Nonsteroidal antiinflammatory drugs and the small intestine.
OBJECTIVE
The small intestine is a more common site for nonsteroidal antiinflammatory drug (NSAID) toxicity than the well-recognized effects on the stomach and duodenum. Although NSAID strictures and perforation are rare, two thirds of regular NSAID users may be prone to small bowel enteropathy. This review highlights this emerging issue in patients requiring antiinflammatory drugs.


RESULTS
NSAID enteropathy is a stepwise process involving direct mucosal toxicity, mitochondrial damage, breakdown of intercellular integrity, enterohepatic recirculation, and neutrophil activation by luminal contents, including bacteria. Unlike upper gastrointestinal toxicity, cyclooxygenase-mediated mechanisms are probably less important. Newer imaging modalities such as capsule endoscopy studies suggest that small bowel erosions may be common in nonselective NSAID users. Sulfasalazine and metronidazole may prove to be useful, therapeutic options for patients who cannot cease their NSAIDs.


CONCLUSIONS
NSAID toxicity to the small intestine is common. Useful research tools have been developed to measure intestinal inflammation and permeability indirectly, but these are not generally available to the clinician, although enteroscopy and capsule endoscopy may be helpful. Anemia or hypoalbuminemia are useful clues to NSAID enteropathy. Cessation of the drug is ideal; otherwise, there is experimental data to support the use of sulfasalazine and metronidazole. Animal models are unraveling new mechanisms for mucosal toxicity beyond the cyclooxygenase model.
Fortun
Paul James
PJ
University of Nottingham, Queens Medical Centre, United Kingdom. Paul.fortun@nottingham.ac.uk
Hawkey
Christopher John
CJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D003251:Constriction, Pathologic / Q000139:chemically induced; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced; D007410:Intestinal Diseases / Q000139:chemically induced*; D007413:Intestinal Mucosa / Q000473:pathology; D007415:Intestinal Obstruction / Q000139:chemically induced
D000894:Anti-Inflammatory Agents, Non-Steroidal