 
 
200 THE UNTOWARi) EFFECTS OF DRUGS. 
 
 santonine undergoes in the system are unknown. It is held by 
 Mialhe* that an oxidation product is formed having the peculiarities 
 of a weak acid. The elimination of the same can be demonstrated 
 in the urine after two or three doses of even 0.2 to 0.4 grammes 
 (gr. iij to gr. vi). In the event of decomposition of santonine urine, 
 the carbonate of ammonium, which is generated, produces in it a red 
 color, which under certain circumstances, such as the existence of 
 vesical catarrh, may cause it to be mistaken for bloody urine. 
 
 In some cases the ingestion of santonine has been observed to 
 cause strangury and itching in the urethra. 
 
 Symptoms which are nearly as constant as those referable to 
 the urine, are' the disturbances of the sense of sight which manifest 
 themselves after even small doses of santonine, changes which 
 manifest themselves chiefly in yellow vision (chromatopsie) and 
 which may continue for several hours. This symptom was first 
 observed by Itzstein and afterwards by Spencer Wells. Rosef 
 investigated this matter most carefully. According to him there 
 occasionally appears before the peculiar yellow sight, after large 
 doses of santonin, a violet color of the field of vision, the intensity 
 of which color is in proportion to the darkness of the objects looked 
 at. All lighter objects, such as windows, paper, etc., appear actually 
 yellow. Red and blue appear often in their complementary colors, 
 orange and green, so that carmine red appears pale, madder red, a 
 bronze color, and the sky and blue objects green. This, however, 
 is not always the case, and it has been noticed after the employment 
 of santonin that red appears violet or light, and dark objects 
 appear orange to one person and to another green. 
 
 This phenomenon is not due to a discoloration of the media of 
 the eye by the products of the decomposition of santonine, after 
 the manner of the action of the coloring matter of the bile in icterus, 
 as was formerly believed to be the case, but is due, according to 
 Rose, to a nervous change in the retina. M. SchultzeJ maintains 
 that the yellow pigment of the macula lutea is changed by the 
 action of santonin, and that it is thus that the vision becomes 
 yellow. The complete absence of santonine in the media of the 
 eye, as also the failure to detect the same by chemical means in the 
 
 *Mialhe, Comptes rendus xlvii., p. 413. 
 
 fRose, Virchow's Archiv, Bd. xvi., p. 233 u. Bd. xviii., pag. 15. 
 
 $M. Schultze, Ueber den gelben Fleck d. Retina, Bonn, 1866. 
 
EVACUANTS ANTIPARASITICA. 20I 
 
 retina, renders a direct action of this substance on the parts which 
 receive the impression of light improbable, but does not, as observed 
 by Hermann,* exclude the possibility of its doing so, because of the 
 fact that the changes are so slight and the quantity of the active 
 substance may be so small as to elude detection by experiment. 
 
 Among other changes in the eyes Martin observed increased 
 lachrymation and a sense of pressure, and others noticed a flicker- 
 ing before the eyes. While Rose, however, denies the occurrence 
 of amblyopia and disturbances of accommodation, other authors, 
 Bianchi-Cogliesi,f for instance, reports the occurrence of 
 amaurosis, appearing in children after medicinal doses, and lasting 
 for two and a half months. 
 
 Besides the eyes many persons experience also a distress in the 
 stomach after the exhibition of santonin. Thus Martin noticed in 
 his own person the appearance of nausea after taking 0.4 gramme 
 (gr. vj) of santonine, and Rose observed vomiting after its employ- 
 ment. Associated with this there may also occur borborygmi and 
 eructations. 
 
 Rose has also reported symptoms referable to the central nerv- 
 ous system, such as hallucinations of smell and taste, headache and 
 a species of depression, symptoms denominated in their totality 
 "Santonine intoxication." 
 
 Affections of the skin very seldom occur after the exhibition of 
 santonin. SievekingJ has described a case of thjs nature. A child 
 to whom 0.18 grammes (gr. iij) of santonin had been given for 
 worms, vomited soon after taking the dose, whereupon an urticaria 
 appeared over the entire body, but soon disappearing. The repe- 
 tition of the same dose was followed by a recurrence of the general 
 urticaria, and the entire skin, and particularly that on the eyes, nose, 
 and lips, became so swollen and cedematous as to render the face 
 completely unrecognizable. Salivation occurred simultaneously. 
 The sensorium was not involved. The symptoms disappeared with- 
 in an hour, under the influence of a warm bath. 
 
 ^Hermann, Lehrbuch der Toxikologie. Berl., 1874, p. 384. 
 tBianchi-Coglicsi, Refer, in Husemann, PfUnzenstoffe, Berlin, 1871, p. 
 JSieveking, British Medical Journal, Febr. 1871. 
 
202 THE UNTOWARD EFFECTS OF DRUGS. 
 
 BENZOLUM. 
 
 J. Munk* found, by experiments on himself, that benzole has a 
 disagreeable, sharp burning taste and that its action in the mucous 
 membranes is almost caustic. Commencing with 25 drops, he 
 increased the amount to 50 drops in twenty-four hours. He found 
 as a result of this a lasting sensation of fullness, oppression and 
 burning in the epigastrium, and slight headache, while no marked 
 effect was manifest on either the pulse or the respiration. The 
 inhalation of benzole for anaesthetic purposes gives rise, according 
 to Simpson, f to intolerable roaring in the head, and Richardson 
 observed twitching of the muscles, dyspnoea and convulsions after 
 such use of the drug. 
 
 A portion of the benzole is eliminated from the stomach in the 
 form of gas, as is manifest in that the eructations, commencing with 
 the exhibition of the substance and continuing for eight hours, have 
 the odor and taste of coal tar. Another portion enters into a group 
 of organic atoms to form the "phenol-forming substance." 
 
 In applying benzole externally to the genitals for the destruc- 
 tion of vermin care must be taken that it do not get in between the 
 scrotum and the thigh. Applied to this or similarly sensitive sur- 
 faces, it causes extremely violent pain, which lasio for several min- 
 utes, and is followed by a more or less extensive eczema. 
 
 ACIDUM PICRICUM. 
 
 Picric acid, which has been recommended as an astringent and 
 tonic, and also as an anthelmintic, occasionally, as stated by Seitz,t 
 ■causes an icteric discoloration of the skin and conjunctiva. 
 
 *J. Munk, Pflüger's Archiv, Bd. xii., p. 147. 
 
 tSimpson, Monthly Journal of Medical Science, 1848 A.pi" 
 
 $Seitz, Deutsche Klinik, 1855, 40. 
 
EVACUANTS SüDORIFERA. 20' 
 
 VI.— SUDORIFERA. 
 
 FOLIA JABORANDI. 
 
 Following the employment of jaborandi, the leaves of the pilocar- 
 pus pinnatus and simplex, nearly all observers have reported a series 
 of unpleasant untoward effects as accompaniments of the normal ac- 
 tion of the drug. The latter is the well known diaphoresis and sub- 
 jective sensation of warmth which, within from ten to twenty minutes, 
 follow the exhibition of an infusion of, for instance, 4 grammes 
 ( 3 i) of the leaves. It first appears on the abdomen and breast, after- 
 wards on the face, and later on both the lower and the upper extrem- 
 ities, and lasting for from about two to four hours. A secretion of 
 viscid saliva, which occurs simultaneously, or somewhat earlier, con- 
 tinues for an equal length of time. The average loss of weight 
 occurring from the perspiration is, according to Riegel*, 750 to 1000 
 grammes (1*2 lbs. to 2 lbs.), but may exceed even 2 kilogrammes 
 (4 lbs). The pulse becomes, shortly after the ingestion of the drug, 
 more frequent and compressible, and later it frequently becomes 
 small, with diminution in the force of the cardiac contraction, pallor 
 of countenance, and a subjective feeling of chilliness. Among the 
 untoward effects which have been observed, the first demanding 
 notice is the vomiting which occurs in from half-an-hour to an hour 
 after taking the drug, and which is always preceded by prolonged 
 nausea. This is extremely distressing and exhausting to the patient, 
 continues for a considerable length of time, and may readily lead to 
 severe collapse. In forty-one observations, Riegel observed its occur- 
 rence' in eighteen cases, while nausea without vomiting occurred ten 
 times. Lohrischf noticed the occurrence of severe vomiting twelve 
 times, and of nausea twenty-two times, in thirty observations. The 
 nausea sometimes occurred immediately after the exhibition of the 
 drug, and again did nor appear until half-an-hour or later. Barden- 
 hewerj attributes the nausea and vomiting to the swallowing of the 
 saliva, which is so freely secreted, and which, through being thus 
 swallowed, irritates the mucous membrane of the palate, throat, etc. 
 
 ■"Riegel, Berliner Klin. Wochenschr., 1875. No. 46. 
 
 tLohrisch, Berliner Klin. Wochenschr., 1875, No. 18, und Inaug.-Dissertat, Berlin, 1875. 
 
 JBardenhewer, Ueber die Therapeut Wirkung des Jaborandi, Bonn, 1875. 
 
204 THE UNTOWARD EFFECTS OF DRUGS. 
 
 Riegel concedes the explanation for a few of the cases only, as he 
 has seen vomiting to occur in patients who have immediately expec- 
 torated the saliva. 
 
 Besides the nausea and vomiting, a desire to urinate is the most 
 common occurrence, it supervening in about forty per cent, of all 
 the cases. This occurs so suddenly and is so pressing as to be quite 
 resistless. Occasionally there is also experienced a burning pain in 
 the urethra and in the lumbar region, which is so severe as to force 
 from the patient loud expressions of pain. 
 
 The frequent disturbances of sight, to which Martindale first 
 called attention, also demand a notice. The patient complains of 
 defective sight, because there seems to be a veil before his eyes. A 
 few authors claim to have detected a contraction of the pupil with 
 this condition, but Riegel was unable to corroborate this claim. 
 
 In addition to the untoward effects noted, there also occurred 
 hiccough, vertigo, and headache with a species of stupor, and, in 
 some patients, a greater or lesser degree of chilliness, and also 
 gastric and abdominal pains, occurring towards the end of the sweat- 
 ing stage. These symptoms also disappear with the cessation of 
 sweating. In very weakly persons collapse, without vomiting, is also 
 occasionally observed 
 
 PILOCARPINUM MURIATICUM. 
 
 After the discovery of the pharmacological peculiarities of jabor- 
 andi, numerous experiments were instituted with a view to isolating 
 its active principle, in the hope that its exhibition might secure the 
 therapeutic action of the plant, without its untoward effects. It 
 remained for Merck to derive from the plant the pure alkaloid, or its 
 muriatic acid compound, a crystallizable, slightly bitter astringent 
 substance, and soluble in its own weight of water. 
 
 Notwithstanding the fact that, in course of time, it has appeared 
 that the use of this principle likewise gives rise to a series of unpleas- 
 ant symptoms, its capability of exerting its action when administered 
 subcutaneously vests it with such advantages over the jaborandi leaves 
 as to give it the preference to the latter when used as a diaphoretic. 
 According to the investigations of Weber*, one ccm. (16 minims) of 
 
 
 *Weber, Centralblatt f. d. Medicin, Wissenschaft, 1876, No. 44. 
 
EVACUANTS SUDORIFERA. 205 
 
 a two per-cent. solution of the muriate of pilocarpine is equal to an 
 infusion of 5 grammes (gr. lxxv.) of jaborandi leaves in 120 grammes 
 ( § j v.) of water. The quantity of saliva secreted after an injection of 
 pilocarpine varies, according to Losch*, with the individuality of the 
 patient. The saliva itself is tough, viscid and often as thick 
 as albumen. The occurrence of salivation follows diaphoresis 
 immediately. The individuality of the patient also plays a role in 
 this connection, some persons being bathed in perspiration through 
 doses which in others cause only slight transpiration. During the 
 secretion of perspiration chills occasionally occur. Consonant with 
 these symptoms there is an acceleration of the pulse, of from thirty 
 to forty beats per minute. Patients often complain of palpitation of 
 the heart, and very sensitive persons of a feeling of anxiety, which, 
 however, speedily disappears. 
 
 Vomiting occurs later on and when it once sets in it is very 
 severe. According to Losch vomiting occurs in women once in five 
 cases, and but once in ten in men. It is usually followed by 
 collapse. Demmef saw in children, in addition to vomiting, 
 debility nigh to fainting, pallor of countenance and distressing 
 hiccough. A burning sensation was also experienced in the urethra 
 or glans penis, ordinarily associated with a frequent desire 
 to urinate. Federschmidt]; also reports dysuria as manifesting 
 itself in two cases. During the secretion of sweat and saliva, 
 patients sometimes complained of a sensation as if the bladder were 
 full of water and they found it impossible to void it. These 
 abnormal sensations failed to appear after subsequent injections. 
 
 Another symptom equally worthy of note is the characteristic 
 disturbance of sight manifesting itself as mistiness of vision. This 
 becomes so intense in some persons of perfectly normal focal dis- 
 tance and acuteness of vision that they are unable, as Losch declares, 
 to read large print at a greater distance than six inches. The 
 symptoms occurred also in cases in which there was not the slightest 
 increase in the quantity of tears secreted. 
 
 The most unpleasant of all the untoward effects, however, is the 
 collapse which frequently occurs alike during the stage of secretion 
 and after it, and even in robust persons. The greatest caution must 
 
 *Losch, Deutsches Archiv für Klin. Medicin, xxi., p. 258. 
 tDemtne, Cemralzeitung für Kinderheilkunde, 1877, No. 1. 
 JFederschmidt, Zur Wirkung des Pilocarpin, muriatic. Erlangen, 1877 
 
20Ö THE UNTOWARD EFFECTS OF DRUGS. 
 
 be exercised against this symptom during the exhibition of pilocar- 
 pine, inasmuch as a disregard for the possibility of its occurrence 
 is apt to result disastrously. In the same manner regard must be 
 had to the well-established excessive acceleration of the heart's 
 action, which is often accompanied by absence of rhythm, and 
 particularly in persons suffering from organic lesion of this organ. 
 
 An observation of Ranneft* may also be mentioned here: In 
 the case of a uraemic patient the hypodermic injection of 0.02 
 gramme (gr. 1) of the muriate of pilocarpin, was followed, the next 
 morning, after the diaphoresis had subsided, by a swelling of the 
 size of a fist of the submaxillary glands and a swelling also of the 
 parotids and tonsils, with absence of fever. Under the influence 
 of atropia these symptoms disappeared in the course of a day. 
 
 Great danger attends the untimely exhibition of pilocarpin in con- 
 vulsions. Sängerf reports three cases of this nature, in which the 
 injection of 0.02 gramme (gr. 1) of pilocarpin was followed by oedema 
 of the lungs. In one case the subcutaneous exhibition of 0.0006 
 gramme (gr. T J-g-) of atropia, as an antidote, saved the patient's life, 
 but the two other cases proved fatal. Sänger accounts for this 
 deleterious action by the deficient expectoration of the masses of 
 mucus thrown off under the influence of the pilocarpine and by 
 their entrance into the lungs. It is impossible for the patient to ex- 
 pectorate, because of the unconsciousness and suspension of reflex 
 irritability resulting from the convulsions. 
 
 The fact that a number of observers have noted the symptoms 
 above mentioned, and that, too, notwithstanding that they all em- 
 ployed the same preparation, excludes the supposition that the 
 quality of the drug was responsible for them. It appears as if they 
 are due to a certain predisposition on the part of the patient, and 
 in many cases also, perhaps, the improper size of the dose is re- 
 sponsible. In regard to the latter, LeydenJ and Curschmann,§ also 
 maintain that the collapse which is occasionally observed may be 
 obviated by a very gradual increase in the size of the dose. In 
 general, however, in the light of experience, we are unable to pre- 
 vent the deleterious untoward effects, and we are obliged to 
 
 *Ranneft, Jahresbericht f. d. ges. Medicin, von Virchow-Hirsch, 1877, n -i P 437- 
 
 tSänger, Archiv, f. Gynäkolog. Bd. xiv., H. 1. 
 
 JLeyden, Berliner Klin. Wochenschrift, 1878, No. 27 u. 28. 
 
 §Curschmann, Eod. loco No. 25. 
 
EVACÜANTS SUDORIFERA. 
 
 content ourselves by combating them as soon as possible after their 
 appearance. 
 
 Atropia occupies the first place among the drugs employed for 
 this purpose, inasmuch as it checks both the diaphoresis and the 
 salivation, and as it also allays the painful sensations and the vomit- 
 ing. It is administered either hypodermically (atropiae sulph., o.i 
 gramme [gr. jss] water 20 grammes [ 3 v] of which inject from 
 five to ten drops) or per os (atropiae sulph. 0.0 1 gramme [gr. -J-], 
 water 20 grammes [ 3 v], of which give from twenty to thirty drops 
 every two hours, until the symptoms have been allayed.) The 
 bromhydrate of homatropin has been proven by Fronmüller, of ser- 
 vice as an antidote to pilocarpine and has been recommended 
 by him as such. He injects it subcutaneously in doses of 
 0.015 gramme (gr. £.) Collapse may be forestalled by the 
 exhibition of stimulants. Demme (1. c.) claims to have ob- 
 viated all the deleterious untoward effects liable to follow 
 the injection of pilocarpin, by giving cognac before the oper- 
 ation. It is, in general, preferable to administer pilocarpin before 
 rather than after the principal meal, and in view of the numerous ob- 
 servations of the great liability to collapse in patients suffering from 
 valvular insufficiency, to regard heart disease as a contraindication 
 for the use of the drug. Ohms* also regards pilocarpin as contra- 
 indicated in ulcer of the stomach and typhoid fever, because of the 
 danger of haemorrhage from the great dilatation of the vessels under 
 the influence of the drug. 
 
 *Ohms, Petersburger medic. Wochenschr. 1878, No. 6, p. 50. 
 
2o8 THE UNTOWARD EFFECTS OF DRUGS. 
 
 Emollients 
 
 GLYCERINUM. 
 
 The healing action of glycerine on wounds, demonstrated par- 
 ticularly by the experiments of Demarquay,* not infrequently fails 
 to manifest itself, a directly opposite effect, indeed, taking its place. 
 The impurity of the glycerine is assigned as the cause of this 
 untoward action. This application of an impure preparation to 
 the surface of wounds, eruptions of the skin, etc., give rise to a 
 burning sensation at the point of application which lasts for several 
 hours, and to a feeling of increased heat. The affected part at the 
 same time becomes swollen. Moist eruptions secrete more freely, 
 and under certain circumstances a pustular eruption is developed. 
 
 Chemically pure glycerine when applied to wounds causes only 
 a temporary burning, due, probably, to its property of abstracting 
 water from the parts. It is necessary in using this drug to bear in 
 mind the fact that its sp. gr., according to Phar. Germ., is from 
 1.23 to 1.25. Preparations more highly concentrated than this are 
 to be avoided in therapeutics, because of their irritating properties. 
 
 VASELINUM. 
 
 Vaseline recently introduced as a basis for ointments and as a 
 vehicle for various substances, may by its application to the skin 
 excite various degrees of inflammation. Lewin observed in his own 
 case that the inunction of it upon a circumscribed spot on the fore- 
 arm, excited an eruption of superficial papules, characterized by 
 intense itching and confined to the seat of the application of the vase- 
 line. It persisted for some ten or twelve days, and disappeared with 
 desquamation. Other authors have also observed the appearance of 
 inflammatory action on the hands and face after the inunction of 
 vaseline. 
 
 *Demarquay, De la Glycerine, Paris, 1867. 
 
EMOLLIENTS OLEUM MORRHU.E. 2O0 
 
 OLEUM MORRHU^E. 
 
 The peculiar, repugnant smell and taste of cod-liver oil, causes 
 at first in different persons, usually adults, either during or subse- 
 quently to its exhibition, nausea and even vomiting, symptoms which 
 do not, however, supervene after the oil has been used for a length 
 of time. The administration of excessive doses is followed by 
 diarrhoea. In addition to this cod-liver oil occasionally gives rise 
 to eczema after it has been used for several days. This observation 
 of S. Bennet* is explained by the fact that after large doses of cod- 
 liver oil the skin gives off the peculiar odor of the volatile fatty 
 acids of the oil. These, while circulating in the system also reach 
 the skin, and there cause the eruptions probably by direct irritation. 
 These, according to Duclosf are always of a vesicular nature and 
 spread over the entire body. 
 
 *Bennet, Treatise on the Oleum Jecoris Aselli, London, 1841, p. 16, and 47. 
 tDuclos, Journal de Medicine. Sept.-Novem,, 1846. 
 
THE UNTOWARD EFFECTS OF DRUGS. 
 
 Rubefacients and Vesicants 
 
 CHLORINUM. 
 
 Aqua Chlorinata. 
 
 Chlorine gas is irrespirable. Even in considerable dilution 
 with atmospheric air it is an energetic irritant to the mucous mem- 
 brane of the air-passages, causing increased secretion, nasal catarrh, 
 cough, constriction of the chest and symptoms of actual bronchitis. 
 
 The effect of the gas on the skin is to cause a pruritic 
 erythema, which disappears after a time with desquamation. In 
 dilution it also, according to Schuchardt,* excites prickling and 
 piercing sensations in the skin, which is sensitive and may take on 
 a papular eruption, which disappears in branny desquamation. 
 
 CANTHARIDES. 
 
 Tinctura — Unguentum — Emplastrum Cantharidum. 
 
 The internal exhibition of cantharides or its tincture, in 
 medicinal doses, excites a number of untoward effects, which take 
 on different degrees of intensity according to the individuality of 
 the patient. A burning sensation is experienced in the prima? vise. 
 After a time there is a pressing desire to urinate, a burning sen- 
 sation in the urethra, and frequent and painful erections. The 
 latter symptom may, as a result of the prolonged use of small doses, 
 as also through increase of the dose within ordinary limits, give rise 
 to threatening symptoms. The mucous membranes of internal 
 organs take on a greater or lesser degree of inflammation, manifesting 
 itself, as regards the stomach and intestines, in nausea, vomiting 
 and diarrhoea, and as regards the urinary passages in increased 
 frequency of desire to urinate, the urine occasionally containing 
 blood, albumen or morphological constituents, and on the part of 
 the genital apparatus, painful chordee. 
 
 The skin also is occasionally attacked with exanthematic 
 
 *Schuchardt, Arzneimittellehre, Braunschweig, 1858, p. ic 
 
RUBEFACIENTS AND VESICANTS FABA ANACARDII. 211 
 
 changes, manifesting themselves as erythematous or papular erup- 
 tions. 
 
 More important than these effects following the internal exhibi- 
 tion of cantharides is the knowledge of those which result from its 
 outward application. These symptoms following the application of 
 a fly blister, which correspond with those already described, may 
 result from the absorption of the active principle of the can- 
 tharides. Thus Ledelius,* among others, noticed vomiting, strang- 
 ury and fever, to set in after a blister had been applied for three 
 hours. • These symptoms, caused by absorption, are intense in pro- 
 portion to the deviation of that portion of the skin to which the 
 drug is applied, from its normal activity. 
 
 The treatment consists in the speedy removal of the blister and 
 the cleansing of the skin with soap. Mucilaginous drinks should 
 be given to allay the irritation of the internal organs. 
 
 FABA ANACARDII. 
 
 The anacardium bean, vulgarly known as cashew nut, con- 
 tains in its capsule a reddish-yellow substance, cardol, soluble 
 in ether, alcohol, etc., which Frerichs has recommended as prefer- 
 able, under certain conditions, to cantharides, as a vesicant. Cardol 
 derived from anacardium occidentale is known as cardoleum 
 vesicans, that from semecarpus anacardium as cardoleum pruriens. 
 The latter, owing to its liability to cause dermatitis, and even ery- 
 sipelas, is not fit for use. But the anacardium occidentale is also 
 often not limited in its sphere of action, diffuse inflammatory oedema 
 and also eczema occurring on remote parts, as, for instance, the 
 face, being liable to follow its application. 
 
 While this preparation is seldom employed by physicians, the 
 anacardium bean is frequently employed in domestic practice and 
 thus gives rise to its typical affections of the skin. Thus E. 
 Schwerin noticed it to produce erysipelas, spreading to an enor- 
 mous extent in a woman who had introduced half a bean into her ear 
 for the relief of a toothache and pain in the face. The face was 
 bloated, the eyelids on both sides infiltrated with serum, the ear, 
 cheek and forepart of the neck as far as the clavicle, swollen and 
 
 -Ledelius, Refer, bei. Wibmer, Wirkungen der Arzneimittel, Bd. III., p. 252. 
 
212 THE UNTOWARD EFFECTS OF DRUGS. 
 
 reddened. The external, auditory canal, the external ear, and the 
 surrounding integument were covered with vesicular crusts. 
 Recovery followed in a few days. 
 
 In another case an anacardium bean perforated longitudinally, 
 and strung on a thread was worn around the neck for a pain in the 
 breast, in such a manner that the bean laid on the manubrium of 
 the sternum. Two days later an erysipelas developed which spread 
 over the entire front of the chest, the mammae, and the neighbor- 
 hood of the shoulders as far as the lower jaw, and was dotted with 
 numerous vesicles. 
 
 According to Bazin* the oil expressed from the pericarp of the 
 bean, if brought in contact with the skin may also cause the appear- 
 ance of one or more vesicles containing purulent matter, within 
 from six to twenty four hours. 
 
 CORTEX MEZEREI. 
 
 Mezereon, which is still occasionally employed as a vesi- 
 cant or is applied to establish superficial issues, causes vesicles 
 on the skin which may develop into ulcers. The latter are very 
 painful, heal extremely slowly, and are frequently surrounded by a 
 pustular eruption. 
 
 After the occurrence of the inflammatory symptoms, symptoms of 
 general poisoning and even death may occur from absorption of the 
 drug. Pluskalf observed a case of this nature. It was attended by 
 headache, dryness of the throat, an irritative cough, fever, uncon- 
 sciousness, convulsions, and finally death. 
 
 SUMMITATES SABIN^E. 
 
 The external application of the powdered tops of savin for the 
 cauterization of condylomata, gives rise occasionally to such intoler- 
 able pain as to necessitate the discontinuance of the application. 
 
 Following the internal use of small and medium doses (0.3 to 
 0.8 gramme [gr. v to gr. xij]) as an emmenagogue, there is disturb- 
 ance of digestion, occasional vomiting and diarrhoea, desire to urin- 
 ate, and, during menstruation, a profuse discharge of blood. In 
 
 * Bazin, 1. c, p. 119. 
 
 tPluskal, Oesterreische medic. Wochenschr., 1842, No. 18 und 1844, No. 50 
 
RUBEFACIENTS AND VESICANTS PETROLEUM. 213 
 
 pregnant females large doses or the prolonged use of small doses 
 may induce abortion. The oil of savin is more energetic in its action 
 than the herb. 
 
 PETROLEUM. 
 
 The external application of petroleum may give rise, in a short 
 time, to a dermatitis. Hillairet made some observations to this effect, 
 which have been reported by Crucis.* According to these there 
 appeared on different persons who had received petroleum embro- 
 cations, and shortly after the application, on the abdomen, thighs, 
 and partially also on the legs, an eruption of confluent vesicles on 
 an inflamed groundwork, but showing no induration. Notwith- 
 standing the suspension of the embrocations there appeared daily 
 for eight days a fresh crop of vesicles. An additional application 
 made on the ninth day was followed by no fresh eruption. 
 
 In other persons the symptoms of systemic disturbance were 
 more prominent, the local symptoms being limited to violent irrita- 
 tion. The constitutional symptoms may consist of a prolonged sen- 
 sation of dizziness, frontal headache, symptoms of slight intoxica- 
 tion, nausea and vomiting. 
 
 CHRYSAROBINUM. 
 
 Goa Powder. 
 
 " Araroba powder or goa powder " has long been used in Eng- 
 land, Brazil and the East Indies, as a secret remedy in the 
 treatment of affections of the skin. The tree whence is derived the 
 powder is most common in the province of Bahia. Araroba is found 
 as a sulphur-yellow powder in the crevices and cavities which tra- 
 verse the tree in the direction of its transverse diameter.]- Accord- 
 ing to an earlier analysis the powder contains 84 per cent of chryso- 
 phanic acid. Liebermann, J however, showed that the substance 
 recovered from goa powder by extraction with benzoleis notchryso- 
 phanic acid, but, according to his chemical synthesis, a body of dif- 
 ferent composition to which he gave the name of chrysarobin. 
 
 *Crucis, Action physiologique et Morbide de la Te'rebinthine et de quelques autrcs Hydro- 
 carbures, Paris, 1874, p. 29. 
 
 tVierteljahrschr. f. Dermatol, u. Syphilis VI., 1879, p. 385. 
 
 ^Liebermann, Berichte der deutsch, ehem. Geseltech., Jahrg. XI., p. 1603. 
 
2 14 THE UNTOWARD EFFECTS OF DRUGS. 
 
 Chrysarobin may be converted into chrysophanic acid by the action 
 of potash-lye and exposure to the air. Experiments of L. Lewin* 
 and Rosenthal have established the fact that chrysarobin suffers 
 similar changes in the bodies of animals. Chrysophanic acid 
 may be detected in the urine after either the internal or the exter- 
 nal exhibition of the drug. 
 
 Balmanno Squiref first employed this drug in the form of oint- 
 ment in psoriasis and later in eczema, acne, etc., with good results. 
 Numerous therapeutic experiments were afterwards made with 
 chrysarobin, in Germany. The ointment is usually applied to the 
 skin, previously cleansed of the psoriatic scales by either mechanical 
 or chemical means (spirit of soap, etc.). 
 
 All observers who have employed chrysarobin report unpleasant 
 local and systemic untoward effects from its use. KaposiJ has de- 
 scribed them most minutely. The rubbing of chrysarobin upon a 
 psoriatic spot is followed by inflammation at the point of application, 
 occurring earlier in some and later in others, and liable to spread 
 extensively over the sound skin. Some persons manifest a peculiar 
 predisposition to this action, in which cases the inflammation is un- 
 usually intense as to duration and extent. The face and genitals 
 are peculiarly susceptible to the irritation of chrysarobin ointment. 
 
 According to Kaposi there are three forms of inflammation: 
 
 i. A diffuse inflammatory redness and swelling. In some per- 
 sons this occurs as a halo of varying breadth around each psoriatic 
 patch, after from four to six applications, and in others after from 
 eight to fifteen. This redness disappears, in the desquamation of 
 the epidermis, in from ten to fourteen days after the discontinuance 
 of the application. Frequently, however, the inflammation and 
 -swelling continue to spread in spite of the suspension of the drug, 
 and is attended by pain, fever, sleeplessness, swelling of the glands, 
 etc. — in short, the general symptoms ensuing on an attack of diffuse 
 dermatitis. 
 
 2. The inflammation may manifest itself also in the appear- 
 ance of reddish brown, firm papules, of pin-head size, some 
 of which also take the form of vesicles and pustules. They 
 correspond to the outlet of follicles, and the patient complains of 
 an annoying itching and burning sensation. 
 
 
 *L. Lewin und O. Rosenthal, Virchow's Archiv, Vol. 85, 1881. 
 tBalmanno Squire, British Medical Journal, May and November, 1877 
 iivaposi, Wiener medicin, Wochenschrift No. 44. 
 
RUBEFACIENTS AND VESICANTS NAPHTOLUM. 215 
 
 3. Painful furuncles may also occur. Cold water compresses 
 have been recommended for the relief of the pain and inflammation. 
 Neumann recommended as a prophylactic measure against this 
 irritation ot the skin, the protection of the circumference of the 
 diseased parts with adhesive plaster. Others believe that these 
 effects may be guarded against by gradually increasing the 
 strength of the chrysarobin ointment. Kaposi discountenances 
 the use of chrysarobin on the face, and permits its application to 
 the genitals only after careful isolation of the adjoining folds of 
 skin, and advises the suspension of the drug as soon as an areola 
 appears around the psoriatic patches. 
 
 As an accompaniment of the inflammatory complications men- 
 tioned, the drug nearly always causes a discoloration of the tissues 
 with which it comes in contact. The sound skin, as well as the 
 nails, assume a reddish or violet-brown aspect, and the hair a golden- 
 yellow or variegated greenish color. The contact of soap with 
 the parts thus changed as to their normal color, causes a change to 
 a dark violet, through the action of the potash on the chrysarobin. 
 This change of color is most marked in the inflamed areola which 
 surrounds the psoriatic patches. The body linen also in the same 
 manner as the skin becomes spotted to a greater or less extent, of a 
 brown or violet color, and these spots are very hard to erase. 
 
 NAPHTOLUM. 
 
 Naphtol, a colorless, crystalline substance, soluble in alcohol, 
 oils and fats, recommended by Kaposi* as a substitute for tar in 
 different diseases of the skin, gives rise by repeated applications of 
 a 10 to 15 per cent, solution, to a burning sensation at the seat of 
 embrocation, which may continue from a quarter of an hour to an 
 hour, without, however, the slightest appearance to indicate the 
 existence of this condition. 
 
 Naphtol is absorbed by the skin and is eliminated with the 
 urine. Larger quantities of the substance taken into the circulation 
 are- poisonous, according to Neisser.f He is convinced, from 
 experiments on animals, that large doses of naphtol give rise to 
 hematuria, through destruction of the blood. He recommends, for 
 this reason, circumspection as regards the dosage, and avoidance of 
 the drug in existing nephritis. 
 
 ♦Kaposi, Wien. Med. Wochenschr. i88i,No. 22-S4. 
 tNeisser, Centra!»!, f. d. Med. Wissenschaft. 1881, No. ?o. 
 
2l6 THE UNTOWARD EFFECTS OF DRUGS. 
 
 Kaposi himself observed hematuria, symptoms of Bright's 
 disease, ischuria, vomiting, unconsciousness and eclamptic attacks 
 in a boy, after the external application of naphtol. 
 
 ACIDUM PYROGALLICUM. 
 
 Pyrogallic acid was introduced by Jarisch* as a remedy in the 
 treatment of cutaneous affections. The untoward effects which 
 manifest themselves after its employment are not important. 
 Applied to the sound skin or to psoriatic patches it causes a 
 brownish discoloration. On the extremities it excites localized 
 inflammation which may develop into vesicles and desquamation of 
 the skin. Applied to firm, infiltrated patches, the ointment causes 
 deep destruction of the skin, even as far as the corium. The cica- 
 trices left after the cauterization of lupus nodules are smooth, 
 white and pliable. Jarisch observed, as a result of the appli- 
 cation of the acid in eczema marginatum, pain lasting for 
 several days and suffering aggravation, particularly on the removal 
 of the dressing. 
 
 On the strength of the observations of Jarisch,* Neisserf also 
 tried the pyrogallic acid in the case of a man afflicted with psoriasis 
 universales. In order to compare their respective effects, the upper 
 and lower extremities of the right side and the back were energet- 
 ically rubbed with unguentum rhei (ext. rhei spirit, as a 20 per cent, 
 ointment), the left side and breast being similarly treated with 
 ointment of pyrogallic acid. The parts thus anointed were then 
 covered with a thin layer of the respective ointments, and 
 the whole body enveloped in gummed paper, which was secured 
 by means of a roller bandage. In a few hours after this 
 operation rigors set in, with diarrhoea and vomiting, which con- 
 tinued for three days, when they were followed by collapse and 
 death. The urine contained the coloring matter of blood. The 
 autopsy revealed the causes of death to be decomposition of blood, 
 nephritis haemaglobinica and desseminated fatty degeneration of 
 the heart. 
 
 Doubtless the majority of these symptoms were due to suppres- 
 sion of the cutaneous perspiration, inasmuch as the effect of such 
 an extensive inunction must be identical with that of covering the 
 body with a coating of varnish. 
 
 ♦Jarsch, Wiener Medic. Jahrb. 1878, H. iv. 
 tNeisser, Zeitschr. f. Klin. Medicin. Bd. i., Heft. 1. 
 
INDEX TO AUTHORS. 
 
 A. 
 
 Adamkiewicz in 
 
 ./Egineta Paulus 94, 133 
 
 Albers 132, 142 
 
 Albertini 11 
 
 Alley 83, 84 
 
 Anrep, v 147 
 
 Apolant 136 
 
 Arndt 162 
 
 Arnold 194 
 
 Arthand 115 
 
 Ascherson 83 
 
 Aschoff 157 
 
 Auspitz no 
 
 B. 
 
 Bader 149 
 
 Badia 157 
 
 Bad in 102 
 
 Baginsky 124 
 
 Bailly 40 
 
 Baker 63 
 
 Bally 135 
 
 Balz 44, 80 
 
 Bamberger 82 
 
 Barbier 55, 129 
 
 Barella 96 
 
 Bardenhewer 203 
 
 Bartscher 1 70 
 
 Bauer 92 
 
 Baumann 75 
 
 Bazin 51, 52, 73, 96, 127, 193 212 
 
 Beau 191 
 
 Beginaud 55 
 
 Behrend 32, 133, 134 
 
 Bell, Benjamin 83 
 
 Beneke 11 
 
 Bengelsdorff 70 
 
 Bennett 209 
 
 B^renger-Feraud 63 
 
 Berenguier 
 
 51, 52, 53> *'i8, 133, 149 
 
 Bergeron 96 
 
 Berghmann 170 
 
 Bernard 49 
 
 Bert 171, 172 
 
 Bertagnini 42 
 
 Bertheau 148 
 
 Bessieres 143 
 
 Betelheim 198 
 
 Bianchi-Cogliesi 201 
 
 Bill 75 
 
 Billroth.. 135, 166,^173, 178, 179 
 
 Binswanger 57, 58 
 
 Binz 40, 94, 97, 180 
 
 Blev 157 
 
 Bceck 93, 193 
 
 Bouchardt 83 
 
 Bouchut 56 
 
 Bouisson 177 
 
 Bourneville 185, 186 
 
 Bouvier 189 
 
 Brand 134 
 
 Brera 108 
 
 Bretet 28 
 
 Brieger 45, 46 
 
 Briquet 40, 41 
 
 Brochin 51, 135 
 
 Brown, Bedford 118, 119 
 
 Brown 163 
 
 Brshesinsky no 
 
 Buchheim in 
 
 Buckell 103 
 
 Burdach 66 
 
 Burkhart ■. 140 
 
 Busch 75, 76 
 
 c. 
 
 Cabot 142 
 
 Carnot 56 
 
 Chapman 163 
 
 Charcot 60, 98 
 
 Charvet 25, 131 
 
 Chassaignac 146 
 
 Chatin 96 
 
 Chauvet 21 
 
 Chevallier 35 
 
 Chevandier 50 
 
 Chirone 35 
 
 Chouppe 137 
 
 Chrestien 98 
 
 Christison 140 
 
 Clark 118, 122 
 
 Clemens 173, 174 
 
 Corlieu 108 
 
 Coullon '. 156 
 
 Crucis 213 
 
 Curci 35 
 
 Curschmann 206, 162 
 
 D. 
 
 Da Costa 135 
 
 Damourette 117, 122 
 
 Daubceuf 36 
 
 Davidson 150 
 
 Declat 74 
 
 Delioux... 36,61, 194 
 
 Demarquay 208 
 
 Demme 205, 207 
 
 Denonvilliers 173 
 
 Denk 38 
 
 Devergie 98 
 
 Dioscorides 133 
 
 Dorval 108 
 
 Duclos 209, 133 
 
 Dujardin-Beaumetz 99 
 
 Dumas 137 
 
 Dupuytren 132 
 
 Durosiez 158 
 
 Duroy 171 
 
 Dworzak 152 
 
 E. 
 
 Eder i 39 
 
 Edlefsen 144 
 
 Edwards 79, 131 
 
 Empis 143 
 
 Engelmann 83 
 
 Eulenburg 69, 154 
 
 Ewald 184 
 
 F. 
 
 Faginoli 41 
 
 Falck 95, 126, 192 
 
 Falkson 182 
 
 Fallopius 188 
 
 Falot 191 
 
 Falret 118 
 
 Federschmidt 205 
 
 Felix 99 
 
 Fiedler 140 
 
 Fischer 109 
 
 Fleischmann 50, 154 
 
 Flemming 139, 140 
 
 Fonssagrives 104 
 
 Forcke 145 
 
11 
 
 INDEX TO AUTHORS. 
 
 Fothergill 42 
 
 Foucaud de 1' Espagne. . . 63 
 
 Fournier 83, no 
 
 Frank 113 
 
 Fräser 155 
 
 Frerichs 142, 211 
 
 Freudenberg 45 
 
 Frommann 60, 61 
 
 Fronmüller . . 148, 207 
 
 Fürstner 161 
 
 c. 
 
 Galezowski 146 
 
 Gamberini 5g, 61, 62 
 
 Garraway 37 
 
 Gatumeau 116 
 
 Gauchet 41, ' 163 
 
 Gellhorn 162 
 
 Gerrard .. 150 
 
 Girl 47 
 
 Glover 114 
 
 Gnauck 144 
 
 Gohlius 193 
 
 Golden 149 
 
 Golding t 143 
 
 Goltdammer 43 
 
 Gowers 122 
 
 Graefe A. v 
 
 39, J 3 6 , J 45, 146: 155 
 
 Grapin 88 
 
 Gregory ,. 156 
 
 Grimaud -65, 66 
 
 Grissac 36, 38 
 
 Gubler 51, 150 
 
 Guder 40 
 
 Guerard 148 
 
 Guipon 59 
 
 Guttmann 22, 120 
 
 Guyochin 41 
 
 Gwalter 85 
 
 H. 
 
 Hager 34 
 
 Hamberg 137 
 
 Hamilton, T. Lawrence . . 57 
 
 Hardy 52 
 
 Harles 97 
 
 Hebra 52,72,83.84, 191 
 
 Hegar 183 
 
 Heiberg 178 
 
 Heim 98 
 
 Heinlein 44 
 
 Heinrich 152 
 
 Heibert 193 
 
 Hemming 37 
 
 Hennig 67 
 
 Henry 181 
 
 Hermann 20, 193, 201 
 
 Herpin 88 
 
 Heusinger 37, 42 
 
 Heyfelder 157 
 
 Hiffelsheim 154 
 
 Hildebrandt 70 
 
 Hillairet 214 
 
 Hiller 145 
 
 Hjaltelin 100, 101 
 
 Hofmeier 124 
 
 Höring 116 
 
 Hollander 182 
 
 Holmgreen 171 
 
 Huet 61 
 
 Hüter 170, 179 
 
 Hütte 115, 117 
 
 Hufeland 66 
 
 Husband 163 
 
 Husemann 79, 142 154 
 
 Uling 144 
 
 Imbert-Gourbeyre 
 
 95, 9 6 , 97, 192 
 
 Isambert 125 
 
 Itzstein 200 
 
 J. 
 
 Jacobi 124, 126, 191 
 
 Jacquot 196 
 
 Jacubasch . . 72, 102 
 
 Jahrisch 216 
 
 Jörg 127, 129 
 
 Johnson m 
 
 Jolly 161 
 
 Kaltenbach 182 
 
 Kaposi 214, 215 
 
 Kappeier 166, 174, 176 
 
 Kin g 34 
 
 Kirchheim 73 
 
 Kidd i 74 
 
 Kirn 161, 164 
 
 Kleinhaus 72, 73 
 
 Knapp 39, 43 
 
 Köbner 37,38,149, 163 
 
 Köhler 47, 156 
 
 Koch 93 
 
 Kohl 66 
 
 Kottmeyer 79 
 
 Kowalewski 141 
 
 Krcemer 145, 147 
 
 Krosz 116,117, I2 4 
 
 Küster 76, 124 
 
 Kussmaul 83,86, 92 
 
 L. 
 
 Laborde 117,135. 146 
 
 Lacombe 125 
 
 Ladenburg 144 
 
 Ladendorf 186 
 
 Laennec 192 
 
 Lahr 140 
 
 Lallemand . , 171 
 
 Landsberg 141 
 
 Langenbeck v 
 
 69, 76, 77, 167, 190 
 
 Largus 132 
 
 Laroche 105 
 
 Lauderer 93 
 
 Ledelius 211 
 
 Lefort 175 
 
 Legrand 98 
 
 Lemattre 96 
 
 Lepine ... 44 
 
 Leube 45 
 
 Leven 155 
 
 Levinstein 140 
 
 Lewin, G 82,89, 9 2 
 
 Lewin, L 68,80,140 
 
 152, 181, 196, 199 214 
 
 Leyden 206 
 
 Lichtheim 45 
 
 Liebermann 213 
 
 Liebreich, R 146 
 
 Lightfoot 42 
 
 Lisfranc 25,' 66 
 
 Lister 78 
 
 Litten 30 
 
 Lcewy 46 
 
 Löfher 54 
 
 Löhlein 79 
 
 Lohrisch . . . f 203 
 
 Losch 205 
 
 Lücke 77 
 
 Lürmann 44 
 
 Lusanna 147 
 
 M. 
 
 Macnal 95 
 
 Maestri 53 
 
 Magitot 59 
 
 Marchaud 124, 126 
 
 Marsh 161 
 
 Martin 122,199, 201 
 
 Martindale 204 
 
 Mattison 140 
 
 Mayer 28 
 
 Mecklenburg 108 
 
 Melsens 91 
 
 Merat 41, 198 
 
 Merck 204 
 
 Mialhe 17, 18, 200 
 
 Mitscherlich 74, 129 
 
 Mcegling 197 
 
 Molodenkow 58 
 
 Monneret 41, 55 
 
 Montegre 51 
 
 Morganti 97 
 
INDEX TO AUTHORS. 
 
 Ill 
 
 Mossop 
 
 
 II 7 
 
 Reimer 
 
 
 162 
 
 Shaw 
 
 
 
 
 161 
 
 Müller 
 
 4Si 
 
 44 
 
 Reinhard 
 
 
 144 
 
 Siegmund. . 
 
 
 
 
 88 
 
 Munk, H 
 
 
 35 
 
 Rfezek 
 
 
 66 
 
 Sieveking. . 
 
 
 
 
 201 
 
 Munk 
 
 199, 
 
 202 
 
 Richardson.. 48, 
 Riche 
 
 160, 182, 
 
 202 
 
 56 
 
 Simon, A. .. 
 Simpson 
 
 
 102, 
 
 103, 
 
 112 
 202 
 
 N. 
 
 
 
 Richet 
 
 Ricord 
 
 Riegel 
 
 
 177 
 
 
 
 
 • 37, 
 
 47 
 
 
 215, 
 
 -if) 
 
 105, ioö, 
 ••43, 44, 
 
 
 
 
 Nelaton 
 
 IO3 
 
 203 
 
 Sobotka. . . . 
 
 
 
 
 131 
 
 Neumann 60, 74, 
 
 121, 
 
 215 
 
 Rieker 
 
 
 J33 
 
 Soltmann... 
 
 
 
 
 12 
 
 
 
 II 7 
 
 t6t 
 
 Riemer 
 
 Riess 
 
 Rilliet 
 
 60 
 
 61 
 
 Sommerfrodt.. .. 
 
 
 
 t?6 
 
 Nötel 
 
 
 Sonnenburg 
 
 
 
 
 167 
 
 O. 
 
 
 
 104 
 
 112 
 
 Spörer 
 
 
 
 
 179 
 
 Oberlaender 
 
 
 t8o 
 
 Ringer 
 
 
 150 
 
 Squire, B... 
 
 
 
 
 214 
 
 Odier 
 
 
 57 
 88 
 
 Rivet 
 
 Rodet 
 
 4 1 
 
 107, 112, 
 
 42 
 113 
 
 Stark 
 
 122, 
 
 124, 
 
 127, 
 
 187 
 T 6- 
 
 CEsterlen 
 
 
 
 
 
 
 
 
 207 
 
 Röhrig 
 
 
 78 
 
 Stille 
 
 
 
 .116, 
 
 Tj6 
 
 Ohms 
 
 
 
 
 
 
 
 77 
 
 Roller 
 
 
 69 
 
 
 
 
 
 42 
 
 Olshausen 
 
 
 
 
 
 Orfila 
 
 
 56 
 
 Romberg 
 
 
 62 
 
 
 T. 
 
 
 
 
 P. 
 
 
 Ronchard, Simon 
 
 de 
 
 41 
 
 Tanquerel des Planches.. 
 
 63 
 
 
 
 Rose 76, 
 
 in, 200, 
 
 201 
 
 Taylor 
 
 
 
 
 131 
 
 Paget 
 
 ,95, 
 
 x 74 
 96 
 
 Rosenthal, M... 
 Rosenthal, O 
 
 
 105 
 214 
 
 Thielmann. 
 Traube 
 
 
 
 
 117 
 
 T 6o 
 
 Pareira 65 
 
 
 J 49, 
 
 159, 
 
 J 32, 
 
 Pearson 
 
 «3, 
 
 92 
 
 Rosenbach 
 
 
 91 
 
 Tralles 
 
 
 J 33 
 
 Pelvet 
 
 "7, 
 
 122 
 
 Roser 
 
 
 100 
 
 Troetcher. . 
 
 
 
 
 154 
 
 156 
 67 
 
 Percival 
 
 Pereira 
 
 
 03 
 151 
 
 Rossbach 
 
 Roosa 
 
 50, 
 
 J 47 
 40 
 
 Trousseau. . 
 Tully 
 
 • • 33, 
 
 97, 
 
 129, 
 
 Perin 
 
 
 171 
 
 s. 
 
 
 
 Turnbull.... 
 
 
 
 
 
 Petit 
 
 
 150 
 
 
 
 
 U. 
 
 
 
 
 Petitjean 107, 
 
 no, 
 
 112 
 
 Saikowski 
 
 
 qi 
 
 Ummethum. 
 
 
 
 79 
 
 Petters 
 
 
 72 
 70 
 143 
 
 Samelsohn 
 
 Samter 
 
 Saenger 
 
 
 186 
 
 139 
 206 
 
 
 
 
 
 198 
 t86 
 
 Phillipi 
 
 Urbantschits 
 
 ch 
 
 
 
 Picard 
 
 V 
 
 
 
 
 Pick 
 
 
 185 
 
 Sander 
 
 126, 185, 
 
 186 
 
 Veiel .. .116, 
 
 Tl8 
 
 119, 
 
 
 
 Pickel 
 
 Pidoux 53, 71, 
 
 129, 
 
 93 
 156 
 
 Sansom 
 
 Santlus 
 
 
 174 
 107 
 
 Vepan 
 
 YeyrieVes. . . 
 
 
 t8s 
 
 36 
 186 
 
 Piorry 
 
 
 4 1 
 93 
 
 Schede 
 
 
 181 
 
 175 
 
 
 
 
 "7, 
 
 tt8 
 
 Pleisch 
 
 
 119 
 
 1 >o, 
 
 
 
 
 
 
 Plouviez 
 
 
 179 
 
 Schlothauer 
 
 
 50 
 
 Virchow 
 
 
 
 7, 12 
 „58, 
 
 , 13 
 
 60 
 
 Pluskal 
 
 
 212 
 
 Schroeter 
 
 
 185 
 
 
 
 Podcopean 
 
 
 125 
 
 Schroff 27, 
 
 142, 151, 
 
 157 
 
 
 w. 
 
 
 
 Prsetorius 
 
 
 78 
 7S 
 
 Schüler 
 
 Schuchardt 
 
 159, 
 
 150 
 210 
 
 Wade 
 
 
 
 
 42 
 
 77 
 
 Preusse 
 
 Wagner .... 
 
 
 
 
 Prowse 
 
 
 
 Schule 
 
 
 162 
 
 Weber 
 
 
 
 
 
 Purkinje 
 
 R. 
 
 SO; 
 
 127 
 
 Schultze 
 
 
 200 
 
 
 
 
 
 150 
 
 I2S 
 
 Schule 
 
 
 165 
 
 Wegscheider. . . . 
 
 
 .124, 
 
 
 
 Schulz 
 
 94,9 
 
 Wells 
 
 
 
 
 
 Rabuteau 
 
 I05, 
 
 117 
 
 Schuetz 
 
 10, 
 
 20 
 
 Werdmann. 
 
 
 
 
 64 
 
 6- 
 
 Radziejewski 
 
 8l, 
 
 192 
 206 
 
 45 
 
 Schuhmacher 
 
 Schweig 
 
 Schwerin, E 
 
 
 43 
 115 
 211 
 
 Werneck . . . 
 
 
 "3, 
 99, 
 
 •57, 
 J 35, 
 189, 
 
 Ranneft 
 
 
 
 t6" 
 
 Rathery 
 
 Wibmer 48. 62 
 
 190 
 130 
 
 Rayer 
 
 
 5i 
 
 Schwilgue" 
 
 
 67 
 
 Wilkinghoff 
 
 Wilson 
 
 Wyss 
 
 Yvonneau.. 
 
 
 v. Recklinghausen. . . 
 
 
 T 6 7 
 
 
 
 132 
 168 
 202 
 
 
 
 
 Regnard 102, 
 
 IO3, 
 
 112 
 153 
 
 SeMillot 
 
 
 
 
 
 149 
 
 Reiche 
 
 Seitz :... 
 
 
 90 
 16R 
 
 Reil 
 
 
 l6o 
 
 Senator 
 
 
 15 
 
 Zesas 
 
 
 
 
 102 
 
INDEX TO SUBJECTS. 
 
 Acetate 01 Lead 62 
 
 Acids 74 
 
 Acidum Arsenicum 31, 94 
 
 Acidum Boracicum 57 
 
 Acidum Bromhydricum 42 
 
 Acidum Carbolicum 74 
 
 Acidum Chrysophanicum 213 
 
 Acidum Citricum 74 
 
 Acidum Hydrochloratum 74 
 
 Acidum Nitricum 74 
 
 Acidum Phosphoricum 74 
 
 Acidum Picricum 202 
 
 Acidum Pyrogallicum 216 
 
 Acidum Salicylicum 42 
 
 Acidum Tannicum 67 
 
 Acidum Tartaricum 74 
 
 Aconite 151 
 
 Aconitine 151 
 
 Aloe 26, 1 87 
 
 Alteratives 81 
 
 Alumen 55 
 
 Amygdalae Amarae , 156 
 
 Amyli Nitritum 184 
 
 Antimonii et Potassii Tartratis 190 
 
 Antimonii Sulphuretum 196 
 
 Antiparasitica 197 
 
 Aqua Calcis 54 
 
 Aqua Laurocerasi 156 
 
 Argenti Nitras 58 
 
 Argyria 60 
 
 Arnica 130 
 
 Arsenious Acid 94 
 
 Astringents 55 
 
 Atropia 30, 145 
 
 Auri Chloridum 98 
 
 Auri et Sodii Chloridum 98 
 
 Balsamum Peruvianum j 97 
 
 Barii Chloridum 25, 66 
 
 Belladonna 148 
 
 Benzolum 202 
 
 Berberina 48 
 
 Bichloride of Ethylidene 183 
 
 Bichloride of Methylene 182 
 
 Bismuthi Subnitras 17, 55 
 
 Bitter Almonds 156 
 
 Boracic Acid 57 
 
 Bromhydric Acid 42 
 
 Bromide of Potassium 113 
 
 Bromine 113 
 
 Cadmii Sulphas 65 
 
 Caffeine 142 
 
 Calabar Bean 755 
 
 Calomel 18, 20, 81 
 
 Camphor 128 
 
 Cannabis Indica 141 
 
 Cantharides 210 
 
 Carbolic Acid 74 
 
 Cardol 211 
 
 Cashew Nut 211 
 
 Castor Oil 187 
 
 Cheledonium 48 
 
 Cherry Laurel Water 156 
 
 Chinolinum 46 
 
 Chloral Hydrate 160 
 
 Chlorate of Potassium 124 
 
 Chloride of Ammonium 195 
 
 Chloride of Barium 66 
 
 Chloride of Gold 98 
 
 Chloride of Gold and Sodium 98 
 
 Chloride of Potassium 126 
 
 Chlorine 210 
 
 Chlorine Water 210 
 
 Chloroform 166 
 
 Chrysarobine 213 
 
 Chrysophanic Acid 213 
 
 Cod Liver Oil 9, 209 
 
 Colchicum 156 
 
 Colocynth 188 
 
 Columbo 47 
 
 Copaiba 51 
 
 Creasote 48 
 
 Croton Oil 189 
 
 Cubebs 53 
 
 Digitalin 160 
 
 Digitalis 158 
 
 Diuretics 194 
 
 Duboisia 149 
 
 Elaterium 19 
 
 Emetics 190 
 
 Emollients 208 
 
 Ergotinum 69 
 
 Eserine 155 
 
 Ether Sulphuricus 183 
 
 Ethylideni Bichloridum 183 
 
 Evacuants 187 
 
 Excitants 128 
 
 Expectorants 195 
 
 Extractum Aconiti 151 
 
 Extractum Belladonnas 148 
 
 Extractum Cannabis Indica 141 
 
 Extractum Cubebarum 53 
 
 Extractum Digitalis 158 
 
 Extractum Fabae Calabaricae 155 
 
 Extractum Filicis Maris 198 
 
 Extractum Hyoscyami 142 
 
 Extractum Secale Cornuti 69 
 
 Faba Anacardii 211 
 
 Ferrum 33 
 
VI 
 
 INDEX TO SUBJECTS. 
 
 Filix Mas 
 
 Folia Salviae 
 
 Fowler's Solution 28, 
 
 Gamboge 
 
 Glycerine 
 
 Goa Powder 
 
 Gratiola , 
 
 Hellebore 
 
 Homatropin 
 
 Hydrargyrum 
 
 Hydrochinon i A 
 
 Hydrocyanic Acid 
 
 Hyoscin 
 
 Hyoscyami 
 
 Hyoscyamin 
 
 Iodide of Potassium 
 
 Iodine 
 
 Iodine Acne 
 
 Iodism 100, 
 
 Iodoform 
 
 Ipecacuanha 
 
 Iron 
 
 Jaborandi 
 
 Jalap 
 
 Lime Water 
 
 Magisterium Bismuth 17 
 
 Male Fern 
 
 Mercurialism 
 
 Mercury 
 
 Methyleni Bichloridum 
 
 Mezereum 
 
 Morphia 
 
 Moschus 
 
 Musk 
 
 Napellin 
 
 Naphtolum 
 
 Narcotics 
 
 Nitrate of Silver 
 
 Nitrite of Amyl 
 
 Oil of Cade 
 
 Ointments 
 
 Oleum Anacardii 
 
 Oleum Juniperi Empyreumaticum. 
 
 Oleum Morrhuae , 
 
 Oleum Ricini 
 
 Oleum Terebinthinse 
 
 Oleum Tiglii 
 
 Opium 
 
 Opium Eating 
 
 Oxide of Zinc 
 
 Peruvian Balsam 
 
 Petroleum 
 
 Phosphoric Acid 
 
 Phosphorus 
 
 Physostigmin 
 
 Picric Acid 
 
 ,75 
 156 
 143 
 142 
 
 x 43 
 104 
 
 100 
 100 
 
 104 
 
 182 
 212 
 
 135 
 129 
 129 
 151 
 215 
 131 
 
 72 
 
 13 
 212 
 
 72 
 209 
 187 
 
 49 
 189 
 
 131 
 
 137 
 
 64 
 
 197 
 
 213 
 
 74 
 
 99 
 
 155 
 
 202 
 
 Pilocarpine 204 
 
 Pix Liquida 71 
 
 Plumbi Acetas 62 
 
 Pomegranate Root Bark % 198 
 
 Potassii Bromidum 113 
 
 Potassii Chloras 124 
 
 Potassii Chloridum 126 
 
 Potassii Iodidum 104 
 
 Potassium Sulphidum 127 
 
 Purgatives 187 
 
 Pyrogallic Acid . 216 
 
 Quassia 48 
 
 Quinine 9, 34 
 
 Resorcin 45 
 
 Rubefacients 210 
 
 Sage 71 
 
 Sal ammoniac 195 
 
 Salicylate of Sodium 42 
 
 Salicylic Acid 42 
 
 Salvia 71 
 
 Santonine 199 
 
 Sarsaparilla 195 
 
 Savin 212 
 
 Scillae . . 194 
 
 Senega 196 
 
 Sodii Nitras 54 
 
 Sodii Salicylas 42 
 
 Squills 194 
 
 Styrax 198 
 
 Strychnia 47 
 
 Subnitrate of Bismuth 55 
 
 Sudorifics 203 
 
 Sulphate of Cadmium 65 
 
 Sulphide of Potassium 127 
 
 Sulphate of Atropia 145 
 
 Sulphur 189 
 
 Sulphuret of Antimony 196 
 
 Sulphuric Ether 183 
 
 Tannate of Soda 68 
 
 Tannic Acid 67 
 
 Tannin 67 
 
 Tannin Albuminate 68 
 
 Tar 71 
 
 Tartar Emetic 190 
 
 The Morphia Habit 137 
 
 Thymol 79 
 
 Tonics 33 
 
 Toxicodendron 195 
 
 Turpentine 49 
 
 Valerian 129 
 
 Vaseline 208 
 
 Veratrine 153 
 
 Veratrium 153 
 
 Vesicants 210 
 
 Zinci Lacticum 64 
 
 Zinci Oxidum 64 
 
J^=Page proofs REVISED and APPROVED by the Author.^gJ 
 
 THE UNTOWARD EFFECTS OF DRUGS, 
 
 A PHARMACOLOGICAL AND CLINICAL MANUAL. 
 BY 
 
 "DTI. Xj. Xj IE TXT I IttT , 
 
 Docent of Materia Medica, Hygiene and Public Health in the 
 University of Berlin. 
 
 TRANSLATED BY J. J. MULHERON, M. D., 
 
 Professor of Principles of Medicine. Materia Medica and Ther- 
 apeutics in the Michigan College of Medicine, 
 Detroit, Michigan. 
 
 Second Edition, revised and enlarged. The only English transla- 
 tion having the author's endorsement. 
 
 DETROIT, MICHIGAN: 
 
 Geo. S. Davis, Medical Publisher. 
 
To the Medical Profession : 
 
 In issuing my edition of Dr. Lewin's work on "The Untoward 
 Effects of Drugs," I am constrained, through circumstances, to offer 
 some explanation for my placing on the market a second transla- 
 tion so shortly after the one issued by another publishing house: 
 I had completed arrangements with Dr. Lewin for bringing out 
 this book on this side of the Atlantic, and had committed the 
 work of translation, some time before any intimation of another 
 translation was made. On receiving notice that others had assumed 
 to issue the work in this country, I was naturally, in view of my 
 contract with the author, very much surprised, and wrote to Dr. 
 Lewin for an explanation. The following is a copy of his reply : 
 
 Berlin, April, iy, 1882. 
 Mr. Geo S. Davis, 
 
 Medical Publisher, 
 
 Detroit, Mich., U. S. A. 
 DEAR SIR: — Your communication has been received. It is with profound 
 indignation that I learn that an unauthorized edition of my tvork "Die Neben- 
 wirkungen der Arzneimittel" (A. Hirschwald, Berlin, 1881), is about to appear 
 in America. I beg herewith to 'affirm that you alone are authorized to have 
 this work translated into the English language, and to publish and sell such 
 English translation in America. I have agreed to revise the translation which 
 you are to issue, and to make such additions as the progress of the same shall 
 render necessary up to the time of publication. The translation to be issued by 
 you is the only one having my endorsement, and being prepared under my super- 
 vision, I respectfully ask for it the attention of the medical profession of 
 America. 
 
 I remain with great respect, 
 
 Yours very truly, 
 
 DR. L. LEW IN, 
 
 Docent 0/ Materia Medica. Hygiene and Public Health in the University of Berlin. 
 
 The facts of the case, in connection with the two translations 
 now in the market, are thus succinctly stated. They are their own 
 comment, and scarcely call for further emphasis. 
 
Of the merits of Dr. Lewin's work on "The Untoward Effects 
 of Drugs," it is not necessary to speak. It has received the universal 
 commendation of the medical press of Germany, and has taken a 
 high place among medical publications. Its peculiar merit is the 
 fact that it is the only work especially devoted to the subject of 
 which it treats. 
 
 In lieu of the many complimentary press notices which it has 
 received, I submit herewith an extract from an extensive review in 
 the Zeitschrift für Klinische Medicin, written by Rossbach, Pro- 
 fessor der Arzneimittellehre in dem Institut für Experimentelle 
 Pharmakologie der Universität Würzburg, an authority whose 
 opinion will be accepted without question : 
 
 "It appears from the foregoing that no small amount of credit is due the 
 author for imposing on himself the great task of collecting and clearly summar- 
 izing the material which existed previously as scattered, and often mentioned 
 merely incidentally, in a multitude of published articles. That this has been an 
 exceedingly tedious task is manifest from the completeness of the facts which 
 have in this manner been rescued from forgetfulness, and which must awaken 
 the keenest interest not only in the practicing physician but also in the 
 professional pharmacologist, and which I am convinced will stimulate to many 
 new observations and experiments. The author first and very properly aims to 
 collect all observations which had been previously made. A criticism of these 
 is impracticable, both owing to lack of time and to deficiency in the necessary 
 kind of knowledge ; in order to give a critical sifting of these, they must from 
 this time on be subjected to frequent deliberate observations, and viewed from 
 all sides. Any criticism based on a defective foundation must be shallow and 
 destructive rather than edifying ; it is permissible only in cases in which the 
 author has considered matters which are somewhat doubtful, and has left their 
 confirmation for time to establish. 
 
 It has, unfortunately, not been possible in this reference to give more 
 than an approximate conception of the richness of the contents of the book ; 
 it must suffice to state that all the drugs in general use are, without exception, 
 investigated in reference to their untoward effects, and that the reporter has 
 not been able to establish an exception in the case of a single drug. 
 
 No physician will be able to lay down the book without having received 
 from it the richest information, and without having incited in him an impulse 
 to further observation." 
 
 Of the translation it is only necessary to state that it has been 
 pronounced by the author to be "ausgezeichnet" (superior). 
 
 The book will be mailed, postage prepaid, on receipt of $2.00. 
 
 GEORGE S. DAVIS, 
 
 P. O. Box 4jo. Medical Publisher, Detroit, Mich. 
 

 
 

 
 
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