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Updated: Apr 7 2024

Anti-inflammatory Medications

  • Introduction
    • Non-steroidal anti-inflammatory drugs (NSAIDS) have the following effects
      • anti-inflammatory
      • antipyretic
      • analgesic
      • antiplatelet
    • Mechanism
      • inhibit the COX (cyclooxygenase) enzymes ultimately inhibiting the synthesis and release of prostaglandins
        • COX enzymes catalyze the formation of prostaglandins and thromboxane from arachidonic acid
      • There are two different COX enzymes targeted
        • COX inhibitors
          • target both COX-1 and COX-2
        • COX-2 specific inhibitors
          • target COX-2 alone and do not affect COX-1 function
    • Indications
      • pain
      • heterotopic ossfication prophylaxis
    • Contraindications
      • severe renal disease
      • gastric ulcers
  • COX Inhibitors
    • NSAIDS inhibit both COX-1 and COX-2
      • Aspirin (ASA)
        • salicylate that irreversibly binds a serine COX enzyme residue
        • half life >1 week
        • binds to COX and blocks active site
        • inhibits thromboxane A2 blocking platelet aggregation
      • ibuprofen
        • reversible competitive COX inhibitor
      • indomethacin
        • acts on the lipoxygenase side of the arachidonic metabolic pathway
        • inhibibits leukotriene inflammatory mediators
  • COX-2 Specific Inhibitors
    • Introduction
      • selectively target COX-2 enzymes and do not affect COX-1 function
        • examples
          • celecoxib (Celebrex)
          • rofecoxib (Vioxx)
    • Benefits
      • selective inhibition of COX-2 results in anti-inflammatory action without disrupting the beneficial effects of COX-1 (maintaining gastric mucosa, regulating renal blood flow, influencing platelet aggregation)
      • can be used in the perioperative period because they do not affect platelet function
      • no more efficacious in treating osteoarthritis than non-specific COX inhibitors
    • Side effects
      • cardiac toxicity
  • Side Effects
    • Renal dysfunction
    • Gastrointestinal side effects
      • pain and dyspepsia
      • peptic ulcer perforation, bleeding, or obstruction
        • 2% to 4% occurence in chronic users
      • risk factors
        • concurrent anticoagulant use (most important)
        • age >60 years
        • history of previous gastrointestinal disorder
    • Delayed fracture healing
      • animal fracture models have shown decreased endochondral ossification in the absence of a COX-2 enzyme
      • delayed union and nonunion due to inhibition of chondrogenic differentiation of mesenchymal stem cells
        • inhibit callus formation by inhibiting endochondral ossification
        • secondary bone healing more likely to be effected than primary bone healing
      • Increased risk with prolonged use, large doses, and adult patients
        • no effect demonstrated in pediatric fracture healing
    • Platelet dysfunction
    • Cardiac Toxicity
  • Corticosteroids (Systemic)
    • Steroid Dose Pack
      • efficacy
      • side effects
    • adverse skeletal effects in the setting of prolonged oral glucocorticoids can be seen within three months and with daily doses as low as 2.5 - 5.0 mg 
      • consider bisphosphonate therapy in patients at high risk for fracture who are receiving extended oral glucocorticoid therapy
  • Corticosteroid Intra-articular-Injections
    • Efficacy
    • Side Effects
      • Local flare
      • Fat atrophy
      • Skin pigmentation changes
      • Facial flushing
      • Epidural steroid injections associated with loss of lumbar BMD
        • loss of lumbar BMD not associated with other medium/large joint injections
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