Comparative mechanisms of action of antiarrhythmic drugs

The most widely used classification of antiarrhythmic drugs, formulated by Singh and Vaughan Williams, divides antiarrhythmic agents into 4 categories: (1) sodium channel blockers; (2) sympatholytic agents; (3) drugs that delay repolarization; and (4) calcium antagonists. Despite some controversy regarding its value, the available evidence indicates that this classification relates well to the most important clinically relevant mechanisms of antiarrhythmic drug action. Amiodarone is unique in that it possesses properties belonging to all 4 of the Singh and Vaughan Williams classes; moreover, all 4 properties contribute to the beneficial actions of the drug. Class 1 effects are responsible for amiodarone's ability to slow ventricular tachycardias, making them hemodynamically better tolerated, and are likely important in amiodarone's premature ventricular complex-suppressing properties. Class 2 effects may contribute to atrioventricular (AV) node-suppressing actions and may confer protection against sudden death in the postmyocardial infarction population. Class 3 actions contribute to amiodarone's ability to prevent reentrant atrial and ventricular arrhythmias, and may be responsible for a superior ability to maintain sinus rhythm after cardioversion of atrial fibrillation. Class 4 properties contribute to amiodarone's ability to slow the ventricular response in atrial fibrillation and to prevent AV node reentrant arrhythmias. Calcium channel antagonism may also suppress arrhythmias (such as torsades de pointes) caused by early after-depolarizations and contribute to the apparent infrequency of torsades, despite substantial QT prolongation, among patients treated with amiodarone. Consideration of the link between amiodarone's pharmacologic properties and clinical effects illustrates well the various mechanisms of antiarrhythmic drug action.