PREVENTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUG-INDUCED GASTRODUODENAL ULCERS - ROLE OF MUCOSAL PROTECTIVE AND GASTRIC ANTISECRETORY DRUGS

One ofthe most serious side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) is upper gastrointestinal mucosal damage that may resul t in erosions, ulcerations and other serious complications. NSAIDs red uce endogenous prostaglandins, and this reduction is relevant to their pharmacology and toxicity. The stomach and to some extent the duodenu m are the major organs involved in the mucosal toxicity of NSAIDs. Wit h the availability of the synthetic prostaglandin misoprostol, it has become possible to prevent NSAID-induced gastroduodenal ulcers without compromising the beneficial antirheumatic and analgesic effects of NS AID therapy. In fact, misoprostol is the only drug with established lo ng-term efficacy in preventing NSAID-induced gastroduodenal ulcers in rheumatic patients. The purpose of this communication is to critically review the efficacy of gastric antisecretory drugs, mucosal protectiv e drugs and misoprostol when used for the prevention of NSAID-induced ulcers, considering only data from well-controlled, randomized, double -blind clinical studies. The histamine H-2-receptor antagonist ranitid ine has been shown to be effective in preventing NSAID-induced duoenal ulcers, but has no efficacy in preventing NSAID-induced gastric ulcer s. In a direct comparative trial with ranitidine, misoprostol (200 mu g qid) was significantly more effective than ranitidine (150 mg bid) i n preventing gastric ulcers in chronic NSAID users. The inactivity of ranitidine in preventing gastric ulcers indicates that the pathogenesi s of NSAID-induced gastric ulcers is not related to gastric acid. Limi ted but conflicting data exist with omeprazole. The mucosal-coating dr ug sucralfate has not been found effective in preventing NSAID ulcers. In fact, in a direct comparative trial, misoprostol (200 mu g qid) wa s significantly more effective than sucralfate (1g qid) in preventing gastric ulcers in patients receiving chronic NSAID therapy. No meaning ful data exist with organic bismuth sails, a group of drugs which has mucosal coating and protective properties. From this brief overview, w e conclude: (1) mucosal-coating compounds have no therapeutic role in preventing NSAID-induced ulceration; (2) gastric antisecretory drugs a re not effective in preventing NSAID-induced gastric ulcers, and (3) m isoprostol is the only antiulcer drug proven to be effective for preve nting NSAID-induced gastric and duodenal ulcers in patients receiving chronic NSAID. Misoprostol represents a major therapeutic advance for the management of NSAID-induced mucosal injury.