30 MEDICAL REVIEW. VOL. XXVIII TBRARY ASS A WEEKLY JOURNAL OF MEDICINE AND SURGERY. ST. LOUIS, JULY 1, 1893. ORIGINAL: ARTICLES The Alkaloids-Their Value in Thera peutics. BY W. W. HIPOLITE, M.D, DE VALL'S BLUFF, ARK. (Prepared for Prairie Co. Med. Society.) MR. PRESIDENT AND GENTLEMEN:-In submitting to you this paper on the subject of the alkaloids and their use in therapeutics, I wish to state that, in its prepara tion, I have not hesitated to call freely from such literature bearing on the subject as I had at hand, where the language used is such as to clearly elucidate the subject which I wish to bring before you. NO. 1. expected results from their use; and this has caused such distrust and vacillation on the part of the physician as often to nullify his efforts in the treatment of disease. Perhaps one of the most perplexing things with which the physician has to contend, is the great variation in the strength of drugs; and especially is this true in relation to those which come from the vegetable kingdom. So varied are these that the physician who trusts to prescription writing feels that the method of sending out his prescriptions to be filled is very unsatis. factory and unsafe. On the one hand the drug dis pensed may be of poor quality, and the desired effect is not, therefore, produced; and, on the other hand, it may be stronger than what he has been in the habit of prescribing; and hence he receives from it the toxical effect. On this account many physicians have adopted the method of dispensing their own drugs, not so much in the belief that they can keep better drugs than their druggists; but that, having tested their own, they know just how much it will take to produce the desired effect. For instance, we are much annoyed in prescribing tincture of Aconite Root. It is not uncommon to find this tincture in the shops having little evidence of medicinal power. When aconite root lays away for any length of time it loses its properties; and a tincture made of such will be proportionally weak. It will take a large quantity of this to have any beneficial effect; and, after using for a time, we may prescribe a large quantity, when, if the prescription falls into the hands of a druggist who has a tincture of full strength, disaster may be the consequence. What the physician desires is, that neither too little nor too much of the active principles of drugs shall enter into the preparations he prescribes. Medicinal plants from which are obtained such na tural products or crude drugs as, for example, opium, digitalis, aconite, strychnia, etc., present variations in activity and power-owing to difference in quantity and quality of their active ingredients. This variability depends on several causes,such as the locality of growth, character of soil, whether grown in the wild or culti vated state, mode of culture, time and manner of gathering, age of samples, state of preservation, etc. The natural products themselves, and their preparations the most simple in appearance, are very complex and contain numerous active substances entirely different in their nature, and often of antagonistic medicinal qualities. Some plants which are very active in their wild state, are almost inert when cultivated; and some contain a number of alkaloids, differing from each other in Therapeutics, to be successful, must have pure, active properties. One of the most striking examples of this and always reliable agents. To secure this, and avoid is that furnished by opium, careful studies of which mistakes, it was proposed some years ago that a certain have revealed the presence of six well defined principal amount of fluid extract should answer to a definite alkaloids and nearly twice that number of minor im- amount of the crude material; and, with this, it was portance-having different and well defined properties. thought that the ultimatum had been reached. But we Narceine, morphine and codeine are soporific; while find that the same difficulty attends the fluid extracts as papaverine,thebeine and narcotine are antispasmodic.It is above alluded to in the tinctures; and that we cannot evident that powders, pills, decoctions, infusions, tinct- expect to get a good fluid extract from a poor quality of ures and extracts which may be prepared from such the crude material. As the activity of a drug is due to crude drugs cannot present uniformity in activity, and one or more definite active principles contained in it, an cannot be considered safe and reliable preparations. In estimation of these active ingredients is the only true fact, their unreliability has been shown by many un critarion by which to judge of its medicinal quality; and this is subject, even in carefully selected drugs, to a far more positive and safe manner. Their undeniable wide variation. The following is a brief abstract of some conclusions presented by the eminent Prof. Leaborde before the French Academy of Medicine. 1. "In every medicamentous preparation, taken from the vegetable kingdom, there exists one or several active substances through which it exercises its physiological and therapeutic action." efficaciousness in the hands of the intelligent physician is now widely recognized; and in them the medical art has a power, a certainty and precision of action which has been most earnestly desired, but was far from being expected. It is difficult to understand why physicians should persist in prescribing medicines of whose strength they cannot be certain, and whose conglomerate nature causes them daily anxiety, when they have 2. "When this active substance has been isolated, definite active principles, invariable in their composi determined and chemically formulated, in which case it tion and whose medicinal effects are constant, and may must be regarded as its proximate principle, it is this to in advance be mathematically counted upon. In satis. which it would be reasonable for us to address our-fying therapeutic indications, the alkaloids have a selves, with a view to its therapeutic use, after having very great superiority over plants, even as atropia is first subjected it to experimental and then to rigid clinical tests." 3. "In fact, while the proximate principle is always the same, identical with itself, invariable in its essen tial constitution, as in its fundamental, physiological and medicamentous action, the substance of the entire plant is essentially complex and variable, not only in its composition, but in its effects, and it does not and cannot result in actions which shall be other than multiple, diverse, undefined and unknown." In the progress of preparing remedies we had, first, the crude drugs; next, decoctions and infusions made from them; then followed the tinctures, the fluid and the solid extracts. Here science halted for a long time, and until chemistry came to our aid by furnishing us with the active principles themselves, leaving out the coarse, inert, and often injurious matters that hinder oc curate calculations as to definite therapeutic results. We were given the alkaloids and the glucosides in place of the crude drugs and their preparations so long in use. superior to belladonna, strychnia to nux vomica. Because of the uncertainty of their composition and their variability in activity, the crude drugs are more dan. gerous and less efficient in therapeutic use, than are their active principles. We may do without the plant itself, as such, but we cannot do without its active principle. The discovery of the alkaloids is one of the most important discoveries of our time. The glory of the discovery belongs to chemistry, a science to which medicine, no less than the great modern group of arts and industries, is indebted for its most powerful instru ments. It is to physiology that we are indebted for a knowledge of their influence on the vital economy; and to therapeutics for a knowledge of their great value in the treatment of disease. In therapeutics we seek an effect. To be effectual therapeutics should be preventive, not limited to the prevention of death, but prevention of the phenomena which lead to death. Certain of the alkaloids, by their The alkaloids are the active principles of plants, iso- power in controlling the vaso-motor nerves, that part of lated from their inert and extraneous parts by chemical the nervous system which presides over the contractions processes. For example, strychnine and brucine are ex- and dilatations of the blood vessels are regulators of tracted from nux vomica; morphine, codeine and others vitality, modifying it according to the action peculiar from opium; aconitine from aconite; digitaline from di- to each agent. In small doses, repeated at short in. gitalis; atropia from belladonna, etc. They are simple, tervals, they lower the pulse and temperature, and pure and active drugs, always identical in chemical com prevent paralysis of the blood vessels. When a person position and uniform in strength and activity. With becomes feverish, the temperature of the body rises and the exception of a small number, such as quinine, mor- the heart's action is hurried; the blood becomes overphine and strychnine, which had been adopted into heated, dark and viscous; embarrasments of circulation general practice, the alkaloids were at first looked upon in the organs are liable to happen and cause serious oras scientific curiosities; and were put away among the ganic lesions. The system may become poisoned by repoisons. As medicinal agents they were regarded with tained morbid matters, the heart exhausted and life suspicion, and were used in a timid and uncertain endangered. Every acute disease is, at the start, but a manner. But, instead of being the venomous principles derangement of function, the vital phenomena are modiof the plants which produce them, they are found to be fied before the occurrence of any structural alteration the true medicinal agents of such plants, capable of ren- of tissue of the organs. The alkaloids, given with dering the greatest service to humanity; and these ser promptness aud boldness, lift up depressed vitality, revices will become general in proportion as their im- store tone to the blood vessels and prevent accidents portance becomes more generally understood. due to fever. These active principles, as now presented for admi- When administering the alkaloids, as when the crude nistration, are rapidly absorbed into the system, produc- drugs are administered, the physician must take into ing prompt and certain effects; and there are no effects account the impressionability of the patient, the reproduced by the crude drugs that may not be obtained sistance of the disease to the remedy, the power of from their alkaloids, singly or in combination, and in a absorption and of elimination and idiosyncrasies; and An Ovarian Tumor Weighing 111 Pounds BY W. W. KEEN, M.D., Professor of the Principles of Surgery and of Clinical Surgery, he must know just how much of the active principle he is giving at a dose. He may then reasonably expect certain physiological or therapeutic effects or both, according to quantity and frequency of administration. The most safe and efficacious manner in ordinary cases, is to administer the alkaloids in small doses at short intervals, proportioned to the acuteness and severity of the disturbance. But they must be continued, regard Miss B, of Benezette, Pa, was first seen by me at less of the quantity already administered; because, in Driftwood, Pa., February 26, 1892, at the request of Dr. order to obtain the desired therapeutic effect, we must V. K. Corbett, of Caledonia. She was then fourteen proceed until the effect is produced. We are safe in years of age and had never menstruated. About this course, for, with small doses, the accumulation in eighteen months before I saw her, her abdomen began the blood cannot become excessive; and when the to enlarge. Six months afterwards Dr. Corbett was effect is obtained, we stop or reduce the dose. There is no danger till the physiological effect is produced. There is a culminating point to be reached; and the small doses should be given at short intervals, in order that the effect may be reached as soon as possible. Excepting in cases of extreme urgency, and where life is in imminent peril, it is not advisable to employ the maximum doses, because of the fear of poisoning. consulted for an attack of considerable pain in the left side of the abdomen. He found that she was only voiding eight ounces of urine in the twenty four hours, but under proper treatment this soon reached a quart in amount, and has remained so ever since. He never discovered any albumin in the urine. In October, 1891, she had been tapped by a gynecologist, who is said to have diagnosticated a solid and probably malignant tumor, connected most likely with the liver, omentum, and ovary, and who deemed its removal not feasible. The foregoing are some of the many reasons which may be given to demonstrate the value of the service which has been rendered by the use of the alkaloids. I found the abdomen enormously distended with The medical world is now paying greater attention to fluid and advised very strongly that a small incision these active principles, because their superiority over should be made in the abdominal wall, so that I could Galenical preparations is self evident; and the current determine the relations of the growth with accuracy. of therapeutic literature is constantly towards a more Her father, however, was not present, and had made it critical study of the medicinally active principles, a condition that nothing beyond tapping should be done. rather than the crude drugs. The character of the future materia medica, so far as the botanical part is concerned, will doubtless be materially changed. More and more space will be devoted to the alkaloids and active principles; and less and less space to crude drugs. I tapped her immediately and removed considerably over three gallons of amber colored fluid. When this was evacuated I discovered a lobulated tumor on the right side of the abdomen, under the liver and apparently attached to it. It was evidently cystic in part, there being at least two cysts perceptible. Each of these I tapped, obtaining from the upper one a light fluid and from the lower one a much darker fluid. On account of her age no vaginal examination was made. The fluids pointed strongly toward an ovarian cystoma. I again advised an exploratory incision. But no one need fear that the successful use of active principles necessitates the learning of a set of new remedies; or that alkaloidal therapeutics bring into the field of medicine drugs never before heard of. On the contrary, it gives the same tools which we and our forefathers have used, greatly improved and capable April 29, 1883. The patient was finally brought to of doing not only the work formerly required of them, the Jefferson College Hospital. She has been tapped but much else besides. But because this claim is made, twice since February, 1892, the last time in February, it must not be supposed that the alkaloids offer every- 1893, when six and a half gallons were drawn off. She thing needful for therapeutics, to the exclusion of the is now enormously swollen. The measurements are as follows: From the ensiform to the umbilicus, 16 many other useful remedies found in other worlds than inches; from the ensiform to the pubes, 294 inches (this the vegetable. We have no patience with the bigotry measurement in myself reaches from the ensiform to the which draws its armamentarium medicine from one to the middle of the calf of my leg); circumference, 49 quarter and excludes good remedies from other sources. inches. The veins over the abdomen are very large. It is the glory of the scientific and sensible physician that he searches he whole range of human knowledge for that assistance which helps him to relieve the suffering of mankind. Nothing can be made out in the interior in consequence of the enormous abdominal distention. Examination of the urine shows no albumin and a very slight trace of sugar (?) Operation. April 30, 1893. A small incision was made in the median line above the umbilicus, as the greater mass of the tumor lay there. A large trocar was Now is the time to subscribe for the MEDICAL thrust in and evacuated a very large quantity of characREVIEW. teristic opalescent ovarian fluid. The escape of this |