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Pathway Description
Fluticasone propionate Action Pathway
Homo sapiens
Drug Action Pathway
Fluticasone propionate is a synthetic glucocorticoid used to treat asthma, as well as inflammatory and pruritic dermatoses. This molecule can also besused as a nasal spray to treat allergic and nonallergic rhinitis. As this molecule is a glucocorticoid, its mechanism of action is that of the glucocorticoid response element (GRE) 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. This drug 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. Fluticasone propionate is administered as an inhaler, a nasal spray or as a topical ointment.
References
Fluticasone propionate 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
Allen A, Bareille PJ, Rousell VM: Fluticasone furoate, a novel inhaled corticosteroid, demonstrates prolonged lung absorption kinetics in man compared with inhaled fluticasone propionate. Clin Pharmacokinet. 2013 Jan;52(1):37-42. doi: 10.1007/s40262-012-0021-x.
Pubmed: 23184737
Phillipps GH: Structure-activity relationships of topically active steroids: the selection of fluticasone propionate. Respir Med. 1990 Nov;84 Suppl A:19-23. doi: 10.1016/s0954-6111(08)80003-0.
Pubmed: 2287791
Crim C, Pierre LN, Daley-Yates PT: A review of the pharmacology and pharmacokinetics of inhaled fluticasone propionate and mometasone furoate. Clin Ther. 2001 Sep;23(9):1339-54. doi: 10.1016/s0149-2918(01)80113-2.
Pubmed: 11589253
Andersson O, Cassel TN, Gronneberg R, Bronnegard M, Stierna P, Nord M: In vivo modulation of glucocorticoid receptor mRNA by inhaled fluticasone propionate in bronchial mucosa and blood lymphocytes in subjects with mild asthma. J Allergy Clin Immunol. 1999 Apr;103(4):595-600. doi: 10.1016/s0091-6749(99)70230-7.
Pubmed: 10200007
Zhang X, Moilanen E, Kankaanranta H: Beclomethasone, budesonide and fluticasone propionate inhibit human neutrophil apoptosis. Eur J Pharmacol. 2001 Nov 23;431(3):365-71. doi: 10.1016/s0014-2999(01)01437-6.
Pubmed: 11730731
Johnson M: Fluticasone propionate: safety profile. Cutis. 1996 Feb;57(2 Suppl):10-2.
Pubmed: 8646863
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
Issar M, Sahasranaman S, Buchwald P, Hochhaus G: Differences in the glucocorticoid to progesterone receptor selectivity of inhaled glucocorticoids. Eur Respir J. 2006 Mar;27(3):511-6. doi: 10.1183/09031936.06.00060005.
Pubmed: 16507850
Sano A, Munoz NM, Sano H, Choi J, Zhu X, Jacobs B, Leff AR: Inhibition of cPLA2 translocation and leukotriene C4 secretion by fluticasone propionate in exogenously activated human eosinophils. Am J Respir Crit Care Med. 1999 Jun;159(6):1903-9. doi: 10.1164/ajrccm.159.6.9810005.
Pubmed: 10351938
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.
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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