Overview of the clinical pharmacology of antiarrhythmic drugs.

Antiarrhythmic drugs have been recognized to possess 1 or more classes of antiarrhythmic action. This classification scheme is useful, but has major limitations because the available drugs and their metabolites have multiple actions. This report presents an overview of the distinguishing features of the most frequently used agents having class I or III actions. Agents with class I actions are local anesthetic agents that depress the fast inward depolarizing sodium current and thereby slow the rate of the rise of the action potential (phase 0). This category is further divided into classes IA, IB, and IC according to the degree of potency as sodium channel inhibitors, and the individual effects of the drug on action potential, conduction velocity and repolarization. Included in the spectrum of agents with class I action are quinidine, procainamide, disopyramide, lidocaine, tocainide, mexiletine, flecainide, amiodarone, encainide and lorcainide. The antiarrhythmic drugs that exert class III action lengthen repolarization and refractoriness; included in this category are amiodarone, quinidine, bretylium and sotalol. Because of the broad range of effects that antiarrhythmic agents may exert, safe and effective therapy requires a thorough familiarity with the pharmacologic profile of each drug administered and a careful evaluation of the presenting condition and the patient history. In some cases, a multiple drug regimen may be most appropriate. Various combinations such as class IA and IB agents, have been shown to slow conduction synergistically and increase refractoriness while keeping adverse effects to a minimum.