Ipecac (ipecacuanha) is the root of Cephaelis Ipecacuanha from Brazil, and of the Carthagena ipecac, Cephaelis acuminata (Fam. Rubiacece), and it is required to yield on assay not less than 2 per cent. of alkaloid. It contains 3 alkaloids - emetine, the important one, and cephaeline and psychotrine. Preparations and Doses. - The expectorant dose is: Ipecac, 1 grain (0.06 gm.). Fluidextract, 1 minim (0.06 c.c.). Syrup, 7 per cent. of fluidextract (acid with acetic acid), 15 minims (1 c.c.). Powder of ipecac and opium (Dover's powder), 10 per cent. each of ipecac and opium, 10 grains (0.6 gm.). The emetic dose is 15 grains (1 gm.). The dose in amebic colitis is 30 grains (2 gm.), decreased about 3 grains (0.2 gm.) daily, and given at bedtime and in enteric pills to prevent vomiting; Morgan recommends that a liquid ipecac preparation be given through a duodenal tube.

Emetine hydrochloride, freely soluble in water and alcohol, is used subcutaneously in doses of 1/3 grain (0.02 gm.) one to three times a day. It should not be continued beyond ten days, but with intervals of a few days may be repeated for a second, third, or fourth period of a week or ten days.

Pharmacologic Action Of Emetine

Microorganisms. - Emetine in solutions of 1: 100,000 is destructive to both pathogenic and non-pathogenic amebae. In strong solutions up to 5 per cent. Kolmer and Smith found its bactericidal value 5 times that of phenol.

Skin, Mucous Membranes, And Alimentary Tract

The drug is irritant locally. Applied to the skin it has a pustulant action, and in solutions of 1: 500 causes marked irritation of mucous membranes. Chauffard set up a violent irritation of the intestines by an irrigation with 1: 10,000. Lyons, 1915, took 1/2 grain (0.03 gm.) by mouth, and quickly developed nausea, followed in one hour by vomiting, and an hour later by loose stools accompanied by griping. In oral administration nausea and vomiting come on almost at once, yet may be prevented by the previous administration of a large dose, 1 dram (4 gm.), of bismuth subnitrate or cerium oxalate. Much larger doses than can be borne by mouth must be given subcutaneously or even intravenously before the development of nausea, vomiting, or diarrhea. These effects would, therefore, seem to be essentially local. But Eggleston and Hatcher have found that in animals with stomachs removed emetine intravenously caused symptoms of nausea and the movements of vomiting, therefore there must be a certain central action as well. After subcutaneous doses Foulkrod found emetine in the stomach, but Lyons failed to find it in the intestines.

Circulation

There is a weakening of the heart muscle with slowing and dilatation similar to that from chloroform and not influenced by atropine or cutting the vagi. Death may result from auricular and ventricular fibrillation. In the frog and turtle heart-block has been observed. From therapeutic doses there is a very short and slight rise in arterial pressure followed by a sharp fall and a quick return to its former level. From toxic doses there is a progressive slowing and weakening of the heart and fall in pressure, with collapse. Pellini and Wallace obtained no change or a slight contraction of the arteries; but Evans, Middleton, and Smith say that there is a transient vasoconstriction followed by definite vasodilation. Sollmann observed a vasomotor paralyzing action. Howell has noted a deficiency in fibrinogen in the blood as the result of which clotting is retarded and the clot is not retractile.

Respiratory

There is some depression from subcutaneous doses, but from intravenous the respiratory center is stimulated and the rate and depth of respiration increased (Pellini and Wallace). From toxic amounts there is a decided tendency to pulmonary congestion or to hemorrhagic pneumonic consolidation, with or without hemoptysis.

Kidneys

There is no effect except in poisoning, when there may be nephritis with albuminuria and chloride and nitrogen retention.

Toxicology

There are many reports of ill effects from the human use of the drug. From 1/2 grain (0.03 gm.) daily by hypodermic for four days Levy and Rowntree report severe diarrhea, abdominal pain, tenesmus, and toxic delirium, with recovery, in a woman of 95 pounds, and death in a man from 29 grains (2 gm.) given subcutaneously in the course of twenty days. They caused death of a dog by hemorrhagic gastro-enteritis from 1/6 grain (0.01 gm.) subcutaneously daily for three days. Spehl and Colard gave 22 grains (1.44 gm.) in eighteen days, when there developed a flaccid paralysis, especially of the neck muscles, followed by difficulty in swallowing, mastication and speech, with edema of the face, kidney retention, and rapid weak heart. The symptoms subsided after stoppage of the drug. Johnson and Murphy, 1917, had two deaths of men after the subcutaneous use of a total of 23 1/2 and 25 grains. These amounts tally with Dalimier's estimation from animal experiments that the toxic dose for a 120-pound adult is about 27 grains (1.8 gm.) whether it is given in a short period or during two or three weeks. Harrison reports a death from the wine of ipecac.

From many reported cases a summary of the toxic effects from subcutaneous doses shows that besides the pronounced gastrointestinal irritation there may be acute renal insufficiency, general edema, hemoptysis, flaccid paralysis, peripheral neuritis, delirium, coma, and failure of the heart.

There is a consensus of opinion that intravenous doses are exceedingly dangerous, and that if used intravenously at all the drug should be well diluted and very slowly administered.

Therapeutics

Ipecac is employed (1) as an expectorant in dry bronchitis, laryngitis, and rhinitis, (2) as a nauseant or emetic in non-diphtheritic croup, (3) as a diaphoretic in the form of Dover's powder at the onset of a cold (see Diaphoretics), and (4) in amebic dysentery to supplement the subcutaneous injections of emetine.

Emetine has its greatest usefulness in the treatment of amebic dysentery, in which it apparently attacks the organisms in the intestinal wall. It does not destroy the encysted forms found in the ameba-carriers. It is to be borne in mind that by prolonged use emetine itself may result in diarrhea or dysentery. In pyorrhea areolaris it may produce improvement by destruction of the Entameba buccalis, but it fails to cure because the ameba is not the cause of the pyorrhea (U. S. Public Health Reports, 1916). It has been recommended in chronic non-amebic follicular enteritis, sprue, and some other diseases. Chauffard employed it in tuberculous hemoptysis, but neither clinical results nor its pharmacologic action justify its use for any internal hemorrhage, and because of its causing pulmonary congestion Zepf and others believe it con traindicated in hemoptysis.