NSAIDS are a structurally diverse group of drugs that all inhibit the enzyme cyclooxygenase (COX), thus inhibiting  the transformation of arachidonic acid to eicosanoids (prostaglandins, prostacyclin, and thromboxanes). Since these COX products are important mediators of the inflammatory response, NSAIDS have potent antiinflammatory effects. 

Several isoforms of the COX enzyme have been described.

  • COX-1 is constitutively expressed in most tissues and regulates cellular processes such as gastric cytoprotection, vascular homeostasis, platelet aggregation, and kidney function
  • COX-2 s a highly regulated, inducible enzyme with increased expression during inflammatory processes
  • An isoform known as COX-3 is a splice variant of COX-1 denoted COX-1b; the role of this enzyme is unclear.

The clinically used NSAIDS inhibit the various isoforms to a different extent, which explains some of the differences between different NSAIDS. Selective COX-2 inhibitors were developed to avoid some of the side effects resulting from non-selective COX inhibition.

Clinical Use: 


Acute Pain, Inflammation


NSAIDS have dose-dependent analgesic effects. Antiinflammatory effects are normally only seen at the higher end of the recommended dose range.

Recommended analgesic and antiinflammatory doses of the NSAIDS most commonly used at UCSF are:

  • Ibuprofen 600mg PO every 6 hours
  • Diclofenac 50mg PO every 8 hours 
  • Naproxen 250 mg PO every 6 to 8 hours
  • Celecoxib 200mg PO every 12 hours
  • Ketorolac  15 mg IV every 6 hours (5 day maximum)
Special Considerations: 

Side Effects nonselective NSAIDs (blocking both COX-1 and COX-2)

  • gastrointestinal adverse effects, such as peptic ulcer disease and GI bleeding
  • development of acute kidney injury due to renal vasoconstriction
  • increased risk for adverse cardiovascular events including myocardial infarction and stroke
  • mildly increased aminotransferase levels (but clinically evident liver injury is exceedingly rare)
  • bronchospasm (rare, but can be severe)
  • platelet inhibition
  • possible effects on fracture healing. The effect of NSAIDS on bone healing is controversial and based on retrospective studies: it is not clear whether NSAID use contributed to the occurrence of nonunion events or resulted from their use to treat painful nonhealing fractures


Side Effects of selective COX-2 inhibitors( Coxibs) when compared to nonselective NSAIDS

  • reduced gastroduodenal toxicity
  • minimal to no effect upon platelet function, therefore reduced bleeding risk
  • little if any risk of precipitating bronchospasm 
  • probably increased risk for adverse cardiovascular events
  • similar risk for kidney injury



  • NSAID hypersensitivity or salicylate hypersensitivity
  • Allergy to sulfonamides (Celecoxib)
  • History of peptic ulcer disease
  • Reduced renal function
  • severe heart disease
  • liver cirrhosis
  • third trimester of pregnancy
  • Breastfeeding (Ketorolac)
  • low-dose aspirin use for the prevention of cardiovascular disease

NSAIDs should be used cautiously in older adults and generally for a limited duration, given the increased risk of toxicity in this population, including gastrointestinal bleeding, renal impairment, and heart failure.