Protective effects of prostaglandins against nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are an integral part of the therapy of rheumatic diseases. All NSAIDs have the potential to cause damage to the gastrointestinal (GI) tract and have been implicated as a cause of peptic ulceration and massive life-threatening bleeding, often without warning symptoms. The basis of the damaging actions of NSAIDs on the GI tract is believed to be a consequence of two events: depletion of endogenous prostaglandins (PGs) and a direct damaging action on the mucosal integrity. Current evidence indicates that PGs play an important role in maintaining the integrity of the GI tract against ulcerogenic stimuli and are therefore ideally suited to counteract the NSAID-induced deleterious actions on the mucosa. With the exception of synthetic prostaglandins, the current therapeutic interventions used for the treatment of NSAID injury are not ideal. Misoprostol, a synthetic E-prostaglandin analogue, has been found to prevent and heal GI lesions induced by NSAIDs. The basis for the protective effect of prostaglandins is a consequence of their gastric antisecretory and mucosal protective properties. The mucosal protective effects of misoprostol are multifactorial and include, in part, the stimulation of mucus and bicarbonate secretion, an increased or sustained mucosal blood flow and the stabilization of the barrier function of the stomach. Misoprostol represents a major new advance in our therapeutic armamentarium for the treatment and prevention of NSAID-induced GI mucosal injury.