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Pathway Description
Meloxicam NSAID Action Pathway
Homo sapiens
Drug Action Pathway
Meloxicam is a nonsteroidal anti-inflammatory (NSAID) used to treat backache and ankylosing spondylitis. Meloxicam possesses anti-inflammatory, analgesic, and antipyretic activity. 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 convert 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. Meloxicam 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 meloxicam decreases PGE2 in the CNS, it has an antipyretic effect. Antipyretic effects result in increased peripheral blood flow, vasodilation, and subsequent heat dissipation. This drug is administered as an oral tablet or as an intravenous injection.
References
Meloxicam 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
Bekker A, Kloepping C, Collingwood S: Meloxicam in the management of post-operative pain: Narrative review. J Anaesthesiol Clin Pharmacol. 2018 Oct-Dec;34(4):450-457. doi: 10.4103/joacp.JOACP_133_18.
Pubmed: 30774225
Turck D, Roth W, Busch U: A review of the clinical pharmacokinetics of meloxicam. Br J Rheumatol. 1996 Apr;35 Suppl 1:13-6. doi: 10.1093/rheumatology/35.suppl_1.13.
Pubmed: 8630630
Ricciotti E, FitzGerald GA: Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011 May;31(5):986-1000. doi: 10.1161/ATVBAHA.110.207449.
Pubmed: 21508345
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