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Pathway Description
Medrysone Action Pathway
Homo sapiens
Drug Action Pathway
Medrysone is a glucocorticoid used in the treatment of various ocular inflammatory or allergic conditions. As medrysone is a glucocorticoid, its mechanism of action is that of the glucocorticoid response element of influencing COX-2/prostaglandin G/H synthase 2 suppression and lipocortin/annexin induction. By binding to the glucocorticoid receptor, it influences transcription factors AP-1 and NF-kB to block the transcription of COX-2/prostaglandin G/H synthase 2 which reduces the amount of prostanoids being produced from arachidonic acid. Prostanoids such as PGI2 and thromboxane A2 influence the effects of inflammation through vasoconstriction/dilation, pain sensitivity, and platelet aggregation. Medrysone also affects the promoter of annexin-1, an important inflammatory protein as it affects leukocytes and blocks phospholipase A2 which reduces the amount of arachidonic acid being cleaved from the phospholipid bilayer. Reducing the amount of arachidonic acid formed further decreases the concentrations of prostanoids mentioned calming inflammation.
References
Medrysone 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
Southren AL, Dominguez MO, Gordon GG, Wenk EJ, Hernandez MR, Dunn MW, Weinstein BI: Nuclear translocation of the cytoplasmic glucocorticoid receptor in the iris-ciliary body and adjacent corneoscleral tissue of the rabbit following topical administration of various glucocorticoids. A rapid screening method for glucocorticoid activity. Invest Ophthalmol Vis Sci. 1983 Feb;24(2):147-52.
Pubmed: 6336597
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. doi: 10.1093/nar/30.1.412.
Pubmed: 11752352
Czock D, Keller F, Rasche FM, Haussler U: Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005;44(1):61-98. doi: 10.2165/00003088-200544010-00003.
Pubmed: 15634032
Kim S. W, Ko J, Kim J. H, Choi E. C, Na D. S. Differential effects of annexins I, II, III, and V on cytosolic phospholipase A2 activity: specific interaction model. FEBS Letters 489: 243-248, 2001
Necela B. M, Cidlowski J. A. Mechanisms of Glucocorticoid Receptor Action in Noninflammatory and Inflammatory Cells. American Thoracic Society 1:239-246, 2004.
Perretti M, Dalli J. Exploiting the Annexin A1 pathway for the development of novel anti-inflammatory therapeutics. British Journal of Pharmacology 158: 936-946, 2009.
Oeckinghaus A, Ghosh S. The NF-kB Family of Transcription Factors and Its Regulation. Cold Spring Harb Perspect Biol 1(4): a000034, 2009.
Kang Y, Mbonye U. R, DeLong C. J, Wada M, Smith W. L. Regulation of Intracellular Cyclooxygenase Levels by Gene Transcription and Protein Degradation. Prog Lipid Res 46(2): 108-125, 2007.
Kirschke E, Goswami D, Southworth D, Griffin P. R, Agard D. Glucocorticoid Receptor Function Regulated by Coordinated Action of the Hsp90 and Hsp70 Chaperone Cycles. Cell 157(7): 1685-1697, 2014.
Perretti M, D’Acquisto F. Annexin A1 and glucocorticoids as effectors of the resolution of
inflammation. Nature Reviews Immunology 9: 62–70, 2009.
Liu T, Zhang L, Joo D, Sun S. NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy 2: 17023, 2017.
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