Assessment of beta-adrenoceptor antagonists in asthmatic patients

1 Bronchial smooth muscle, skeletal muscle and cardiac beta-adrenoceptor antagonism have been compared in twelve asthmatic patients after three beta-adrenoceptor antagonists at two dose levels. The non-selective antagonist propranolol (40 and 160 mg), the non-selective antagonist with partial agonist activity pindolol (5 and 20 mg) and the beta 1-selective antagonist atenolol (50 and 200 mg) were studied on separate occasions. 2 Six placebo days were used in this double-blind crossover study to allow interpretation of individual as well as group results. 3 Bronchial smooth muscle effects were assessed by resting spirometry, histamine inhalation test and spirometric response to inhaled fenoterol. Skeletal muscle effects were assessed by resting tremor and fenoterol induced tremor. 4 Cardiac beta-adrenoceptor antagonism was assessed by measuring the effect on resting heart rate and on maximum heart rate in a standard exercise test. 5 Pindolol tended to cause least change from placebo in resting spirometry, caused significant tremor response, inhibited the fenoterol airway response, and tended to protect against inhaled histamine. 6 Atenolol 60 mg was the only drug to allow a fenoterol airway response similar to placebo. Atenolol increased the inhaled histamine responsiveness. 7 Propranolol 160 mg caused the most reduction in spirometry but also tended to cause the maximum reduction in exercise heart rate. Propranolol caused increased inhaled histamine responsiveness. 8 Initial sensitivity to inhaled histamine did not necessarily predict significant reduction in an asthmatics' spirometry by a beta-adrenoceptor antagonist. The effect of a beta-adrenoceptor antagonist on histamine responsiveness does not correspond to its effect on inhaled beta 2-adrenoceptor agonist responsiveness.