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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The comparative actions and adverse effect profile of single doses of H1-receptor antihistamines in the airways and skin of subjects with asthma.

BACKGROUND: The development of potent H1-receptor antagonists that are free of adverse effects has renewed interest in their use in the treatment of asthma. METHODS: We performed a study of the action of chlorpheniramine, terfenadine, brompheniramine, cetirizine, cyproheptadine, clemastine, and astemizole compared with placebo on histamine-induced skin wheals and bronchoconstriction in a single group of patients with asthma. Another group underwent methacholine bronchoprovocation. RESULTS: 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 brompheniramine and clemastine. Compared with placebo, all antihistamines provided significant protection against histamine-induced bronchoconstriction when measured as the provocation concentration required to cause a 20% fall in FEV1; terfenadine and cetirizine provided significantly greater protection than other antihistamines. Protection against histamine-induced skin wheals, measured as the slope of the log concentration-response curve, was only significant for the new drugs, terfenadine and cetirizine. There was a good correlation between the protective effect of the drugs in the skin and airways (r = 0.85; p < 0.01). No significant difference in methacholine provocation concentration required to cause a 20% fall in FEV1 values between treatments was found. CONCLUSIONS: The new H1-receptor antagonists terfenadine and cetirizine provided significantly better protection than the older antihistamines 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.[1]


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