Effect of oral terfenadine on the bronchoconstrictor response to inhaled histamine and adenosine 5'-monophosphate in non-atopic asthma.
Inhaled adenosine 5'-monophosphate (AMP) causes bronchoconstriction in atopic asthma, probably after in vivo conversion to adenosine. It has been suggested that adenosine potentiates preformed mediator release from mast cells on the mucosal surface of the airways by interacting with specific purinoceptors, without affecting the release of newly generated mediators. The airway response of nine non-atopic subjects with "intrinsic" asthma to inhaled AMP and the influence of the oral, selective H1 histamine receptor antagonist terfenadine on this response was investigated. The geometric mean provocation concentrations of histamine and AMP required to produce a 20% fall in FEV1 (PC20) were 1.82 and 13 mmol/l. In subsequent placebo controlled time course studies the FEV1 response to a single inhalation of the PC20 histamine was ablated after pretreatment with oral terfenadine 180 mg. This dose of terfenadine caused an 80% inhibition of the bronchoconstrictor response to the PC20 AMP when measured as the area under the time course-response curve and compared with the response to PC20 AMP preceded by placebo. Terfenadine 600 mg failed to increase protection against AMP further, but both doses of terfenadine delayed the time at which the mean maximum fall in FEV1 after AMP was achieved. Terfenadine 180 mg had no effect on methacholine induced bronchoconstriction in the same subjects. These data suggest that inhaled AMP may potentiate the release of preformed mediators from preactivated mast cells in the bronchial mucosa of patients with intrinsic asthma.
D000249:Adenosine Monophosphate / Q000008:administration & dosage / Q000494:pharmacology*; D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001249:Asthma / Q000503:physiopathology*; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects; D001985:Bronchial Provocation Tests; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016593:Terfenadine
D001559:Benzhydryl Compounds; D006634:Histamine H1 Antagonists; D000249:Adenosine Monophosphate; D016593:Terfenadine; D006632:Histamine