Editing Analgesic (section)

==== COX-2 inhibitors ====
{{Main|COX-2 inhibitor}}

These drugs have been derived from NSAIDs. The [[cyclooxygenase]] enzyme inhibited by NSAIDs was discovered to have at least two different versions: COX1 and COX2. Research suggested most of the adverse effects of NSAIDs to be mediated by blocking the COX1 ([[Constitutive enzyme|constitutive]]) enzyme, with the analgesic effects being mediated by the COX2 ([[Adaptive enzyme|inducible]]) enzyme. Thus, the COX2 inhibitors were developed to inhibit only the COX2 enzyme (traditional NSAIDs block both versions in general). These drugs (such as [[rofecoxib]], [[celecoxib]], and [[etoricoxib]]) are equally effective analgesics when compared with NSAIDs, but cause less gastrointestinal hemorrhage in particular.<ref name="Conaghan2012">{{cite journal | vauthors = Conaghan PG | title = A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy, and toxicity | journal = Rheumatology International | volume = 32 | issue = 6 | pages = 1491–502 | date = June 2012 | pmid = 22193214 | pmc = 3364420 | doi = 10.1007/s00296-011-2263-6 }}</ref>

After widespread adoption of the COX-2 inhibitors, it was discovered that most of the drugs in this class increase the risk of [[cardiovascular event]]s by 40% on average. This led to the withdrawal of rofecoxib and valdecoxib, and warnings on others. Etoricoxib seems relatively safe, with the risk of [[thrombotic]] events similar to that of non-coxib NSAID diclofenac.<ref name="Conaghan2012" />