In 1785, Sir William Withering described the use of the foxglove plant, Digitalis purpurea, for treatment of heart failure . More than 200 years later, cardiac glycosides are still prescribed for patients with atrial fibrillation and heart failure or left ventricular dysfunction.
While the overall use of digitalis has declined, the number of patients admitted with digitalis toxicity has remained stable and the use of digitalis antibody fragments has increased . In 2011, there were 2513 cases of cardiac glycoside exposures reported to US poison control centers. Of these, 132 patients suffered major toxicity and 27 died .
In addition to digitalis, other cardiac glycosides exist and have been associated with toxicity. These include: the xenobiotics ouabain and lanatoside C; various plants, including foxglove, dogbane, red squill, lily of the valley, oleander, and henbane; and bufadienolides, cardioactive steroids found in the skin of toads belonging to the Bufonidae family . In 2011, there were an additional 1376 cases of cardiac glycoside exposure from various plant species .
The pharmacology, diagnosis, and management of acute and chronic digitalis poisoning will be reviewed here. The dosing of digoxin-specific antibody (Fab) fragments for the treatment of digoxin toxicity and the therapeutic use of digoxin are discussed separately. (See "Dosing regimen for digoxin-specific antibody (Fab) fragments in patients with digoxin toxicity" and "Use of digoxin in heart failure due to systolic dysfunction" and "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy", section on 'Digoxin' and "Treatment with digoxin: Initial dosing, monitoring, and dose modification".)
PHARMACOLOGY AND CELLULAR TOXICOLOGY
Cardiac glycosides all possess a steroid nucleus with an unsaturated lactone at the C17 position, and at least one glycosidic residue at the C3 position (figure 1) . Cardiac glycosides are used primarily to increase inotropy in cardiac myocytes, but also affect cells in the vascular smooth muscle and sympathetic nervous system [5-7].