Effects of cardioselective beta adrenoceptor blockade on specific airways resistance in normal subjects and in patients with bronchial asthma.
The effects of single oral doses of the cardioselective beta adrenoceptor blocking drugs, metoprolol and tolamolol, on specific airways resistance (SRaw) were compared with those of propranolol and practolol in 6 healthy volunteers and in 12 patients with bronchial asthma. Whole-body plethysmography was used to measure SRaw and the blocking potency of different antagonists assessed by the degree of inhibition of tachycardia due to exercise on a treadmill. The changes correlated with plasma drug levels. Propranolol and practolol were measured fluorometrically and metoprolol by electron-capture gas-liquid chromatography. In normal subjects, about 30% reduction in exercise-induced tachycardia resulted from single doses of 80 mg propranolol (plasma levels, 50.3, SD, 29.5 to 60.8, SD, 26 ng/ml), 250 mg practolol (plasma levels, 1.05, SD, 0.32 to 1.10, SD, 0.55 mug/ml), 100 mg metoprolol (plasma levels, 137, SD, 111 to 152, SD, 100 ng/ml), and 100 mg tolamolol. In patients, these doses of the drugs produced significant increases in SRaw. These increases were greater than those after placebo but significantly so only during the peak effect 1 hr after propranolol. Compared with changes after placebo, significant effects on SRaw were also found in 3 patients given 200 mg of tolamolol. None of the drugs had a significant effect on SRaw in normal subjects. It is concluded that metoprolol, practolol, and tolamolol may impair ventilatory function in asthmatics less than propranolol and that at high doses this difference may not be demonstrable.
Effects of cardioselective beta adrenoceptor blockade on specific airways resistance in normal subjects and in patients with bronchial asthma. The effects of single oral doses of the cardioselective beta adrenoceptor blocking drugs, metoprolol and tolamolol, on specific airways resistance (SRaw) were compared with those of propranolol and practolol in 6 healthy volunteers and in 12 patients with bronchial asthma. Whole-body plethysmography was used to measure SRaw and the blocking potency of different antagonists assessed by the degree of inhibition of tachycardia due to exercise on a treadmill. The changes correlated with plasma drug levels. Propranolol and practolol were measured fluorometrically and metoprolol by electron-capture gas-liquid chromatography. In normal subjects, about 30% reduction in exercise-induced tachycardia resulted from single doses of 80 mg propranolol (plasma levels, 50.3, SD, 29.5 to 60.8, SD, 26 ng/ml), 250 mg practolol (plasma levels, 1.05, SD, 0.32 to 1.10, SD, 0.55 mug/ml), 100 mg metoprolol (plasma levels, 137, SD, 111 to 152, SD, 100 ng/ml), and 100 mg tolamolol. In patients, these doses of the drugs produced significant increases in SRaw. These increases were greater than those after placebo but significantly so only during the peak effect 1 hr after propranolol. Compared with changes after placebo, significant effects on SRaw were also found in 3 patients given 200 mg of tolamolol. None of the drugs had a significant effect on SRaw in normal subjects. It is concluded that metoprolol, practolol, and tolamolol may impair ventilatory function in asthmatics less than propranolol and that at high doses this difference may not be demonstrable.