Bretylium tosylate, the only approved class III antiarrhythmic agent, is a unique
quaternary ammonium compound with prominent experimental and clinical antifibrillatory effects. Intravenous
bretylium causes a biphasic hemodynamic response; initial
norepinephrine release is followed by sympathetic ganglionic blockade. Cardiac output is well maintained. Electrocardiographic intervals are unchanged, and global conduction unchanged or facilitated. With long-term experimental use, proportionate lengthening of ventricular action potential and refractory period occurs.
Bretylium is largely eliminated unchanged in the urine, with a long terminal half-life of about 13 hours.
Bretylium demonstrates substantial activity in several animal models and clinical circumstances of
ventricular fibrillation, including those in which standard antiarrhythmic
therapy is ineffective.
Bretylium is thus currently approved as a first-line agent for prophylaxis and treatment of
ventricular fibrillation, and as a second-line agent for
ventricular tachycardia and other prefibrillatory ventricular arrhythmias. In contrast,
bretylium's weak antiectopic activity and limited oral absorption make it a poor choice for management of simple ventricular ectopy. Side effects of
bretylium are generally limited to its hemodynamic actions (eg,
postural hypotension).
Nausea may occur with rapid
intravenous administration. Emerging clinical concepts emphasize the clinical importance of antifibrillatory action over antiectopic effects alone.
Bretylium is thus likely to continue to find increasing usage in the acute management of malignant ventricular
arrhythmia.