@article {HATCHER113, author = {ROBERT A. HATCHER and CARY EGGLESTON}, title = {THE EMETIC ACTION OF THE DIGITALIS BODIES}, volume = {4}, number = {2}, pages = {113--134}, year = {1912}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Emesis is one of the most common symptoms of poisoning with the members of the digitalis group. All of the digitalis bodies are capable of causing emesis, but the different members of the group apparently show much greater differences in emetic, than in cardiac, activity with a given species of animal. The view generally held that this emetic action occurring with the clinical use of the digitalis bodies is due wholly or chiefly to the direct irritant action on the mucous membrane of the stomach, is based upon the fact that all of the drugs of the group exert an irritant action upon certain mucous membranes and upon subcutaneous tissues, and upon the results obtained by introducing into the stomach amounts much greater than those used clinically. Such massive doses of the digitalis bodies may cause emesis by their direct irritant action on the gastric mucous membrane but we are not concerned at present with that phase of the question. The intensity of this irritation of the mucous membranes probably depends largely upon the solubility, and other physical properties, of the agent, and upon the function of the mucous membrane, particularly, its capacity for absorbing the drug, or resisting its absorption. The absorbability of the different digitalis bodies from the gastro-intestinal tract of the cat and dog, and their emetic activity after oral administration to those animals go in the same direction but not strictly parallel. Ouabain apparently does not irritate the mucous membrane of the rat{\textquoteright}s gastro-intestinal canal, from which it is not absorbed even after the administration of very large doses. We know little of the distribution of the digitalis bodies in the animal organism during the period after they leave the blood stream and before they are excreted, hence there is no sufficient basis for the argument that a drug of this group which induces emesis promptly after its intravenous administration, and only after a much longer interval following its oral use, must therefore be capable of acting directly upon the vomiting center in the medulla. It is quite true, however, that such emetic action after the intravenous administration does serve to direct attention to the probability of its being of central origin in those cases. All of the digitalis bodies which we have tested in this way induce emesis more promptly when they are injected intravenously than when they are administered by the mouth, and smaller doses are required by the vein than by the mouth for this purpose. No conclusive evidence has been afforded hitherto concerning the seat of the emetic action of moderate doses of any of the digitalis bodies. The amounts of ouabain and strophanthus which are required by the vein to induce emesis in eviscerated dogs are very much less actually, as well as relatively in proportion to their weight, than are the amounts of these drugs which have been used clinically by the mouth, and in some cases without perceptible effects. Our experiments on eviscerated dogs prove conclusively that those digitalis bodies which we employed in this way are capable of inducing emesis, or nausea and vomiting movements, in dogs without the participation of the action on the gastro-intestinal tract. The results obtained after the oral administration of strophanthus and ouabain to man and the similarity of the behavior of the digitalis bodies in man, to that observed in the cat and dog, leave no ground for supposing that the mechanism of the emetic action in man is in any way different from that seen in those animals, hence we are led irresistibly to the conclusion that the emesis sometimes seen in man after the oral administration of therapeutic doses of digitalis bodies is due mainly, if not exclusively to their action on the vomiting center in the medulla.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/4/2/113}, eprint = {https://jpet.aspetjournals.org/content/4/2/113.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }