Mechanisms of Antiarrhythmic Drug Actions and Their Clinical Relevance for Controlling Disorders of Cardiac Rhythm

This review on antiarrhythmic drugs traces the evolution of the fundamental mechanisms of action of drugs that have been used to control disorders of cardiac rhythm. It describes the very earliest data from experimental studies that dealt with the effects of acute and chronic administration of drugs in whole animals combined with the measurements of the action potential duration and the effective refractory period in isolated tissues. Antiarrhythmic drugs were found to have properties consistent with the block of fast sodium channel conduction, adrenergic blockade, repolarization block, and the block of slow-channel mediated conduction especially in the atrioventricular node. Over the past 15 years, the attention has focused on atrial tissue with atrial fibrillation emerging as the most common arrhythmia in clinical practice. Drug-induced increases in refractoriness as a function rate and in wavelength (product of refractoriness and conduction velocity), and a reduction in numbers of wavelets have been found to be critical in the conversion of atrial fibrillation and maintenance of sinus rhythm. The continued development of newer pharmacologic agents is likely to lead to the resolution of the controversy regarding rhythm versus rate control in various clinical subsets of the arrhythmia by controlled clinical trials.