Bretylium (Bretylol) was introduced for the treatment of essential hypertension but subsequently was shown to suppress the ventricular fibrillation often associated with acute myocardial infarction.
The net effects of bretylium on the electrical and me-chanical properties of the heart are a composite of the direct actions of the drug on cardiac tissues and indirect actions mediated through the drug’s effects on the sym-pathetic nervous system.
Bretylium administration produces an initial brief increase in sinus node automaticity that is probably the result of a drug-induced release of catecholamines from sympathetic nerve terminals. No change or a slight de-crease in sinus heart rate is observed after the initial phase of catecholamine release.
At therapeutic concentrations, the only significant ef-fect of bretylium is to prolong the action potential. This results in prolongation of the ERP of the atrial muscle.
Moderate doses increase conduction velocity and decrease the A-V nodal refractory period; this effect may result from the initial drug-induced catecholamine release. The net effect of bretylium on A-V transmission during chronic therapy is unknown.
The most prominent electrophysiological action of bretylium is to raise the intensity of electrical current necessary to induce ventricular fibrillation. This action, which is more prominent with bretylium than with any other available antiarrhythmic agent, can be observed in both normal and ischemic hearts.
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, in-cludes an initial release of neuronal stores of norepi-nephrine followed shortly by a prolonged period of inhibition of direct or reflex-associated neuronal nor-epinephrine release. The onset of bretylium-induced hy-potension is delayed 1 to 2 hours because the initial cat-echolamine release maintains arterial pressure before this time.
The pharmacokinetic characteristics of bretylium:
Oral bioavailability : Not applicable
Onset of action : 5–10 mm
Peak response : 6–9 hours (TM)
Duration of action : 6–24 hours
Plasma half-life : 6.9–8.1 hours
Primary route of metabolism : None
Primary route of excretion : Renal (unchanged)
Therapeutic serum concentration: 0.5–2.5 : μg /mL
Bretylium is not to be considered a first-line antiar-rhythmic agent. However, because of its ability to pro-long the refractory period of Purkinje fibers and to ele-vate the electrical threshold to ventricular fibrillation, bretylium has been found useful in the treatment of life-threatening ventricular arrhythmias, especially when conventional therapeutic agents, such as lidocaine or procainamide, prove to be ineffective. In addition, bretylium is known to facilitate the reversal of ventric-ular fibrillation by precordial electrical shock. Its use should be limited to no longer than 5 days.
The most important side effect associated with the use of bretylium is hypotension, a result of peripheral va-sodilation caused by adrenergic neuronal blockade (a guanethidinelike action). Nausea, vomiting, and diar-rhea have been reported with IV administration and can be minimized by slow infusion. Longer-term prob-lems include swelling and tenderness of the parotid gland, particularly at mealtime.
The associated initial release of catecholamines may re-sult in an excessive pressor response and stimulation of cardiac force and pacemaker activity. The resulting in-crease in myocardial oxygen consumption in a patient with ischemic heart disease may lead to ischemic pain (angina pectoris). Patients in a state of circulatory shock probably should not be administered bretylium because of its delayed sympatholytic action.
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