Current Topics of Strategy of NSAID-Induced Small Intestinal Lesions

Abstract

Small intestinal mucosal injuries have been recently recognized as common complications associated with non-steroidal anti-inflammatory drugs (NSAIDs) because video capsule endoscopy and balloon enteroscopy are now available for the detection of small intestinal lesions. Small intestinal injury occurs not in an acid-dependent mechanism but by various factors such as enteric bacteria, bile acids, prostaglandin (PG) deficiency and topical factors (abnormal intestinal mucosal permeability, mitochondrial dysfunction, reactive oxygen species, endoplasmic reticulum stress and so on), and there is no well-established prophylactic approach. Several experimental and clinical studies found the effectiveness of some of the mucoprotective drugs, PG analogs, but not that of acid suppressants. Considering the effect of proton pump inhibitors (PPIs) for upper gastrointestinal (GI) disease and in the small intestine, the following 2 kinds of strategies against NSAID-induced GI injuries may be recommended. In patients with a high risk of upper GI disease (peptic ulcer etc.), simultaneous administration of a PPI (for upper GI disease) and a mucoprotective drug (for small intestine) is needed to prevent NSAID-induced GI injury. In other cases, an effective mucoprotective drug is enough for the protection of the entire digestive tract, that is, starting from the esophagus to the small intestine. These strategies may fulfill both economical and curative effects.

Review article: drug‐induced small bowel injury

“…18 5) alterations in the innate immune system to include tumour necrosis factor (TNF) activation. 19,20…”

Impact of proton pump inhibitors on the risk of small bowel or colorectal bleeding: A systematic review and meta‐analysis

“…Unnecessary use of PPIs should be discontinued unless the patient has indications for PPI use, such as peptic ulcer, reflux esophagitis, or a history of UGIB. Because mucoprotective agents, including rebamipide, irsogladine, and misoprostol, are helpful in the protection and healing of NSAID‐induced enteropathy, it is necessary to administer a mucoprotective agent together in patients requiring PPI use 31 . Our strategy will help reduce the risk of LGIB while simultaneously providing maximum beneficial effects on the UGI tract.…”

Effect of egualen sodium hydrate on small-intestinal mucosal damage induced by low-dose aspirin: a prospective randomized clinical trial

“…Indeed, some reports describing the risk of PPIs on the small intestinal injury in human have been recently published although the interaction between NSAIDs and PPIs use for small intestinal bleeding have been still under controversial. ( 36 – 39 ) Therefore, we consider that mucosal protection, which is independent of acid-suppression, will be necessary to prevent NSAID-induced enteropathy for patients receiving long-term treatment with aspirin.…”