Editing Aspirin (section)

===COX-1 and COX-2 inhibition===
At least two different types of [[cyclooxygenase]]s, [[COX-1]] and [[COX-2]], are acted on by aspirin. Aspirin irreversibly inhibits COX-1 and modifies the enzymatic activity of COX-2. COX-2 normally produces [[prostanoid]]s, most of which are proinflammatory. Aspirin-modified COX-2 (aka [[prostaglandin-endoperoxide synthase 2]] or PTGS2) produces [[epi-lipoxin]]s, most of which are anti-inflammatory.<ref>{{cite journal |vauthors=Goel A, Aggarwal S, Partap S, Saurabh A, Choudhary |date=2012 |title=Pharmacokinetic solubility and dissolution profile of antiarrythmic drugs |journal=Int J Pharma Prof Res |volume=3 |issue=1 |pages=592–601}}</ref>{{Verify source|date=August 2016}}<ref>{{cite journal | vauthors = Clària J, Serhan CN | title = Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 21 | pages = 9475–9479 | date = October 1995 | pmid = 7568157 | doi = 10.1073/pnas.92.21.9475 | doi-access = free | pmc = 40824 | bibcode = 1995PNAS...92.9475C }}</ref> Newer NSAID drugs, [[COX-2 inhibitor]]s (coxibs), have been developed to inhibit only COX-2, with the intent to reduce the incidence of gastrointestinal side effects.<ref name=COX2002/>

Several COX-2 inhibitors, such as [[rofecoxib]] (Vioxx), have been withdrawn from the market, after evidence emerged that COX-2 inhibitors increase the risk of heart attack and stroke.<ref>{{cite journal | vauthors = Martínez-González J, Badimon L | title = Mechanisms underlying the cardiovascular effects of COX-inhibition: benefits and risks | journal = Current Pharmaceutical Design | volume = 13 | issue = 22 | pages = 2215–27 | year = 2007 | pmid = 17691994 | doi = 10.2174/138161207781368774 }}</ref><ref>{{cite journal | vauthors = Funk CD, FitzGerald GA | title = COX-2 inhibitors and cardiovascular risk | journal = Journal of Cardiovascular Pharmacology | volume = 50 | issue = 5 | pages = 470–9 | date = November 2007 | pmid = 18030055 | doi = 10.1097/FJC.0b013e318157f72d | s2cid = 39103383 | doi-access = free }}</ref> Endothelial cells lining the microvasculature in the body are proposed to express COX-2, and, by selectively inhibiting COX-2, prostaglandin production (specifically, PGI<sub>2</sub>; prostacyclin) is downregulated with respect to thromboxane levels, as COX-1 in platelets is unaffected. Thus, the protective anticoagulative effect of [[PGI2|PGI<sub>2</sub>]] is removed, increasing the risk of thrombus and associated heart attacks and other circulatory problems.{{medical citation needed|date=April 2025}}

Furthermore, aspirin, while inhibiting the ability of COX-2 to form pro-inflammatory products such as the [[prostaglandins]], converts this enzyme's activity from a prostaglandin-forming cyclooxygenase to a [[lipoxygenase]]-like enzyme: aspirin-treated COX-2 metabolizes a variety of [[polyunsaturated fatty acids]] to hydroperoxy products which are then further metabolized to [[specialized proresolving mediators]] such as the [[Epi-lipoxin|aspirin-triggered lipoxins]](15-epilipoxin-A4/B4), aspirin-triggered [[resolvins]], and aspirin-triggered [[maresin]]s. These mediators possess potent anti-inflammatory activity. It is proposed that this aspirin-triggered transition of COX-2 from cyclooxygenase to lipoxygenase activity and the consequential formation of specialized proresolving mediators contributes to the anti-inflammatory effects of aspirin.<ref name="pmid25895638">{{cite journal | vauthors = Romano M, Cianci E, Simiele F, Recchiuti A | title = Lipoxins and aspirin-triggered lipoxins in resolution of inflammation | journal = European Journal of Pharmacology | volume = 760 | pages = 49–63 | date = August 2015 | pmid = 25895638 | doi = 10.1016/j.ejphar.2015.03.083 }}</ref><ref name="pmid23747022">{{cite journal | vauthors = Serhan CN, Chiang N | title = Resolution phase lipid mediators of inflammation: agonists of resolution | journal = Current Opinion in Pharmacology | volume = 13 | issue = 4 | pages = 632–40 | date = August 2013 | pmid = 23747022 | pmc = 3732499 | doi = 10.1016/j.coph.2013.05.012 }}</ref><ref name="pmid26546723">{{cite journal | vauthors = Weylandt KH | title = Docosapentaenoic acid derived metabolites and mediators - The new world of lipid mediator medicine in a nutshell | journal = European Journal of Pharmacology | volume = 785 | pages = 108–115 | date = August 2016 | pmid = 26546723 | doi = 10.1016/j.ejphar.2015.11.002 }}</ref>