One of the most serious side effects of nonsteroidal anti-inflammatory drugs (
NSAIDs) is upper gastrointestinal mucosal damage that may result in erosions, ulcerations and other serious complications.
NSAIDs reduce endogenous
prostaglandins, and this reduction is relevant to their pharmacology and toxicity. The stomach and to some extent the duodenum are the major organs involved in the mucosal toxicity of
NSAIDs. With 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
NSAID therapy. In fact,
misoprostol is the only
drug with established long-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
protective 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 H2-receptor antagonist
ranitidine has been shown to be effective in preventing
NSAID-induced
duodenal ulcers, but has no efficacy in preventing
NSAID-induced
gastric ulcers. In a direct comparative trial with
ranitidine,
misoprostol (200 micrograms qid) was significantly more effective than
ranitidine (150 mg bid) in preventing
gastric ulcers in chronic
NSAID users. The inactivity of
ranitidine in preventing
gastric ulcers indicates that the pathogenesis of
NSAID-induced
gastric ulcers is not related to gastric acid. Limited but conflicting data exist with
omeprazole. The mucosal-coating
drug sucralfate has not been found effective in preventing
NSAID ulcers. In fact, in a direct comparative trial,
misoprostol (200 micrograms qid) was significantly more effective than
sucralfate (1 g qid) in preventing
gastric ulcers in patients receiving chronic
NSAID therapy. No meaningful data exist with organic
bismuth salts, a group of drugs which has mucosal coating and protective properties. From this brief overview, we conclude: (1) mucosal-coating compounds have no therapeutic role in preventing
NSAID-induced ulceration; (2) gastric antisecretory drugs are not effective in preventing
NSAID-induced
gastric ulcers, and (3)
misoprostol is the only antiulcer
drug proven to be effective for preventing
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.