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Pathway Description
Hydrochlorothiazide Diuretic Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2020-07-24
Last Updated: 2023-10-25
Hydrochlorothiazide is an oral diuretic drug that acts in the kidney, specifically in the distal convoluted tubule of the nephron. It is used to treat conditions such as hypertension, heart failure, severe resistant edema, nephrogenic diabetes insipidus, and to prevent kidney stone formation in idiopathic hypercalciuria. 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. Hydrochlorothiazide targets this Na+/Cl- cotransporter. Hydrochlorothiazide is transported from the blood into the epithelial cells via organic anion transporter-1, then is transported into the urine through the multidrug-resistant associated protein-4. In the lumen in 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. Side effects such as hypokalemic metabolic alkalosis, impaired glucose tolerance, hypernatremia, weakness and fatigue, hyperlipidemia, impaired uric acid metabolism, gout, allergic reactions, and impotence can occur from taking hydrochlorothiazide. This drug is administered as an oral tablet or capsule.
References
Hydrochlorothiazide Diuretic Pathway References
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