New Antiarrhythmic Drugs: Tocainide, Mexiletine, Flecainide, Encainide, and Amiodarone

Abstract

Tocainide, mexiletine, flecainide, encainide, and amiodarone are antiarrhythmic agents that have recently been approved by the Food and Drug Administration for general use in the treatment of ventricular arrhythmias. All five agents are effective in the treatment of patients with ventricular arrhythmias, whereas encainide, flecainide, and amiodarone are also useful in patients with supraventricular arrhythmias and the Wolff-Parkinson-White syndrome (although not yet approved for these indications). Tocainide and mexiletine are similar to lidocaine and are as effective as quinidine in patients with ventricular arrhythmias. Encainide and flecainide are superior to quinidine for the control of ventricular ectopic beats and as effective as quinidine for patients with ventricular tachycardia. Amiodarone is the most effective agent available for treating patients with ventricular tachycardia, but it is also the most toxic antiarrhythmic agent and should be used only when other antiarrhythmic drugs have not been effective or tolerated.

Comparison of the electrophysiological effects of Org 7797, disopyramide, mexiletine and propafenone in anaesthetized dogs with myocardial infarcts

“…JTc was, if anything, shortened but no other electrophysiological changes were seen. Intravenous (2-3 mgkg-') canine studies (Yoon & Han, 1982;Costard-Jackle & Franz, 1989), intravenous clinical studies (Seipel & Breithardt, 1978;Jewitt, 1978) and clinical oral studies (reviewed by Kreuger et al, 1987;Nestico et al, 1988) have reported little or no effect of mexiletine on intracardiac conduction, refractory periods or repolarization although shortening of the latter has sometimes been observed. Experimental studies using 2 mgkg-' do however suggest that mexiletine may slow ventricular conduction (Bajaj et al, 1987) and prolong the ventricular refractory period (Costard-Jackle & Franz, 1989) but only at cycle lengths substantially shorter than those used in our study whilst at long cycle lengths, prominent short- In contrast to Org 7797, disopyramide (2mgkg-1) in antiarrhythmic doses (Marshall & Parratt, 1979;Hashimoto et al, 1982) increased JTc (by 6%) and QT during pacing (by 16%) indicating a clear prolongation of ventricular repolarization.…”

CYP2D6 genotype affects age-related decline in flecainide clearance

“…We found an age-related decline in the oral clearance (CL/F) of flecainide acetate [5], which is a CYP2D6 substrate and a strong sodium channel blocker commonly used to treat various supraventricular tachyarrhythmias [6][7][8]. Flecainide undergoes renal excretion and hepatic metabolism by its conversion to m-O-dealkylated flecainide (MODF) and subsequent oxidation to m-O-dealkylated lactam [9,10].…”

Impact of serum flecainide level on control of atrial fibrillation in a case treated with cardiac resynchronization therapy

“…Flecainide acetate, a Vaughan–Williams class Ic anti‐dysrhythmic agent, is commonly used as a strong sodium channel blocker for a variety of supraventricular tachydysrhythmias (1, 2) that cannot be controlled by other anti‐dysrhythmic agents or by catheter ablation. Therapeutic levels of serum flecainide are currently reported to be 300–1000 ng/mL for supraventricular tachydysrhythmias, including atrial fibrillation (AF) (3).…”