Celecoxib

Summary

Celecoxib is a non-steroidal anti-inflammatory drug or NSAID with protective effects on the GI tract. It works by selectively blocking COX2 or cyclooxygenase 2, while sparing the actions of COX1. This selective effect on COX2 allows the drug to reduce inflammation without decreasing COX1-mediated mucus protection at the GI tract, thereby lowering or reducing the risk of GI ulcer formation. Celecoxib is clinically used for treating inflammatory diseases like rheumatoid arthritis and osteoarthritis, especially in patients who have a history of peptic ulcers. Side effects to note include an increased risk for thrombotic events like myocardial infarction or stroke. Celecoxib is a sulfa drug containing a sulfonamide group, so it is contraindicated in patients with sulfa allergy.

Key Points

• Celecoxib (and Rofecoxib)
  • Mechanism
    • Selective cyclooxygenase 2 (COX2) Inhibitor
      • “Selective cox inhibitor” = CELE coxib
      • COX2 is found in inflammatory cells and vascular endothelium and mediates inflammation and pain via production of prostaglandins, leukotrienes and other stuff (arachidonic acid metabolites)
      • Spares COX-1
        • Less effect on gastric mucosa (maintained COX1) - lower risk of GI ulceration and bleeding
        • Less anti-platelet function (TXA2 production is COX1 dependent)
  • Indications
    • Anywhere you would use an NSAID but where you have GI ulcer problems
      • E.g. Rheumatoid arthritis, Osteoarthritis
  • AEs
    • Note: minimal GI toxicity (vs. COX1 non-selective NSAIDs)
      • Potent anti-inflammatory effect without bleeding & GI ulceration
    • Increased risk of cardiovascular events (thrombosis)
      • E.g. MI, stroke, “cardiovascular incidents”
      • “For celecoxib, is it worth talking about how the increased risk of adverse Cardiovascular events is caused by decreased PGI2 (Prostacyclin) synthesis. PGI2 is normally produced by health endothelium and serves to vasodilate + keep platelets inactive. When COX-2 inhibitor is given, the platelets become more active because of less PGI2.”
    • Sulfa allergy (sulfa drug)
      • Patients with sulfa allergies may develop fever, urinary tract infection, Stevens- Johnson syndrome, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria (hives).
      • Symptoms range from mild to life threatening.
  • Peptic ulcer disease
  • Celecoxib
  • Celecoxib, b/c this patient likely suffers from peptic ulcer disease. Selective COX-2 inhibitors such as celecoxib are preferred in patients with PUD due to their lower incidence of GI side effects