<unk>  reduces reabsorption of sodium and chloride primarily through inhibition of the Na+/Cl− symporter in the apical membrane of distal convoluted tubule cells in the kidney. Although<unk>  is often referred to as a "thiazide-like" diuretic, it is unlike thiazide diuretics in that, in addition to its inhibition of the Na+/Cl− symporter, it also strongly inhibits multiple isoforms of carbonic anhydrase. Some of<unk> 's diuretic effect is also due to this inhibition of carbonic anhydrase in the proximal tubule. Chronic exposure to<unk>  decreases the glomerular filtration rate.<unk> 's diuretic effect is diminished in persons with kidney impairment. By increasing the delivery of sodium to the distal renal tubule,<unk>  indirectly increases potassium excretion via the sodium-potassium exchange mechanism (i.e. apical ROMK/Na channels coupled with basolateral Na+/K ATPases). This can result in a low blood concentration of potassium and chloride as well as a mild metabolic alkalosis; however, the diuretic effect of<unk>  is not affected by the acid-base balance of the person being treated. There is uncertainty about the mechanism of the blood pressure-lowering effect that occurs during chronic exposure to<unk> . Initially, diuretics lower blood pressure by decreasing cardiac output and reducing plasma and extracellular fluid volume. Eventually, cardiac output returns to normal, and plasma and extracellular fluid volume return to slightly less than normal, but a reduction in peripheral vascular resistance is maintained, thus resulting in an overall lower blood pressure. The reduction in intravascular volume induces an elevation in plasma renin activity and aldosterone secretion, further contributing to the potassium loss associated with thiazide diuretic therapy.
Chlortalidone
Primidone
Rimonabant
Thioridazine
Ziprasidone
Domperidone
Methylphenidate
Paliperidone