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NSAID-induced intestinal damage: are luminal bacteria the therapeutic target?
  1. C Scarpignato
  1. Professor Carmelo Scarpignato, Laboratory of Clinical Pharmacology, School of Medicine and Dentistry, University of Parma, Via Volturno, 39 - 43100 Parma, Italy; scarpi{at}

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Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used medications in patients suffering from different rheumatic and musculoskeletal conditions. They represent a very effective class of drug, but their use is associated with a broad spectrum of untoward reactions in the liver, kidney, skin and gut.1 Although the upper gastrointestinal (GI) toxicity of NSAIDs is well documented, the appreciation that NSAID damage extends beyond the duodenum is less well recognised.2 NSAID-associated toxicity to the small and large bowel has several different manifestations, including sub-clinical and clinically evident damage (table 1).35 The prevalence of NSAID-associated lower GI side effects may exceed that detected in the upper GI tract and the frequency of life-threatening complications due to the lower GI tract represents nowadays no less than a third of all GI complications associated with the use of these agents.5 NSAIDs may also exacerbate underlying diseases, such as inflammatory bowel disease (IBD), which is a difficult clinical problem since many patients suffer from both IBD and arthritic diseases.4 5

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Table 1 Sub-clinical and clinical consequences to the distal gastrointestinal tract associated with NSAIDs use (from Lanas and Scarpignato5)

Although the inhibition of mucosal prostaglandin (PG) synthesis during NSAID use occurs along the entire digestive system, there are significant differences between the distal and the proximal GI tract in the concurrence of other pathogenic factors that may add to damage. Among them, the absence of acid (which plays a pivotal role in the pathogenesis of upper GI damage6) and the presence of bacteria and bile in the intestine, which may trigger specific NSAID-related pathogenic mechanisms at the distal GI tract level, are the most evident.

Despite knowledge of the existence of two COX isoenzymes, it is still unclear whether the inhibition of one or both enzymatic activities is needed for the intestinal damage to develop. An increasing body of experimental evidence7 8 suggests …

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  • CS is member of advisory boards for Pfizer, Boehringer-Ingelheim and Alfa Wasserman and belongs to the Speakers’ Bureau of Astra-Zeneca, Merck Sharp & Dohme and Negma-Gild.

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