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 Corticosteroid Intra-articular-Injections Efficacy Side Effects Local flare Fat atrophy Skin pigmentation changes Facial flushing