Thiazide Diuretics

3. Thiazide Diuretics
Thiazides block the NCC channel in the distal convoluted tubule. This prevents the reabsorption of Na+ and Cl-. Hydrochlorothiazide is a benzothiadiazine derivative while chlorthalidone lacks the benzothiadiazine structure. Chlorthalidone has a longer half-life than hydrochlorothiazide. Thiazides have a moderate diuretic effect. They cause kidney to excrete Na+, Cl-, K+ and titratable acid. However they also cause an increase in Ca2+ reabsorption.

Unlike loop diuretics, the increase in Na+ delivery to the DCT will not cause activation of RAAS. Thus the kidney is unable to compensate for the Na+ excretion, resulting in concentrated urine.

Thiazides can be used to treat:
-congestive heart failure
-hepatic cirrhosis
-nephrotic syndrome
-chronic renal failure
-acute glomerulonephritis
-hypertension
-nephrogenic diabetes

Adverse effects of thiazides include:
-hyponatremia
-hypotension
-hypokalemia
-metabolic alkalosis
-hypomagnesemia
-hypercalcemia
-hyperuricemia (gout)
-hyperglycemia
-hypersensitivity to sulfonamides

Drug interactions with thiazides include:
-Digitalis glycosides (hypokalemia --> arrhythmia)
-Lithium (enhanced Na+ excretion --> lithium toxicity)
-Antihypertensive drugs (hypotension)
-Vitamin D analogs (increase Ca2+)
-Anti-diabetic drugs (hyperglycemia)
-Probenecid (blocks OAT so drug can't get in)
-NSAIDs (block COX-2 --> decreased prostaglandins --> decreased vasodilation --> decreased GFR --> blunted response because not much is filtered)
-Amphotericin B (hypokalemia)
-Glucocorticoids (hypokalemia)
-ACE Inhibitors (increased nephrotoxicity)