Effects of inhibition of thromboxane A2 synthesis in aspirin-induced asthma.
Since inhibition of cyclo-oxygenase precipitates asthmatic attacks in patients with aspirin idiosyncrasy, we have evaluated the effects of pharmacological inhibition of the next enzyme in arachidonic acid cascade, i.e., thromboxane synthetase. Twelve patients with aspirin-induced asthma received on 3 days increasing doses (25-400 mg) of an imidazole derivative, OKY-046, which specifically blocks TXA2 synthetase. Twelve healthy controls received a single dose of 400 mg OKY-046. The drug neither precipitated asthmatic attacks nor altered pulmonary function tests throughout a 24-hr observation period. Five of 12 patients, but none of the controls, developed nasal congestion, approximately 1 hr after ingestion of the inhibitor. Though initial platelet aggregation evoked by arachidonic acid or ADP did not differ between the two groups, inhibitory effects of 400 mg OKY-046 on the aggregability were more pronounced in the patients than in the controls. Thus, inhibition of TXA2 synthetase, contrary to inhibition of cyclo-oxygenase, does not affect bronchopulmonary function in patients with asthma and aspirin intolerance. It does, however, often produce nasal congestion, possibly through reorientation of prostanoid synthesis from TXA2 to PGD2. It remains to be established whether pronounced depressive effects of a TXA2 synthetase inhibitor on platelet aggregability constitute a treat of aspirin idiosyncrasy or is a more general phenomenon associated with bronchial asthma.
D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000209:etiology* / Q000378:metabolism; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*
D001095:Arachidonic Acids; D008689:Methacrylates; D016718:Arachidonic Acid; D013930:Thromboxane-A Synthase; C034364:ozagrel; D001241:Aspirin