Expansion
Cyclo-oxygenase makes prostaglandins; lipoxygenase makes leukotrienes
Expansion
Membrane phospholipid is released as arachidonic acid by phospholipase A2, then follows two branches:
Cyclo-oxygenase branch
- COX-1: constitutive. Gastric mucosal protection, platelet thromboxane A2, renal perfusion
- COX-2: inducible in inflammation, and constitutive in kidney and endothelium (prostacyclin)
- Products: prostaglandins, prostacyclin, thromboxane
Lipoxygenase branch
- Leukotrienes, notably LTC4, D4 and E4 (the slow reacting substance of anaphylaxis) causing bronchoconstriction and increased vascular permeability, and LTB4 for neutrophil chemotaxis
Drug actions follow directly:
- Corticosteroids inhibit phospholipase A2 (via lipocortin), blocking both branches
- Non-selective NSAIDs inhibit COX-1 and COX-2, giving anti-inflammatory benefit with gastric and renal harm
- COX-2 selective agents spare the stomach but shift the thromboxane to prostacyclin balance towards thrombosis, hence their cardiovascular risk
- Aspirin irreversibly acetylates COX, and at low dose selectively suppresses platelet thromboxane
- Montelukast blocks leukotriene receptors, and aspirin-sensitive asthma is explained by shunting arachidonate down the lipoxygenase branch