The mode of action of cardiac glycosides

Throughout the 200 years during which the cardiac glycosides have been in therapeutic use, they have challenged the understanding of clinician and scientist alike. For the clinician the task has been to define the circumstances in which drugs of this class are indicated and to tread the narrow line between pharmacological activity and serious toxicity; neither problem has been entirely solved. For the scientific investigator, a curious paradox has emerged: whereas early workers sought to identify the precise site of action of digitalis, recent research has revealed that cardiac glycosides specifically inhibit a ubiquitous membrane transport process and this makes the apparent tissue specificity of these drugs the more surprising. The gap between the empirical knowledge of clinical experience and the scientific insights derived from laboratory biochemistry and electrophysiology has not yet been closed.