Current classification of antiarrhythmic drugs

Antiarrhythmic drugs can be divided into four Vaughan Williams classes (I-I V) according to defined electrophysiological effects on the myocardium. Thu s, the Vaughan Williams classification also co-incides with the main myocar dial targets of the antiarrhythmics, i.e., myocardial sodium-, potassium; a nd calcium-channels or beta-adrenergic receptors. A more detailed character ization which is also based on the myocardial targets of a drug is given by the "Sicilian Gambit'' approach of classification. Nevertheless, the appro priate drug for the management of a given clinical arrhythmia has to be cho sen according to the electrophysiological effects of the respective drug. A main determinant of the antiarrhythmic or proarrhythmic propel-ties of a d rug is the frequency dependence of its electrophysiological effects. The so dium-channel blockade induced by class-I substances is enhanced with increa sing heart rates. Thus, class-I antiarrhythmics can be subclassified as sub stances showing a more exponential: an approximately linear, or rather satu rated block-frequency relation. Class-III antiarrhythmics (potassium-channe l blockade) can be further differentiated according to the component of the delayed rectifier potassium current (I-K) which is inhibited by a drug. Cl ass-III drugs inhibiting selectively the rapidly activating and deactivatin g I, component exhibit a marked reverse rate dependence, i.e., the drug ind uced prolongation of the cardiac action potential is minimized at high rate s. On the other hand, during bradycardia the pronounced action potential pr olongation may cause early afterdepolarizations and triggered activity lead ing to torsades de pointes arrhythmias (acquired QT syndrome). Class-m subs tances inhibiting the slowly activating I, component are currently under in vestigation and are expected to show a direct rate dependence. Experimental data available so far point to an action potential prolonging effect at le ast independent of rate. However, it is uncertain whether proarrhythmic eff ects can be thus avoided, especially in light of the fact that one form of congenital QT syndrome (LQT1) seems to be linked to dysfunction of the I-Ks -channel.