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World J Gastroenterol. Mar 28, 2013; 19(12): 1861-1876
Published online Mar 28, 2013. doi: 10.3748/wjg.v19.i12.1861
Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy
John L Wallace
John L Wallace, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada
John L Wallace, Inflammation Research Network, University of Calgary, Calgary, AB T2N 4N1, Canada
Author contributions: Wallace JL solely contributed to this paper.
Supported by A grant from the Canadian Institutes of Health Research
Correspondence to: John L Wallace, PhD, MBA, FRSC, Farncombe Family Digestive Health Research Institute, McMaster University, 1280 Main Street West, HSC-3N4, Hamilton, ON L8S 4K1, Canada.
Telephone: +1-905-5156132 Fax: +1-905-5289862
Received: January 23, 2013
Revised: March 6, 2013
Accepted: March 7, 2013
Published online: March 28, 2013

This article reviews the latest developments in understanding the pathogenesis, detection and treatment of small intestinal damage and bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs). With improvements in the detection of NSAID-induced damage in the small intestine, it is now clear that this injury and the associated bleeding occurs more frequently than that occurring in the stomach and duodenum, and can also be regarded as more dangerous. However, there are no proven-effective therapies for NSAID-enteropathy, and detection remains a challenge, particularly because of the poor correlation between tissue injury and symptoms. Moreover, recent studies suggest that commonly used drugs for protecting the upper gastrointestinal tract (i.e., proton pump inhibitors) can significantly worsen NSAID-induced damage in the small intestine. The pathogenesis of NSAID-enteropathy is complex, but studies in animal models are shedding light on the key factors that contribute to ulceration and bleeding, and are providing clues to the development of effective therapies and prevention strategies. Novel NSAIDs that do not cause small intestinal damage in animal models offer hope for a solution to this serious adverse effect of one of the most widely used classes of drugs.

Keywords: Anti-inflammatory, Ulcer, Prostaglandin, Non-steroidal, Bleeding, Intestinal, Bile, Enterohepatic, Bacteria, Hydrogen sulfide, Aspirin, Hemorrhage