Vol 15, No 3 (2008)
Review Article
Published online: 2008-04-14
Relationship among amiodarone, new class III antiarrhythmics, miscellaneous agents and acquired long QT syndrome
Cardiol J 2008;15(3):209-219.
Abstract
Class III drugs prolong the QT interval by blocking mainly the delayed rectifier rapid potassium
outward current (IKr), with little effect on depolarization. This K+ channel in encoded by
the human ether-a-go-go-related gene (hERG). Inhibition of hERG potassium currents by class
III antiarrhythmic drugs causes lengthening of cardiac action potential, which produces
a beneficial antiarrhythmic effect. Excessive prolongation of the action potential may lead to
acquired long QT syndrome, which is associated with a risk of “torsade de pointes”. Class III
agents can block all types of potassium channels: IKs, IKr, IKur and IK1. The main representing
class III agent is amiodarone. It is the gold standard in the prevention of recurrence of
atrial fibrillation. Although it is highly effective in treating many arrhythmias, large number of
adverse effects limits its clinical use. Dronedarone is a synthetic amiodarone analogue, iodinefree
compound, with fewer adverse effects, and shares amiodarone’s multichannel blocking
effects, inhibiting transmembrane Na+, IKs, IKur, IK1, and slow Ca++L-type calcium currents.
The main new generation class III drugs are: dofetilide, dronedarone, azimilide, and
ibutilide. Oral dofetilide did not increase mortality in patients with a recent myocardial
infarction or congestive heart failure. It is an alternative for the pharmacological conversion of
atrial fibrillation and flutter. Azimilide blocks both rapid and slow potassium channels components.
Azimilide is not a methanesulfonanilide compound. Trecitilide, tedisamil, ersentilide,
ambasilide, chromanol and sematilide are class III miscellaneous agents. Old mixed agents
are sotalol and bretylium. The present article reviews the main trials accomplished with these
drugs. (Cardiol J. 2008; 14: 209–219)
Keywords: antiarrhythmic drugssudden cardiac deathlong QT syndrome