All drugs currently marketed for the treatment of arrhythmias were developed in the absence of knowledge of the specific molecules the drugs target to achieve their therapeutic and adverse effects. Nevertheless, combining the characterisation of drug effects in vitro and in whole animal models with medicinal chemistry approaches to modify existing molecules has led to new compounds with related pharmacologic actions derived from older drugs (for example, procainamide begat flecainide). It has thus been natural to group drugs with common mechanisms of action. This approach can be useful for the clinician to the extent it allows prediction of a patient's response to a given drug. One widely used scheme is that popularised by Vaughan Williams in which drugs are subdivided into four broad “classes”.1 The Vaughan Williams classification has been criticised because many drugs fall into multiple classes (table1): quinidine both blocks sodium channels and prolongs action potentials (class I + III), while amiodarone blocks sodium channels, exerts antiadrenergic actions, prolongs action potentials and QT intervals by blocking potassium channels, and blocks calcium channels (classes I + II + III + IV, respectively).2 ,3 Moreover, both compounds exert other important pharmacologic actions, such as inhibition of specific pathways of drug elimination (both), α blockade with vasodilation (quinidine), and interaction with nuclear thyroid hormone receptors (amiodarone). These actions probably contribute to some of the effects observed during treatment with these compounds.

A virtue of the Vaughan Williams' approach to classification is that drugs of a common “class” frequently exhibit similar toxicities, notably proarrhythmia. This likely reflects the fact, discussed below and elsewhere in this series, that while the mechanisms whereby drugs suppress arrhythmias are incompletely defined and likely highly variable from patient to patient, the mechanisms underlying proarrhythmia are …