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Pathway Description
Tenoxicam Action Pathway (New)
Homo sapiens
Drug Action Pathway
Tenoxicam is an anti-inflammatory analgesic used to treat mild to moderate pain as well as the signs and symptoms of rheumatoid arthritis and osteoarthritis. It also has antipyretic effects. 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. Tenoxicam inhibits the action of COX-1 and COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. Fever is triggered by inflammatory and infectious diseases. Cytokines are produced in the central nervous system (CNS) during an inflammatory response. These cytokines induce COX-2 production that increases the synthesis of prostaglandin, specifically prostaglandin E2 which adjusts hypothalamic temperature control by increasing heat production. Because tenoxicam decreases PGE2 in the CNS, it has an antipyretic effect. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss.
References
Tenoxicam Pathway (New) 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
Kothekar V, Sahi S, Srinivasan M, Mohan A, Mishra J: Recognition of cyclooxygenase-2 (COX-2) active site by NSAIDs: a computer modelling study. Indian J Biochem Biophys. 2001 Feb-Apr;38(1-2):56-63.
Pubmed: 11563332
Ozgocmen S, Ardicoglu O, Erdogan H, Fadillioglu E, Gudul H: In vivo effect of celecoxib and tenoxicam on oxidant/ anti-oxidant status of patients with knee osteoarthritis. Ann Clin Lab Sci. 2005 Spring;35(2):137-43.
Pubmed: 15943176
Galvao RI, Diogenes JP, Maia GC, Filho EA, Vasconcelos SM, de Menezes DB, Cunha GM, Viana GS: Tenoxicam exerts a neuroprotective action after cerebral ischemia in rats. Neurochem Res. 2005 Jan;30(1):39-46. doi: 10.1007/s11064-004-9684-5.
Pubmed: 15756931
Yamada M, Niki H, Yamashita M, Mue S, Ohuchi K: Prostaglandin E2 production dependent upon cyclooxygenase-1 and cyclooxygenase-2 and its contradictory modulation by auranofin in rat peritoneal macrophages. J Pharmacol Exp Ther. 1997 May;281(2):1005-12.
Pubmed: 9152412
Kothekar V, Sahi S, Srinivasan M, Mohan A, Mishra J: Recognition of cyclooxygenase-2 (COX-2) active site by NSAIDs: a computer modelling study. Indian J Biochem Biophys. 2001 Feb-Apr;38(1-2):56-63.
Pubmed: 11563332
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