Ingvar Bjarnason1, Ken Takeuchi. 1. Department of Gastroenterology, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
Abstract
BACKGROUND: The pathogenesis of nonsteroidal antiinflammatory drug (NSAID)-induced small bowel disease suggests that increased intestinal permeability is the central mechanism that translates biochemical damage to tissue damage. The purpose of this review is to summarize studies on the effect of NSAIDs to increase intestinal permeability in humans and methods for limiting this effect. METHODS: A Medline search was made for papers that described measurements of increased intestinal permeability in humans. RESULTS: Virtually all studies agree that all conventional NSAIDs increase intestinal permeability in the human within 24 h of ingestion and that this is equally evident when they are taken long term. Various methods have been tried to limit the damage. The most promising agents are coadministration of synthetic prostaglandins, micronutrients, pre-NSAIDs, and COX-2 selective agents. However, their efficacy in preventing the development of NSAID enteropathy in the long term has not been studied in detail, and, in the case of COX-2 selective agents, small bowel damage is comparable to that which is seen with conventional NSAIDs. CONCLUSIONS: NSAID enteropathy is associated with significant morbidity and occasionally mortality. There are no proven effective ways of preventing this damage. Because increased intestinal permeability appears to be a central mechanism in the pathogenesis of NSAID enteropathy, it becomes a potential therapeutic target for prevention. At present there are a number of ways to limit the increased permeability, but additional studies are required to assess if this approach reduces the prevalence and severity of NSAID enteropathy.
BACKGROUND: The pathogenesis of nonsteroidal antiinflammatory drug (NSAID)-induced small bowel disease suggests that increased intestinal permeability is the central mechanism that translates biochemical damage to tissue damage. The purpose of this review is to summarize studies on the effect of NSAIDs to increase intestinal permeability in humans and methods for limiting this effect. METHODS: A Medline search was made for papers that described measurements of increased intestinal permeability in humans. RESULTS: Virtually all studies agree that all conventional NSAIDs increase intestinal permeability in the human within 24 h of ingestion and that this is equally evident when they are taken long term. Various methods have been tried to limit the damage. The most promising agents are coadministration of synthetic prostaglandins, micronutrients, pre-NSAIDs, and COX-2 selective agents. However, their efficacy in preventing the development of NSAID enteropathy in the long term has not been studied in detail, and, in the case of COX-2 selective agents, small bowel damage is comparable to that which is seen with conventional NSAIDs. CONCLUSIONS:NSAID enteropathy is associated with significant morbidity and occasionally mortality. There are no proven effective ways of preventing this damage. Because increased intestinal permeability appears to be a central mechanism in the pathogenesis of NSAID enteropathy, it becomes a potential therapeutic target for prevention. At present there are a number of ways to limit the increased permeability, but additional studies are required to assess if this approach reduces the prevalence and severity of NSAID enteropathy.
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