V -yy .^ Class 1^.3 lAV BooklBali: ()ORyiightN''_ COPYRIGHT DEPOSm THE PHARMACOPEIA AND THE PHYSICIAN A Series of Articles which Originally Appeared in the Journal OF THE American Medical Association, Discussing the Chief Substances in the United States Pharmacopeia, Class- ifying Them According to Their Uses and De- scribing Their Methods of Combination and How They May Take the Place of Many Proprietary Preparations for Which Extravagant Claims Have Been Made. By ROBERT A. HATCHER, Ph.G., M.D. Assistant Professor of Pharmacology, Cornell Universitv Medical SchooF, New York AND MARTIN I. WILBERT, Ph.M., Apothecary to the German Hospital, Philadelphia [Second, Revised, Edition.] <;iiiCA<;u : AMKKICAX MKUICAL ASSOCI.VJIi IN J'Ul 1908 LIBRARY of CONcSRESS! Two Copies Hecri.._.^ MAR 12 1908 1 COHV 9 / a. ^ ('\'u\ as a disinrcctanl. It will be considci'i'd later a! greater lengtli. The strong mineral acids are destructive to bac- 4-2 PHARMACOPEIA AND PHYSWIAN. toria, but their application as disinfectants is nec- essarily very limited. As noted before, mercuric chlorid is to be classed with the most powerful of all disinfectants in gen- eral use, one part in 10,000 being fatal to spores. Like all other chemical disinfectants, its activity is increased by heat. It precipitates albumin and its efficiency is, therefore, materially lessened by the presence of any appreciable amount of such organic material; this disadvantage of mercuric chlorid may be obviated in part by the addition of an equal amount of sodium or ammonium chlorid (or a small amount of hydrochloric acid), the tablets found on the market for preparing the solutions always containing the requisite quantity of one of those salts. As it attacks metals, it is not suited for the disinfection of instruments or metallic vessels. One part of mercuric chlorid in 50,000 parts of water has been demonstrated to possess decidedly antiseptic properties. Its com- parative non-volatility, its property of attacking metals and of combining with albumin, and its extreme toxicity limit its field of application, but it remains by far the cheapest antiseptic we have for general use. Copper sulphate shares with copperas (crude ferrous sulphate) the power of deodorizing decom- posing organic matter, though it is but little used for this purpose. It has recently been claimed that the merest trace of copper sulphate, or of copper, in water readily destroys the bacillus of typhoid fever, or at least completely inhibits its growth; even though the copper is present in quantities too small to interfere with the use of the water for GENERAL DISINFECTANTS. 43 drinking. The results of different investigators are not uniform, however, and some maintain that the antiseptic power of copper and its salts has been greatty overestimated. The soluble salts of zinc, particularly the chlorid, have also been used for disinfecting purposes, but as they share with copper the disadvantage of being comparatively expensive, without any accompanying material ad- vantages, a more detailed consideration of these substances may be omitted in this connection.^ CLINICAL THERMOMETEES AND HYPODERMIC SYRINGES. The disinfection or sterilization of clinical ther- mometers and of hypodermic syringes and needles deserves especial mention. With the present com- paratively low price of clinical thermometers there is little or no excuse for not having an individual thermometer for each patient ill with an infec- tious or a contagious disease or a continued fever. But, even this precaution, desirable as it certainly is, does not obviate the necessity for disinfecting or sterilizing the thermometer. The necessary dis- infection may be effected in any one of a number 2. The following quotation, talcen from Wood's "Thera- peutics," page 823, contains suggestions that are of interest in this connection. "There are not many affairs in life in which the public has been so superabundantly fleeced as in the matter of disinfection. A most extraordinary part of this swindling is the ease with which distinguished members of the medical profession have given certiflcates of efliciency and value to comparatively Inert and extraordinarily expen- sive proprietary compounds. Oddly enough, the cat that has drawn the chestnuts out of the lire for avaricious manufac- turers has not even had the sense to smell the odor of its own paws when burning." It is evident that Dr. Wood knew less of the resources and the wiles of nostrum makers, and llielr shrewdness in duping physicians, than he supposed, else he would not think It extraordinary that so many have been deceived. 44 J'HAIx'MACOI'EIA AND PHY>ilClAN. of ways ; the thermometer may be dipped for a few- minutes in strong plienol, the solution of cresol, or in the, now official, solution of formaldehyd, after which it is thoroughly rinsed in water. Where an individual thermometer is provided it may be ster- ilized by keej^ing the l)ulb immersed in 75 per cent, alcohol, a saturated solution of boric acid, the of- ficial liquor antisepticus, or in a mixture of equal parts of antiseptic solution and of solution of hy- drogen dioxid. It must appear even to the least careful that the disinfection of clinical thermom- eters is a precaution so important that it should never he neglected. The hypodermic syringe and needle should be disinfected with strong phenol or cresol solutions, solution of formaldehyd or by repeated washing with very hot water as a purely routine procedure. When a syringe and needle are known to be in- fected the disinfection should be as thorough as that of other surgical instruments. Solutions intended for hypodermic injection can be sterilized by boiling, when this does not cause decomposition. With the now widely used hyjDodermic tablets it is preferable to boil the nec- essary quantity of water, or, better, distilled water, for a minute or two, then add the tablet, avoiding all unnecessary handling, and warm sufficiently to insure thorough solution. Cocain, being readily decomposed, can not be boiled, but the solution may be sterilized by heating to about 80° C. (176° F.) for thirty minutes on two successive days. It is usually preferable, however, to use freshly pre- pared solutions that have been made in a sterile bottle with recently boiled and sterile distilled GEXERAL DIfilXFECTAyTS. 45 water. Eiicain and stovain solutions may be boiled, but these substances themselves are not entirely free from objections. Under the subject of internal antiseptics we shall have occasion to mention the disadvantages of sterilized milk, but here we may call attention to the widespread use of formaldehyd, salicylic and boric acids, borax and other chemical antisep- tics for the preservation of foods. While we are not certain that minute quantities of many of these chemical antiseptics are in themselves in- jurious, we have ample authority for the opinion that their continued use in appreciable quantities is by no means beneficial. Schmiedeberg regards the constant use of even small quantities of sali- cylic acid, for a continued period, as imwise in the present state of our knowledge, and Sollmann says that the use of formaldehyd can not be too strong- ly condemned, because of the specific irritation of the mucous membranes which it causes. Liebreich has written a number of treatises on the use of boron compounds as food preservatives, but The Prussian Scientific Deputation on Medical Conditions gives a written opinion at the request of the Berlin police, in which the conclusions of Liebreich are rejected, and these preparations are ])ronounced injurious to the human organism even when taken in small quantities. The whole subject of food preservatives, from its vital importance, is one in which the physician should, and indeed must, be actively interested, but it is entirely too extensive to be discussed at length here. The subject of preservatives is also of interest 40 PHARMACOPEIA AND PHYSICIAN. in connection with medicines and medicinal prepa- rations. The antiseptic action of alcohol, glycerin, sugar and of volatile oils is well known and gen- erally recognized, and, while not of sufficient im- portance to be considered in connection with gen- eral disinfection, these substances are widely used as preservatives not alone for medicinal prepara- tions and foods, but also for other substances. The use, or abuse, of preservatives in connection with medicinal preparations, particularly in connection with proprietary remedies, is a matter that is de- serving of more attention than is now being ac- corded it; as the presence of preservatives un- doubtedly influences the physiologic action of other ingredients. CHAPTER II. LOCAL DISmFECTANTS AND ANTISEP- TICS. Lister's use of local antiseptics in surgery is usually spoken of as a discovery, but, without de- tracting in any way from the credit due to Lister, it should be referred to more correctly as a prac- tical application of previous discoveries. Eeicbenbach, in 1832, obtained a substance from wood tar which he named creosote. Finding later that it consisted of phenol and phenol ethers, and also finding these same substances in smoke, he concluded, and later conclusively proved, that to them is due the meat preserving activity of smoke. Runge, in 1834, found that the phenol which ho obtained from coal tar also possessed the power of preventing putrefaction. Tar and a number of products of a similar nature were long ago rec- ommended and widely used for foul smelling ul- cers, but the fact remains that to Lister is univer- sally, and very properly, accorded the distinction of having placed antisepsis in surgery on a sure basis. Since the early days of antisepsis there have been many improvements, and we now know that the most perfect cleanliness, or asepsis, that is attainable is much to be preferred even to the most elaborate antisepsis. It is, of course, entirely beyond the scope of this treatise to consider the details of major surg- ery, but the principles of antisepsis which obtain in this branch are equally applicable to minor 48 PHARMACOPEIA AND PHYSICIAN. operations, and their disregard by many, who are not surgeons, is the best justification for their present brief consideration. Tlie necessity for scrupulous cleanliness is seen in such a common, but admittedly important, procedure as vaccin- ation. The careful physician will perform even this simple operation under aseptic conditions, thereby saving himself much annoyance in case of accident. The first, and really the most important, duty of the physician with regard to infections is to see that he does not carry them to other patients. There can be no doubt that physicians have played no small part in the spread of infectious diseases, particularly in the past, but fortunately, with the better understanding of the subject, this occurs now less frequently than it did formerly. The disinfection of clothing and of instruments belongs to the subject of general disinfection, that of the hands and person to local disinfection. The cleansing of the hands, as it is done in a number of American hospitals, is about as fol- lows : "Trim and clean the nails, wash the hands and forearms for five minutes in very warm, sterile water, using soft soap or a liquid soap^ and 1. An efficient and satisfactory liquid soap can be pre- pared by any pharmacist from the following formula : Sodium hydrate 40 Gm. Potassium hydrate 40 Gm. Cottonseed oil 500 Cc. Alcohol 250 Cc. Distilled water, a sufficient quantity to make 2500 Cc. In a suitable container, preferably a glass-stoppered bottle, dissolve the potassium hydrate and the sodium hydrate in 250 Cc. of distilled water, add the alcohol, and then add the cottonseed oil in three or four portions, shaking vigorously after each addition. Continue to agitate the mixture occa- sionally until saponification has been completed. Then add the remaining portion of distilled water and mix. LOCAL ANTISEPTICS. 49 scrubbing them energetically with a brush or a gauze pad, cleansing the nails again during this part of the process. Rinse the hands for three minutes in 75 per cent, alcohol, to remove soap and to aid in sterilization; then in 1 to 1,000 solution of mercuric chlorid, or in a solution of 1 to 2,000 mercuric chlorid with 1 to 40 phenol, and finally ]-inse in sterile warm water." This may be some- wliat more elaborate than is necessary in most cases of minor surger}^, but even here it is well to err on the safe side. For the disinfection of the whole body a full bath in warm water with the liberal and judicious use of soap is sufficient, and the clothes may un- dergo disinfection separately at the same time. This procedure is so simple that the physician can not escape blame should he carry infection from one patient to another through the omission of necessary precautions. When minor surgical operations are to be per- formed it is always well to thoroughly disinfect the surface at and around the prospective seat of operation. For this purpose the procedure given for cleansing the hands of the surgeon is sufficient, though in some cases it may be found necessary to supplement the soap and water with oil of tur- pentine. Wounds and ulcers require disinfection to de- stroy those bacteria which can be reached, and antiseptic dressings to prevent the development of colonies from those which escape destruction or which may afterward reach the spot. Tlio compound solution of iodin has been used to disinfect cysts in which pntrofactive processes 50 PHARMACOPEIA AND PHYSICIAN. are going on, bnt tliis jKocess is extremely painful and sometimes dangerous. It is not recommended. Aqua Hydrogenii Dioxidi.- — U. S. P. — Solu- tion of H3^drogen Dioxid, or, as it is frequently called, Solution of Hydrogen Peroxid, is useful for decomposing pus, in which bacteria are protected from the action of other disinfectants. It thus secures the rapid cleansing of freely exposed pus cavities or ulcers, and at the same time it acts powerfully on bacteria, though they are not all destroyed so long as any pus remains. The offi- cial solution is equal, in disinfectant power, to a 1 to 1,000 solution of mercuric chlorid. The ac- tion on pus of hydrogen dioxid is so extremely rapid that it frequently detaches small masses which may escape decomposition. The use of this solution is not unattended with risks, particularly in sinuses or deep, partially closed, wounds. Mucous membranes decompose hydrogen dioxid rapidly, and the skin slowly, with the liberation of nascent oxygen. It is not certain whether the bactericidal property is due to the liberation of oxygen alone, or whether the prepara- tion possesses a special influence on the micro- organisms. The decomposition whereby the oxygen is liberated is supposed to depend on a ferment, catalase, which is widely distributed, and, as the preparation loses its bactericidal powers, once the oxygen has been liberated, it is, of course, useless 2. It is commonly, but erroneously, believed that the amount of free gas confined in the bottle is an index of the value of the solution of hydrogen peroxid. It is, in fact, an index of the amount of decomposition that has occurred. Many manufacturers of hydrogen dioxid now use acetanilid as a preservative. When such a solution develops an odor resembling nitrobeuzol it should be discarded. LOCAL ANTISEPTICS. 51 as an antiseptic, though extremely useful as a disinfectant. Hydrogen dioxid has an especial reputation in the treatment of sore throat and even diphtheria, for which it is used as a spra}^ or as a gargle, with entire safety. It attacks met- als readily, and only rubber or glass should be used in connection with it. Diluted with an equal amount of water, it is an excellent wash for the mouth and throat, but not infrequently it contains a little acid, and the mouth should be rinsed after its use.^ After the disinfection of ulcers and wounds an antiseptic dressing is applied. Cotton, gauze and lint impregnated with various antiseptics are found on the market. Only the active substances that are used in this connection will be discussed, as the application of dressings belongs to surgery. IoDOFOR]\[Uir. — IT. S. P. — Iodoform, Tri-iodome- thane is usually obtained by the action of iodin on alcohol, in the presence of an alkali or an al- kaline carbonate. Iodoform was discovered by Serullas, in 1822, but was not used in medicine until some time after 1837. Despite its disagree- able penetrating odor, iodoform continues to hold first place among local antiseptics, used for the dressing of wounds. At first it was supposed to share with chloroform (from which it differs chem- ically only in containing iodin in place of the clilorin) a strong antiseptic action, but in the case of iodoform this has been found to be but slight; it is, however, materially increased by the slow ■'!. An aRrcrcable, and at the samp time efUcicnt, month wash Is oljtalnofl by mixing equal parts of aqua hydrofronll flioxldl, liquor antlseptlcus (U. S. P.) and a saturated solu- tion of potassium chlorate. 52 PHARMACOPEIA AND PHYSICIAN. liberation of iodin. When its local use as a dress- ing is long continued, enough of it nia}^ be absorbed to produce poisoning, which does not, however, re- sult in typical narcosis, such as. chloroform pro- duces, but gives rise to disturbances of cerebration, headache, delirium and other symptoms. These are due to the iodoform molecule; but exanthem- ata, which are sometimes severe, are usually attrib- uted to the liberated iodin, which, when liberated, is thought to circulate in the blood as an alkaline iodid or in combination with albumin. Hem- aturia, albuminuria and urinary casts may also result from its absorption, and many attempts have been made to find a substitute for iodoform with- out its poisonous effects. Some surgeons deny that iodoform exerts any direct antiseptic power, and attribute the bene- fits from its use to its limitation of the secretion on which the bacteria would otherwise develop. Binz observed that iodoform lessened the emigra- tion of leucocytes, and it is said to be particularly useful in local affections with free secretions. When iodoform is intended for use as a dust- ing powder, its odor may be rendered very much less disagreeable by incorporating with it from 1 to 4 per cent, of cumarin. The following has been used to some extent: B. lodoformi 3v 20 Ciimarini gr. xv 1 Acidi borici q. s. ad Sxiii 50 Misce bene. Sig. : To be used as a dusting powder. Pulvis Iodoform! Compositus (N. ¥.), contain- ing iodoform 20, boric acid 30, naphthalin 47, and oil of bergamot 3 parts, also constitutes a use- LOCAL ANTISEPTICS. 53 ful and comparatiyely unobjectionable antiseptic dusting powder. Where iodofonn is to be used in the form of an ointment the addition of from 5 to 10 per cent, of balsam of Peru, or of 2 per cent, of oil of anise lias been found to be advantageous. The addition of oil of anise, in somewhat larger quantities, has also been recommended for iodoform gauze, par- ticularl}' when the gauze is to be used in appre- ciable quantities or for an}' continued length of time. If the antiseptic action of iodoform is due to the liberated iodin, then necessarily many of the pro- posed substitutes must be practically devoid of an- tiseptic power, since the iodin is too firmly bound to be liberated by the tissues. loDOLUM. — TJ. S. P. — lodol, designated chemic- ally as tetra-iodopyrrol, is one of the recent addi- tions to the Pharmacopeia. The iodin in this case is so firmly bound that the substance has been recommended as being comparatively non-toxic, but iodin is liberated in the body, being excreted as iodid. Other preparations, such as nosophen, losophan and curophen, depend largely for their antiseptic action on the cresol or the phenol com- pounds united to the iodin. Loretin and vioform arc combinations of iodin and quinolin, and there is no reason to suppose that they have any advan- tage over the other preparations just mentioned. TiTYMOLTS loDiDUM. — U. S. P. — Thymol Iodid, much better known by the formerly trademarked name "Aristol," is a condensation product of two molecules of thymol with two atoms of iodin, and more propci'ly, therefore, should be designated by 54 PHARMACOPEIA AND PHYSICIAN. its true chemical title, clithymol di-iodid. This preparation, which really belongs to the phenol group of iodin compounds, has met with a better reception than many of the other iodoform sub- stitutes. It is probable, now that the patents have expired on aristol and the substance is available at much more reasonable prices, that its popular- ity and use will be extended gtill further. This, however, is problematic. Schmiedeberg specific- ally states that aristol, losophan, sozoiodol, picrol, loretin and antiseptol, all of which contain iodin, are not more actively antiseptic than are the cor- responding iodin free compounds, while the latter are, of course, much less expensive. Since the number of possible combinations of this t^^pe is practically unlimited, we will do well to exercise circumspection in accepting those which appear from time to time. Phenol. — A sharp distinction is to be drawn between the anesthetic and antiseptic uses of phenol. Solutions of phenol in oil, or mixtures with fats, are excellent anesthetics when brought in contact with painful surfaces or wounds, but they possess very little antiseptic action, because phenol is more soluble in fats and oils than in water or weak saline solutions, hence it does not leave the oil to penetrate the bodies of bacteria, without doing which it does not injure them. Practically the same holds true of its affinity for alcohol, and it is for this reason that alcohol is such an excellent antidote for carbolic acid, exter- nally as well as internally. The absorption of phenol is followed by its appearance in the urine, LOCAL ANTISEPTICS. 55 which usually becomes dark-greenish or nearly black in color. The toxicology of ^ohenol deserves a passing no- tice. Despite the well-known fact that it occasions great pain when swallowed, it was selected as the agent of destrnction by more than one-third of all those who committed suicide by poison in England for a number of years. It is probable that poison- ing by it is equally frequent in this country. Sodium sulphate is commonly stated to be the proper antidote, though experiments made on ani- mals have never demonstrated that it possessed anj very decided value, and Sollmann and Brown have recently shown that it has practically no effect on the course of the poisoning. Kobert relates that each of two children swal- lowed a teaspoonful of liquefied phenol; ten min- utes afterward their stomachs were washed out and their lives were thus saved. Phenol. — U. S. P. — (Acidum Carbolicum U. S. P., 1890) is hydroxybenzene ; it may be obtained from coal tar by fractional distillation and subse- sequent purification, or it may be made synthetic- ally. In its pure state it occurs as colorless, needle- shaped crystals, or as a white crystalline mass. Phenol Liquefactum. — U. S. P. — Liquehed Phenol, Liquid Carbolic Acid, contains from 85 to 89 per cent, of absolute phenol, and is the form in which phenol is usually seen and used. When first prepared this solution is colorless, but it fre- quently develops a reddish tint on keeping, Piienol is now used as an antiseptic dressing for wounds very much less frequently than it was some years ago, because of tlio danger of poison due to 56 PHARMACOPEIA AND PHYSICIAN. absorption. It may be applied in the form of a 3 per cent, solution in water; stronger solutions are used, but many cases of gangrene have followed the use of even dilute solutions on the extremities, particularly the hands, for a continued length of time. Cresol. — U. S. P. — and its more desirable form : Liquor Cresolts Compositus. — TJ. S. P. — ■ Compound Solution of Cresol is well known and has been extensively used, particularly in the form of one or the other of the numerous projjrietary preparations, as a local disinfectant and also as an antiseptic. The saponaceous properties of this particular preparation make it very useful in a variety of instances in which a detergent action is to be attained in addition to the disinfection. Thymol. — TJ. S. P. — This is a phenol occur- ring in the volatile oil of Thymus vulgaris and in some other volatile oils. It possesses strong anti- septic properties, but its comparative insolubility in water, 1 in 1100, has interfered materially with its extended use. Thymol iodid, the only official combination of thymol, has been referred to in con- nection with iodoform substitutes. An ideal disinfectant, or antiseptic dressing for wounds, should act not strongly on the living pro- toplasm, should be slowly absorbed, and should af- fect the central nervous system but slightly after absorption. Phenol has the disadvantage of being rapidly absorbed and of profoundly affecting the central nervous system. Thymol, being but slight- ly soluble in water, but volatile at ordinary tem- peratures, is slowly absorbed, and, as its excretion keeps pace with its absorption, there is little dan- LOCAL ANnSEPTIGS. 57 ger that it will exert a poisonous action when used locally. The practice of dermatology involves a special knowledge of antisepsis, and the subject can be given only general consideration at this time, so that we must content ourselves with little more than a simple enumeration of some of the official substance's that are used, merely suggesting the number and variety of the available materials. Eesorcixol. — U. S. P. — (Eesorcinum U. S. P. 1890), a diatomic phenol that is usually referred to by its popular name, resorcin, was at one time extensively used in dermatologic practice, but is now seldom employed except for scalp diseases and sometimes internally. Pyrogallol. — U. S. P. — This is better known as pyrogallic acid and is a triatomic phenol, some- times used in dermatologic practice. AciDUM Salicylicum. — IT. S. P. — Salicylic Acid has been used to some extent as a local anti- septic, particularly in the form of dusting powders, diluted witli talcum, zinc oxid or boric acid. Sali- cylic acid is used extensively in dermatologic prac- tice, particularly in the form of ointment. It is only slightly soluble (1/310) in water. Pix LiQUiDA. — U. S. P. — Tar, a product ob- tained by the destructive distillation of the wood of one of several species of Pinus, has been widely used in the treatment of skin diseases, usually in the form of an ointment. Unguentui^i Picis LiQUiD^rE. — U. S. P. — Tar Ointment contains 50 per cent, of tar. Oleum Cadixum. — U. S. P. — Oil of Cade, or oil of juniper tar, is a product of the dry distilla- 5S PHARMACOPEIA AND PHYSICIAN. tiou of J'lmipm-us Oxycedrus and is closely allied to tar, being used in the same way, Balsamum Peeuvianum. — U. S. P. — Balsam of Peru will be referred to again imder expector- ants. Its antiseptic properties are probably due to the benzoic and cinnamic acids which it contains. It is used in dermatology,, either in ointment or in collodion. Naphthalenum. — U. S. P. — Naphthalene or naphtalin 'and Betanaphthol. — U. S. P. — Naphtol, are used in dermatologic practice, though the former, at least, has practically fallen into disuse for medici- nal purposes. Among other substances having antiseptic prop- erties, used locally, we have : Sulphur Peecipitatum. — U. S. P. — Precipi- tated Sulphur. This and the other official forms of sulphur will be mentioned also in connection with cathartics. Sulphur constitutes a most im- portant agent in the treatment of a number of skin diseases. It is applied either in the form of lo- tions or of ointments. For the former, precipi- tated sulphur is usually preferred, while in oint- ments either SuLPHUE SuBLiMATUM. — U. S. P.— Sublimed Sulphur, or Sulphur Lotum.— U. S. P.— AVashed Sulphur is used. In the official Unguentum Sulphueis. — U. S. P. — Sulphur Ointment, 15 per cent, of washed sulphur is di- rected to be used. This ointment is now only half the strength of that formerly official and is, there- LOCAL ANTISEPTICS. 59 fore, better suited as a mildly stimulating anti- septic application. SoDii Thiosulphas. — U. S. P. — Sodium Thio- sulphate, better known as sodium h3-posulphite, is another useful antiseptic that is now little used medicinally, except in dermatology. It is freely soluble in water and is usually prescribed in the form of a lotion. It is said to be particularly use- ful in the destruction of parasitic fungi which in- fest the skin. Glycerixum. — U. S. P. — -Glycerin is not alone useful as a mild antiseptic, but is also extensively used as a vehicle for many other substances in the treatment of skin lesions. Glyceritum Amyli. — U. S. P. — Glycerite of Starch is a preparation that was introduced many years ago to serve as an ointment base in cases in which lard or fat might prove objectionable. It was formerly used as a poultice in erythema, ery- sipelas, furuncle and various other local inflamma- tions of the skin, and may be considered as the prototype of the almost innumerable glycerin clay mixtures now offered. MERCURIALS. Hydrargyri Iodiddm Eubrum. — U. S. P. — Red Mercuric lodid or biniodid of mercury is the most active of all the official germicides and anti- septics. It is comparatively expensive, however, and is only slightly soluble in water. Hydrargyri Ciilohidum Corrosivum. — U. S. P. Corrosive Sublimate is by far the most popular and most generally used of all local chemical disinfect- 60 PHARMACOPEIA AND PHYSICIAN. ants and antiseptics. It is extremely poisonous and many fatalities have occurred from its use, even in the vagina and in the vi^ashing of wounds. Mercuric chlorid is slowly but completely solu- ble in 13 parts of water and in 3 parts of alcohol. The solubility of this substance in water is much facilitated by the presence of other soluble chlorids. This fact has been utilized in the preparation of the commercial tablets of mercuric chlorid that are sold for making antiseptic solutions. These tablets usually contain about 0.5 gm. (7.5 grains) each of mercuric chlorid and ammonium chlorid, the sal alembroth of the alchemists, which, when dissolved in 500 c.c. (1 pint) of water make a solu- tion of 1 to 1,000. This solution is useful for the disinfection of the hands, for walls and floors and for many fabrics that are not injured by water. Gauze impregnated with a solution of mercuric chlorid is often placed over small or closed wounds to prevent the access of bacteria. It is widely used as an antiseptic and disinfectant, but it is ex- tremely caustic and can not be applied to mucous membranes and to open wounds except in very dilute solutions, for fear of absorption. Mercuric chlorid attacks metals and must be avoided, therefore, with metallic instruments. It is a very popular insecticide and a number of the mercurials are used as parasiticides, notably for pediculi. For this purpose, however, the various ointments of mercury are more frequently used. Unguentum Hydrargyei. — U. S. P. — Mercu- rial Ointment contains 50 per cent, of mercury. Unguentum Hydrargyei Dilutum. — U. S. P. — Blue Ointment, a new addition to the Pharmaco- LOCAL ANTLSEPTIC^. 61 peia^ contains 33 per cent, of mercury and con- forms more closely to the proposed international standard for mercurial ointment. Another oint- ment that is sometimes used as a parasiticide is IJN^GUENTUjr Htdrakgyri Oxidi Eubki. — TJ. S. P. — Ointment of Eed Mercuric Oxid, or red pre- cipitate ointment, containing 10 per cent, of red mercuric oxid. ANTISEPSIS OF THE MUCOUS MEMBRANES. The antisepsis of the mouth is important, not only because of the infectious diseases pertaining to it^ but also because of the excellent opportunity that is afforded to micro-organisms to multiply there in enormous numbers on the particles, of food in the cavities of teeth or wedged between tliem. That this is true is shown by the putrid smell acquired by particles of meat which remain Init an hour or so in the mouth. The extent to wbich bacteria may increase may be inferred from the calculation, given by N"ovy, that 30,000,000,- 000 contain less than one-sixth of a milligram (1/400 grain) of organic matter. The main factor in securing antisepsis of the mouth is cleanliness. If the teeth are carefully cleansed and all organic matter removed, the bac- teria have less on which to thrive, and mild anti- septics then fully suffice to keep the number with- in bounds. Liquor Antisepticus. — U. S. P. — Antiseptic Solution is a new addition to the Pharmacopeia, containing 2 per cent, of boric acid with aromatic iiiitisej)tic volatile oils. It is designed to be used (i2 PHARMACOPEIA AND PHYSICIAN. as a mildly antiseptic lotion or wash,* as are numerous similar proprietary preparations. It must be remembered that the name of this official antiseptic solution is a misnomer in effect, if not in fact, since it possesses, at most but very weakly antiseptic properties, being a detergent rather than an antiseptic. Antiseptic Solution is also useful as a gargle, preferably diluted with an equal quantity of water. The use of solution of hydrogen dioxid as a spray or gargle, as well as its use in connection with the official antiseptic solution, has been mentioned. PoTAssi Chloras. — U. S. P. — Potassium Chlor- ate, while not a particularly active antiseptic, has long been favorably known to be a desirable addi- tion to gargles and mouth washes. It is soluble in 16 parts of cold water and is generally used in saturated solution, from which, traces of chloric acid may possibly be liberated. Alum and boric acid are also useful as gargles. Free chlorin is an effective disinfectant and it may be utilized in the form of a gargle, being lib- erated by the action of hydrochloric acid on po- 4. The official antiseptic solution is slightly acid. When an alkaline antiseptic month wash is desired it will be w'ell to nse the "Alkaline Antiseptic Solution" of the National Foi-mularly. Either one of these preparations can be pre- pared readily by any trained pharmacist. They are inex- pensive and should be given the preference over the various nostrums that are not alone exploited as local antiseptics, but are also advertised as sure cure remedies for a number of in- testinal disorders. LIQUOR ANTISEPTICUS ALKALINUS, N. P., represents 3.2 parts each of potassium bicarbonate and sodium benzoate, 0.8 parts of sodium borate in a mixture of alcohol, glycerin and water, flavored with thymol, eucalyptol, oil of peppermint and oil of gaultheria and colored red with tincture of cud- bear to make 100 parts. LOCAL ANTISEPTICS. 63 tassium chlorate. This occurs in such a mixture as tlie following : IJ. Potassii chloratis 3iss 61 Acidi hydrochlor 3i 4 AquiB q. s. ad §iii 100 1 M. Sig. : Use as a gargle. After the use of any of these gargles the mouth should he well rinsed with water to prevent injur}- to the teeth. The antisepsis of the nasal passages is usuall}' accomplished hy thorough cleansing with warm sa- line solution (0.9 per cent.), nine grams (135 grains) of sodium chlorid to a liter (quart) of water, or hy a mild alkaline solution made by add- ing nine grams (135 grains) of sodium bicarbon- ate to the saline solution Just mentioned; after which a mildly antiseptic solution, such as the of- ficial properly diluted, is used as a spray or douche, or, in lieu of this, one-tenth of 1 per cent, of phenol may be added to the saline douche, but the latter is not recommended as a routine practice." It may be permissible here to enumerate some of the substances that have been used as mild anti- septic applications to the mucous membranes. AciDUM BoRicuM. — U. S. P. — Boric Acid, gen- erally referred to as boracic acid, is quite free ."). The i)liaimafoi)pia of the German IIosi»itaI, Philadel- phia, (.-ontains a foi'rmila for an alkaline antiseptic tablet that has foiiiul favor with some. It contains 0.'17> ^m. (about 4 Ki-ains) each of sodium bicarbonate, sodium borate, sodium chlorid and sodium phenolsulpbonate with 0.005 Km. (about 0.1 minim) of oil of cinnamon. One of these tablets (the same mixture can also be directed in powder) is to be dissolved In sI.k tablespoonfuls of recently boiled water and (ised as a wa.sh for the nose. 64 PHARMACOPEIA AND PHYSICIAN. from toxicity. It is soluble in about 16 parts of water and is but slowly absorbed. Glycekitum Boroglycerini. — U. S. P. — Glycerite of Boroglycerin, contains 30 per cent, of boric acid and has the same uses as that acid. SoDii Boras. — U. S. P. — Sodium Borate, or borax, has an alkaline reaction and is sometimes preferred to boric acid on this account. It is solu- ble in sixteen parts of water. SoDii Chloridum. — U. S. P. — Sodium Chlorid, common table salt, has been in use as an antiseptic from time immemorial; its uses are well known, and the only reason we have for presenting it here is to call attention to the fact that the Pharmaco- peia recognizes it as a valuable article of the ma- teria medica and provides certain standards and tests for purity. SoDii Phen^olsulphonas. — U. S. P. — Sodium Phenolsulphonate, the sodium sulphocarbolate of former editions of the Pharmacopeia, is another mild antiseptic that has limited but well-defined uses. Practically all the salts of the alkalies have anti- septic properties, but it is obviously not necessary to recount all of them at this time. Complete disinfection of the nose, mouth, throat, vagina and urethra is not practicable, and is not even necessary; the main thing to be sought is the cleansing of those regions from pus and organic matter on which bacteria thrive. Mucous mem- branes decompose the solution of hydrogen dioxid with such copious evolution of oxj-gen that it can not be used in the nose, and because of this rapid action by the mucous membrane itself a large LOCAL ANTISEPTICS. 65 amoimt frequently repeated is necessary to com- pletely disinfect such cavities." The antisepsis of the eye is confined largely to the use of camphor water, boric acid and sodium borate. In virulent affections more active antisep- tics are sometimes indicated; in these cases weak solutions of mercuric chlorid, copper sulphate, zinc chlorid, silver nitrate or formaldehyd are used. These substances, however, are all extremely irri- tating and great caution is required. Their use by the general practitioner is not advised.^ 6. For use in the vagina, where a simple detergent and antiseptic action is sought, the official Liquor Cresolis Com- positus in 0.5 to 1 per cent, solution will be found to be all that is required. When an astringent effect is desired the following formula for an antiseptic astringent powder will be found to answer the purpose very well : R. Sodii boratis Si 601 Alumin. exsicc ox 40 1 Thymol, I Phenol, Eucalyptol, Olel gaultherise, fia gr. viii |5 M. SIg. : A heaping teaspoonful to be dissolved in one liter (1 quart) of hot water, to be used as a douche. Pulvis Antisepticns. N. P., contains 12.5 parts of zinc sulphate, 86.6 parts of boric acid. 0.5 part of salicylic acid and 0.1 part, each, of phenol, eucalyptol, menthol and thymol. It may be used in the same way and for the same purposes as the prescription given above. Tyree's Antiseptic Powder formerly had a considerable vogue among physicians ; since the exposure of its true char- acter by The Journal of the American Medical Association (Oct. 20, 1906, p. 1316), it Is to be hoped that physicians will depend on it less than they did. Campho-phenique Powder affords another example of ex- traordinary discrepancy between the formula claimed by the manufacturer and the composition shown by analysis. See Thk .TounxAL A. M. A., April 20, 1007, p. 1365. 7. The method of using boric acid in the eye varies greally, but usually a 2 per cent, solution of boric acid in equal parts of distilled wafer and camphor water will be found to be snfflcient. When it is desired to use sodium borate In connection with boric acid the following will be found satisfactory' : R. Acid! borlcl gr. xv 1 Sodii boratis gr. xxx 2 Aqua; dest.. AqujE campborii'. fia ,?iss 50 66 PHARMACOPEIA AND PHYSICIAN. Burns or scalds resulting in. destruction of the skin should be treated antiseptically. Treves di- rects that the burn be washed with a solution of hydrogen dioxid and then with a .solution of boric acid; the vesicles are then opened with an aseptic needle and the surface dusted with iodoform and dressed with aseptic cotton. PoTAssii Permanganas. — U. S. P. — Potassium Permanganate, already referred to under the head of general disinfectants, is often considered to be devoid of antiseptic properties because of the readi- ness with which it oxidizes all organic matter. It is true that potassium permanganate is readily de- composed by the organic matter with which it first comes in contact, and that it would be unusual in- deed to find bacteria the only form of organic mat- ter present in any one case. When we remember, however, that a very large number of bacteria represent but an infinitesimally small amount of organic matter, we will appreciate why potassium permanganate is capable of destroying vast num- bers of micro-organisms in those cases in which its action can be confined to them. This substance finds its greatest usefulness as a local apjDlication in rendering foul ulcers odorless. For this purpose a fairly strong solution, 2 per cent., is freely used as a wash. Much weaker solu- tions are sometimes used with great benefit as urethral irrigations in gonorrhea and as vaginal douches. A hot 1 per cent, solution of potassium permanganate will be found extremely useful as a deodorizer for instruments after use in the vagina while awaiting sterilization. LOCAL ANTISEPTICS. 67 Potassium permanganate destroys some alkaloids miicli more quickly than others, e. g., morphin more readily than strychnin. It can not enter the circulation ; hence, when swallowed, it can act only on the substances found in the stomach. Obvious- ly it is not suited for hypodermic injections. CHAPTER III. INTERNAL ANTISEPTICS. The great strides made in the use of antisep- tics, after Lister had employed them in surgery with such brilliant results, led to the hope that they might be made available for limiting the de- velopment of bacteria in various parts of the hu- man body. From time to time clinicians have re- ported favorable results from the use of internal antiseptics in such diseases as typhoid fever, but- at the present time it is generally acknowledged that complete disinfection of the intestinal tract is impossible and that the treatment of constitutional diseases by means of antiseptics is possible only in a few isolated cases; for example, in malarial fever by quinin, in articular rheumatism by sali- cylic acid and its compounds, and in syphilis by means of mercurials. Quinin has been shown to have a peculiarly selective and destructive action on the protozoon which causes malarial fever, and perhaps mercury and salicylic acid may possess similar selective action against the agents produc- ing syphilis and certain forms of rheumatism. It is not probable that any agent will be found which will protect the blood and tissues against many species of bacteria, but we may discover substances, each with a specific action analogous to that of quinin in malaria. The discussion of in- ternal antiseptics will be limited, therefore, to the substances just mentioned — quinin, mercury and INTERNAL ANTISEPTICS. 69 salicylic acid — and substances used as antiseptics in the alimentary canal. It is impossible to form a correct idea of the probable effect of an internal antiseptic without having at least some idea of the organisms on which, it must act. Nuttall and Thierfelder took guinea-pigs from their mother by Cesarean section under aseptic conditions, and fed one of them on sterilized food for thirteen days, during which it continued to thrive, but Schotelius found that chickens died of starvation when fed only on sterilized food. G. X. Stewart accepts Nuttall and Thierf elder's re- sults as demonstrating that animals, including man, exist, despite the bacteria which infest the alimentary canal from a few hours after birth until death. Strassburger concludes, from a review of the extensive literature pertaining to intestinal bac- teria, that Nuttall and Thierfelder have shown that no single process of alimentation is absolutely dependent on bacteria, but that the chief function of certain of them, notably the colon bacillus, which is always abundantly present, is actually to destroy other bacteria and thus to protect the host against those disease germs which, may gain en- trance to the alimentary canal. The destruction of all the bacteria in the alimentary canal at any one time, therefore, might prove fatal, in that any disease germs which chanced to gain access to the intestine could so multiply as quickly to destroy the life of the host. The proof that Ijacteria do play some part in the process of digestion is found in the fact that man 70 PHARMACOPEIA AND PHYSICIAN. can digest the cellulose of delicate vegetables to a limited extent, though he secretes no enzyme cap- able of splitting cellulose, which, therefore, must be split by bacteria present which have been shown to possess that power. Then, too, certain crj^stal- line bodies other than leucin and tyrosin have re- cently been found among the ultimate products of digestion, and as none of the known digestive enzymes are capable of forming these bodies they likewise must result from bacterial action. While we must admit that bacteria are concerned in digestion, we have no positive information at the present time as to how important a part they ac- tually take. It has been shown that the colon ba- cillus, which is universally present in milk, inhib- its, to a certain extent, the action of putrefactive bacteria, and it is well known that untreated milk of good quality is more digestible than is the same milk after sterilization.^ 1. Tests made on the several constituents of milk show that they have no power to inhibit putrefaction, though such a power is unquestionably possessed by fresh milk. That this is due, at least in part, to certain bacteria nor- mally present in the milk is shown by the fact that sterilized milk putrefies much more rapidly than untreated milk on the addition of the bacillus of putrefaction (B. piitriflcus) : but if with the Bacillus putrificiis the colon bacillus be added to sterilized milk, the milk acts as does normal milk, thus proving that the colon bacillus is actually capable of inhibiting the development of certain bacteria. It is. of course, possible that fresh milk also possesses antibacterial properties which are destroyed by the sterilization. These conditions help to explain why sterilized milk Is not so wholesome as new milk of good quality. It must be remem- bered, however, that milk is an excellent culture medium in which a great many bacteria are normally present, and that if it be allowed to stand in a warm place for some hours the micro-organisms multiply to such an extent that the milk is wholly unfit for use, and we do not wish to be mis- understood as implying that the colon bacillus is an un- mixed blessing. Whilst during health the micro-organism probably does not emigrate from the uninjured intestine it may do so in states of lowered general resistance, or in the IXTERNAL AyTISEPTIGS. 71 We are thus forced, by this and other like evi- dence, to conclude that it is by no means desirable to render the intestines sterile and that, instead of attempting intestinal antisepsis in the broader sense, we should seek rather to modify the flora in that region than to destroy it. Various methods have been proposed, from time to time, for determining the relative degree of putrefaction taking place in the intestines, but at the present time it is not positively known what constitutes the best method at our disposal for doing this. The procedure most frequently em- ployed, one which is considered to afford a fair es- timate in a large proportion of cases, consists in estimating the ethereal sulphates in the urine. Strasslnirger claims that weigliing the bacteria after separation from the feces and drying affords the surest means of estimating the number of bacteria present. Others count the number of colonies which can be cultivated from a milligram of feces, but this has been shown to be unreliable. In view of the fact that laboratory methods are far from satisfactory in determining the number of the sev- eral varieties of bacteria present in the feces, the general practitioner will probably be obliged, for some time to come, to depend largely, if not en- tirely, on the clinical data presented by each in- dividual case. prpsenre of defects of the intestinal epithelium, and mav s've rls sulphatis.. grs. Ixxv .')) Fluid oxt. glvcvrrbl/.ii" .3lv 15 Syrn|)l .■t .■Ilx. aromat. aa q. s 3111 lOO] so PHARMACOPEIA AND PHY8ICfAN. fever is expected to occur, and the dose repeated in two hours, the maximum effect of the quinin on the organism is obtained and the chill is usually prevented. The quinin existing in the blood at the time that sporulation occurs destroys the newly liberated organisms and the blood is rendered asep- tic so far as that particular organism is concerned. This process has to be repeated at intervals, some- times for three or four weeks. Salicylic acid is closely related, chemically and pharmacologically, to phenol. Salicjdates of the alkalis are decomposed in the stomach and sali- cylic acid is liberated. Salicylic acid is very slightly volatile; hence it does not penetrate so readily as phenol, and that property, non-volatility, explains its more lasting antiseptic action. It is much more potent than phenol in preventing the action of enzymes. It is irritant to mucous surfaces, often inducing nausea, but it is not nearly so caustic as phenol. Strong solutions applied to the skin cause the destruction of tissue^ as in the case of warts and corns. The salicylates are practically valueless as ehologogues, though they may have some slight effect on the production of bile. Salicylic acid and the salicjdates cause increased metabolism and increased production of heat, but they also cause increased blood pressure and dila- tation of the cutaneous vessels. The result of these two actions taken together is a greatly increased cutaneous circulation, with increased loss of heat and consequent fall in the temperature. This ef- fect on the peripheral vessels may also explain the IXTERNAL ANTISEPTICS. 87 rash sometimes observed after the use of the sali- cylates. Salicylic acid circulates in the blood as sodium salicylate. This in sufficient concentration is an antiseptic, but the salt passes too rapidly from the intestine to permit of its acting beneficially there, and it is excreted from the blood so rapidly that it is never in sufficient concentration to possess any antiseptic action. The salic3dates pass into nearly all the secretions of the body and are particularly abundant in the urine as salicjduric acid. Gaglio explains the action of the salicylates in rheumatism by the rapid excretion into the joints by the s3Tiovial membrane by which the salt is se- creted from the blood. Salol, or phenjd salicylate, is much less soluble in water than is sodium salic3date. It is decom- posed in the stomach very slowly, but much more rapidly in the intestine, with the liberation of phenol and salicylic acid. Owing to the slight solubility of salol in the stomach, it may be used to coat capsules of sodium salicylate which will then pass into the intestine without causing gastric disturbance. The liberated phenol exerts its ac- tion, and it may give rise to toxic symptoms if too hirge a dose of salol has been used. Salicin is converted in part into salicylic acid when taken internally, but much of it escapes de- struction and is excreted in tlie urine unchanged. ACIDUM SalicylicuiM. — U. S. P. Average dose 0.5 gm. ,{7^2 grains). SoDii Salicylas. — U. S. P. Average dose: 1 gm. (15 grains). Ammoxii Salicylas. — U. S. P. 88 PHARMACOPEIA AND PHYSICIAN. Average dose: 0.25 gm. (4 grains). LiTHTi Salicylas. — U. S. P. Average dose: 1 gm. (15 grains). Strontii Salicylas. — U. S. P. Average dose: 1 gm. (15 grains). Phbnylis Salicylas.— U. S. P.— Salol (U. S. P., 1890). Average dose: 0.5 gm. (7% grains). Methylts Salicylas. — U. S. P. Average dose: 1 c.c. (15 minims). Oleum Betul.t:. — U. S. P. Average dose: 1 c.c. (15 minims). Oleum Gaultheri^. — U. S. P. Average dose: 1 c.c. (15 minims). Salicinum.— IT. S. P. Average dose: 1 gm. (15 grains). The salicylates of ammonium, sodium lithium and strontium may be dispensed in solution, but the other salicylates and salicylic acid itself are best dispensed in capsules. The salicylates were employed at one time as antipyretics, and they have also been used in place of quinin in malaria, but they have no curative value in that disease and are not so employed at present, having been superseded by less dangerous antipyretics. In acute articular rheumatism the salicylates enjoy a reputation akin to that of quinin in ma- laria. As previously stated, they are excreted into the urine, and, as they exert their irritant action on the kidneys, they must be used only with great caution when renal inflammation exists, as they are capable of giving rise to the gravest symptoms. Whether the salicvlates should be used when car- IXTERXAL AXTI8EPTWS. 89 diac symfjtoms arise is an unsettled question. They should certainly be used only with caution in such an event. Any of the salicylates may be used, but the sodium salt is much the most popular. Large doses are often necessary in the beginning of treatment, but these must be diminished as the symptoms of the disease abate. Sodium salicylate may be prescribed as follows: I^. Sodii salicylatis Siiss 10| Ft. eapsulae No. xx. Sig. : Two capsules every three hours. It may be prescribed in liquid form somewhat as follows : IJ. Sodii salicylatis Siiss 10| Syrupi aurantii flgiss 50 Aqua;, q. s. ad fl^iii ^OO] Misee. Sig.: Two teaspoonfuls every three hours. Such doses are too large for continued use, and are to be regulated according to the needs of the case. The capsules may be coated with salol after the manner described on page 87 to prevent gastric disturl)ance. The oil of wintergreen or oil of sweet birch is sometimes borne for a time when the sodium salt causes nausea. These oils may be given in capsules mixed with a bland fixed oil. The mercurials will be discussed under the sub- ject of alteratives. CHAPTEE IV. GENEllAL TONICS. Tonics are defined by Gould as ''medicines or agents wliich promote nutrition and give tone to the system.'^ Since these conditions are met by any improve- ment in the general health, the use of the term is often an admission of our want of exact knowledge of the mode of action of the drugs or remedies so classed. Strychnin increases the reflexes and may thus improve the muscular tone. Bitters may increase the impaired appetite and digestion, which will, of course, improve the general condition, hence these agents may be spoken of as tonics ; and, if we were not acquainted with the organism which causes malarial fever, and with the effect of quinin on that organism, but merely knew this condition to be relieved by quinin, we would be justified in attributing the action to the tonic effect of quinin. Therefore, as our knowledge of the exact mode of action of the various remedies of this group increases, the importance of the term itself will correspondingly decline. Among the tonics we may include hematinics, or agents which assist in the regeneration of blood, including iron, arsenic, codliver oil and hypophos- phites ; the alteratives, the mode of action of which • is unknown, and stomachics. GENERAL TONICS. 91 HEMATINICS. Ordinary food is the most important of the hematinics, if, indeed, we have any others which are of considerable importance, especially if we ac- cept the definition which includes iron in any as- similable form as food. IRON. Most of the iron in the body, amounting to from 2^ to 3 grams (38 to 45 grains) occurs as a con- stituent of hemoglobin, an extremely complex sub- stance in which the iron is much more firmly bound than in the ordinary iron albuminate. In addition to that found in the blood, some iron is held in reserve in the liver and spleen in the form of the ferratin of Schmiedeberg (not the commer- cial Ferratin) and the cells of the body also con- tain small amounts of iron. The subject of the absorption and assimilation of iron has been the subject of many investigations, and the results have often proved contradictory, but it may be accepted now as definitely established that both the organic and the inorganic forms of iron are absorbed from the small intestine, that they are carried by the blood io the liver and the blood-building organs and are utilized in the form- ation of hemoglobin.^ This occurs even with doses of inorganic iron which are incapable of causing corrosion of the mucous membrane of the stomach prior to absorp- tion. 1. Prior to the discovery by Wohlor of the synthesis of such a comparatlvoly simple substance as hlppurlc acid In the kidney It was supposed that no synthesis could occur In the animal body. 92 PHARMACOPEIA AND PHYSICIAN. Dogs were rendered anemic by giving them food poor in iron and subjecting them to repeated hemorrhage. After the reserve iron of the liver was greatly diminished the animals were given the same kind of food poor in iron, but to the food of some was added iron in various forms, inorganic in some cases, organic in others. Those which received only the food poor in iron were unable to make good the loss of hemoglobin, but those re- ceiving the same kind of food with the addition of any form of iron not only increased the hemo- globin of their blood, but added to the reserve store of the liver. Bunge's theory that inorganic iron is useful in chlorosis only because it combines with the hydrogen sulphid in the intestine and thus spares the iron of the food from being rendered non-absorbable, has been proved erroneous, as no hydrogen sulphid could be found in the duodenum, where iron is mainly absorbed, and the other heavy metals, such as bismuth, combine with hydrogen sulphid, but they have no such aption as the inor- ganic salts of iron in anemia. Even if Bunge's theory concerning the absorb- ability of organic forms of iron were correct his warning against the nostrums containing iron should not be forgotten. Bunge specifically states that meat and other foods are decidedly preferable to those preparations. Abderhalden isolated from spinach a compound similar to hematogen, and Bunge's remarks apply with equal force to those preparations which con- tain iron of vegetable origin. It has been shown that a part at least of the GENERAL TONICS. 93 organic iron- of the food is broken clown into sim- pler forms during its passage through the intes- tinal wall. This and the fact that ferratin of the liver (the probable precursor of hemoglobin) is not so stable as the food iron, point strongly to the utilization of inorganic iron in the formation of l)emoglobin. While much diversity of opinion has been held concerning the precursor of hemoglobin, the ques- tion is of less therapeutic importance than it would seem at first thought, in view of the fact that it is a comparatively infrequent occurrence that a pa- tient is unable to take a sufficient amount of iron in the food. We have devoted so much space to the subject mainly because the manufacturers of cer- tain nostrums, used as hematinics, are prone to quote such results as those obtained in Bunge's laboratory only so far as they show that organic iron preparations are assimilable while the inor- ganic are not. OFFICIAL TREPAEATIONS OF IRON. The list of official preparations of iron is a long one and comprises a number of substances that are not generally used as hematinics. 2. Cushny : 'Tharmacology and Therapeutics" says : "The words organic and inorganic in connection with these prepa- rations have no reference to the combination to wliicli iron is attached, but to the method of attachment. Thus the acetate and albuminate of iron are both classified among the inor- ganic iron compounds, because they are capable of dissocia- tion, and the iron is precipitated by ammonium sulphld. Masked iron is a preferable term for organic iron, but has not been so widely used. A large number of the proteid com- pounds that have been Introduced in the last few years promise to be rel(>gated to merited oblivion in the near future. The albuminate of iron and the peptonate of iron are generally prepared by the action of the chlorid on egg albumin or on i/cptoiu', and dllTer very considerably in the percentage of Iron, 'ilicse prei)arations are not organic iron In the sense dellned above, for the iron can be split off easily, and Is precipitated by sulphids almost as readily as the ordinary salts." 94 PHARMACOPEIA AND PHYSICIAN. The use of the salts of iron as astringents will be referred to in Chapter VIII. Probably the most widely used of the several ])reparations of iron is TiNCTUEA Ferri Chloridi. — U. S. P. — This preparation contains 35 per cent, by volume of solution of ferric chlorid. It should be prepared at least three months before being used. Tincture of ferric chlorid, or tincture of iron, as it was for- merly called, has long been considered one of the most efficient of the inorganic iron preparations. Average dose: 0.5 c.c. (8 minims). Ferri Sulphas and Ferri Sulphas Granu- LATUS. — U. S. P. — These differ only in the size of the crystals; they consist of ferrous sulphate con- taining 7 molecules of water of crystallization. Ferrous sulphate is soluble in less than one part of water, but is insoluble in alcohol. Average dose: 0.2 gm. (3 grains). Ferri Sulphas Exsiccatus. — U. S. P. — Ex- siccated Ferrous Sulphate is a grayish-white pow- der that is slowly but completely soluble in water. About 65 grams of the exsiccated preparation are equivalent to 100 grams of the granulated. Average dose: 0.12 gm. (2 grains). PiLULiE Aloes et Ferri. — U. S. P. — Each pill contains 0.07 gm. (about 1 grain) each of exsic- cated ferrous sulphate, purified aloes and aromatic powder. Average dose: 2 pills. PiLULJS Ferri Carbonatis. — U. S. P. — This preparation is variously known as Blaud's pills, Griffith's pills or Vallet's pills. Each pill contains GENERAL TONICS. 95 about 0.06 gm. (1 grain) of ferrous carbonate, ^yith potassium sulphate, althea, tragacanth and gl)'cerin. Average dose: 3 pills. Ferri Carbonas Saccharatus. — U. S. P. — The saccharated carbonate of iron should contain not less than 15 per cent, of ferrous carbonate. Average dose: 0.25 gm. (4 grains). Massa Ferri CARBOisrATis. — U. S. P. — Mass of ferrous carbonate, better known as Vallet's mass, contains nearly 5 per cent, of ferrous carbonate. Average dose: 0.25 gm. (4 grains). MisTURA Ferri Composita. — U. S. P. — Com- pound iron mixture, or Griffith's mixture, is much more popular in England than in this country. It contains freshly precipitated ferrous carbonate sus- pended in a mixture of potassium sulphate, myrrh, S3Tup, spirit of lavender and rose water. Average dose: 16 c.c. (4 fluidrams). Of the several official preparations containing ferrous carbonate the pill of ferrous carbonate, more generally known as Blaud's pill, is probably the most efficient and most satisfactory. This pill should be freshly prepared and should not contain free or unchanged ferrous sulphate or potassium carbonate. The practice that has been adopted by some manufacturers of massing these pills witli- out allowing the chemical reaction to take place is a reprehensible one, as it is not at all probable that the necessary reaction will take place in the acid medium of the stomach. Should a nasfont ferrous carhoiiaic.' be desired it can readily he provided by using the foHowing solution : no PHARMACOPEIA AND PHYSICIAN. Ferrous sulphate 3.2 gm. 50 gr. Potassium carbonate 1.6 gm. 25 gr. Distilled water 2.0 c.c. 30 min. Glycerin to make 100.0 c.c. 3 fl.oz. Dissolve the potassium carbonate in 45 c.c. of glycerin and add this to the solution of ferrous sulphate, made by dissolving the latter, by means of heat, in the water and subsequently diluting ^ith 40 c.c. of glycerin. Finally, add sufficient glycerin to make the mixture measure 100 c.c. Each teaspoonful (5 c.c.) of this mixture, when diluted with half a glass of water, will produce a quantity of freshly precipitated ferrous carbonate that is equivalent to one Blaud's pill. All the preparations of ferrous carbonate have the decided advantage over the previously men- tioned preparations of iron that they are not astringent and, therefore, are not likely to cause digestive disturbances. Another preparation that is free from the ob- jectionable feature of being astringent is : Ferrum Eeductum. — U. S. P. — Eeduced Iron occurs as a fine grayish-black lusterless powder without odor or taste. It is insoluble in water and in alcohol and, therefore, is generally directed to be dispensed in powders, capsules or pills. Average dose: 0.05 gm. (1 grain). SCALE SALTS OF IRON. Feeri Citras. — U. S. p. — Ferric Citrate occurs in thin garnet-red scales that are slowly but com- pletely soluble in water. Average dose: 0.35 gm. (4 grains). Ferri et Ammonii Citras. — U. S. P. — Iron and Ammonium Citrate is much more freely solu- GENERAL TONICS. 97 ble in water than the simple citrate, an advantage that it is not likely to lose on keeping. Average dose: 0.25 gm. (4 grains). Feeei et Ammoxii Tartras. — U. S. P. — This occurs in thin transparent scales varying in color from garnet red to reddish brown. It is freely soluble in water, but insoluble in alcohol. Average dose: 0.25 gm. (4 grains). Ferri et Potassii Tartras. — U. S. P. — This is very similar in physical properties to iron and am- monium tartrate. Average dose: 0.25 gm. (4 grains). Ferri et QuiNiNiE Citras. — U. S. P. — Iron and Quinin Citrate contains about 11.5 per cent, of quinin, and ferric citrate corresponding in amount to 13.5 per cent, of metallic iron. It is slowly but completely soluble in water. Average dose: 0.25 gm. (4 grains). Ferri et QuiNiNiE Citras Solubilis. — U. S. P. — This preparation has practically the same composition as iron and quinin citrate, but with ammonium citrate present to insure its solubility. Average dose: 0.25 gm. (4 grains). Ferri et Strychnine Citras. — U. S. P. — Iron and Strychnin Citrate contains aljout 1 per cent, of strychnin. It is readily and completely soluble in water. Average dose: 0.12 gm. (2 grains). These several scale preparations of iron are com- paratively free from astringent properties, are gen- erally freely soluble in water, do not attack the teeth, and are not obnoxious to the taste. They are preferably directed to bo dispensed in aqueous 98 PHARMACOPEIA AND PHYBlCIAy. solution, with or without the addition of elixir or some other flavoring admixture. LIQUID PREPARATIONS OF IRON. ViNUM Ferri.— U. S. P.— This contains 4 per cent, of iron and ammonium citrate with syrup and white wine, flavored with tincture of sweet orange peel. Average dose: 8 c.c. (2 fluidrams). ViNUM Ferri Amarum.— U. S. P.— This prep- aration contains 5 per cent, of soluble iron and quinin citrate with syrup and white wine, flavored with tincture of sweet orange peel. Average dose: 8 c.c. (2 fluidrams). Gltceritum Ferri Quinine et Strychnine Phosphatum.— U. S. P.— The Glycerite of the Phosphates of Iron, Quinin and Strychnin con- tains 8 per cent, of the soluble ferric phosphate, 10 per cent, of quinin and 0.08 per cent, of strychnin with phosphoric acid, glycerin and water. Average dose: 1 c.c. (15 minims). Strupus Ferri, Quinine et Strychnine Phosphatum. — U. S. P. — This syrup contains 25 per cent, of the glycerite of the phosphates of iron, quinin and strychnin in syrup. Average dose: 4 c.c. (1 fluidram). Elixir Feeri, Quinine et Strychnine Phosphatum.— TJ. S. P.— This popular ferrugin- ous bitter tonic contains soluble ferric phosphate, quinin and strychnin. The average dose given below contains nearly 0.07 gm. (1/16 gr.) of sol- uble ferric phosphate, 0.035 gm. (7/12 gr.^ of quinin, and 0.001 gm. (1/60 gr.) of strychnin. Average dose: 4 c.c. (1 fluidram). GENERAL TONICS. 99 LiQUOE Feret et Ammonii Acetatis. — U. S. p. — This Solution of Iron and Ammonium Acetate, more popularly Imown as Basham's mixture, con- tains a double salt of iron and ammonium acetate and is directed to be made by mixing 4 parts of tincture of ferric clilorid, 6 parts of diluted acetic acid, 50 parts of solution of ammonium acetate, 12 parts of aromatic elixir, 12 parts of glycerin and a sufficient quantity of water to make 100 parts. This preparation, being quite dilute, is not very stable and should be freshly prepared when wanted. Average dose : 16 c.c. (4 fluidrams) . There are two additional preparations of iron that, while they are not prescribed as hematinics, might well be mentioned in this connection. ANTIDOTES FOR ARSENIC. Ferri Hydroxidum. — U. S. P.- — This is the hy- drated oxid of iron of the previous Pharmacopeia which is directed to be made by precipitating 100 parts of solution of ferric sulphate with 133 parts of ammonia water that has been diluted with 1.000 parts of cold distilled water. The resulting precipitate is directed to be washed until free from .soluble sulphates. This preparation is not par- ticularly adapted for extemporaneous preparation. and, as it does not keep well, the following has been added as an efficient, extom.porancous arti- dote for arsenic : Ferri Htdroxtdttm cum Maonesti Oxido. — TT. S. P. — This is dirocted to bo made by diluting -10 parts of solution nf ferric siilpliate witli 125 parts of water, and kept in a largo \vell-stop]-)oro(l LOfC. 100 PHARMACOPEIA AND PHYSICIAN. bottle. The magnesia mixture is directed to be made by rubbing 10 parts of magnesium oxid with suflScient water to make a smooth and thin mixture, then diluting it to about 700 parts. When wanted for use the magnesium oxid mixture is to be well shaken and then gradually added to the solution of ferric sulphate, and the resulting mixture again well shaken. Average dose: Arsenical antidote, 120 c.c. (4 fluidounces). INDICATIONS FOE IRON. Hematinics are demanded when the amount of blood or of any of its essential constituents have been greatly reduced. After severe hemorrhage involving the loss of less than half the blood, regeneration takes place rapidly, if the general condition of the patient is otherwise good and the food ample. Iron has long been used in chlorosis, and ex- perience has shown that it is more useful in those forms of anemia in which the loss of hemoglobin is greater than that of red blood cells; in other words, when the red blood cells present, whether in normal or diminished number, are individually poor in hemoglobin. As to the form of iron to be given, of first im- portance is the selection of food. Eeference to the table given below will enable the physician to com- pute approximately the amount of food iron which the patient is receiving, and by computing the daily normal loss at 10 milligrams he can see about how much of this is left for the regeneration of hemo- GENERAL TONICS. 101 globin. The figures given are for material as usually served at table^ and are only approximate. If the food contains an insufficiency of iron, he- matin, or one of the inorganic forms of iron will prove beneficial. In our choice of medicinal iron we must be guided by the individual case in select- ing the one which causes the least disturbance of the digestion. In the absence of fever it will sel- dom occur that the patient can not take a selected diet containing an ample supply of iron. If the appetite and digestion are deficient, stomachics are indicated. Inorganic iron very often gives better results in the first few weeks of the administration than it does later, whicli may possibly be explained by its interference with the dijrestion — a matter to be 3. The following table Is based on computations made by Bunge of the iron content in dried substances. The figures given here serve as an indication of the approximate content, in milligrams, in the amount of each article as ordinarily served at meals : Teacupful of boiled oatmeal 0.2- 0.5 Teacupful of boiled rice 0.2- 0..5 r>00 gm. of grapes (about one pound) 0.4- 1.0 Two apples 0.1- 0.4 Two oranges 0.1- 0.5 Yolk of two eggs 2.0- 5.0 Glass of cow's milk 0.4- 1.0 Four small slices of white bread, about 100 gm. . . . 0.5- 1.0 Four slices of whole wheat bread 1.0- 3.0 Plate of pea soup, thick 0.4- 2.0 Slice of roast beef, about 50 gm 2.0- 6.0 Teacupful of mashed potato 0.3- 1.5 Teacupful of boiled cabbage 0.5- 3.0 Two heaping tablospoonfuls of spinach 2.0-10.0 Two heaping tablospoonfuls of boiled carrots 0.3- 1.5 Two heaping tablospoonfuls of string beans 0.4- 2.0 Two heaping tablospoonfuls of green peas 0.3- 1.5 SI.^ to eight leaves of lettuce 0.1- 1.0 Four to sl.x stalks of asparagus 0.5- 3.0 Ton or twelve almonds, blanched 1.0- 2.0 Ton or twelve almonds, whole 2.0- 5.0 Ten or twelve hazel nuts 1.0- 4.0 Four to six flgs 0.5- 2.0 Slice of "blut-wurst," about 100 gm 10.0-25.0 Sugar and whit'- of egg are froo from Iron. 102 PHARMACOPEIA AND PHYSICIAN. guarded against carefully. Large doses, if they do not disturb the digestion, are often required. While warm blood may be tolerated by some in- dividuals, the aversion to it is frequently uncon- querable and hematin seems to be equally service- able in any case.* The etiology of some of the anemias is so ob- scure that treatment must be mainly empirical, but we may feel reasonably certain that we shall do more harm than good if we depend on the nos- trums so glowingly advertised instead of directing our efforts toward improving the appetite and di- gestion. The selection of a proper diet, together with proper doses of inorganic iron in most cases, or of organic and inorganic iron in comparatively few cases in which they are needed, will usually bo found to be all that is required. When iron tends to cause constipation, laxatives must be employed, preferably one of the prepara- tions of cascara sagrada, or the pills of aloes and iron, one of which may be given three times daily. As examples of the innumerable combinations in which iron may be prescribed we give the follow- ing: B. Ferri sulphatis exsic 3i 4| Extract! nucis vom. | Extract! rhamni pursh., aa. . . .gr. xv 1| ' M. Ft. pil. No. Ix. Sig. : One pill half an hour after meals. Eeduced iron or ferric citrate may be substi- tuted for the dried ferrous sulphate, and a slightly larger amount of aloes (30 grains — 1.3 gm.) can be used in place of the extract of cascara sagrada. 4. A practical method for the economic preparation of a hematin product was described by Torald Sollmann, in the Am. Jour, of Phar., June, 1902, p. 275. GENERAL TONICS. 103 Clinical experience seems to show that a formula of this kind is not so useful in those conditions in which there is a deficiency of hydrochloric acid in the gastric secretions; in such cases small doses, from half to one teaspoonful. of the solution of iron and ammonium acetate may be given, after meals. This preparation rarely gives rise to con- stipation or other symptoms of indigestion. It is not very stable and should be dispensed in small amounts. The pills of ferrous carbonate, Blaud^s pills, may be given either alone, or the mass of ferrous carbonate, which is practically identical, may be used in combination with such a laxative as the extract of cascara sagrada, in the dose mentioned above. If desirable a bitter substance such as the extract of nux vomica may also be included as follows : IJ. MassjE ferri carbonatis 3ii 8| Extracti micis vom. | Extraeti rhamni pursli., aa . . . .gr. xv 1| M. Ft. pil. No. Ix. Sig. : One pill half an hour after eating. Other bitter extracts, or other bitter substances, such as quinin or strychnin, and other laxatives may be substituted for those given above. A rep- resentative formula for a pill of this general com- position would be as follows: IJ. Ferri reducti [ Qiiinina; sulphatis Aloos pnrificat, afi gr. xlv 3| Strychninaj snlph -gr. i |0G Ext. gentian q. s. | M. Ft. pil. No. Ix. Sig.: One pill three times a day after eating. While it is true that the salts of the alkaloids might bo substituted by t1io alkaloids themselves, 104 PHARMACOPEIA AND PHYSICIAN. the amount of acid present is so small that it is really of very little moment. In this same connection it may be pointed out that the dried ferrous sulphate or the ferric citrate may be substituted for the reduced iron, or, by omitting the extract of gentian, the mixture may be directed to be dispensed as a powder in capsules. The tincture of ferric chlorid is best given well diluted with water, a glass tube being used to pre- vent the corrosive action of the acid on the teeth, and the mouth should then be well rinsed with water, or a dilute solution of an alkali such as lime water. The scale salts of iron, being generally com- binations with organic acids, are much less cor- rosive than the chlorid, or either of the sulphates, and may frequently be used with advantage in their stead. A representative formula for a simple solution of this kind would be as follows : IJ. Ferri et ammonii citratis 3i 4 Aquae dest fld. 3xii 50 Elixir q. s. ad fld. giii 100 M. Sig.: One teaspoonful three times a day before eating. Any one of the soluble scale salts of iron can be substituted for the iron and ammonium citrate, and one of the aromatic waters can be used in place of the distilled water, or of the water and the elixir. The official bitter wine of iron, given a few min- utes before meals, is an excellent ferruginous stim- ulant of the appetite and digestion which women will usually find acceptable. GENERAL TONICS. 105 MANGANESE. Manganese is not absorbed in appreciable amounts from the alimentary canal after medici- nal doses. Its use as a hematinic is based on its supposed property of neutralizing the hydrogen sulphid in the intestine^ and thus sparing the iron of the food^ but the fallacy of this theory has been mentioned. Manganese would, therefore, not be mentioned here if it were not for its widespread use, thanks mainly to the methods used in exploit- ing the nostrums containing it. The report of the Commission for the Study and Treatment of Anemia in Porto Eico was pub- lished by the government of that island in Decem- ber, 1904. This report, which was the subject of editorial comment in The Journal of the Ameri- can Medical Association, confirms the use of inor- ganic iron in anemia. The misuse of this report by the M. J. Breiten- bach Company furnishes an example of the distor- tion of facts by nostrum makers to suit personal ends. The Journal of Sept. 23 and Oct. 7, 1905, exposed tliis misrepresentation of the report of the commission, and later it gave a careful anal- ysis of a report of tlie use of Gude's Pepto-mangan in 32 cases of anemia in the Infants' Hospital on Kandall's Island. The analysis is brief and con- vincing and will repay perusal by any one who uses that nostrum. The so-called peptonized manganese prepara- tions, generally solutions of peptone to which some salt of manganese has l^een added, may be obtained from reput-ible dealers in pharmaceuticals, or may be made by any rotail pharmacist who lins the 106 PHARMACOPEIA AND PHYSICIAN. necessary educational qualifications to conduct even the very simplest chemical experiments. Peptonates were introduced, upwards of twenty years ago, by E. Dietrich, who published detailed directions for preparing them. His formulas have frequently been republished, and his processes are sufficiently simple to be followed by even a tyro. A number of manufacturers in this country and abroad have adopted them, and not a few of the proprietary preparations now on the market, con- sisting of variable mixtures of iron, manganese and peptone, are but poor substitutes for the original preparation proposed by Dietrich. The commercial dry peptonates are not elegant preparations, and physicians who are desirous of avoiding the use of proprietary articles will do well to have their neighboring pharmacist prepare for them a solution of the peptonates according to Dietrich's original formula, or the modification, proposed by Dunning, in the Proceedings of the American Pharmaceutical Association for 1905. OFFICIAL PREPARATIONS OF MANGANESE. The official preparations of manganese are lim- ited in number, and, as suggested above, are even more limited in their practical application as tonics or hematinics ; they are : Mangani Dioxidum Pr^cipitatum. — U. S. P. — Precipitated Manganese Dioxid is a new prepar- ation that has been added to replace the crude product formerly official. Manganese dioxid is directed to be made from manganese sulphate and should contain not less than 80 per cent, of man- ganese dioxid. Average dose: 0.25 gm. (4 grains). GENERAL TONICS. 107 Man-gani Sulphas. — U. S. P. — This occurs as colorless or pale pink crystals that are soluhle in less than one part of water, but insoluble in al- cohol. Average dose: 0.25 gm. (4 grains). PoTASsii Permangan-as. — IT. S. P. — This sub- stance has been mentioned in the chapters on dis- infectants and antiseptics. In connection with tonics or hematinics it is of interest only as the source of some of the now popular organic prepara- tions of manganese. ARSENIC. It is not positively known whether arsenic is an essential constituent of the human body or not. Segale, using penicillium brevicaule, with which infinitesimal quantities of arsenic may be detected, found it widely distributed in animal tissues, and Bertrand found it in eggs, particularly in the yolk. Wieser concluded that arsenic is not a constant constituent in animal and himian tissues, but that it is accidentally present. When one considers the distribution of arsenic in plants, in sea water and in many springs, it is apparent that abundant opportunity occurs for its entrance into the body, and, owing to its slow ex- cretion, tbe organism may rarely be without traces of it. If minute traces of arsenic are essential to the well-being of the body we may be sure that the ordinary food insures an abundant supply. Gies found tbat those members of a litter of rabbits which received arsenic grew faster than the others, while female rabbits under its influence bore larger young. This increased rapidity of 108 PHARMACOPEIA AND PHYi minims) to each dose, makes the mixture sharp and pungent and may be desirable, particularly In cases of alcoholic gastritis. 14G PHARMACOPEIA AND PHYSICIAN. Fluidextractum Calumb.'e. — U. S. P. — This is made with 70 per cent, alcohol. Average dose: 2 c.c. (30 minims). TiNCTUEA CALUMBiE. — U. S. P. — This repre- sents 20 per cent, of the crude drug. Average dose: 4 c.c. (1 fiuidram). Quassia. — U. S. P.- — The wood of Picarasma excelsa — Jamaica quassia or of Quassia amara — Surinam quassia, appears to be more popular in England than in this country. Tlie official prepa- rations are : Fluidextractum Quassi^e. — U. S. P. — This is made with 33 per cent, alcohol. Average dose: 0.5 c.c. (8 minims). ExTRACTUM Quassia. — U. S. P. — This is an aqueous extract of quassia, representing ten times its weight of the crude drug. Average dose: 0.05 gm. (1 grain). TiNCTUEA QuASSi.^i;. — U. S. P. — This represents 20 per cent, of quassia in 35 per cent, alcohol. Average dose: 2 c.c. (30 minims). Two other drugs which are frequently used by American physicians are chirata and berberis. Chirata. — TJ. S. P. — The dried plant of Sioer- tin cliirayita is a comparatively recent addition to European medicine, though it has long been used and held in high esteem by the Hindus. The only official preparation in our Pharmacopeia is : Fluidextractum Chirata. — U. S. P.— This is made with diluted alcohol. Average dose: 1 c.c. (15 minims). Berberis. — U. S. P. — (Barberry) — The rhiz- ome and roots of BerheKis aqnifoliuni. STOMACHICS. 147 Fluidextractum Berbekis. — JJ. S. p. — This is made with diluted alcohol. Average dose: 2 c.c. (30 minims). aeo:matics. Aromatics contain volatile oils, on which they depend for their flavor and for a slightly irritant action on the mucous membranes. Brandl found tliat the irritation and the consequent hyperemia of the mucous membrane of the alimentary canal, due to sharp tasting substances, caused increased absorption of certain products of digestion. As the aromatics usually have an agreeable taste, they ])robaljly increase gastric secretion by reflex stimu- lation, but it has not been demonstrated that they increase the amount of hA'drochloric acid or of the digestive ferments. All volatile oils have an antiforment action, and the aromatics. therefore, may lessen gastric fer- mentation. The slightly irritant effect, with the hyperemia, must be the main factors in their effects on diges- tion after that of reflex "stimulation. In this connection it is to be remembered that nau.sca. pain in the stomach and other symptoms of functional disturl)ances of tlio gastrointestinal canal are often promptly relieved by external ap- ])licatioii of heat or even l)v a inustni'd footbath. whicli can only act reflexly. It is easy to understand why pine aii' and inter- esting surroundings play such an important role in appetite and digestion wlicii we consider how com|>let<'ly those functions aiv iimh'i- (he control of the reflexes, mere change of local ion heiiig much less im|)orlant than the suhslii nl ion of inleresl in--. 148 PHARMACOPEIA AND PHYSICIAN. for monotonous, siiri-oundings, and in advising change of scene with outdoor life these details can not ))e too carefully considered. The official aromatic bitters include : Calamus.— U. S. P.— (Sweet Flag).— The dried rhizome of Acorus calamus was known to the ancients and is still largely used in Europe, though not so popular in this country. Pluidextractum Calami. — U'. S. P. — This is made with 75 per cent, alcohol. Average dose: 1 c.c. (15 minims). AuEANTii Amaei Cortex. — U. S. P. (Bitter Orange Peel). — -The dried rind of the unripe fruit of Citrus vulgaris has long been used as an aro- matic bitter, but is chiefly used as an addition to other drugs, as in the compound tincture of gen- tian and the compound tincture of cinchona. ■ Pluidextractum Aurantii Amari.— IT. S. P. — This is made with 65 per cent, alcohol. Average dose: 1 c.c. (15 minim.g). TiNCTURA Aurantii Amari. — U. S. P. — This represents 20 per cent, of the crude drug and con- tains 60 parts of alcohol. Average dose: 4 c.c. (1 fluidram)._ ASTRINGENT BITTERS. Drugs that might properly be classed as astrin- gent bitters are numerous, and, therefore, we shall enumerate but a few of the more important. CiMiciFUGA. — U. S. P. — The dried rhizome and roots of Cimicifiiga racemosa, a plant that is a na- tive of North America, have been used extensively in some sections of the United States. t ,S'rOiIACHICS. 149 Fluidextractu:\i Cimicifug-^. — U. S. P. — This is made with strong alcohol. Average close: 1 c.c. (15 minims). TiNCTURA CiMiciFUGiE. — U. S. P. — This is. made with alcohol. Average dose: 4 c.c. (1 fluidram). Serpentaria. — U. S. P. — The rhizome and roots of Arlstoloclna serpentaria, popularly known as Virginia snakeroot. have been used in Europe for over 200 years. FlUIDEXTRACTUM SERPEXTARIaTl. — U. S. P. — This is made with 80 per cent, alcohol. Average dose: 2 c.c. (30 minims). . TiNCTCRA Serpentari^. — U. S. P. — This rep- resents 20 per cent, of the crude drug and is made with a menstruum containing G5 parts of alcohol. Average dose: 4 c.c. (1 fluidram). Hydrastis. — U. S. P. — The rhizome and root- lets of Hydrastis caruidensis. a perennial plant that is indigenous to Canada and the United States east of the Mississippi Eivcr. Fluidextractu.m Hydrastis. — U. S. P. — This is made with a menstruum containing 60 parts of alcohol, with glycerin and water, and should con- tain not less than 2 ])er cent, of hydrastin. Average dose: 2 c.c. (30 minims). Tikctura Hydrastis. — ^tJ. S. V. — This wprc- scnts 20 per cent, of the crude diiig nnd is made with 65 per cent, alcohol. Average dose: 4 c.c. (1 iluidrain). CiNCiioxA.— U. S. P.— While undoni)((>,llv l.d- tor known and more extensively used as a bitter stomachic than any of the preceding, it is unneces- sary to rcfoiint the origin or the uses of this drug. 150 PHARMACOPEIA AND PHYSICIAN. It is official under two titles : Cinchona and Cin- chona Eubra. Of the former we have : Fluidextractum CiNCHONiE. — U. S. P. — This is made with 80 per cent, alcohol and contains 4 per cent, of the ether-soluble alkaloids of cinchona. Average dose: 1 c.c. (15 minims). TiNCTUEA CiNCHONvE. — U. S. P. — This repre- sents 20 per cent, of the crude drug and should contain 0.75 per cent, of cinchona alkaloids. Average dose: 4 c.c. (1 fluidram). The only official preparation of red cinchona is the old, and still popular, Huxham's tincture of bark. TiNCTURA ClNCHON.^ COMPOSITA. — U. S. P. — This represents 10 per cent, of red cinchona, 8 per cent, of bitter orange peel and 2 per cent, of serpentaria. Average dose: 4 c.c. (1 fluidram). Nux Vomica. — U. S. P. — The dried ripe seed of Stnjchnos mix vomica, although not containing sufficient tannin to be classed as an astringent bit- ter, forms an inky mixture when iron is added to it. It is frequently used as a bitter stomachic. The available preparations are: Fluidextractum Xucis Vomica. — U. S. P. — This contains 1 per cent, of strychnin. Average dose: 0.05 c.c. (1 minim). TiNCTUEA Nucis VoMicai:. — IJ. S. P. — This contains 2 per cent, of extract of nux vomica and is assayed to contain 0.1 per cent, of strychnin. Average dose: 0.6 c.c. (10 minims). Bitters, and more particularly the aromatic bit- ters, are indicated in loss of appetite when it is not due to ofrave o-astric disturbances. AVhen catarrh STOMACHICS. . i^l of the gastric mucous membrane complicates the condition, an astringent bitter, such as serpenta- ria, cimicifiiga or cinchona, should be used. In the absence of catarrh, indigestion accompanied by in- sufficient gastric secretion, ma}- be treated with a simple bitter, such as gentian or calumba, which may be used alone, but it is very much more often advisable to combine the simple bitters with aro- matics. The individual taste of the patient should al- wa3's be considered in the choice of the aromatic. Men often like simple bitters, such as gentian or gentian and orange, a fact attested by the extraor- dinary popularity a few years ago of a certain bit- ters, which consisted practically of compound tinc- ture of gentian. Women usually prefer mildly aro- matic and not very bitter substances, while chil- dren are generally averse to them altogether. When excess of acidity exists bitter substances will probably increase the trouble. Just as bitters and aromatics produce a greater effect in cases of functional disturbances. 50 iron is useful in ane- mia, though it has little influence in health, and it is often found advisable to combine iron with bit- ters, in which case the astringents are to be avoided because of the chemic reaction, whereby an inky mixture is formed, disagreeable alike to sight and taste — two groat ol)jections in this class of reme- dies. ^fany Ijittcr.s wliic-li iin; ikjI usually classed as astringents contain enough tannin or similai-ly aci- ing substances to give inky mixtures willi fei-i'ic sails: siicli. \nv instance, are genlian am! mux vomica. Calumlni, therefore, is to be given the 152 PHARMACOPEIA AND PHYSICIAN. preference in all cases in which a bitter is to be combined with a soluble salt of iron. Detannated preparations of cinchona and even solutions of the cinchona alkaloids have little to recommend them in preference to calumba as a simple bitter. The following illustrates the combination of a simple bitter with iron: IJ. Tinct. calumbse giii lOO Tinct. ferri chloridi m. Ixxv 5 Aquae q. s. ad gvi 200 M. Sig. : A tablespoonful may be given half an hour before meals to men, while a teaspoonful will usually suffice for women.- The possible combinations of aromatic liitters are infinite, and, as previously stated, the indi- vidual taste is to be considered rather tlian slavish adherence to any one formula. For an astringent bitter the fluid extract or the tincture of cinchona, cimicifuga or serpentaria may be combined somewhat as follows : IJ. Fluidextract cinchonfe I Tinct. gentianse comp., aa 3xii 501 M. Sig.: .One teaspoonful to be given before meals. For women it will be well to increase the amount of aromatics, in which case the compound tincture of cardamom may be substituted for the compound tincture of gentian and the mixture even further diluted with aromatic elixir, if thought desirable, as follows : IJ. Fluid extract, cinchonse 3v 20| Tinct. cardamomi comp. I Elixir aromatici, afi 3x 40] M. Sig.: One teaspoonful of this mixture with water, to be given before meals. 2. While small closes of iron, well diluted, may be given with bitters before meals, if larger closes are given after eating they are borne better than they would be if given on an empty stomach. STOMACHICS. 153 A mixture of nux vomica and sodium bicarbon- ate offers a number of advantages as an efficient and comparatively barmless stomacbic. It is made as follows : IJ. Tinct. nucis vom m. Ixxv 5] Sodii bicarb gv. el 10 Aquae dest q. s. ad gv 150 1 Altbougb tecbnically tbis formula involves an incompatibility — sodium bicarbonate and the alka- loids of nux vomica — practically it is very satisfac- tory indeed. If the mixture is filtered and allowed to stand for 24 hours before being dispensed it will be found to have developed a very pleasant ethereal odor that adds materially to its effectiveness. The usual dose for adults is one tablespoonful before meals. For a patient with chronic constipation the addition of 1 or 2 c.c. (15 to 30 minims) of the fluidextract of cascara sagrada will be found to be highly satisfactory. One argument in favor of this combination is that it contains little alcohol — virtually none. CARMINATIVES. The origin of this word is in doubt, some au- thorities maintaining that it comes from carmen, a charm, and the term is even now used somewhat loosely for those agents which produce a sense of warmth and well-being and Avhich act as antispas- modics, or which expel gases from the gastrointes- tinal canal. Wbcn given with cathartics tbey lessen the griping ])ain of tlicsc drugs, and. being antis('j)tic, tliey inliilni the foniiiilion of gas by I'ennentatioii. According to the accepted dcliiiilion ;i unalrr or less numbf'r of snl)stanees can be iiichuled in Ibis 154 PHARMACOPEIA AND PHYSICIAN. particular class. The official carminatives afEord a very wide range of choice, as the}^ include practi- cally all aromatic bitters, nearly all the aromatic volatile oils, besides such substances as ginger and capsicum, which contain pungent resinous constitu- ents, alcohol, ether, chloroform and many other agents which produce a sense of warmtli when swal- lowed. Carminatives are among the most ancient of rem.- edies and are indicated in pain in the stomach or bowels when due to simple indigestion or disten- sion by gas, but not when there is inflammation; in the latter case — for instance, in appendicitis oi in peritonitis — carminatives are apt to augment the trouble. Many of these substances are well known as household remedies and it will suffice to enumerate only the more important ones. Zingiber. — U. S. P. — Ginger has been used from time immemorial in eastern Asia ; it was well known to the ancient Greeks, and is even now, perhaps, the most popular of all the carminatives. The most widely used of the official preparations is the tincture. TiNCTUEA ZiNGiBERis. — U. S. P. — This repre- sents 20 per cent, of the crude drug exhausted with alcohol. Average dose: 2 c.c. (30 minims). Fluidextractum Zingiberis. — U. S. P. — This is an alcoholic extract. Average dose: 1 c.c. (15 minims). Oleoresina Zingiberis. — U. S. P. — This is now prepared by means of acetone. Average dose: 0.03 gm. (% grain). STOMACHICS. 155 Half a teaspoonful of the tincture may be given in a little hot water or with sugar. The oleoresin is much more active, and a drop of it may be thoroughly well mixed with powdered sugar and from one-eighth to one-fourth of the quantity given to a child, but not to an infant. It may also be added in half-drop doses or less to bulky cathartic pills or mixtures, but in either case it should be well diluted. While ginger is very commonly used alone as just mentioned, it may be prescribed somewhat as follows : IJ. Tinct. zingiberis 3iv 16 Chloroformi 3i 4 Elixir aromat. q. s. ad giii 100 M. Sig. : One teaspoonful thirty minutes after eating. Capsicum. — U. S. P. — Capsicum has been in use as a condiment, in eastern countries, from a very early period. It is intensely pungent and is particularly useful in cases of alcoholic gastritis. Average dose: 0.05 gm. (1 grain). TiNCTDRA Capsici. — U. S. P. — Tiucture of Capsicum represents 10 per cent, of the drug in 90 per cent, alcohol. Average dose: 0.5 c.c. (8 minims). Fluidextractum Capsici. — U. S. P.— Fluidex- tract of capsicum is directed to l)c made with strong alcohol. Average dose: 0.05 c.c. (1 minim). Oleohesina Capsici. — U. S. P. — Is directed to be made by using acetone as the solvent. Average dose: 0.030 gm. (30 mg. I/2 grain). 15G PHARMACOPEIA AND PHYSICIAN. THE OFFICIAL MIXTS. Of the large number of aromatic drugs of the mint famil}', two have attained more than ordinary popularity as carminatives. The revisers of the Pharmacopeia have, indeed, been impartial in their description of these two substances and have treated them absolutely alike, so that from their status as official drugs it would be difficult to say whether peppermint or spearmint should be ac- corded the preference. It wall be safe to assert, however, that peppermint is the more widely used. It is official as : Mentha Piperita. — U. S. P. (Peppermint). — The dry leaves and flowering tops. Average dose: 4 gm. (1 dram). This is some- times used in infusion. Oleum Mentha Piperit.f:. — U. S. P. — This is a volatile oil distilled from the fresh and partly dried leaves and flowering tops of peppermint. Spiritus Mentha Piperit.^. — U. S. P. — This is an alcoholic solution of 10 parts of oil of pepper- mint filtered through 1 part of bruised pepper- mint, W'hich imparts to it a distinct greenish color. Average dose: 2 c.c. (30 minims). Aqua Menth^e Piperit^e. — U. S. P. — This is a saturated aqueous solution of oil of peppermint. Average dose: 15 c.c. (4 fluidrams). As above noted, spearmint, Mentha viridis, is official under corresponding headings and the doses are. of course, the same. The uses of these official mints are too numerous and too well known to require description in detail. They appear to be particularly useful in gastric fermentation, for which purpose they are usually STOMACHICS. 157 given in connection with a mild alkali, like sodium bicarbonate, preferably in the well-known mixture of soda mint of the National Formulary or the widely used soda-mint tablets.'^ Accumulations of gas in the stomach which prove most distressing can often be promptly re- lieved by administration of 20 grains of sodium bicarbonate or potassium l)icarbonate dissolved, preferably in hot water, to which from 10 to 30 drops of spirit of peppermint or spearmint may be added. ASAFETIDA. AsAFG-TiDA. — T^. S. P. — A gum resin obtained from the root of one or more species of Ferula, was held in iiigli esteem l)y the ancient Greek physicians and has been in general use since that time. x\verage dose: 0.25 gm. (4 grains). PiLULiE AsAFCETiD.ii:. — U. S. P. — Eacli pill con- tains 0.2 gm. (3 grains) of asafetida and O.OG gm. (1 grain) of soap. Average dose : 2 pills. TiNCTURA AsAFGiTiDiE. — U. S. P. — This repre- sents 20 per cent, of asafetida in alcohol. Average dose: 1 c.c. (15 minims). 3. The Mistura Sodse et Menthoe of the National Korimi- hu-y consist.s of : Sodium Ijicnilidiialc grs. Ixxv .")! Aromatic spirit of aiiiMioiiia m. xv 1 Spi-armliit water to inMJjr r,iii I()(i[ Mix and liltcr. Tlic average dosi' ol" lliis |ii-c|i;ir:i I icn is rmin :.' In :; {i-.\ spooiifuis. Soda mint tal)lcls as fiiriiislu'd l.y iii;i iinl:irl iin'rs nsnall.v POHhIhI of d.."! Kill. (.'> ni-;iiiisi (if soilluiii liic;irl)(ilialf wilii ().()<)•_' (i;:',i) iiiiiiiiii) ..r oii ,,r |,r|,|„.iijiini. 158 /'IIA/niArrn i 11 use a.>+ a canninativr. Average dose: 1 c.c. (15 minims). 4. See Thi; Jouknal A. M. A., vol. xllv, p. COO. KiO PHARMACOPEtA AND PHYSICIAN. Spiritus ^theris. — U. S. P. — This contains about 33 per cent, of ether. Average dose: 4 c.c. (1 flnidram). Spiritus ^theris Compositus. — U. S. P. — The well-lmown and widely-nsed Hoffman's ano- dyne contains, in addition to ether, about 2.5 per cent, of ethereal oil. Average dose: 4 c.c. (1 fluidram). Compound spirit of etlier, in addition to its other uses^ has long enjoyed a special reputation in hysteria due to gastric disturbances. It is disagree- able to the taste, however, and probably possesses no advantage over hot whisky and water, or spirit of nitrous ether. The spirit of chloroform, diluted Avith aromatic elixir, or the emulsion of chloroform given alone, promptly affords a sense of warmth in the stom- ach and will usually give relief in cases of colic and pain. Chloroform may be prescribed as follows as a carminative : IJ. Tinct. capsici Siii 12 Spiritus camphorae 3iii 12 Chloroformi 3i 4 Alcohol diluti q. s. ad Siii 100 M. Sig. : Half a teaspoonful as a dose. Alcoholic liquids in general are often useful, but their use and their numerous disadvantages can not be advantageously discussed in this connection. CLOVES AND OTHER AROMATIC SUBSTANCES. Cartopiiyllus. — U. S. P. — (Cloves.) — The dried flower buds of Eugenia aroniaUca. This rem- edy appears to have been known to the early Egyp- tians, but was not known to the later Greeks. In STOMACHICS. 161 Europe this drug, probabl}- introduced by the Arabians, has been known for centuries. Average dose: 0.25 gm. (4 grains). OLEUii Caryopiiylli. — U. S. P. — This is a vol- atile oil distilled from cloves. Average dose: 0.05 c.c. (1 minim). The oil of cloves is much more frequently used for its anesthetic and caustic effect on exposed nerves in carious teeth than as a carminative, but it ma}' be used for the latter purpose, in vrhich case it is better to add it to spirit of peppermint or some other alcoholic carminative preparations be- fore diluting vrith water. Oil of cinnamon resembles oil of cloves in its carminative effect, and the official tincture of cin- namon is also useful for the same purpose, but is more commonly employed as an adjuvant or flavor for other more active carminative agents, and in diarrhea. Mustard, pepper and nutmeg are not used med- icinally as carminatives, but are much employed as condiments to serve practically the same purpose. CHAPTEE VII. " DIGESTAXTS AND DIETETICS. The digestive ferments are of only minor im- portance in therapeutics, and most often they are entirely useless. We know but little of the condi- tions demanding their use, and in the great ma- jority of cases of indigestion there is no lack of these enzymes in the alimentary canal. The general subject of dietetics presents a very great number of difficulties even to the most skil- ful specialist. Frederich Miiller closed a series of lectures on "the pathology of digestion" with the remark that there were few subjects in medicine on which he would be so loath to write a l)ook as on that of dietetics. In view of this attitude the title of this chapter is almost a misnomer, for it is our purpose to call attention to some of the abuses which obtain in connection with these substances rather than at- tempt to give extended information for the use of the digestive ferments and the predigested foods. The general subject of nutrition, on the other hand, is so extensive that it can be touched on only very briefly. It has been shown repeatedly that where several of the digestive ferments are contained in a mix- ture one or the other of them is rapidly destroyed. The actions which mainly concern us may be stated briefly as follows : Dilute hydrochloric acid and gastric juice destroy trypsin (pancreatin) and DIGESTAXTS AXD DIETETIC!^. 103 diastase or ptyalin in a few hours, the rate depend- ing on the degree of acidity. Hydrochloric acid and pepsin act much more energetically in destroying these ferments. Alkalies alone destroy pepsin, and alkalies plus trypsin destroy pepsin very much more rapidly. As Sollmann has put it, it is as ahsurd to expect the simultaneous action of pepsin and trypsin or panereatin as to expect the simultaneous action of an acid and an alkali from a mixture of the two. Alcohol and numerous other antiseptics slowly destroy pepsin so that ready-made preparations are of necessity varial)le and very commonly inert. The better class of manufacturers claim that they make preparations containing pepsin with panereatin only in response to a demand. This is not wholly true, however, for every text-book worthy of note which deals with the subject at all states distinctly that pepsin and panereatin are incompatil)le, that pepsin acts only in an acid medium in which it destroys panereatin, and that panereatin destroys pepsin in a neutral or alkaline mixture. No writer worthy of attention at present pretends that pepsin and panereatin are useful in combination, and it is not reasonable to suppose that a disreputable firm, making false claims, would create so great a demand for a rival's goods that the rival would be compelled to put out a mix- ture known to be wortliless. Tt is difricnlt to understand liow any reasonably (•aivriil physician can I'cad tlic c\i(lciicc dii (I)is sul)jccl given in 'I'm; .Ioik-n \i. of llie American Medical Associal i.m ( Im'Ii. •!. '.» and 1(1. U)07), including the article by Sollmann, and continue to 1C)4 PHARMACOPEIA AND PHYSICIAN. prescribe these substances in combination, or even singly, except in rare cases. The ptyalin of the saliva acts on starchy foods, converting them into dextrin and maltose and finally into glucose. When the food is thoroughly masticated, and thus insalivated, the action of the ptyalin may continue in the interior of the food masses in the stomach, since the gastric juice acts mainly on the external surfaces and, therefore, does not come at once into contact with all of the contained ptyalin. Starchy foods, such as gruel, may be partially digested by the addition of diastase (from grain) before being taken, but it is wholly useless to take diastase in solution, since, as already stated, it would be inliibited by the hydrochloric acid and destroyed by the pepsin before it could exert any important action on the food, because it is not then protected by being enclosed in masses of food. It is evidently irrational to give pepsin unless there is some reason to suppose that there is a de- ficiency of that enzyme in the gastric juice, and then it should be given in powder or only in fresh- ly made solutions, unless the glycerin extract is used. The practice of giving pepsin, or even a mixture of the digestive enzymes in every case of indiges- tion, regardless of whether proteids, carbohydrates or fats are the disturbing factors, is as irrational as would be the practice of trying to cure every disease of which fever is a symptom by the use of one of the coal tar antipyretics. The only conceivable method of giving pan- DIGE8TANTS AND DIETETICS. 1G5 creatin with benefit consists in protecting it from solution in the stomach, by coating with keratin or salol, or b}' administering it toward the close of gastric digestion, in alkaline solution, when it would probabh' pass fairly rapidly into the intes- tine, but it could exert only a minor influence under the latter circumstances. Hydrochloric acid is much more frequently wanting tlian is pepsin or trypsin and it is some- times useful to administer the dilute acid. Hydrochloric acid is not a proprietary article, however, and there are no financial interests to be served by recommending its use. It has been sug- gested that much larger doses than those common- ly given may be required, but Osier does not advise very large amounts. It is quite needless to mention the various pro- prietary preparations by name which have been exploited witli so little credit to the medical pro- fession and with such large financial returns to their manufacturers, for every intelligent physi- cian can supply a liberal number of these names for himself, and it can not be too plainly stated that all alcoholic preparations of digestive enzymes,, whatever the alcohol content may be, are variable or inert, and that all mixtures of the various diges- tive enzymes are as absurd as mixtures of acids and alkalies, wlicrc llie action of the resulting salt is not desired, or as it would be to attempt to apply heat and cold simultaneously by putting hot water and ice in an ice cap. It is very much more rational to assist tlie di- gestion by dainty appetizing dishes and pleasing l(i(i PHARMACOPEIA AND PHYSICIAN. surroundings than to administer digestive fer- ments.^ "N^niiile rennin, occurring in the gastric juice, curdles milk, its precise use in digestion is not known; in a practical way.it is used to prepare curds and whey and is of considerable importance in the diet kitchen. Trypsin has been suggested as a cure for cancer and has been noisily praised as such in the public press; it is as yet quite impossible to say whether it possesses really curative value or not. It may be recalled, however, that it was just as noisily proclaimed, some years ago, for the removal of the diphtheritic membrane. The vegetable pepsin, so called, papayotin, which is said to act in acid, alkaline or neutral media, has not proved to be of any distinct value, and this is only what was to be expected in view of the fact that the fault probably seldom lies in the want of secretion of the digestive enzymes. Hydrolysis or digestion of proteids may also be accomplished by means of mineral acids or super- heated steam, and it is reported that the resulting artificial peptones and albumoses have been of- fered as foods. Whatever may be said of the value of the predigested foods as a class, it must be ad- mitted that the best of them are of little actual value, and there is considerable evidence to indi- cate that when prepared, by means of mineral acids 1. That sufficient attention is not paid to this may be shown by the experience of one of the authors in one of the larger hospitals of New York. While convalescent from typhoid fever he was given ice cream and other food with a dirty piece of rubber adhesive plaster attached to every spoon and article of tableware (except such as he had brought from home), and some surprise was expressed that he ate almost nothing while in the hospital. DIGEHTAyTii AXD DIETETIClS. 167 or steam, the resulting i^eptones do not act as food. Predigested foods should at least be obtained by tlie action of the digestive enzymes. OFFICIAL PREPARATIOXS. Pepsixum. — U. 8. p. — Pepsinum is described as a proteolytic ferment or enzyme, derived from the glandular la3-er of the fresh stomach of the hog. ^Mien assayed according to the process de- scribed in the Pharmacopeia, pepsin should be capable of digesting no less than 3,000 times its own weight of freshly coagulated and disintegrated egg albumin. Pepsin is soluble in about 50 parts of water, but is insoluble in alcohol. It is incompatible with alkalies, alcohol, many of the salts of the heavy metals and strong mineral acids; even the pres- ence of more than 0.5 per cent, of hydrochloric acid rapidly destroys its proteolytic activity. Average dose: 0.25 gms. (4 grains). Paxcreatixum. — U. S. P. — Pancreatin is a mixture of enzymes naturally existing in tbe pan- creas of warm-blooded animals. The commercial article is usually obtained from the pancreas of the hog or the ox. It is officially descril)ed as con- sisting principally of amylopsin, myopsin, trypsin and steapsin, and when assayed Iw the process given in tbe Pharmacopeia should be capable of converting no less than 25 times its own weight of starcli into substances soluble in water. i'aiK ivMtin is slowly, but not completely, soluble ill water; it is insoluble in alcohol and is incom- |)atible with pepsin and mineral acids. Average dose: 0.50 gni. (8 grains). 168 PHARMACOPEIA AND PHYSICIAN. ExTRACTUM Malti. — U. S. P. — Extract of malt, as now official, has the consistency of thick honey and jDossesses amylolytic properties. It is frequently used as a vehicle for other sub- stances. Average dose: 16 c.c. (4 fluidrams). NATIONAL FORMULARY PREPARATIONS. The abuse and the general uselessness of many of the combinations of digestive ferments is well illustrated by the preparations that are included in the recent, third, edition of the National For- mulary. No less than 18 preparations, many of them involving well known chemical incompatibil- ities, are included. We may enumerate : Elixir Pepsini, Bismuthi et Strychnine. — N. F. Elixir Pepsini et Bismuthi.^N. F. Elixir Pepsini et Ferri. — N. F. Elixir Cincpion.^, Ferri et Pepsini.^N". F. Elixir Cinchon.^, Pepsini et Strychnine. — N. F. Glyceritum Pepsini. — N. F. Liquor Pepsini. — IST. F. Liquor Pepsini Aromaticus. — N". F. Liquor Pancreaticus. — N. F. Pulvis Pepsini Compositus. — N. F. Pepsinum Saccharatum. — ]Sr. F. Among the more widely used preparations we have: Elixir Digestivum. — N. F. — Compound di- gestive elixir represents a mixture of pepsin, pan- creatin and diastase with hydrochloric and lactic acids, dissolved in a mixture of glycerin, com- DIGESTAXTS AXD DIETETICS. 169 pound tincture of cardamom and aromatic elixir, colored red with tincture of cudbear. "While this preparation is generally recognized as being inert, so far as digestive properties are concerned, it is nevertheless widely used, chiefly as a vehicle. It is perhaps needless to add that be- cause of the absurdities involved its future use should be discouraged, and it is to be hoped that future revisions of the ISTational Formulary will present in its stead a less objectionable red elixir. Average dose: 8 c.c. (2 fluidrams). Essentia Pepsixi. — J^. F. — Essence of pepsin represents a mixture of pepsin, rennin and a small amount of lactic acid in an aromatic vehicle con- taining glycerin and wine. In common Avith the numerous proprietary preparations of a similar nature now on the market, it is essentially a rennin preparation and has its chief uses in the making of junket, curds and whey, as described below. It is also popular as a vehicle for iodids and bromids, though tliese, in turn, tend to destroy the con- tained pepsin. Average dose: 8 c.c. (2 fluidrams). PuLvis Pancreaticus Compositus. — jST. F. — Peptonizing powder consists of a mixture of two parts of pancreatin and eight parts of sodium bi- carbonate. It is used in tbe preparation of pep- tonized milk and in the making of : PULVIS PRO LaCTE HuAfANISATO. — N. F. — Milk powder, or humanized unlk powder, represents a iiii.xture of 35 parts oL' coinpoiiiiil pancreatic pow- der X. F. and 905 parls <.r sii-ar of milk. Tiiis pi-("])ai-iiti(»n is designed for use in |ire|i;iiiiig liii- nianized milk. 170 PHARMACOPEIA AND PHYfllCIAN. Humanized milk. The directions for this prep- aration, as given in the National Formulary, are as follows: Triturate G.o gms. (100 grains, or about a heap- ing teaspoonful) of the humanizing powder with 60 c.c. (2 fluidounces or about 4 tablespoonfuls) of water and transfer the mixture to a clean bottle containing 60 c.c. (2 fluidounces or about 4 table- spoonfuls) of fresh cows' milk and 15 c.c. (I/2 fluidounce or about 1 tablespoonful) of fresh sweet cream. Mix thoroughl}^ and immerse the bottle in water heated to 38° C. (100° F.) for 15 minutes, then pour the mixture into a suitable vessel and heat it quickly to boiling and then immediately allow it to cool to the body temperature. Humanized milk should be prepared imme- diately before use and the above directions should be closely followed. If digestion is too prolonged the resulting milk will be bitter and unpalatable. For this reason it is necessary to heat the milk to boiling at the end of the required time for digest- ing the same. The milk, and also the cream, should be fresh and sweet and quite free from preservatives of all kinds. Liquor Seriparus. — N". F. — Liquid rennet is directed to be prepared from fresh calves' rennet and represents approximately about 10 per cent of the rennet. This preparation may l)e used in the making of junket, curds and whey. Where it is to be used merely for curdling the milk without separating the whey as a distinct layer it should be added to the milk previously warmed to a temperature of I DIGESTAXTS AXD DIETETICS. 171 about 35° C. (95° F.) but not exceeding 40° C. (104 F.). One part of liquid rennet should coag- ulate between 200 and 300 parts of cows' milk so that the average direction would be to use half a teaspoonful to 500 c.c. (1 pint) of milk. Junket and whev may also be prepared by using, in place of the liquid rennet, the essence of pepsin N. F. This preparation contains rennin, and the manufacturers of corresponding proprietary prep- arations advocate the use of their particular prod- ucts because tlie contained pepsin tends to sup- ply the proteid matter contained in milk, in a partially digested form. Wbile this is of doubt- ful advantage, at best, the claim is mis- leading unk'ss the preparation is comparatively fresh ; the contained rennin has been foUnd to retain its activity for a considerable length of time and the preparation may be used in place of the liquid rennet, in (juantities from four to five limes greater. Peptonized milk may be prepared by adding 1.5 gms. (25 grains) of compound pancreatic powder N. F. to 125 c.c. (4 fiuidounces) of tepid Avater contained in a suitable flask or bottle, and after- ward add 500 c.c. (1 pint) of fresh cows' milk, previously beated to 38° (100° F.). Maintain the lieat at tbis temperature for thirty minutes, then transfei- the container to a cool place. Peptonized uiilk, prepared in lliis way, should not l)e used wbeu it has been kept o\(m- i wenty-four liours, or wlicii il bas dcNi'loix'd ;i \i'i-y liiltcr taste. The above gcticrnl process for |ic|il(iiii/,('d milk may be varied in a niiinln'i- of ways. ;iiiil llic degree of digestion may be regulated at will l>y lengthen- 172 PHARMACOPEIA AND PHYSICIAN. ing or shortening the time during which the mix- ture is kept warm. It should he remembered, too, that digestion takes place even at low temperatures and a cold process for peptonizing milk is some- times recommended. This consists simply of mix- ing the ingredients enumerated in a clean sauce- pan or a suitable flask or bottle and placing the same on ice without subjecting it to the warming process. Partially peptonized milk may l)e prepared by placing the mixture of peptonizing powder, water and milk, in a clean saucepan or suitable flask or bottle and gradually heating on a water bath until the mixture boils. Then remove and allow to cool, or the milk thus prepared may be given while still warm. The final boiling destroys the ferment and milk thus prepared will not undejgo further pep- tonization on standing. Peptonized milk may be served with cereals, or in the form of jellies flavored with fruit juices or other desired flavoring. Where its use must be continued for a long period of time it may at times be made more acceptable by mixing with equal portions of aereated water, or by the addition of an alcoholic beverage with or witbout spices, such as freshly grated nutmeg. The simplest form of partially predigested food is toasted bread. Heat converts some of the starch into dextrin (brown color) and by making the bread more brittle favors insalivation. Burning sliould bo avoided, as it not only renders the toaist loss pleasant to the taste but the carbonized par- ticles are wholly indigestible and may prove irri- tating to the stomach and intestines. DIGE8TAXTS AXD DIETETICS. 173 DIETETICS. Infant feeding presents a great many problems which can only be discussed with profit by special- ists, but there are certain simple facts in dietetics with which the physician should be more familiar tlian he is now and'which require but little thought and study. Infant starvation is not at all uncom- mon, and many physicians are utterly unable to compute the food requirements of the infant (or adult) and the food values of various foodstuffs. These are exceedingly simple in ordinary cases, in contradistinction to the extreme difficulty of the subject of infant feeding and dietetics in abnor- mal conditions. Food values or the energy values of food are commonly expressed in calories (from the Latin, Calor, heat), a calory being that amount of heat wliich is recjuired to raise the temperature of a liter of water one degree centigrade. An infant under 3 months requires about 100 calories per day for every kilogram of body weight (about 45 calories per pound). The proportionate requirement diminishes, and between the ages of 3 and G montlis the re(iuirement is 90 calories per kilogram ( H) caloiics per pound), and between 6 months and 1 year S(i calories per kilogram (36 calorics jx-r pound), and tliereafter about 70 calorics per kilogram (;J0 calories per pound). Il i,- iiici-cly necessary to weigh llic cliild and limit i|»lv the weight in kilograms nv pounds by llic rc(|iiiiriiiciii ill ca1r)rics lo ascertain tlic food \;diic needed in ;iny case. 'I'llis riiiMl \;illle reipiii-einelli is also. Id an ex- lent at Icii-^t, dcjjcndcni on ilie siirrace area of the 174 I'/IAh'.UACOI'ElA AND I'llYSICIAN. bod}', hence iimisiially large children will require somewhat less food per pound than Mali small ones, or, in other words, the food value per pound of a large child of 6 months will approximate that of a small child of a year. Having ascertained the weight and energy re- quired in a given case, it is easy to compute the calorific value of the food ingested by multiply- ing the weight of the carbohydrates and protei*ds (starches, sugars and albumin) in grams by 4, and the weight of the fats (butter in cream) by 9 to ascertain approximately the number of calories represented. One ounce avoirdupois may be taken as 30 grams roughly (28, more accurately), and an ounce of sugar rej^resents about 120 calories, while an ounce of butter represents about 250 calories, an ordinary egg about 75 calories, a pint of aver- age good cows' milk represents about 350 calories, mothers' milk somewhat less. The actual value should 1)6 determined by examination in any case where it seems probable that a breast-fed infant' does not get sufficient nourishment. Adults require less food per pound of body weight than do infants, and in the case of adults the requirements vary from 25 calories per kilo- gram (12 calories per pound) during rest in bed (without fever) to 50 or 60 calories per kilogram (22 to 27 calories per pound) during hard labor. Increased activity in the adult does not demand a proportionate increase in the proteid of the diet, if enough carbohydrates and fats are taken, but proteid may supply the increased demand. DIGE8TAXTS AXD DIETETICS. 175 During convalescence, when flesh is being added to the body, more proteid is required than is needed ,ljy a healthy person of the same weight. It should be remembered that the food value of such vegetables as celery, tomatoes, lettuce and cabbage is wholly negligible, so far as calorific val- ues are concerned, also that potatoes and rice, as they appear on the table, represent probably not more than 20 per cent, of starch. Sugar, however, is pure carbohydrate except for a wholly negligible amount of moisture. The commercial liquid predigested foods possess no practical food value. It has been sho^vn that when predigested proteids are given in amounts sufficient to have any practical value their ten- dency to cause diarrhea interferes with their use, and, furthermore, a person would be kept in a state of continued intoxication by the alcohol con- tained in much less of the artifi'cial food than would be needed for sustaining life, granting that life could be sustained by the use of predigested foods of this kind. For a comparison of the theoretic food values of a number of these artificial foods, such as pano- pepton, liquid peptonoids, tonic beef and others, the reader is advised to read the report of the Coun- cil on Pharmacy and Chemistry of the American Medical Association {Jour. A. M. A., May 11, 1007, page 1G12). The figures that are included in this r('|)oi-t ai-c I'cally sui-pi'ising, particularly rroiii an (■cniKiiiiic iMiiiil ol' \\r\\\ and wci'c it not lor the I'act thai Aiiici'ican nici lical men have paiil allogetlior too little atteiilion h II a cai'd'Hl slii.ly (»r the subject of dietetics, the iv| Mii't ilscir might he 17G PHARMACOPEIA AND PHYSICIAN. held to be evidence of onr absolute carelessness as medical men. The table that is embodied in tlie report includes data obtained from a careful study of eighteen samples of medicinal foods made hy ten different manufacturers. The calories, as proteids and carbohydrates, contained in 500 grams varied from 54.7 to 397.5, while the approximate cost of this quantity varied from $1.00 to $1.54 as compared with milk cost- ing approximately 5 cents and containing upward of 180 calories of food value in proteids and car- bohydrates. The additional calories of available food value in medicinal foods are embodied in the contained alcohol, while in the cows' milk the additional food values consist of fat in a readily assimilable form. Granting that alcohol has the same food value as fat, the cost per day to supply the mini- mum number of calories necessary to sustain life would vary from $1.56 to $3.39 for the medicinal foods as compared to 20 cents for cows' milk. If, however, it were practicable to eliminate the consideration of the alcohol in medicinal foods and of the fat in the milk we would have a cost of from $4.33 to $28.97 for the required calories in medicinal foods as compared to 39.5 cents for the corresponding number of calories, in proteids and carbohydrates, to be found in cows' milk. In one of these artificial foods the food value of the daily dose, exclusive of alcohol, was found to be less than 10 calories, or about 1/150 of the total amount required by an adult resting in bed. To put it in another way, the total daily dose of this DIGESTANT8 AND DIETETICS. 177 medicinal food equalled in food value about one- seventh of an egg or an ounce and a half of milk — and yet on such frail reeds are we expected to lean in a crisis. The value of alcohol as a food has been the suli- ject of a great deal of discussion. It may be said that alcohol may replace carbohydrates or fats, to a very small extent, but it does not lessen in the slightest degree the minimum amount of proteid metabolized, which must be supplied in the food or drawn from the tissues. In other words, if a patient is able to take a bare sufficiency of carbo- hydrates and fats the addition of alcohol does not diminish the amount of proteid which must bo taken to prevent loss of weight. According to the researches of Chittenden, the minimum proteid requirement for adults is mucli less tlian was formerly supposed. He found that 40 grams (li/j ounces) of ordinary beef or six eggs (roughly), with carbohydrates sufficed to keep himself, weighing GO kilograms (130 pounds) in nitrogen equilibrium. "\Miilc the minimum re(iuirement is a matter of importance when one wishes to supply the actual needs of the body, it is not often that the diet of healthy adults does not contain an excess of i)ro- teid except among tbe very poor. Professor Chittenden thinks proteids greatly in excess of the minimum ref[uircmcnts arc injurious, Init this view is not generally accepted, and some standard dietaries give 150 grams (5 ounces) or more of proteid corresponding to about ()')0 grams (1/4 pounds) of beef a.s the daily amount for 178 PHARMACOPEIA AND PHYSICIAN. a man weighing 70 kilograms (150 pounds) doing liard work. Standard dietaries show considerable variation, ^vhether it he for prison fare or the ration of the soldier or hospital diet. Two of these are given in order to afford an ap- proximate idea of the kind and quantity of foods required under different conditions. The amounts in the first table are for a man weighing 70 kilo- grams (150 pounds) with work varying from light work to hard labor. Proteid 100 to 150 grains ( 3 to 5 ounces) Fat 46 to 100 grams ( ly, to 3 ounces) Carbohydrates 375 to 565 grams (13 to 20 ounces) The total calories in this list vary from 2,450 to 4,150. The following table represents approximately the average diets of several hospitals in Germany : Proteid 100 grams (3 ounces) Fat 50 grams (1^2 ounces) Carbohydrates 150 to 400 grams (5 to 13 ounces) Here the calorific values varv from about 1,400 to 2,300. It should be remembered that ordinary beef or other meat may contain more fat than proteid, but the leanest meat obtainable may be considered as about one-third proteid. An egg contains approxi- mately 6 grams of proteid, while cereals contain little or none. CHAPTEE YIII. ASTEIXGEJsTTS. Astringents are substances which produce a con- striction of all the solid tissues with' which they are brought into intimate contact. Substances of this chiss have a peculiar action on mucous membranes, causing wrinkling of their surfaces and diminution of secretion; they precipitate not only proteids and gelatin, but also alkaloids and many glucosids. The action of astringents, irritants and caustics is largely a matter of degree, the caustics acting as astringents when sufficiently diluted, while all as- tringents produce at least a transient and slight irritation, and when applied in concentrated form to mucous membranes many of those classed as mere astringents are capable of causing consider- al)le irritation, which in the stomach may give rise to vomiting,, and in the intestine to diarrhea. Some astringents are essentially mild in tluir action, wbile others, being nearly insohil)lr. cnii not be brought into intimate contact witli the tissues in concentrated ff)rni ; these can not produce more than a \(it mild and fleeting irritation, or stimu- hilioii. wliicli is followed by lessened permeability i)\' the cjiiiillai-y walls ami diminished congestion. Uy tlicii- ii-i-iiaiit aclioii. drii-s of this partic- ular class nuiy inci'casc a scscrc aculc iullamma- tii)M wiiiioul being able bi pi'ddiicc their lypical as- ti'ingent cflVct. Ik'Mcc they arc ikiI nearly so useful in such conditions as in chronic inllamiiuitions. 180 PHARMACOPEIA AND PHYSICIAN. The vegetable astringents owe their action mainly to the presence of tannins, substances belonging to an ill-defined group, possessing an astringent ac- tion as their best defined property. Other or- ganic acids play only a minor role as astringents. The tannins give blue-black or greenish-black re- actions with ferric salts; they precipitate proteids (leather being the product formed with connective tissue), alkaloids, metals and some other sub- stances; they yield pyrocatechin or pyrogallol on destructive distillation. Their therapeutic actions are independent of their chemical peculiarities, and they are severally indicated rather with reference to the presence or absence of extractive matter. The combination of tannin with peptone is in- soluble in the gastric juice, and this and the insolu- ble albumin tannates are decomposed in the alka- line juice of the intestine, the tannin forming alka- line tannates which possess little or no astringent action. If the free tannins reach the intestine after the administration of extracts of the crude drugs,, they act on the mucous membrane, lessening intes- tinal secretion; this greatly modifies the bacterial development, and, therefore, the general intestinal conditions. Some of the metallic albuminates are soluble in an excess of proteid, and when in such a case the liberated acid is corrosive there is a pen- etrating corrosive action such as that of zinc or mercuric chlorid. With an insoluble precipitate, such as lead albuminate^ which forms an imper- vious coating, and a mildly astringent acid, like acetic, there is a typical astringent and non-irri- tant effect. The same astringent substance may be used in a ASTRIXGENTS. 181 variety of conditions^ and a number of different astringents are applicable to a given condition. A better acquaintance with the different tannins may lead to the selection of certain ones for particular cases, but at the present time we are guided more by the physical condition in which a given one is available; thus the official tannic acid is readily dissolved in the stomach, where it combines with the proteid of the content, or with the mucous membrane, whereas the tannin of gambir (gambir replaces the catechu of the Pharmacopeia of 1890) is protected by the presence of gum and extrac- tives, and so passes into the intestine, there to exert its astringent effect. We can not attempt anything like a complete enumeration of the various uses of the astringents, but must content ourselves with summarizing briefly the principal indications of astringents and some of the chief characteristics of the more common remedies of this type. USES OF ASTRINGENTS. Astringents are used internally in the treatment of diarrhea and dysentery, in congestion of the mu- cous membrane of the stomach and intestines, and for hemorrhage in the alimentary canal and other directly accessible regions. The use of astringents — either organic or inorganic — for their effects on parts which can only be reached by way of the blood vessels is wholly irrational, and when benefit follows it is not due to the astringent action, since by their very nature astringents can not exist free in the blood in sufficient concentration to exert an astringent action. Traces of tannin are not as- tringent any more than they are irritant, and as- 182 PHARMACOPEIA AND PHYSICIAN. tringents act only when lirought into intimate con- tact with the tissue in sufficient concentration. The metals are poisonous when absorhed, and, as a rule, vegetable astringents are to be preferred for internal administration, particularly when they must be used for a considerable period. Pure tan- nin, or tannic acid^ as it is designated in the Pharmacopeia, may be used locally whenever a purely astringent action is indicated ; for example, when secretion is excessive, and when it is desired to harden the skin in order to prevent excessive sweating. The treatment of accessible, inflamed mucous membranes with antiseptic solutions, and more particularly with solutions of hydrogen dioxid, has greatly lessened the use of astringents, and the cleansing of an infected surface should be a rou- tine procedure even when an astringent is to be applied subsequently. Dry tannin insufflated against an elongated palate often affords instan- taneous relief. Tannin in the pure state is rarely used inter- nally because of its irritant action on the stomach, one of the preparations of astringent drugs being preferred in such cases. The dry powder acts as a styptic when applied to bleeding surfaces, but it must be borne in mind that tannic acid and all other astringents when given l)y mouth exert their astringent action only on the alimentary canal. The various proprietary remedies, composed of tannin and albumin, gelatin or albuminoids, have not been shown to possess any decided therapeutic advantages over the official astringents, and sev- eral of the proprietary compounds, owing to their ASTEINGEyrS. 183 variable composition, must necessarily be uncertain in their actions. Tannic acid in simple solution combines with the albuminous contents of the .stomach, and with the mucous membrane itself if the stomach be empty and the tannin in concentrated solution; it may tben give rise to vomiting and even to diarrhea. Tbis irritant action of the astringents leads to the use of several of them — alum, and zinc and copper sulphate — as emetics. Tannin, being a precipitant of alkaloids, is use- ful as an antidote to those poisons when they are in the stomach — not when they have been given bypodermically, except possibly in the case of morphin, which is excreted into the stomach. The tannates tbus formed are slowly broken up, and the stomach must Ije evacuated by emetics, or, jjreferably, by tbe .stomach pump, as promptly as possible, tannin being added to the water which is used to wash tbe stomach after evacuation. Tea and coffee contain tannin, and, since they are al- most universally available in emergencies, their use is very common. Toi'ald Sollmann^ deter- mined the cnicicncy of in fusions of tea and coffee as pi'ccipiliuils fdi' \ai-i()us alkaloids and metals, and fouiid the infusion of lea innrli tbe more ac- tive, Ijut licit bor of ilicni voiT ivlialilc foi- tlie com- nionlv u.^od alkaloids, wliilo llir only uietals for \\lii(li I'M (infusion) would \>r useful are mercury, lead and silver. As a siuL;lc dose of lead never gives rise to acute sym|)lonis, and as poisoning with silver salts is cxti-cnidy larc we must con- clude Hull [)oisoning wilb inei-cui'ic salts is practi- 18-4 PHARMACOPEIA AND PHYSICIAN. cally the only instance likely to be encountered in which tea would prove to be an effective precipi- tant. The use of tea and coffee as stimulants in poisoning depends mainly on the caffoin, and, of course, these remarks as to their limitations do not apply to the stimulant use of them. VEGETABLE ASTRINGENTS. AciDUM Tannicum. — U. S. p. — This is a light yellowish amorphous powder of a characteristic odor and a strongly astringent taste; it is very soluble in M'ater. alcohol or glycerin. Average close: 0.5 gm. (8 grains). Glyceritum Acidi Tannic:. — U. S. P. — A 20 per cent, solution of tannic acid in glycerin. Average dose: 2 c.c. (30 minims). Teochisci Acidi Tannici. — IT. S. P. — Each troche contains 0.06 gm. (1 grain) of tannic acid with sugar and tragacanth, flavored with orange- flower water. ' Gambie. — U. S. P. — Gambir was introduced into the present Pharmacopeia to replace catechu 'of the earlier editions. It is an extract prepared from the leaves and twigs of Ourouparia gambir and occurs in irregular masses, varying in color from reddish browu to a pale brownish gray. It is inodorous, but has a slightly bitter, very astringent taste, with a sweetish after-taste. Average dose: 1 gm. (15 grains). TiNCTUEA Gambir Composita. — U. S. P. — This represents 5 per cent, of gambir and 2.5 per cent, of Saigon cinnamon in diluted alcohol. Average dose: 4 c.c. (1 fluidram). ASTRINGENTS. 185 Trochisci Gambir. — U. S. P. — Each troche contains 0.06 gm. (1 grain) of gambir with sugar and tragacanth, flavored with orange-flower water. Kixo. — U. S. P. — The inspissated juice of Pterocarpus marsupium was introduced into medi- cine by Dr. John Fothergill about 1757. Average dose: 0.5 gm. (8 grains). TiNCTURA Kixo. — U. S. P. — The strength of this preparation has been reduced to 5 per cent, to obviate its tendenc}' to gelatinize. Average dose: 4 c.c. (1 fluidram). The vegetable drugs that contain tannin are so numerous, and their general therapeutic actions are so similar, that we shall merely enumerate the following well-known vegetalde astringents and official preparations : RUBUS (blackberry-root l^ark).- — Fhiidextract and Syrup. Red Rose. — Fhiidextract and Syrup. Geranium. — Fhiidextract. Heaiatoxylon. — Extract. Rhus Glabr.v. — Fhiidextract. A combination of chalk which has attained very great popularity in tbo treatment of diarrhea is tbe MiSTURA Vm^TjR. — U. S. P. — Chalk ]\rixtiire lias the following composition : Prepared chalk, G gm. (90 grains) ; powd. aca- cia, 4 gm. (()0 grains) ; powd. sugar, 10 gm. (150 grains); cinnamon water. K) c.c. (10 fliiidrams), with water cnmigli i.. make 1 00 ,■.<•. (;) fluid- ounces). The average dose is 4 teaspoonfuls (15 c.c). 186 PHARMACOPEIA AND PHYSICIAN. Chalk mixture is so well known that it is men- tioned merely as a reminder of one of our best and simplest remedies for diarrhea. It is peculiarly adapted for combating the diarrliea of children. Severe c^ses may require the addition of a few drops of the deodorized tincture of opium to each adult dose or a suitable amount of paregoric (the camphorated tincture of opium) for children. Troches of tannic acid are used almost exclusive- ly in affections of the mouth and throat. Gambir (catechu), kino, krameria and many other vegetable drugs contain large amounts of their peculiar tannins, together with mucilaginous and other extractive matter which tends to pre- vent the tannin from forming compounds in the stomach and thus preclude its action on the mu- cous membrane before it comes into the intestine, hence the preparations of these substances are more useful in the treatment of diarrhea than are pure tannin and its preparations. Troches of gambir are well adapted for use in sore throat, after the throat has been sprayed with a solution of hydrogen dioxid, instead of the as- tringent gargles which were formerly so much in vogue. Kino, like Gambir, may be given as a powder, prefejably combined with opium and aromatics, as in the "Compound Kino Powder," N. F., which contains : Kino, 75 ; cinnamon, 20 ; powdered opium, 5 parts. The following prescription, though somewhat complex, is a slightly modified form of one used in certain hospitals with satisfactory results; al- though the chalk is alkaline, it does not appreci- ASTRINGENTS. 187 ably lessen the astringency of the mixture, as do the carbonates of the alkalies which exist in the intestine. The compound tincture of gambir, or the tincture of krameria, may be used instead of the tincture of kino : ft. Cretae prseparatae 3i 4 Tincturse kino 3iv 15 Tincturte opii m. v 3 Spiritus chloroformi m. Ixxv 5 AqUcT menthpe piperitae 3x 40 Sj'iupi aurantii q. s §iii 100 For children of from 3 to 10 years of age, from one-half to one teaspoonful of this mixture may be given every two or three hours ; for adults the dose is one tablespoonful. Gallic acid is sometimes recommended as an astringent, but it possesses no such action except that of any very weak acid, and it is absolutely useless for hemorrhage in the lungs, kidneys and other regions reached only by the circulation. Thougii opium does not contain tannin, it would be a distinct omission if we failed to mention some of its indications in this place, since this work is intended primarily to call attention to the pos- sible therapeutic uses of the official substances, and since the arrangement into groups, such as as- tringents, is merely for convenience. Small doses of any of the opium preparations afEord one of the surest means of iclid' in diarrhea. They are commonly coiiihiufil with astringents, inorganic, as well as organic, with excellent results, despite the chemical incoiii]iiitiliiliiy existing between the alkaloids and tlie varidii- taiiiiiiis or' iiielallic sails. The jireiiai-atioiis (if npiiini will lie nienlioiKMl in the later chapters, and we now niei'i-ly wish lo call attention to methods of condiinin": these a"-onts. 188 PHARMACOPEIA AND PHYHICIAN. I^. TineturtE gambir conipositiP gi 30| Tincturse opii deodorati m. x 5 Bismiithi subnitratis 3iiss 10 Aquae camphorae q. s ^iii 100 Sig. : One teaspoonful hourly for three or four hours, then every two or tln-ee hours. Any one of the insoluble bismuth salts may be used, and tincture of kino or krameria substituted for the compound tincture of gambir. Similarly, an appropriate amount of the camphorated tinc- ture of opium may be substituted for the deodor- ized tincture. . When it is desired to give the same active ingredients in the form of a dry powder the following may be used : I^. Opii pulveris gr. v 13 Bismuthi subnitratis gr. cl 10 1 M. Et div. in chart, x. Sig. : One powder to be given every two, three or fovu' hours, according to the needs of the patient. Here, again, the combination may be varied almost endlessly by using one of the other in- soluble bismuth salts, the deodorized opium, or by adding a small proportion of one of the veget- able astringents like kino or gambir. The pill of lead and opium is well adapted for securing a very slowly soluble form for adminis- tering these drugs. The pill is useful in diarrhea, but must not be long continued, lest it give rise to lead poisoning. IJ. Plumbi acetatis gr. xx 113 Opii pulveris gr. x J6 M. Fac pilulas No. x. Sig.: One pill to be given three or four times a day. Inflammation of the stomach and intestine and gastric ulcer may be treated by an insoluble as- tringent powder which not only relieves conges- tion by its astringent property, but also forms an ASTRINGENTS. 189 insoluble protective covering, preventing the con- tact of irritating particles of food and the gastric and intestinal secretions, besides lessening the amount of these secretions. METALLIC ASTRIXGEXTS. The insoluble salts of bismuth are admirably adapted for the protection of the intestinal mu- cosa from irritants of various kinds. While as much as thirt}-. times the average single dose of bismuth salts has been given in the course of a day, by the mouth, without any distinct evidence of un- toward results, absorption and poisoning have fol- lowed the external use of bismuth salts as a dusting powder when used over a large surface. Owing to the extremely poisonous nature of bis- muth when absorbed, the solu])le salts seem to us to be entirely superfluous, particularly as their solubility, until precipitation occurs, precludes the very object for M'hich bismuth compounds are chiefly used — that is, for the mechanical coating of the surface with a protective layer of insoluble powder. It must be admitted, of course, that even the soluble salts of bismuth are astringent, but we have many safer astringents which ai-c harmless that might well be used in their stead. The activity of the noslniin-iiinkcrs has resulted in ])lacing on the market a iiiinilici' n\' picparations that are intended to coml)ine the aiiliscptic proper- tics of the benzene derivatives willi the astringent |ir()|icrtics of hismiith. hut iiiilil \vc kimw more of the possihilitics ;iii(l the I i in i1 ;ili..n> nF int. ■Mini an- tiseptics it is prel'crahh' to use the siniph' astrin- gents and to use our aiitiscplics separately. inn PHARMACOPEIA AXD PHY8ICIAN. BiSMUTHi SuBNiTEAS.- — U. S. P. — All insolu- ble white powder, without odor or taste. BisjruTTii SuBCAEBOxAs. — U. S. P. — Closel}" re- sembles the subnitrate. Average dose (of cither salt) : 0.5 gm. (8 grains). BiSMUTHI SUBSALICYLAS. — U. S. P. — This preparation closely resembles the subnitrate in physical properties and is intended to combine the antiseptic properties of the salicylic acid with the astringency of bismuth salts. Average dose: 0.35 gm. (4 grains). BiSMUTHI SuBGALLAS. — U. S. P. — This prepa- ration was at one time widely advertised and is even now occasionally prescribed by its proprietary name, dermatol. It occurs as a bright yellowish, insoluble, odorless and tasteless powder, which is mostly used externally as a substitute for iodo- form. It possesses the advantage over the subnitrate of 2. A typical prescription for gastri<' iiu-itation. or ulcer, is as follows : R. Bismuthi subnitratis grs. cl 101 Mucilaginis acacisB 3xii 50 Aquae cinnamomi q. s. ad Siii lOOf M. Sig. : Shake well and take one or two teaspoonfuls three or four times a day. In cases in which marked irritability persists, the addi- tion of 0.01 gm. (1/6 grain) of cocain hydrochlorid to each dose, as a local anesthetic, may be advantageous, but we do not advise it as a routine procedure. For diarrhea one or two drops of the deodorized tincture of opium may be in- cluded for each dose, or, if preferred, tincture of opium. For this purpose, it is usually preferable to give one dose every hour for three or four doses, then every two to four hours as needed. Bismuth subcarbonate may be used instead of the subnitrate and tincture of kino, tincture of krameria or the compound tincture of gambir (catechu) may be added in the treatment of diarrhea. ASTRINGENTS. 191 not being very liable to absorption when used as a dusting powder. Average dose: 0.25 gin. (4 grains). PLinrBi AcETAS. — IT. S. P. — Acetate of lead, or sugar of lead, is said to have been known to Geber. It was described by Eaymund Lully in the thirteenth centur}', but was not used in medicine until introduced by Goulard a little more than a century ago. It occurs in crystals or as a heavy white powder, having an acetous odor and a sweet- ish, astringent, afterward metallic taste. Average dose: 0.05 gm. (1 grain). Liquor Plumbi Subacetatis. — U. S. P. — An aqueous solution containing not less than 25 per cent, of lead subacetate. Liquor Plumbi Subacetatis Dilutus. — U. S. P. — This contains about 1 per cent, of lead sub- acetate and is made by mixing 4 parts of the solu- tion of lead subacetate with 96 parts of distilled water. The official salts of zinc that are of interest as astringents are: Zixn SuT.iMrAS. — T". S. P. — Colorless crystals, wilboiit ddni'. li;i\iiig an asti'ingont nictallie taste. Zinc sulpbate is soluiile in loss than 1 ]iart of water, but is insoluble in nlcnlml. Average dose: Emetic, 1 gm. (15 grains). ZlNCI PllENOLSULPTTONATE. — IT. S. P. — The zinc per cent, of anhydrous aluminum and potas- sium sulphate. 194 PHARMACOPEIA AND PHYSICIAN. OFFICIAL LEAD SALTS. Lead is of interest cliiefly because of the crironic lead poisoning so often encountered. The principal internal use of lead is in the form of the pill of the acetate, usually combined with opium, in the treatment of diarrhea. It has also been recommended for dysentery, but is not nearly so useful in that disease. This preparation should not be given for any considerable length of time, lest it give rise to chronic lead poisoning. The solution of lead subacetate is unfit for internal administration, but is of value in painful swell- ings and local inflammations and burns. The well-known mixture of laudanum and lead water has long been popular as an external application, but any mucilaginous liquid could probably be used in place of the tincture of opium without detriment, since the astringency of the lead is the main factor, the local application of the opium alkaloids being entirely superfluous because they are not absorbed from the unbroken skin. The local use of lead watei- itself is so thorouglily well estal)- lished that it scarcely requires further comment.' THE LOCAL TREATMENT OF MUCOUS MEMBRANES. The local treatment of inflammation of the mu- cous membranes in the mouth, nose, throat, vagina and urethra, after thorough cleansing, preferably 3. The foUowing mixture wiU probably answer the pur- poses for which laudanum and lead water are commonly used : R.. Liq. plumbi subacet min. Ixxv 5| Mucil. acac min. xlv 31 AquiB q. s. ad f. Siii 100 1 The solution of lead subacetate is diluted with oo c.c. (16 fluidrams) of water and the mucilage with 37 c.c. (10 fluidrams) : the two are then mixed. Fifteen c.c. (4 fluidrams) of the water may be replaced by alcohol, but the amount of alcohol present in the mixture of laudanum and lead water is too small to be of any benefit. ASTRINGENTS. 195 ■with a solution of hydrogen dioxid, may require mild astringents of either organic or inorganic sub- stances, though, as previously stated, the use of the solution of hydrogen dioxid has greatly lessened this necessity. Alum has long enjoyed a particular reputation in the treatment of stomatitis, and has also been used as a gargle, but it is injurious to the feeth. and the necessary solution, made of 1 part of ahim in 20 parts of water, is preferably applied directly to the affected parts by means of a camel's- liair pencil or a swab made of absorbent cotton. After gargling, the moutli should be rinsed with water. Alum is not given internally so often as it was formerly; it is irritating and possesses no ad- vantages over otlier astringents. Because of this irritaut action it is emetic, and, while not very dependable, may serve in an emergency if no surer emetic is at hand. Small ulcerations of the throat, after having been cleansed witli an antiseptic so-' lution. may be touched with a mixture of 1 part of fci-ric subsulphate and 2 parts of gh^cerin. using a caiiicrs-liair pencil or a cotton swab. A \ci'y lai'^v miinbcr nf a-tringent gargles are in coiiiiiion iiM'. lull tin- following is a good represen- tative of the class : R. TinetuviP foni dihjridi ni. el 10 Potassii c'hloratis Siii 12 Aquae q. s f^vi 200 Tliosc who olijccl to the use of ferric chlorid iiiav liiid tlir r.,|lo\viii,- |)rcrcMil)lc: li. Clvcriili aci
  • ^alis. (• ci'lain a Ikaloids ])()S.-;('.ss a Jiiarki cdlv asl riiigent, or, more |i iropcrly. 198 PHARMACOPEIA AND PHYSICTAN. vasoconstrictor, effect when applied to mucous membranes. Of these, the most useful are hydras- tinin, a derivative of hydrastin, from which it is obtained by oxidation, and the alkaloid of the suprarenal gland. Here we are compelled to admit that this latter alkaloid, which is now being mar- keted at the modest price of some $800 per ounce, despite Abel's simple and inexpensive method of preparation, is superior to the official desiccated suprarenal gland. The application of a 1 to 1,000 solution of hydrastinin or a 1 to 5,000 solution of the suprarenal alkaloid, in 0.9 per cent, solution of sodium chlorid, to an inflamed conjunctiva or inflamed nasal mucous membrane often affords prompt relief. In view of the very great difference in cost without a corresponding difference in ef- fect, the physician can well afford to use hydras- tinin in preference to the more expensive alkaloid in such conditions. The desiccated suprarenal gland may be mace- rated in water and the fluid filtered and used, but any of the preparations of the alkaloid which appear under a variety of trade names will usually be preferred. Slight hemorrhages are also stopped by either of these means. When the flow of blood is copious and hot water is ineffective, styptics are useful; they are not alone astringent, but also cause a sudden coagula- tion of the blood, and this plugs up the oriflce. Large clots must be removed, as they prevent the immediate contact of the astringent or styptic and may conceal a hemorrhage occurring in cavities — the uterus, for instance — in which case the clot may fill the upper part of the vagina. ASTRIXGEXTS. 199 It is necessary to bear in mind the dijfference be- tween the action of vasoconstrictors, like the alka- loid of the suprarenal gland, and the action of styptics, like tannin or the ferric salts. With the former the action is transitory and the hemorrhage may recur as soon as the action of the drug has worn away, while styptics, when effective, form a plug in the normal d'stended ])lood vessel. An- other point to be remembered, in this connection, is the fact that the absorption of a vasoconstrictor, following its continued or too liberal use, will cause a general rise of blood pressure and thus actually increase the flow of Ijlood at the bleeding points. At least one death following an injection of ad- renalin has been attributed to that drug. The pa- tient died eight days after adrenalin and cocain had been used in the extraction of a carious tooth. GLANDUL^Ti: SUPRAREXALES SlCCE. — U. S. P. — Desiccated Suprarenal Glands are directed to be ob- tained from the shcej) or ox. freed from fat, cleaned, dried and powdoivd. (Jnc part of desic- cated suprarenal gland represents a})proximatcly parts of fresh glands free from fat. Average dose: 0.25 gm. (4 grains). The alkaloid contained in the suprarenal glands lias been variously designated as epinephrin by .Vbel, suprarenin by Fiirth and adrenalin liy Taka- iiiine. The trade names that are now :i|)|ilied to the solutions of the same substance ai'c K'gion, and it seems very unfortunate indeed that the commit- tee on revision of the Pharmacopeia did not recog- nize-the alkaloidal substance in an official way and give it an official title. The only effect to be ex- 200 PHARMACOPEIA AND PHYSICIAN. pected from the internal administration of the gland or its alkaloid is the local constriction that is noticed when it is applied to the mucous mem- brane. The solution of the alkaloid is without ef- fect on blood pressure when given by the stomach and when injected just beneath the skin it pro- duces practically no effect, except a local vasocon- striction. The dried gland is unsuited, of course, for intravenous use. CHAPTER IX. lEEITAXTS. EMOLLIENTS AND - DEMUL- CEXTS. There are so many substances which have been used as irritants under varying conditions that we can not attempt to do more than mention the more useful of the agents frequently employed for this purpose, together with some of the conditions in which clinical experience has shown them to be most beneficial. While the enn)lnyinent of counter-irritants is almost wholly empirical, the regions of the skin which Brunton has indicated for their use when it is desired to influence the internal organs corre- spond well with those which Head has shown to exhibit tenderness of the skin in connection with diseases of the same organs. Brunton directs the irritant to be placed over the larynx, ovaries or sciatic nerve for affections of tbose parts, over the ensiform cartilage for gastric ili^llll'liaiicc. ;l i()\c aiK lieldw tlie knee in rheuma- lisiii. i)\cr tlic )all (.r t le great toe (dorsal surface) in gout, bchiii 1 llie e; V in facial neuralgia, at the base of the ln'; in ami laek of [he neck for cerebral airc.'ti(.ii^. ami alnii- t le (loi'sal ivujon lo all'eet the iiici'iis. Till- iniM(>l (if iiTil aiils is water oi- ,-aline solu- tinii used a- a halli. riie .-lioek of (lie cold water ai)])li('d to the skill an 1 tho -light iri'iiation of tlu> subsequent Iri ■li.m. pi eferahl}- wil li a coarse towel. 202 PHARMACOPEIA AND PEYmCIAN. are followed by a reaction attended with a consid- erable and lasting stimulation. Very cold water may produce too great a shock in persons who are not robust, and the result will be depression, but there can be little doubt that baths are extremely beneficial when the temperature is so regulated that a healthy glow and a feeling of well-being succeed. It seems that the question of the useful- ness or the harm of cold baths, about which there has been so much contention, resolves itself into a question of individual experience. If a feeling of exhilaration, hut no subsequent depression, fol- lows the l)ath it is not harmful; if no such exhila- ration occurs, l)ut a distinct depression is observed, there can be but little doubt that the bath is doing harm. In such cases a slight increase in the tem- perature of the water, with a shorter time and more rubbing, may secure the benefits sought. The same person may require different conditions of temperature at different times, corresponding to variations in the general health. A mixture of salts is sometimes added to the bath to increase the slight irritant action. Even milder than the friction, which forms so essential a part of the bath, is the irritant action of the astringents, which have been discussed in Chapter VIII^ but these are followed by lessened irritation, hence they are not considered among the irritants. RUBEFACIENTS. Rubefaction is the result of a slight irritation of the skin. There is a slight increase in the exudate from the capillaries, and if the irritation be not HVBEFACIENTS. 203 long continued this exudate is reabsorbed and the part speedily returns to the normal condition. While all irritants, mild and caustic, cause rube- faction, we shall first consider those which are used for that stage alone, and take up the vesi- cants, pustulants and caustics later. ALCOHOL, Alcohol alone, diluted with water or in the form of hanuimelis water, alcoholic tinctures, spirits or liniments, is used more frequently, perhaps, than any other mild irritant, with the possible exception of "the bath. Applications containing alcohol are useful in painful swellings, bruises and a great variety of minor complaints commonly treated in the house- hold without calling on the physician. While it is probably (|uite unnecessary, at this late date, to c-all iiarticular attention to the fact tliat there is a very great diiference between tlic official, or ethyl, alcohol and the various forms of wood, or methyl, alcohol, nevertheless the insidi- ously poisonous properties of the latter substance do not appear to be Well appreciated by the general j)ublic. The number of cases of blindness and of death that have been rcjiorted l)y Biiller and Wood^ amply demonstrate tliat cxi'ii tlic cxlci'iial use of aiiv toriii of wood alcohol is iiol ciitii'cly Tree from danger and that its use in any foi-m of mrdicinal pivparaiinn sIioiiM nn( \>r (Mumtcnan.vd or (olcr- alcJ. .\mong the numerous prejiarations of the 1. 'I'irK jMiitNAi, A. M. A., Oct. 1, 8, 15, 22 nnd 20, 1904. 204 PHARMACOPEIA AND PHYSICIAN. United States Pharmacopeia tliat have been used as topical applications, largely l)ecause of the rube- facient properties of tlic alcohol that they contain, we may enumerate: Aqua Hamameltdis. — U. S. P. — This prepara- tion, more popularly known as extract of witch- hazel, or distilled extract of witchhazel, is now, for the first time, included in the Pharmacopeia. While the preparation itself has been known for many years, and has been used extensively as a household remedy, it has never met with much favor on the part of the medical profession. The official preparation is directed to contain 15 per cent, of alcohol and should be free from methyl alcohol or any of its derivatives. TiNCTURA Arnica. — U. S. P. — Tincture of arnica represents 30 parts of the dried and pow- dered flower heads of Arnica montana in diluted alcohol. This preparation was at one time very popular with medical practitioners as a topical application in so-called "sprains" and in bruises, but is now seldom employed. The same is true of : TiNCTUUA Calendula. — U. S. P. — This prepa- ration represents 20 per cent, of the dried and powdered florets of Calendula o-fficinalis, the well- known marigold of our gardens. Probably the most objectionable feature in con- nection with the use of any of the official tinctures as topical applications is their tendency to stain. This objection is largely overcome by the use of the simple diluted alcohol, one of the numerous unofficial toilet waters or colognes, or by the use of one or the other of the official spirits. RUBEFACIEXTS. 205 In addition to Spieitus Frumexti. — U. S. P. — Whisky, and Spiritus Vini Gallici.^U. S. P. — Brandy, the most frequently used of this class of prepara- tions is : Spiritus Campiior-t;. — U. S. P. — This is an alcoholic solution containing 10 per cent, of cam- phor. Spiritus Gaultheri^. — U. S. P. — This con- tains 5 per cent, of oil of gaultheria in alcohol. The most widely used, as well as the most pop- ular, of the mildly rubefacient liniments of the Pharmacopeia is : LiNiMEXTUM Sapoxis. — U. S. P. — Soap Lini- ment is variously known as liquid opodeldoc, cam- phorated soap liniment and camphorated tincture of soap. It contains 6 parts of soap, 4.5 parts of camphor, 1 part of oil of rosemary and 72 parts of alcohol with sufficient water to make 100 parts. This preparation has long been popular as a topical application and is not infrequently used as a ve- hicle for other more active rubefacients, sedatives and anodynes. A soinewbat tyi)ical compound liniment is the Linimextu:m Ciiloroformi. — U. S. P. — This is a simple nii.xture of 30 parts of chloroform with 70 parts of soap liniment, and constitutes a very good illustration of the possible uses of soap lini- ment as a solvent or vehicle. CHLOROFORM. Chloroform is one of the more active rube- facients and the action quickly passes this stage if its use be continued. Chloroform readily dissolves fat, and, being very volatile, it penetrates quickly, 206 PnARMACOPEIA AND PHYSICIAN. causing considerable redness and pain. A few drops of chloroform placed on a little absorbent cotton and applied over a painful joint, such as. a bunion, in such a way that evaporation of the chloroform is prevented, causes a good deal of pain but ofien affords speedy relief. It should not be applied in this way for longer than ten or fifteen minutes. Chloroform may be used as a counter- irritant by putting a few drops on cotton in a wide-mouthed bottle and applying the mouth of the bottle to the area to be treated for a few minutes at a time. Chloroform liniment, noted above, is much less painful, or not at all so in most cases, and is much slower in producing its effects. Chloroform lini- ment is usually directed to be applied to the af- fected part by being thoroughly rubbed in, thus securing the additional rubefacient action of fric- tion. It may, however, be more economically ap- plied, and is frequently quite as effective, if di- rected to be put on cotton, applied to the affected surface and then covered with several layers of cloth or otherwise prevented from evaporating too rapidly. VOLATILE OILS. All the volatile oils are irritant, their action ranging from that of the mild sandalwood or copaiba oil to the extremely irritant volatile oil of mustard or even the caustic action of oil of cloves. The use of the milder members of this series for their effects on the urinary tract will be mentioned in connection with diuretics. Some of the volatile oils, such as pennyroyal and savin oils, which are somewhat more irritant, have been employed to RUBEFACIENTS. 207 produce abortion by reason of irritation of the in- testine and the consequent participation in the effects b}- the uterus. Of the official substances that are more or less closely connected with the turpentine group and are frequently used externally, we have : Oleum Eosmaeini. — U. S. P. — This is a vola- tile oil distilled from the fresh flowering tops of Rosmarinus officinalis and is one of the ingredients in the well-known soap liniment. Oleum Sabix^. — U. S. P. — Oil of Savin has been quite extensively used as a local irritant. It must be used with caution in order to guard against the tendency to act as a vesicant. Oleum TEREBiXTHiNiE.— U. S. P.— Oil of Tur- pentine is the volatile oil distilled from turpen- tine. Even as an external application it is not in- frequently used in the form of Oleum TEREBiNTHiNiE Eectificatum. — U. S. P. — This is identical with oil of turpentine in chemical properties, but it has a more agreeable odor. Terebinthina. — U. S, P. — This is officially de- scribed as the concrete olcoresin of Finns palustris and of other species of Pinus. Resixa. — U. S. P. — Eosin, resin or colophony, is the residue left after distilling off the volatile oil from turpentine. The last two articles, rosin and turpentine, arc interesting only as constitu- ents of several official preparations, of which the best known are: Cefjatum Eesin^e. — U. S. P. — This is a cerate containing 35 parts of rosin, 15 parts of yellow wax and •"»() jwirls f)f liTrd. 208 PHARMACOPEIA AND PHYSICIAN. Ceratum Eesin^ CoisirosiTUM. — U. S. P. — This is a revival of the one-time official Deshler's salve. It contains rosin, yellow wax, prepared suet, turpentine and linseed oil. LiNiMENTUM Tebebinthin^.— ^U. S. P. — This is a solution of 65 parts of resin cerate in 35 parts of oil of turpentine. It has been recommended to be used in place of the oil of turpentine as a local application when the action of the latter might be considered as too irritating. Plasters of Burg-undy pitch, Burgundy • pitch with cantharides and of resin were formerly of- ficial. In practice these old-time resin plasters have long since been replaced by the more modern rubber-base plasters. CAPSICUM. Capsicum.— U. S. P.— The dried ripe fruit of Capsicum fastigiatum constitutes one of the most popular of the rubefacients used at the present time. Of the available official preparations we have : Fluidexteactum Capsici.— U. S. P.— This is made with strong alcohol. TmcTURA Capsici.— IT. S. P.— This is made with a mixture of 95 parts of alcohol with 5 parts of water, and represents 10 per cent, of the crude drug. Either of these preparations may be used diluted wdth alcohol or with soap liniment as a local rube- facient or irritant. Oleoresina Capsici.— U. S. P.— This is made bv extracting capsicum with acetone and may be used in the shape of the plaster, as noted above, or RUBEFACIENTS. 209 in the form of the now popular mixture with pe- trolatum. The best representative of the rubefacient plas- ters now in use is the EiiPLASTRUM Capsici. — U. S. P. — This is di- rected to be made by applying a thin coating of oleoresin of capsicum to adhesive plaster. MENTHOL. . Mextiiol. — U. S. P. — This is a secondary alco- hol obtained from the oil of Mentlia piperita or other mint oils. Camphorated Chloral. — X. P. — This prepa- ration, quite popular in some parts of the United States as a local application, consists of equal parts of hydrated chloral and camphor. It is a thick, oily-looking liquid, which is extremely irri- tating. It may be diluted with the fatty oils, al- cohol or soap liniment. MUSTARD. Mustard is official as : SiNAPis Alba. — U. S. P. — White Mustard is the seed of Sinapis alha. SiNAPis Nigra. — U. S. P.— Black Mustard is the seed of Brassica nigra. Oleum Sinapis Volatile. — U. S. P. — This is a volatile oil obtained from black mustard (freed from its fatty oil) by maceration with water and subsequent distillation. Ciiarta Sinapis. — U. S. P. — jMustard Paper is directed to be made by coating rather thick, well- sized paper with a mixture of i-iibber cement and jiowdered bhu-k imistard wbicli bus been deprived of its fatty oil. 210 PHARMACOPEIA AND PHYSICIAN. Mustard foot baths, containing one or two ounces of powdered or ground mustard, prefer- ably the black, thoroughly mixed with a gallon of warm water, are extremely useful for the relief of mild congestions of the head and of the gastro- intestinal tract. Prompt relief is often obtained in this way from headache and from pain in the stomach. In many cases, even mild attacks of indigestion show decided improvement almost immediately; the action is further accelerated if a hot-water bag is placed over the region of the stomach at the same time. The feet should be placed in the bath while the legs and feet are briskly rubbed with the mustard water for ten minutes or until the skin is red and some irritation is felt. The extremities are then rubbed dry with a coarse towel and wrapped in flannel or a blanket. When a slight degree of counter-irritation is desired for some time, a mus- tard poultice is employed. This is made by mixing one part of the ground black mustard with about five parts of flour (or ten parts of flour in the case of children), and mixing with enough water to form a mass. This is then spread on cheesecloth and applied at once. Mustard poultices have been largely replaced by the much more convenient mustard papers, which are dipped in tepid water and applied at once. They are prone to become worthless in damp cli- mates, since the absorption of moisture causes the slow development of the volatile oil, which then evaporates as fast as it is formed. With proper precaution, however, they may be preserved for a R UBEFA CIENTS. 2 1 1 considerable length of time, and they will usually be found to afford the most convenient means of applying counter-irritation. Baths are used for their tonic and antipyretic action. The importance of friction — rubbing with a towel — after a bath can not be insisted upon too strongly, for the cold bath is potent for much harm in certain conditions, and the patient may pass into collapse if the proper technic is not observed in such cases. The antipyretic effect is only one, and perhaps even a minor, nse of the bath in typhoid fever. The tonic effect is absent, and much injury may be done when the cutaneous cir- culation, as evidenced by the redness of the skin, is not re-established after the bath. The regular use of the cold bath in the morning is very commonly supposed to lessen the tendency to catch cold. Mild ruljofacicnts, such as alcohol, soap lini- ment, tincture of arnica and hamamelis water, are used for bruises and painful swellings. They induce redness of the skin and temporary changes in the cutaneous circulation, but their use bej^ond this stage is not indicated in these affections. Oil of turpentine may be applied either in the form of the official liniment, diluted with a fatty oil., or it may be used in substances as a stupe; the latter is made by saturating a cloth with hot water, wringing it out and then dropping on it a little oil of turpentine, or dipping the moist doth into the oil of turpentine and again wringing it out and applying while still Avarm. Loc-al applications of this kind will lie rnuin'I useful in broncliitis. 212 PHARMACOPEIA AND PHYHICIAX. Oil of turpentine is used internally, and it i.s applied as a stupe externally for the excessive flatulence often seen in typhoid fever; the lini- ment of turpentine is occasionally used as a pro- tective in the trcatinent of burns. Eesin cerate and the compound resin cerate are used to stimulate indolent ulcers such as are often seen after burns and scalds. Spirit of camphor may be used in much the same way, as well as by local application for head- ache and neuralgia. Chloroform, particularly in the form of the lini- ment, is useful as an anodyne in painful inflam- mations of the superficial tissues, but its evapora- tion must be prevented by an impermeable cover- ing, such as oiled silk. Capsicum plaster and other rubefacients are used for muscular rheumatism, neuralgia and colic. Menthol in cones, or in alcoholic or ethereal so- lution, is applied to the skin for headache and neu- ralgia. It causes a burning sensation and then that of coolness. Oleoresin of capsicum may be used as a rul)e- facient in the form of an ointment made as fol- lows : IJ. Oleoresinae capsici gr. xv 11 Petrolati §iii 100| M. Ft. unguentum. Sig. : Use locally. Chloral camphor is an active rubefacient, but it is said never to cause blistering. It is used in toothache and in neuralgia. RUBEFACIENTS. 213 HEAT. The uses of heat are so numerous and so well known that they scarcel}' require further mention at this time. We may be permitted to call atten- tion, however, to some of the various forms of cataplasms or poultices that are frequently used for their rubefacient or irritant properties. Among the official substances that are frequently used for the preparation of poultices we have : LiNUM. — IJ. S. P. — Linseed or flaxseed is the ripe seed of Linum usitatissimum. UL:\rus. — U. S. P. — Elm or slippery elm is the dried bark of VJnius fulva, deprived of its peri- derm. Carbo Ligni. — U. S. P.— This is charcoal pre- pared from soft wood and powdered. Poultices are ordinarily prepared by mixing the requisite amount of ground flaxseed, ground elm bark or other substance with enough boiling water to make a rather stifE mass, inclosing this in a piece of gauze or muslin and applying to the sur- face as hot as it can be borne. The rubefacient properties of a poultice may be increased by the addition of ground mustard, tincture of capsicum or of oil of turpentine. For removing fetor or to act as disinfectants, poultices may have added to them powdered charcoal, chlor- inated lime or tlie official solution of chlorinated soda. The present edition of the United Slates Pluir- macopoia has included one poultice, as : Cataplasma Kaolini. — U. S. P. — This con- sists of kaolin, glycerin and boric acid, with tliy- niol, methyl salicylate and oil of peppermint as •214 PHARMACOPEIA AND PHYSICIAN. admixture to give it a pleasing odor. This prepa- ration, like other poultices, is most efficacious when applied hot, but, as its action depends to a very great extent on the rubefacient properties of undi- luted gl3'cerin, due precaution should be taken to prevent the absorption of water or of watery vapor during the course of preparation or when heating it preparatory to applying. Practically the same preparation is being of- fered to the medical profession at the present time under a variety of trade names, and, while the combination undoubtedly has uses, many, if not all, of the positive claims that are made in con- nection with it are, to say the least, somewhat ex- aggerated, and the preparation should not be ex- pected to accomplish more than might reasonably be expected from an equivalent application of heat and mild rubefacients. One other point in connection with this particu- lar preparation that has been the cause of some controversy in the advertising pages of medical journals is the question of priority. This question may safely be ignored, as the mixture, apart from the flavoring ingredients, can not be said to be new. Glycerin magmas have been known and used for upward of half a century, and a formula for practically an identical preparation may be found in the Pharmaceutical Journal, London, for March, 1858. Formic acid has long been known and used in domestic practice as a rubefacient. In Germany it has found considerable favor in regular medicine and is official in the S. 219 cantharides in a mixture of liquid petrolatum, yellow wax^ rosin and lard. Cantharides cerate is most frequenth' used in the form of a plaster, spread on the official adhesive plaster or some other suitable grease-proof material. CoLLODiini Cantharidatum. — U. S. P. — Can- tharidal Collodion represents the chloroform sol- uble portion of 60 parts of cantharides dissolved in sufficient flexible collodion to make 100 parts. Ti^^CTUEA Cantharidis. — IT. S. P. — This prep- aration represents 10 parts of cantharides ex- tracted with alcohol. It is not usually efficient as a vesicant, but is frequentl}- used externally as an irritant or rubefacient. The active principle of cantharides is not soluble in water, and, as the normal skin is usually covered with a thin film of perspiration, the necessary pre- cautions must be taken to have the blistering prep- aration come in contact with the dry skin. This is most readily accomplished by washing the part with soap and water and wiping it with a small amount of strong alcohol. In the case of the cerate or plaster the alcohol may be followed by a fatty oil, or, better stilk the surface of the plaster may be thinly coated with a coating of oil. In directing the use of a blister it should be re- incmberod that the resulting vesicle is usually larger than the plaster that has been applied, and the size of the latter, therefore, should be gauged accordingly. Cantharidal orillodion is simply painted on the surface, and is more ilcniily than the cerate. In using blistering collodidn Ihc same precaution of 220 PHARMACOPEIA AND PHYSICIAN. thoroughly cleansing the skin, with soap and water, and alcohol, should be observed so as to insure vesication. Vesication usually ensues in about six hours after the application of the vesicant, .but a some- what longer period may elapse even in cases in which all the necessary precautions have been ob- served, and the physician should allow ample time before he concludes that the preparation is worth- less. Cantharides is prone to deteriorate with age, and one is often inclined to attribute the failure to cause blistering, to the worthlessness of the pro- duct, but even a faultless preparation may at times fail to produce vesication. The now widely used rubber-base plaster con- taining cantharides, although not official, has many points of advantage over the less cleanly extem- poraneous plaster made from the cerate. After preparing the surface of the skin, as indicated above, the plaster is smeared over with a thin film of oil and applied at once. After causing sufficient vesication it can be removed readily, and in this respect offers some advantage over the blistering collodion which continues to act until exhausted. While cantharides is commonly employed as a vesicant, it is sometimes applied for a shorter time to produce rubefaction, and its irritant action is also made use of in hair tonics, as it is supposed to stimulate the growth of hair. The following formula fairly represents the form of mixture commonly used as a hair tonic : , VESICANTS. 221 IJ. Tineturae cantharidis fSii S Ammonii carbonatis 3i 4 Spiritus myrcifB f 51! 60 Aqua? q. s. ad f 5vi 200 M. Sig. : Apply with brush, rubbing into the scalp after washing with tar soap. For this preliminary cloaning, or shampooing, the expensive Packer's tar soap has no advantage over the very much cheaper tar soap generally used by machinists for wasliing grease from the hands. Cantharides is commonly recommended for the treatment of baldness, but, like every other agent used for this purpose, it is usually ineffective. Where an oleaginous preparation, containing cantharides, is desired, the following may be used : B. Olei rieini Tincturse cantharidis, afi fSii 8 Spiritus myrcia; f^i 30 Alcoholis q. s. ad ..fgvi 200 M. Sig.: Apply locally to scalp. The toxicology of cantharides is of some im- portance because the laity has an exaggerated idea of its efficiency as an aphrodisiac without a cor- responding appreciation of its Imrinfiil elfects on the kidneys. Poison oak has l)cen used as an irritant, but it is wholly unsuited for the purpose because of the extraordinary activity of the irritant principle, tlie uncertainty of its action, and the innl)i]ity to control it, wliicli render it I'ai' infciMor to many otlier available irritants. It is of considerable toxicologic interest because of the frequency with which accidental poisoning occurs, either from handling it or merely coming into the immediate neighl)orhood. since even dust 222 PHARMACOPEIA AND PHYSICIAN. particles ma}' carry enough of the extraordinarily active fixed oil, toxicodendrol or glucoside which, according to Acree and Syme, is the active sub- stance on vrhich the action depends, to poison sus- ceptible persons. Toxicodendrol penetrates the skin very easily and is, therefore, difficult to remove. Even bland oils are to be avoided in the treatment of poisoning by it, since they but serve to dissolve and spread the poison, the same being true, of course, of oint- ments, vaselin and cerates. In treating a case of rhus poisoning as much^as possible of the poison should be removed by re- peated washing with soap and fresh portions of warm water, after which a paste of soap or a so- lution of lead acetate is applied. If vesicles form they should be opened with care and the liquid received on absorbent cotton or a powder such as baking soda, since it would but extend the irrita- tion if the exuding liquid were allowed to spread over the surface of the skin. S}Tne used a solution of potassium perman- ganate in numerous cases of intentional and acci- dental poisoning on himself, and found it uni- formly effective. He rubbed a 1 per cent, solu- tion of the permanganate into the vesicles, whereby the poison was destroyed by oxidation. He found it very much more eft'ective when the part affected was immersed for a time in a hot solution of the permanganate. The resulting staining of the skin is a small matter compared to the discomfort of the poison in severe cases, but this stain may be re- moved with a solution of oxalic acid. The place should then be carefully washed with PUSTULANTS. 223 soap and warm water to remove even traces of the fluid from the vesicles, and the soap paste or the solution of lead acetate applied. Fluidextract of grindelia robusta, diluted with water, or with a saturated solution of sodium bi- carbonate (about 6 per cent.) has had a special reputation as a wash for the treatment of poison oak. PUSTULANTS. Pustulants are those irritants which give rise to pustules instead of vesicles. The pustulants ap- pear to be unable to affect the skin through the horny layer as a rule, but can only penetrate the orifices of the glands. They are much less fre- quently used than the rubefacients and the vesi- cants. As tartar emetic is not irritant except in acid solution it has been suggested that it is decom- posed by acids in the cutaneous glands, and there produces pustulation. Croton oil owes its irritant action to crotonoleic acid, which exists mainly in combination as a fat. This fat is not affected by the gastric juice, but is split up in the intestines and the crotonoleic acid is then able to exert its violent irritation result- ing in purgation. Applied to the skin croton oil causes pustuhi- tion. It is not now so much used externally or internally as it was fonncrly. (JI-FrCI.VL PUSTULANTS. Antimomi kt Potassii Tartras. — U. S. P. — Antimony and Potassium Tartrate, more common- ly known as tartar emetic, is usually seen as a 224 PHARMACOPEIA AND PHYSICIAN. white granular powder, without odor, and having a sweet, afterward disagreeable metallic taste. It is soluble in about 16 parts of cold water, but is much more readily soluble in hot water. Antimony and potassium tartrate may be used externalh', as a pustulant, either in the form of the powder, in aqueous solution, or in the form of an ointment. The German Pharmacopeia contains a formula for the latter preparation that appears to be quite popular on the continent of Europe. This is a simple mixture of 20 parts of antimony and potassium tartrate, with 80 parts of petrola- tum. Because of its irritant action tartar emetic pro- duces nausea or emesis^ when taken internally, ac- according to the amount employed. It is much more frequently used as a nauseant than as an emetic, and least often as a pustulant; for the latter pur- pose it will be found to be preferable to use it in the form of an ointment, similar to the one re- ferred to above, simply rubbed on the skin. Oleum Tiglii. — U. S. P. — Croton oil is de- scribed as a fixed oil expressed from Croton Tig- li'um. It occurs as a pale yellow, or brownish yel- low, viscid, fluorescent liquid, having a mild, oily, afterward acrid and burning taste. In eastern countries croton oil appears to have been known from a very early period. It was known in Europe several centuries ago, but fell into disuse and was reintroduced there with several other drugs from India, about 1813. CAUSTICS. Caustics are irritants which either cause violent inflammation, resulting in necrosis, or dissolve the tissue bv direct chemic action. CAUSTICS. 225 Caustics may be used to iDroduce counter-irrita- tion alone, to remove exuberant or diseased tissue or, in diluted form, to stimulate non-granulatin^ surfaces. * Apart from the use of the thermocautery in surgery, that of lunar caustic for exuberant growths and non-granulating tissues, and of ar- senic for the destruction of the nerves of teeth, caustics are not very widely used at the present time. The number of substances possessing a corrosive action is, of course, very great, but many of them are not suited for therapeutic use, thus the strong alkalies, such as caustic potash and caustic soda, dissolve the tissue and penetrate deeply, hence their action is not easily controlled, besides they are very painful. Potassium hydroxid, better known, perhaps, as potassa, is sometimes used to soften and to remove the callus of corns and warts. The action of silver nitrate, and of copper sul- phate, in the form of molded sticks, or cones, is so easily controlled that they are very commonly used. Argenti Nitras.— U. S. P.— Silver Nitrate, which appears to have been known to Geber as lapis infoi-nalis in the eighth century, has been used extensively. It occurs as colorless crystals, which are freely soluble in about one part of water and melt or fuse at 200° C. (392° F.). This hitter feature is taken advantage of in making the ofHcial forms of fused silver nitrate, and is also of advantage in forming extemporaneous prcpai'a- tions, for local application, by melting or fusing 226 PHARMACOPEIA AND PHYSICIAN. silver nitrate on to suitable metallic instruments such as sounds. Argenti Nitras Fusus. — U. S. P. — Molded Silver Nitrate contains about 95 per cent, of silver nitrate, with a small amount of silver chlorid, which is added to make the sticks tough and fibrous. Argenti Nitras Mitigatus. — U. S. P. — Miti- gated Silver Nitrate is composed of one part of sil- ver nitrate and two parts of potassium nitrate fused together. CuPRi Sulphas. — U. S. P. — Copper Sulphate or blue vitriol occurs as large, transparent deep blue crystals. For external use these crystals maji be rasped or filed into suitable shape, and are then used in very much the same way as are the sticks of silver nitrate. The various uses of these agents are so well known that they scarcely require extended treat- ment here. When the lunar caustic is used on exuberant granulations care should be taken to avoid bring- ing it into contact with the newly formed skin, which is recognized only as a bluish line, since this occasions pain and is, of course, destructive of the very object it is intended to promote. arsenic and zinc chlorid. Arseni Trioxidum. — U. S. P. — Arsenic Tri- oxid, also known as arsenous acid and as white arsenic, occurs most frequently as an odorless and tasteless white powder, that is but slowly soluble in about 100 parts of water. ZiNCi Chloridum. — U. S. P. — Zinc Chlorid oc- curs as a white granular powder or a porcelain- CAUSTICS. 227 like mass. It is freely soluble in water, but tlie solution decomposes, on long standing or boiling, depositing a basic salt. Arsenic and zinc chlorid have been used to de- stroy cancerous growths. Arsenic, particular!}^, has been widely used as the active constituent of various cancer cures that have been proposed by regular, as well as irregular, practitioners. Its action is very slow, and, therefore, it can be readily controlled, Ijut it occasions considerable pain. Arsenic may be employed in the form of powder, as an ointment, either with lard or petrolatum, or as a paste. In the latter case the arsenic is suitably diluted with cither starch or powdered althaea, and subsequently mixed with water to which a trace of gum or mucilage has been added. At present arsenic is frequently used for the de- struction of the nerves in carious teeth. Zinc chlorid is seldom used for its local corro- sive action. It may be used in aqueous solution or fused on to suitable metallic instruments, much as silver nitrate is employed. Mercuric chlorid is the most corrosive of the metallic salts, but it is too toxic to permit of its general employment for its local caustic action. SOME OTHER OFFICIAL CAUSTICS. AciDUM NiTRicuM. — U. S. P. — The official Nitric Acid contains G8 per cent, by weight, of ai)Solutc nitric acid, and occurs as a colorless, fuming liquid that is very caustic and corrosive. Liquor llYDitAnoYRi Nitratis. — U. S. P. — So- lution of IMercuric Nitrate occurs as a clear, nearly colorless liquid, having a faini ddni' of nitric acid and a strongly acid reaction. It should contain 228 PHARMACOPEIA AND PHYSICIAN. about 60 per cent, of mercuric nitrate and about 11 per cent, of free nitric acid. Unguentum Hydrargtri Nitratis. — U. S. P. — Ointment of Mercuric Nitrate is made by dis- solving 7 parts of mercury in 10.5 parts of nitric acid and adding this solution to 76 parts of lard that has previously been partially decomposed by 7 parts of nitric acid, and continuing the heat, if necessary, until the reaction is completed. The re- sulting ointment should have a bright yellow color, whence its popular name, "citrine ointment." Unguentum Hydrargyri Ammoniati. — U. S. P. — The Ointment of Ammoniated Mercury is now directed to be made by mixing 10 parts of am- moniated mercury with 50 parts of white petro- latum and 40 parts of hydrous wool fat. Chromii Trioxidum. — U. S. P. — Chromium Trioxid, commonly called chromic acid, should be kept in glass stoppered bottles and great caution should be observed to avoid bringing it in contact with organic substances, such as cork, tannin, sugar alcohol, etc., as dangerous accidents might result because of its violent action as an oxidizing agent. Nitric acid is a popular domestic remedy for the removal of warts. The surrounding surface should be thickly covered with petrolatum and a single drop at a time of the acid applied to the excrescence. Solution of mercuric nitrate is sometimes used for chancres and where it is desired to destroy the tissue. The ointment of mercuric nitrate is used more frequently than the solution ; it is not so corrosive, EMOLLIENTS. 229 but is an active stimulant in sj^philitic ulcers; it is also used in parasitic diseases of the skin. In the undiluted state it is too caustic for general use and is, therefore, usually diluted with lard. Oint- ment of ammoniated mercur}^ is used in much the same conditions as the ointment of the mercuric nitrate. A 20 per cent, solution of chromium trioxid is sometimes used for the removal of warts as well as for condylomata. Its use is not without danger and it should not be applied to a large surface. EMOLLIENTS. The word emollient is derived from emollio, to soften; demulcent comes from demulc&o, to smooth. Since the same agent is usually demulcent as well as emollient, the term to be used depends on the tissue to which the agent is to be applied, rather than on the medicinal agent itself. Mucous membranes rarely require softening, but an in- ilamed skin is frequently hard and rough, we therefore speak of applying demulcents to mucous membranes and emollients to the skin. Xot only bland oily substances and fats, but mucilages and diluted glycerin act as emollients. Glycerin, \\\\v\\ diluted with water, and rubbed into the skin, prevents it from becoming dry and liai'sh, and the tendency to crack. Oils and fats penetrate the skin and render it soft. SOME OFFICIAL EMOLLIENTS. AuEPS Lan^e Hyduosus. — U. S. P. — This prep- aration, formerly called lanolin, is tiie purified fat of the wool of sheep {Ovis aries)^ mixed with about 30 per cent, of water. 230 PHARMACOPEIA AND PHYSICIAN. Glycerinum. — U. S. P. — Glycerin or glycerol is a clear colorless liquid of syrupy consistence, ob- tained by the decomposition of vegetable or animal fats. Anhydrous glycerin is slightly rubefacient, but when diluted it is, as previously stated, an effi- cient emollient, MuciLAGO Tragacanth^. — U. S. P. — Mucilage of Tragacanth contains 6 per cent, of tragacanth and 18 per cent, of glycerin, with enough water to make 100 parts. Petrolatum. — U. S. P. — Under this general heading the present Pharmacopeia includes what was formerly known as hard and soft petrolatum. Petrolatum, a mixture of hydrocarbons, of the methane series, is obtained from petroleum and should be of about the consistence of an ointment. The oflficial substance may vary in color from yel- low to light amber and have a melting point vary- ing from 45° to 48° C. (113° to 118.4° F.). In addition to this, which is popularly known as yel- low petrolatum, the Pharmacopeia also includes : Petrolatum Album. — TJ. S. P.^This is a white unctuous mass, of about the consistence of ointment, that otherwise has the same chemical and physical characteristics as petrolatum. Petrolatum Liquidum. — U. S. P. — Liquid Petrolatum is a colorless or only slightly yellowish, oily, transparent liquid without odor or taste, but giving off, when heated, a slight odor of petrola- tum. Of the vegetable oils that are useful as demul- cents, it will suffice to enumerate : Oleum Amygdala Expressum. — U. S. P. — Expressed Oil of Almonds. EMOLLIENTS. 231 Oleu:m Gossypii Semixis. — U. S. P. — CottoD Seed Oil. , Oleum Oliv^.— U. S. P.— Olive Oil. 0leu3j: Theobromatis. — ^TJ. S. P. — Oil of Theobroma, so-called "cocoa" butter. Of the several official preparations used as emollients, we may mention: Ceratum. — U. S. P. — Cerate consists of 30 parts of white wax, 20 parts of white petrolatum and 50 parts of benzoinated lard. Unguentum. — U. S. P. — Ointment consists of 20 parts of white wax and 80 parts of benzoinated lard. These two preparations are used as emol- lients or as the bases for active medicinal sub- stances. LiNiMENTUM Calgis. — U. S. P. — Lime Lini- ment, or Carron oil, so called from the name of the iron works in England where this preparation had its origin, consists of equal parts of lime water and linseed oil. It has long been in use as a popular dressing for superficial burns and constitutes a readily applied and effective non-antiseptic remedy that rapidly allays the accompanying pain. If there has been extensive destruction of tissue, this remedy should be avoided, as it is not alone diffi- cult to remove, but also forms a covering beneath which bacteria may proliferate safe from the reach of antiseptics. Unguentum AqujE KosiE. — U. S. P. — Oint- ment of Rose Water, or, as it is usually called, cold cream. This ointment consists of a mixture of spermaceti, white wax, expressed oil of almonds, sodium borate and rose" water, and in one form or 232 PHARMACOPEIA AND PHYSICIAN. another has been the most popular of the mild emollients from the time of its originator, Galen. Emollients are used for the protection of in- flamed skin against irritants, the choice depending on individual preference or convenience rather than on the nature of the drug. Thus mucilage of tragacanth, ointment of rose water and petrolatum differ widely in their phj^sical properties, but they are all used for chapped hands, sunburn, and to soften the skin when it is rough and hard. The bland oils and ointments penetrate the skin more readily than does diluted glycerin, and, therefore, they are to be preferred as emollients when they are also to serve as carriers of medicinal substances intended for absorption. Diluted glycerin is an excellent agent for soft- ening the skin, but is somewhat irritant, and when the sensitive layers of the skin are exposed, a bland oil or ointment, such as cold cream, is to be pre- ferred. To prevent chapping of the skin when it is ex- posed to the wind, to alternate wetting and drying, or to irritants, tlie mucilage' of tragacanth, pre- ferably mixed with an equal portion of glycerin, will be found useful. The exposed surface is washed with warm water and soap to soften the akin, and while it is still moist, but not wet, a little of the mucilage, or the mixture of mucilage and glycerin, is rubbed into the surface until the latter feels smooth. Instead of the tragacanth mixture the following may be preferred by some, but it is somewhat irritant to very delicate skin : One ounce of glycerin soap is reduced to shav- ings and dissolved with the aid of gentle heat, in EMOLLIENTS. 233 half a pint of a mixture of equal parts of gh'cerin and water. This mixture solidifies on cooling, and a piece about twice the size of a pea is to be rubbed into the moist skin as often as ma}- be necessar}-. Those who work with irritant or corrosive chemi- cals will find this an excellent agent for keeping the hands soft. A liquid preparation that has met with consid- erable favor may be made by mixing ten parts of tincture of benzoin, fifty parts of water, and forty parts of glycerin. To secure a homogeneous mix- ture the water should be gradually added to the tincture of benzoin, and the glycerin added to this mixture. If the resulting mixture should still be irritating the amount of glycerin may be further reduced, with a corresponding increase in the quantity of the water. If rose water were substi- tuted for the water in the above formula the re- sulting mixture would simulate some of the well- known and widely-advertised proprietary toilet preparations of glycerin and roses. CHAPTEE X. LOCAL ANESTHETICS AND ANODYNES. The introduction of cocain marked a decided ad- vance in the production of local anesthesia. Previous to that, freezing the part by immersion in a mixture of salt and snow^ or shaved ice, or by spraying with ether or other volatile liquid, was used, and, while a procedure of this kind does pro- duce complete anesthesia, the pain experienced during the freezing and thawing greatly exceeds that which would be caused by such a simple operation as opening an abscess or the removal of a small foreign body, such as a splinter or piece of glass, when readily accessible. It is because of the inherent dread which the average person has of the surgeon's knife, that he will undergo suffering akin to that with which he is familiar, rather than endure a lesser one which seems dreadful because it is unfamiliar. It is also true that the injection of cocain some- times causes more pain than would the operation for which it is given, and, since surgical operations have become so much more common than they were formerly, many adults willingly bear the brief, sharp pain of a simple incision, rather than resort to cocain, 'which has come into a certain disrepute because of the abuse of it by its victims, the ma- jority of whom have become such through the use of supposedly harmless nostrums pretending to be Local AyESTHETics. 235 valuable remedies for hay fever and other minor affections. Cocain, which is methyl-benzoyl-ecgonin, shows a certain chemical analogy to atropin and aconitin, which reseml)le it somewhat in their action on sensory nerves, and it is also related to phenol through the benzoyl group, since benzoic acid dif- fers from phenol only by having a COOH group in place of the OH of the phenol. The anesthetic action of phenol is second only to that of cocain. Aside from the systemic effect, which Ave need not fully detail here, cocain paral3'zes sensory nerve endings with which it comes in contact and even nerve trunks when in sufficient concentration; if the solution is sufficiently dilute and the action not too long continued, the nerve endings rapidly re- turn to normal (the nerve trunk more slowly), when the application is discontinued and the co- cain removed by absorption into the general circu- lation, or evacuated. It is denied that cocain has a specific action on the sensory nerve endings, their more exposed situ- ation explaining the more prompt effect on them. When a fairly strong solution (3 per cent.) is injected into the area about a nerve trunk, or an even weaker solution, 2 per cent., within the nerve sheath, both sensory and motor paralysis occur in about fifteen minutes, affecting, of course, the en- tire distribution of the nerve, the effect lasting for some hours after intraneural injection. Since aqueous solutions are not absorbed from the unbroken skin, they must be injected beneath the epidermis, at least, in order that they may come into actual contact with the nerve ends. 236 PHARMACOPEIA AND PHYSICIAN. When the solution is injected deeply into the muscular tissue the greater part of it passes into the general circulation and is lost so far as local action is concerned. To avoid this, it is better to inject the solution between the layers of the skin, at the same time limiting the circulation in the part as much as possible by compressing the blood vessels, preferably with a rubber band or other tight bandage. Practically, the same object may be achieved by the use of a solution of the alkaloid of the supra- renal gland immediately preceding the injection of the solution of cocain. The injection of the solu- tion of sujjrarenal alkaloid (epinephrin, adrenalin or one of the other trade preparations) causes a local vasoconstriction that in turn prevents tlie rapid absorption of the cocain solution into the general circulation, and also prevents, for the time being, the excessive hemorrhage that is so objec- tionable in minor operations. When it is neces- sary for the solution of cocain to diffuse through a part, a moment should elapse after the injection before applying the constricting bandage. The combined use of suprarenal alkaloid and of cocain has proved to be of particular advantage in the eye and in the nose. One reason, and prob- ably the most weighty one, is to be found in the fact that normal mucous surfaces have a tendency to absorb cocain very rapidly. When cocain is applied to mucous membranes, either in powder or in solution, it causes its local effects for a short time and is then absorbed, pro- ducing its systemic action. Herein lies one of the chief sources of danger of the many so-called hay- LOCAL AXESTHETICS. 237 fever remedies, which virtually consist of cocain with some diluent powder, such as sugar of milk, and are intended to induce and to continue the trul}- terrible cocain habit. Owing to the brief action and rapid absorption. frequent repetition is necessarv to secure relief in "colds" and the user is peculiarl}- liable to become addicted to the habit which, in its baneful effects, is not exceeded, perhaps, in the whole range of drug addiction, not even excepting alcoholism. As a matter of fact, many of the so-called hay-fever nostrums are intended primarily for supplying those who are already victims of the habit and who would find difficulty in buying the drug imdcr its correct name. This practice may be said to con- stitute a disgraceful example of the lack of proper control of the nefarious nostrum traffic by the law. We should be particularly careful to warn pa- tients and others against the insidiousness of this type of self-medication that our skirts may at least be kept clean in connection witli t])is one phase of the evil. Cocain in solution i.s readily decomposed on l)oiling, but if the solution lie made with sterile, cold water there, will be little cause to anticipate sepsis from its injection with the usual precau- tions. The solution may be sterilized, however, by heating to 80° C. (176° F.) for half an hour at a time on two successive days, care being taken to cliniiiiatc all ])0ssible contaminations of even a ti'ac(.' of alkali. I'hicain and .slo\ain have the advantage of resist- ing decomposition hy boiling, but, as just sug- gested, the disaiKanliiLic ])ossessed hy cocain is 238 PHARMACOPEIA AND PHYSICIAN. more apparent than real, and the general action of cocain, particularl}^ its possible complications, being well known, that drug, no doubt, will con- tinue to hold first place as a local anesthetic, ex- cept where the ubiquitous detail man succeeds in frightening the more timid members of the profes- sion into an exaggerated idea of the various dan- gers attending the proper use of the official article, and into a corresponding credulousness concerning the entire harmlessness of the particular substitute in which he is interested. Cocain, when dropped into the eye, or taken in- ternally, causes an incomplete dilatation of the pupil by stimulating the sympathetic nerve, reac- tion to light being maintained, differing therein from atropin, which abolishes this reflex. OFFICIAL PREPARATIONS OF COCAIN. Cocaine Hydrochloridum. — IT. S. P. — Co- cain Hydrochlorid, the most widely used prepara- tion of cocain. is officially described as the neutral hydrochlorid of an alkaloid obtained from several varieties of coca. It occurs as colorless, trans- parent crystals or a white crystalline powder. It is soluble in less than one part of cold water and in 2.6 parts of alcohol, but is insoluble in petroleum benzin and in ether. CocAix.— U. S. P.— This is a^i alkaloid oh- tained from several varieties of coca, resembling cocain hydrochlorid in many of its properties, but being only slightly (1-GOO) soluble in water. It is soluble in 5 parts of alcohol and even more soluble in ether and in petroleum benzin. The alkaloid cocain is also soluble in about 13 parts of olive oil LOCAL ANESTHETICS. 239 and it, or the oleate, is to be used in making solu- tions of cocain in oil. Oleatum Cocain,^.— U. S. P.— Oleate of Co- cain contains o per cent, by weight of cocain in a mixture of oleic acid and olive oil. The liquid preparations of coca, the fluid extract and the wine, are never iised externally, although, if applied to the mucous surfaces, or to the abraded skin, their use would not be devoid of danger, from the absorption of the contained cocain, and other coca alkaloids. Cocain is used locally on mucous membranes to allay irritation and inflammation as in hay fever, but it should be used very guardedly and not be too long continued. It is very much less useful in this condition than was formerly supposed and it has been very lai-gely replaced Ijy the now com- monly used alkaloid of the suprarenal gland, which, it is claimed, allays the inflammation equally well and has the marked advantage of not inducing the habit. Solution of cocain is very commonly injected hypodermically, to produce local anesthesia during such slight operations as the evacuation of al)- scesses, the removal of splinters, bullets, and other foreign bodies. W'iien there is considerable inflammation and ex- treme tenderness, stronger solutions ai-c r('(|uired than when a healthy surface is to be incised. In the former case, a syringe having a Imig, liiu^ needle, is filled with a 4 per cent, solution of co- cain hydrochlorid, the needle is then iiiscilcd ob- liquely, or almost parallel with the surface, be- tween the layers of the skin, ])eyond the zone of 240 PHARMACOPEIA AND PHYSICIAN. increased tenderness, and a small drop of solntion is forced beneath the epidermis; a white spot is seen in a moment and the needle is then advanced through that toward the more tender area without removing the point of the needle from beneath the epidermis; with each advance a drop of the solu- tion is injected. When the needle has been passed under the epidermis for its full length, it is with- drawn and the point inserted into the most ad- vanced blanched area; in this way, using a curved needle, a complete circuit may be made of the seat of inflammation. The object of injecting the solu- tion between the layers of the skin is to secure anesthesia with a minimum of absorption into the general circulation. The psychic effect on the patient of having pain- less injections made into such an extremely tender region tends to allay the nervous dread of the knife, which is a more important factor than we, who are accustomed to seeing pain, are apt to realize. The injection of a solution of cocain into the hand is apt to prove ineffective when the trouble is deep seated, as in palmar abscess, and in such cases it is better to inject a small amount of a 2 or 3 per cent, solution around or into the nerve trunks in the forearm. The injection of strong solutions into nerve trunks has given rise to much trouble and it is preferable, therefore, to try to secure the effects from weak solutions. Kast and Meltzer have very recently shown that the abdominal organs are capable of exhibiting sensations of pain, and that these sensations are LOCAL AyESTHETIGS. 241 increased ])y inflammation, but that they may be completely abolished by a subcutaneous injection of cocain. Anesthesia involving all the body below the site of the injection may be secured by injecting about ten or fifteen minims of a 2 per cent, solution of cocain hydrochlorid into the subarachnoid cavity through a sterilized platinum needle which is in- serted at the side of the fourth lumbar vertebra. The patient must be placed in a sitting position, in order that gravity may not favor the passage of the solution up to the medulla. This method of using cocain (or any other drug) is attended with so much danger that it is not justifiable except when, for some reason, general anesthesia is not practicable. The anesthesia is induced in ten or fifteen min- utes, with cocain, but its duration is very variable, lasting from half an hour to five hours. When the application of a constricting band is not feasible the previous injection of a solution of the suprarenal gland, as previously suggested, will delay the absorption of the solution of cocain into the general circulation. It should be remembered, however, that the use of a vasoconstrictor only de- lays and does not prevent the absorption of the co- cain. When a large amount of the cocain solu- tion is necessary it will probably be preferable to use the infiltration method as proposed by Schleich. It is difficult to see what advantage is to be gained by the addition of morphin to a solution instead of directing the injection of the desired amount at once so as to secure its sys- 242 PHARMACOPEIA AND PHYSICIAN. temie effect. Schleich recommended solutions containing from 0.01 gm. (1/6 grain) to 0.2 gm. .(3 grains) of cocain hvdrochlorid and from 0.005 gm. (1/12 grain) to 0.25 gm. (I/2 grain) of mor- phin hvdrochlorid in 100 c.c. (3 fluid ounces) of 0.2 of 1 per cent, solution of sodium chlorid to which was added one-fourth of a drop of phenol. Strong solutions of cocain should not be used in carious teeth, and only small amounts of the weak solution. One or two drops of a 1 per cent, solu- tion often affords relief from toothache. Cocain is sometimes applied to hemorrhoids to lessen the pain and it may be said that its local use is much more rational than is that of opium, since the alkaloid morphin has no local analgesic or vasoconstrictor action^ a fact to be remembered when prescribing urethral injections, and lotions for inflamed surfaces of the skin. Cocain has also been used, in small doses, to re- lieve nausea. It may be given alone or with other antiemetics. The following is an example of a combination with cerium oxalate, the latter being used empirically : IJ. CocairtfE liydrochloridi gr. i 06 Cerri oxalatis gv^ xvi 1 Aquae aurant. flor f^i 30 M. Sig. : Shake the mixture and give one teaspoonful every half hour when needed. Many substitutes for ' cocain, of greater or less merit, have been brought forward by manufac- turers, and, while they have been widely heralded as being superior to cocain, they are not free from disadvantages; though the manufacturers have not; as yet, devoted much time or space to the LOCAL AXESTHETICS. 243 exploitation of these several disadvantages or dangers. Their further consideration, however, does not belong in a treatise on the Pharmacopeia. Hydrocyanic acid is a general protoplasmic poison rapidly causing paralysis and death to any tissue to which it is applied. It induces anesthesia when applied to mucous membranes, but owing to its rapid absorption and extreme toxicity it is not well suited for the purpose, though it is occasion- ally employed to depress the sensory endings when d^'spepsia is attended with pain in the stomach. Death occurs so quickly from fatal doses, owing to the rapidity of al)Sorption from the mouth and stomach, that there is rarely a chance for medical interference. It causes paralysis of the heart and respiration; hence artificial respiration is of no avail in the majority of cases, but if the dose has been insufficient to paralyze the heart strychnin may be used as a respiratory stimuhmt. Sodium hyposulphite is said to be useful as a cliemic anti- dote, since it forms the sulphocyanid. From 2 to 4 drams (S to IG grams) of the hyposulphite dis- solved in water is directed to be injected sulicu- taneously. ACIDUM HYDltOCVAXlcr.M DlLlTUM. 1". S. P. — Diluted Hydrocyanic Acid contains 2 ])er cent, of absolute hydrocyanic acid. As found in the shops it is of variable strength, owing to its ten- dency to decompose. Dilute hydrocyanic acid is sometimes used on tbo unbroken skin to allay itching, and it iiiny lie used internally with extreme eaiition to prevent the vomiting of pregnancy. 244 PHARMACOPEIA AND PHYSICIAN. THE ATROPIN GROUr. Atropin, which will be mentioned among the tinalgesics, acts locally as an anesthetic, its effects resembling those of cocain, but being weaker. Atropina.^U. S. p. — Atropin is officially de- scribed as an alkaloid obtained from Atropa Bel- ladonna and from other plants of the same fam- ih^ As it occurs in commerce, it is usually con- taminated l)y a small amount of hyoscyamin, from which it can not be readily separated. Atropin is soluble in 450 parts of water and in 1.5 parts of alcohol. It is very poisonous, the average dose being 0.0004 gm. (1/160 grain), and it should, therefore, be tasted with the utmost cau- tion and only in dilute solution. Atropin.e Sulphas. — U. S. P. — This is the sulphate of the alkaloid atropin. In its physiologic properties and dose, atropin sulphate corresponds closely fo atropin. It is soluble in less than one part of water and in about four parts of alcohol. Oleatum ATROPiN.^i:. — U. S. P. — Oleate of Atropin is a mixture of equal parts of oleic acid and olive oil, containing 2 per cent, of atropin, in solution. EXTRACTUM BELLADONX^Ti: FOLIORUM. U. S. p. — Extract of Belladonna Leaves is directed to be made with a menstruum consisting of two parts of alcohol and one part of water, and should contain, when assayed according to the process given in the Pharmacopeia, 1.4 per cent, of mydriatic al- kaloids. Unguentum Belladonna. — U. S. P. — Bella- donna Ointment contains 10 per cent, of extract of LOCAL AXESTHETICS. 245 belladonna leaves in a mixture of liydrous wool fat and benzoinated lard. E:MPLASTEUii BELLADOXNiE. — U. S. P. — Bella- donna Plaster is now directed to be made by mix- ing 30 parts of extract of belladonna leaves with 70 parts of adhesive plaster, and corresponds close- ly with the widely used, commercial, rubber-base plasters. It is further directed that spread bella- donna plasters should yield, when assayed by the process given in tlie Pharmacopeia, not less than 0.38 nor more than 0.42 per cent, of mydriatic alkaloids. Fluidextractuji Belladoxx.e Eadicis. — U. S. P. — Fluidextract of Belladonna Boot is directed to be made with a mixture containing four parts of alcohol and one part of water, and should yield, when assayed by the process given in the Phar- macopeia.. 0.5 per cent, of mydriatic alkaloids from belladonna root. LixiMEXTU.M Belladoxn^^ — U. S. P. — Bella- donna Liniment is virtually a solution of five parts of camphor in a sufficient quantity of fluidextract of belladonna to make 100 parts. Fluidextkactum Stramoxii. — U. S. P. — This i.s directed to be made from the leaves of Datura Stramonium with a menstruum containing two parts of alcohol and one part of water. The fin- ir axd similar solutions. The constant search for less dangerous anesthet- ics than ether and chloroform brings many sub- stances into notice. Morphin and scopolamin have found an ardent champion in Korff, who has used them for several years. He employs up to 0.035 gm. (1/2 grain) of morphin and 0.0013 gm. (1/45 grain) of scopolamin. Unconsciousness does not occur, and he claims absolute quiet must be maintained, while he stops operating long enough for pain to subside. He advises "drops" of chloroform or ether when necessary. The tongue must not be permitted to fall back into the throat. The use of this method of ' anesthesia in major surgery must obviously be very limited. A discus- sion of a nu7nber of fatalities attending the use of morpliin and scopolamin for general anesthesia will be found in La Semaine Medicale, Nov. 8, 1905, p. 529, and in The Journal of the Ameri- can Medical Association during 1906 and 1907. The combination of scopolamin and morphin may have certain advantages in obstetrics, but it is of the utmost importance that the proper technic be observed. Gauss has elaborated a method most carefully, and those who employ the combination will do well to read his article in the Centralblatt fi'ir Gyn., Jan. 12, 1907. Other authorities con- demn the practice on the grounds that it is liarm- ful to mother and cliild without accomplisliing tlie desired results. In view of tlio loiowii (hiiiu'crs altiMiding tlic use of scopolamin and morijhiii \\r must view the statements of those wlio are fiiiaiicinlly interested in the sale of this combination with extreme sus- 258 PHARMACOPEIA AND PHYSICIAN. picion. It can not be stated too emphatically that cactin adds nothing whatsoever to the safety of this combination. Morphin sulphate alone or in combination with atropin sulphate is very commonly employed pre- liminary to chloroform or ether narcosis, and ap- pears to have well-established uses in this connec- tion. E. Fraenkel reported some ten years ago that he had habitually used a mixture of morphin, atropin and chloral for hypodermic injections, pre- liminary to narcosis, for twenty-two years, without an accident. He claimed that this procedure less- ened to an extraordinary degree the amount of chloroform or ether used to maintain anesthesia. The solution used by Fraenkel was made as fol- lows : Morphin muriate gr. iiss Atropin sulphate gr. i^ Hydrated chloral gr. iv Distilled water 5ss 15 15 015 25 He injected hypodermically from 1 c.c. to 1.25 c.c. (15 to 19 minims) fifteen minutes before the commencement of the ether or chloroform admin- istration. Fraenkel further asserts that this mixture is free from the objectionable side actions of mor- phin, being well borne by patients who could not take morphin by the mouth or hypodermically. ETHYL CHLORID. A substance which bids fair to rival chloroform and ether as a general anesthetic, under certain conditions at least, is ethyl chlorid. GENERAL ANESTHETICS. 259 This substance is extremely volatile, boiling at from 12° to 13° C. (53.6° to 55.4° F.), and it is necessary, therefore, to keep it in sealed tubes. The ends of the tubes are drawn out to fine capil- lary tubes which are then sealed, or the capillary opening is closed by a metal cap which may be re- placed when a part of the contents of the tube has been used. When required for use the glass tip is broken off, or the metal cap unscrewed, when the heat of the hand causes the ethyl chlorid to vola- tilize, forcing out a fine stream which may be di- rected against the surface which is to be frozen for local anesthesia, or the stream may supply the vapor for inhalation to produce general anesthesia. Ethyl chlorid induces anesthesia more rapidly than ether docs, and when it is withdrawn the pa- tient recovers more quickly, thus saving an average of some twelve minutes on each operation, hence it is likely to prove useful on the battlefield and in great calamities when a number of operations must be performed with a minimum loss of time. Figures purporting to give relative degrees of danger for various anesthetics are notoriously un- reliable, but it seems probable that ethyl chlorid is less dangerous than chloroform and somewhat more dangerous than ether. Among the objec- tionable features of ethyl chlorid are increased cost, the explosive character of the vapor, extreme volatility, tlie accompanying waste of material and the difficulty of maintaining anesthesia. A numlxT of masks have been devised for use with etbyl chlorid. It has been suggested that the mask should be so arranged that the anesthetic docs not come too near the face, as freezing may 2G0 PHARMACOPEIA AND PHY^SIGIAN. thus ensue. Ethyl chloric! appears to be especially adapted for short operations, and in some hos- pitals it is replacing nitrous oxid preliminary to ether anesthesia. ACTION or CHLOROFORM AND ETHER. It would hardly be profitable to discuss here in detail the actions of chloroform and ether, but there are certain important points concerning them which are so frequently overlooked that we will consider them briefly. While there are records of as many as 40,000 consecutive anesthetizations with chloroform with- out a fatality, this is only possible in case of skilled anesthetists working with carefully selected cases. Certainly no such results are possible in ordinary practice, and with that alone we are concerned at present. We must always remember that the production of general anesthesia is a grave matter, in which death is an ever-present possibility despite the ut- most care, and of which there is actual danger un- less' caution is observed. The possibility of fatal complications in all cases of general anesthesia would appear to make it necessary that the patient or his friends be informed of this fact, if for no other reason than to- protect the physician admin- istering the anesthetic. Each case must be carefully considered when se- lecting the anesthetic, and neither chloroform nor ether should be used exclusively. Ether being the safer, however, should have the preference, when it is not contraindicted, and chloroform should not be used unless the anesthetist is experienced and is reasonably skilled in the use of it. GENERAL ANESTHETICS. 261 The following are some of the princijjal advan- tages and contraindications of both of these agents : The vapor of ether is inflammable, that of chlo- roform is not, and the latter is to be preferred when operations are to be performed bj' gas or lamp- light. In this connection, however, we must not forget that chloroform vapor coming in contact with an open flame is readily decomposed into chlorin and hydrochloric acid, and that it will be necessary, therefore, to provide for free ventila- tion to eliminate these decomposition products. If ether must be used under such circumstances, the light should be placed as high above the level of the mask as practicable, since ether vapor is heavier than air. The thermocautery can, of course, also ignite the vapor of ether. An acute cold is a contraindication to the use of any anesthetic, but more particularly to the use of ether. Ether is also contraindicted in bronchitis, because of the great irritation caused by the rela- tively large amount necessary to maintain anes- thesia; it is likewise contraindicated in nephritis, since the kidneys take part in the excretion, and suffer from the irritant action. In extremely hot weather, that is, when the ther- mometer is above 93° to 95° F. (34° to 35° C), ether is volatilized so rapidly that the atmosphere contains amounts which may prove objectionable, and it often becomes very difficult to maintain complete anesthesia. When it is absolutely imperative to reduce tlie stage of excitement to the minimum, or when it becomes necessary to secure complete anesthesia rapidly, ether is contraindicated and chloroform is 262 PHARMACOPEIA AXD PHYSICIAN. to be preferred when it is not specifically contra- indicated for other and more important reasons. In the latter event eth}-! chlorid may be used, or preliminary imconscionsness may be induced by nitrous oxid. and this followed up by the use of ether. Chloroform is very commonly preferred by ob- stetricians, but deep anesthesia is not usually in- duced in such cases. In fatty disease of the heart chloroform is con- traindicated because it also induces fatty degenera- tion of that organ, and for this reason it is not ad- visable to use it repeatedly on the same person in succeeding operations. Chloroform is much more toxic to the heart than ether, and there is a much narrower margin for safety between the amount necessary to induce an- esthesia and that which causes death, chloroform being much more active than ether in inducing anesthesia, but very much more toxic. A matter of the greatest importance, especially for the unskilled anesthetist, is the very brief in- terval between the cessation of respiration and the stopping of the heart beat with chloroform, giving very little chance to resuscitate the patient after respiration has stopped. With ether the interval is much longer, and the prompt resort to artificial respiration, while the body is raised higher than the head, very commonly results in saving the pa- tient. This difference in the action of anesthetics and also the fact that the condition of anesthesia is a dangerous one, according to the degree to which it is carried, will be more fully appreciated if we GENERAL ANESTHETICS. 263 have a clear conception of the several stages of an- esthesia and the rapidity with which a patient may pass from one stage into the other. These several stages are usually designated as : 1, the stage of excitement; 2, the narcotic and anodyne stage; 3. complete anesthesia; 4, paraly- sis and death. The acceleration of the circulation noticed in the first stage is similar to that produced by the inges- tion of alcohol or alcoholic beverages^ and the pro- duction of this stage was one of the uses to which ether was put long before it was used as an anes- thetic in surgical operations. From this stage the patient usually passes quite gradually into the second or narcotic stage. In the narcotic stage sensibility becomes im- paired, but there is not infrequently a persistence of reflex action which manifests itself in a form of delirium or wild excitement. This is usually an indication of faulty anesthetization and is a com- plication that can be avoided in many instances by the more careful preparation of the patient for the anesthetic. In the majority of instances, however, the patient passes rapidly into the third stage, that of complete anesthesia. In this stage there is complete absence of reflex action, even of the conjunctiva, which is usually, though erron- eousl}', advocated as the most satisfactory test for complete anesthesia. A satisfactory surgical anes- thesia is indicated by complete relaxation of nearly all of the muscles of the body, regular breathing, ilcep inspirations ami a fully relaxed lower jaw. Tiie widely prevailing though barbarous habit of 264 PHARMACOPEIA AND PHYSICIAN. touching the conjunctiva should never be re- sorted to. By the careful administration of the anesthetic this stage of surgical anesthesia may be continued for a considerable period of time, but we must never forget that it is ever bordering on, and may at any moment pass into, the fourth or paralytic stage, when respiration ceases, the heart beats be- come feebler, and, unless vigorous and prompt restorative measures can be resorted to, may cease entirely. THE ADMINISTRATION OF ETHER. While it has been asserted that the administra- tion of anesthetics is an art that can not be taught or learned, but must be acquired, it is also true that there are certain points or rules that have been sufficiently well established to warrant their being heeded, and the general conduct of anesthetization can best be illustrated, perhaps, by giving the method pursued by an ordinarily careful anes- thetist, when nitrous oxid is not used. The patient, who should not have had food for five hours preceding, is made thoroughly comfort- able, in a recumbent position, on a table or wheel stretcher, if in a hospital, with a pillow just suffi- cient to raise his head but slightly. The mouth is freed from false teeth and other foreign materials, and the lips and nose are an- ointed with petrolatum to avoid the accompanying irritation from contact with the anesthetic. A pad of moistened gauze is then placed over the eyes to avoid irritation by the fumes of the anes- thetic. GENERAL ANESTHETICS. 265 All these several stages should be carefully ex- plained to the patient so as to assure him that every possible precaution is being taken to provide for his comfort and well-being, and to gain his confidence, for the more important feature of ad- ministering the anesthetic itself. After the patient has been prepared and his con- fidence gained by explanation of the several stages of the preparation, he is allowed to accustom him- self somewhat gradually to the taste and smell of ether. To accomplish this the cone or gauze con- taining the anesthetic is held some slight distance from his face, and gradually brought closer as the patient becomes more and more accustomed to the inhalation. If the anesthetist has been successful in gaining the confidence of the patient he will find that the latter will pass through the prelim- inary stages of anesthesia without a struggle, and that complete relaxation will l)o secured witli a minimum of the anesthetic. When a patient has been completely anesthetized less of the anesthetic will suffice to nuiintain the condition and the further efforts of the anesthetist can be devoted to observing the respiration and the surface reflexes of the patient in order to pro- vent his reverting to the second stage of anes- thesia, or passing on into the much-to-l)c-(lrca(]o(l stage of paralysis of the respiratory center. With chloroform the passing from one stage of,, aiu'stbesia to the next is mucli moi'c rapid tlian witb ether, less of the anesthetic is used, more aii- must be allowed, and there is. of coui'so, a cor- respondingly siiiallfT iiiai'gln of safely in the stage of complete surgical anesthesia. 2GG PHARMACOPEIA AND PHYmCIAV. Since all of us can not become expert anesthet- ists and yet must at times perform that office, this advantage of ether is well worth consideration. The greatest immediate danger from inhalation of ether or chloroform, but more especially of the latter, is the administration of the vapor in too great concentration. One hundred volumes of air require approximately from three to four volumes of ether vapor, and 100 volumes of air require about one volume of the vapor of chloroform to in- duce anesthesia, but an increase of from two to three volumes in the concentration of the ether, or of only one volume of chloroform in 200 of air will prove fatal in a short time. While we do not actually measure the relative volumes of air and vapor, as a rule, these figures will serve to show the comparative danger of the two substances, for it is many times more difficult to avoid overstepping narrow boundaries than broad ones. When a perfectly safe ratio is maintained the delay in inducing anesthesia often proves vexa- tious, and the anesthetist may be urged to expedite the operation by increasing the concentration, but he should never forget the grave responsibility which he has assumed and should never permit the impatience of others to induce him to exceed the limits of caution, save only in those grave emer- gencies where delay in operating may mean death to others who are awaiting their turn. OFFICIAL ANESTHETICS. tEthylis Chloridum. — U. S. P. — Ethyl chlorid occurs as a colorless, transparent, very vol- flEXERAL AXESTHETICS. 267 atile liquid, having a characteristic, rather agree- able odor and a burning taste. It is only slightly soluble in water, but is readily miscjble with alco- hol. Ethyl chlorid is a haloid derivative, and is pre- pared by the action of hydrochloric acid gas on ab- solute ethyl alcohol. It is usually marketed in hermetically sealed glass tubes, and when liberated at ordinary room temperature volatilizes almost in- stantly. The resulting gas is very inflammable and the substance itself should never be used in ])roximity to an open flame or fire. For local anesthesia the liquid in a fine spray is applied to the surface to be anesthetized. The average amount necessary to induce general anesthesia is from 5 to 10 c.c. (75 to 150 minims). iETHER. — U. S. P. — Ether is a transparent, colorless, volatile liquid having a characteristic odor and a pungent, sweetish taste. It should con- tain 96 per cent, by weight of absolute ether or ethyl oxid and about 4 per cent, of alcohol contain- ing a little water. The per cent, content of ethyl oxid or absolute ether in a given specimen is a matter of consider- able importiince when the substance is to be used for anesthesia. The official other, when exposed to air, absorbs moisture, thus materially re- ducing the anesthetic value of the ether. The practice that has long been followed of sending out ether in hermetically sealed cans is an efficient safeguard against this absorption of moisture. CiiLOHOFOijMUM. — U. S. P. — Chloroform is a heavy, clear, colorless liquid having a characteristic ethereal odor and a burning, sweet taste. It should 268 PHARMACOPEIA AND PHYSICIAN. contain not less than 99 per cent, by weight of ab- solute chloroform and from 0.6 to 1 per cent, by weight of alcohol. Chloroform when not pnre is readily decom- posed, forming chlorin compounds that may prove to be extremely dangerous to the patient. Even chloroform that corresponds to the requirements of the Pharmacopeia may be decomposed in the presence of damp air and heat, and the substance should, therefore, be carefully preserved in small, well-stoppered bottles. CHAPTER XII EXPECTOEAXTS. The expectorants official in the United States Pliarmacopeia afford a great variety of choice. In- numerable combinations are possible, but we shall suggest only a few of these, in connection with some of the drugs and preparations available. It should be remembered that coughing serves to remove mucus from the respirator}^ tract and often requires no treatment. If, however, the cough becomes unduly severe, it may require alleviation; if the secretion is scanty it may he increased or rendered more liquid. Acute bronchitis may be divided into two gen- eral stages, with certain expectorants useful in each stage, but this is not to l)e taken as a rigid classification. The first stage — that of dryness of the mucous membrane, with considerable cough — calls for sed- atives; the second — that of free secretion — may require stimulant expectorants.^ The prevalence of coughs and "colds'" in the winter montlus is sufficient evidence of tlic iiii])<)i'- tancc of this class of ageuls. Tlicir use in donics- tic practice — largely as "•patciil incdicincs,"' so- called — ])robabIy exceeds llial (lircclcd hy tbe pliysieian as ten to one. 1. The terms "stlniiilfttlnfj" nnd "sedative" used In con- ned Um with expectoinnts refer only to the effect on the centrTM. 270 PHARMACOPEIA AND PHYSICIAN. Physicians are supplied liberally with literature by manufacturers of proprietary remedies of this type, but the pharmacology of this literature is not always worthy of the faith that some physicians place in it. As an example we quote from a circu- lar distributed exclusively to physicians: "In se- vere and frequent cough, when little mucus is se- creted, as shown by the scanty viscal sputum, mor- pliin, or, better, its derivative, ethtjl-morpliin, is indicated, which increases secretion and lowers excitability of the respiratory center." For com- parison with this interested statement by the man- ufacturers we quote (merely for the sake of com- parison) from an article on opium in Wood's Therapeutics (11th ed., 716) : "Its tendency to check secretion forbids its use, however, in a very large proportion of cases, notably in those in which there is persistent dryness of the bronchial mucous membrane." Sollmann, Cushny and others state that morphin possesses the same property, though to a lesser degree than opium, which is very gener- ally recognized. The manufacturer of each cough mixture advo- cates the use of his particular remedy for all coughs, but we may be pardoned if we again quote Wood for comparison : "It is plain that the medi- cal practitioner must study in each individual case the relations between the cough and the amount of work required." The discovery of a medicinal agent is the signal for a host of imitators whose product may differ, if at all, merely in the substitution of an ethyl for a methyl grouj), or of one harmless acid radical for another. These are presented in increasing num- EXPECTORANTS. 271 bers to the physician, who can by no possibility remember them all. Or, some well-known drug, whose length of service, if not merit, entitles it to some respect, is seized on to serve as a basis for fabulous claims, perhaps long since voiced, dis- proved and forgotten. There is still another interesting phase con- nected with these various nostrums. Many of us pride ourselves on the fact that we use only "eth- ical" preparations and also that we insist on know- ing just what we are prescribing or using. It must be rather embarrassing, therefore, to find that even the public is more exacting in this respect than we are and that the manufacturers of popular medicines, when they do advertise the com|3osition of their particular mixture, publish a full and complete formula and not an incomplete one such as we frequently find in the advertising pages of medical journals, or in the circulars that come to our desks. SEDATIVE EXPECTOR^VNTS. Among the official sedative expectorants to be used in the first, or dry, stage of cough, we have ipecac, tartar emetic, apomorphin, senega and other nauseants. Ipecac contains two alkaloids, emctin and ccplia?- lin, of which emetin is the more abundant and much the more active, and upon which the action of the crude drug mainly depends. Ipecac is extremely irritant to mucous surfaces, causing conjunctivitis and irritation of the nasal passages, with active secretion when brought into contact with those tissues, and nausea and vomit- ing when it is taken into the stomach. If a suffi- 272 PHARMACOPEIA AND PHYSICIAN. cient amount of the drug escapes evacuation dur- ing emesis and passes into the intestine the irrita- tion causes increased peristalsis, diarrhea, and even bloody stools. It is generally accepted as a fact that ipecac causes vomiting by its direct action on the stomach, and not ])y acting on the center, as apomorphin does. As in the case of other nauseants, ipecac causes increased secretion by the salivary glands and by the mucous glands of the respiratory tract. This effect is more lasting with ipecac than with apo- morphin and certain other emetics; hence its greater value in expectorant mixtures. Further- more, 'it causes much less depression than tartar emetic, and this is a decided advantage in many cases. Emetin is not well suited for subcutaneous in- jection, as it is extremely irritant. The mode of action of ipecac in tropical dysen- tery is unknown. Tartar emetic, like ipecac, acts directly on the stomach to cause emesis. This conclusion is not materially affected by the oft-quoted fact that emesis may be induced in an animal by this drug after the stomach has been replaced by the bladder of a pig. Most of the drug is evacuated during the vomit- ing which it causes, but if a sufficient amount escapes into the intestine it gives rise to symptoms closely resembling those caused by 'arsenic, and it is stated that as small a dose as two grains has proved fatal. EXPECTORA^'TS. 273 The nausea is accompanied by the usual effects on the pulse and mucous and salivar)'- secretion. Emesis usually follows an effective dose within twenty minutes, but. owing to the great depression which this drug produces, it is not nearly so useful as an emetic a? apomorphin. ipecac or one of the other metallic emetics, such as copper sulphate, but the nauseant dose is only about one-fifth that necessary for emesis ; hence it does not cause suffi- cient depression to interfere with its use in the case of robust patients. Apomorphin induces vomiting by direct action on the medulla, acting much more promptly and in smaller doses after subcutaneous injection than when given by the mouth. Small doses cause nausea, with the usual attendant symptoms, in- creased pulse rate and increased secretion of mu- cus and saliva. The nausea is usually of but brief duration. Init it is sometimes very persistent. Therapeutic doses of apomorphin have very little narcotic action and no perceptible effect on the heart. Ipecacuanha. — IJ. S. P. — Ipecac is the dried root of Cephaelis I pe.caciumha (Brotero), A. Eich- ard (Fam. Ruhi/jcea'). It is known commercially as Rio. Brazilian or Para ipecac, or the correspond- ing portion of C. aciimiruiUi, Ivarsten, known com- mercially as Carthagena ipecac, yielding, when as- sayed l)y the ])rocess given in the Pharmacopeia, not less than 2 per cent, of ipecac alkaloids. Ipe- cacuanha was first (lescrilx'd by Piso and ]\rarkgraf, in 1648, in tli<'ii- naliinil lii>lniT of I',i';i/.il. The drug appears to ha\c Ikmh well known to the na- 274 PHARMACOPEIA AND PHYSICIAN. tives of Brazil and to have been much prized for a variety of therapeutic purposes. It was introduced into Europe, about 1675, by John Helvetius, of Paris. The Carthagena variety of ipecacuanha is a comparatively recent introduction, being first noted as a distinct variety, about 1870. Ipecacu- anha is official in all pharmacopeias, but up to the present time the Pharmacopeia of the United States is the only one to recognize the Carthagena variety as being the equal of the Brazilian. PuLvis Ipecacuanhli:. — TJ. S. P. — Average dose: Expectorant, 0.050 gm. (1 grain) ; emetic. 1 gm. (15 grains). Fluidexteactum Ipecacuanha. — U. S. P. — Fluidextract of Ipecac. — This should contain 1.75 per cent, of alkaloids. Average dose: Emetic. 1 c.c. (15 minims) ; ex- pectorant, 0.05 c.c. (1 minim). PuLvis Ipecacuanha et Opii. — U. S. P. — Powder of Ipecac and Opium (Dover's powder). This contains 10 per cent, of ipecac. 10 per cent, of powdered opium and 80 per cent, of sugar of milk. Average dose: 0.500 gm. (7^/0 grains); used chiefly as a diaphoretic. Syrupus Ipecacuanha. — U. S. P. — Syrup of Ipecac. This contains 7 per cent, of fluidextract of ipecac and 1 per cent, of acetic acid in a mixture of glycerin, sugar and water. Average dose: Expectorant, 1 c.c. (15 min- ims) ; emetic, 15 c.c. (4 fluidrams) . ViNUM Ipecacuanha. — U. S. P. — AVine of Ipe- cac. A mixture of 10 per cent, of fluidextract of EXPECTORANTS. 275 ipecac, 10 per cent, of alcohol, and 80 per cent, of white wine. Average dose: 1 c.c. (15 minims). Senega. — U. S. P. — Eoot of Polygala senega. — This is one of the few drugs of American origin that has found a place in ever}^ recent pharmaco- peia. It contains a saponin which is locally irri- tant, but which is not absorbed ; hence, the drug is not depressing. It is almost invariabl}^ used in small amount as an addition to other expectorants. It has the disadvantage of an unpleasant acrid taste. The oflficial preparations are : Fluidextractum SENEGiE. — U. S. P. — Average dose, 1 c.c. (15 minims), and Syrupus Seneg^e. — U. S. P. — This contains 20 c.c. fluidextract of senega in 100 c.c. Average dose: 4 c.c. (1 fluidram). See also compound syrup of squill. Another irritant nauseant more notable for its abuse than its use is : Sanguinaria. — U. S. P. — Ehizome of San- guinaria canadensis (bloodroot). This drug, usual- ly omitted by modern therapeutists or dismissed Avith a line, contains sanguinarin, belonging to the morphin group, and causing depression of the res- piratory center. It is mentioned here more par- ticularly Ijecause of its widespread use by the nos- trum makers. The common name — bloodroot — appears to possess considerable psychical effect. 'J'lie only official preparation is : Fluidextractum Sanguinari^e. — U. S. P. Average dose: 0.1 c.c. (V/^ minims). 270 PHARMACOPEIA AA^Z) PHY8ICIAts\ The "Compound Syrup of White Pine" of the "Rational Formulary represents the "popular" ex- pectorant. It is not recommended, however, as it is too complex. - Antimonii et Potassii Tartras. — U. S. P. — Antimony and Potassium Tartrate; tartar-emetic. Colorless, transparent crystals or a white, granu- lar powder, soluble in 15.5 parts of water. This is the most popular and widely used of the medicinal compounds of antimony, and is now official in all recent pharmacopeias. Average dose: Expectorant. 0.005 gm. (1/10 grain) ; emetic, 0.03 gm. (14 grain). ViNUM Antimonii. — U. S. P. — Wine of Anti- mony. This contains 0.4 per cent, of antimony and potassium tartrate dissolved in a mixture of 1 part of alcohol and 5 parts of white wine, and en- ters into the well-known compound mixture of glycyrrhiza — a deservedly popular expectorant. Average dose: Of the wine 1 c.c. (15 minims). Tartar emetic is also an ingredient (0.3 per cent.) in the compound syrup of squill. ApomopvPHin.5; Hydrochloeidum. — U. S. P. — Apomorphin Hydrochlorid. — The hydrochlorid of an alkaloid prepared from morphin by the abstrac- 2. The following is the formula for the Compound Syrup of AVhlte Pine : White pine bark (piuus strobus) . . . .oiiss 75 Wild cherry bark 5ilss 75 Spikenard i-oot 3iiss 10 Balm of Gilead buds Siiss 10 Sanguinaria root 3ii 8 Sassafras bark grs. cv 7 Morphin sulphate grs. viiss 5 Chloroform 3iss 6 Sugar Sxxvss 750 Alcohol Water Syrup (U. S. P.), of each to make . .Oii lOOOi EXPECTORANTS. 277 tion of one molec-ule of water. It is soluble in 40 parts of water, in the same proportion of alcohol, practically insoluble in all other solvents. Apomorphin is much less useful as an expector- ant than as an emetic, its action being brief. Average close: Expectorant, 0.002 gra. (2 mg. or l/';30 grain) ; emetic, 0.005 gm. (5 mg. or 1/12 grain). IPECAC. When the bronchi are inflamed and the secretion is scanty or thick and tenacious, nauseants, such as ipecac, lead to increased secretion which secures its removal by cougliing. The choice of nau- seants is guided by the general condition of the l)atient, ipecac being preferred to antimony and potassium tartrate in those cases (children and weakly persons) in which great depression would 1)0 dangerous. The active principle of ipecac is not usually emploj-ed in the pure state as an ex- pectorant, the syrup of ipecac being preferred, as the tannin present retards absorption and prolongs the action. The expectorant dose of nauseants is always very much less than the emetic — approximately one- iciith or less' in the case of ipecac. "The average doses -given are approximate and the expectorant dose is to be repeated every two oi- llii-cc hours; the emetic dose is to be repeated half-bourly until .■llV.-tivc. For ciiiiii) in Hinall cliildi'cu Few I'cincdics enjoy a greati'r i'c|iu(;il ion ilmn syi'iip of ipecac, whicb is given alone in (|o.-es of tVom ten to tliirly di'ops, r('|)catcd a1 intei-\al.- of tliirt\- minutes until xoni- itiuL'' occurs. 278 PHARMACOPEIA AND PHYSICIAN. The preparations of ipecac are seldom used alone as expectorants, but are usually added to mixtures of allied use. The following may be considered a typical pre- scription for ipecac to be used in teaspoonful doses every two hours; for the syrup of ipecac a corre- sponding amount of fluidextract or wine may be substituted. When an opiate is imperatively de- manded 15 c.c. (4 drams) of comphorated tinc- ture of opium may be added without other change: IJ. Syrupi ipecacuanhae fSvi 25 Ammonii chloridi Siss 6 Syrupi tolutani, q. s. ad f^iii 100 Sig. : A teasjDOonful at a dose. ANTIMONY. Antimony and potassium tartrate is a more depressing nauseant than ipecac and senega. It may be used on robust persons, but not with safety on children or the infirm. Its mode of action is similar to that of ipecac, and here, too, we have a variety of official preparations. For the administration of antimony and potas- sium tartrate, the official compound mixture of glycyrrhiza (6 per cent, wine of antimony, 0.024 per cent, antimony and potassium tartrate) is used alone or with ammonium chlorid as fol- lows: I^. Ammonii chlor 3i 4| Mist, glycyrrhiza; comp., q. s. ad.f^iii lOOJ Misce, Sig.: Shake the bottle and take a teaspoonful. Another very popular form of expectorant into Avliich tartar emetic enters is the compound syrup of squill, combining the stimulation of squill and the nauseant action of the tartar emetic. It may EXPECTOBANTS. 279 be given alone or Avitli ammonium chlorid as fol- lows: IJ. Syrupi scillte corap f§iss 50 Ammonii chloridi . . . 3ii 8 Aqute, q. s. ad fgiii 100 Misce. Sig. : A teaspoonful every three hours. STIMULATING EXPECTORANTS. The stimulating expectorants include a number of balsamic resins (of which benzoic or cinnaraic acid is a constituent), creosote, terebene, ammo- nium carbonate and to a less extent the chlorid. The preparations of tolu are to be regarded more as vehicles than as activel}- stimulating expector- ants. Squill is used as an expectorant mainl}^ for its nauseant effect. Terebene and terpin hydrate are excreted by the lungs and exert a mild stimulation and antisepsis, but the latter properly must be insignificant. While ammonium carbonate is distinctly stimu- lating, therapeutic doses of the chlorid have but little action on the centers. Both of these salts assist in the liquefaction of mucus. Balsamum Tolutanum. — U. S. P. — Balsam of Tolu is a balsam obtained from Toluifera hal- samum, and occurs as a yellowish-brown plastic solid that has a pleasant aromatic odor and a mild aromatic taste. It is readily soluble in alco- liol, nearly insoluble in water. Balsam of tolu was first described by Monardes, a Spanish physi- cian, about 1574. The drug, it is said, was col- lected in a district called Tolu, near Carthagcna, and appears to liave been well known to, and used 280 PHARMACOPEIA AND PHYSICIAN. by, the natives of N'orthern South America. Bal- sam of toll! is widely iised at the present time and is official in all the leading pharmacopeias. Average dose: 1 gm. (15 grains). Syrupus Tolutanus. — U. S. P. — Syrup of Tolu, containing the water-soluble principles of 5 per cent, of tincture of tolu in syrup. Average dose: 15 c.c. (4 fluidrams). TiNCTURA ToLUTANA. — U. S. P. — Tincture of Tolu, a 20 per cent, solution of tolu in alcohol. Average dose: 2 c.c. (30 minims). The mildest of the stimulant expectorants is syrup of tolu, if, indeed, this can be considered as anything more than a flavored syrup. The balsam is not frequently used in medicine, but may be given in the form of an emulsion made with acacia and water and sweetened with sugar. The benzoic acid and volatile oil in the balsam give it the advantage of Joeing mildly antiseptic, the syrup, however, being too weak to be effective in the dose usually employed. Balsamum Peruvianum." — U. S. P. — Balsam of Peru may be used in the same dose and for the same purpose as balsam of tolu. Attention is called to the fact that the urine of persons taking such amounts of these balsams gives a precipitate with nitric acid which may be mis- taken for albumin, but the precipitated resins dis- solve in alcohol, while albumin does not. Benzoinum. — U. S. P. — This balsamic resin is also a harmless stimulant, useful in bronchial irri- tation. Tincture Benzoini. — U. S. P. — A 20 per cent, solution of benzoin in alcohol, or: EXPECTORANTS. 281 TixcTUR-V Bexzoixi Co:mposita. — U. S. P. — "Turlington's balsam/*' commonl}- called "Friar's baJsam" (containing benzoin, aloes, storax and tolu), may also be given. Average dose: 1 c.c. (15 minims) every two hours. The fact that these expectorants are harmless is a very great advantage — and is a point to be par- ticularly remembered in the treatment of small children, in whom opiates and such depressants as antimony and potassium tartrate are to be avoided. SciLLA. — U. S. P. — Squill. The bulb of Urginea maritima, containing several potent principles; it is exceedingly irritant and in large doses toxic. Average dose: 0.1 gm. (3 grains). Of all official drugs used in the treatment of cough,- few are better known than squill, the syrup being the most popular of its preparations. This drug is both stimulant and nauseant; hence, it is used in both stages of bronchitis. Syrupus Scil^LiE. — U. S. P. — Syrup of Squill. This represents o per cent, of squill; made from vinegar of squill, and, therefore, containing dilute acetic acid; it is, of course, incompatible with am- monium carbonate — a fact not infrequently lost sight of by the prescriber. Average dose: 2 c.c. (30 uiiiiiiiis). AcETUM SciLL.'K. — U. S. P. — A^iuegar of Squill. 'I'his represents 10 per cent, of the drug extracted with dilute acetic acid. Average dose: 1 c.c. (15 minims). Flu I DKXTRACTUM SciLLyE. — U. S. P. Average dose: 0,1 c.c. (2 minims). 282 PHARMACOPEIA AND PHYSICIAN. TiNCTURA SciLL^. — U. S. P. — This represents 10 per cent, of the drug. Average dose: 1 c.c. (15 minims). These last three preparations of squill are sel- dom employed, but the following is widely used : Sykupus Scill.e Compositus. — U. S. P. — Compound Syrup of Squill (Hive Syrup). This represents 8 per cent, of the fluidextracts of squill and senega and 0.3 per cent, of antimony and potassium tartrate or about 0.01 gm. (1/6 grain) to the teaspoonful. Average dose: 2 c.c. (30 minims). Syrupus Picis Liquids. — U. S. P. — Syrup of Tar. — Containing one-half of 1 per cent, of the soluble principles of tar in syrup, is mildly stimu- lant and the taste is not unpleasant. Average dose: 4 c.c. (1 fiuidram). Tar itself has a disagreeable acid taste and is not often used in substance. Teepini Hydras. — U. S. P. — Terpin Hydrate. — This is a substance closely related to turpentine, camphor, etc. It occurs in colorless, lustrous, rhombic prisms, or a white crystalline powder, nearly colorless, of a slightly aromatic and some- what bitter taste, soluble in about 200 parts of water and in 10 parts of alcohol. Average dose: 0.1 gm. (2 grains) in capsules or elixir. Terpin hydrate has been known for some time, but was not used in medicine until after Lepine published the results of his physiologic investiga- tion in 1885. It is supposed to possess the anti- septic and stimulating effects of turpentine with- out possessing its irritating properties. The sub- EXPECTORANTS. 283 stance soon became popular and was included in the United States Pharmacopeia for 1890. It is official in the German Pharmacopeia and in the French Codex. . Terebexum. — IT. S. P. — Terebene. — This is a polymerization product derived from turpentine, which it closely resembles. It is a colorless liquid, having a rather agreeable odor and an aromatic, somewhat terebinthinate taste, readily soluble in 3 times its volume of alco- liol, but only slightly soluble in water. First obtained by Soubeiran and Capitaine about 1841, it was introduced into medicine by Dr. Wil- liam Murrell about 1885 ; it was made official in 1890 and in the British Pharmacopeia of 1898. Average dose: 0.5 c.c. (8 minims). Creosotdm. — XJ. S. P. — (or Guaiacol. — U. S. P., which constitutes up to 90 per cent, of creo- sote) . Average dose: 0.2 c.c. (3 minims). Ammonii Chloridum. — U. S. P. — A white crystalline powder, without odor, having a cooling saline taste, permanent in air, soluble in 2 parts of water and in 50 parts of alcohol. As sal ammoniac, this substance has been known from a very early time. It is popularly supposed to have been first obtained from the neighborhood of the Temple of Jupiter Amnion, in Northern Africa. Average dose: 0.5 gm. (8 grains). Ammonium chlorid was known to the Arabian physicians and was described by Geber. It is now official in all pharmacopeias. Wood recom- mends this salt in the stage just before secretion 284 PHARMACOPEIA AND PHYSICIAN. becomes free; for this purpose the following may be used : Trochisci Ammonii Chloridi. — U. S. P. — Each troche contains 0.1 gm. (1% grains) ammo- nium chlorid and 0.3 gm. (3 grains) extract of glycyrrhiza. Ammonium chlorid is much used as an addition to compound mixture of glycyrrhiza in the propor- tion of 4 gm. (60 grains) to 60 c.c. (2 ounces), and it may be added to nearly any expectorant mixture which is not strongly alcoholic. Ammonii Carbonas. — U. S. P. — Ammonium Carbonate. This consists of white, hard, translu- cent, striated masses of a strong odor of ammonia without empyreuma, and a sharp, saline taste, slowly but completely soluble in about 4 parts of water and decomposed by hot water. Squill in the form of the simple syrup is rec- ommended for use in the latter stages of bronchitis. The compound syrup, containing antimony, is not generally suited for young children, but it has been used in spasmodic croup. The use of squill as an emetic is not free from danger and the drug is seldom so employed alone. The following is suggested as a form of pre- scribing the syrup : U. Syrupi scillae fgi 30 Syrupi ipecac f3i 4 Ammonii chlor 3i 4 Syrupi tolut., q. s fgiii 100 M. et Sig. : A teaspoonful as required. When the inflammation affects the upper part of the respiratory passages it is treated with anti- septics, demulcents and anodynes. The lozenges of ammonium chlorid will be found very useful EXPECTORANTS. 285 for this condition. Ammonium cliloricl is very commonl}'' used with the compound mixture of gl3-cyrrhiza, but it is not well suited for combina- tion with terpin hydrate, since the latter requires a strongly alcoholic menstruum which precipitates ammonium chlorid. Terpin hydrate has been suggested as a remedy in a variety of ailments, but it appears to be useful mainly as an expectorant, enjoying a reputation particularly among the nostrum venders. It is in reality useful in aiding to get rid of secretion from the bronchial mucous membrane. It may be prescribed as the unoflBcial Elixir of Terpin Hydrate and Codein Sulphate. Dose: Two teaspoonfuls, containing 0.12 gm. (3 grains) ter- pin hydrate and 0.015 gm. (^ grain) codein. Owing to its slight solubility in water, the elixir must be strongly alcoholic — a serious objection to its general use. It is very commonly associated with codein, which is not to be recommended for routine practice. Terebenc is used in much the same conditions as terpin hydrate, but its immiscibility with the mix- tures usually employed as expectorants has inter- fered in no small way with its employment. It may be proscribed in alcoholic solution, in cap- sules or in the lonu of an emulsion as follows: U. Tcrebcni Svi 25 Pulv. acaciai 3iv 15 Syriipi tolut f^i 30 Aquii', q. s. ad giii 100 Af. Ft. eimilsum. .Si<,'. : A tcaspoonful as required. Creosote is used as a stimulant expectorant. 'I'liere is considerable diversity of opinion as to its 28G rBARMAGOPEIA AND PHysICIAN. mode of action. It seems to possess little germici- dal action so far as the lungs arc concerned. When it is administered in a bland oil very large doses are tolerated, but these are not necessary for its expectorant effect. Numerous compounds of creosote and of guai- acol have been suggested as substitutes for the offi- cial products, but it is not probable that they pos- sess any decided advantages over the official. Those which are less poisonous are probal^ly absorbed from the alimentary canal to a much less degree than are the official creosote and guaiacol. Among the guaiacol compounds is the proprie- tary "Ethacol," containing ethyl-morphin, a fact to be carefully borne in mind, as the name of the preparation is not nearly so suggestive of morphin as of guaiacol. The manufacturers of this article recommended morphin or ethyl-morphin in bron- chitis for increasing secretion ! A condition deserving especial mention is that in which the mucus is particularly thick and tena- cious, requiring liquefaction; for this purpose, ammonium carbonate is frequently added to other expectorants; it has the disadvantage of an un- pleasant taste, which can not be disguised with di- luted acids because these decompose the carbon- ates. The cough of chronic bronchitis requires the use of one of the stimulant expectorants, such as terebene or terpin hydrate, bearing in mind the avoidance of those which will prove objectionable with continued use. While urging the advantage of using the phar- macopeial expectorants, we particularly suggest EXPECTORANTS. 287 that the physician consider the several ingredients of any nostrum instead of accepting the ahsnrd, and often grotescjue. claims of the maniifactnrer. AXODYNES. When the irritaljilitv of the throat causes exces- sive coughing, anodynes are indicated. The pharmacolog}' of morphin, codein and some of the morphin derivatives will he discussed hriefly in the succeeding chapter, hut we wish to reiterate the oft-repeated warning concerning the indis- criminate use of the drugs of this class which do uncjuestionahly relieve coughing, thus giving the patient the impression that he is being cured, whereas the inflammatory process may be progress- ing. The derivatives of morphin, such as codein and heroin, lessen the irritability of the center without causing so much gastrointestinal disturb- ance as morphin. Morphin is particularly to be avoided when the cough is attended with free secretion, since the cough is necessary in that event. CoDEiXA. — U. S. P. — Codein. Very sohible in alcohol, much less soluble in water. Codeix.t: Pitospilvs. — U. S. P. CoDEiN.E Sulphas. — U. S. P. — Both are quite sohible in water, but not in alcohol. Average dose: 0.03 gm. (30 mg. or i/> grain). AciDUM Hydhocyanicum Dilutum. — U. S. P. — Contains 2 per cent, absolute HCN. Average dose: 0.1 c.c. (1^2 minims). Syi!('!'['w Pifrxr VrifoixiAX-i:. — IT. ,S. P. — Syriip of Wild CImtit ivpivsciits i:. per (■•■iit. of bark and l."J per cent, of glycerin. 288 PHARMACOPEIA AND PHYSICIAN. . Codein imdoiibtedly lessens cough, but, as al- ready stated, this is not always desirable. Codein phosphate or sulphate, being soluble in water, may be added to almost any cough mixture which is not alkaline. The following is suggested as a simjile prescrip- tion containing codein: IJ . Codeinse sulph gr. viii 5 Ammonii chloridi Siss 6 Syrupi priini virg., q. s. ad fgiii 100 M. Sig. : A teaspoonful every two or three hours. Compound mixture of glycyrrhiza, syrup of tar, syrup of squill or syrup of tolu may be substituted wholly or in part, for the syrup of wild cherry. Codein, rather than its salts, is suited for com- bination with tcrpin hydrate, since both require al- cohol as solvent. Codein has come very largely into use in expec- torant mixtures in recent years, partly because its action resembles that of morphin without disturb- ing digestion or causing constipation in moderate doses, partly, no doubt, because manufacturers have popularized it in order to avoid the stigma attaching to the general use of morphin and opium. Numerous substitutes have been introduced for morphin and codein, but it has not been demon- strated that they possess all the advantages and none of the disadvantages of the officials. It must not be forgotten that the habit may be formed with any of the morphin derivatives, including codein. The bromids of ammonium, potassium and so- dium are safer than morphin, and are frequently beneficial when anodynes are indicated. Their EXPECTORANTS. 289 doses should^ however^ be more than proportion- ately reduced for children. Hydrocyanic acid may he added to expectorant mixtures, hut its action is fleeting and it must be frequently repeated. DEirULCENT EXPECTOEANTS. Demulcents are frequently employed to allay the irritation of the mucous membrane, and they pos- sess the great advantage of being harmless. They may be administered in the form of lozenges or troches. The following demulcents may be used as ve- hicles : SyRUPUS ACACIiE. — TJ. S. P. MuciLAGO Acacia. — TJ. S. P. Glycyrritiza. — TJ. S. P. — Licorice Eoot is so well known as to require Imt little comment. Its preparations afford a variety of forms for adminis- tering it. Fluidextractum GLYCYRRHizJi:. — U. S. p. — This is the Fluidextract of Licorice Eoot, from which a satisfactory syrup may be prepared by mixing 25 c.c. of the fluidextract with enough syrup to make 100 c.c. Average dose: 2 c.c. (30 minims). EXTRACTUM GLYCYRRiriZin; PURUM. — TJ. S. P. — This is a semi-solid extract prepared from the root and is well adapted as an addition to extem- poraneous mixtures. ,\vcrage dose: 1 gm. (15 grains). Trociiisci Glycyrrhiz^ et Opii. — U. S. P. — Those contain 0.005 gm. (5 mg. or 1/12 grain) of opium. 290 PHARMACOPEIA AND PHYSICIAN. Glycyrrhizinum Ammoniatum. — U. S. P.— Ammoniated Glvcyrrhizin is an excellent demul- cent; it is readily soluble in water, but incompati- ble with acids. Average dose: about 0.25 gm. (4 grains). PuLvis Glycyrrhizje Compositus. — XJ. S. P. — Compound Powder of Glycyrrhiza, a laxative, containing senna, washed sulphur, glycyrrhiza, sugar and oil of fennel, and popularly believed to be a desirable adjuvant to expectorant medi- cines. Average dose: 4 gm. (GO grains). ]\IlSTURA GLYCYRRHIZiE COMPOSITA. U. S. P. — Compound Mixture of Glycyrrhiza, brown mix- ture, containing purified extract of glycyrrhiza and acacia, each 3 per cent., syrup 5 per cent., with camphorated tincture of opium 13 per cent., wine of antimony 6 per cent, and spirit of nitrous ether 3 per cent. Average dose: 8 c.c. (2 fluidrams). This is a deservedly popular expectorant. It is very often prescribed alone, but is also much used as a vehicle for other expectorants, particularly ammonium chlorid. The demulcents are useful when they may be applied directly to the seat of the inflammation, but they are of less service when the lower pas- sages are affected. The Mistura Ammonii Chloridi, N. F., affords an example of the use of a demulcent as a vehicle. It consists of 21/2 per cent., each, of ammonium chlorid and purified extract of glycyrrhiza with water. The average dose is two teaspoonfuls. CHAPTEE XIII. AXALGESICS AND SOPORIFICS. Analgesics and soporifics are among the most important articles in the materia medica, and at the same time, owing to their abuse, among the most harmful. Pain, accompanied by sleeplessness, oecurs in a great variet}' of conditions, often with an inten- sity or persistency that imperatively demands alle- viation. When such a condition requires medi- cines for a long time there is danger that the pa- tient will learn the name of the remedy employed and continue its use after the actual necessity for it has passed. Certainly no other class of reme- dies requires more painstaking care on the part of the physician, not only in the choice of the par- ticular agent to be used, but also in the regulation of the dose. The only way to secure the best results in the treatment of such conditions is by acquiring an in- timate knowledge of the various remedies in this class and by learning how to use them singly or in combination as may be required. In a given case a combination of hydraled eliloi'al and potassium bromid iiiny be necessary, while in another the bitter alniie may suffice. The more (hirigeroiis hvdratcd chloi-d should nevei' be used 292 PHARMACOPEIA AND PHYSICIAN. when the less liarniful bromid will serve the pur- pose.^ If we find that scarcely any two successive pa- tients demand exactly the same prescription of but two ingredients, how very much less is the proba- bility of finding any considerable number each re- quiring a "shotgun" prescription of five or six substances of widely different action, agreeing only in the one property of producing unconscious- ness. It should be obvious that the conscientious use of analgesics and soporifics demands the thought- ful selection of the remedy with the careful com- putation of the dose according to the necessities of the individual case — a condition manifestly im- possible when one relies on complex, ready-made mixtures, with doses and indications suggested by an interested layman — the manufacturer. The greater the number of individuals who acquire 1. Should the physician desire to use a compound mixture of hydrated chloral and potassium bromid of the bromidia type he may have the "Mistura Chloralis et Potassii Bromidi Composita" of the National Formulary compounded, as fol- lows : R. Chlorali hydrati Potassii bromidi. aa 5i-gr. xv 5 Ext. cannab. ind. Ext. hyoscyami, aa gr. % 04 Aquse q. s. ad 5vi 25 The hydrated chloral and the potassium bromid are dis- solved in a little water and the extracts are then dissolved in the solution of the salts mixed with some powdered pumice stone, and the mixture filtered. Each teaspoonful will contain approximately 1 gm. (15 grains) each of hydrated chloral and potassium bromid ; 0.008 gm. (Vs gr.) each of extract of Indian cannabis and extract of hyoscyamus. The mixture should be used with caution, and it will usually be found advantageous to omit the extract of Indian cannabis. This mixture is unscientific in the extreme and we do not commend its use. AXALGESICS AXD SOPORIFICS. 293 such harmful habits the greater are the profits of the nostrum maker. It is -well known that the habitual use of opium, hydrated chloral, the bromids and other narcotics is widespread, but there are few who appreciate the full extent of these practices, or in how far physicians are responsible because of the careless use of these agents, either in simple form or as an ingredient of some nostrum. For convenient consideration we shall divide these remedies into opium, atropin, acetanilid, hydrated chloral and bromid groups, the first three being more properly analgesics and the last two soporifics, though no absolute distinction can be drawn 1)etween them. MORPHIN. The importance of opium and morphin are such that their actions and uses should be carefully studied in standard works of the day, an^ we shall pass to the minor members of the group after discussing the official preparations briefly. Morphin constitutes about one-eighth of the weight of opium, the therapeutic properties of whicli it represents fully; hence we shall consider the pharmacology of the alkaloid briefly. The action of morphin on the central nervous system has been compared to the "law of dissolu- tion," the higher centers being affected first, reason and judgment are impaired, the sensitiveness to constant pain is diminished, and the patient be- comes drowsy, falls asleep or sinks into a coma- tose condition dependent on the dose. It is a curi- ous fact that, despite the lessened sensibility to a 294 PHARMACOPEIA AND PHYSICIAN. constant stimulus, such as pain, there may be, after moderate doses, a hypersensitiveness to l)right flashes of light and sharp noises. The widespread use of opium and morphin for local action — injections and lotions — is based on an erroneous idea. Opium contains gum which is a demulcent, a rather expensive one, however, while its active principle, morphin, must be ab- sorbed before it can produce its effects, which arc constitutional, not local. The excitement caused by morphin, in some pa- tients, is explained by the fact that reason and judgment, which under normal conditions impose restraint, are in abeyance, and not by any stimula- tion by the drug. The cat reacts to morphin by an extraordinary degree of excitement and the theory of the abey- ance of self-imposed restraint as suggested in man is not a satisfactory explanation of this excitement in the cat. Stimulation of the cord sometimes follows the use of morphin in children, and, after large doses, in the frog this gives rise to strychnin-like convul- sions. Small doses of morphin depress the respiratory center, causing a much slower and somewhat deep- er respiration, but the volume of respiration is markedly diminished. The depression of this cen- ter explains the use, and also the contraindications of opiates in cough. Morphin exerts very little influence, in moder- ate doses, on the other medullary centers, so that the heart and blood pressure are not materially affected, except indirectly as the result of nausea, ANALGESICS AXD SOPORIFICS. 295 when that occurs, but there is a dilation of the cutaneous vessels of certain regions, particularly of the head and face. The seat of this action is not determined with certainty, but it probably ex- plains the diaphoretic action of opium. The secretion of mucus is usually diminished, except in the case of nausea. The urine is not af- fected appreciably, but the bladder may become distended owing to the loss of reflex from the sphincter. Small doses of morphin lessen peristalsis, while an enormous dose given to a. dog results in vomit- ing and diarrhea. These actions are not fully understood, but it seems probable that the action is partly central, though mainly local. The effect of the reflex mechanism in the intestinal wall diminishing peristalsis in the one case and irrita- tion of the intestine during excretion causing the diarrhea. Against this latter and in favor of the participation by the center is the rapidity of ac- tion after subcutaneous injection. The toxicology of morphin is important because of the frequency with which it is taken with suici- dal intent. The tincture of opium perhaps' is the preparation most frequently used for that purpose, and when this is swallowed the odor may, usually, be detected in the breath. Morphin is excreted from the blood into the stomach and intestine; hence the stomach should 1)0 washed out in all cases of opium and morphin poisoning, regardless of the method of adminis- tration, and particularly when the case is seen early. When the stomach has been emptied of food, a very dilute solution of potassium perman- 296 PHARMACOPEIA AND PHYSICIAN. ganate should be added to the water used in wash- ing that organ. Death, in cases of morphin poisoning, results from failure of respiration, and, after evacuating the stomach, measures of relief are directed to sustaining the respiratory center. Caffein, by hypo- dermic injection, or, better, by very strong hot tea, made quickly, not by long standing on the leaves, or strong hot coffee, stimulates the respiratory cen- ter directly, also indirectly and more beneficially, by increasing the blood pressure and, therefore, the circulation in the respiratory center. The head may be lowered if the patient is asleep. Violent measures, such as enforced motion and painful slapping, stimulate the respiratory center, but they also increase the work and help to exhaust it, and should not be used. Strychnin injected subcutaneously, but no more than the therapeutic dose, should be given, but this must not be repeated. Warm, not hot, tea or coffee may be absorbed from the intestine when the pa- tion can not be aroused. Unlike most alkaloids, morphin is not excreted in the urine; hence diuretics are useless for hasten- ing elimination. Codein is methyl-morphin. Morphin appears to have the formula: /.N(CHOCH„ C,,H,o(OH), \OCH2 and codein has a similar formula, except that an OCH3 group replaces one of the CH groups. Dionin is ethyl-morphin and heroin is di- ANALGESICS AXD SOPORIFICS. 297 acet3'l-morphiii ; in the latter case both CH groups have been replaced. Cushn}' states that most impartial observers have failed to obtain better results from heroin and dionin than from morphin and codein in coughs, and that further investigation is required before they can be recommended as being superior to the older and better known alkaloids. The action of codein resembles that of morphin in a general way, but it is much weaker. It has less of the narcotic and more of the stimulating action on the cord. The respiratory center is not depressed to the same extent and there is less in- terference witli peristalsis. The danger that the patient Avill form the truly terrible opium habit from even a short use of the drug or of any of its derivatives should always Ijc Ijorne in mind, and when it is necessary to use tliem they, should be masked. Hypodermics in pain have come to be almost synonymous with mor- phin in the minds of the laity. This idea should 1)0 uprooted both l)y the use of the method for many other substances and by avoiding it as much as possiMc willi morphin. The odor and the taste of opium and dT the tincturC; unfortunately, are well known and tlicy should be disguised if possi- ble. 'I'o disguise the identity of opium and its pre"|D- arations it is customary with some practitioners to employ the old designation thebaica for opium, tincture tliebaica for the tincture. The use of the deodorized preparations of opium is also to Ije rec- ommended for this purpose. 298 PHARMACOPEIA AND PHYSICIAN. The official titles coining under the heading opium are numerous and important. Opium and granulated opium are never used directly in the practice of medicine, but powdered opium and deodorized opium are frequently prescribed. Opii Pulvis. — U. S. P. — When assayed, by the process given in the Pharmacopeia, this .should yield not less than 13 per cent, nor more than 12.5 per cent, of crystallized morphin. This require- ment is somewhat higher than the provision adopted for the International Standard, which limits the morphin contents of powdered opium to 10 per cent. Average dose: U. S. P. powdered opium is 0.050 (50 mg. or 1 grain). Opium Deodoratum.- — U. S. P. — This is pow- dered opium which has been treated with purified petroleum benzin to remove the caoutchouc, wax, oil and the odorous substances that are present; the alkaloidal strength and the dose of deodorized opium are the same as for the official powdered opium. ExTRACTUM Opii. — IT. S. P. — Assayed to con- tain 20 per cent, of morphin. This preparation is now little used, except in suppositories and the official opium plaster. Average dose: 0.30 gm. (30 mg. or % grain). Pilule Opii. — U. S. P. — These are each com- posed of opium, 0.065 (1 grain), and soap 0.020 2. This preparation is superior to the widely used pro- prietary preparation of opium "Svapnia," over which it has the advantage of economy, activity and even general reliabil- ity, since the accompanying directions for assay are not alone accurate, but are readily followed by any one versed in chemical assay work. AX ALGESICS AXD SOPORIFICS. 299 (1/3 grain). . These pills constitute a very ancient form of administering opium. There are five liquid preparations, the least use- ful of which will Ije mentioned first : ViNCii Opii. — U. S. P. — Containing 10 per cent, of opium in fortified white wine, aromatized with 1 per cent., each, of cinnamon and cloves. It rcsemhles the well-known "Laudanum of Syden- ham.^' Average dose: 0.5 c.c. (8 minims). AcETUM Opii. — U. S. P. — Vinegar of Opium, formerly known as hlack drop, Lancaster drops or Quaker drops, has long heen known and extensively used. It contains 10 per cent, of opium and 3 per cent, of nutmeg in diluted acetic acid, sweetened with sugar. Average dose: 0.5 c.c. (8 minims). TixcTCRA Opii. — U. S. P. — Tincture of Opium is the well-known and widely used laudanum, and consists of 10 per cent, of opium in diluted alco- hol. Average dose: 0.5 c.c. (8 minims). TiNCTURA Opii Camphorata. — U. S. P. — This, also known as paregoric or paregoric elixir, is the most widely used of the compound preparations of opium now official. It is so well known as a mild anodyne and sedative tliat further notice is not necessary. Average dose: 8 c.c. (2 fluidrams). Tliis amount contains al)Out 0.03 gm. (i/> grain), oacli, of pow- dered o|)iiiin. henzoif neid. (■;iiii]ili(ir nnd oil (if anise. TixcTURA Oi'ii i)i:oi)(»i;A'ii. — U. S. I'. — Deo- dorized Tincture of ()j)iuin is ))ractically a 10 per 300 PHARMACOPEIA AND PHYSICIAN. cent, aqueous extract of opium that has been treated with purified petroleum benzin to remove tlie odorous and other objectionable constituents, and subsequently preserved by the addition of 20 per cent, of alcohol. This, like the simple tincture of opium, is directed to yield, on assay, not less than 1.2 per cent, uor inore than 1.25 per cent, of morphin in crystals. The average dose is 0.5 c.c. (8 minims). While there has been some controversy con- cerning the origin of this particular preparation, there has never been any difference of opinion as to its potency for harm. From the sedative elixirs of nearly a century ago to the Scotch oats essence of the present day there have been many attempts to exploit deodorized or masked opium preparations, as harmless vegetable compounds. Another class of preparations, like "McMunn's Elixir of Opium,-' has been exploited as em- bodying some wonderful discovery in the treat- ment of opium.^ The official deodorized tinct- ture is in every way distinctly superior to all of these nostrums, because, as noted under deodorized opium, it has the advantage of economy, efficiency and reliability. There are but three other galenical preparations of opium official in the present Pharmacopeia. 3. "Papine" would be a gem among these if the claims made for it were true, but we can not believe that any prep- aration of opium containing the pain relieving principle (which we know to be morphin) can be "a safe opiate for children under one year." This affords a good example of the audacity of the nostrum vendor who seeks to delude the physician and induce him to foster such vicious habits even in the cradle. ANALGESICS AXD SOPORIFICS. 301 TixcTDRA Ipecacdaxhje et Opii. U. S. P. Liquid Dover's powder. This is of practical!}- the same strength as the well-known powder of ipecac and opium. Average dose: 0.5 c.c. (8 minims). PuLvis Ipecacuanha et Opii. — U. S. P. — This has been noticed under ipecac (see Chapter IX). It contains 10 per cent., each, of ipecac and of powdered opium. Average dose: 0.500 gm. (Ti/o grains). TiiocHisci Glycyrriiiz.t^ et Opii. — U. S. P. — These have been previously noticed. The alkaloids, morphin and codein. are of near- ly as much interest as opium. Morphin was discovered by Sertiirner, a German apothecar)', in 1805, and was used in medicine as early as 1820. Tliere are four official prepara- tions : MoKPiiiXA.— r. S. p.— This alkaloid, ohtainiMl from opium, occurs as colorless or white shining rhombic prisms or as fine needles or as a crystal- line powder. It is odorless and has a bitter taste. Average dose: 0.010 gm. (1/5 grain). MoHPiiix.i-: Acetas. — I'''. S. P. — This salt of morphin should be kept in well-stoppered, dark amber-colored bottles, and a minute quantity of free acetic aeiil slioulil he ju'eseiit to ])revent de- composition. Average dose: O.dl.') oi,,. ( i 'j ui-iin). MOIU'IIIX.K IlVDItOCIILOUIDl A[. 1". S. P. Like tlie acetate, this should be kept in well-stop- |)ere(l dark bottles. .\vei-age dose: 0.015 gin. {% grain). 302 PHARMACOPEIA AXD PHYSICIAN. MoRPHiN.^; Sulphas.— U. S. P.— Like the other morphin salts, this should he kept in well- stoppered dark bottles. Average dose: 0.015 gm. (14 grain). Sulphate of morphin is much the most fre- quently used in this country, while the hydro- chlorid is generally given the preference in Eu- rope. The acetate is the most readily soluble in water, but is quite unstable, losing acetic acid on exposure to the air, and, as the alkaloid morphin requires 3,300 parts of water for solution at or- dinary temperatures, considerable care should be exercised in the use of old, and possibly decom- posed, samples of morphin acetate. While the new Pharmacopeia gives 0.015 gm. (1/4 grain) as the average dose of the salts of morphin, we believe that this is too high as the "average" dose. Codein and two of its salts are official : CODEINA.— TJ. S. P. CODIEN^ PhOSPHAS. — JJ . S. P. CoDEiNJi: Sulphas. — U. S. P. Average dose (of either) : 0.03 gm. (1/2 grain). Codein, in addition to being obtained from opium, is also prepared from morphin by methyl- ation. It was discovered by a French chemist, E. Eobiquet, in 1832, but was not generally used in the practice of medicine until many years later. It was admitted into the U. S. Pharmacopeia in 1880; the phosphate and the sulphate are now official for the first time. The sulphate is the form most frequently employed in this country, though it appears to be but little known abroad, where the phosphate is mainly used. The phosphate was AX ALGESICS AXD SOPOBIFICS. 303 considered under "Expectorants." Codein has been considered a somewliat uncertain drug, owing to its frequent contamination with morphin, but the Pharmacopeia provides a test for its purity, and particuhirly for detecting the presence of the more poisonous alkaloid. The phosphate being readily soluble in 2.5 parts of water, is particularly well suited for hypoder- mic use ; or it may be prescribed alone in syrup or combined with hydrated chloral or the bromids ; in the latter case the mixture should be directed to be shaken before using. The average dose of codein or of any of its salts is 0.03 gm. (30 mg. or % grain). Apomorphix.e Hydrochloridum. — XJ. S. P. — which was also mentioned under "Expectorants," lias been recently brought to notice as a hypnotic, in doses of 0.002 gm. (1/30 grain). It is said to have the great advantage of not producing a drug habit. Heroin and dionin are proprietary names for articles of the morphin group possessing some ad- vantages, but they are not free from danger. Tlie heroin habit is beginning to be common and sliould be carefully guarded against. Cannabis Indica. — U. S. P. — Indian Canna- bis is a well-known member of the opium group, ft occurs in dark-green or brownish compressed masses, having an agreeable narcotic odor and cliaracteristic taste. It appears to Imvc liccn ii.-cil Ity the Hindoos Iroiii very early iiiiio. It was also known to tin- Egyj)tians and to J)ioscoriil( >. Imt it wa.s not in- troduced into England until al)out 1.S35. ;{04 PHARMACOPEIA AND PHYSICIAN. Average close: 0.05 gm. (1 grain), but rarely used in substance. EXTRA.CTUM Cannabis iNDicyE.— U. S. P. Average dose: 0.01 gra. (10 mg. 1/5 grain), Fluidextractum Cannabis Indict. — U. S. P. Average dose: 0.05 c.e. (1 minim). TiNCTURA Cannabis Indict. — U. S. P. — rep- resents 10 per cent, of the drug extracted with al- cohol. Average dose: 0.5 c.c. (10 minims). At one time Indian Cannabis was supposed to have great virtues as an antispasmodic, analgesic and narcotic, and it was highly recommended by a few ph3'Sicians as a vasomotor stimulant, uterine stimulant, etc. It is now but little used and there seem to be few conditions in which one of the prep- arations of opium could not be used advantageous- ly in its stead.* Two other members of the opium group are sanguinaria, which we have had occasion to men- tion elsewhere, and the feebly-acting 4. It may be worth while to notice the importance at- tached to the extract of cannabis indica by the makers of bromidla, who claim that their preparation is the only hyp- notic that has stood the test in every country for thirty years. Since all the other constituents are very commonly used, one must infer that they considei: the genuine im- ported extract of cannabis indica of exceptional value. Bromidla, it is claimed by the manufacturer, contains 15 grains each of hydrated chloral and potassium bromid, and Vs grain each of genuine imported extract of cannabis indica and extract of hyoscyamus. to the teaspoonful. Thus a sin- gle repetition of the dose — one teaspoonful — might prove fatal, since 30 grains of hydrated chloral have caused death ; but the manufacturers advise hotirUj doses so long as may be necessary to induce sleep. The extravagant claims made by the manufacturers of this nostrum liave induced many physi- cians to use it in preference to prescribing the several offi- cial constituents according to individual needs, and today it is offered direct to the public at cut-rate prices. AXALGESICS AXD SOPORIFICS. 305 LACTTCARIUil. — U. S. P. Average dose: 1 gm. (15 grains). TixcTURA Lactucaeii.^ — U. S. P. — This is a 50 per cent, preparation of lactucariiim made with diluted alcohoh Average dose: 2 c.c. (30 minims). Syrupus Lactucarii. — U. S. P. — This is much more commonly employed than the tincture, its popularity heing largely due to a nostrum. Average dose: 8 c.c. (2 fiuidrams). The indications for opium and niorphin are too varied for anything like a comprehensive treatment here. This is well illustrated hy the remark of S^-denham, who said that few Avould he callous enough to practice therapeutics without opium. We should always rememl)er, however, that no drug is more frequently misused or lends itself so readily to ahuse as opium and its derivatives. Pain calls for opium. Bearing in mind its nu- merous disadvantages and po.?sibilities for harm, this is the principal guide to its emplo3'ment. Cough, at certain stages, ' diarrhea, severe colic, especially lead colic, inaccessible hemorrhage and conditions calling i'oi- a diaphoretic (with ipecac), are among Die numerous indications for its use. For sleeplessness, in the absence of pain, luor- phin is not nearly so useful as chloral and (lie l.n.niids. Tb.' (lan.ucr of cv.'U very small doses ..!' niorjjliin and o|iiiiiii I'oi- children must he lionic in mind constant Iv. jiikI parents should lie llioi'- oughly warned ol' the (lungers of soolJiinu' syi'ups. A single drop of tinelure of (ipiimi is snid Id liavo proved fatal to a child under 1 year of age. 300 PHARMACOPEIA AND PHYSICIAN. THE ATROPIN GROUP. The atropin group includes the crude drugs yielding the mydriatic alkaloids, such as atropin, hyoscvamin and hyoscin, or sdopolamin, all of the latter heing closely related chemically. The actions of atropin and its congeners are so important and so complex that it is entirely beyond the scope of the present article to attempt any- thing like a complete description of them. 'The reader can not avail himself of this potent and im- portant class of agents without a careful study of their pharmacologic and therapeutic actions. We shall, therefore, call attention to a few of the more important applications and contraindications with- out entering deeply into the reasons. Atropin is not nearly so important as an anal- gesic as morphin, but it has a variety of uses, sev- eral of which will be considered now, while others will be discussed under circulatory stimulants. Atropin is useful as an analgesic mainly when the pain is of spasmodic origin and when the appli- cation may be made directly to the nerve ends of the affected tissues. In the pains of lead colic this mav be accomplished by the internal u.se of one of the preparations of belladonna, preferably a pill of the extract coated with salol or keratin. Atropin stimulates the central nervous system, being antagonistic to morphin to a considerable degree. The stimulation of the medulla is much the more important in therapeutics. Atropin paralyzes the terminations of nerves concerned in nearly all the body secretions (mucus, saliva and gastric juice, but not the pancreatic), the vagus endings in the heart (besides those con- i AXALGESICS AXD SOPOBIFWS. 307 ccrned in secretion), and most- endings in plain muscle, except those in the vessels. The influence of atropin on peristalsis is not positively determined. l)ut it seems probable that it only prevents colic pain caused by purgatives without interfering Avith peristalsis. Among the results of the action of atropin arc : mental excitement,'" increased respiration (respira- tory center), dryness 'of throat (mucous glands), dilation of the pupil (endings in circular muscle), rapid heart (vagus depression), increased blood ])ressure (vasomotor stimulation). Atropin de- ]n-esses sensory endings in the skin when applied locally, but not after internal use. The most prominent action of atropin is seen in the dilation of the pupil, but the more rapidly act- ing and less enduring homatropin hydrochlorid is usually preferred for this purpose, if the object is merely to examine the eye — atropin, if it is de- sired to paralyze accommodation for some time, as in inflammatory conditions. While the mydriatic effect is so similar with the different members of this grou]). it must l)e re- membered that tliey have very dissimilar actions on the brain. The crude drugs and their ])reparations belong- ing to this class are so numerous and so well known that it is hardly necessary to enumerate them. Be- sides r)clhi(l(iiiii;i Konl niid Leavcs, Hyoscyamus and Straiiiniiiuin l.caxcs. a nieinber now official for the first time, is 8coj)ola. Scoi'OLA. — U. S. p. — The di'icd rjiizome of ScojKihi. ((irninlicd (.]a(i|uiii) ( I^'ain. Solanacaa'), vielding. when assayed as directed in the Pharma- ;50S PHARMACOPEIA AND PHYt^ICIAN. copeia, not less than 0.-") per cent, of its alkaloids, has little odor and a sweetish, afterward bitterish, acrid taste. Though described bv Dr. Scopoli in 1771, it attracted but little attention from the medical profession until it was used in manufac- turing "belladonna" plasters. Average dose: 0.04 gm. (2/3 grain). FlUIDEXTRACTUM SCOPOL.I^.^-U. S. P. Average dose: 0.05 c.c. (1 minim). Scopolamin.t: Hydrobromidum. — U. S. P. — This is chemically, and otherwise, identical with Hyoscinffi Hydrobromidum, U. S. P. See also Chapter XI. It has been used in the treatment of nervous excitement, particularly of the insane. It often induces quiet sleep at night — not usually in the day — and may also lessen sexual excitement. Atropin, on the other hand, has been used to stim- ulate the brain in cases of depression. Average dose: 0.005 gm. (0.5 mg. or 1/125 grain). Hyoscyamin^e Hydrobromidum, IT. S. P.. and Hyoscyamhs^.e Sulphas. — TJ. S. P.^These are used very much as scopolamin is. Average dose: 0.005 gm. (0.5 mg. or 1/120 grain). Xone of the mydriatic alkaloids should be used as soporifics except in case of urgent need, a.s the benefits -may be more than counterbalanced by the disadvantages. Hyoscin or scopolamin and hyos- cyamin are of little use directly in relieving pain; hence, they can hardly be considered as analgesics. Anv of these alkaloids mav be given alone as ANALGESICS AXD SOPORIFICS. 309 taljlet triturates or as compressed tablets, hypoder- mically or alone in aqueous solution. The following is a common method of exhibit- ing belladonna, particularly in asthma : 1$. Tinctume belladoiinae fol. I TiiK-tura? lobeliie. aa f3ii 10| Spiritus aetheris nitrosi, q. s. ad. .fBiii lOOJ Of this a teaspoonful is given every hour or two until relief is obtained. The In-omids of ammonium, sodium or potas- sium may be used with the prescription given, but in that case adjuvant or aromatic elixir should be suljstituted for the spirit of nitrous ether, and, as in every case when bromids or iodids are combined with alkaloids, the mixture is directed to be shaken. The extracts of the crude drugs are much to be preferred to the alkaloids as additions to purga- tives, since the latter would be largely absorbed from the stomach, whereas the local action on the intestine is desired. TTTE AC'KTAXILID (ilJOUP. Phciiacctin. antijjyiin and acotauilid reduce the febrile temjieraturc through their action on the heat-regiilating center. This reduction is due to increased heat loss mainly, for the lessened pro- duction of heat folloirs the change. The increased loss of heat is accoiii|ilish(d by the dilation of the cutaneous vessels, intlicr llian by sweating, for it occuis wIkii -wcjilinu- is prevented Ijy the use of alropiii. The dilation is of central origin and does not affect the splanchnic area, the lilood ])res- suro being affected but little. 'IMierapeutic doses of the antipyretics increase the heart rate somewhat at first, but tiiis is unim- 310 PHARMACOPEIA AND PHYSICIAN. portant, and when the fever abates from any cause the pulse and the respiration become slower and stronger. Ver}' large doses induce sleep, then convulsions, cyanosis and collapse. Small doses relieve headache and neuralgia, but their mode of action is unknown. Acetanilid is rapidly, phenacctin slowl}', oxi- dized in the body with the formation of para- amido-phenol or a closely related substance, which acts on the hemoglobin of the blood, forming methemoglobin, and to this the cyanosis caused by these drugs is usually attributed, but this does not seem to be a wholly satisfactory explanation in every case. Since phenacetin is decomposed more slowly than acetanilid, it is not so active, but it is safer and the action is more prolonged. Anti- pyrin is not decomposed in the body, but is ex- creted in the urine unchanged. It is decidedly preferable for the practitioner to study the action of one or two of these agents while accurately observing the effects on his pa- tients, rather than experiment with a large num- ber of them. While large doses of these antipyretics are usual- ly borne very well, it should be remembered that many people present a peculiar idiosyncrasy and even ordinary doses may cause cyanosis and alarm- ing collapse, while the heart becomes extremely weak and even death may result, particularly in febrile patients. Even the same patient may react quite differently at different times toward the same antipyretic. The official salicvlic acid, discovered in 1839, ANALGESICS AXD SOPORIFICS. 311 was introduced as an antiseptic in 1873 and later as an antipyretic. The salicylates now find their greatest usefulness in the treatment of acute rheu- matism. They have been discussed in connection with internal antiseptics. CHEMISTRY OF THESE PREPARATIONS. A brief review of the chemistry of the antipy- retic group will show the relationship of the various memljers to each other. Quiuin Ijcing a derivative of quinolin, many at- tempts were made to produce it synthetically, with the resulting discovery of a number of quinolin derivatives which possess antipyretic properties, but all of them dangerous because of their ten- dency to produce collapse. All of these are now practically obsolete. Another substance having antipyretic action is phenylhydrazin, which is of interest because of its derivative, antipyrin. Hydraziu. N^H^ (or HoN — XH,), which is formed by the union of hydroxylamin and ammonia, usually exists in com- bination with an organic radical. Slarliiiii- with tlie bonzune ring CrH,., H C HC CH HC in c H benzene phenol (c;nli( ilic iicid ) is foiiiiod by replacing an H with on. if this (.)11 in turn be displaced by 312 I'HAh'MACOl'EIA AND PHYt^ICIAN. the hydraziii radical, phenyl hydrazin is formed thus : C[OH HjHN-NHj CH3N.2+H.O BC \aI HC CH 11+ =11 HC CH HO CH C C H H phenol+hydraziii= phenyl-hydrazin+ water. Though many derivatives of phenyl-hydrazin have been exploited, antipyrin and its compounds are the only ones in general use. When the practitioner uses drugs which at best are so potent for harm he will do well to employ them in their simplest form rather than in such unofficial combinations as hypnal (chloral and an- tipvrin) or salipyrin (salicylic acid and antip}-- rin). Acetanilid or phenyl-acet-amid is obtained by the action of boiling glacial acetic acid on anilin. By introducing "acet" before "amid" the chemic name is derived. CNH[H+HO]OC.CH:i CNH.OC.CHa+H.O / \ / \ HC CH HC CH ~ HC CH iu = -1 i- c c H H Anilin+acetic acid — acetanilid +water When other acid radicals replace that of acetic acid similar compounds are formed, which are in no wise superior to the official. Thus we have benz- anilid and exalgin (or methyl acetanilid), the lat- ter differing from acetanilid only in having a CH3 group replacing an H. It will be understood from its chemistry why acetanilid can be prepared so cheaply and, there- AXALGE.'^ICS AXD SOPORIFICS. 313 fore, why it is so extensively employed in the nos- trum traffic. Phenetidin is important as the basis of the phen- acetin group. Chemically it is the ethyl ester (sulphuric, so called) of amido-phenol. We have par-amido-phenol, and if the OH is then replaced by the ethyl radical we have phenetidin. HC CH HC CH II II HC CH CH CH \ / \ / C C H NHo Phenol Par-amido-phenol Various acid radicals may replace an li of the NH,. If it be the acetic radical we have phenace- tin, if lactic aeid we have lactophenin. These formulas may appear complex, but a care- ful examination of them will show the relationship existing between the various members of the group. If the practitioner finds the official phenacetin un- suitcd to his purpose in a given case, it is not probable that another compound, differing merely in the nature of an aeid radical, will prove more beneficial. Among the' phenetidin series there are, besides the official phenacetin, many in which the syllable "phen" indicates the phenetidin source. They in- clude phenocoll, salophen, lactophenin and many others. 'Wo .shall liave occasion In mciiiioii in'ctlianc^ (ethyl c;ii-li;iinalr) ;iin,.nu- ||ic li vd I'nlcd .■liloral groii|i, mid il may lie said llial several of its deriv- aliv.'S have Keen \\>i'>\ as aid i|iyrel ics. I. ill (hey do iiol merit riiillier coiisideral ion here. .'514 PHARMACOPEIA AND PHYSICIAN. In connection with the subject of antipyretics we ma}' mention a number of substances which, except historically, are now of little interest. Kairiri, discovered by Dr. 0. Fisher in 1882, was the first of the coal-tar compounds to be introduced as an antipyretic on the strength of physiologic experiments. It was also one of the first of the medicinal synthetic chemicals to be patented. The older physicians may remember its widespread use and some of the exaggerated claims that were made for it and how, despite this, it fell into dis- favor and was soon forgotten. Thallin, made by Dr. Skraup in 1884 and inves- tigated in the clinic of ISTothnagel, soon shared the fate of kairin, despite liberal advertising. The enormous growth of the traffic in proprie- tary remedies mainly composed of acetanilid and allied substances was probably the most potent fac- tor in arousing physicians to a realization of the part they play — often unconsciously — in further- ing the selfish schemes of unprincipled manufac- turers. The Council on Pharmacy and Chemistry of the American Medical Association has shown that antikamnia, phenalgin, salacetin and am- monol were mere mixtures of acetanilid with other substances, and the federal pure food and drugs law has demonstra-ted that some of them, at least, have been changed in composition and now contain phenacetin. We can, therefore, no longer prescribe these mix- tures under the impression that we are using true chemical compounds. It is probable that acetanilid figures more extensively in self-drugging than does any other single substance. ANALGESICS AXD SOPORIFICS. 315 The following are official : AcETAXiLiDUM. — U. S. P. — Acetaiiilitl, antifeb- rin or phenylaeetamicl, the monacet}'! deriyative of anilin, occurs in colorless crystalline laminse or powder, permanent in air, odorless, of a slightly burning taste, and very slightly soluble in water. It was first prepared by Gerhard in 1852, but was not used medicinally until nearly thirty years later, when it was introduced under the trade- mark name of autifebrin. It is now employed very extensively, its extreme cheapness^ — less than 2 cents an ounce — causing it to be used as the basis of many pretended synthetics. Average dose: 0.20 gm. (3 grains). PULVIS ACETAXILIDI COMPOSITUS. — U. S. P. - This has been made official to serve as a substitute of uniform standard for the host of more or les? similar compounds, such as we have enumerated above, wliieli have come into such unfortunate vogue. The official preparation consists of 70 per cent. of acetanilid. 10 per cent, of caffein and 20 per cent, of sodium bicarbonate. Average dose: 0.3 gm. (5 grains)." AcKTPiiEXETiDiNUM. — U. S. P. — iVcetphencti- din, jjctter known as phenacetin, is official in the 5. It should be noticed that the dose of acetanilid in the mixture is larger than the official dose of acetanilid ; yet it Is supposed to act more effectively when mixed with so- (Ihiin bicarboiiale. It is to be regretted tliat such a combi- nation lias been given ofBcial recognition. The reason, of course, is evident — persistent advertising of certain nostrums has created an abnormal demand' for acetanilid combined with a supposed heart stimulant. IJiit, as it is extremely liiiprr)l)al)le that calTeln does countenicl the liiiiinin! i-UVcts of airtaiillld, it Is not wise to recogni/.r sinli a i cniblnation I'VfU III meet a suppr)sed demand. 31 G PHARMACOPEIA AND PHYSICIAN. British, German and other European pharmaco- peias as Phenacetinum. It is officially described as Acet-para-phenetidin, a phenol derivative, the product of the acetylization of par-amido-phene- tol. Phenacetin occurs as white glistening scales or a fine crystalline powder, odorless and nearly tasteless. It is soluble in 925 parts of water and in 12 parts of alcohol. Average dose: 0.5 gm. (8 grains). Antipyrina. — U. S. P. — Antipyrin is official in France as Analgesin, in Great Britain as Phena- zonum, and in Germany as Pyrazolonum — phenyl- dimethylicum. Chemically, it is described as phenyl-dimethyl-pyrazolon, and is obtained by the condensation of phenyl-hydrazin Avith aceto-acctic acid and subsequent methylation of the product. Antipyrin occurs as a colorless, almost odorless, bitter tasting, crystalline powder, that is readilji soluble in water and soluble in about 1 part of alcohol. Average dose: 0.250 gm. (4 grains). Antipyrin was. first prepared by Dr. L. Knorr of Erlangen, in 1884; it was investigated physiologic- ally by Professor Filehne, who reported it as an active antipyretic. It will be more satisfactory to consider the therapeutics of these antipyretics collectively, with occasional comments on the separate meml)ers of the group. They are mostly used for headache and for the reduction of temperature in fevers of an intermit- tent type, Ijut it must not be forgotten that they do not remove the underlying cause, and that the ANALGESICS AXD SOPORIFICS. 317 use of these drugs in continued fevers is liable to be harmful, since the temperature is sure to return to its former height, or to go even higher, when the action of the antipyretic has worn off. The alarming collapse that may follow even a moderate dose of acetanilid serves as a warning against its use when there is reason to suspect any tendency to that condition. On the other hand, a sudden lowering of the temperature in fever may result in collapse symptoms wholly independently of the nature of the remedy employed. Acetanilid has the greatest and phenacetin the least tendency to produce collapse among the official preparations of this nature. It is. in part, to overcome this tendency that caffein is used in the official com- pound acetanilid powder, but it is doubtful if it is of any great value in guarding against this col- lapse, though it does appear to enhance the anal- gesic action of this class of remedies. There can be little doubt that many of the sudden deaths, of which we so constantly read, occurring without ap- parent cause on the streets and elsewhere, are in reality due to overdosing with nostrums containing acetanilid. Women should ho pai'ticuhirly faulioncd against the })romiscuous use of nostrums of the compound acetanilid powder type during menstruation. When it is reinemhi'i'cd that antipyrin and ace- liiiiilid are derivctl IVom phenylhydrazin, and aiiiliii — :i(li\c l)hi(ti| poisons — it is not surprising that the ollicial (h'i'i val ivcs ])0ssess the ]iropor(ics of these drugs in a niiiior (h'Lii'i'o. The collaj)sc .-ecu nfici' inguslion of the anti- 318 PHARMACOPEIA AXD PHYSICIAN. pyretics, particiilarh' acetanilicl (least with phen- acetin), is due to several causes. Probably the most frequent cause is the mere lowering of the temper- ature which exposes the collapse actually existing but hidden by tlic high temperature. This result is not to lie charged to the antipyretic. It is treated exactly as collapse from any other cause Avould be — by stimulation. Very large doses of the antipyretics act on the heart muscle, causing de- pression, and on the vasomotor center, causing col- lapse. The acetanilid hal)it is not rare and it leads to a deplorable condition, but the symptoms generally disappear when the drug is withdrawn. Profuse perspiration is a disagreeable effect, more frequently seen after acetanilid and anti- pyrin than after phenacetin. If this is so annoy- ing as to demand interference, a hypodermic in- jection of 0.5 mg. (1/120 grain) of atropin will be found effective. Eedness and irritation of the skin are frequently seen after the use of the various antipyretics of this group. They are probably due to vasomotor changes. Antipyrin in solution has been used extensively to check the bleeding of superficial wounds, and all the various members of tliis group are to some ex- tent antiseptic. While so much space has been devoted to the contraindications and untoward effects of these agents, it is not with a view of discouraging their use, but rather that the physician may avoid the disappointments which arise from their use in im- favorable conditions. ANALGESICS AND SOPORIFICS. 319 Acetanilid ma}- be o:iven alone in powder or in capsules, in adjuvant or aromatic elixir, or sus- pended in syrup or mucilage of acacia. The com- pound acetanilid powder affords a convenient form for the relief of headache. A dose of 0.3 gm. (5 grains) in powder or capsule is usually effective; this may be repeated once in an hour if necessary, but further repetition is to be avoided. Compressed tablets of such insoluble substances as phenacetin and acetanilid are not recommended as they disintegrate slowly. An acetanilid powder, containing ammonium carbonate instead of caffein, is used in the German Hospital of Philadelphia,*' when it is desired to avoid tlie cerebral stimulation of caffein. Antipyrin is very soluble in water and in alco- hol, and hence it may be given in simple aqueous solution, in aromatic elixir or in powdered form, but not in combination with other active remedies, as it is readily decomposed. Acetphenctidinuin (phenacetin), being less ob- jectional)U' than acetanilid and antipyrin, may be expected to replace them very largely now that the price is reduced. Its insolubility in water has led to its extensive use in powder and in capsules. A combination of phenacetin. calTein and sodium 0. R. A 'I'hls Is siillicii'iil for ti'n powders of about 0.3 gm. (."» grains) cacli. one l)i'iiig givoii every threo or four hours to r(?duc(' fi'vrr. For licadaihc one is given niul repeale^l, if necessary, in an hour. a20 PHARMACOPEIA AND PHYSICIAN. bromid has attained considerable popularity; these may be combined in various ways." The antipyretic action of these drugs is obtained best by administering them when a natural remis- sion of the fever begins. Acetanilid causes a more prompt fall of the tem- perature, while the action of phenacetin is more lasting. Small doses are usually effective in typhoid fever, but even large amounts are often ineffective in pneumonia and septic conditions. The relative value of the antipyretics of this class and the cold bath is still the subject of dis- pute, and circumstances must determine which is to be used in any case. In districts where trained attendants are not to be had the careful use of the antipyretics is certainly preferable to the cold bath given by inexperienced nurses, or by indifferent orderlies, as is the custom in some of the large hospitals in New York, for example. R. Acetphenetidini (phenacetin) ...grs. xy 11 CaffeiuiE grs. via o Sodii bi-omidi ■■?.] ^ 4 Elixir adjuvantis iSm 1UU| The mixture is to be shaken and two teaspoonfuls givenas a dose. This is often used for headache, one dose being usually sufficient. . . . Still another, widely used, mixture containing acetanilid, is a migraine elixir that is being exploited by a number of manufacturers. A representative formula, for a preparation of this kind, may be given as follows : R. Acetanilidi S^'- ^^^. Caffeinse S^.u] Sodii bromidi ^l\ Alcoholis • f3i , ^4 Elixir aromatici q. s. tt tjiu 100 Average dose .5 c.c, or 1 teaspoonful. If 20 c. c of tincture of cardamom be added to this, or if adjiivant elixir (which is also official) be used instead of the aromatic, the appearance of the mixture will be much enhanced and the psychical effect increased. ANALGESICS AND SOPORIFICS. 321 THE HYDRATED CHLORAL GROUP. The hydrated chloral group includes, besides h\- drated chloral, chloralformamid (chloralamid), paraldehyd, ethyl carbamate (urethane), sulphon- methane (sulphonal) and suljjhonethylmethane (trional). Several of these preparations are so well known that we may dismiss them in a few words, but some of them may 1)0 profitably dis- cussed at greater length. It was formerly supposed that hydrated chloral was decomposed in the body Avith the formation of chloroform, on which the action of the drug de- pended. This is now known to be incorrect, for the drug is excreted in the urine, for the most part, as trichlorethyl glycuronic acid. Hydrated chloral acts very much like chloro- form on the heart and on the central nervous sys- tem. Small doses act only on the brain, resulting in a lessened mental activity and a diminished receptivity of impressions, thus inducing sleep. The pulse and respiration become slower as in nor- mal sleep. With larger doses there is a depression of the spinal reflexes and of the respiratory and vasomotor centers, the heart is slowed by direct action, as after chloroform. The cutaneous ves- sels are markedly dilated, and this may cause fall of temperature and sometimes a skin rash. Death follows large doses, from paralysis of the heart as with chloroform, and the respiration may be paralyzed at the same time. ''I'he same degenerations are seen after hydrated cliliiral as al'dT fiilorofdnii. and the contraindica- lions for the two drugs arc the same, degcncra- 322 PHARMACOPEIA AND PHYSICIAN. tion of tlie heart and vessels, nephritis, gastritis, and depression of tlie respiratory center. Hydrated chloral acts as a ruljefacient when ap- plied locally, and this irritant action is manifested in the stomach Avhen taken in concentrated solu- tion. It should, therefore, be given well diluted, and large closes are apt to cause gastric irritation even when this precaution is observed. The same train of symptoms which characterize chronic alcoholism are seen when hydrated chloral is taken for a prolonged period. Sulphonal is excreted more slowly than it is ab- sorbed, and cumulation may occur. It is contra- indicated in nephritis. It is easy to drug anyone into unconsciousness, but the members of this group do not possess cura- tive properties and at most they only secure rest and sleep for the patient. Hydrated chloral is not free from danger, and we wish to point out some of the dangers attending its use, either alone or in the nostrums whicli contain it. or closely related substances.^ All authorities agree that it is unjustifiable to use large doses of hydrated chloral, either alone or in combination with other official drugs. When a moderate dose of hydrated chloral fails to induce 8. Attention has been called to Bromidia, which is di- rected to be given in as much as teaspoonful doses every hour until sleep is produced, pain being mentioned as one of the indications for its use. Since hydrated chloral is not an anesthetic, except in unsafe doses, it is readily seen how dangerous this advice Is. particularly when we are dealing with such intense pain as that encountered in appendicitis, even admitting that the preparation contains the other in- gredients claimed. It will be noticed that the dose of hydrated chloral given here is only about 7 grains (0.5 gm.), but combined with sodium bromid is effective and quite safe. AyALOESICS Ayo >'()| Two teaspoonfuls arc >;iven at a dose. Tiiis may he twice repeated at Intervals of an liour if necessary, but more than two doses are rarely re(|ulred in suitable cases. 'I'lie hydrated chloral may be slightly increased in the pre- scription, in which case the dose should not bo repeated more tlian once. 324 PHARMACOPEIA A.A^Z) PHYSICIAN. action is the same as that of hydrated cldoral, but isopral is more active and more toxic. Dormiol is a combination of amylene hydrate and liydrated chloral, and chloralose. a combina- tion of hydrated chloral and glucose, partakes of the action of morphin and is rather expensive. Chloretone. another of the more recent products. is not entirely devoid of danger and is not always so certain in its action as hydrated chloral, while butyl chloral hydrate or croton chloral hydrate, is one of the older compounds that has been found wanting and is now little used. Of the official compounds of this group we have : Chloealformamidum. — U. S. P. — Chloralfor- maraid. Chloralamid. This has practically the same action as therapeutic doses of hydrated chloral, the latter being formed in the body by de- composition of chloralformamid. Average dose: 1 gm. (15 grains). Paraldehydum. — U. S. P.— Paraldehyd, a transparent liquid, is slower in its action than hy- drated chloral, but also safer. It has the disad- vantage of a persistently disagreeable taste and odor. It is locally irritant and should not be used in irritable conditions of the stomach. It may be prescribed dissolved in 10 parts of water or in aromatic elixir, and is l)est administered cold, or followed by a cold drink. Average dose: 2 c.c. (30 minims). SuLPHONMETHANUM. — IJ. S. P. — Sulphonmeth- ane, sulphonal, diethylsulphonedimethylmethane, and SULPHONETIIYLMETHANUM. — U. S. P. — Sul- phonethylmethane, trional, disulplionmethylethyl- I AyALGEiilOi AND SOPORIFICS. 325 methane, ma}' be considered together, as the}^ differ chemically only in the addition of an ethyl group in the latter. Average dose (either) : 1 gm. (15 grains). The therapeutic action of these two preparation.s is practically identical, and the closely related tetronal might also be included in this statement. Trional is somewhat more soluble than sulphonal. While these substances are safer than hydrated chloral they are not wholly free from danger, as fatal cases of poisoning have been reported and the sulphonal and trional habits, while of more recent origin, bid fair to equal, if not to exceed, the chlo- ral habit in the number of their victims. These agents are usually given in powder, and owing to their slow absorption should be given about two hours before they are expected to act. To insure more speedy action they may be given in solution, for which purpose they can be dissolved, or at least suspended, in a cup of hot milk. ^Etiiylis Carbamas. — U. S. P. — Ethyl Car- l)amate, urethane. This is a new official prepara- tion whicli is chiimed to be much safer than hy- drated chloral, to which it would be distinctly su- perior l)ut for the fact that its action is n8t so cer- tain and because tolerance is soon acquired. It is Ijest given in water, in which it is very soluble. The average dose is 1 gm-. (15 grains). The therapeutic use of this group of agents is indicated by the term soporific, and by what has been said concerning their pharmacology. THE BROMID GROUP. "IMic bi'omids depress the central nervous system - Iiiiiiii. iiirduUa and cord — siniullaiK.'ousI v. 'I'be 326 PHARMACOPEIA AND PHYtiWIAN. action on the psychic centers results in mental con- fusion and impaired memory, the action on the medulla and cord in diminished reflexes. This is especially noticeable in the lessened reflex from the throat, and the bromids were used before the introduction of cocain in examination of the lar3^nx. This also explains the lessened sexual desire, and the depression of the motor and sen- sory cells explains the value of these agents in epilepsy. Long continued use of the bromids leads to the condition known as bromism, the most prominent symptoms of which are the skin eruptions of dif- ferent kinds, the fetid breath, coryza, nausea and vomiting. The mental depression results in a tendency to sleep, but this is not so restful as that following hydrated chloral, and the patient usually experi- ences some dulness and mental confusion for some time after awakening. Large doses of potassium bromid depress the heart, but this action is mainly due to the potassium ion, and it does not occur after the use of the other alkaline bromids. Owing to their depression of the cord the bro- mids are antagonistic to strychnin. The excretion of the bromids begins very soon after they are taken, but a long time elapses be- fore they are completely eliminated. Monobromated camphor has no such action as that of the alkaline bromids, because the bromin ion is not dissociated. It belongs to the camphor group, and, having no advantage over camphor, it should be dismissed from the Pharmacopeia. The bromids are of considerable historic, as well ANALGESICS AND SOPORIFICS. 327 as of practical, interest. Potassium bromid was introduced by Balard about 1826, who supposed it to have properties analogous to those of potassium iodid. It was not until some time after 1850 that the present, sedative, uses of the bromids were ac- cidentally discovered. During the past four dec- ades the several alkaline bromids have received con- siderable attention, and several of them are now oflficial in every pharmacopeia. The abuses that have arisen in connection with substances belonging to this group are largely due to the misrepresentations that are made in connec- tion with the efficiency or the character of the nostrums containing them. Strontium salts, particularly the bromid, were brought forward some years since, at exorbitant prices, as being infinitely superior to the corre- sponding compounds of other elements. Experi- ence has shown that, in the main, these claims were unfounded, though many, even now, claim that strontium bromid disturbs the stomach less than the corresponding sodium or potassium salt. An- other claim that is frequently made by manufac- turers of nostrums like "Peacock's Bromides," is that they use "chemically pure" salts. Exactly what is meant by this claim it is difficult to say, but tlie Pharmaco])eia gives us a number of readily applied tests by which the salts themselves may be tested. 'Flic niJiiiiiraciiirci's of nostrums, on tlie other hand, nol in ri'('(ni('n(ly add the vei'v sul)- staiiocs tliat are considered contaminations. 'J'hc official bromids are freely polnl)l(> in waicr. and they are best directed to be d is [k used in aqueous solution, with or witliouL the addition 328 PHARMACOPEIA AND PHYSICIAN. of some one of the aromatic sj^rups. The avail- able salts are : x\mmonii Bromidum. — U. S. P. Calcii Bromidum. — U. S. P. LiTHii Bromidum. — U. S. P. PoTASsii Bromidum. — U. S. P. SoDii Bromidum. — U. S. P. Strontii Bromidum. — U. S. P. Average dose (of anj- one of these) : 1 gm. (15 grains). AciDUM Hydrobromicum Dilutum. — U. S. P. — Diluted Hydrobromic Acid contains 10 per cent, of absolute hydrobromic acid. Average dose: 4 c.c. (1 fluidram). The bromids are useful in the treatment of epi- lepsy, for, while a cure is very rarely effected, they lessen the frequency of the attacks in a very large proportion of the cases. Potassium bromid is usually preferred, but some use a mixture of the alkaline bromids. No perceptible effect may be seen for some time after the commencement of the treatment, but with persistence the benefits usually follow. In such cases the skin eruptions may prove very annoying; scrupulous cleanliness should be enjoined, and arsenic may prove useful for the acne. The bromids are very useful in sleeplessness caused by mental worry, but they are ineffective when it is due to pain. Bromism increases the patient's susceptibility to contagious diseases, such as pneumonia and bron- chitis. Hydrated chloral acts as a soporific in smaller AXALGE^e most simply reduced by slowing the lienii witli- oiil increasing its stivngtb, or by acting on llie \-essels |)ei-i|)l)erally or through the vasomoloi' cen- lers. eaiisiiiL;' dilation. 'j'he aeeiimnlalioii of an limine amount of l>lood 332 PHARMACOPEIA AKD PHYSICIAN. in the veins is relieved by increasing the efficienc}^ of the heart as mentioned for raising the blood pressure — by slowing and strengthening its beat — for, as we have seen, this improves the drainage from the veins by lengthening the diastole, while the strengthening throws a larger volume of blood into the arteries. We uiay arrange the agents affecting circulation into two groups as follows : Those mainly affect- ing the heart, directly or indirectly; those mainly affecting the vessels, directly or indirectly. The most important group of circulatory stim- ulants consists of digitalis and a number of sim- ilarly acting substances. While, as is well known, barium chlorid has an action to some extent simi- lar to that of digitalis, nearly all the other mem- bers of this group that are of therapeutic impor- tance are somewhat allied chemically; for the most part the active principles of these drugs are glucosids or resins. The exact chemistry of the drugs of this class is still obscure, despite numer- ous investigations, and it demands but little con- sideration here; their pharmacologic action, how- ever, serves to explain their therapeutic indica- tions, and may aid in choosing the one l)est suited to a given condition. The circulatory conditions demanding stimula- tion are mainly those in which undue relaxation occurs, and in which an imperfectly acting heart, including such conditions as valvular insufficiency and stenosis, permits the blood to accumulate in the veins. Any increase in the work of the heart must tend to relieve, these conditions, particularly if there is at the same time just sufficient slowing CIRCULATORY STIMULAXT8. SXi to secure eoiuplete distention of the heart with blood during diastole. An increase in the strength of the contraction more coni2)letely squeezes the venous blood out of tbe heart muscle, which is then supplied with a larger j^roportion of arterial blood. The increased force of the jjulse wave must first be felt more strongly in the coronary artery than elsewhere, since there is less inertia to be overcome in the much shorter column of blood between the aortic valve and the opening into the coronary artery. The longer diastole then j)ermits a more perfect supply to the capillaries in the heart, thus improv- ing the nutrition of the heart to an even greater degree than would correspond to the extra work thrown on the ventricles by their being compelled to contract against an increased arterial pressure. As we have just said, the slowing of the heart. should be just sufficient to enable the heart to be- come fully distended, for a greatly slowed heart would suffer in lessened nutrition, because, other tbings being equal, the rate of flow through the coronary circulation varies with the number of the ])uisations in a given space of time. 'I'liis improved nutrition of the m3'ocardium is llic lirst essential for a sustained increase in the force of the beats, cither from a more energetic ac- tion of the uiuiltci'cd licart or after hy))ortrop]iy ; because, ho\\r\ci-. siidi a iiiiisclc mi^iht he stimu- hited to unusual a(li\ity. cNliaustiou and paralysis must follow unless nulrilioii keeps pace with llie work j)erfonne(l. Langendoi-JV lias shown experi- iMcntally that the energy of the lieait is enor- mously influenced by the available blood supply. 334 PHARMACOPEIA AND PHYSICIAN. A drug might affect one or more phases of the heart beat, or the local and central action may be in part antagonistic and the effect on the blood pressure in the general circulation will in the lat- ter case be dependent on the kinds of influence and the degree to which each is excited. Slight slowing with increased strength of con- traction may improve the nutrition, and it will be readily" understood why it is difficult to secure equally perfect nutrition of the heart when it is made to beat more rapidl}', since the only factor here which makes for an improved coronary circu- lation is the more frequent squeezing out of venous blood by the contractions while all other conditions are unfavorable, a greater number of contractions, each throwing out less blood and meaning more energy expended for a given amount of work per- formed — a more frequenf overcoming of the iner- tia of the blood in the arteries — so that a very rapid heart soon exhausts itself. For these reasons we do not often seek to raise blood pressure or to improve the general circulation by increasing the rate of the heart unless it is extremely slow. Shock and collapse are conditions that are due to depression of the respiratory, cardiac and vaso- motor centers. The depression of the vasomotor center permits the vessels to dilate and the blood gravitates to the vessels of the splanchnic area, which are capable of holding a very large amount. This dilatation is accompanied by a fall of pres- sure in the general circulation, less blood goes to the centers and to the coronary circulation, the heart beats more feebly and the respiration be- comes weaker. This condition obviouslv calls for CIRCULATORY STlMlLiyTti. 335 prompt stimulation of the circulation. It is ap- parent, however, that a stimulation of the heart alone would only result in increased work while its own nutrition would not he correspondingly improved hccause the pressure in the coronary cir- culation can not be greatly increased so long as the voluminous vessels of the splanchnic area offer cavernous spaces for the blood which is pumped from the heart. Stimulation of the constrictor mechanism of the vessels is urgently demanded in collapse, and this is secured in the mildest cases l^y gravity deter- mining the blood to the head when the head is placed lower than the body. The centers are toned up by the better blood supply, and this in- creased tone of the vasomotor center causes con- striction of the splanclinic vessels, raises the blood pressure and improves the general circulation, which, in turn, further tones up the centers as well as the heart, which is also stimulated by the improved tone of the cardiac center. The respira- tion is improved at the same time owing to the improved tone of the respiratory center. Dr. George Crile has devised a pneumatic suit whereby pressure may be applied to the surface of the limbs, thus forcing a large amount of blood into the body and head, and gravity (lowering the head) may be made to assist in driving it to the head — the essential fact Ix'iii.u- (o supply ilic iiicdnlhi with blood. I'll VSIOLOOIC SALT SOLUTION. Hciii, mainly su])i)licd by hot water bottles, slioiild lie used widi auv olhcr iiicasiii-os in shook. 330 rilARMACOPFAA AXD PHYHICIAN. The amount of lliiid in the vessels may he consid- erahly increased by injecting, under aseptic pre- cautions, into a vein, or even under the skin, nor- mal saline solution, or, as it is hetter to term it, physiologic salt solution, made by dissolving 9 grams of sodium clilorid in enough water to make one liter (approximately 132 grains of sodium chlorid to 1 quart of water) . The solution should be .boiled (to render it sterile) and then cooled to about 40° C. (104° P.). As noted above this solution may be used hypodermically or it may be injected directly into a vein. Another, and at times a very satisfactory, method of attaining the same result is to inject slowly one or two liters of this solution into the rectum, whence it is readily absorbed into the circulation. Drugs which act on the vasomotor centers are indicated in collapse, but the simple means just enumerated serve, as explained, to tone up the centers in mild cases by an improved blood sup- ply, and they are, of course, preferable to mere stimulation by drugs. Then, too, in proportion to the urgency of the case is the difficulty of secur- ing stimulation of the centers. In profound shock the stimulants of the vasomotor centers ap- pear to have no lasting effect, or to increase the trouble. In collapse of a mild character, however, a vaso-constrictor acting more powerfully on the vessels of the splanclmic area causes the general blood pressure to rise, more blood goes to the cen- ters, and they are placed in a better tone, exactly as is the case when gravity sends the blood to the head. Hot alcoholic drinks are very commonly em- CIRCULATORY STIMULAXTS. 337 ployed in collapse and shock; they probalily act reflexly from the stomach. Some clinicians maintain that morphin im- proves a weakened heart. As a depressed center is less susceptible to shock from reflex influences, morphin may lessen shock or depression due to pain, and the centei- will then ])e able to exert a better influence on the heart. It has often been claimed that opium or morphin caused an in- creased supply of Ijlood to the brain by dilating the vessels of that organ, and this may account for an increased circulation in the cardiac center and hence an improvement in the heart. The depression of tlie respiratory center by morphin is i-ather strong evidence against any stimulation of the cardiac center, however. Morphin has no direct action on tlic licart and its vasomotor effects are variable. THE DIGITALIS GROUP. The pharmacologic action of digitalis and that of its available active ])rinciples have been more extensively studied tlian has been done in the case of any other member of the group. The isolated frog's heart, and latcM- tlio mammalian, has been used to determine the iulioii lui i])at organ apart from the influence tlirougli the cciitcu-. The rate of the isolated uiamiiialiaii heart is citlicr in- creased or little afl'ected by digitalis or its pi-iu- ciples, but Gottlieb and Magnus found that ilic strength of the iiidi\'idiial coulraclioiis is iiicrcasnl by it and that iimmv adiial wnvk is done hy tlir isolated heart. In llif iidad luaiiiinal digitalis slows tlie heai'l liy si iimdai ion of ilio \agiis cen- ter, and the slreiigili of the lieat is ineivased hv 338 PHARMACOPEIA AND PHYSICIAN. the action on the myocardium. The vasomotor centers are stimulated at the same time. The direct results of these several actions have been detailed in the introductory paragraphs. Digitoxin, the most active of the principles that have been isolated from digitalis, has essen- tially the same action on the circulatory system as the drug itself, but, being insoluble in water, it is slow in producing its effects, x^lbert Fraenkel has found that about sixty hours elapsed after a single effective dose was injected, hypodermically, into a cat before the typical action was induced. Digitalin, or "Digitalinum verum," is somewhat more soluble in water and its action was elicited in twenty-four hours after a dose, corresponding in activity to that of digitoxin just mentioned, was injected into a cat, while strophanthin (ob- tained from strophanthus seeds), which is very soluble in water, produced its effects much more rapidly. The therapeutic action of these three substances is very similar, but Gottlieb and Mag- nus found that digitoxin is capable of restoring an irregularly beating heart to rhythmic pulsations to an astonishing degree ; indeed, they were able to restore isolated and perfused hearts to strong reg- ular beats after they had gone into delirium cordis. Digitalis and other members of this group have the great disadvantage of causing cumulative ef- fects when used continuously for some time. Digi- toxin produces these effects more readily than strophanthin and digitalin. Fraenkel was able to continue the administration of digitalin daily for many weeks at near the toxic dose without cumu- lative action. No habituation occurred in this CIRCULATORY 8TIMULAXTS. 339 period, however, tlius disproving the claims of Heide, based on a much more shorter period of experimentation, that such takes place. Gastric irritation is the first evidence of a toxic action from a single toxic dose or from cumulative action, and digitalis, or any of its congeners with- out exception, must be stopped for a time when cimiulative effects are seen. When the heart is slowed by any member of the digitalis group the action is very persistent. Digitoxin causes constriction of the coronary arteries, but this does not occur after strophanthin. As noted before, there are other drugs and chemicals that possess a somewhat similar action, but it must be evident to all that nothing is to be gained, and that much harm may result from giving heed to unwarranted and exaggerated claims of the nostrum maker who lauds a prepara- tion which ostensibly depends on some little known drug, such, for , instance, as the several species of cactus. By far the most interesting as well as the most important of the official drugs of the group now under consideration is : Digitalis.^ — U. S. V. — This consists of the dried leaves of Dir/Halis purpurea, collected from 1. From what wo know of liio chemistry of this partic- ular druK, and from tho action of tho Itnown isolated proxi- mate princiiiies. it would ap^iear that in this connection it was particularly unfortunate that the committee on revision did not see its way clear to adhere more strictly to the pro- posed internal ional standards for the formulas of potent medicaments and direct, for Ihe extraction of digitalis, the proi)osed 70 i)er cent, alcohol in place of the diluted alcohol of the U. S. riiarmacopeia. The strouRer alcohol would have had Ihe advantajje of insuring: a more ready and more coinplcto solution of the active principles, of answoriiifr hettcr as a preservative and of matei'ially reducing llie amount of Inert extractive now contained In the ofllcial tincture. ;U() PHARMACOPEIA AND PHYSICIAN. tlic second year's growth at the commencement of flowering. This drug is official in all pharmaco- peias and is generally considered as being particu- larly susceptible to chemical change. It sbould be carefully preserved and should not l)e kept for more than one year. Average dose: 0.05 gm. (1 grain). While the chemistry of digitalis is far from be- ing thoroughly understood, there are a number of proximate principles derived from digitalis that are now lacing marketed in a commercial way and which have well-defined chemical as well as physio- logic properties; several of them are being exten- sively used in this country as well as abroad. The most potent of these unofficial articles is : Digitoxin: This, as has been noted before, is soluble in alcohol, but is nearly insoluble in water. The older and in some respects better known French preparations, variously called digitaline crystallisee, or French digitalin, closely resemble digitoxin in physical properties and also in physio- logic activity. Digitalin (Digitalinum verum, Kiliani) : This is a white amorphous glucosid that is readily solu- l)le in alcohol, but only slightly soluble in water.' While it is less toxic than digitoxin and may be given in much larger doses, it closely resembles that principle in its therapeutic action and uses. Digitin (Merck) : This is also readily soluble in alcohol and only slightly soluble in water. While still available it is now generally thought to be physiologically inactive as a circulatory stimu- lant. CIRCULATORY SriMULAXTS. 341 Digitalein (Scliiniedeberg) : This is reaclily sohible in water and is jirobably a mixture of sev- eral proximate principles. Digitalin "German" : This occurs as a yellow- ish white, amorphous powder that is soluble in both water and alcohol. It is said to consist of a varial)le mixture of Digitalinum verum (Kiliani), digitalein and digitonin. The following are official : ExTRACTUit Digitalis. — U. S. P. — Tliis is made from the fiuidextraet by evaporation. Average dose: 0.01 gm. (10 mg. or 1/5 grain). Fluidextractuji Digitalis. — IT. S. P. — Fiuidextraet of Digitalis is made with dihited alcohol. Average dose: O.O.") c.c. (1 minim). Infusum Digitalis. — U. S. P. — Infusion of Digitalis contains I.-") ]X'v cent, of digitalis, 10 per cent, of alcohol and L") per cent, of cinuamon water. Average dose: 8 c.c. (2 fluidrams). Tixctura Digitalis. — T'. S. P. — Tliis now rep- resents 10 per cent, of the ci-iidc drug in diluted alcoliol in ])l;icc (.r l."i pel- cent, as fornici-h- olTi- .-ial. Average dose: 1 c.c. (lo minims). STROlMIAXTIflXU.M. — V. S. I'. — 'i'llis is a ghlco- sid, or uiixture of glucosids. olitaincd from stro- pbantbus. .\vcragc dose: (i.nii;; -ni. ((>.;; mg. or 1/200 grain). STitoi'iiANTiirs. — r. S. I*. This consists oi' the ripe .seeds of Slrophujilli ti.s Kunibv. 11 is pret- 342 PHARMACOPEIA AND PHYSICIAN. erably administered in the form of the official tincture. TiNCTURA Strophanthi. — U. S. P. — This preparation now represents 10 per cent, of the drug in 65 per cent, alcohol, and is double the strength of the tincture official in the U. S. Phar- macopeia, 1890. Average dose: 0.5 c.c. (8 minims). Apocynum. — U. S. P. — This is the dried rhi- zome of Apocynum cannahinum, or of other close- ly allied species of Apocynum. This drug is said to have been used by the American Indians in various ailments, and has long been in use as a household remedy. More recently it has again attracted attention by its possible uses as a circu- latory stimulant, though the practical results that have been attained so far do not appear to warrant its use in all cases. The only official preparation is: Fluidextractum Apocyni. — U. S. P. — The Fluidextract of Apocynum is directed to be made with a mixture of 10 per cent, of glycerin, 60 per cent, of alcohol and 30 per cent, of water. Average dose: 1 c.c. (15 minims). Convallaria. — U. S. P. — This consists of the dried rhizome and roots of Convallaria majnlis. Average dose: 0.5 gm. (71/2 grains). Fluidextractum CoxvALLARiiE. — U. S. P. — This is made with a mixture of 65 parts of alcohol and 35 parts of water. Average dose: 0.5 c.c. (8 minims). THERAPEUTIC ACTIONS OF THE DIGITALIS GROUP. Digitalis will be referred to again under the heading of diuretics (Chapter XVI). CIRCULATORY STIMULANTS. 343 As a circulatory stimulant one of the drugs of the digitalis group is indicated when the heart is M-eak and rapid and the blood pressure low, con- ditions which arise under a variety of circum- stances. In cardiac dilatation with wea^v systole digitalis affords our best remed}', as may be readily under- stood from the pharmacologic action. In pneu- monia the right ventricle suffers primarily and digitalis is indicated, for, while it affects the right ventricle less than the left, and the auricle least, tliis does not affect its usefulness in this condition, liecaiise the nutrition of the heart — both left and right — is supported by the improved coronary cir- culation, a most important factor, as we have seen, when extra work is thrown on the heart, and the pulmonary circulation is not affected directly by the general vasoconstrictor action of the digitalis. In this connection, the lengthened diastole, while it undoubtedly affords a better chance for the empty- ing of the pulmonary veins, is a factor of but minor importance. The use of digitalis in mitral insufficiency is familiar to all and the pharmaco- logic action readily explains its usefulness in this connection. Digitalis and its congeners arc said to be harm- I'ul in some cases of mitral stenosis, and they may fail to prove beneficial in insufficiency of the aortic valves. U is suggested ili;i( in (bis condition the Ijlood may gravitate from the brain through the aortic valve during the lengthened diastole. This action of the drugs also must be observed care- fully in these conditions and they must be with- drawn if they appear to be doing harm. 344 PHARMACOPEIA AND PHYSICIAN. Drugs of the digitalis series are contraindicated in cases of fatty degeneration of the heart, since a lieart so weakened could scarcely support the addi- tional burden imposed by the increased arterial tension, and hypertrophy can not be expected to occur in such a heart. They are also contraindi- cated in all conditions in which an increasing l)lood pressure would be dangerous, for instance, in aneurism. AYith digito-xin particularly, one must constantly watch for the first symptoms of cumulative action, usually gastric disturbance, and it, or other mem- bers of the same group, should be temporarily withdra\\Ti when suggestive s}Tnptoms occur. The tincture of digitalis contains a larger pro- portion of the alcohol-soluble digitoxin than does the infusion, in which the digitoxin present is held in solution by means of digitonin. Digitoxin be- ing the most irritant of the known principles of digitalis, the infusion, containing digitalin prin- cipally, will often be preferred. AMien the heart is weak and irregular, digitoxin is proliably the most efficient remedy we possess for restoring it to normal contraction. An alcoholic solution of digitoxin may be used to advantage, provided it be well diluted with water when ad- ministered. The dose of digitoxin as given by the different authors is somewhat variable. Cushny states that 1/12 mg. (1/750 grain) of crystalline digitoxin may be given three times daily. Schmiedeberg recommends 1/5 mg. (1/330 grain) of the crys- talline digitoxin three times dailv, and this has CIRCULATORY STIMULAXTS. 34.3 been supjDorted b}- clinical experience. The physi- cian will do well not to exceed this latter dose too greath^, bearing in mind that cumulative effects sometimes develop quite suddenl}-, even with a dose which has been apparently harmless. Digitoxin and digitalin, pure or in the leaf, are changed into substances with a convulsive action in the presence of moisture, by bacteriologic ac- tion, hence old infusions should not be used nor should those leaves be employed which bear evi- dences of not having been properly dried and care- fully preserved. Wlien Oloetta announced the discovery of a sol- uljle amorphous form of digitoxin, which he named Digalen, it was generally accepted because of Cloetta's standing in the scientific world, but it appears that this preparation has no advantages over other prc'i^arations of digitalis, that it is not an aqueous preparation, that its subcutaneous use is painful and finally that it difi'ers but little from a hydroalcoholic solution of ordinary digitoxin. It is to be hopetl lb at in the next revision of the I'harmacopeia digitalis leaves will be directed to be piiysiologically assayed, dried with proper care and sealed with the date of assay, for the leaf so j)repared has proved more satisfactory in the hands of many clinicians than any of the isolated priu- ciplcs or llic (ialenical preparations of the dni^-. Digitoxin and digilaliii iii;iy be l;c|)( dissoUcd in alcohol and diluted as i-ci|iiinMl. Tlio dose oL' digitalin, or digitaliiiiiiii \cniiii, is Cioin 2 tod iiig. (l/;}() to J/10 grain) tlirce tijnes daily. 340 PHARMACOPEIA AND PHYSICIAN. Digitoxin ma}^ be i^rcscribed as follows : R. Digitoxini (cryst.) gr. 1/12 |005 Alcohol, q. s. "ad fgiii 100| M. Ft. solutio. Sig. : One teaspoonful in a little water three times a day. Digitalin can be prescribed in tbe same way, but 0.05 is nsed in place of 0.005 gm. thus : I^. Digitalini veri gr. i [05 Alcohol, q. s. ad f giii 100| M. Ft. solutio. Sig.: One teaspoonful in water three times daily. The tincture of digitalis, diluted with' water, is given alone three times a day. Owing to the slow excretion it is not necessary to repeat the dose more frequently, and the drug should be stopped for two days about once a week to avoid cumu- lative effects, whether one of the active principles or a Galenic preparation of digitalis is being used. Sollmann has suggested that strophanthin may deserve an even greater popularity than digitalis, and this suggestion has found support in more re- cent investigations. Strophanthin is now official whereas the active principles of digitalis have not as yet been included in our Pharmacopeia. Strophanthin causes but little vasoconstriction and itj therefore, deserves the preference over digi- talis and its principles when increased blood pres- sure is to be avoided. Thus, when dilatation of the heart is due to high blood pressure from in- creased arterial tension, strophanthin may be used, or, if digitalis is employed, a vasodilator such as nitroglycerin or one of the nitrites should l)e given at the same time. Because of its more prompt effect on the heart, CIRCULATORY 8TIMULAXTS. 347 strophanthin may be employed to usher in the action when digitalis is to be employed. This promptness of action would also render it prefer- able to digitalis in shock or collapse were it not that the vasoconsti'ietor action is wanting. Digitalis, or one of its principles, may be given several hours before an operation when there is reason to apprehend shock, so that its action may coincide with the time that shock occurs instead of waiting till that condition has actually developed before giving the slowly acting remedy. Strophanthus seed and the tincture were for- merly of very variable quality, Init at the present time they are fairly uniform. Strophanthin, the active principle of strophan- thus seed, is of constant composition, is very solu- l)le in water and may, therefore, be dispensed in simple solution. However, it undergoes decompo- sition, in aqueous solutions, and it is, therefore, better to prescriljc it in diluted alcohol: 0.01 gm. (1/5 grain) may be directed to be dissolved in 100 c.c. (3 fluidounces) of diluted alcohol and one teaspoonful of this solution, diluted with water, may be given three times a day. The official strophantliin must not be confused with crystallized strophanthin, g-strophanthin, gratus strophanthin or strophanthin Thorns, as it is variously termed, which is obtained from the seeds of strophanthus gratus, and which is rec- ommended in doses of 5 milligrams (1/13 grain) or .30 milligrams (i/. grain) per day, while as much as 0.075 gm. (1^4 grains) per day have Ix-cn given to an adult. Gratus strophanthin is said to be identical with oualjain, l)iit lliat, on tbe 348 PHARMACOPEIA AM) PHYSICIAN. other liand. has been said to be much more toxic, to the frog's lieart at least, than ordinary stro- phantliin. Tbe dose of stroplianthip gratus men- tioned above is only for internal use, as the gluco- sid is much more toxic when used subcutaneously. We may call attention to the fact that the dose of strophanthin given in the Pharmacopeia — 1/3 mg. (1/200 grain) — is smaller than that contained in the ordinary dose of the tincture, 0.5 c.c. (8 minims), of which certainly represents more than lialf a milligram (1/135 grain) of strophanthin, and it has been suggested that the latter has been advised in wholly inadequate doses. It is extreme- ly toxic, however, and the dose must be increased only witli great caution. Dr. H. C. Wood, Jr., recommends Canadian hemp as a satisfactory and reliable circulatory stimulant, but as his published work appears to have been done with a fluidextract of Apocynum cannahinum and as the Pharmacopeia itself recog- nizes closely allied species of apocynum, that may or may not have similar physiologic properties and therapeutic uses, it may be well to await the re- sults of further investigations before trusting too implicitly in the possible results to be obtained from this drug. Other official memljers of this group have little to recommend them in preference to the more prominent ones just described. It might be added that the alkaloid of tlie supra- renal gland is not suited for long continued admin- istration. It does not influence blood pressure when given by the stomach, and l)ut slightly or not at all when injected just l^eneath tlie skin. CIRCULATORY STIMVLAyTS. :34!) When injected into the muscle there is a transient rise of blood pressure. Its local use has been dis- cussed at greater length in connection with as- tringents (Chapter VIII). STRYCHXIX. Strychnin, unlike digitalis, has no perceptible direct action on the lieart when therapeutic doses are used, but it produces its circulatory effects wholly by its influence on the centers, except in so far as the local action on the alimentary canal is concerned; this may be disregarded in the pres- ent consideration of strychnin, which is commonly injected hypodermically when its circulatory ef- fects are desired. Therapeutic doses of strychnin cause a rise of blood pressure by stimulation of the vasomotor center; the reflexes are increased, leading to im- proved tone of the voluntary muscles, and in- creased muscular activity always tends to increase the heart rate; this tendency, however, is counter- acted by the stimulation of the vagus center by strychnin, tlie heart being slowed or showing littlo (•bange in frequency. When the slowing is exces- sive there is a fall of blood pressure despite the vasoconstriction, but this does not usually occur. If the tendency to increased frequency predomin- ates over tbe vagus stimulation the rise of blood pressure is further augmented. As strychnin operates readily to produce its ef- fects it is a most valuable remedy when a quick rise of blood pressure is required. So rapidly are its effects elicited that convulsions may occur in a frog within two minutes of Die injection of a toxic 350 PHARMACOPEIA AND PHYSICIAN. dose, and after a massive dose a rabbit may give a single convulsive leap into the air and be appar- ently lifeless from paralysis of the respiratory and other centers when it strikes the operating table. Biberfeld has investigated its mode of action on the respiratory center. He depressed the res- piration by morphin, after Mdiich str3^chnin was injected; this usnally resulted in a greater in- crease in the volume (sometimes even exceeding that before the administration of morphin) than in the frequency. The following preparations are official : Strychnina.^ — U. S. P. — This is an alkaloid obtained from nux vomica; it is also obtainable from other plants of the Loganiacew. Strychnin is only slightly soluble in water, 1 to 6400, but it is soluble in 110 parts of alcohol. 2. Owing to the frequency with whi'ch poisoning by strych- nin occurs, its toxicology deserves brief mention here. As is well known, strychnin causes a characteristic type of convulsion rather closely resembling tetanus. The amount of the alkaloid that is necessary to produce this toxic effect Is much greater, however, than is usually supposed ; but, ou the other hand, when once a large amount has actually en- tered the circulation, there is little hope of ultimate recovery. As death is due to paralysis of the respiratory center life may be prolonged, and a possible recovery brought about, by carrying on artificial respiration. This, however, should be begun before natural respiration ceases or even before It be- comes very greatly depressed. Strychnin requires several days (3 to 8) for its total elimi- nation. Diuretics hasten elimination and may be of benefit when the amount of the poison that has been taken does not greatly exceed the minimum fatal dose. Cushny advises strong tea (infusion) when the patient is seen with the strychnin in the stomach. This advice seems to be based on a misconception of the capacity of tea tannin for forming the insoluble tanuate. The fact that strychnin acts directly by paralyzing the re- spiratory center fully explains the possible danger that may result from the use of a stomach tube, and it will not be nec- essary to repeat this frequent caution. CIRCULATORY STIMULANTS. 351 STRTCHNlN-iE SULPHAS. — U. S. P. — This is the salt of str3X-hnin that is most extensively used in this country; it contains five molecules of water and approximately 78 per cent, of strychnin alka- loid. Strychnin sulphate is soluble in 31 parts of water and in 65 parts of alcohol. On the continent of Europe the preference is usually accorded to the nitrate. This is official in our Pharmacopeia as : Strychnin"^ ISTitras. — U. S. P. — This repre- sents 84 per cent, of strychnin alkaloid and is solu- ble in 42 parts of water or in 120 parts of alcohol. The average dose of either of the official prep- arations is given as 0.001 gm. (1 mg. or 1/64 gr.). Strychnin is useful in all forms of low blood pressure because of its action on the vasomotor center. There can be little doubt of the beneficial ef- fects of strychnin in many cases of shock or col- lapse, but when irrecoverable shock exists it ap- pears to depress further the centers after an ex- tremely brief stimulation.^ To secure its greatest usefulness in conditions of this kind strychnin should be given hypodermic- ally, or to secure an even quicker action it should be injected deeply into the muscle of the arm or tliigh. This method of hypodermic injection is 3. Crilo deflnos surgical shock as an exhaustion of the vasomotor centers, the cardiac and respiratory centers being only secondarily Involved, and collapse as due to a suspen- sion of the functions of the cardiac or vasomotor centers or to hemorrhage. Of course, an exhausted or paralyzed structure can not be stimulated. Sollraann defines both shock and collapse as a sudden depression of the activity of the medullary center; If of reflex origin, shock; if direct, col- lapse. We employ the terms in the latter sense. A depressed renter may be stimulated. 352 PHARMACOPEIA AND PHYSICIAN. usually to be preferred, as it is less painful than injections just beneath the skin. Str3^chnin is one of the best respiratory stimu- lants and in an emergency large doses may be given. It is always to be remembered that strych- nin is a remedy for the crisis and is not to be used as digitalis is, to maintain blood pressure for a considerable length of time. AVhen paralysis of the limbs is due to a lesion in the cord which completely blocks the transmis- sion of nerve impulses strychnin can do no good, since it has no peripheral action, but if the paraly- sis results. from a lesion in the brain the increased reflexes which strychnin causes will serve to delay muscular atrophy. It may also serve to restore the tone of the reflexes when these are lowered by functional disturbances of the cord. Thus incon- tinence of feces and urine may be relieved when these are due to the lowered reflex centers for the sphincters of the bladder and anus. Caffein is closely related to strychnin, to which, however, it is greatly inferior, so far as any in- fluence on the circulation is concerned. It stimu- lates the vasomotor and respiratory centers and is useful, therefore, in the treatment of poisoning by morphin and other narcotics, in the form of strong tea, but strychnin serves the same purpose and perhaps more efficiently. Hoffmann noticed that theobromin possessed a stimulant action on the myocardium, similar to that sho-wTi by caffein, but no vasoconstrictor effect. In therapeutic doses of either agent, however, this cardiac effect is of little importance. CIRCULATORY STIMULANTS. 353 Atropin causes acceleration of the heart b}^ par- alyzing the vagus endings, and this also causes an increased systole and a lessened diastole. The rate of the heart may be twice as great as under normal conditions, the result being a considerable increase in the output of the heart in a unit of time. The effect on the circulation of the increased heart action is supplemented by the constriction of the arterioles of the splanchnic area, due to stimulation of the vasoconstrictor area, due to stimulation of the vasoconstrictor center by atro- pin, which also stimulates the vasodilator center for the vessels of the skin, particularly those of the face and neck, but this is of comparatively little influence on the general blood pressure which rises in response to the two actions just mentioned. The influence of atropin on the heart rate is much less in children and in old age than it is be- tween the ages of 20 and 60 years, because the vagus inhibition is slight at the extremes of life in man. The vagus is much more active in some animals than in others. In this respect the dog resembles man. Atropin may cause a brief but unimportant slowing of the heart, due to stimulation of the cen- ter, preceding the acceleration which depends on the paralysis of the vagus endings. A^Hiilc it has been undeniably shown that atropin may power- fully stimulate the myocardium, this efTect with therapeutic doses is so slight that it may be en- tirely disregarded. Atropin acts as a stimulant to the respiratory center, but it is inferior in this re- 354 PHARMACOPEIA AND PHYSICIAN. spect to stiychnin; it increases the rate, and prob- ably the depth, of the respiration. The central action of atropin is exerted mainly on the motor area, but it has been suggested that the differences between the action of atropin, caffein and strychnin on the various parts of the central nervous system are in degree rather than in kind. Thus, while caffein acts mainly on the higher centers in man, stimulating the psychic functions, it is capable of causing strychnin-like convulsions in the frog. All three act as powerful respiratory stimulants in mammals. Atropin is official as : Atropina. — U. S. P. — Atropin is an alkaloid prepared from Atropa Belladonna, or from other plants of the same family. It is soluble in 450 parts of water and in less than 2 parts of alcohol. Atropine Sulphas. — U. S. P. — This salt of atropin is official in many, if not all, pharmaco- peias and is the best known and most widely used preparation of the atropin group. It is soluble in less than 1 part of water and in 4 parts of alcohol : Average dose (alkaloid or salt) : 0.0004 gm. (0.4 mg. or 1/160 gr.). Atropin is indicated when the lieart is consider- ably slowed. For this purpose the average dose given above is not usually sufficient, about 1 mg. (1/65 grain) being necessary to increase the rate; so large a dose being necessary to produce paral}'- sis of the vagus endings in the heart. It must be remembered, however, that in children and in the very old (after 70) the effect to be expected is much less than that seen between the ages of 20 and 60. This larger dose causes stoppage, or, at CIRCULATORY STIilULAMS. 355 least, a marked diminution of salivary secretion with consequent dryness of the mouth and throat. Wliile atropin has been used in shock and col- lapse, it can have but little influence on blood pres- sure or respiration in such cases. Atropin may be used to determine whether an abnormally slowed oi' intermittent heart results from central influences or from causes within the heart itself, since it cuts off all impulses from the center arriving through the vagus, but produces no appreciable effect if the cause lies within the heart. Atropin has been used to prevent the reflex stop- page of the heart occurring at the commencement of anesthesia, but it has been shown that there is no danger of such a catastrophe if the anesthetic is not used in too great concentration. Poisoning by certain fungi which contain mus- carin, while rare, may best be treated with moder- ate doses of atropin. Pilocarpin is also antag- onized in nearly all of its actions by atropin, but tlie latter does not counteract the cardiac effects of physostigmin, which acts on the myocardium. The value of atropin in opium poisoning has been much disputed. It seems to possess no ad- vantage over caffein and strychnin in such cases and it has the disadvantage of adding to the de- pression of the respiratory center if more than a therapeutic dose is given. Clinical experience seems to have abundantly proved that small doses of atro- pin are corrective for ordinary doses of morphin, and it is almost universally so used.* 4. A widely used combination consists of morpbin sul- phate O.Ol.'j gm. C/i grain) and atiopln sulphate 0.0004 gm. d/l.')© grain) prepared In the form of the now popular hy- podermic tablets or dissolved in distilled water sullicient for one dose. 356 PHARMACOPEIA AND PHYSICIAN. Atropin is usually given hypodermically when the central effects are desired. CAMPHOR. In shock or collapse camphor given by the stom- ach produces a feeling of warmth and probably acts reflexly for the most part. The respiratory and vasomotor centers, as well as the heart muscle, are stimulated, thus causing a rise of blood pres- sure. The heart is usually slowed and the con- traction strengthened. Camphor is almost insolu- ble in water and only slightly volatile at the body temperature, and its action, therefore, is very un- certain; 0.03 gm. (1/4 grain) may improve the ]iu]se in some cases, while twenty times as much may be required in others ; hence but little reliance can be placed on it in crises, though it is very often effective. The spirit, diluted with water, is fre- quently used for internal administration. A num- Ijer of camphor derivatives have been employed from time to time, but they have not been shown to possess any advantages over camphor itself, or one of its more simple preparations. C AMPHORA. — U. S. P. — Camphor is a white, volatile, solid substance having a crystalline struc- ture and a characteristic aromatic odor and taste. Cam|)hor has been used in the Far East for many centuries, but was not known in Europe until in- troduced by the Arabians. It is now official in all pharmacopeias. Average dose: 0.12 gm. (2 grains). Aqua Camphor.^;. — IT. S. P. — This is a satur- ated solution of camphor in distilled water. It is CIRCULATORY STIMULANTS. 357 frequently used as a vehicle for other medical sub- stances. Average dose: 4 e.c. (3 fluidrams). Spiritus Camphor.^-:. — U. S. P. — This is a 10 per cent, solution of camphor in alcohol. Average dose: 1 c.c. (15 minims). LiNiMEXTUM Camphors. — U. S. P. — This jjreparation, variously known as camphor liniment and camphorated oil, contains 20 per cent, of camphor dissolved in cottonseed oil. While large- ly used as a mildly rubefacient local application it is not infrequently used for hypodermic injections or for the internal administration of camphor in the form of an emulsion. The average dose would be al)out half of that given under spirit of cam- phor. Camphor is frequently employed as a diapho- retic, particularly in combination with other agents, because of its stimulation of the vasodila- tor centers for the cutaneous vessels. As noted above, camphor water alone has little* therapeutic value and is useful mainly as a vehicle for other substances. Camphor may be given in pill form, in capsules or in the form of an emul- sion. Probably the best method of administering camphor consists in suspending the finely pow- dered substance in twenty parts or more of milk. For this purpose from twenty drops to one tea- spoonful of the spirit of camphor may be directed to be given in one or two tablespoonfuls of milk. The several preparations of camphor are com- monly employed externally as a mild rubefacient, l»nt tlie action of camphor when applied in this way is largely, if not entirely, a local one. PHARMACOPEIA AND PHYSICIAN. MoscHus. — U. S. p.— This substance has been used in Europe for several centuries, and in China and other far Eastern countries from time im- raemoriaL The portion that is now official is de- scribed as "The secretion from the preputial fol- licles of AloscJius moschiferus" (musk deer), an animal which inhabits Thibet and other parts of Central Asia. Average dose: 0.25 gm. (4 grains). TiNCTUEA MoscHi. — U. S. P. — This represents 5 per cent, of musk in diluted alcohol. Average dose: 1 c.c. (15 minims). Musk was brought forward nearly a century ago as a powerful circulatory stimulant, and S. Solis- Cohen recently recommended it as an efficient and dependable remedy when it can be obtained of good quality, but it is extremely expensive and subject to gross adulteration. Musk probably resembles camphor in its action ' on the centers and has the advantage of greater solubility in proportion to the amount required. Castor fiber and sumbul root, which have been recommended as substitutes for musk, are entirely devoid of any such central action as that claimed for the latter. Musk may be given in capsules, or in some cases the tincture may be preferred. AMMONIUM PREPARATIONS. Miile ammonia, as one of the products of the decomposition of nitrogenous materials, was known from a very early period, the volatile salts of this substance were not available in Europe as CIRCILATORY ,ST1MVLANTS. 359 medicines until after the thirteenth century, when Ea^Tiiundus Lullus first produced ammonium car- bonate from urine. The stimulating action of tliis salt, it is said, was kno-«Ti for man}^ centuries to the Hindoos, and was probably Imown to the Arabians. It is now official as : Ammoxii Carboxas. — ^U. S. P. — This is a white, hard, translucent solid having the charac- teristic odor of ammonia and a sharp saline taste. The official salt is described as being "a mixture of acid ammonium carbonate and ammonium car- bamate.'^ Average dose: 0.25 gm. (4 grains). Aqua Ammonia. — JJ. S. P. — This is an aqueous solution of ammonia containing 10 per cent., by weight, of gaseous ammonia. Average dose: 1 c.c. (15 minims). Spiritus Ammoni.!!: Aromaticus. — U. S. P. — This is a hydroalcoholic solution containing 3.4 per cent, of ammonium carbonate, 9 per cent, of ammonia water and 70 per cent, of alcohol aroma- tized with oil of lemon, oil of lavender flowers, and oil of nutmeg. Average dose: 2 c.c. (30 minims). The volatile salts of ammonium, in the form of the well-known "smelling salts," are very com- monly employed by inhalation for their reflex ef- fects on the respiratory and cardiac centers. The aromatic spirit of ammonia when taken by llic stomach has a similar action. Other actions of ammonium salts have been enumerated in previous chapters. The water of ammonia, wlien taken internally, merely acts as a caustic alkali. It is seldom so 3(i0 PHARMACOPEIA AND PHYSICIAN. used. The aromatic spirit is usually added to water at the moment of taking. Smelling salts consist of varying mixtures of anmionium carbonate, or of ammonium chlorid with potassium carbonate, and spirit of ammonia, to which oil of lavender flowers is usually added as an aromatic. ALCOHOL AND DERIVATIVES. Alcohol has been considered under dietetics. Chapter VII, and it will be mentioned here only so far as it affects the circulation. Small doses increase the pulse rate slightly by direct action on the cardiac muscle, and reflexly also, from the stomach if the alcohol has been taken in a concentrated form. Large doses de- crease the rate by a stimulation of the vagus. The dilation of the vessels of the skin is a mat- ter of very common observation. This leads to a fall of temperature, even though it gives rise to a feeling of warmth in the skin. The general blood pressure rises somewhat after small doses, but falls after large amounts. Alcohol, or distilled spirit, was probably intro- duced into Europe by the Arabians in the tenth or eleventh century.^ Apart from the several forms of alcohol that are official we have : Spiritus Frumenti. — U. S. P. — An alcoholic liquid obtained by the distillation of the mash of fermented grain, such as Indian corn, rye, wheat and barley, or their mixtures. To conform with the official requirements, whisky should be at least 5. According to Pereira the Arabians obtained their knowledge of distilled spirit from the Chinese, who knew and used it at a much earlier period. CIRCVLATORY STIMULA^'TS. 301 four years old and comply with a number of physi- cal requirements and chemical tests that are now provided. Spiritus Yixi Gallici. — U. S. P. — Brandy. This is an alcoholic liquid obtained by the distilla- tion of the fermented unmodified juice of fresh grapes. Like whisky, it should be at least four years old and should conform to the tests for iden- tity and purity that are described in the Pharma- copeia. ^THER. — U. S. P. — Ether or ethyl oxid was discovered by Valerius Cordus, about 1540, and described as "Oleum vitrioli dulce." The prepara- tion appears to have been entirely forgotten and was rediscovered by Frobenius, a London apoth- ecary, about 1730. Sulphuric ether, the name given it at the time, although long known to l)e a misnomer, is still re- tained in connection with commercial varieties of the substance. Average dose: 1 c.c. (15 minims). Spiritus ^Etheris. — U. S. P. — This contains .32.5 parts of ether and 67.5 parts of alcohol. Average dose: 4 c.c. (1 fluidrara). Spiritus .^Etheris Compositus. — U. S. P. — This preparation, more popularly known as Ilof]'- mann's anodyne, contains 2.5 per cent, of ethereal oil, in addition to the ether. It has no evident advantages over the simple spirit of ether and may be given in the same dose. Alcohol in the fomi of whisky or brandy is inucli used in shock or collapse in connection with other agents, such as strychnin and digitalis. Its 362 PHARMACOPEIA AND PHYSICIAN. value is strongly asserted by some authorities and disputed by others. Ordinary doses of alcohol liave little effect on the circulation in animals, but clinical evidence seems to prove that alcohol does possess some value in the conditions mentioned, particularly when a very brief respite for the heart tides over a crisis. Spirit of ether may be given by the stomach, or used by hypodermic injection, and probably acts reflexly on the centers in such cases. ERGOT. Ergot has been recommended in shock and in hemorrhage in inaccessible locations. The use in the latter condition is based on its undoubted power of causing vasoconstriction in certain areas. It is much less useful than strychnin in shock be- cause of its slow action, and in hemorrhage there is no reason to expect a greater vasoconstriction at the bleeding point than elsewhere and a rise in the general blood pressure beyond that necessary to sustain the circulation in the medulla, is contra- indicated in hemorrhage. This, of course, does not apply to postpartum hemorrhage, because er- got has a specific action on the uterus, causing a firm contraction and thereby closing the bleeding vessels by compression. Sollniann and Brown have recently studied the action of ergot when injected intravenously into dogs.^ They found that it influenced the general circulation but little, particularly when the blood pressure was much lowered, and that it caused a temporary fall in the blood pressure Avith speedy 6. The Joukxal A. M. A., July 22, 1905, p. 229. CIRCULATORY STIMULANTS. 363 recovery, generally followed by an unimportant rise. The effects were mainly due to the action on the heart; as the vasomotor action was very slight. The further discussion of its obstetrical use does not belong here. Ergota. — U. S. P. — The sclerotium of Claviceps purpurea, gathered from rye, and not more than one year old. While ergot has been used in Germany for cen- turies as a household remedy, it was not generally recognized as an efficient drug until some time after 1777, when Desgranges j^nblished several es- says on the use of ergot. The vasoconstrictor properties of this drug ap- pear to be due to the alkaloid cornutin, discovered by Kobert in 1884, and more fully descri1)ed by Keller in 1894. ExTRACTUM ERGOTiE. — U. S. P. — This is a hydroalcoholic extract of ergot partially purified l}y the addition of hydrochloric acid subsequently neutralized with sodium carbonate. It should rep- resent eight times its weight of ergot. Average dose : 0.25 gm. (4 grains) . Fluidextractum ERGOTiE. — U. S. P. — This is directed to be made with diluted alcohol that has l)ecn acidified by the addition of acetic acid. Average dose: 2 c.c. (30 minims). VixuM ErcotvE. — U. S. P. — This represents 20 per cent, of the fluidextract of ergot in fortified white wine. Average dose: 8 c.c. (2 fluidrams). 3()4 PHARMACOPEIA AND PHYSICIAN. Ergot is preferably given in the form of the fluidextract without other additions. There are a number of water-soluble preparations on the market at the present time that are intended for hypodermic use, which, it is claimed, possess all the active principles of ergot, without the odorous and nauseating constituents. CHAPTER XV. CJKCULA'J'ORY DEPKES8ANTS. 'I'ho circulation may be depressed l)v acting on those structures the stimulation of which causes an increase in blood pressure. Hence we might divide these agents into two grou^js: 1. Those acting on the heart mainly, directly or through the centers. 2. Those acting for tlie most part on the vessels, directly or indirectly. An agent which s1oa\-s the lieart without caus- ing a compensating increase in the strength or the amplitude of the contraction, or a constriction of the vessels, must cause a fall in the arterial pres- sure, as will be readily understood by reference to wliat has previously been said in regard to acceler- ation of the heart causing a rise in pressure. Plere, too, we have in every case a combination of effects, and the resulting change in tlie cii'cidation nuisl (|c])ciiil on the predominance of one or anotlici-. As a matter of fact, we have no circulatory depres- sant which is used thei-a])eutically to slow tlie licart by direct action (in tlic myocardiiiin, l)iil thi-rc arc a luinibcr wliicli iii(hicc slowing by in- direct acticm. ACOXITR. 'I"h(!rapeutic doses of aconite cause slowing;- of tbe lieart by stimulating ibe vagus cenlei-. uith- onl iiialci-iiilly alVecling ll„. sircngtb of Ihc in- (li\iihial cunliaclions or Ibc condition of ibe vaso- ;i(i(l I'HARMAVOI'EIA AND PHYSICIAN. motor center. The result, therefore, is a fall in arterial pressure. The lessened cardiac action is accompanied by a decline in the temperature, whether this was pre- viously normal or that of fever. The effect is commonly ascribed to the change in the- circula- tion, but it has not been proved that the heat regulating center is not involved in the action. It will be noticed that the effects of digitalis and aconite on the circulation are diametrically opposed, except for the slowing of the pulse rate, which both induce. Toxic doses of aconite act directly on the heart, causing acceleration with diminished force of con- traction. In mammals the acceleration is pre- vented for a time by the vagus stimulation, and the heart is actually slowed, but in reality only a therapeutic dose has been absorbed in the early stage of the action; this stimulation rapidly gives place to depression and then to paralysis of the center, the acceleration becoming marked and be- ing soon followed by great irregularity. Delirium cordis occurs before the heart stops in diastole. Paralysis of the respiratory center is usually the immediate cause of death ; hence atropin is capable of saving a certain percentage of animals experi- mentally poisoned with a barely fatal dose of acon- ite. If an excessive dose has been taken even ar- tificial respiration will prolong life only for a short time, as the heart soon becomes paralyzed after the phenomena enumerated above. AcoNiTUM. — U. S. P. — This is the dried tuber- ous root of Aconitum napcllus, collected in au- tumn. When assayed by the process given in the CIRCULATORY DEPRESSANTS. 307 Plianiiacopeia it yields not less than 0.5 per cent, of acomtin. Despite the fact that it was well known and long in use as a poison, particularly for wild ani- mals, aconite is a comparatively recent addition to our materia medica, having been introduced by an Austrian physician, Storck, about 1762. Average dose: 0.05 gm. (1 grain). The official preparations of aconite are as fol- lows : Fluidextractum Aconiti. — U. S. P. — This is made with a mixture of 75 parts of alcohol and 25 parts of water and should contain 0.4 per cent. of aconitin. Average dose: 0.05 c.c. (1 minim). TiNCTURA AcoxiTi.— U. S. P. — Tliis prepara- tion has been materially reduced in strength and now represents 10 per cent, of the crude drug, or approximately one-third of the strength of the tincture that was official in the Pharmacopeia for 1890. It may be added that the change was made in conformity with the recommendations of the inter- national conference for the unification of formulas of potent medicaments and that, in addition to lac- ing in harmony with this international standard it will be found to be more uniformly active than the stronger but more varial)le tincture official in tlic cailier pharmacopeias. Average dose: O.G c.c. (ID iniiiims). AcoxiTiXA. — I). S. p. — This is an alkaloid ob- tained from aconite. It is the most active and most potent substance in the Phariuacopcia. The aconitin now official is the crystalline alkaloid aiul .308 PHARMACOI'JJIA AM) PHYSICIAN. hihould not be confoimded with tlie amorphous sul)stance formerly official or the comparatively weak eclectic prei^aratioii of aconite. Average dose: 0.00035 gm. (0.1,5 nig. or 1/400 grain) . Aconite finds its greatest usefulness in cases of high blood pressure with a strong, rapid heart, particularly in fever in ro1:>ust persons. It then simply slows the heart, lessening its output and causing a fall in temperature and in arterial ten- sion. Fever alone is not an indication in every case for the use of aconite. In continued fevers and in any case in which the heart is feeble or the arterial tension low from any cause (even though the pulse may be rapid), aconite is contraindicated. Since the antipyretic benzene derivatives have come into general use the employment of aconite in fever has correspondingly declined, but we have seen that the s}Tithetic antipyretics are far from being the harmless substances that some of the manufacturers would have us believe, and aconite deserves to be used more frequently in suitable cases of fever. "Colds" are troublesome forms of congestion re- sulting from circulatory disturbances which are often relieved by repeated small doses of aconite. For this purpose 3 drops (about 1 minim) of the tincture of aconite of the present Pharmacopeia, which would be equivalent to about 1 drop (l/o minim) of the tincture official in the Pharma- copeia, 1890, well diluted with water, may be given every fifteen minutes for two hours, tlien hourly until relief is obtained. CIRCULATORY DEPRES>^A^'TS. 309 Aconitin is so intensely irritant that it is not suitable for use without great dilution, and, as there is some chance of confusing the much more potent article now official with the eclectic or the amorphous preparations, it will be found prefer- able to use the tincture of aconite in nearly every case, more ])articularly, since this is now required to be of a definite aconitin strength. Because of its irritant action aconitin is not adapted for liypodermie use, but it may be given, largely diluted with water, as follows: Aquae, q. s. ad fgiv 120 Alcohol fSiv 15 Aqua% q. s. ad fgiv 120 Sig. : A teaspoonful may be taken every three hours. The disadvantage, not to say danger, of trying to weigh such small amounts is apparent, and serves to further illustrate the advantage of using the tincture. The tincture is usually given alone, except for the water used in diluting it. vj:ratru:m. \'cratruiii i-alher closely resembles aconite in its tbciapcutic action, and it was widely used at one time for the reduction of fever. The extent of its use was largely due to its popularization in llie lonii of Norwood's Tincture of ^^eratrum, l)ut it seems to ])ossess no advantage over aconite, and ii is now but seldom used internally. VkKATKUM. — U. S. P. (VlClUTKUM VlUlUK.— IJ. S. P., 1890). — Under the single heading vera- trum, the Pharmacopeia now recognizes the dried rlii/.ome of Verutriiin viridc or of Vcralruin album. While it is tni<- tbiit tbere is no marked din'ei-ene(> 370 PHARMACOPEIA AND PHYSICIAN. between the two drugs, some physicians prefer the American root and, therefore, should specify "Yeratrum viride, U. S. P., 1890." Average dose: 0.12 gm. (2 grains). The official preparations are: Fluidextractum Veratri. — U. S. P. — This is directed to he made with alcohol. Average dose: 0.1 c.c. (II/2 minims). TiNCTURA A-'eratri. — IT. S. P. — This prepara- tion represents 10 per cent, of the crude drug in alcohol and is practically one-fourth the strength of the corresponding preparation in the Pharma- copeia for 1890. Average dose: 1.0 c.c. (15 minims). Veratrina. — U. S. P. — This is a mixture of alkaloids obtained from the seeds of Asagrcea offi- cinalis. Veratrin should not be confounded with the eclectic preparation of the same name. Average dose: 0.002 gm. (2 mg. 1/30 grain). ' THE NITRITES. The nitrites, organic as well as inorganic, lower the blood pressure by causing vasodilation. Thera- peutic doses exert but little influence directly on the heart. It has been sho\\Ti that the nitrites act on the muscles and nerve endings of the arterioles, and that even the veins undergo dilatation. Any considerable dilatation of the arterioles and veins of the splanchnic area must inevitably lead to a decline in the general arterial pressure, regardless of the action on the heart. In man the heart actually does show acceleration in the first stage of the action with amyl nitrite because of tlie depression of the vagus center; the blood CIRCULATORY DEPRE.^i^AXTS. 371 pressure remains high and the vasodilation affects the face and neck, because of depression of the vasoconstrictor centers for those areas; but, as the dilatation extends to the splanchnic and other areas, the general arterial pressure falls. There has been some diversity of opinion in re- gard to the effect of am^d nitrite on the cerebral circulation. Leonard Hill agrees with those who believe that there are no nerves controlling the di- ameter of the cerebral arteries, and he declares that the arterial pressure in the brain simply fol- lows that in tlie carotids. Wiggers has found that adrenalin constricts the cerebral vessels and we bave Elliott's dictum, based on his masterly re- search, that the constrictor effect of adrenalin on vessels is proof of sympathetic nervous control. Brodie and Dixon also found that the action of adrenalin is exerted on nervous elements. Should Wiggers' results be confirmed there would be little reason to doubt that tlie nitrites do affect the cali- ber of the cerebral vessels. The nitrites are capable of causing some dilata- tion of the vessels in excised muscles when the nerve endings are not concerned ; hence they must also act on the museiilai' elcniciils of the vessels to some extent. The nitrites produce methemoglobin in the !>lood, but do not cause the destruction of the cor- puscles, as other methemoglobin formers do, and in man this does not arrest oxidation completely, l)ecause-the tissues reduce methemoglobin slowly. 'I'liis is not an important factor, however, with the llicrapeutic doses of the nitrites. 0. Loeb suggested as a possible explanutiun of 372 PHARMACOPEIA AND PHYSICIAN. tlie value of amyl nitrite in angina pectoris that the coronary vessels, like those of the face and brain, may be dilated at first, before the action on the general circulation begins. Filehne showed that the therapeutic dose of amyl nitrite caused vasodilatation by central action, and Loeb found it did not affect the vessel tonus independently ex- cept when in such concentration as to prove poison- ous. Small doses were found to have no constant effect on the vessels of the coronary circulation in the excised heart. Amyl nitrite acts very rapidly when inlialed, but the action is over in about twenty minutes. The effects of glyceryl trinitrate or nitrogly- cerin are much more slowly induced and they per- sist for some hours. Sodium nitrite is decomposed by the hydrochloric acid of the gastric juice, thus giving rise to irritation of the stomach. Gh'-ceryl trinitrate is not decomposed in the stomach, but it has the disadvantage of often causing headache. In some cases this action does not occur after the drug has been used for some time. Glyceryl trini- trate is decomposed in the blood, with the libera- tion of the nitrous acid radicle; hence it acts like the nitrites. Spiritus Glycerylis Kitratis. — IT. S. P. (Spiritds Gloxoini. — U. S. P., 1890) — Com- monly, though incorrectly, termed nitroglycerin, is an alcoholic solution containing 1 per cent, by weight of glyceryl trinitrate. iVverage dose: 0.05 c.c. (1 minim). Amylis IsTitris. — U. S. P. — This is a liquid containing about 80 per cent, of amyl nitrite. Average dose: 0.2 c.c. (3 minims). CIRCULATORY DEFRESt<. 373 SoDii XiTKis. — U. S. P. — This usually occurs in white, or nearly white, fused masses, soluble in Il'SS tlian two parts of water. The salt deliquesces oil exposure to air and is also gradually oxidized to sodium nitrate and thus becouies unfit for use. Average dose: O.OG gm. (1 grain). The nitrites, and glyceryl trinitrate, arc oL' j)riine iuiportance in the dx;'pression of the circula- tion ami may 1)C used wlien it is deemed necessary to lower the blood pressure, for example, when a weakened heart is becoming exhausted by contract- ing against a great arterial resistance, and the con- tractions are incomplete, as in arteriosclerosis. A slight lowering of the aortic resistance often en- ables the heart to contract more perfectly while a coronary vasodilation secures a better nutrition of the heart. The group is contraiudicated, however, when the blood pressure is already low (however weak and rapid the heart may be), because a certain de- gree of arterial tension is al)sue 1 fibron s, Ihl IS nai'i'ouii Ig the lui is obvious tliat such vessels c dilate by any means. It must not be fo rp.llcu often obla ined in I In !■ acute 374 PHARMACOPEIA AND PHYHWIAN. stages of angina pectoris, the nitrites are merely palliative and in no sense curative. The nitrites, and more particularly amyl nitrite, are indicated in vasomotor spasm occurring in any disease, un- less specifically contraindicated by other condi- tions. The action of arayl nitrite is very speedily eli- cited when it is inlialed, but when spasm of the respiratory muscles interferes with the inhalation it may be injected into the deep muscles of the thigh. Spirit of glyceryl trinitrate is to be preferred in chronic conditions of abnormally high blood pres- sure, because of its more protracted action. One minim is given three times a day, or the dose is increased till effective. It may be injected hypo- dermically or given by the stomach, as it passes through that organ unchanged, and, therefore, causes no such disturbances as are seen with so- dium nitrite. AVhile this substance is usually considered as be- ing extremely poisonous, it is said that large amounts have been given in the course of a day with no l^ad effects. Aqueous solutions of glyceryl trinitrate are unstable and are frequently quite worthless. The spirit sometimes gives almost im- mediate relief in headache, when this is attended with high blood pressure, but, on the other hand, it may increase the headache if the blood pressure is low. As is well knoA\Ti, the headache which glyceryl trinitrate commonly causes is one of the greatest objections to its use. The nitrites, and particularly the spirit of glyceryl trinitrate, may be used to counteract the CIRCULATORY DEPRESSAlsTS. 375 vasocoustrictor effect of digitalis or stryclmin when that action is undesired. Spirit of nitrous ether does not yield enough of the nitrous acid radicle to exert any therapeutic action on the circulation. The action of the spirit is exerted reflexly as in the case of alcohol and ether. The spirit of nitroglycerin may be given in simple solution in order to avoid the measuring of such small does as one minim. It may be pre- scribed as follows : IJ. Spiritus iiitrogh'cerini ni. xv 1] Aquae ". fgii 6o| The dose of this solution is a teaspoonful. Large amounts should not be prescribed or dis- pensed. The following illustrates the method of pre- scribing sodium nitrite : IJ. Sodii nitritis gr. xv 11 Aquae dest Sii 60| This solution should be kept well corked. The dose is one teaspoonful. The Avell-known "pearls*' of amyl nitrite afford the most convenient form for dispensing that sub- stance; they must be kept cool to avoid loss by breakage, and, when used, one is crushed in a handkerchief and the contents inhaled by the patient at once. Bloodletting was formerly in vogue as a routine jjrocedure wlien it was desired to reduce tlie blood pressure, but in healthy animals the vasomotor center exercises sucli perfect control over tlie blood pressure that tlie loss of blood produces very little lasting effect unless it is so great as to cause col- 370 FHliniAVOl'ElA AXD I'HYHIGIAN. lapse symptoms. While the loss of a moderate amount of blood is Avell borne by robust patients, and ill some cases maj' even prove beneficial, acon- ite and the nitrites are nearl}- always to be pre- J'crred as temporary measures, while the control of the diet (including^ liquids) and the nse of saline purgatives will serve to diminisli the amount of blood for a longer time in suitable cases. Ilydrated chloral is one of the most effective agents in our possession for lowering the blood pressure by depressing the vasomotor centers, and, while this action is much employed in laboratory experiments, it is not elicited in man by perfectly ^afe doses such as are used to induce sleep. CHAPTER XVI. DIUKETICS AXD DIAPHOEETICS. Diuretics and diaphoretics may Ije considered together, since they are often used for the same piu'iDose, the one being used to supplement the other, and because the same agent which produces diuresis nnder certain conditions may cause dia- phoresis when these conditions are sliglitly changed. Diuretics may be divided broadly into those which influence the circulation and those which act on the secretory cells of the kidney. Though the same agent may possess both actions to some extent, we shall consider these remedies with ref- erence to the principal effect according to this classification. While the exact mechanism of urinary secretion remains a problem, the indications for diuresis and the method of causing it are fairly clear. When the official remedies all fail to produce this effect we may usually attribute the failure to tlu' condition of the kidney, feeling sure that the secre- tory cells are incapable of performing their riiuc- tion and that nothing short of the creation of new- cells can be efl'ective. Even this task is not beyond the powers of some of the much-vaunt(>d mineral waters and nostrums if we are to believe llie state- menls made in the circulars and olliei' iidvei-l ise- menls of the proprietors. Diuretics are especially indicaled in (h()j)sv of 378 PHARMACOPEIA AND PHYSICIAN. cardiac, or even of renal, origin, provided the cells are capable of free secretion. In renal dropsy agents of the first class (those which influence the circulation), or those which mildly stimulate the kidney cells without producing irritation, are to be preferred. If the renal cells are incapable of increased secretion, diaphoresis should be resorted to in order to give rest to the kidneys. Diuretics are also important in causing the re- moval of toxins and substances which form con- cretions (urates and phosphates). DIGITALIS. Nearly all authorities agree that digitalis is the most important of the official remedies in the treatment of dropsy of cardiac origin, its action being directed mainly toward the increase in the efficiency of the heart, with a consequently im- proved circulation in the kidney and increased diuresis. For this purpose the tincture is fre- quently employed, but, perhaps, the most efficient remedy is the combination of digitalis with squill and calomel, commonly called Niemeyer's pills.^ The official squill is too irritant to permit of its employment in nephritis. This is very important and should be borne in mind if one uses any of the much-heralded diuretic nostrums which contain squill or its active principles. 1. The formula for this piU is as follows : Pulveris digitalis | Pulveris scillse, aa grs. x 160 Hydrarg. chloridi mit grs. 1^4 108 This amount is to be divided into ten pills, or preferably, capsules. One of these pills every three hours will be found effective. The calomel is often omitted, or it may be re- placed by 0.06 gm. (1 grain) of the blue mass (massa hydrargyri) in each dose, if it is to be made into pills, or gray powder (hydrargyrum cum creta), if into capsules. DIURETICS AXD DIAPHORETICS. 379 That squill is extremely active in causing a watery diuresis is true, but in overdoses it is equally potent to lessen or even to suppress the flow by reason of its irritant action. This may result in bloody urine. The dose of squill, in powder, is 0.05 to 0.1 gm. (one or two grains) every three hours until some nausea occurs. Eather closely resembling digitalis in its action on the heart and as a diuretic, if, indeed, it may not surpass the older drug in the latter case, is strophanthus, which does not cause the same de- gree of vasoconstriction which sometimes inter- feres with or prevents the diuretic action of digi- talis. It is mostly used in the" form of the tinc- ture. While stroplianthus has some advantages, such as the more prompt action and a sligliter tendency to cause cumulative effects, clinicians have not found it so generally useful as digitalis. Apocynum has enjoyed a considerable reputa- tion in domestic practice as a remedy in dropsy, but appears to be inferior to digitalis in tlie same group with which it belongs. Digitalis, strophanthus, apocynum and other members of this group have been considered in ( 'liapter XIV. CAFFEIN. AVhen cardiac stimulants or other agents cause such vasoconstriction as greatly to lessen the amount of blood wliicli passes tlirough the kidney, and consequently the diuresis, a vasodilator is Komotimes employed, but it is more rational to avoid tlie necessity for tliis when possible. 380 J'JIAh'MACOPEIA AND I'HYSWIAN. Wlwn the ol)ject of diuresis is to get rid of fluid wliicli lias accumulated, it is, of course, better to avoid unnecessary amounts of Avater, and in such cases diuretics arc given in solid, or at least con- centrated, form. Calfein, theobromin, para-.xantliin and theocin are derived from xanthin by the introduction of methyl groups, caifein being trimethylxanthin, and theobromin, para-xanthin, and theocin being dimethylxanthins, the last three differing only in the arrangement of the methyl groups in the mole- cule. These dimethylxanthins act more strongly on the muscles of the vessels and cause a greater diuresis than does caffein, while the latter acts more energetically on the centers, causing greater wakefulness and greater stimulation of vasomotor and respiratory centers. Therapeutic doses of caffein increase the heart rate somewhat by acting directly on tlie muscula- ture; the force is changed but little, being slightly increased, resulting in an increased output in a unit of time; this, with the stimulation of the vasomotor center, causes a rise of blood pressure. The vasoconstriction at first may interfere with diuresis, despite the increased blood pressure, but the vasoconstriction is transient and in about twenty minutes it is succeeded by a slight dilation of the vessels of the kidney, while the general blood pressure remains a little above normal and the diuresis is increased. Cafl'ein is supjiosed to stimulate the renal epithelium, causing a consid- erable increase in the secretion of the watery part of the urine, but not so great an increase in the solid portion; hence the specific gravity of the DWRETICti AXD DIAPHOIiETICS. 3S1 urine falls. Caffein is said to bring about a dila- tion of the vessels by a direct action on the walls. The effect of caffein on the psychic centers is a matter of common observation. Small doses re- sult in an increased capacity for mental work, particularly noticeable after the centers have had a short rest, as after a brief sleep. It lessens the feeling of fatigue and increases the capacity for physical work after a period of rest, Init not when it is taken during exhaustion or very severe fatigue. Tea and coffee owe their stimulating effects, in part, to the volatile oils which they con- tain and which are dissipated by boiling. Caffein is a constituent of tea, coffee, kola, and. more alnindantly (o per cent.), of guarana, wliieli is official. Caffein is not very soluble in water or alcohol, luit its solubility in water is greatly increased by such salts as potassium bromid and sodium ben- zoate or salicylate; this well-known fact has been appropriated as a "discovery" l)y manufacturers of certain nostrums. Caffein is most effective wlicn given in the iDnu of hot tea or coffee, tiic effect being heigblciu'd by certain volatile oils present and by tbe reflex stim- idation of the hot fluid in the stomach. Tea made by quick extraction contains but little tannin and ildcs not disturl) digestion to the same extent as that made by long contact of the water with t]i(> liMves. Caffein (and pai-ticniarly hot tea) is usc- fiil as an anlidotc to sikIi narcotic poisons as inor- phin and alc.linl. and it, is ;dso added to ilic anti- pyretics to lessen central dcincssion. ]Jiiircsis serves to i-cmovc certain toxins which 382 PHARMACOPEIA AND PHYSICIAN. arc excreted by the kidneys, and a copious watery diuresis may serve to lessen tlie action of such metals as mercury and lead. Diuretics are useful in dropsy, and, since the object is the removal of liquid, caffein, digitalis, theobromin and those which are used with but little water are to be preferred in such cases. Digitalis is used in the form of the tincture, or more frequently, perhaps, as an infusion. Caffein may be given in the form of hot tea or coffee. If the former made quickly, removed from the leaves and the clear infusion then boiled, the volatile oils are dissipated. This may be advantageous when it is desired to minimize the wakefulness which tea causes. One of the soluble forms of caffein sug- gested below may be used if preferred.- Theo- bromin may be given in the form of hot cocoa. When digitalis or other diuretics produce a more than temporary vasoconstriction in the kid- ney, one drop of the 1 per cent, solution of nitro- glycerin may be given at the same time. Caffein Sodio-Benzoate, N. F., and Caffein Sodio-Salicylate, N. F., consist of 50 per cent, of caffein, with sodium benzoate and sodium sali- cylate, respectively. Caffeina. — IT. S. P. — This is a feebly basic (alkaloidal) substance obtained from Thea sinen- 2. The following mixture, to be varied according to needs, represents the method of using caffein in this soluble form : Caffein (allialoid) | Sodium salicylate, each 3i 4| Cinnamon water to make Siii 100 1 Each teaspoonful contains about 0.2 gm. (3 grains) of caffein. Sodium benzoate or lithium salicylate or benzoate may be substituted for the sodium salicylate. This formula requires no unusual pharmaceutical skill to compound and the cost is very much less than that of the proprietaries used for the same purpose. DIURETICS AND DIAPHORETICS. 383 sisj Coffea arahica or other plants. It does not form stable salts. Average dose: 0.05 gm. (5.0 mg. or 1 grain). The other soluble forms of caffein are : Caffeixa Citrata. — U. S. P. — This consists of equal parts of caffein and citric acid. Average dose: 0.1 gm. (2 grains). Caffeixa Citeata Effervescens.^U. S. P.— This contains 4 per cent, of citrated caffein. Average dose: 4 gm. (60 grains). Diuretin is a trade name applied to a mixture of theobromin-sodium and sodium salicylate, while agurin consists of theobromin-sodium and sodium acetate. Diuretin and agurin are decomposed on exposure to the air and become much less soluble. The official sugar of milk and the unofficial urea cause diuresis, probably by acting on the renal epithelium. Scoi'AUius. — U. S. P. — This is sometimes in- correctly classed with digitalis because it slows the heart, l)ut it weakens the beat, while digitalis strengthens it. The alkaloid, spartein, is respon- sible for the cardiac and vasoconstrictor effect of scoparius, but the diuretic effect is due to scoparin, a glucosid. Average dose (of sc()])arius) : 1 giii.( 15 grains). 'I'he infusion or decoction is recommended foi- producing diuresis, except in dropsy.^ Sl'AKTEINyi: SULl'IIAS.— U. S. P.— While this is obtained from scoparius, it is not a true diuiclir. 3. Soparhis I Potassium bitartrato, each Sss 151 Tills qiiantlly of matorial Is to bo adtlotl to \ litor (1