Analgesia
NSAIDs
- widely used for anti-inflammatory and analgesic properties with traditional non-selective and latterly selective cyclooxygenase (COX)-2 inhibitors
- COX inhibitors implicated in poor bone healing but NOT proven
- COX-1 said to be gastro-protective so selective COX-2 inhibitors are safer from GIT point of view, but COX-2 inhibition now thought to have adverse cardiac and neurological adverse effects
- COX-1 inhib + PPI considered to be equivalent GIT protection to COX-2 inhib alone
- adverse effects - renal function, BP, hepatic injury and platelet inhibition resulting in increased bleeding.
- Most serious adverse effects of tNSAIDs (non-selective eg. ibuprofen, diclofenac and naproxen) are gastrointestinal
- Most serious adverse effects concern for selective COX-2 inhibitors (eg. rofecoxib, valdecoxib and lumiracoxib) are cardiovascular
- Evidence indicates that COX-2 inhibitors as a group have a small but absolute risk of cardiovascular adverse effects
- In terms of GIT bleeding risk, meta-analysis suggests that in general, ibuprofen has the lowest risk among tNSAIDs, diclofenac and naproxen have intermediate risks, and piroxicam and ketorolac carry the greatest risk.
COX-1
- in most tissues and governs homeostatic production of arachidonic acid metabolites necessary to maintain physiologic integrity, including gastric cyto-protection via prostacyclin (PGI2)
- The ulcerogenic properties of tNSAIDs to a large extent relate to their capacity to inhibit COX-1 in the gastric mucosa
COX-2
- almost undetectable in most normal tissues except in the brain, kidney, uterus, and prostate
- induced in response to inflammatory stimuli. Responsible for enhanced production of eicosanoid mediators for inflammation and pain
- implicated in oncogenesis