THE COMPARATIVE ACTIONS AND ADVERSE EFFECT PROFILE OF SINGLE DOSES OFH(1)-RECEPTOR ANTIHISTAMINES IN THE AIRWAYS AND SKIN OF SUBJECTS WITHASTHMA

Background: The development of potent H-1-receptor antagonists that ar e free of adverse effects has renewed interest in their use in the tre atment of asthma. Methods: We performed a study of the action of chlor pheniramine, terfenadine, brompheniramine, cetirizine, cyproheptadine, clemastine, and astemizole compared with placebo on histamine-induced skin wheals and bronchoconstriction in a single group of patients wit h asthma. Another group underwent methacholine bronchoprovocation. Res ults: Antihistamine pretreatment increased mean baseline measurements of forced expiratory volume in 1 second (FEV1) between 2.58% and 9.28% compared with placebo, which was significant for all drugs except bro mpheniramine and clemastine. Compared with placebo, all antihistamines provided significant protection against histamine-induced bronchocons triction when measured as the provocation concentration required to ca use a 20% fall in FEV1; terfenadine and cetirizine provided significan tly greater protection than other antihistamines. Protection against h istamine-induced skin wheals, measured as the slope of the log concent ration-response curve, was only significant for the new drugs, terfena dine and cetirizine. There was a good correlation between the protecti ve effect of the drugs in the skin and airways (r = 0.85; p < 0.01). N o significant difference in methacholine provocation concentration req uired to cause a 20% fall in FEV1 values between treatments was found. Conclusions: The new H-1-receptor antagonists terfenadine and cetiriz ine provided significantly better protection than the older antihistam ines against the action of histamine in the skin and airways. None of the antihistamines showed evidence of anticholinergic activity in the asthmatic airways at the doses studied.