Expansion
Cyclo-oxygenase inhibition giving analgesia at the cost of gastric, renal and cardiovascular risk
Expansion
Mechanism: inhibition of cyclo-oxygenase, reducing prostaglandin synthesis.
- COX-1 is constitutive: gastric mucosal protection, platelet thromboxane, renal perfusion
- COX-2 is inducible in inflammation, but also constitutive in kidney and endothelium
Adverse effects, all predictable from the mechanism
- Gastrointestinal: ulceration and bleeding, from loss of mucosal prostaglandins. Co-prescribe a proton pump inhibitor in those at risk
- Renal: loss of afferent arteriolar dilatation causes acute kidney injury, sodium and water retention and hyperkalaemia. Particularly dangerous in hypovolaemia and with ACE inhibitors and diuretics, the triple whammy
- Cardiovascular: increased thrombotic risk, greatest with COX-2 selective agents and diclofenac, since they suppress endothelial prostacyclin while sparing platelet thromboxane
- Respiratory: aspirin-sensitive asthma, from shunting arachidonate down the lipoxygenase pathway
- Aspirin specifically: irreversible platelet inhibition for the platelet lifespan; Reye syndrome in children
Contraindications to remember: active peptic ulcer, significant renal impairment, severe heart failure, third trimester of pregnancy, and previous NSAID-induced asthma.