A comparison of the actions of H 1 and H 2 antihistamines on histamine-induced bronchoconstriction and cutaneous wheal response in asthmatic patients

Abstract

The effect of an H 1 antihistamine, an H 2 antihistamine, and the combination of the two drugs on both histamine-induced bronchoconstriction and dermal whealing was examined in five patients with mild asthma. Chlorpheniramine 8 mg, cimetidine 300 mg, the combination of both, and placebo were administered orally to each patient for a single dose and for seven consecutive doses given every 6 hr after a double-blind, randomized protocol. The airway response to inhaled histamine and the wheal size induced by the intradermal injection of histamine were determined in every patient 2 hr after the final drug dose. The results indicate that a single dose of chlorpheniramine produces a significant increase in the threshold of histamine-induced bronchoconstriction as measured by the provocative histamine dose producing 20% decrease in 1-sec forced expiratory volume (PD 20 -FEV 1 ), and this effect was significantly enhanced after seven doses. Cimetidine caused a significant decrease in the threshold of histamine-induced bronchoconstriction, but this was not augmented by seven doses. Only chlorpheniramine, when given for seven doses, improved the baseline FEV 1 and forced expiratory flow during middle half of forced vital capacity (FEF 25%–75%). Chlorpheniramine in both single and multiple doses and the combination of chlorpheniramine and cimetidine given for seven doses produced a significant inhibition of histamine-induced dermal wheals, whereas cimetidine alone had no effect. These results confirm our previous observation that both H 1 and H 2 receptors are present in the airways of asthmatic patients and that they mediate opposite effects. We also demonstrated a cumulative effect with the repeated administration of chlorpheniramine but not with cimetidine. Finally, the results suggest that the role of H 1 and H 2 receptors differs in the bronchi from that seen in the dermal vessels of asthmatic patients and are in contrast to these of normals. The H 2 receptor effect on histamine-induced skin wheals appears deficient, further supporting earlier suggestions of the presence of an H 2 receptor defect in asthmatic patients.