=====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.
{{ :wiki:cox_pathway.jpeg?300|}}

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

==References include:==
[[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1855338/|Evidence based update NSAIDs 2007]]\\ 
[[https://academic.oup.com/bjaed/article/13/4/131/345292|COX-2 inhibitors]]\\ 
[[https://www.nps.org.au/australian-prescriber/articles/the-vascular-effects-of-cox-2-selective-inhibitors|Aust Prescriber. Vasc effects of COX-2 inhibitors]]\\