[Pathogenesis of gastroduodenal lesions induced by non-steroidal anti-inflammatory drugs].
The pathogenesis of the gastroduodenal lesions induced by non-steroidal anti-inflammatory drugs and aspirin is primarily caused by a reduction in mucosal blood flow, which is the consequence of inhibition of cyclooxygenase-producing vasodilator prostaglandins. The subsequent phase is adherence of leukocytes to the endothelium, which may depend on cyclooxygenase-2. Endothelial lesions accentuate the fall of mucosal blood flow and promote the inflammatory process in the gastric mucosa. The inflammatory process is amplified by expression of TNFalpha in polymorphonuclears induced by non-steroidal anti-inflammatory drugs. A few days after starting treatment, epithelial proliferation and increased mucosal blood flow, partly dependent on cyclooxygenase-2 and nitric oxide expression, compensates for the damaging process. Selective inhibitors of inducible cyclooxygenase-2 have reduced gastrointestinal toxicity, which could partially be explained by the protection effect of cyclooxygenase-2 on the gastrointestinal mucosa during inflammation or epithelial repair. Selective inhibitors may worsen inflammatory bowel disease. Non-steroidal inflammatory drugs and aspirin, but perhaps not selective inhibitors, increase the mucosal lesions associated with Helicobacter pylori-induced gastritis. Co-administration of selective inhibitors and aspirin leads to gastrointestinal toxicity equivalent to that of non-specific anti-inflammatory drugs.
Lamarque
Dominique
D
Service d'Hépato-Gastroentérologie, Hôpital Bichat, Paris. dominique.lamarque@bch.ap-hop-paris.fr
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects; D004378:Duodenal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000503:physiopathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D009569:Nitric Oxide
Physiopathologie des lésions gastro-duodénales induites par les anti-inflammatoires non stéroïdiens.