Class III antiarrhythmics

Antiarrhythmics (class III) Longer elimination ti/2 Lower initial dose... 

Trade names Aratac Corbionax Cordarex Cordarone (Wyeth) Cordarone X Pacerone (Upsher-Smith) Tachydaron Indications Ventricular fibrillation, ventricular tachycardia Category Antiarrhythmic class III Half-life 26-107 days... 

Trade names Bretylate Critifib Indications Ventricular tachycardia and fibrillation Category Antiarrhythmic class III Half-life 4-17 hours... 

Category Adrenergic beta-receptor antagonist Antiarrhythmic class III... 

Antiarrhythmics, class III (amlodarone, azimlllde, cibenzoline, dofetlllde, Ibutlllde, sotalol ) Erythromycin oral (see also high risk)... 

Fleca.inide, Elecainide acetate, a fluorobenzamide, is a derivative of procainamide, and has been reported to be efficacious in suppressing both supraventricular and ventricular arrhythmias (26—29). The dmg is generally reserved for patients with serious and life-threatening ventricular arrhythmias. Elecainide depresses phase 0 depolarization of the action potential, slows conduction throughout the heart, and significantly prolongs repolarization (30). The latter effect indicates flecainide may possess some Class III antiarrhythmic-type properties (31). 

Pirmenol. Pirmenol hydrochloride, a pyridine methanol derivative, is a racemic mixture. It has Class lA antiarrhythmic activity, ie, depression of fast inward sodium current, phase 0 slowing, and action potential prolongation. The prolongation of refractory period may be a Class III property. This compound has shown efficacy in converting atrial arrhythmias to normal sinus rhythm (34,35). 

The Class III antiarrhythmic agents markedly prolong action potential duration and effective refractory period of cardiac tissue. The QT interval of the ECG is markedly prolonged. 

Other Glass III Antiarrhythmic Agents. Clofihum phosphate is a benzene-butanaminium derivative that has highly specific Class III antiarrhythmic activity. It is orahy active, has a rapid onset of action, and a reasonably long duration of antiarrhythmic activity. In preliminary clinical studies, clofihum has shown efficacy against spontaneous ventricular tachycardias (69). 

A cell may produce early afterdepolarizations that are depolarization during incomplete repolarization. This is possible if the action potential is considerably prolonged. This is the typical mechanism for elicitation of Torsade de Pointes arrhythmia, a typical complication of class III antiarrhythmics and many other drugs. 

The Vaughan-Williams classification of antiarrhythmic drugs has been criticized for a number of reasons. The classification is based on the effects of drugs on normal, rather than diseased, myocardium. In addition, many of the drugs may be placed into more than one class. For example, the class IA drugs prolong repolarization/refractoriness, either via the parent drug8,9 or an active metabolite,10 and therefore also maybe placed in class III. Sotalol is also a 3-blocker, and therefore fits into class II. Amiodarone inhibits sodium and potassium channels, is a non-competitive inhibitor of 3-receptors, and inhibits calcium... 

Myocardium Cardiac action potential Class III antiarrhythmics block hERG Many noncardiac drugs block... 

Jurkiewicz, N.K. and Sanguinetti, M.C., Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agent. Specific block of rapidly activating delayed rectifier K+ current by dofetilide, Circ. Res., 72, 75-83, 1993. 

An Overview of Class III Electrophysiological Agents A New Generation of Antiarrhythmic Therapy... 

PVC s alone with Class IC drugs was not sufficient to reduce mortality in the specific post-infarction population chosen for the CAST study. The failure of Class IC agents in the CAST study and their low efficacy in preventing induction of SVT during electrophysiological testing has increased the interest in alternative approaches to antiarrhythmic therapy, particularly towards Class III agents, a number of which are in Phase II clinical evaluation. 

Bunaftine (21) is a naphthalenecarboxamide derivative, that has been developed as an antiarrhythmic agent. The compound exhibits both Class I and Class III electrophysiological effects. Fenici and co-workers studied bunaftine in patients with paroxysmal atrial tachyarrhythmia and recorded right atrial monophasic action potentials [72]. A mean increase of 18% in atrial repolarization time and an increase in monophasic APD during pac-... 

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