NSAID-induced gastrointestinal damage. A critical review of prophylaxis and therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) cause acute diffuse injury to the gastroduodenal mucosa, and also cause chronic focal ulcers that may bleed or perforate without warning symptoms. Acute and chronic lesions are distinct, are pathogenetically different, respond differently to drugs, and require different management strategies. The principal rationale for antiulcer therapy in NSAID users is to prevent or reduce potentially fatal outcomes; to date no evaluated drug meets this criterion for efficacy. Antacids and H2-receptor antagonists, based on open uncontrolled studies, appear to heal both gastric and duodenal ulcers, and maintain them healed during continued NSAID use; larger gastric ulcers show delayed healing with conventional doses of H2-receptor antagonists during NSAID therapy. No such delay occurs with omeprazole therapy. The suggests that if NSAID-associated gastric ulcers are treated with H2-receptor antagonists, larger doses should be given for longer periods. In patients with no pre-existing ulcer disease, H2-receptor antagonists given prophylactically prevent duodenal but not gastric ulcers; sucralfate does the same. In individuals without peptic ulcer disease taking NSAIDs, misoprostol, given as prophylaxis, reduces the development of gastric ulcers; its beneficial effects on ulcer healing or symptoms during continued NSAID therapy, or its ability to prevent duodenal ulcers or ulcer complications, are not established. Because of diarrhea, the 400 micrograms/day dosage is recommended, especially in the elderly. 