Digitalis Folia, B.P. Digitalis Leaves.
Digitalis or foxglove leaves (Digitalis, U.S.P.) are obtained from the foxglove, Digitalis purpurea, Linn. (N.O. Scrophularineae), a biennial herb, widely distributed throughout Europe and common in England. The leaves should be collected when the plant is in full flower, and dried immediately after collection. They are from 10 to 30 centimetres in length, and may be as much as 12.5 to 15 centimetres in breadth, with a winged petiole of varying length, down which the lower lateral veins are usually decurrent; broadly ovate to lanceolate in shape, the apex being blunt or sub-acute, the margin irregularly crenate or crenate-dentate. The upper surface is rugose, dull green in colour, and bears numerous short hairs; the under surface is paler and very hairy; the mid-rib is prominent, the lateral veins leaving it at a somewhat acute angle, and curving round towards the apex. Odour, faint; taste, bitter. The Brussels Conference agreed that the second year's leaf alone should be used, and that the entire leaf should be powdered. No well-defined characters are known by which the leaves of the second year's plant, which are alone official, can be distinguished from those of the first year, but the former usually contain a larger proportion of broadly ovate leaves than the latter. The separation is, however, not material, as the two appear to have identical therapeutical value. The epidermis of both surfaces consists of cells with thin wavy walls, is provided with small stomata, and numerous simple and glandular hairs. The simple hairs commonly consist of three to five (occasionally more) elongated cells with thin and often warty walls, the cells being frequently collapsed. The glandular hairs are short and provided with a unicellular or bicellular gland. The leaf contains no sclerenchymatous fibres, or crystals of calcium oxalate. Digitalis leaves and powder should be dried in a desiccator and kept in hermetically sealed vessels. Some growers of repute now supply the leaves carefully dried in small sealed containers; these should alone be employed in making pharmaceutical preparations. The leaves may be of English or German origin. The proportion of digitoxin in these two varieties shows no appreciable difference. The leaves, especially those offered in the crushed or powdered state, are occasionally adulterated, leaves of the following plants being liable to be substituted or mistaken for the true drug:—Mullein leaves (Verbascum Thapsus, Linn.), which are woolly, and have branched hairs; comfrey leaves (Symphytum officinale, Linn.), lanceolate, with isolated stiff hairs; primrose leaves (Primula vulgaris, Huds.) which are spathulate, and have straight lateral veins; ploughman's spikenard leaves (Inula Conyza, D C.), with an entire or dentate margin, the teeth bearing horny points. Matico leaves (Piper angustifolium, Ruiz and Pay.) are distinguished by the depressed veinlets on the upper surface.
Constituents.—The chief active constituents of digitalis leaves are the glucosides digitoxin and digitalin, but distinctive names have been given to various other substances or mixtures extracted from the leaves. Digitoxin, the most powerful constituent, is a well-defined crystalline substance, and is present to the extent of about 0.22 to 0.40 per cent., the average being 0.28 during August and September, after which the quantity rapidly diminishes. Digitalin is amorphous and completely soluble in chloroform. The name "digitalein" has been given to a white amorphous powder, which is soluble in water, but insoluble in chloroform or ether; it is doubtful, however, if this is a definite body. A crystalline substance named digitophyllin has also been obtained from the leaves, but it is equally doubtful if this is a definite body. Digitonin is a crystalline glucoside belonging to the class of saponins; it is present in the leaves and possibly also in the seeds, dissolves with difficulty in water, but is much more soluble when mixed with digitalin, the solubility of which it also increases. The substance named digitoflavone has been shown to be identical with luteolin. The name "gitalin" has recently been given to an alleged definite glucoside obtained from an aqueous extract of digitalis; it is described as forming a crystalline hydrate. The existence of much of the confusion regarding the chemistry of digitalis is due to the fact that investigations have been mostly conducted with the seeds rather than the leaves.
Action and Uses.—Digitalis increases the activity of all forms of muscle tissue, but more especially that of the heart and arterioles. The arterioles become constricted and blood pressure in consequence rises. Upon the heart it exerts a double action; the diastole is prolonged on account of vagus stimulation, and the efficiency of systole is much increased, so that in spite of the slowing the output of blood per minute is augmented. Digitalis is employed in most forms of cardiac failure. It improves the nutrition of the heart by increasing the amount of blood forced through the coronaries, and also by prolonging diastole, i.e., increasing the period of rest. It improves the circulation generally by sending more arterial blood from the left ventricle, so that in cases of venous congestion from cardiac failure it removes oedema and increases the urine. It is not, however, a diuretic to the normal individual. In Bright's disease it is generally inferior to strophanthus, because in this condition the blood pressure is already high, and digitalis by further constricting the vessels will make it higher. In specific fevers and other conditions in which cardiac failure may ensue, it should be given early, so that the drug may be acting when the danger threatens. In ordinary conditions it takes about twelve hours before its effect on heart muscle is appreciated. Digitalis is cumulative, and when given over a prolonged period should be employed with caution. The constant use of digitalis, by increasing the activity of the heart, leads to hypertrophy of that organ. Digitalis has also been employed in the treatment of internal haemorrhage. It must not, however, be forgotten that in proportion as it constricts vessels, it raises blood pressure. Digitalin possesses the action on the heart peculiar to digitalis without being cumulative. Digitoxin is cumulative in its action, and is the most poisonous of all the constituents of digitalis. Although digitoxin is the most active constituent of digitalis leaves the relative activity of the drug cannot be determined by the chemical estimation of this substance, since digitalin and possibly other bodies also contribute to the medicinal action of the leaves, and because purification of the glucoside alters its toxicity; nor has the proposal to effect a valuation of the leaves by determining the quantity necessary to kill a certain weight of frog within a certain time been generally accepted, although in the absence of a chemical standard this is the only method by which even an approximate estimation of physiological activity can be obtained. The pharmacist should collect the leaves at the proper time, dry them thoroughly, and keep them perfectly dry, under which conditions they retain their activity, whereas air-dry leaves rapidly become less efficacious. Powdered digitalis leaf isadministered in pill form as Pilula Digitalis Composita. Tincture of digitalis is in the commonest use. Infusion of digitalis is an active and reliable preparation preferred by many to the tincture. The glucosides of digitalis are more soluble in warm water in their natural state of combination than when separated from the leaves. The freshly prepared infusion contains the digitoxin and digitalin of the leaf. Infusum Digitalis Concentratum and Succus Digitalis are alternative liquid preparations. It should be noted that pure digitalin is not a commercial article, and that, when the name "digitalin" appears without qualification in prescriptions, Digitalinum pulverisatum burum Germanicum (see Digitalinum) should usually be dispensed. Amorphous or "chloroformic" digitalin (Digitaline amorphe, Homolle) consists largely of digitoxin, with some true digitalin, French "crystalline digitalin" (Digitaline cristallisée, Nativelle) consists almost entirely of digitoxin, but German "crystalline digitalin" consists of digitonin. Digalen is a standardised solution of digitoxin, containing 0.3 milligram in 1 mil. Digipuratum is a standardised extract of digitalis, which is stated to be of uniform strength and to contain all the constituents of digitalis leaves which are of therapeutic value; it is said to contain digitalin and digitoxin in the form of tannates, and to be free from digitonin. In cases of poisoning by digitalis, with a very slow and irregular pulse the administration of atropine is generally all that is necessary. In the more severe cases with the very rapid heart beat the stomach pump must be used and drugs may be used which depress and diminish the irritability of the heart; such as chloral and chloroform; amyl nitrite may also be found useful.
Dose.—3 to 12 centigrams (1 to 2 grains).
- Extractum Digitalis, U.S.P.—EXTRACT OF DIGITALIS.
- Fluidextract of digitalis, 100. The fluidextract is evaporated at a temperature not exceeding 50° to a pilular consistence. Average dose.—10 milligrams (1/5 grain).
- Fluidextractum Digitalis, U.S.P.—FLUIDEXTRACT OF DIGITALIS.
- Digitalis, in No. 60 powder, 100; alcohol (49 per cent,), sufficient to produce 100. Average dose.—5 centimils (0.05 milliliters) (1 minim).
- Infusum Digitalis, B.P.—INFUSION OF DIGITALIS.
- Digitalis leaves, in No. 20 powder, 0.68; distilled water, boiling, 100. Infuse the drug in the water for fifteen minutes, in a covered vessel, and strain. Infusion of digitalis is considered by many physicians the most active and trustworthy preparation of digitalis. Dose.—8 to 16 mils (2 to 4 fluid drachms).
- Infusum Digitalis, U.S.P.—INFUSION OF DIGITALIS, U.S.P.
- Digitalis, bruised, 1.5; alcohol (95 per cent.), 10; cinnamon water, 15; boiling water, 50; cold water, sufficient to produce 100. Infusion of Digitalis, U.S.P., is prepared by pouring the boiling water upon the bruised digitalis, allowing to macerate for one hour, then straining, adding the alcohol and cinnamon water, and passing sufficient cold water through the strainer to produce 100 by volume. Average dose.—8 mils (2 fluid drachms).
- Infusum Digitalis Concentratum, B.P.C.—CONCENTRATED INFUSION OF DIGITALIS.
- A product closely resembling infusion of digitalis is obtained by diluting 1 part of this preparation with 7 parts of distilled water. This preparation deteriorates on keeping for more than a month, and should only be used in emergencies. It should be stored in small, completely filled, and well-closed bottles, protected from light. Dose.—1 to 2 mils (15 to 30 minims).
- Pilulae Digitalis Compositae, B.P.C.—COMPOUND DIGITALIS PILLS. Syn.—Pilulae Digitalis cum Scilla; Guy's Pills; Niemeyer's Pills.
- Each pill contains 1 grain each of powdered digitalis leaves, powdered squill, and mercury pill; with syrup of glucose. Bailie's or Gilmour's Pills contain twice as much squill as is specified in the above formula. Dose.—1 or 2 pills.
- Pilulae Digitalis et Opii Compositae, B.P.C.—COMPOUND DIGITALIS AND OPIUM PILLS. Syn.—Dr. Heim's Pills.
- Each pill contains 1/2 grain of powdered digitalis leaves, 1/4 grain of powdered opium, 1/6 grain of powdered ipecacuanha root, 1 grain of quinine sulphate, with syrup of glucose. Dose.—1 or 2 pills.
- Succus Digitalis, B.P.C.—DIGITALIS JUICE.
- An active preparation reputed not to cause nausea. Dose.—3 to 6 decimils (0.3 to 0.6 milliliters) (5 to 10 minims).
- Tinctura Digitalis, B.P.—TINCTURE OF DIGITALIS.
- Digitalis leaves, in No. 20 powder, 12.5; alcohol (60 per cent.), sufficient to produce 100. Prepared by the percolation process. This tincture is best made in small quantities, and should be preserved in bottles which are quite filled, until required for use; it should be recently prepared, as it deteriorates if kept for a prolonged period. Tincture of digitalis is used for its action on the heart and circulation. Dose.—3 to 10 decimils (0.3 to 1.0 milliliters) (5 to 15 minims).
- Tinctura Digitalis, P.I.—TINCTURE OF DIGITALIS, P.I.
- Strength, 10 per cent. Prepared by percolation with alcohol (70 per cent.).
- Tinctura Digitalis, U.S.P.—TINCTURE OF DIGITALIS, U.S.P.
- Digitalis, in No. 60 powder, 10; alcohol (49 per cent.), sufficient to produce 100. Average dose.—1 mil (15 minims).
The British Pharmaceutical Codex, 1911, was published by direction of the Council of the Pharmaceutical Society of Great Britain.