Nonsteroidal Anti-Inflammatory Drugs and Lower Gastrointestinal Complications

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Mechanisms of intestinal damage by Nonsteroidal Anti-inflammatory Drugs

It is not completely clear how NSAIDs initiate damage in the lower GI tract. The widespread view is that upper GI toxicity by NSAIDs is mediated by both a non–prostaglandin-dependent local injury and, overall, by the systemic inhibition of the cyclooxygenase (COX) -1 enzyme.4, 6 This leads to a subsequent reduction in cytoprotective prostaglandins required for an effective mucosal defense.6 The pathogenic mechanism leading to inflammatory changes in the distal GI tract is less well known at

Lesions induced by Nonsteroidal Anti-Inflammatory Drugs in the distal gastrointestinal tract

The prevalence of NSAID-associated lower GI side effects, including both clinical and subclinical side effects, may exceed those detected in the upper GI tract and include a wide spectrum of lesions (Table 1).1, 4

Life-threatening complications from the lower gastrointestinal tract

Although increased permeability, inflammation, or even GI ulceration is the most common manifestation of NSAID toxicity, GI bleeding and perforation are the most clinically relevant side effects, since they contribute significantly to the increased risk of morbidity and mortality associated with these drugs. There is evidence that NSAIDs and/or aspirin are associated with complications from the lower GI tract since the early 1990s.37, 50, 51 Current evidence suggests that NSAIDs increase the

Lower Gastrointestinal damage with COX-2 selective inhibitors

COX-2 selective NSAIDs could be safer than tNSAIDS for the lower GI tract. The lack of intestinal damage with this type of agents in some animal experiments62 has been confirmed in preclinical study and, in 2000 and 2001, in clinical studies in humans.8, 63 In the short term, these agents do not increase mucosal permeability and have displayed a 50% reduction of serious lower GI side effects compared with tNSAIDS in some but not all post hoc analysis of outcome studies.20, 55

Smecuol and

Lower gastrointestinal damage by low-dose aspirin

It is generally believed that low-dose ASA does not cause any small bowel damage, since the drug is largely absorbed before reaching the intestine, and this would limit the topical action on the intestinal mucosa. GI injury by ASA therapy is the result of both local topical effects and a decrease in mucosal COX-1–derived prostaglandins, which could be a systemic effect. Very little clinical information is available so far. A recent study has evaluated the effect of low-dose enteric-coated

Diagnosis of Nonsteroidal Anti-Inflammatory Drug enteropathy

Probably the single most important reason for underestimating the clinical importance of NSAID enteropathy is the difficulty in making a diagnosis. Barium radiologic examination of the small-bowel mucosa is very deficient in detecting flat lesions. A number of noninvasive tests have been developed to evaluate indirect parameters of mucosal damage. Inflammatory markers (fecal calprotectin excretion) and permeability tests (urinary recovery of orally administered probes) assess the functional

Misoprostol, COX-2 Selective Inhibitors, and NO-Donating Agents

At present, effective means to prevent NSAID-associated intestinal lesions in patients are not available. The efforts to generate safer NSAIDs, including ASA, have followed different routes such as the development of enteric-coated or slow-release formulations. As commented here, these formulations could shift the problem to a more distal site within the digestive tract. Since all conventional NSAIDs appear to cause NSAID enteropathy, there is little sense to switch from one to another. The

Summary

In addition to the upper GI tract, NSAIDs can damage the small bowel and the colon. NSAID enteropathy is frequent and may be present in more than 60% of patients taking these drugs long term. In most cases, damage is subclinical, including increased mucosal permeability, inflammation, erosions, ulceration, but other more serious clinical outcomes such as anemia, and overall bleeding, perforation, obstruction, diverticulitis and deaths have also been described. The magnitude of these serious

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    Funding Support: This manuscript has been supported by funds from the Government of Aragón (B01) and grant from Fondo de Investigaciones Sanitarias (FIS 05/2445).

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