Prophylaxis and treatment of NSAID-induced gastroduodenal disorders

A significant percentage of patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) experience some type of adverse gastrointestinal symptoms, l esions of the gastroduodenal tract being clinically the most relevant, NSAIDs cause gastrointestinal damage by 2 independent mechanisms: a topical effect, which is pH and pKa related, and a systemic effect mediated by cyc looxygenase (COX) inhibition with a reduction in prostaglandin synthesis, U sing endoscopy, gastroduodenal lesions identified include subepithelial hae morrhages, erosions and ulcers, The prevalence of ulceration in NSAID users has been reported as being between 14 and 31% with a 2-fold higher frequen cy of gastric ulcers compared with duodenal ulcers, Among the strategies used to decrease the risk of ulcer development are: (i ) the use of analgesics other than NSAIDs; iii i use of the lowest possible dosage of NSAID; (iii) the use of a COX-2 selective NSAID; (iv) the use of low doses of corticosteroids instead of NSAIDs; (v) avoidance of concomita nt use of NSAIDs and corticosteroids; and (vi) use of preventive therapy. In an attempt to reduce the incidence of NSAID-induced gastrointestinal les ions, the following approaches have been proposed: (i) use of the prostagla ndin analogue misoprostol, which is an antiulcer drug which has been proven to be as effective in the prevention of NSAID-induced gastric and duodenal ulcers as in the reduction of serious upper gastrointestinal complications ; iii histamine Hz receptor antagonists (H-2 antagonists), e,g, ranitidine, cimetidine and famotidine, which are useful in the prevention of NSAID-ind uced duodenal ulcers during long term treatment, but not in the prevention of NSAID-induced gastric ulcers; (iii) proton Dump inhibitors, e.g omeprazo le. and pantoprazole, whose efficacy in preventing NSAID-associated ulcers has been recently demonstrated; and (iv) barrier agents, e.g, sucralfate, w hich cannot be recommended as prophylactic agents to prevent NSAID-induced gastropathy. The first step in the treatment of NSAID-associated ulcers lies in a reduct ion in the dosage of the NSAID or discontinuation of the drug. If NSAID tre atment cannot be withdrawn, a proton pump inhibitor appears to be the most effective treatment in healing ulcers, accelerating the slow healing observ ed with H-2? antagonists.