Although therapeutically beneficial, nonsteroidal anti-inflammatory drugs are associated with serious gastrointestinal side effects, including ulceration,
hemorrhage, and perforation. Endoscopic studies indicate that up to 30% of chronic
NSAID users will develop gastroduodenal ulceration. Various case-control studies have reported an association between
ulcer-related complications or deaths and
NSAID use. An imprecise correlation has been found to exist between the presence of
NSAID-induced gastrointestinal damage and symptoms, such as
dyspepsia and
pain. It is now thought that the major deleterious effects of
NSAIDs on the gastrointestinal tract are related to the ability of systemically absorbed
NSAIDs to alter gastric and duodenal defense mechanisms, primarily via inhibition of mucosal
prostaglandin synthesis. Although various therapeutic agents have been investigated for their ability to prevent
NSAID-induced
ulcers, only the
prostaglandin analogue misoprostol has been shown to significantly reduce the incidence of both gastric and
duodenal ulcers in
NSAID users. Recently, the
Misoprostol Ulcer Complications Outcomes Safety Assessment trial demonstrated that
misoprostol also reduces the most serious complications of
NSAID-induced
ulcers, namely
bleeding, perforation, and
gastric outlet obstruction.