Nonsteroidal anti-inflammatory drugs (
NSAIDs) are most frequently used for the treatment of
rheumatic disease due to their anti-inflammatory and
analgesic properties. All
NSAIDs have the potential to cause damage to the gastrointestinal (GI) tract and have been associated with the induction of
peptic ulcers and massive life-threatening
bleeding. The therapeutic approaches for the treatment and prevention of
NSAID-induced
ulcers is critically reviewed using data derived from carefully controlled, world-wide clinical studies with
anti-ulcer drugs.
Histamine (H2) antagonists,
omeprazole,
sucralfate and E-
prostaglandin (
PGE) analogs are effective for the treatment of
NSAID-induced gastric and
duodenal ulcers, if
NSAIDs are discontinued. However, if
NSAIDs are continued while GI damage is present, the
PGE analogs
misoprostol,
arbaprostil and
enprostil have shown efficacy in healing
NSAID-induced
ulcers. Furthermore, one limited clinical study demonstrated that
omeprazole has efficacy in healing
NSAID-associated
ulcers. Neither H2 antagonists,
sucralfate and
sulglycotide (a cytoprotective
drug) have shown efficacy in preventing
NSAID-induced
gastric ulcers. However H2 antagonists have shown efficacy in preventing
NSAID-induced
duodenal ulcers. In contrast, only
misoprostol prevents the development of
NSAID-induced gastric and
duodenal ulcers. Such pharmacological observations suggest that the pathophysiologic mechanisms for the induction of
NSAID-induced
gastric ulcer are distinctly different from those of
NSAID-induced
duodenal ulcers. Mild
diarrhea and GI intolerance were the predominant adverse reactions experienced by patients receiving synthetic PGEs, particularly
enprostil and
arbaprostil. From the published data, we conclude that
misoprostol is the only anti-
ulcer drug proven to be well tolerated and effective for the treatment and prevention of
NSAID-induced gastric and
duodenal ulcers in patients receiving chronic
NSAIDs therapy.