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Long-term use of NSAIDs (non-steroidal anti-inflammatory drugs) is associated with an increased risk of gastrointestinal bleeding. This effect is primarily due to NSAIDs' mechanism of action, which inhibits the cyclooxygenase (COX) enzymes involved in the synthesis of prostaglandins. Prostaglandins play a crucial role in maintaining the protective lining of the gastrointestinal tract. When NSAIDs are used over extended periods, they can reduce the production of these protective prostaglandins, leading to mucosal damage, ulcers, and ultimately gastrointestinal bleeding.

This risk is particularly concerning for individuals with other risk factors such as older age, history of peptic ulcer disease, concurrent use of anticoagulants, or substance abuse. Regular monitoring and, when appropriate, concurrent use of proton pump inhibitors or other gastroprotective strategies are often recommended for patients requiring long-term NSAID therapy to mitigate this risk.