EFFECT OF ORALLY-ADMINISTERED CIMETIDINE ON HISTAMINE-INDUCED AND ANTIGEN-INDUCED BRONCHOSPASM IN SUBJECTS WITH ASTHMA 1-3

Publisher Website
Google Scholar
Abstract
The effects of cimetidine on sensitivity to both histamine- and antigen-induced bronchospasm were studied in 12 subjects with mild asthma (baseline FEV1 [forced expiratory vol in 1 s] > 70% predicted). Bronchial challenges with inhaled histamine or antigen were performed 2 h after a single dose of 300 mg cimetidine or placebo orally administered in a random, double-blind manner on separate days. The provocative concentration of antigen or histamine that produced a 20% decline in FEV1 from the postdiluent control value (PC20) was determined and log transformed. Plasma cimetidine concentrations 2 h after oral administration (mean 1.5 .mu.g/ml; range 0.9-2.4) were above the minimal concentration required for suppression of gastric acid secretion. No difference was noted in FEV1, specific airway conductance or partial expiratory flow rates after cimetidine compared with that after placebo, indicating the lack of any bronchospastic effect of cimetidine in the absence of histamine or antigen challenge. Mean log PC20 of histamine (but not of antigen) was significantly less after cimetidine than after placebo (P < 0.05), indicating that cimetidine augmented histamine- (but not antigen-) induced bronchospasm. Of 12 subjects, 4 exhibited a significant (.gtoreq. 4-fold) decline in PC20 for histamine after cimetidine compared with that after placebo but no subject demonstrated a significant (.gtoreq. 10-fold) decline in PC20 of antigen. No relationship was apparent between baseline sensitivity to histamine and cimetidine effect on histamine sensitivity in individual subjects. Evidently, in subjects with mild asthma, cimetidine in the usual recommended orally administered dose can increase sensitivity to bronchospasm induced by histamine but not by antigen. Evidently cimetidine in this dose has a blocking effect on H2 receptors in airway smooth muscle, but this effect is not sufficient to alter the net impact of immunologic release of mediators on the airways.

This publication has 0 references indexed in Scilit: