Active Ingredients. - The rhizome, which is the only officinal portion, contains about 3 to 3.5 per cent. of a peculiar resin, called Podophyllun It also contains a certain proportion of the alkaloid Berbera (the main active ingredient of Calumba, under which head it will be discussed), and it is possible that the tonic properties of this latter may render it, in some cases, a valuable adjunct to the resin, so that a preparation of the root which should contain them both in known proportions is perhaps a desideratum. Podophyllin is a greenish yellow powder, with a bitter and acrid taste: it is entirely soluble in rectified spirit and ammonia, and nearly so in pure ether.

Physiological Action. - Given in poisonous doses (two grains and upwards), podophyllin attacks the gastro-intestinal mucous membrane, by whatever channel it may be introduced into the system. Percy1 administered an alkaline solution subcutaneously to dogs, and (after a few hours) observed the animals to suffer from colic, tenesmus, and vomiting; and Anstie3 injected an alcoholic solution into the peritoneum of dogs, cats, and rats with the uniform result of provoking vomiting, bloody stools, and death from exhaustion, with some appearances of a very peculiar respiratory paralysis. Ulceration of the duodenum was found in several, and inflammation in all cases; but the absorption had been so prompt and complete that no inflammation of the peritoneum was produced. This is the more remarkable since both the rhizome and the resin are undoubtedly powerful local irritants, and in some cases, when applied to mucous membrane, even act as escharotics. Other effects of physiological doses that have been noted, are profuse sweats and salivation.

1 Zeitsch. f. rat. Med. (3), xxvi. 1; Husemann. op. cit.

2 Amer. Med. Times, iv. 243.

3 Med. Times and Gaz., 1863, p. 326.

(The action on the liver of podophyllin and several other American chalagogues has been carefully studied by Rutherford and Vignal by means of experiments on dogs. They say: "1. Podophyllin, when injected into the duodenum of a fasting dog, increases the secretion of bile. It is inferred that the increased biliary flow in the preceding experiments was due to increased secretion, and not merely to expulsion, because the gallbladder had been well emptied by compression, and the cystic duct had been clamped, moreover the increased flow was far too prolonged in some of the experiments to be attributable to spasm of the larger bile-ducts; therefore an increase in secretion must have been the case. 2. When the bile is prevented from entering the intestine, podophyllin acts less powerfully and less quickly than when bile is introduced. 3. Augmentation of the biliary secretion is most marked when the purgative effect is not severe; indeed, if the purgative be very decided, diminution and not augmentation of the biliary secretion may be the chief result. 4. Podophyllin purgation is apparently due to local action, for the irritation of the intestinal mucous membrane extends gradually from above downwards. 5. The bile secreted under the influence of podophyllin, although it may be in increased quantity, contains as much of the special biliary matter as bile secreted under normal conditions." Brit. Med. Jour., Oct. 30, 1875.)

Therapeutic Action. - The rhizome of the podophyllum was employed by the aborigines of America as a vermifuge; and in modern times has been greatly esteemed by the profession as a hydragogue purgative, having a special reputation as a cholagogue, whence the name sometimes given to it of "vegetable calomel." 1 In this country the cholagogue action of podophyllum has been denied by Dr. Hughes Bennett, on the strength of a number of experiments upon dogs with doses of from 2 to 8 grains, which diminished the secretion of bile. Dr. Anstie also concluded (from finding that fatal doses injected produced no visible change in the liver) that no direct action on that organ is produced by the drug, and that the increase of bile, when it does occur, is an accidental result of the intestinal irritation. For my own part I am convinced that, whatever the modus operandi, podophyllin, in suitable doses, is often capable of correcting a deficient secretion of bile, especially in children and infants. When the motions have become white or clay-colored, podophyllin, in a few doses of 1/20 to 1/10 of a grain every six hours for a child, and of 1/16 to 1/12 of a grain for an adult, has frequently, in my experience, restored the natural character of the evacuations, at the same time regulating the bowels. So far are these doses from acting in a specially irritant manner, that they will often allay the vomiting and diarrhoea of gastroenteric inflammation; and will also cut short the symptoms in the remittent fevers of children, with high temperature, headache, and delirium, dry, brown, and furred tongue, nausea or vomiting of bilious matter, pain or uneasiness in the stomach, sleeplessness, with a general sense of weariness, grinding of teeth in sleep, etc. The effect is much improved by the exhibition of occasional doses of aconite. As another example of the favorable action of podophyllin on the intestinal canal, I may mention that prolapsus of the rectum, in children, may sometimes be removed by similar small doses, administered night and morning.

1 E. Schmidt: Bayer, aerzt. Intell-Blatt., 1866, p. 13.

As a laxative in general, and especially for the purpose of removing habitual constipation, podophyllin should be given in moderate doses. A single dose of half a grain (or at most an entire grain), though somewhat slow in acting, will usually, after some hours, produce decided watery and bilious purging; and often this effect, instead of being followed by a con-stipative reaction, will be succeeded by increased and long-sustained habitual activity of the bowels. For habitual constipation, it is perhaps better, however, to give from 1/12 to 1/6 grain every night and morning for a little time. This treatment is especially useful when the constipation is accompanied by nervous and bilious headaches. Moreover, in some fevers. as typhus, though decided purgation is not to be thought of, it sometimes happens that at the commencement, along with constipation and biliary derangement, there is much congestive headache and delirium; or, at any period of the disorder, marked constipation, with sleeplessness, may constitute an evil requiring to be dealt with. I do not for a moment believe, as has been asserted by some, that podophyllin will shorten the course of specific fevers; but I am convinced that 1/6 to 1/4 grain doses every six hours will often speedily relieve such symptoms as the above, and at the same time much relieve the general distress, and frequently lower the temperature by one or two degrees. It is needless to say that the action must be stopped as soon as it has produced mild laxation; otherwise, in such a disease as fever, the debilitating results might be mischievous.

In dyspepsia, and in hepatic derangement characterized by loss of appetite, acid regurgitation, putrid taste in the mouth, flatulence, and a tendency either to constipation or to diarrhoea, fa grain of podophyllin every night and morning will often produce the best results. I have often found it particularly useful in chronic vomiting after meals, and in obstinate heartburn connected with liver derangement.

In a variety of liver diseases, both acute and chronic, podophyllin will again often be found to justify the high reputation which it has acquired in America and elsewhere.

Preparations and Dose. - Extractum podophylli, gr. v.-x. (.30-.65); resina podophylii, gr. 1/5 - 1/2 (.01 - 03). These are purgative doses. It is somewhat the fashion to give a large dose and tie it up with opium, belladonna or hyoscyamus, a plan which can hardly commend itself to science or good sense. If the larger dose is too active, it is simpler and better to diminish it than to complicate its action with an additional ingredient. The tendency of the present age is toward mono- rather than poly-pharmacy, and prescriptions with the orthodox "adjuvans" and "corrigens" are less frequently seen than formerly.