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Abstract
Pain affects the quality of life for millions of individuals and is a major reason for healthcare utilization. As populations age, medical personnel will need to manage more and more patients suffering from pain associated with degenerative and inflammatory musculoskeletal disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are an effective treatment for both acute and chronic musculoskeletal pain; however, their use is associated with potentially significant gastrointestinal (GI) toxicity. Guidelines suggest various strategies to prevent problems in those at risk for NSAID-associated GI complications. In this article, we review the data supporting one such strategy - the use of histamine type-2 receptor antagonists (H2RAs) - for the prevention of GI adverse events in NSAID users. Older studies suggest that high-dose H2RAs are effective in preventing upper GI ulcers and dyspepsia. This suggestion was recently confirmed during clinical trials with a new ibuprofen/famotidine combination that reduced the risk of ulcers by 50% compared with ibuprofen alone.
Highlights
It is estimated that at least 50 million people in the United States suffer from chronic pain conditions while an additional 25 million people suffer from acute pain [1]
Similar conclusions were reached by Rostom and colleagues in their 2009 review of cyclooxygenase-2 inhibitors and nonsteroidal antiinflammatory drug (NSAID) plus gastroprotection in preventing GI toxicity. They noted that misoprostol, proton-pump inhibitor (PPI) and high doses of histamine type-2 receptor antagonist (H2RA) are all effective at reducing the risk of both endoscopic gastric and duodenal NSAID-induced ulcers, while standard doses of H2RAs are not effective at reducing the risk gastric ulcers but do reduce the risk of duodenal ulcers [27]
One should note that studies directly comparing high-dose H2RAs with PPIs or misoprostol for preventions of NSAID-associated upper GI lesions are not available
Summary
It is estimated that at least 50 million people in the United States suffer from chronic pain conditions while an additional 25 million people suffer from acute pain [1]. Like the many studies included in the Cochrane review, both of these REDUCE trials use endoscopic ulcer prevention as a primary endpoint; there is some uncertainty as to how this translates to clinical outcomes such as serious GI complications, there was significantly less dyspepsia noted with combination therapy compared with ibuprofen alone. One should note in the previous study that significantly more patients in the misoprostol group than the placebo group withdrew prematurely from the study due to side effects such as diarrhea, cramping and flatulence [34] Another large prospective, double-blind multicenter study found that standard-dose misoprostol was superior to PPIs such as lansoprazole for the prevention of NSAID-induced gastric ulcers, but when poor compliance and potential adverse effects associated with misoprostol were considered the PPIs and misoprostol were clinically equivalent [35]. The increased risk of pneumonia and C. difficile colitis is lower in patients taking H2RAs compared with patients taking PPIs [51,52]
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