§ 537. Fatal Dose.—The circumstance of commercial digitalin consisting of varying mixtures of digitoxin, digitalin, and digitalein, renders it difficult to be dogmatic about the dose likely to destroy life. Besides, with all heart-poisons, surprises take place; and very minute quantities have a fatal result when administered to persons with disease of the heart, or to such as, owing to some constitutional peculiarity, have a heart easily affected by toxic agents. Digitoxin, according to Kopp’s[563] experiments, is from six to ten times stronger than digitalin or digitalein. Two mgrms. caused intense poisonous symptoms. Digitoxin is contained in larger proportions in Nativelle’s digitalin than in Homolle’s, or in the German digitalin. The digitalin of Homolle is prescribed in 1 mgrm. (·015 grain) doses, and it is thought dangerous to exceed 6 mgrms.
[563] Archiv f. exp. Pathol. u. Pharm., vol. iii. p. 284, 1875.
Lemaistre has, indeed, seen dangerous symptoms arise from 2 mgrms. (·03 grain), when administered to a boy fifteen years old. It may be predicated from recorded cases and from experiment, that digitoxin would probably be fatal to an adult man in doses of 4 mgrms. (1⁄16 grain), and digitalin, or digitalein, in doses of 20 mgrms. (·3 grain). With regard to commercial digitalin, as much as from 10 to 12 mgrms. (·15 to ·18 grain) have been taken without a fatal result; on the other hand, 2 mgrms. gave rise to poisonous symptoms in a woman (Battaille). Such discrepancies are to be explained on the grounds already mentioned. It is, however, probable that 4 mgrms. (or 1⁄16 grain) of ordinary commercial digitalin would be very dangerous to an adult.
It must also, in considering the dose of digitalin, be ever remembered that it is a cumulative poison, and that the same dose—harmless if taken once—yet, frequently repeated, becomes deadly: this peculiarity is shared by all poisons affecting the heart. When it is desired to settle the maximum safe dose for the various tinctures, extracts, and infusions of digitalis used in pharmacy, there is still greater difficulty, a difficulty not arising merely from the varying strength of the preparations, but also from the fact of the vomiting almost invariably excited by large doses. Individuals swallow quantities without death resulting, simply because the poison is rapidly expelled; whereas, if the œsophagus was ligatured (as in the experiments on the lower animals formerly favoured by the French school of toxicologists), death must rapidly ensue. The following table is a guide to the maximum single dose, and also the amount safe to administer in the twenty-four hours in divided doses. As a general rule, it may be laid down that double the maximum dose is likely to be dangerous:—
TABLE SHOWING THE MAXIMUM SINGLE DOSE, AND MAXIMUM QUANTITY OF THE DIFFERENT PREPARATIONS OF DIGITALIS, WHICH CAN BE ADMINISTERED IN A DAY.
| Single Dose. | Per Day. | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Grains or Minims. | Grammes or c.c’s. | Grains or Minims. | Grammes or c.c’s. | |||||||||
| Powdered Leaves, | 4 | 1⁄2 | grns. | ·3 | grm. | 15 | ·4 | grns. | 1 | ·0 | grm. | |
| Infusion, | 480 | m. | 28 | ·3 | c.c. | 1440 | m. | 84 | ·9 | c.c. | ||
| Tincture, | 45 | m. | 3 | c.c. | 135 | m. | 9 | c.c. | ||||
| Digitalin, | ·03 | grn. | ·002 | grm. | ·09 | grn. | ·006 | grm. | ||||
| Extract, | 3 | ·0 | „ | ·2 | „ | 12 | ·0 | „ | ·8 | „ | ||
§ 538. Statistics.—The main knowledge which we possess of the action of digitalis is derived from experiments on animals, and from occasional accidents in the taking of medicines; but in comparison with certain toxic agents more commonly known, the number of cases of death from digitalis is very insignificant. Of 42 cases of digitalis-poisoning collected by Husemann, 1 was criminal (murder); 1 the result of mistaking the leaves for those of borage; 42 were caused in medicinal use—in 33 of these last too large a dose had been given, in 3 the drug was used as a domestic remedy, in 2 of the cases the prescription was wrongly read, and in 1 digitalis was used as a secret remedy. Twenty-two per cent. of the 45 were fatal.