Timed effects of an oral adrenergic bronchodilator on pulmonary function and measurements of plasma and leukocyte cyclic AMP: divergence in duration of drug action and development of tolerance.
The time course of response to initiation and withdrawal of treatment with terbutaline (5 mg orally, three times daily) was examined in eight normal subjects and 14 asthmatic patients. The various indices of response, examined simultaneously, yielded divergent estimates of the duration of drug action and the development of tolerance during continuous treatment. Bronchodilator responses were observed after each dose of terbutaline, but within 8 hr after a dose, pulmonary functions were similar to those observed in the absence of treatment. There was a suggestion of moderate tolerance to the bronchodilator effects of medication in that areas under the curve for increments in pulmonary function after terbutaline were lower during treatment than after the initial doses of medication; but the variations in magnitude of pulmonary response on different study days did not achieve statistical significance. Measurements of plasma cyclic AMP concentration suggested a much longer duration of drug action, with elevated levels observed 24 hr after a treatment dose; there was a progressive decrease in the plasma cyclic AMP responses to medication during the course of treatment. Conversely, leukocyte cyclic AMP responses to adrenergic stimulation were suppressed within 4 hr after the first dose of medication; the suppression persisted throughout treatment and for 1 to 3 days thereafter. These observations indicated that duration of drug action and induction of tolerance vary in different organ systems.
D000284:Administration, Oral; D000328:Adult; D001249:Asthma / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000097:blood*; D003692:Delayed-Action Preparations; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000032:analysis*; D008168:Lung / Q000502:physiology*; D008297:Male; D013566:Sympathomimetics / Q000008:administration & dosage*; D013726:Terbutaline / Q000627:therapeutic use; D013997:Time Factors
D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D013566:Sympathomimetics; D000242:Cyclic AMP; D013726:Terbutaline