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Pathway Description
Benzthiazide Action Pathway
Homo sapiens
Drug Action Pathway
Benzthiazide is a diuretic that acts by promoting water loss from the body. This drug is used in the treatment of hypertension and edema. They act on the kidneys by inhibiting the sodium-chloride reabsorption (via the Na+/Cl- cotransporter) from its early distal tubules. This inhibition of the cotransporter results in the increased excretion of sodium, chloride, and, in consequence, water. At the same time, it inhibits sodium transport across the renal tubular epithelium (by binding the Na+/Cl- cotransporter). In consequence, this will increase potassium excretion via the sodium-potassium exchange mechanism. The exact name of the inhibited transporter is the solute carrier family 12 member 3. The antihypertensive function of the drug is not well defined, but it is thought to act by the drug inhibition on the carbonic anhydrase or on the large-conductance calcium-activated potassium (kCa) channel, in the smooth muscles. An overdose of benzthiazide would result in symptoms like nausea, vomiting, drowsiness, and urinary problems. This drug is administered as an oral tablet.
References
Benzthiazide 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
Blanchard A, Vallet M, Dubourg L, Hureaux M, Allard J, Haymann JP, de la Faille R, Arnoux A, Dinut A, Bergerot D, Becker PH, Courand PY, Baron S, Houillier P, Tack I, Devuyst O, Jeunemaitre X, Azizi M, Vargas-Poussou R: Resistance to Insulin in Patients with Gitelman Syndrome and a Subtle Intermediate Phenotype in Heterozygous Carriers: A Cross-Sectional Study. J Am Soc Nephrol. 2019 Aug;30(8):1534-1545. doi: 10.1681/ASN.2019010031. Epub 2019 Jul 8.
Pubmed: 31285285
Ellison DH: The thiazide-sensitive na-cl cotransporter and human disease: reemergence of an old player. J Am Soc Nephrol. 2003 Feb;14(2):538-540. doi: 10.1681/ASN.V142538.
Pubmed: 12538756
LEIBMAN KC, ALFORD D, BOUDET RA: Nature of the inhibition of carbonic anhydrase by acetazolamide and benzthiazide. J Pharmacol Exp Ther. 1961 Mar;131:271-4.
Pubmed: 13760527
Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. doi: 10.1038/nrd2199.
Pubmed: 17139284
Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24.
Pubmed: 19119014
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