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Classification and mechanism of action of antiarrhythmic drugs *

Summary— The present paper reviews classification and mode of action of agents that suppress extrasystoles and tachyarrhythmias. These are classified according to their electrophysiological effects observed in isolated cardiac tissues in vitro (Vaughan Williams, 1989). Fast sodium channel blockers (class I) which reduce the upstroke velocity of the action potential are usually subclassified into three groups, class I A‐C, according to their effect on the action potential duration. Beta‐adrenergic antagonists (class II) exert their effects by antagonizing the electrophysiological effects of beta‐adrenergic catecholamines. Class III antiarrhythmic agents (eg amiodarone) prolong the action potential and slow calcium channel blockers (class IV) suppress the calcium inward current and calcium‐dependent action potentials. The classification of antiarrhythmic drugs is still under debate. This particularly applies to agents of class I and III. The effect of class I agents is frequency‐dependent because the binding affinity of these drugs to the sodium channel is modulated by the state of the channel (modulated receptor hypothesis). Class I agents bind to the channel in the activated and inactivated state and dissociate from the channel in the rested state. This occurs at a drug‐specific rate so that class I agents can be subclassified into only two groups, namely in those of the slow‐ and fast‐recovery type respectively (time constant of reactivation greater or smaller than 1 s). Slow‐recovery class I agents affect regular action potentials at normal heart rates which can more easily lead to a lengthening of the QRS duration in the ECG, to conduction disturbances and hence to pro‐arrhythmic effects. Class I antiarrhythmic agents have also been subclassified according to the saturation behaviour of frequency‐dependent sodium channel blockade (Weirich and Antoni, 1990), but the relevance of this subclassification remains to be elucidated. This applies also to a recent attempt (Hondeghem) to subclassify class III agents according to the frequency dependency of their antiarrhythmic actions.