NSAIDs may be grouped according to their preference for COX-1 and COX-2 enzymes. Those that favor COX-1 are more likely to cause gastrointestinal side effects. Those that favor COX-2 have a higher risk of cardiovascular effects but less gastrointestinal effects. Higher dosages of NSAIDs tend to result in more COX-2 enzyme inhibition (and more cardiovascular side effects), even in those NSAIDs traditionally seen as low risk (such as ibuprofen). NSAIDs with higher activity against COX-2 enzymes should be used with caution in people with cardiovascular disease or at increased risk of cardiovascular disease.
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NSAIDs cause erosions, ulcers, hemorrhage, perforations, strictures, and complications of diverticulosis in the large bowel. 86 NSAID-induced injury is more common in the right colon (80%) but can occur in the transverse and left colon. Suppositories containing NSAIDs can cause erosions, ulcers, and stenoses in the rectum. NSAID colonopathy is in the differential diagnosis of inflammatory bowel disease. Patients with NSAID-induced colonopathy are typically older, and the erosions are more likely to be transverse or circular. 87 There is also a concern that treatment with traditional and COX-2–selective NSAIDs may exacerbate inflammatory bowel disease. 88 NSAIDs are also implicated in the development of collagenous colitis. 89