CARDIAC GLYCOSIDES are a class of drugs derived from the leaf of Digitalis spp. foxgloves. These drugs have a pronounced effect on the failing heart, increasing the force of contraction, so they have commonly been used to increase the force of contraction in congestive HEART FAILURE TREATMENT (see also CARDIAC STIMULANTS). Also, they correct certain abnormal heart rhythms (especially rapid atrial fibrillation) and are therefore used in antiarrhythmic treatment (see ANTIARRHYTHMICS). The greater effectiveness of ACE inhibitors in prolonging survival in patients with heart failure has led to a decrease in their use in patients with sinus rhythm (though they are effective).
Cardiac glycosides are used much less than previously, because doses that are useful therapeutically are close to those that are toxic, and the dose must be carefully adjusted in the individual. An important determinant of concentration in the body is the rate of metabolism and excretion, and some of the shorter-acting glycosides (e.g. ouabain) are now no longer used. Examples of cardiac glycosides include digitoxin and digoxin. Chemically, they are comprised of three components, a steroid ring structure, a lactone and a sugar moiety containing some unique monosaccharides. The lactone ring is essential for activity, but the steroid moiety can be replaced.
The mechanism of action of cardiac glycosides has always been a subject of debate. The main site at which glycosides act is the Na+/K+-ATPase of the cell membrane, which constitutes the Na+/K+ pump, and they bind to the K+-binding site, thus inhibiting the enzyme (see ATPASE INHIBITORS). This inhibition, through a series of interrelated actions, eventually causes depolarization and affects cardiac rhythm. There is also an eventual increase in sarcoplasmic calcium content and an increase in the amount of calcium released by the action potential — and thus the force of contraction is increased. These are the principal beneficial actions.