Clinical Use of Class Ic Antiarrhythmic Drugs

Abstract

In 1969, Vaughan Williams proposed a classification for antiarrhythmic drugs at an international meeting of cardiologists and electrophysiologists in Elsinor, Denmark (Vaughan Williams 1970). The majority of the antiarrhythmic agents, then and now, restrict the fast inward sodium current. However, distinct differences within this class I action have necessitated subdivision of class I drugs into a, b, and c groups. The most distinctive characteristic of the Ic agents is that then bind slowly and dissociate slowly from the Na channel (Campbell and Vaughan Williams 1983). Thus, during tachycardias, not enough time will elapse between beats to permit the drug to dissociate from the Na channel, causing a population of channels to be “blocked” and thus slowing conduction markedly (Vaughan Williams 1984). These cellular electrophysiologic characteristics of the class Ic agents provide a rationale for both their potency and possible disadvantages. By binding to Na channels and remaining bound throughout the cardiac cycles at fast (though physiologic) heart rates, the drugs will decrease ectopy, the trigger for initiating ventricular tachycardia. Conduction will be slowed and the substrate critical for sustained ventricular tachycardia (VT) leading to sudden death may be favorably modified. The same electrophysiologic actions, however, in patients with an already diseased conducting system could delay conduction to the point of impairment with asystole, requiring insertion of a pacemaker.