Lack of bronchial beta adrenoceptor resistance in asthmatics during long-term treatment with terbutaline.
The increasing mortality in acute asthma noted during the sixties has been ascribed to resistance of the beta 2 receptors of the bronchi due to treatment with beta-stimulating drugs. This study questions that theory. Eight patients with reversible airways obstruction were studied. Treatment with oral terbutaline 5 mg 3 times a day was given for 1 yr. Thereafter, terbutaline as metered aerosol was added in the dose of 2 puffs (0.5 mg) 4 times a day for 4 days and 6 puffs (1.5 mg) 4 times a day for further 4 days. The responsiveness of the receptors of bronchi, heart, skeletal muscles, and peripheral vessels was tested before and after 1, 2, 3, 6, 9, and 12 mo of treatment with oral terbutaline and after the two 4-day periods with inhaled terbutaline. The receptors were tested by infusion of increasing doses of isoprenaline, so that dose-response curves for isoprenaline were recorded. No signs of resistance of the beta 2 receptors of the bronchi developed during the terbutaline treatment period. Thus no even spray in moderate overdose caused resistance. Within 1 mo of treatment with oral terbutaline, resistance developed to the tremorogenic effect of terbutaline. Six of the 8 patients showed no signs of development of resistance to the chronotropic effect of isoprenaline. No signs were found of resistance of the beta 2 receptors of peripheral blood vessels.
D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi; D001986:Bronchial Spasm / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005541:Forced Expiratory Volume; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol; D008875:Middle Aged; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013726:Terbutaline / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D014202:Tremor / Q000139:chemically induced
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D013726:Terbutaline