THIAZIDES [Chlorothiazide]

• Inhibit NaCl reabsorption in the early segments of the distal convoluted tubule

—> increased Na⁺ and Cl^- in urine

• May also stimulate Ca²⁺ reabsorption in DCT [Ca²⁺ reabsorption in DCT is modulated by PTH] —> may decrease Ca²⁺ excretion [useful for inhibiting kidney stones]

CARBONIC ANHYDRASE INHIBITORS [Acetazolamide(Diamox)]

• Block reabsorption of in the PCT by inhibiting carbonic anhydrase —> increased HCO₃^- in tubule acting as an osmotic diuretic

• Normally the carbonic anhydrase that lines the luminal border of the proximal convoluted tubule catalyses the association of H₂O & CO₂ into carbonic acid -> H⁺ & HCO₃^-—> reabsorption of HCO₃^-

• Note that metabolic acidosis 2° to renal HCO₃^- loss is a danger

• Na⁺ accompanies the HCO₃^-

POTASSIUM-SPARING DIURETICS [spironolactone]

• compete with aldosterone for receptor sites at the cortical collecting tubule—>

i) block Na⁺ reabsorption effect of aldosterone —> Na⁺ acts as a diuretic in tubules

ii) block aldosterone effect on K⁺ secretion —> maintain/increase extracellular K⁺

• Also has a direct effect in inhibiting the effect of aldosterone in stimulating H⁺ secretion —> metabolic acidosis