Strophanti Semina, B.P., Strophantinum.
STROPHANTHI SEMINA, B.P.
STROPHANTHUS SEEDS.
Strophanthus seeds (Strophanthus, U.S.P.) are obtained from Strophanthus Kombé, Oliver (N.O. Apocynaceae), a climbing plant indigenous to eastern tropical Africa. The fruit of the strophanthus consists of two large elongated, divergent follicles, with fleshy pericarp; these, deprived of their epicarp and mesocarp and dried, are sometimes imported. They contain numerous seeds, each with a long awn terminating in a feathery plume. The dried, ripe seeds are usually imported deprived of their awns and plumes. They are then oval and acuminate, about 15 millimetres long and 4 millimetres broad, of a greyish or greenish-fawn colour, and covered silvery, appressed hairs directed towards the apex. They are flattened and narrowed towards the base, and provided on one side with a longitudinal ridge running from the centre to the apex of the seed. The transverse section shows a whitish, oily kernel, consisting of two straight cotyledons surrounded by a narrow endosperm. The odour, especially of the crushed seeds, is characteristic; the taste, very bitter. A transverse section moistened with sulphuric acid (preferably 80 per cent. strength) assumes, at least in the endosperm, but sometimes in the cotyledons as well, a fine, green colour. The seed-coats, examined under the microscope, are seen to be free from crystals of calcium oxalate. The commercial drug is not unfrequently mixed with the seeds of other species of strophanthus; the genuine seeds are best recognised by their greenish or fawn colour, by their hairs, which are satiny, not woolly, by the absence of calcium oxalate from the embryo, and almost total absence from the seed-coat, and by the green reaction with sulphuric acid. On incineration, the drug yields about 4 per cent, of ash. The following are the chief varieties of strophanthus seeds, other than those of S. Kombé, that have been met with in commerce:—(1) S. hispidus, DC.;these are smaller than the genuine, brownish in colour, bear scattered hairs, and give with sulphuric acid a green reaction; they contain strophanthin. (2) S. Courmonti, Sacleux;these usually have a brownish tinge, but sometimes closely resemble the B.P. variety, from which, however, they may be distinguished by their smaller size, more lanceolate shape, less bitter taste, abundant, prismatic crystals of calcium oxalate in the seed-coat, and by the red reaction with sulphuric acid. (3) S. Nicholsoni, E. M. Holmes;the seeds are whitish and woolly, the hairs project beyond the apex of the seed, and the reaction with sulphuric acid is red. (4) S. gratus, Baill.;the seeds are brown and glabrous, they give a red reaction with sulphuric acid, and contain the glucoside ouabain, identical with that found in the wood of Acokanthera Schimperi, and much more toxic than strophanthin. (5) S. Emini, Aschers;the seeds are greyish-green, contain cluster-crystals of calcium oxalate, and give a red reaction.
Constituents.—The seeds contain from 8 to 10 per cent. of a crystalline glucoside, named strophanthin, together with about 30 per cent. of fixed oil. Strophanthin yields, on hydrolysis with a dilute mineral acid, strophanthidin. The drug also contains kombic acid, choline, and trigonelline.
Action and Uses.—The properties of strophanthus seeds are virtually those of the glucoside strophanthin (see Strophanthin), but the tincture or extract of the seeds is generally preferred to the active principle. They are used in place of digitalis when a heart action only is required and the tension of the pulse is already high. Strophanthus differs from digitalis, not only in its smaller effect on blood vessels, but in its smaller action on the vagus nerve. It does not, therefore, slow the heart to the same extent as digitalis. It is, however, undoubtedly a more dangerous drug to use, since it is easily absorbed and much more readily induces delirium cordis. In mitral disease with failure of compensation, in the cardiac weakness of pneumonia and other acute illnesses, strophanthus is of especial value, and it sometimes succeeds when digitalis fails. Strophanthus may be standardised by determining the minimal lethal dose for a certain weight of heart. One-quarter minim of the B.P. tincture should be sufficient to arrest the heart in systole of a frog weighing 20 grammes in about one hour. The tincture is the most generally used preparation of strophanthus; it is extremely rapid in its action, and should be given in small doses, 1 to 3 decimils (0.1 to 0.3 milliliters) (2 to 5 minims); the B.P. dose is considered to be too large. Extract of strophanthus is used in pills when a slower and more prolonged action is desired. In cases of poisoning by strophanthus, apply the stomach pump, or give emetics, followed in either case by all aqueous solution of gallic or tannic acid, and stimulants. The heart becomes very rapid, beats are dropped, and later it becomes uncountable, entering into the condition known as "delirium cordis." Death occurs suddenly. Everything should be done which is likely to depress the increased irritability of the heart; perhaps inhalations of chloroform are most likely to be successful.
Dose.—3 to 6 centigrams (½ to 1 grain).
PREPARATIONS.
- Extractum Strophanthi, B.P.—EXTRACT OF STROPHANTHUS.
- Strophanthus seeds, in No. 30 powder, 50; purified ether, a sufficient quantity; alcohol, a sufficient quantity; milk sugar, sufficient to produce 100. Dry the powdered strophanthus seeds at 43°, pack in a percolator, moisten with ether, allow to macerate for twenty-four hours, then percolate with ether until it passes through uncoloured. Dry the marc at a temperature not exceeding 49°, reduce it to powder, moisten with the alcohol, allow to macerate for forty-eight hours, then allow percolation to proceed slowly until the product measures 500. Remove most of the alcohol by distillation or evaporation, concentrate the residue until it begins to thicken, and mix with sufficient finely-powdered milk sugar to make up to the required weight of powdered extract. It is officially directed that the powder, after treatment with ether, should be repacked in the percolator and then moistened with the alcohol, but it is better to moisten the drug before placing it in the percolator. Extract of strophanthus, when ordered in pills, may be rubbed with a little powdered liquorice root and massed with syrup of glucose. Dose.—15 to 60 milligrams (¼ to 1 grain).
- Tinctura Strophanthi, B.P.—TINCTURE OF STROPHANTHUS.
- Strophanthus seeds, in No. 30 powder, 2.5; alcohol (70 per cent.), sufficient to produce 100. Add 0.6 of the alcohol to the drug, after packing it in a percolator, and allow to macerate for forty-eight hours; then percolate slowly with successive portions of the alcohol until the product measures 50, filter, and add sufficient of the alcohol to make up to the required volume. Tincture of strophanthus is used as a cardiac tonic. Its action is extremely rapid, and it is therefore preferred in sudden heart failure. It is given in small doses to prevent cardiac failure in acute diseases. The B.P. dose is considered to be too large; the best results are obtained with doses of 1 to 3 decimils (0.1 to 0.3 milliliters) (2 to 5 minims). It is well to use a standardised tincture of such a strength that ¼ minim will kill a 20-gramme frog in an hour by causing the heart to stand still in systole. As tincture of strophanthus varies so greatly in its activity, this method of adopting a physiological standard is the only one which, at present, ensures a reliable tincture. Dose.—3 to 10 decimils (0.3 to 1.0 milliliters) (5 to 15 minims).
- Tinctura Strophanthi, B.P. 1885.—TINCTURE OF STROPHANTHUS, B.P. 1885.
- Strophanthus seeds, in No. 30 powder, 5; ether, a sufficient quantity; rectified spirit, sufficient to produce 100. The seeds are defatted with the ether, and then percolated with the spirit. Dose.—1 to 6 decimils (0.1 to 0.6 milliliters) (2 to 10 minims).
- Tinctura Strophanthi, P.I.—TINCTURE OF STROPHANTHUS, P.I.
- Strength, 10 per cent. Prepared by percolation with alcohol (70 per cent.), the seeds not being previously freed from fat.
- Tinctura Strophanthi, U.S.P.—TINCTURE OF STROPHANTHUS, U.S.P.
- Strophanthus, in No. 60 powder, 10; alcohol (62 per cent.), sufficient to produce 100. Average dose.—5 decimils (0.5 milliliters) (8 minims).
STROPHANTHINUM.
STROPHANTHIN.
C40H66O19 = 850.528.
Strophanthin, C40H66O19, is a glucoside obtained from the seeds of Strophanthus Kombé, Oliver (N.O. Apocynaceae), and other species. It is official in the U.S.P. It may be isolated from the freshly powdered seeds by extracting first with ether or carbon bisulphide to remove fat, and then with 70 per cent. alcohol, distilling off the latter, dissolving the residue in water, and filtering. To the filtrate tannic acid is added, but an excess must be avoided as the precipitate is soluble in excess; the precipitate is washed and then mixed with lead oxide, dried, and extracted with alcohol. To this alcoholic solution a considerable volume of ether is added, and the separated strophanthin collected, and dried in vacuo. Strophanthin occurs in the form of a pale yellow, amorphous powder, or as a white, micro-crystalline powder containing varying amounts of water of crystallisation, having an intensely bitter taste and a faintly acid reaction; it is very poisonous. The aqueous solution is optically inactive, and neutral to litmus. Melting-point, 170° to 172°; on complete ignition the strophanthin burns without leaving any residue. The air-dried substance contains three molecules of water of crystallisation, which, on heating, is given off, but not without decomposition of the glucoside. The anhydrous substance is said to melt at 167°. With concentrated sulphuric acid it is immediately coloured green to orange, then quickly red to red-brown, and on warming dark brown and finally green. If to an aqueous solution a trace of ferric chloride and a few mils of sulphuric acid be added, a red-brown precipitate will be produced, turning dark green after one or two hours. On heating with diluted mineral acids (about 10 per cent.) various shades of a green colour, changing to violet or blue are produced, and are more or less characteristic. Strophanthin is precipitated from its solutions by tannic acid. Concentrated hydrochloric acid dissolves it, making a colourless solution which, later, assumes a greenish shade, and on warming a yellowish-green colouration, finally, with separation of the coloured products. A solution of phenol in strong sulphuric acid dissolves it, on warming, with a violet colouration, later becoming green. By decomposition with mineral acids the glucoside is split up into strophanthidin, C27H38O7 (insoluble in water or ether, but easily soluble in alcohol and acetone; melting-point, 169° to 170°), and strophanthobiose methyl ether, C12H21O10CH3. Pseudo-strophanthin, C40H60O16, is a glucoside which has been isolated from an undetermined variety of strophanthus seeds, but is not present in Strophanthus Kombé. It melts at 179°, is slightly laevorotatory, and gives a red colouration with sulphuric acid. It is hydrolysed on boiling with weak hydrochloric acid. It differs from strophanthin both chemically and physiologically, and is nearly twice as toxic. It is probably identical with ouabain obtained from S. gratus, Baill.
Freely soluble in water and in alcohol; almost insoluble in ether, chloroform, benzene, or carbon bisulphide; slightly soluble in acetone; very slightly soluble in amyl alcohol, which extracts it in small quantity from aqueous solution.
Action and Uses.—Strophanthin acts on the heart similarly to digitalis, but while digitalis produces marked peripheral vasoconstriction, strophanthin is almost without this action. It is absorbed more rapidly, is non-cumulative, and is less likely to produce gastro-intestinal irritation than digitalis. It is a more efficient diuretic, as it raises blood pressure without producing constriction of the renal vessels, so that more blood passes through the kidneys. Strophanthin is rarely employed, on account of its variable toxicity. It is an extremely powerful poison, arresting the action of the heart in systole; commercial specimens of the active principle vary in toxicity, and it should be used with great caution. A freshly prepared solution in distilled water (1 in 1000) is used by intramuscular injection; hypodermic injections are absorbed less readily, and may give rise to inflammation. Small doses have been given intravenously with great success in urgent cases. In cases of poisoning by strophanthin, apply the same treatment as in the case of strophanthus seeds.
Dose.—⅕ to ⅓ milligram (1/300 to 1/200 grain) increased to 1 milligram (1/60 grain).
