Digitalis Glycosides and Vagomimetic Drugs
Digitalis glycosides, especially digoxin (Lanoxin), be-cause of their positive inotropic effects, are widely used for treating patients with congestive heart failure. They also continue to be used for the management of patients with supraventricular arrhythmias. Since the digitalis glycosides are discussed elsewhere , a full discussion of their mechanism of action is not pro-vided here.
Digitalis glycosides enhance the inotropic state by increasing the intracellular calcium concentration. Intracellular calcium overload is also the mechanism for proarrhythmia associated with digitalis intoxication. The direct effect of digitalis on the electrophysiology of the myocytes is to increase the slope of phase 4 depo-larization, an effect that enhances automaticity.
The principal antiarrhythmic effect is achieved via prominent vagotonic actions. The vagotonic influence leads to inhibition of Ca++ currents in the A-V node and activation of acetylcholine-sensitive potassium channels in the atrium (these channels are not present in the ventricle). This results in a slowing of conduction through the A-V node, a hyperpolarization of the rest-ing membrane potential, and a shortening of the refrac-tory period in atrial tissue. The principal antiarrhythmic actions are associated with the effects on the A-V node. Digitalis can therefore be used on reentrant arrhyth-mias that use the A-V node as one limb of the circuit and for limiting A-V conduction during rapid atrial ar-rhythmias, such as in atrial fibrillation.
Digitalis glycosides have theoretical advantages over other medications that limit conduction through the A-V-node, such as β-blockers and Ca++ channel blockers, by providing a positive rather than negative inotropic effect on the ventricles. The effects on the A-V node are limited, however, in states of height-ened sympathetic tone, such as during advanced heart failure.
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