clinical pharmacology

SELECTIVE {3 1 -BLOCKERS SAFE WITH {3 2 -STIMULATORS IN ASTHMATICS

There is a need for {3 1 -blocking drugs safe for use in asthmatics to be used in place of practolol, which was withdrawn because of serious side-effects. This study showed that the doses of metoprolol effective in hypertension and angina could safely be given to asthmatics receiving isoprenaline (isoproterenol) or a selective {32 -stimulator. Placebo and practolol were included as reference substances. Eight patients with asthma of 2-28 years duration received on 5 different days in random order propranolol40mg, metoprololSOmg and lOOmg (a new selective {3 1 -blocker with no intrinsic sympathomimet activity), practolol 200mg or placebo. The {31 -blocking activity of the selective drugs at these dose levels was higher than or equal to that of propranolol.

After 12 hours off their usual bronchodilator drugs (except theophylline derivatives which were withdrawn 36 hours previously) the effects of the test agents on heart rate, BP, ventilatory capacity (FEY 1) and skeletal muscle tremor were studied at rest and during infusion of increasing doses of isoprenaline (0.005-0.094J..Lg/kg/min). FEY 1 decreased slightly after propranolol and both doses of metoprolol. After placebo, isoprenaline produced a dose-dependent increase in heart rate, systolic BP, FEY 1 , and tremor, and a decrease in diastolic BP. Propranolol almost completely blocked the effects

of all doses of isoprenaline on the heart rate, FEY 1 , and tremor, and, to a lesser extent, change in systolic and diastolic pressures. Practolol and the 2 doses of metoprolol did not inhibit the effect of isoprenaline on FEY 1 • Propranolol and metoprolol 1 OOmg significantly decreased the effect of isoprenaline on heart rate. The isoprenaline-induced increase in tremor was blocked by propranolol, but not by the selective {3 1 -blockers. Although isoprenaline was used in this study to investigate the effects on {3 1 -receptors too, the {3 2 -agonist salbutamol, usually used in asthma, produces the same maximal bronchodilator effect.

'Thus, a selective beta 1 -receptor blocker may be given together with a beta2 -stimulator in optimal dosage to asthmatics without risk of impaired ventilatory function. '

Tiuinger, G. and Svedmyr, N.: European Journal of Clinical Pharmacology 10: 163 (No 3/4, 1976)

INPHARMA 25th September, 1976 p13