Definition
- Cyclo-oxygenase converts arachidonic acid to prostaglandin H2, the precursor of prostaglandins, prostacyclin and thromboxane
- Enzyme has cyclo-oxygenase and peroxidase activity
- Aspirin acetylates COX irreversibly, while other NSAIDs bind reversibly
- Paracetamol acts weakly on central COX with little peripheral effect
Pathway
- Phospholipase A2 releases arachidonic acid from membrane phospholipids
- Corticosteroids inhibit phospholipase A2
- Cyclo-oxygenase produces prostanoids
- Lipoxygenase produces leukotrienes
- Thromboxane A2 promotes platelet aggregation and vasoconstriction
- Prostacyclin inhibits platelet aggregation and causes vasodilatation
- Prostaglandin E2 mediates fever, pain sensitisation and inflammation
- Leukotrienes are not inhibited by NSAIDs
Isoforms
| Isoform | Expression | Functions |
|---|---|---|
| COX-1 | Constitutive | Gastric mucosal protection, platelet thromboxane A2, renal blood flow |
| COX-2 | Induced by inflammation. Also constitutive in kidney and endothelium | Inflammatory prostaglandins, pain, fever, endothelial prostacyclin |
Clinical Relevance
- COX-1 inhibition causes gastric and platelet side effects
- COX-2 selectivity spares the stomach but leaves thromboxane unopposed by prostacyclin, raising thrombotic risk
- Prostaglandin E2 promotes bone formation and resorption. See NSAIDS
- Rofecoxib was withdrawn in 2004 after an increase in cardiovascular events (VIGOR and APPROVe)
- Celecoxib, parecoxib and etoricoxib remain in use in Australia
- NSAIDs reduce renal blood flow, a concern in dehydration, renal impairment and with ACE inhibitors
- Short courses after fracture have little effect on union in most studies
- Low dose aspirin blocks platelet thromboxane for the life of the platelet
Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 10 October 2026.