Antiarrhythmic agents bretylium

A unique property of bretylium as an antiarrhythmic agent is its positive inotropic action. This effect, related to its actions on the sympathetic nervous system, includes an initial release of neuronal stores of norepinephrine followed shortly by a prolonged period of inhibition of direct or reflex-associated neuronal norepinephrine release. The onset of bretylium-induced hypotension is delayed 1 to 2 hours because the initial catecholamine release maintains arterial pressure before this time. 

For patients in cardiac arrest, usual antiarrhythmic agents and direct-current countershock are frequently ineffective until the core temperature is above 32-35°C (90-95°F). Provide gastric or peritoneal lavage with warmed fluids and perfonn CPR. For ventricular fibrillation, bretylium, 5-10 mg/kg IV (see p 421), may be effective. 

Bretylium was first introduced as an antihypertensive agent. It interferes with the neuronal release of catecholamines but also has direct antiarrhythmic properties. 

Bretylium Tosylate. Another neuronal blinking agent is the aromatic quaternary ammonium compound bretylium tosylate (Bretylol). This agent is used as an antiarrhythmic drug. Its antiarrliythmic actions are not believed to be due to iLS neuronal blocking effects, however. This agent is dis-cu.sscd in more detail in Chapter ID. 

Interest in the antiarrhythmic activity of quaternary ammonium compounds continues. Unlike bretylium (11a). its o-iodobenzyl trimethyl-ammonium analog (UM-360, lib) did not inhibit release of norepinephrine from sympathetic nerve endings and did not cause adrenergic stimulation on its own.UM-36O effectively antagonized ventricular arrhythmias produced by ouabain in dogs, an action bretylium did not possess. Both agents elevated the threshold to electrically induced ventricular fibrillation. The same group of workers also studied the profile of a quaternary propan-2-ol derivative (UM- 2h, 12). ° In contrast to tertiary compounds of... 

Type III antiarrhythmics include agents that specifically prolong refractoriness in atrial and ventricular tissue. This class includes very different drugs bretylium, amiodarone, sotalol, ibutilide, and recently, dofetilide they share the common effect of delaying repolarization by blocking potassium channels. The electrophysiologic actions of bretylium are related to its multifaceted pharmacology. 

---