Sectral is a cardioselective, β-adrenoreceptor blocking agent, which possesses mild intrinsic sympathomimetic activity (ISA) in its therapeutically effective dose range.

Pharmacodynamics

β1-cardioselectivity has been demonstrated in experimental animal studies. In anesthetized dogs and cats, Sectral is more potent in antagonizing isoproterenol-induced tachycardia (β1) than in antagonizing isoproterenol-induced vasodilatation (β2).In guinea pigs and cats, it is more potent in antagonizing this tachycardia than in antagonizing isoproterenol- induced bronchodilatation (β2). ISA of Sectral has been demonstrated in catecholamine-depleted rats by tachycardia induced by intravenous administration of this agent. A membrane-stabilizing effect has been detected in animals, but only with high concentrations of Sectral. Clinical studies have demonstrated β1-blocking activity at the recommended doses by: a) reduction in the resting heart rate and decrease in exercise-induced tachycardia; b) reduction in cardiac output at rest and after exercise; c) reduction of systolic and diastolic blood pressures at rest and postexercise; d) inhibition of isoproterenol-induced tachycardia.

The β1-selectivity of Sectral has also been demonstrated on the basis of the following vascular and bronchial effects: Vascular Effects: Sectral has less antagonistic effects on peripheral vascular β2-receptors at rest and after epinephrine stimulation than nonselective β-antagonists. Bronchial Effects: In single-dose studies in asthmatics examining effects of various beta-blockers on pulmonary function, low doses of acebutolol produce less evidence of bronchoconstriction and less reduction of beta2 agonist, bronchodilating effects, than nonselective agents like propranolol but more than atenolol.

ISA has been observed with Sectral in man, as shown by a slightly smaller (about 3 beats per minute) decrease in resting heart rate when compared to equivalent β-blocking doses of propranolol, metoprolol or atenolol. Chronic therapy with Sectral induced no significant alteration in the blood lipid profile.

Sectral has been shown to delay AV conduction time and to increase the refractoriness of the AV node without significantly affecting sinus node recovery time, atrial refractory period, or the HV conduction time. The membrane-stabilizing effect of Sectral is not manifest at the doses used clinically.

Significant reductions in resting and exercise heart rates and systolic blood pressures have been observed 1.5 hours after Sectral administration with maximal effects occurring between 3 and 8 hours postdosing in normal volunteers. Sectral has demonstrated a significant effect on exerciseinduced tachycardia 24 to 30 hours after drug administration.

There are significant correlations between plasma levels of acebutolol and both the reduction in resting heart rate and the percent of β-blockade of exercise-induced tachycardia. The antihypertensive effect of Sectral has been shown in double-blind controlled studies to be superior to placebo and similar to propranolol and hydrochlorothiazide. In addition, patients responding to Sectral administered twice daily had a similar response whether the dosage regimen was changed to once daily administration or continued on a b.i.d. regimen. Most patients responded to 400 to 800 mg per day in divided doses.

The antiarrhythmic effect of Sectral was compared with placebo, propranolol, and quinidine. Compared with placebo, Sectral significantly reduced mean total ventricular ectopic beats (VEB), paired VEB, multiform VEB, R-on-T beats, and ventricular tachycardia (VT). Both Sectral and propranolol significantly reduced mean total and paired VEB and VT. Sectral and quinidine significantly reduced resting total and complex VEB; the antiarrhythmic efficacy of Sectral was also observed during exercise.

Pharmacokinetics and Metabolism

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