Selectivity of beta adrenoreceptor antagonist drugs assessed by histamine bronchial provocation

Abstract

In a double-blind, within-patient, randomized study, 12 mild asthmatics were given single oral doses of propranolol (80 mg), metoprolol (100 mg), timolol (10 mg), or placebo. Resting heart rate and forced expiratory volume in one sec (FEV J were measured before and 90 min after treatment. Nonspecific bronchial reactivity was measured by inhaled histamine at 90 min. Following each active drug, resting heart rate changed to a similar extent and to a greater degree than after placebo (p < O.OJ). Changes in FEV 1 were small and not different from those after placebo. In contrast, after each active drug, bronchial reactivity increased more than after placebo. The degree of reactivity with each active drug was similar but the differences from corresponding placebo values were significant (p < 0.05). We conclude that, in mild asthmatics, nonspecific bronchial reactivity is a more sensitive index of airway effects than resting FEV l' Moreover, in the context of this study, since the (3-blockers were given in doses likely to induce equivalent cardiac (3-blockade, there is no evidence to suggest that anyone of them is more "cardioselective" than the others.

Influence of intrinsic sympathomimetic activity (ISA) during beta‐ adrenoceptor blockade in asthmatics.

“…The difference between the results of these authors and those reported here is probably attributable to differences in the sensitivities of the patients participating in the two studies. In contrast to the present study where a histamine concentration of 7.4 mg/ml was necessary to reduce FEV1 by 20% in the pretreatment period, in their patients, Ruffin et al (1979) were able to illicit the same response with a histamine concentration of 3.7 mg/ml.…”

“…In similar experiment in which a larger dose of propranolol (80 mg) was used, Ruffin et al (1979) found that the histamine concentration needed to produce a 20% reduction in FEV1 was 47.8% lower than that necessary before treatment. The difference between the results of these authors and those reported here is probably attributable to differences in the sensitivities of the patients participating in the two studies.…”

Propranolol‐induced airway hyperreactivity in guinea‐pigs

“…Nicolaescu et al (1972) showed that treatment with propranolol and the cardioselective drug, practolol, produced a similar degree of potentiation of acetylcholine bronchospasms in their patients and they therefore proposed that the increased sensitivity might not be due to P-adrenoceptor blockade. In a more extensive double blind study, Ruffin, Frith, Anderton, Kumana, Newhouse & Hargreave (1979) compared the effects of propranolol on histamine bronchoconstriction with those of the Pl-selective drugs, metoprolol and timolol. The drugs were given in equivalent cardiac blocking doses, assessed from heart rate measurements, yet despite the corresponding differences in their P2-antagonistic properties, all three enhanced histamine responses to the same extent.…”

Comparative beta‐adrenoceptor blocking effects of propranolol, bisoprolol, atenolol, acebutolol and diacetolol on the human isolated bronchus.

“…There are, however, differences in the degree of selectivity of the cardioselective ,-adrenoceptor blockers since they displace to varying extents the bronchial dose-response curves to 32-adrenoceptor stimulants. In clinical studies, atenolol or bisoprolol appeared to be more selective than other compounds, such as acebutolol, metoprolol or oxprenolol (Greefhorst & van Herwaarden, 1982;Gribbin et al, 1981;Lammers et al, 1984;Lawrence et al, 1982;Macquin-Mavier et al, 1988;Perks et al, 1978;Ruffin et al, 1979;Tattersfield et al, 1984). Bronchial rings from a segmental bronchus were prepared and suspended in parallel in Krebs solution under an initial tension of 2.5 g. After 1.5 h of equilibration, the resting tension was between 1 and 2 g. Tensions were measured isometrically with strain gauges, amplifiers and .O.S..-Moise 2 recorder system (Celaster, Celle l'Evescault, 86600 Lusignan, France) (Advenier et al, 1986).…”