Ipecacuanha. U. S. (Br.) Ipecac.

[Ipecacuanhae Radix P. I.]

"The dried root of Cephaelis Ipecacuanha (Brotero) A. Richard, known in commerce as Rio Ipecac, or of Cephaelis acuminata Karsten, known in commerce as Cartagena Ipecac (Fam. Rubiaceae), without the presence or admixture of more than 5 per cent. of stems or other foreign matter and yielding not less than 1.75 per cent. of the ether-soluble alkaloids of Ipecac." U. S. "Ipecacuanha Root is the dried root of Psychotria Ipecacuanha, Stokes." Br.

Ipecacuanhae Radix, Br., Ipecacuanha Root; Poaya, Braz. Ipecacuanha annele ou officinale, Fr. Cod.; Racine bresilienne, Fr.; Radix Ipecacuanha, P. G.; Ruhrwurzel, Brechwurzel, Ipecacuanha, G.; Ipecacuana, It.; Ipecacuana (Raiz de), Sp.

The term ipecacuanha, derived from the language of the aborigines of Brazil, has been applied to various emetic roots of South American origin. The botanical character of the ipecac plant of commerce was long unknown. At the present time the plant is well known, but there is considerable conflict regarding the proper botanical name to designate it. The several Pharmacopoeias differ from each other in the generic names used, and hence there may be some confusion. The U. S. Pharmacopoeia wisely retains the generic name Cephaelis, this having been recognized for years in this country. The British Pharmacopoeia uses the generic name Psychotria, which practice has been followed in that country for many years. The Swiss and German Pharmacopoeias follow Ehgler and Pranti, and use the generic name Uragoga. The latter is probably correct, but in view of the unstability of this subject, particularly as other generic names have been proposed and may even supersede all of these it is wise to adhere to the old name Cephaelis, thus causing no confusion.

Cephaelis Ipecacuanha is a small shrubby plant, with a slender root from four to six inches long, marked with annular rugae, simple or somewhat branched, descending obliquely into the ground, and here and there sending forth slender fibrils. The stem is two or three feet long, but, being partly under ground, and often procumbent at the base, usually rises less than a foot in height. It is slender; in the lower portion leafless, smooth, brown or ash-colored, and knotted, with radicles frequently proceeding from the nodes; near the summit, pubescent, green, and furnished with leaves seldom exceeding six in number. These are opposite, petiolate, oblong-obovate, acute, entire, from three to four inches long, from one to two broad, obscurely green and somewhat rough on their upper surface, pale, downy, and veined on the under. At the insertion of each pair of leaves are deciduous stipules, embracing the stem, membranous at the base, and separated above into numerous bristle-like divisions. The flowers are small, white, each accompanied with a green bract, and collected in a semi-globular head, supported upon a round, solitary, axillary footstalk, and embraced by a monophyllous involucre. The latter being deeply divided into four, sometimes five or six, obovate, pointed segments. The fruit is an ovate, obtuse berry, which is at first purple, but becomes almost black when ripe, and contains two small plano-convex seeds.

Cephaelis tomentosa, of Trinidad, has been studied by Francis Ransom, who finds that it contains emetine, but in too small quantity for commercial purposes. For description of the root, etc., see P. J., xix, p. 258.

The Rio ipecac plant of Brazil flourishes in moist, thick, and shady woods, being most abundant within the limits of the eighth and twenty-second degrees of south latitude. It flowers in January and February, and ripens its fruit in May. The root is active in all seasons, but, as it has to be dried rapidly, collection during the rainy season is relaxed. The native collector, or poayero, seizes all the stems of a clump, loosens them by a zigzag motion, and then, thrusting a pointed stick under the roots, tears up the whole mass. The roots, freed from dirt by shaking, are then dried. The amount gathered daily varies from 8 to 30 pounds, according to skill and locality. Extirpation does not take place, because, as shown by the Edinburgh gardeners McNab and Lindsay, a very small fragment of the root, or even a petiole of a leaf, will rapidly produce a new plant. Weddell, indeed, many years since, stated that the remains of the root, often purposely left in the ground, serve the purpose of propagation, each fragment giving rise to a new plant. Ipecac of commerce comes chiefly from the interior province of Matto-Grosso, upon the upper waters of the Paraguay (from which in some years as much as 450,000 kilos are shipped), although some is said to be gathered near Philadelphia north of Rio Janeiro. The chief places of export are Rio Janeiro, Bahia, and Pernambuco. It is brought to the United States in large bags or bales. The importation into the United States have increased from 78,654 pounds in 1914 to 203,734 pounds in 1916.

UNOFFICIAL VARIETIES OF IPECAC.—From time to time there have been imported into Europe various drugs stated to be ipecac, but differing from the official drug. Of these the most important are White Ipecac; the Larger Striated Ipecac of Planchon (J. P. C., Dec., 1872); and the Lesser Striated Ipecac of Planchon.

Larger Striated Ipecac (Planchon). Violet Striated Ipecac. Ipecac of St. Martha. Ipecac of Carthagena. Striated Elastic Ipecac (Attfield).—This variety of ipecac is generally acknowledged to be the product of Psychotria emetica L., growing in the deep forests of Colombia. The drug occurs in rather long fragments, sometimes 9 or 10 cm., with a thickness of from 5 to 9 mm. The pieces are for the most part almost straight, sometimes sinuous, more rarely tortuous. At distant intervals they are marked by contractions, or circular furrows. Their whole surface is largely striated longitudinally. To their upper part are often attached one or more remaining portions of the stem, distinguished from the root by their much smoother surface. Their color is a grayish-brown, tending sometimes to reddish-brown. Like other ipecacs, they have an outer cortical and a central ligneous portion. The former is soft, so that it may even be penetrated by the nail. It has a horny aspect, and a variable color, passing from whitish, by shades of rose, violaceous, and blackish violet. Its thickness is at least two-thirds of the root, and becomes still greater when this is immersed in water. The central part is yellowish-white. The root has little odor, and a taste scarcely nauseous, sometimes flat, and often sweetish. As to the microscopic characters, the most striking are probably the total absence of the starch granules, and the relatively very small diameter of the vessels in the central part. Chemically this variety is characterized by the presence of sugar. It also contains 0.027 per cent. of emetine.

Lesser Striated Ipecac (Planchon). Ipecac des Cotes d'Or (Pelletier). Black Ipecac. Black Striated Ipecac. Striated Brittle Ipecac (Attfield). False Ipecac (Holmes).—It is probably obtained from a species of Richardsonia. It occurs in very short fragments, 2 or 3 cm. long, and 2 or 3 mm. in thickness; some nearly cylindrical, others narrowly fusiform; others again formed of roundish or pyriform segments, somewhat thicker than the preceding, placed end to end. The color is generally of a gray-brown, darker than that of the other kind. The longitudinal striae are fine, and regular on the transverse section. The cortical portion is horny, and its consistence firmer than in the larger kind; the wood is yellowish, and porous. The presence of the starch granules is another of the distinguishing characters of this variety. It contains a larger proportion of emetine than the preceding, yielding, according to the analysis of Pelletier, 9 per cent.

White Ipecac is obtained from Ionidium Ipecacuanha St. Hil. (Fam. Violaceae). It is obtained from Brazil. The root is much branched, free from annulations and of a grayish-white or light brownish-yellow color. The bark is very thin and the wood is light-yellow and porous. It is distinguished by the presence of stone cells and freedom from starch. It contains inulin and no emetine.

According to Pelletier, 100 parts contain 5 of an emetic substance, 35 of gum, 1 of nitrogenous matter, and 37 of lignin. (Histoire abregee des Drogues simples, i, 514.)

The root of a species of Ionidium growing in Quito has attracted some attention as a remedy in elephantiasis, under the South American name of cuichunchulli. The plant received from Bancroft the name of I. Marcucci; but Hooker found the specimen received from Bancroft to be the I. parviflorum of Ventenat.

Lindley thinks a specimen he received under the same name from Quito to be the I. microphyllum of Humboldt. If useful in elephantiasis, it is so probably by its emeto-purgative action. (See A. J. P., vii, 186.)

Under the name of East Indian Ipecac there has appeared in the London markets a root of a pale pinkish-brown color, tapering rapidly from the base to the apex, and having annulations much closer than in the true ipecac. It is especially distinguished from the latter root by being evidently monocotyledonous—that is, without the central woody column—the vascular bundles appearing under a pocket lens as a more or less irregular ring of brownish dots. R. A. Cripp obtained from it a minute quantity of an alkaloidal substance, certainly distinct from the alkaloids of ipecac. (P. J., Iv.) Ranwez and Campion have also described a false ipecac derived from a monocotyledonous plant, Cryptocoryne spiralis. (Ann. Pharm., i.)

In 1866 the cultivation of ipecac was introduced into India by King, but it was not until twenty years later (1886), when it was found that ipecac flourished in the Straits Settlements equally as well as in the Province of Minas, Brazil, that its cultivation became successful.

Cephaelis acuminata Karsten is the source of the drug of commerce known as Cartagena, Panama, or Savanilla Ipecac. The plant is indigenous to Colombia. The leaves according to Karsten are elliptical, pointed, the stipules being separated, often almost to their base in a subulate fringe. The root is much larger and the percentage of active constituents is different from that of Rio ipecac. Humboldt considered C. acuminata merely as a different geographical form of C. Ipecacuanha. Owing to the scarcity of Rio ipecac the importations of the Cartagena variety is considerable, at times being the only form obtainable. It was for this reason that it was included in the U. S. Pharmacopoeia. Braun discussed the subject of the cultivation of ipecac (Der Pflanzer, Tanga, i, p. 50) and commented on the available varieties to be selected and the best methods for collecting and treating the drug. Derry states (C. D., lxxx, p. 822) that when established it grows well on virgin soils or where there is a depth of vegetable humus and the situation is moist and shady, but the properties, of the root deteriorate with continued cultivation.

Properties.—Rio ipecac is in pieces 2.4 to 4 mm. thick, variously bent and contorted, simple or branched, consisting of an interior slender, light straw-colored, ligneous cord, with a thick, brittle, brownish, finely wrinkled, cortical covering, which presents on its surface a succession of circular, unequal, prominent rings or rugae, separated by very narrow fissures, frequently extending nearly down to the central fiber. This appearance of the surface has given rise to the term annele, or annulated, by which the true ipecac is designated by French pharmacists. The cortex is hard, horny, and semi-transparent, breaks with a resinous fracture, and easily separates from the tougher ligneous fiber, which possesses the medicinal virtues of the root in a much inferior degree. On microscopic examination the very thick bark is seen to be formed of uniform parenchymatous cells, without traces of the medullary rays, which are very distinct in the woody central cylinder. Attached to the root is frequently a smoother and more slender portion, which is the base of the stem, and should be separated before pulverization. Pereira has met, in the English market, with distinct bales composed of these fragments of stems, with occasionally portions of the root attached. Much stress has been laid upon the color of the external surface of the ipecac root, and diversity in this respect has even led to the formation of distinct varieties. Thus, the epidermis is sometimes deep brown or even blackish, sometimes reddish-brown or reddish-gray, and sometimes light gray or ash-colored; hence the varieties of ipecac root which were formerly recognized, the brown, red and gray. It is now known that the color of the root varies according to the circumstances of growth and soil, so that coloration as the basis of classification has been abandoned, and the ipecacs of commerce are divided according to their geographical sources, into the Brazilian or Rio Ipecac, the Cartagena or Colombia Ipecac, and the Johore or Indian Ipecac; of these, the two varieties which are recognized by the U. S. Pharmacopoeia are described as follows: "Rio Ipecac.—In cylindrical pieces, curved, and sharply flexuous, occasionally branched, from 3 to 15 cm. in length and from 2.4 to 4 mm. in thickness; externally dark brown, closely annulated, with thickened, incomplete rings, and usually exhibiting transverse fissures with vertical sides; fracture of bark short, of wood tough, bark very thick, light brown, easily separable from the yellowish-white wood; odor very slight, distinctive, the dust sternutatory; taste bitter and nauseous, somewhat acrid. Stems cylindrical, attaining a length of 10 cm. and a thickness of 2 mm., dark brown, finely longitudinally wrinkled and with a few elliptical scars. Cartagena Ipecac.—Cylindrical or slenderly fusiform, more or less tortuous, from 3 to 12 cm. in length and from 4 to 6.5 mm. in thickness; externally grayish-brown, the annulations usually not so numerous as in Rio Ipecac, occasionally transversely fissured and with circular scars of roots; bark 2 mm. in thickness, dark brown, smooth, somewhat horny, and easily separable from the light brown wood. Stems attaining a length of 10 cm. and a thickness of from 2 to 3 mm., cylindrical, somewhat zigzag, due to the prominent nodes with their elliptical stem-scars, grayish or dark brown and longitudinally wrinkled; bark thin. The powder from both varieties of Ipecac is light brown; starch grains numerous, single or from 2- to 4- or more compound, the individual grains spherical or polygonal, from 0.003 to 0.017 mm. in diameter; calcium oxalate in raphides, from 0.015 to 0.04 mm. in length, few; tracheids with bordered pores and oblique slit-like pores. The stem bark shows a few, slightly elongated stone cells, from 0.03 to 0.045 mm. in length with thick lignified walls and simple branching pores. Ipecac yields not less than 1.8 per cent. nor more than 4.5 per cent. of ash." U. S.

"In somewhat tortuous pieces seldom more than fifteen centimeters long or six millimetres thick; from dark brick-red to very dark brown; closely annulated externally, the annulations not taking the form of narrow ridges partially encircling the root (distinction from Cartagena ipecacuanha). Fracture short, the fractured surface exhibiting a thick greyish bark and small dense wood. Bark consisting of thin' walled parenchymatous cells, some containing slender raphides, but most filled with simple or compound starch grains, the simple seldom exceeding fifteen microns in length; wood consisting chiefly of tracheids and containing no vessels or typical medullary rays. In the powdered Root, thin-walled parenchymatous tissue, abundant simple or compound starch grains, the single grains seldom exceeding 15 microns in diameter, acicular calcium oxalate crystals, fragments of brown cork, lignified tracheids and wood-parenchyma; but not more than a very occasional vessel or strongly thickened sclerenchymatous cell. Slight odor; taste bitter. Ash not more than 5 per cent. Yields not less than 2 per cent. of alkaloids when tested by the following process." Br.

(Six pages of painful Ipecac pharmaceutical minutae deleted - MM)

Uses.—Ipecac was employed as an emetic by the natives of Brazil when that country was first settled by the Portuguese, but, though described in the work of Piso, it was not known in Europe until 1672, and did not come into use until some years afterwards. John Helvetius, grandfather of the famous author of that name, having been associated with a merchant who had imported a large quantity of ipecac into Paris, employed it as a secret remedy, and with so much success in dysentery and other bowel affections that general attention was drawn to it, and the fortunate physician received from Louis XIV a large sum of money and public honors on the condition that he should make it public.

Ipecac is in large doses emetic, in smaller doses, diaphoretic and expectorant, and in still smaller, stimulant to the stomach, exciting appetite and facilitating digestion. In quantities not quite sufficient to cause vomiting, it produces nausea, and frequently acts on the bowels. As an emetic it is mild, but tolerably certain, and free from corrosive or narcotic properties. The emetic effect seems to be due partly to the local irritant effect of the drug upon the mucous membrane of the stomach, although the experiments of Hatcher show that there is some direct stimulant action upon the vomiting center in the medulla. Of the two alkaloids to which the drug owes its activity it would seem from the experiments of Wild (L. L., 1895, ii, p. 1274) that cephaeline is much more active as an emetic than emetine, although the latter is capable, in sufficient dose, of causing vomiting. Because of the promptness with which the emesis occurs it is scarcely possible for enough of the active principles to be absorbed from the stomach to produce direct systemic effects. When injected subcutaneously or intravenously in large dose, however, the alkaloids act as depressants to the motor side of the spinal cord and probably also to the respiratory center. It would seem that they have some special predilection for the lungs for after toxic doses alternating areas of pallor and intense hyperemia have been found in the pulmonary tissue.

Originally introduced into Europe as a remedy for dysentery, ipecac for centuries was alternately lauded as a specific and condemned as useless in this disease. In 1911 Vedder (Bull. Manila Med. Soc., March, 1911; also J. A. M. A; 1914, lxii, p. 501) showed that an infusion of ipecac representing one part of the drug in ten thousand destroyed the viability of the Entamoebae; and that the alkaloid emetine in a one to one-hundred thousand solution had the same effect. He also showed that the drug was possessed of no bactericidal virtues. Since this research reasons for the diversions of opinion as to the usefulness of ipecac are apparent. There are two types of dysentery, one due to a specific amoeba and the other caused by a bacillus. In the latter form of the disease the drug is useless but is probably the most efficacious remedy we possess in the amoebic type of dysentery. The great difficulty in its employment has always been to obviate the emetic effect which sometimes made it almost impossible to get enough of the drug into the intestinal tract to have an effect. In 1912 Rodgers (B. M. J., 1912, i, p. 1424, and ii, p. 405) introduced the hypodermic administration of the alkaloid emetine which has since then become the standard treatment of amoebic dysentery. For this purpose from one to three grains of the emetine hydrochloride (0.065-0.2 Gm.) should be injected daily; preferably divided into two or three doses. The treatment is also of value in the various sequelae of dysentery, such as abscess of the liver, although it does not always produce complete cures. In 1914 Smith and Barrett (J. A. M. A., 1914. lxiii, p. 1746) brought forward evidence that pyorrhea alveolaris, or Rigg's disease, is due to a specific amoeba, and suggested the use of emetine in its treatment. Their discovery has been confirmed by Bass and Johns (J. A. M. A., 1915. lxiv, p. 553) and others. Smith and Barrett recommended the direct application of a 1 per cent. solution directly to the pus pockets but Bass and Johns prefer the hypodermic administration.

As an emetic ipecac is rarely used merely for the purpose of evacuating the stomach, but when an action upon the portal circulation is desirable, as in the so-called biliousness or acute alcoholism, it is often of service. Many clinicians believe that it has a direct influence upon hepatic secretion, but it is more probable that its effects upon the liver are due simply to its emetic action. By virtue of their nauseating effect small doses of ipecac tend to increase various secretions of the body, thus it is widely used as a diaphoretic, especially in combination with opium (see Pulvis Ipecacuanhae et Opii) in the early stages of acute coryza and other mild infections. In the same way it acts as an expectorant, and in the early stages of acute bronchitis it is one of the most valuable remedies we possess. Many years ago Trousseau affirmed that ipecac possessed valuable hemostatic powers, especially useful in hemoptysis, but this use of it failed to receive general recognition. The treatment has been revived by Flandin (Press. Med., 1913) and other French clinicians.

As an emetic ipecac may be given in substance .in the dose of twenty to thirty grains (1.3-2.0 Gm.), repeated in fifteen to twenty minutes if necessary. As an expectorant the syrup is generally preferred. If ipecac itself is used in dysentery it should be given in doses of five grains every hour combined with opium to prevent vomiting. To obviate the nauseating effect of emetine when given by the mouth, Bass and Johns have used a combination with Lloyd's reagent.

Under the name of riopan, a preparation asserted to contain 50 per cent. of combined cephaleine and emetine has been introduced. This is marketed in the form of tablets each containing one-thirtieth of a grain (0.002 Gm.), which is stated to be equivalent to about a grain and a half of ipecac (0.096 Gm.).

Dose, emetic, twenty to thirty grains (1.3-2.0 Gm.); nauseating, two grains (0.13 Gm.); diaphoretic, one grain (0.065 Gm.); stomachic, one-fourth to one-half grain (0.016-0.032 Gm.).

Preparation: Acetum Ipecacuanhae.

Off. Prep.Fluidextractum Ipecacuanhae, U. S. (Br.); Pilula Ipecacuanhae cum Scillae, Br.; Pulvis Ipecacuanhae et Opii, U. S. (Br.); Syrupus Ipecacuanhae, U. S.; Trochiscus Ipecacuanhae, Br.; Trochiscus Morphinae et Ipecacuanhae, Br.; Vinum Ipecacuanhae (from Fluidextract), Br. N. F.; Mistura Rhei Composita (from Fluidextract), N. F.; Pilulae ad Prandium (Chapman's), N. F.; Pilulae Antidyspepticae, N. F.; Pilulae Laxativae Compositae, N. F.; Pilulae Laxativae Post Partum, N. F.; Syrupus Aisari Compositus (from Fluidextract), N. F.; Syrupus Cimicifugae Compositus (from Fluidextract), N. F.; Syrupus Ipecacuanhae et Opii (from Tincture), N. F.; Tinctura Ipecacuanhae et Opii (from Fluidextract), N. F.

The Dispensatory of the United States of America, 1918, was edited by Joseph P. Remington, Horatio C. Wood and others.