Chlorthalidone is an oral diuretic drug which acts in the kidney, specifically in the distal convoluted tubule of the nephron. Chlorthalidone is indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension. Chlorthalidone is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Chlorthalidone has also been found useful in edema due to various forms of renal dysfunction, such as nephrotic syndrome, acute glomerulonephritis, and chronic renal 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. Chlorthalidone targets this Na+/Cl- cotransporter. Chlorthalidone is transported from the blood into the epithelial cells, then is transported into the urine through the multidrug-resistant associated protein-4. 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. Side effects such as nausea, vomiting, stomach cramping, diarrhea, constipation, loss of appetite, dizziness, headache, and increased thirst can occur from taking chlorthalidone. This drug is administered as an oral tablet.

Chlorthalidone Diuretic Pathway References