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Pathway Description
Piroxicam NSAID Action Pathway
Homo sapiens
Drug Action Pathway
Piroxicam is an NSAID used to treat the symptoms of osteoarthritis and rheumatoid arthritis. It targets the prostaglandin G/H synthase-1 (COX-1) and prostaglandin G/H synthase-2 (COX-2) in the cyclooxygenase pathway. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 converts arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. The anti-inflammatory effect of Piroxicam may result from the reversible inhibition of cyclooxygenase, causing the peripheral inhibition of prostaglandin synthesis. The prostaglandins are produced by an enzyme called Cox-1. Piroxicam blocks the Cox-1 enzyme, resulting into the disruption of production of prostaglandins. Piroxicam also inhibits the migration of leukocytes into sites of inflammation and prevents the formation of thromboxane A2, an aggregating agent, by the platelets.
References
Piroxicam NSAID Pathway References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Blanco FJ, Guitian R, Moreno J, de Toro FJ, Galdo F: Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular chondrocytes. J Rheumatol. 1999 Jun;26(6):1366-73.
Pubmed: 10381057
Bugajski J, Glod R, Gadek-Michalska A, Bugajski AJ: Involvement of constitutive (COX-1) and inducible cyclooxygenase (COX-2) in the adrenergic-induced ACTH and corticosterone secretion. J Physiol Pharmacol. 2001 Dec;52(4 Pt 2):795-809.
Pubmed: 11785774
Veiga AP, Duarte ID, Avila MN, da Motta PG, Tatsuo MA, Francischi JN: Prevention by celecoxib of secondary hyperalgesia induced by formalin in rats. Life Sci. 2004 Oct 22;75(23):2807-17. doi: 10.1016/j.lfs.2004.05.028.
Pubmed: 15464832
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