Nonsteroidal anti-inflammatory drugs
Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve pain, fever, and inflammation by inhibiting cyclooxygenase (COX)-1 and COX-2, and that single mechanism predicts every major toxicity: gastric ulceration, platelet dysfunction, and hemodynamic renal injury. First-line agents are naproxen or ibuprofen (or topical diclofenac for knee or hand osteoarthritis) at the lowest effective dose for the shortest duration, with a proton pump inhibitor such as omeprazole 20 mg once daily added for patients at increased gastrointestinal risk.
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What this article covers
- Overview
Definition: NSAIDs inhibit the cyclooxygenase (COX) enzymes; the class spans reversible nonselective agents (naproxen, ibuprofen, indomethacin, diclofenac, ketorolac, meloxicam, etodolac, nabumetone…
- Epidemiology
Gastrointestinal event rate: about 1 to 2 percent of long-term users have a significant upper gastrointestinal event annually, rising to 14 percent in elderly users.
- Risk factors
Age over 65 years: most consistently linked to gastrointestinal/renal complications.
- Pathophysiology
COX-1 versus COX-2 sets the toxicity map: COX-1 protects gastric mucosa, supports platelet thromboxane A2, and vasodilates the renal afferent arteriole; COX-2 also produces vascular prostacyclin, an antithrombotic vasodilator.
- Clinical features
NSAID gastropathy and ulcer bleeding: dose- and duration-dependent, typically antral, presenting as acute bleeding or perforation; risk peaks in the first month.
- Differential diagnosis
Naproxen versus ibuprofen versus diclofenac by cardiovascular risk: naproxen lowest, ibuprofen intermediate but antagonizes aspirin, diclofenac nearing selective COX-2 risk.
- Diagnosis
The diagnosis is established clinically, by the temporal link between exposure and symptom onset and each syndrome's pattern, not a single test.
- Management
First, confirm the indication and use the lowest effective dose for the shortest duration.
- Complications
Upper gastrointestinal bleeding, perforation, or obstruction: the most common serious toxicity (rates above).
- Prognosis
Reversible when caught early: hemodynamic acute kidney injury and most acute interstitial nephritis recover with prompt discontinuation, though nephritis recovery can take weeks to months.
- Prevention
Avoid NSAIDs entirely once estimated GFR falls below 30 mL/min/1.73 m2, and across chronic kidney disease per American Society of Nephrology guidance.
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