Effects of inhibition of thromboxane A2 synthesis in aspirin-induced asthma.
Since inhibition of cyclooxygenase precipitates asthmatic attacks in patients with aspirin idiosyncrasy, we have evaluated the effects of pharmacologic inhibition of thromboxane A2 (TXA2) synthetase, next to cyclooxygenase enzyme in arachidonic acid cascade. Sixteen patients with aspirin-induced asthma received increasing doses on 3 days (25 to 400 mg) of an imidazole derivative, OKY-046, which specifically blocks TXA2 synthetase. Twenty-three healthy control subjects received a single dose of 400 mg of OKY-046. In both patients and control subjects, the inhibitor at a dose of 400 mg produced (1) a pronounced fall in thromboxane B2 serum levels, (2) a rise in serum 6-keto-prostaglandin F1 alpha, and (3) a depression in platelet aggregability to arachidonic acid and adenosine diphosphate. The drug, however, neither precipitated attacks of asthma nor impaired pulmonary function tests throughout a 24-hour observation period. Five patients, but none of the control subjects, developed transient nasal congestion about 1 hour after taking the drug. Thus, inhibition of TXA2 synthetase, contrary to inhibition of cyclooxygenase, does not affect bronchopulmonary function in patients with asthma and aspirin intolerance.
Szczeklik
A
A
Department of Allergy and Clinical Immunology, Copernicus Academy of Medicine, Cracow, Poland.
Nizankowska
E
E
Splawinski
J
J
Dworski
R
R
Gajewski
P
P
Splawinska
B
B
D000179:Acrylates / Q000627:therapeutic use*; D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008689:Methacrylates / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D012129:Respiratory Function Tests; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000097:blood
D000179:Acrylates; D008689:Methacrylates; D013928:Thromboxane A2; C034364:ozagrel; D001241:Aspirin