This section is from the book "A Treatise On Therapeutics, And Pharmacology Or Materia Medica Vol2", by George B. Wood. Also available from Amazon: Part 1 and Part 2.
This is the active principle of digitalis, first obtained separate by M. Homolle, of France, and abundantly proved, by the experiments of MM. Homolle and Quevenne, to concentrate in itself all the virtues of the medicine.* It is prepared, as recommended by these authors, in their elaborate trea-tise on the subject, published in Bouchardat's Archives (Jan. 1854), by forming an infusion, precipitating inert matter by subacetate of lead, precipitating the excess of the salt of lead by carbonate and phosphate of soda, separating the lime contained in the infusion by oxalate of ammonia, and then treating the filtered liquor with tannic acid. This forms with the digitalin an insoluble compound, which is mixed with protoxide of lead, then dried, and treated with alcohol. The oxide of lead separates the tannic acid, and the digitalin is dissolved by the alcohol, from which it is separated by distilling off the latter. It is purified from accompanying substances by means of highly concentrated ether, which leaves the digitalin sufficiently pure for use. The British Pharmacopoeia gives a process for its preparation, which is that of M. Homolle, simplified by M. 0. Henry.
Digitalin is in the form of a slightly yellowish powder; scarcely crystal-lizable; unalterable in the air; of a feeble, peculiar, aromatic odour; sternutatory when brought near the nostrils; of a taste intensely bitter, but slowly developed in the mouth; soluble in about 2000 parts of cold, and 1000 of hot water; very soluble in alcohol and chloroform, but very slightly so in concentrated ether; fusible by heat, but not volatilizable without change; inflammable; and neuter in its relations to acids and alkalies. It contains no nitrogen. Its characteristic property is that of forming a green solution in concentrated muriatic acid.
It has been claimed for digitalin that it is a perfectly well characterized principle, capable of being prepared of definite strength, possessing all the medical virtues of digitalis, and producing, as shown by numerous observations, precisely the same effects as that medicine, both in health and disease. Viewed in this light, it would form an excellent substitute for digitalis in substance, and has been used for the purpose to a very considerable extent. The advantages over the leaves, and their officinal preparations, which have been claimed for it, are the uniformity of its strength, and its facility of administration. According to MM. Homolle and Quevenne, it is most advantageously given in the form of minute pills or globules, in which the medicine is enveloped in a coating of sugar, so as to cover its taste. Upon the same authority, one part of it is equal to 50 parts of good digitalis, and 15 parts of that medicine of medium quality. According, however, to Dr. Stadion, of Kiew, who has experimented with digitalin, one part represents only 30 parts of the leaves. (Journ. de Pharm. et de Chim., 3e ser., xlv. 96.) Each globule, as prepared by MM. Homolle and Quevenne, contains one milligramme (about 1/65 part of a grain) of the digitalin, and five centigrammes (about | of a grain) of sugar, and may be considered as representing a grain of digitalis. In several instances, from forty to fifty of these granules, taken at once, have produced the most alarming effects, from which, however, the patient recovered, probably from the circumstance that the medicine produced copious vomiting. (Ibid., Nov. 1857, p. 393.) In a fatal case of poisoning, with symptoms similar to those produced by digitalis, a substance was obtained from the tissues and dejections of the patient, which answered to the chemical tests for digitalin, and which, administered to the lower animals, caused death with the characteristic phenomena of that poison; and the inference was that the patient died from an excessive dose of digitalin. (Archives Generates, 6e ser., iii. 755, Juin, 1864.)
* Unfortunately, the discoverer conferred upon it the name of digit aline, reserving that of digitalin for another peculiar principle contained in the leaves, which, however, is quite inert. According to the English pronunciation of these words, there is too little difference in their sound to admit of the retention of them both; and I therefore use the term digitalin to express the active principle, which is in accordance with the nomenclature for substances of this kind, adopted in the U. S. Dispensatory.
The symptoms of poisoning by digitalin are essentially the same as those of digitalis. Attention, however, has been called by Dr. Stadion to a severe irritation of the nasal passages, with violent coryza, as one of the peculiar and characteristic effects of that principle. (Journ. de Pharm. et de Chim , 3e ser., xlv. p. 96.) Dr. Faure, from his experiments with digitalin, inferred that the vomiting, so generally produced by it, is peculiar; differing in some respects from that resulting from ordinary emetics. The action of the stomach is not the first nor principal one. On the contrary, it succeeds a series of contractions occurring elsewhere; generally beginning in the limbs, and lower part of the abdomen, and thence extending to the thorax, which hollows itself as in forced expiration. The vomiting too is intermittent, and during the interval the animal appears almost in its natural state till the paroxysm returns. (Archives Generates, Oct. 1864, p. 413.)
The dose of digitalin is one globule, to be given twice or three times a day, and managed in other respects as recommended above for the powdered leaves. A tincture of digitalin, prepared by dissolving one grain in a fluidounce of alcohol, would have the average strength of good tincture of digitalis, and might be given in the same dose.* in regard to the other effects of digitalin, Dr. Stadion found it first to increase, then to diminish the frequency of the pulse; to produce rapid emaciation, and retardation of nutrition; to resemble digitalis in its action on the circulation, the nervous and muscular functions, and that of generation, but to be less disposed than digitalis to disturb the alimentary canal; to produce a characteristic coryza; and to have 30 times the strength of the leaves. (See Am. J. of Med. Sci., July, 1864, p. 220.)
* Influence of digitalin on the urine, etc. Dr. B. H. Stadion, of Kiew, inferred from his experiments that digitalin lessens the proportion of liquid in the urine in health; diminishes also the amount of its solid constituents generally, as urea, chloride of sodium, the sulphates and the phosphates, but increases the uric acid; and lowers the specific gravity of the secretion. But. Dr. Stadion is quite premature in deciding from these experiments that it is not diuretic. To produce an increased action on the kidneys, it must be given in general for several days; and sometimes even one or two weeks elapse before this effect is experienced; but, when digitalis does begin to act on the kidneys, I know no medicine which equals it in efficiency. Nor is this effect owing, as some have supposed, to its ameliorating influence on cardiac disease; for I have seen it equally efficacious when the heart was perfectly healthy.
These claims of digitalin, as procured by the process of M. Homolle, have been disputed of late; and it is asserted that, instead of being a single, distinct, and well-characterized principle, it is in fact complex, and often separable into three different substances, of which the proper bitter principle, or digitalin, is one. Nevertheless, experience seems to have shown that it has sufficient uniformity of character and of power to be capable of beneficial use as a substitute for the leaves or their ordinary preparations. (Bouchardat, Ann. de Thérap., 1866, p 121.)
Attempts have been made to employ both digitalis and digitalin by the endermic method; but they occasion so much irritation in the denuded surface, that their use in this way is inconvenient. Digitalin has been administered, with asserted benefit, in cases of cardiac disease, by subcutaneous injection. it is said, thus administered, to act much more promptly and powerfully than by the stomach. But there can be few conditions in which this mode of giving the medicine can be desirable, and with a substance so powerful and yet so uncertain, I do not think that the subcutaneous method of exhibition is advisable.
Physiological test of digitalin. A series of very elaborate experiments were instituted by Drs. C. \l. Fagge and Thos. Stevenson, to discover some reliable physiological test for digitalin, as there is no chemical test upon which a sure reliance can be placed. They determined that, when introduced into the subcutaneous tissues of frogs, whether simply dissolved, or in diversified mixture, it produced three characteristic effects with almost absolute certainty; 1. a peculiar irregularity in the heart's action; 2. the stoppage of the action while in the contracted state, and 3. the retention of voluntary power at least 15 or 20 minutes after the heart has ceased to act. No other known poison produces this series of effects. (Guy's Hospital Reports, 1860, p. 80.) - Note to the third edition.