Aspirin-induced asthma. Hypersensitivity to fenoprofen and ibuprofen in relation to their inhibitory action on prostaglandin generation by different microsomal enzymic preparations.
Eighteen patients with asthma and aspirin hypersensitivity have been challenged with increasing doses of aspirin, fenoprofen, ibuprofen, and dextropropoxyphene. Low doses of the first three drugs induced bronchoconstriction in all the patients as evidenced by fall in peak expiratory flow and appearance of clinical symptoms. There were no reactions to therapeutic doses of dextropropoxyphene. Aspirin, fenoprofen, and ibuprofen, but not dextropropoxyphene, inhibited prostaglandin synthetase activity in three different microsomal preparations, i.e., in bovine seminal vesicles, in rabbit brain, and in rabbit kidney medulla. Expected in vivo antienzymic potency of a drug, calculated from experiments using rabbit brain microsomes, corresponded roughly with its potency to induce bronchoconstriction in the challenge tests. An individual pattern of sensitivity to threshold doses of prostaglandin synthetase inhibitors was demonstrated for each patient. The results obtained suggest that precipitation of asthmatic attacks by nonsteroidal anti-inflammatory drugs is mediated through inhibition of prostaglandin biosynthesis. The degree of enzymic inhibition, which is sufficient to precipitate bronchoconstriction, is an individual hallmark. Knowing the threshold dose for any of prostaglandin synthetase inhibitors in a patient, one can predict the threshold doses for the rest of aspirin-like drugs in this particular patient.
D000293:Adolescent; D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000209:etiology*; D003251:Constriction, Pathologic / Q000209:etiology; D011431:Dextropropoxyphene / Q000494:pharmacology; D004342:Drug Hypersensitivity / Q000209:etiology*; D005260:Female; D005279:Fenoprofen / Q000009:adverse effects*; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D010366:Peak Expiratory Flow Rate; D010666:Phenylpropionates / Q000009:adverse effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*
D010666:Phenylpropionates; D006899:Mixed Function Oxygenases; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D005279:Fenoprofen; D011431:Dextropropoxyphene; D007052:Ibuprofen