Cyclothiazide is an oral diuretic drug which acts in the kidney, specifically in the distal convoluted tubule of the nephron. Cyclothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension. In the distal convoluted tubule (DCT), the regulation of ions such as sodium, potassium, calcium, chloride and magnesium occur. 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 which transports calcium from the lumen into the epithelial cell, a potassium channel which transports K+ out of the epithelial cell and a Na+/Cl- cotransporter which transports Na+ and Cl- into the epithelial cell. Cyclothiazide targets this Na+/Cl- cotransporter. Cyclothiazide 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 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 urine rather than be absorbed in the blood where it increases blood volume. Side effects such as hypokalemia, hyponatremia, metabolic alkalosis, hypercalcemia, hyperglycemia, hyperuricemia, hyperlipidemia and sulfonamide allergy are possible from taking thiazide diuretics and can occur from taking cyclothiazide.

Cyclothiazide Diuretic Pathway References