What are the adverse effects of NSAIDs?

It is only a slight exaggeration to say “all medicines are poisons” in that medicines usually accomplish their mission by inhibiting, that is, poisoning, some natural process.

Non-steroidal anti-inflammatory drugs work by partially inhibiting prostaglandin synthesis. That can be very helpful and desired in musculoskeletal medicine, as prostaglandins potentiate (and effectively amplify) pain and inflammation.

Non-steroidal anti-inflammatory drugs (NSAIDs) have long been considered a staple in the management of musculoskeletal pain. This class of drugs includes aspirin, ibuprofen, naproxen, indomethacin, and ketorolac. Compared to steroids, NSAIDs are better tolerated long-term by many populations and have less associated risk.

The problem with NSAIDs is that their “poisoning” effect might not be limited to controlling the pain and inflammation that the doctor and patient desires.

NSAIDs have been reported to cause headaches and dizziness, tinnitus, and allergic reactions. These are usually minor and self-limited issues. There is, however, the possibility or more significant complications including the following:

  • NSAIDs inhibit platelets, and thus can cause excessive bleeding. This might manifest as a gastrointestinal hemorrhage or stroke. Serious gastrointestinal (GI) bleeding leading to perforation has been seen, especially in elderly patients with a history of peptic ulcer disease or other conditions associated with GI bleeding.
  • NSAIDs can increase the chance of heart attack.
  • NSAIDs can interfere with kidney function and worsen hypertension by constricting the vessels that supply the kidneys and by impeding perfusion.
  • NSAIDs can interact with other medicines (e.g., warfarin) causing problems that would not be seen with either medicine taken alone.
  • It is also possible that NSAIDs may interfere with musculoskeletal repair, leading to non-unions of fracture and less robust healing of tendinous/ligamentous injuries.

Bottom Line: In general, NSAIDs are safe, well tolerated, and effective. Nonetheless, they (like all medicines) can have adverse effects. Particular attention must be paid to their chronic use, especially in older patients who are at increased risk for adverse effects because of their age-related decline of physiological organ reserve, increased comorbidities, and likelihood that they are taking other medications that might negatively interact with the NSAID.

Additional Points to Consider

To mitigate some of the more severe risks of NSAIDs, drugs were made to selectively inhibit the cyclooxygenase-2 enzyme (COX-2), which was thought to be specific for inflammation. This attempt was unsuccessful. In 2004, Merck announced a voluntary worldwide withdrawal of this drug because of cardiovascular issues. For further information, please refer to the FDA website: https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/vioxx-rofecoxib-questions-and-answers

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