- NSAIDS
- COX enzymes
- COX 1
- Constitutive
- Causes GI irritation, nephrotoxicity
- COX 2
- Induced at sites of inflammation
- Increased risk of cardiac events
- Aspirin acetylates COX
- Prostaglandin synthesis
- MEMBRANE PHOSPHOLIPIDS
- ARACHIDONIC ACID
- LEUKOTRIENES
- PROSTANOIDS
- PG
- ↓PGE₂/F2α leads to anti-inflammation
- TXA₂
- ↓TXA₂ leads to decreased platelet adhesiveness
- PGI₂
- Specific drugs
- Ketorolac
- Acetic acid derivative
- Limited anti-inflammatory action
- T½(e) = 5hrs
- 99% protein bound
- Paracetamol
- Acetanilidine derivative
- May work as a central COX3 inhibitor
- Mainly metabolised to glucorinide, sulphate & cysteine conjugated before urine excretion
- Toxic metabolite is N-acetyl-P-amino-benzylquinonamine which is conjugated with glutathione. Once glutathione stores are exhausted, hepatotoxicity ensues
- N-acetylcysteine is a precursor of glutathione
- Methionine increases glutathione production
- Ibuprofen
- Proprionic acid
- 20mg/kg
- Lower incidence of S/E
- T½(e) 2-3 hrs
- 99% protein bound
- LOX
- COX