COX-2 specific inhibitors in NSAID-intolerant patients.
Most adverse NSAID-induced respiratory and skin reactions appear to be precipitated by the inhibition of cyclooxygenase-1 (COX-1); this in turn activates the lypoxygenase pathway, which eventually increases the release of cysteinyl leukotrienes (Cys-LTs). Recent studies have reported that patients with NSAID-induced asthma have a low production of PGE2 in respiratory epithelial cells, bronchial fibroblast and peripheral blood cells. Low production of PGE2 may be due to an insufficient cyclooxygenase-2 (COX-2) expression in the inflammatory response underlying asthma. Since PGE2 administered by inhalation inhibits NSAID-induced bronchoconstriction and the parallel increase in Cys-LTs release, a reduced PGE2 synthesis may render NSAID-patients more susceptible to the COX-1 inhibitory effects of NSAIDs. Recent studies have shown that selective COX-2 inhibitors (rofecoxib and celecoxib), unlike COX-1 inhibitors, are very well tolerated by NSAID-sensitive patients and do not elicit increased Cyst-LTs production. However, these drugs can still can precipitate cutaneous reactions in a significant proportion of patients with skin reactions to NSAID. The heterogeneity of the NSAID-intolerance syndrome suggests that subjects who do not tolerate NSAID can use coxibs only after first having been exposed to the drug under the supervision of a specialist with experience in these procedures.
Picado
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Servei de Pneumologia i Respiratória, Hospital Clinic, Department de Medicina, Universitat de Barcelona, Barcelona, Spain. cpicado@medicina.ub.es
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases