NSAID-induced peptic ulcer disease: a critical review of pathogenesis and management

Nonsteroidal anti-inflammatory drugs (NSAIDs) initiate gastroduodenal ulceration and promote complications such as bleeding and perforation. Age greater than 60 years, a prior history of ulcer disease, and concomitant corticosteroid use are important risk factors for ulcer development. NSAIDs interfere with mucosal defense via direct toxic effects in addition to cyclooxygenase inhibition and subsequent depletion of endogenous prostaglandins. While all NSAIDs are ulcerogenic, drugs which avoid topical injury and do not inhibit mucosal prostaglandins appear to have lesser risk of toxicity. Although NSAID injury requires luminal acid, prophylactic use of H2 receptor antagonists has been disappointing, preventing duodenal injury only. Greater acid suppression with proton pump inhibition appears promising. Prostaglandins are effective for prevention of NSAID-induced gastroduodenal injury, but are not well tolerated. Recent evidence suggests NSAID ulcers heal rapidly with proton pump inhibitors compared to H2 receptor antagonists in those patients who require continued NSAID therapy.