Cardiac glycoside

Overview
Cardiac glycosides are drugs used in the treatment of congestive heart failure and cardiac arrhythmia. These glycosides are found as secondary metabolites in several plants, but also in some animals. Some of these compounds (ouabain and some frog poisons) are used in Africa as arrow-poisons for hunting.

Function
Cardiac glycosides work by inhibiting the Na+/K+ pump. This causes an increase in the level of sodium ions in the myocytes, which then leads to a rise in the level of calcium ions. This inhibition increases the amount of Ca2+ ions available for contraction of the heart muscle, improves cardiac output and reduces distention of the heart.

They do this by stabilizing the E2-P transition state of the Na+/K+ pump. The proposed mechanism is the following: inhibition of the Na+/K+ pump leads to increased Na+ levels, which in turn slows down the extrusion of Ca2+ via the Na+/Ca2+ exchange pump. Increased amounts of Ca2+ are then stored in the sarcoplasmic reticulum and released by each action potential.

They have an antiarrhythmic effect by prolonging the refractory period of the AV node (Atrioventricular node), reducing the number of impulses reaching the ventricles. Cardiac output is restored but atrial fibrillation or atrial flutter are not abolished.

Examples
Examples of plants producing cardiac glycosides:
 * Strophanthus - ouabain g/k/e-strophanthin
 * Digitalis lanata and Digitalis purpurea - digoxin, digitoxin
 * Scilla maritima - proscillaridine A
 * Adonis vernalis, Adonis aestivalis
 * Acokanthera oblongifolia
 * Convallaria (lilly of the valley)

Some frog-poison contain bufalin, marinobufagenin and bufadienolides, cardiac glycosides.