Ipecacuanha

IPECACUANHA (Ipecacuanha), the name of the plant Cephaelis Ipecacuanha Willd., or Psychotria Ipecacuanha Mull. Arg., or Ipecacuanha officinalis Arruda, or Uragoga Ipecacuanha Baillon of the madder family (Rubiaceae). Ipecacuanha grows wild in Brazil and eastern Bolivia, and is successfully cultivated in British India. The roots of Ipecacuanha are straight or worm-like curved pieces of varying size, gray-brown in color, 4-5 mm in thickness [Radix Ipecacuanhae verae minoris s. brasiliensis (Fig. VII)] or 6-8 mm in diameter (Radix Ipecacuanhae annulatae majoris, s. Carthagenae verae) with ring-like constrictions and thickenings like beads at places where starch accumulates. The thick, mealy, horn-like inner bark with smooth breaks easily separates from the yellowish wood, which resembles a thin and very strong rod. The taste of the root is unpleasant, slightly bitter; the odor is weak, characteristic; the powder of Ipecacuanha is light gray in color and causes sneezing, coughing, and tearing. The active substances of the root are in the bark layer; there is very little of them in the wood; therefore, the powder for medical use is prepared only from the bark layer. Ipecacuanha contains (2-2.8%): emetine, cephaeline, psychotrine, methylcephaeline, ipecacuanhine, hydroipecacuanhine, amorphous emetoïdine, ipecacuanhic acid, saponin substances, sugar, and a large amount of starch. Pelletier and Magendie first obtained an alkaloid from Ipecacuanha in 1817, which they named emetine, which was a mixture of emetine and cephaeline. On the market, even now, a mixture of the mentioned alkaloids is sold under the name emetine. Pure emetine—an amorphous white powder that quickly yellows in light, easily soluble in ether, alcohol, acetone, chloroform, and very little in water; melts at t° 68°. The composition of emetine, as well as other Ipecacuanha alkaloids, has not yet been finally established; for emetine two formulas are given: C17H21NO3 and C29H40N2O4. Emetine can be synthetically obtained from cephaeline by methylation of the latter. Emetine hydrochloride C₂₉H₄₀N₂O₄·2HCl +6H₂O is a colorless crystalline powder, easily soluble in water, not sensitive to light. Cephaeline (formula C₂₈H₃₈N₂O₄ or C₂₈H₃₈N₂O₄)—a crystalline white powder that quickly yellows in light, difficult to dissolve in ether; melts at t° 115-116°; with hydrochloric acid forms an easily soluble, light-stable salt—Cephaelini hydrochloricum. Psychotrine, C₂₈H₃₈N₂O₄, a yellow powder with blue fluorescence, by reduction (+H) turns into cephaeline, and by methylation into methylpsychotrine, C₂₉H₄₀N₂O₄, from which by treatment with sodium in an alcoholic solution emetine is obtained. Emetine and the above-mentioned Ipecacuanha alkaloids are derivatives of isoquinoline, like papaverine, and approach the latter in their action, for example in their effect on smooth muscle, the tone of which they lower. Emetine, like cephaeline, locally produces an irritating effect, especially strong on mucous membranes. The finest powder of Ipecacuanha, getting on the mucous membranes of the eye, nose, and respiratory tract during the grinding of the Ipecacuanha root into powder, causes acute inflammatory, extremely painful phenomena on these mucous membranes. The mucous membranes of the gastrointestinal tract are also very irritated by emetine (resp. cephaeline)—vomiting and diarrhea occur; with large doses of emetine the mucous membranes become strongly hyperemic, swell, are covered with ecchymoses, and bleed. At the same time, the large intestine suffers less, while the pylorus and small intestines suffer most. With subcutaneous or intravenous administration of emetine, irritation also occurs at the injection site, accompanied by pain, but with the absorption of emetine the irritation phenomena soon cease. Rubbing an ointment with emetine into the skin also causes skin irritation, and often pustular rash. The general effect of large doses of emetine (in cats over 0.02) is expressed in a sharp drop in blood pressure, diastolic arrest of the heart due to paralysis of its muscles, as well as paralysis of respiration and paralysis of the trunk muscles. Smaller doses of emetine cause vasodilation, a short-term drop in blood pressure, which however soon equalizes, slowing and irregularities of heartbeats, shortness of breath, and muscle relaxation. From small doses the vessels dilate, and the activity of the heart and muscles is almost unaffected. For warm-blooded animals, the average single lethal dose of emetine with subcutaneous administration is 0.057 per 1 kg, and for cephaeline—0.032; in particular for rabbits—0.045 of emetine and 0.023 of cephaeline. In humans, the single lethal dose of emetine and cephaeline is unknown. 0.26 of emetine, administered subcutaneously, does not cause significant changes in humans; 0.3-0.4 of emetine, injected intravenously, caused severe acute poisoning, but the patients still survived. The absorption of emetine (resp. cephaeline) from the mucous membranes and with subcutaneous administration begins quickly, and after 20-50 minutes this substance can be found in the blood, in the liver, in the stomach, in the urine. The excretion of emetine is delayed for up to 60 days, with only 1/10-1/5 of the administered amount being excreted in the urine. The cumulative properties of emetine have been proven experimentally: a single subcutaneous administration of 0.002 of emetine per 1 kg of weight in cats and rabbits is completely harmless, but repeated over 3-10 days causes poisoning, and with further administration—death of the animal. With larger repeated doses (0.005-0.03), death in animals occurs depending on the dose size on the 22nd-4th day. From these experiments it is clear that emetine accumulates in the body and eventually causes the death of the animal. In humans, its cumulative effect manifests itself in the onset of vomiting and diarrhea, weakening of heartbeats with a slow pulse, general weakness, difficulty in swallowing, trembling, and neuritis. The mentioned phenomena disappear, health is restored if the administration of emetine is stopped. With the injection of large doses of emetine under the skin or intravenously and with its administration orally in the form of Ipecacuanha powder (1.0-1.5) in humans, as in animals, after a few minutes (5-10) increased secretion of saliva and mucus occurs, and finally after 15-20 minutes vomiting, which is usually preceded by a long and very distressing period of nausea. The vomiting from Ipecacuanha is of reflex origin due to irritation of the sensory nerves of the gastric mucosa; this is proven by the fact that subcutaneous and intravenous administration of emetine not only does not accelerate, but even delays the onset of vomiting, and that with subcutaneous and intravenous administration of emetine, the dose causing vomiting must be increased compared to the dose causing vomiting when emetine is administered into the stomach. The abundant secretion of mucus and saliva observed during the nausea period from large doses of Ipecacuanha, as with all emetic agents, occurs with medium and small doses of Ipecacuanha to a more moderate degree and therefore serves as the basis for the therapeutic use of Ipecacuanha as an expectorant. Preparations of Ipecacuanha, as containing alkaloids that irritate mucous membranes (emetine, cephaeline, etc.) and which probably also cause increased secretion of mucous membranes of the respiratory tract, are preferred as expectorants over other agents belonging to the group of emetics, all the more so because the slow absorption and relatively long stay of emetine in the body contribute to a more stable action of Ipecacuanha preparations. The therapeutic value of Ipecacuanha is not limited to its use as an expectorant and emetic. Preparations of Ipecacuanha have long been (Helvetius; 1686) famous as an excellent remedy for bloody diarrhea. In the last 20 years, it has been clarified that the basis for the successful use of Ipecacuanha in tropical forms of dysentery is the property of Ipecacuanha alkaloids—emetine, cephaeline, and methylpsychotrine—to act detrimentally on amoebas. In this regard, however, the sensitivity of different types of amoebas varies, and their resistance also depends on different living conditions; therefore, different results were obtained by researchers when they acted on amoebas with emetine in vitro and in vivo. If the disease dysentery (see Amoebas) is caused by Entamoeba histolytica living in the tissues of the intestinal walls, then emetine, injected under the skin into the patient, spreading with the blood through the tissues, penetrates into the intestinal walls and strongly affects the parasite living here, especially sensitive to emetine; in such cases the therapeutic effect of emetine is great and gave rise to talk of a special, "specific" effect of emetine in amoebic dysentery. But the stages preceding encystment (forma "minuta") and the cysts of the above-mentioned amoeba are very little sensitive to emetine; they live mainly in the cavity of the intestine and almost do not come under the effect of emetine, circulating mainly in the tissues, and not in the cavity of the intestine. Therefore, cases of amoebic dysentery arising from the life activity of the mentioned forms are little amenable to emetine therapy.

The direct action of emetine in vitro on Entamoeba histolytica made it possible to conclude that in many cases the sensitivity of this amoeba varies, for which reason many researchers do not recognize any particular specificity for emetine in this regard, all the more so since emetine and other alkaloids of I. act parasitotropically on other amoebas (e.g. Entamoeba buccalis), paramecia, and bacilli, and in some cases even more actively than on the dysentery amoeba. Only psychotrine does not exhibit parasitotropic properties among the alkaloids of ipecacuanha. In therapy: Purvis ipecacuanhae (ФУП) is used in doses of 0.005-0.05 three to five times a day as an expectorant and against dysentery, and rarely - 1.0 as an emetic; powder of I. is also given in the form of pills, cakes.-Infusum from powder of I. (0.4-0.6 per 200.0) is given by the tablespoonful at a time, usually adding to it an infusion of ammonia-anise drops and sodium bicarbonate with the aim of promoting more rapid dissolution of bronchial mucus. Such a prescription is irrational, since alkalis cause the precipitation of the alkaloids from the infusion of I.; it is more advisable to give the infusion of I. separately from alkalis. Ph. VII prescribes the preparation of Infusum Ipecacuanhae concentratum, which can be kept in stock. "When prescribing an infusion of I., a concentrated infusion is dispensed in the appropriate dilution with water" - states Ph. VII. The form of concentrated infusion, introduced for practical purposes, can hardly be considered rational, as this form remains to this day unenlightened from a scientific standpoint.-T-ra Ipecacuanhae (ФУП), highest dose 2.0 per dose, is used as an expectorant and in bloody diarrhea. Sirupus Ipecacuanhae (ФУП), a mixture of 1 part of T-rae Ipecacuanhae and 9 parts of Sirupi simplicis, is given 2.0-4.0 per dose orally.-A mixture of 1 part of Sirupi Ipecacuanhae and 2 parts of Sirupi Althaeae is called chest syrup (Sirupus pectoralis); given as an expectorant 2.0-4.0-8.0 per dose. The previously used Vinum Ipecacuanhae is an irrational form and in case of prescription is replaced by the tincture of I. (T-ga Ipecacuanhae).-Pulvis Ipecacuanhae opiatus (ФУП), highest single dose 1.0, contains ipecac and opium at 10% each. Emetinum hydrochloricum, is given 0.02-0.2 subcutaneously or intravenously in amoebic dysentery, in abscesses of the liver developing on the basis of dysentery, and prophylactically in the threat of the occurrence of amoebic abscesses; in alveolar pyorrhea; to stop spontaneous bleeding, and sometimes postoperative bleeding.-Cephaeline and other alkaloids of I. are not used in practice. Previously, the cortex of I., deprived of alkaloids, was used - Cortex radicis I. de-emetinisata, and its application was accompanied by good therapeutic results; now such a preparation is considered superfluous, since the action of the de-emetinized cortex is due either to the tannins of the cortex or to the emetine remaining in the cortex, which was repeatedly confirmed by analysis.