Abstract

Capsule endoscopy and balloon endoscopy, advanced modalities that allow full investigation of the entire small intestine, have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) can cause a variety of abnormalities in the small intestine. Recently, several reports show that traditional NSAIDs (tNSAIDs) and acetylsalicylic acid (ASA) can induce small intestinal injuries. These reports have shown that the preventive effect of proton pump inhibitors (PPIs) does not extend to the small intestine, suggesting that concomitant therapy may be required to prevent small intestinal side effects associated with tNSAID/ASA use. Recently, several randomized controlled trials used capsule endoscopy to evaluate the preventive effect of mucoprotective drugs against tNSAID/ASA-induced small intestinal injury. These studies show that misoprostol and rebamipide reduce the number and types of tNSAID-induced small intestinal mucosal injuries. However, those studies were limited to a small number of subjects and tested short-term tNSAID/ ASA treatment. Therefore, further extensive studies are clearly required to ascertain the beneficial effect of these drugs.

Highlights

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed drugs worldwide

  • Most studies on traditional NSAIDs (tNSAIDs)/acetylsalicylic acid (ASA)-associated injury have focused on the upper gastrointestinal tract, since the stomach and duodenum are the sites generally associated with major morbidity and mortality in the clinical setting

  • Capsule endoscopy and double-balloon endoscopy [11,12], advanced modalities that allow for full investigation of the entire small intestine, have revealed that tNSAID/ASA can cause a variety of abnormalities in the small intestine; such as erosions, ulcerations, perforation, bleeding and diaphragm-like stricture (Figure 1–3) [8,9,13,14,15,16,17,18]

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Summary

Introduction

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed drugs worldwide. We conducted our own study using a larger number of patients to re-evaluate the effect of rebamipide on diclofenac-induced small intestinal injuries in healthy subjects, in a double-blind, randomized controlled trial [24]. Niwa et al reported that geranylgeranylacetone reduced diclofenac-induced gastric and small intestinal injuries, from 9.5 ± 8.5 in the placebo group to 2.6 ± 3.2 in the geranylgeranylacetone group as evaluated by capsule endoscopy (p = 0.027) [57] Their data were obtained in a double-blind, randomized, cross-over study where subjects were treated with diclofenac and omeprazole in the presence or absence of geranylgeranylacetone (300 mg/day) for seven days; when their analysis was confined to small intestinal injuries, the difference between the two groups was not significant. Data for this last study were obtained in a double-blind, randomized, cross-over study where subjects were treated with indomethacin (50 mg/day) for five days in the presence or absence of fish hydrolysate starting two days prior to indomethacin

Conclusions
Findings
Study design

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