"The seed of Strophanthus hispidus, De Candolle, deprived of its long awn (U. S. P.).
ILLUSTRATION: Köhler's Medizinal Pflanzen.
Botanical Source and History.—The genus Strophanthus which produces this drug, is chiefly of African origin, and consists, at present, of more than 25 species. (Regarding the geographical distribution of the various species in Africa, see E. M. Holmes, Pharm. Jour. Trans., Vol. XXIII, 1892-93, pp. 868 and 927.) Plants of this genus have usually woody stems, emitting a milky juice when wounded, and are generally twining vines, which climb the highest trees. The seed of commerce is probably collected from various species indiscriminately, which have been classified and differentiated by Pax, Planchon, Hartwich, Holmes, Blondel, and others. The medicinally valuable strophanthus seeds are yielded chiefly by two species—S. hispidus and S. Kombé. Both are official in the German Pharmacopoeia, only the former in the U. S. P., and the latter in the Br. Pharm.
Strophanthus hispidus, De Candolle, was one of four species described by De Candolle as early as 1802, and is the species to which this drug was first ascribed. Its habitat is Senegambia and Guinea, and other parts of western Africa. The stem is a twining, milky shrub, with opposite hirsute leaves (hence the name hispidus, Latin for bristly, hairy). The flowers are borne in terminal, many-flowered, dense cymes. The calyx consists of 5 hairy, green sepals about the length of the corolla tube. The corolla is white, with a short, funnel-shaped tube, yellowish within, and furnished with 10 small, nectariferous glands. The segments of the corolla are very long, tapering, slender, hairy without, having a length sometimes of 8 inches, and are the conspicuous part of the flower, giving the plant its generic name (from strophos, Greek for twisted cord). The stamens are 5, with sagittate anthers and slender filaments. The pistil consists of 2 distinct carpels, each of which, if fertilized, ripens into a long pod, filled with numerous seed. The seed, each bearing a slender style, terminating in a plumose pappus, consisting of long, fine hairs, is the part used in medicine, after being deprive, of their awns.
Strophanthus Kombé, Oliver, is a similar plant, native, however, of eastern Africa, and was differentiated from S. hispidus by Oliver, in 1885. It has the same hirsute leaves, but they are more coriaceous. The sepals are shorter than the corolla tube, and cymes are fewer flowered than the S. hispidus. Some botanists contend that S. Kombé is merely a variety of S. hispidus.
Although, as before stated, the genus Strophanthus was established as far back as the year 1802, it was not until the early 60's that the drug came to the general notice of Europeans as being one of the several arrow-poisons (e. g., inée or onaye, in Senegambia, from S. hispidus, and S. Kombé, on the east coast, from S. Kombé) used among the African native tribes. (Regarding details on arrow-poisons, see article on Strophanthus, by J. U. Lloyd, in Western Druggist, 1897, p. 403, from which most of the subject herein presented is derived.) In this connection, the following observation, regarding arrow-poisons among the American Indians, may be of interest: "In some of my western work I have found among the Indians that the poisoning of their arrows, while mixed up a great deal with useless ceremonials, and often, no doubt, nearly useless plant extracts, has a basis in some sort of poison, probably ptomaine, or something of that character, derived from rotten meat. This was the case among the Klamath and Modoc Indians" (Frederick V. Coville, botanist to United States Government, in a private letter to Prof. Lloyd).
The powerful cardiac properties of the drug were recognized by Sharpey (1862), Pelikan (1865), Fraser (1871), but not until about 1885 did strophanthus gain a foothold in medical practice. As the demand for strophanthus began to increase, substitution by allied, though often inert, species became frequent. It was, therefore, recommended that the seeds be purchased in the follicles, and that chemical tests for the active principle, strophanthin, be applied to the seeds (see Chemical Composition). (Regarding substitution of the seeds by Kickxia Africana, Bentham, see E. M. Holmes, Pharm. Jour. Trans., Vol. XVII, 1886-87, p. 903; and P. Siedler, Ber. d. Deutsch. Pharm. Ges., 1898, pp. 222-228.)
Description.—The U. S. P. describes strophanthus thus: "About 15 Mm. (⅗ inch) long and 4 or 5 Mm. (⅙ to ⅕ inch) broad, oblong-lanceolate, flattened and obtusely edged, grayish-green, covered with appressed, silky hairs, one side with a ridge extending into the attenuated, pointed end; kernel white and oily, consisting of a straight embryo, having 2 thin cotyledons, and surrounded by a thin layer of perisperm; nearly inodorous.; taste very bitter. A decoction, prepared with 1 part of the seed and 10 parts of water, has a brownish color, and is not changed in appearance on the addition of iodine T.S., ferric chloride T.S., or potassium mercuric iodide T.S."—(U. S. P.).
Chemical Composition.—In 1877, the name strophanthin was given by Hardy and Gallois (Jour. Pharm. Chim., Vol. XXV, p. 177) to a crystalline but non-glucosidal substance obtained from the seed of Strophanthus hispidus by extracting the latter with alcohol acidulated with hydrochloric acid. Thus it might have been strophanthidin (see below), but it is described as being soluble in cold, more soluble in warm water. Prof. T. R. Fraser, of Edinburgh, isolated from the same source amorphous, glucosidal strophanthin capable of being hydrolyzed with diluted acids (slowly in the cold, more rapidly by heat) into sugar and strophanthidin, a crystallizable body (Pharm. Jour. Trans., Vol. XX, 1889-90, pp. 328-335). In addition to strophanthin, Prof. H. Thoms (Berichte der Deutsch. Chem. Ges., 1898, p. 271) found the seeds of this species to contain the bases choline and trigonelline, the latter being the characteristic alkaloid of fenugreek. An alkaloid (ineïne) was previously indicated by Hardy and Gallois (loc. cit.) in the awns of the seeds; the observation could not be subsequently verified. As to the seeds of Strophanthus Kombé, Catillon (1880) affirmed the existence of two glucosids, one being strophanthin, the other nitrogen-bearing and splitting with acids into sugar and a distinct alkaloid. Arnaud in 1888 gave strophanthin from Kombé seeds the formula C31H48O12, and concludes that it is methyl-ouabain (see Related Principles, p. 1849).
Strophanthin of Fraser, is a very bitter, amorphous, nitrogen-free glucosid, freely soluble in water and alcohol, insoluble in pure ether or chloroform (A. W. Gerrard, 1887). It is also insoluble in a concentrated solution of ammonium sulphate (H. Thoms, 1898). Strophanthin produces with concentrated sulphuric acid a bright-green color which is permanent for some time. The seeds containing strophanthin (occurring in the endosperm and sometimes also in the cotyledons) give the same reaction, hence may be readily distinguished from seeds devoid of this active principle (see e. g., Hartwich, Archiv der Pharm., 1892, p. 411). Strophanthidin is crystallizable, insoluble in ether, "very slightly soluble in cold water" (Fraser), soluble in alcohol, moderately soluble in chloroform and amyl alcohol. According to F. Feist (Berichte der Deutsch. Chem. Ges., 1898, p. 534), it yields by oxidation, among other products, benzoic acid. It is stated that strophanthin from S. hispidus is amorphous, that from S. Kombé crystallizable.
Kombic acid is a peculiar acid obtained by Fraser from Kombé seeds. Its aqueous solution is precipitated by lead acetate. To assay tincture of strophanthus for strophanthin, Mr. Barclay proposes to convert this active principle by hydrolysis into the more positive strophanthidin. (See two interesting papers on this subject in Pharm. Jour. Trans., Vol. III, 1896, p. 463, and Vol. VII, 1898, p. 655.)
Action, Medical Uses, and Dosage.—Externally applied, strophanthus preparations appear to exert no special effects unless applied with hydrous wool fat, when the effects of the drug are said to be apparent. The seeds, however, applied to the cornea produce prolonged anaesthesia (Steinbach). Three or 4 drops of a solution of strophanthin (1 in 1000) applied to the cornea also produce total anaesthesia, including sensibility to heat and cold (difference from cocaine), these sensations being the last to yield and the first to revive after its application. A disagreeable irritation of the conjunctiva has been produced by this use of strophanthin; it has no effect on intraocular pressure or upon vision-accommodation. Strophanthus is a muscle poison. When taken internally its action is primarily upon the voluntary muscles, increasing their contractility, and if the dose be poisonous it causes tetanic paralysis, the muscles being unable to regain their former normal flexibility. Under its toxic influence the muscles first become enfeebled, then somewhat rigid, fibrillary twitchings, which are spontaneous, non-rhythmical and increasing contractions, somewhat similar to those of chorea, are observed, and finally the muscles become pallid, non-contractile and hard. It is these effects that render strophanthus an efficient arrow-poison, the muscular paralysis produced rendering the animal an easy prey to its pursuer. When the muscles are in extreme paralysis lactic acid has been observed to replace the normal alkaline condition. Strophanthus muscular paralysis consists chiefly in diminishing the ability of the muscles to relax, and then in destroying this capability, producing a condition difficult to distinguish from rigor mortis.
Strophanthus does not appear to affect either the spinal cord or to act upon its nerve trunks. Its specific action upon the heart is due to direct contact (through the blood) with the muscular fibres of that organ and not to any effect upon the cardiac nerves. A large dose so increases contractility that a more perfect, energetic, and prolonged systole is the result, and the capability of the muscle to relax is lost, or so diminished that diastole can not take place; after death the ventricle is so completely contracted as to almost efface the cavity, the heart passing from life directly into rigor mortis. According to some it may cease either in systole or diastole. The caliber of the blood vessels is but little influenced by strophanthus; it is strongly diuretic in so far as lack of secretion depends upon low blood pressure, i. e., it increases diuresis in so far as increased blood pressure produces an increased urinary product. It is also thought by some to act specially upon the renal secreting structures. When one is in good physiological condition it is said to have little or no diuretic action; but in diseased conditions, with low blood pressure, it is asserted to excel digitalis in diuretic power.
If strophanthus be given in large doses it produces gastro-intestinal irritation with vomiting and diarrhoea. Small doses, however, act as a bitter tonic, improve the appetite, augment gastric action, and promote digestion. In proper doses it strengthens the heart-muscle, slows cardiac action, increases the interval between beats, reduces the pulse-rate, and powerfully increases arterial tension, not by any effect (to any extent at least) upon the vessels, but by strengthening the heart-muscle, giving increased power. Whether or not the drug is cumulative is still an unsettled question, though it probably is not cumulative unless given too freely in over-lapping doses. The action of strophanthus upon the heart is probably greater than that of any other drug, and its active principle is of far greater potency than the digitalis derivatives.
Strophanthus is a remedy for weak heart from debility of the cardiac muscle, with lack of proper contractile power, as shown by a rapid, weak pulse, and very low blood pressure. The disordered action of the heart is due to lack of tonicity and not from weak walls due to depositions of fat, in which case the drug must be used with extreme circumspection, though in small doses it has been recommended by some as a remedy for cardiac fatty degeneration, as it has also in atheroma of the arteries in the aged. It is a remedy for praecordial pain and for cardiac dyspnoea. It has been strongly endorsed in heart affections with disorders of compensation. Strophanthus is a remedy for valvular heart disease only so far as there is muscular insufficiency, where the compensatory increase of muscular action is not sufficient to offset the valvular insufficiency. "It has been reported useful in cases of mitral regurgitation with dilatation; mitral stenosis with regurgitation; regurgitation with oedema, anasarca, dyspnoea, etc.; mitral insufficiency with palpitation, praecordial pain, cyanosis, dyspnoea, etc." (Annual of Eclectic Med. and Surg., Vol. I, 1890, p. 25). Dr. S. Schiller (ibid., p. 40), a keen observer, says: "When the balance in the circulation has become impaired, as a result of insufficiency of the valves of the heart from organic disease with a general dropsical condition, strophanthus, although affording temporary relief in some cases, has failed in every case in my hands to reestablish the compensation. The result was the same whether the mitral, the tricuspid, or the semilunar valves were most involved. These are the cases of heart disease in which digitalis is the remedy. However, evidence is strong to show that when the muscular insufficiency can be corrected in these cases then the remedy will do good service. Dr. Schiller looks upon the drug as a remedy for what is ordinarily termed functional heart disease, when not sympathetic. The heart-action is rapid or abnormally slow, or the rhythm is bad, a condition common in school children at puberty when forced to overstudy. Strophanthus is well endorsed as a remedy for the irritable heart of tobacco smokers, masturbators, and those addicted to the use of alcoholics and narcotics.
Acute endocarditis and the reflex palpitation of neurasthenic, hysterical, and chlorotic subjects have been signally benefited by strophanthus, while it appears to give better cardiac power during or after typhoid and other adynamic fevers, when heart failure threatens. It should be remembered as a remedy for threatened cardiac failure in any disease. Full doses should be given for the relief of angina pectoris, and the remedy should be continued for a period after the attack. It is less efficient, because slower in action, than amyl nitrite or nitroglycerin, but may be given for more permanent effects after the evanescent action of these agents has passed off. In pulmonary congestion and in acute bronchitis or acute pneumonia it may be employed when there is deficient heart-action.
Strophanthus has been praised for prompt results in cardiac asthma and bronchial asthma, with oedema; in whooping-cough it has many advocates; it assists the action of iron salts in pernicious anemia and is credited with the cure of traumatic tetanus. Goitre is asserted to have been cured with it, and large doses (8 to 25 drops several times a day) have been said to cure a large proportion of cases of exophthalmic goitre, with irregular cardiac action. Dr. S. Schiller reports great relief to the heart symptoms in two cases of exophthalmic goitre, with disappearance of the bronchocele in one case (Annual of Eclectic Med. and Surg., Vol. I, p. 40). Strophanthus has also been lauded as a remedy for chronic nephritis, with albuminuria, in anasarca, and in ascites from hepatic cirrhosis. It is of little value in oedema and other forms of dropsy or kidney-affections unless dependent upon cardiac disorders. Dr. W. E. Bloyer (Ec. Med. Jour., 1897, p. 51) reports a case of anasarca in which 5-drop doses, every 2 hours, produced an enormous flow of urine and thin alvine discharges, completely draining the tissues in less than 12 hours. Finally, strophanthus is given credit for the cure of a large number of cases of Asiatic cholera, and it has been asserted useful in urticaria and psoriasis.
This agent does not take the place of digitalis, each having its own field of action. It may, however, follow the use of other heart tonics, and particularly those evanescent in action, as amyl nitrite and nitroglycerin. As it does not affect the caliber of the vessels it may be used in preference to digitalis when it is not desirable to add extra work to the heart. It is well borne by the aged and by children. Wilcox (see Ec. Med. Jour., 1897, p. 394) sums up the advantages of strophanthus over digitalis as follows: "Greater rapidity, modifying pulse-rate within an hour; absence of vaso-constrictor effects; greater diuretic power; no disturbance of digestion; absence of cumulation; greater value in children; great safety in the aged." He further summarizes its uses as follows: "All cases in which we wish to establish compensation; all cases of arterial degeneration in which a remedy which causes more energetic cardiac contraction is required; all cases of cardiac disease where diuresis is necessary; all cases of weak or irritable hearts; all cases of cardiac disease in childhood or old age." These we would qualify by adding when the heart-muscle is at fault.
Strophanthus should be avoided or very cautiously used in advanced muscular degeneration, in pronounced mechanical defects of the heart, and in fully and over-compensated hearts. There is great variation in strength in various batches of tincture of strophanthus owing to lack of uniformity in the crude drug employed. The dose of tincture of strophanthus is from 1 to 10 drops; of specific strophanthus, ½ to 10 minims; of strophanthin, 1/500 to 1/60 grain. All of which should be cautiously administered.
Specific Indications and Uses.—Weak heart, due to muscular debility; muscular insufficiency; rapid pulse, with low blood pressure; cardiac pain, with dyspnoea.
Ɣ Related Principles and Preparations.—UKAMBIN. If not identical with Kombé arrow-poison, this substance is at least closely related. The active crystalline principle belongs to the digitalis group, and produces death by arresting cardiac action.
EXUJA or ECHUGIN.—Said to be derived from Adenium Boehmianum (Nat. Ord.—Leguminosae), and employed as an arrow-poison by southwest African Ovambos. Its active principles were found to be a glucosid whose physiological effects were much like those produced by strophanthin, and a resinous substance (echugon). The glucosid echugin (C5H8O2) forms small, satiny, colorless plates insoluble in ether but easily dissolved by water and alcohol. It constitutes about 10 per cent of exuja, which is an odorless, very bitter, blackish-brown crumbly mass.
HIPPO and VAKAMBA.—The Sakayes and Somangs of Africa employ these two arrow-poisons. They induce emesis and tetanic convulsions and paralyze both heart and lungs simultaneously. The action of vakamba, however, is less tetanic, though the effects upon the muscle are observed sooner than with hippo (Laborde).
OUABAÏO.—A poison said to be derived from Carissa Schimperi, A. De Candolle (Acokanthera Schimperi [De C.], Bentham and Hooker; A. Ouabaio, Cathelineau). Arnaud (1888) obtained therefrom an active principle ouabaïn (C30H46O12) a very poisonous, amorphous glucosid which he also obtained from Strophanthus glaber to the extent of nearly 5 per cent (Pharm. Jour. Trans., Vol. XIX, 1888-89, pp. 162 and 606). It resembles strophanthin chemically, and is intensely deadly, 1/65-grain reputed to have been fatal. Locally it is reputed tenfold more powerful than cocaine as a local anaesthetic. It kills by its action upon the lungs and heart. It has been proposed as a remedy for whooping-cough (1/500 grain), but is evidently too dangerous a poison to be employed in such a malady.
ONOBAIO.—This arrow-poison is used by the inhabitants of Obok, situated on the Gulf of Aden. It occurs in small, brown resinous balls. Small doses of it arrest pulmonary action; large doses promptly arrest the action of both heart and lungs.
DAJAKSH.—The Borneo arrow-poison paralyzes the heart (Braidwood).
INCASSA POISON.—An ordeal bark of Africa said to be a violent heart-poison (Liebreich). (For other arrow and ordeal poisons, see under Nux Vomica.)