Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

Abstract

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 NSAIDenteropathy, 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 NSAIDenteropathy 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 in- FRONTIER

Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity

“…The adverse drug reactions in the duodenum, jejunum, and ileum are collectively termed enteropathy. Obvious small intestinal damage and bleeding occur in 70% of chronic NSAID users, although most patients do not show obvious clinical symptoms [2] . Some reports have shown an association between NSAID use and significant damage to the more distal regions of the small intestine [3] .…”

NSAID enteropathy and bacteria: a complicated relationship

“…Although an abundance of evidence exists to suggest that bacteria contribute to the development of NSAID enteropathy, whether the bacteria directly initiate the damage once the intestine has been rendered susceptible to injury through inhibition of mucosal prostaglandin synthesis or whether bacteria exacerbate pre-existing tissue injury and impede repair remains unclear [1,2]. An additional layer of complexity in determining the role of bacteria in NSAID enteropathy is that the intestinal microbiota, enterohepatic circulation, and bile are all closely interrelated.…”

“…Although there are drugs available for preventing the upper GI tract adverse effects of NSAIDs (inhibitors of gastric acid secretion), no measures have been identified that have been proven to be effective at preventing the small intestinal injury caused by these drugs [1,4,5]. There are also no proven-effective treatments for NSAID enteropathy once it has occurred [1,2,4]. With improved means of detection, such as video capsule endoscopy, physicians are becoming more aware that the small intestinal damage caused by NSAIDs is much more common and much more serious than previously recognized [4,[6][7][8][9][10][11].…”

“…Nonsteroidal anti-inflammatory drugs (NSAIDs) remain among the most widely used drugs worldwide despite significant adverse effects that include gastrointestinal (GI) ulceration and bleeding [1,2] and an increased risk of serious cardiovascular events [3]. Although there are drugs available for preventing the upper GI tract adverse effects of NSAIDs (inhibitors of gastric acid secretion), no measures have been identified that have been proven to be effective at preventing the small intestinal injury caused by these drugs [1,4,5].…”

A Comprehensive Evaluation of Peripheral Analgesic and Antipyretic Activities of Divalent Metal Complexes of Indomethacin

“…10,11 The most significant among all of the adverse effects of these drugs include gastrointestinal (GI) ulceration and bleeding. 12,13 There are also increased risks of cardiovascular events. 14,15 Though widely used, the ulceration and bleeding caused by these drugs remain a major clinical concern.…”