Ventilatory and haemodynamic effects of terbutaline infusion during beta1-selective blockade with metoprolol and acebutolol in asthmatic patients
A double-blind, placebo-controlled study of the haemodynamic and ventilatory effects of two beta1-selective adrenoceptor blockers and their interaction with the beta2-adrenoceptor agonist terbutaline was carried out in eight asthmatic patients. One hour after intake of placebo, metoprolol 100 mg or acebutolol 400 mg, increasing doses of terbutaline were infused. Before and one hour after ingestion of the medication and after each infusion of terbutaline, ventilatory and haemodynamic indices were measured. The two beta-blocking agents caused equal changes in basal ventilatory and haemodynamic indices. Terbutaline infusion caused a dose-dependent increase in forced expiratory volume in one second (FEV1) and peak expiratory flow rate (PEFR), both during placebo and beta-blockade. Metoprolol did not affect the terbutaline-induced bronchodilatation. During acebutolol medication, however, the increase in FEV1 and PEFR induced by terbutaline was partly inhibited. Terbutaline infusion during placebo caused a dose-dependent increase in heart rate (HR) and systolic blood pressure (BP), and a decrease in diastolic BP. During acebutolol medication, these haemodynamic effects of terbutaline were completely blocked, but during metoprolol medication terbutaline still caused small changes in the same direction as during placebo, presumably because the vasodilator action of terbutaline was not inhibited. A negative correlation was found between the plasma levels of acebutolol and its metabolite N-acetyl acebutolol at the end of the study and changes in FEV1 and PEFR induced by terbutaline during acebutolol therapy as compared with placebo. The ventilatory and haemodynamic findings suggest a lower degree of beta1-selectivity after oral administration of acebutolol as compared to metoprolol.