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Pathway Description
Indapamide Diuretic Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2020-12-01
Last Updated: 2023-10-25
Indapamide is an oral thiazide-like diuretic drug that acts in the kidney, specifically in the distal convoluted tubule of the nephron. It is used for the treatment of hypertension or to treat fluid and salt retention associated with congestive heart failure. In the distal convoluted tubule (DCT), the regulation of ions such as sodium, potassium, calcium, chloride, and magnesium occurs. In epithelial cells of the DCT, the basolateral membrane consists of the Na+/K+ ATPase, which pumps Na+ into the interstitium-blood area and K+ into the epithelial cell; the Na+/Ca2+ exchanger, which pumps Na+ into the cell and Ca2+ into the interstitium-blood; and the chloride transporter which transports chloride into the interstitium-blood. The apical membrane contains a calcium channel that transports calcium from the lumen into the epithelial cell, a potassium channel that transports K+ out of the epithelial cell, and a Na+/Cl- cotransporter which transports Na+ and Cl- into the epithelial cell. Indapamide targets this Na+/Cl- cotransporter. Indapamide is transported from the blood into the epithelial cells. In the lumen, it has access to the Na+/Cl- transporter and inhibits it preventing Na+ reabsorption. The inhibition of Na+ reabsorption results in a low cytosolic concentration of Na+ and increases the solute concentration of the lumen. This decreases the lumen-epithelial cell concentration gradient and as a result, less water would be reabsorbed from the urine. This effect is valued in conditions such as hypertension because it allows more water to be excreted in the urine rather than be absorbed in the blood which increases blood volume. This effect leads to reduced plasma volume, reduced venous return, lower cardiac output, and eventually decreased blood pressure Side effects such as headache, dizziness, confusion, fast/irregular heartbeat, increased urination, muscle cramps or spasms and fatigue, weakness, or loss of energy can occur from taking indapamide. The drug is administered as an oral tablet.
References
Indapamide Diuretic Pathway References
National Center for Biotechnology Information (2020). PubChem Compound Summary for CID 3702, Indapamide. Retrieved December 2, 2020 from https://pubchem.ncbi.nlm.nih.gov/compound/Indapamide.
Ritter, James (2020). Rang and Dale’s Pharmacology (9th ed). The kidney and urinary system. Retrieved from: https://www-clinicalkey-com.login.ezproxy.library.ualberta.ca/#!/browse/book/3-s2.0-C2016004202X
Wishart, D., Knox, C., Guo, A., Shrivastava, S., Hassanali, M., Stothard, P., . . . Woolsey, J. (2005, June). Indapamide. Retrieved November 30, 2020, from https://go.drugbank.com/drugs/DB00808
WebMD. (n.d.). Indapamide Oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing. Retrieved December 02, 2020, from https://www.webmd.com/drugs/2/drug-12360/indapamide-oral/details
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