The protective effect of inhaled chlorpheniramine and atropine on bronchoconstriction stimulated by airway cooling.
We examined the role of histamine release and reflex bronchoconstriction in the bronchoconstriction stimulated by airway cooling. In 8 asthmatic subjects, dose-response curves were determined to isocapnic hyperventilation of cold air 30 min after inhalation of chlorpheniramine maleate (18 mg nebulized during tidal breathing), 2 doses of atropine sulphate (3 mg and 18 mg nebulized), or placebo. Treatments were given on separate days, in random order and under double-blind conditions. The bronchial antihistamine and anticholinergic actions of chlorpheniramine were determined by the effect on histamine and methacholine dose-response curves on another 4 days. Chlorpheniramine was selective as an antagonist against histamine; it increased the mean provocation concentration of histamine to reduce the FEV1 by 20% (PC20) 14.2-fold but increased the mean PC20 methacholine only 1.85-fold. Atropine in the 3-mg dose, previously shown to increase the PC20 methacholine at least 100-fold, had no effect on heart rate or saliva output in contrast to 18 mg, which significantly reduced saliva output and increased heart rate. Chlorpheniramine caused no bronchodilation and a small 1.28-fold increase in the amount of respiratory heat exchange needed to reduce the FEV1 by 10% (PD10RHE). Atropine caused maximal bronchodilation after 3 mg and a dose-dependent increase in PD10RHE (1.16-fold increase after 3 mg and 1.32-fold increase after 18 mg atropine). The effect of chlorpheniramine and atropine 18 mg on PD10RHE was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects*; D001985:Bronchial Provocation Tests; D002744:Chlorpheniramine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002986:Clinical Trials as Topic; D003080:Cold Temperature; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006339:Heart Rate; D006632:Histamine; D006801:Humans; D008297:Male; D008688:Methacholine Compounds; D010812:Physical Stimulation; D012463:Saliva / Q000378:metabolism
D008688:Methacholine Compounds; D002744:Chlorpheniramine; D001285:Atropine; D006632:Histamine