[Principles for the classification of anti-arrhythmia agents in cardiac arrhythmias]

Clinically useful antiarrhythmic drugs are a group of heterogenous compounds, both with respect to chemical structure and to cellular mechanism of action. The classification of antiarrhythmic agents according to Vaughan Williams is based on electrophysiological findings in isolated heart muscle and defines four classes of drug actions. The criteria for classification include blockade of ion channels (classes I and IV), interaction with receptors (class II), and alteration of electrophysiological parameters, e.g., prolongation in action potential duration (class III). Several antiarrhythmic drugs possess actions in more than one class. The classification does not include all established antiarrhythmics, e.g., digitalis. Class-I action is further subdivided on the basis of extent of Na+ channel block and additional change in action potential duration. The kinetics of the onset and offset of Na+ channel block can be explained by models in which association and dissociation from the receptor are functions of channel state, i.e., activated, inactivated or resting. Detailed analysis has led to the concept of saturation block (24). Recently, the European Society of Cardiology has presented a classification of antiarrhythmics based on a more comprehensive compilation of drug action (18). Any useful classification of antiarrhythmic agents should offer guidance for their clinical use. This goal has not yet been reached. The criteria of classification are physicochemical properties or cellular mechanism of action as detected with sophisticated electrophysiological techniques. However, in spite of this fact, successful therapeutic use of antiarrhythmic drugs remains, to a large extent, still empirical.