Thiazides Diuretics: Mechanism and Therapeutic Uses

Thiazides (Low Ceiling Diuretics)

• Impair Na+ and Cl- reabsorption in the early distal tubule, increasing Ca2+ reabsorption and K+ excretion
• Increase urinary excretion of Na+, Cl-, K+, and water, reducing ECF volume, cardiac output, and blood pressure
• Therapeutic uses: treatment of hypertension, mild edema, and calcium nephrolithiasis
• Adverse effects: hypokalemia, hyperuricemia, hyperglycemia, and hyperlipidemia

Loop Diuretics (Furosemide, Bumetanide, Torsemide, Ethacrynic acid)

• Inhibit the apical Na+-K+-2Cl- cotransporter in the thick ascending limb of the loop of Henle
• Therapeutic effects: treatment of severe edema, pulmonary edema, acute renal failure, and hypercalcemia
• Adverse effects: profound ECFV depletion, hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalcemia, hyperuricemia, and ototoxicity

Potassium-Sparing Diuretics

• Mechanisms of action:
  • Spironolactone: antagonizes aldosterone at intracellular cytoplasmic receptor sites, preventing Na+ reabsorption and K+ and H+ secretion
  • Triamterene and amiloride: block Na+ transport channels, decreasing Na+/K+ exchange
• Therapeutic uses: induction of diuresis, treatment of secondary hyperaldosteronism, heart failure, resistant hypertension, ascites, and polycystic ovary syndrome
• Adverse effects: gastric upset, gynecomastia, menstrual irregularities, hyperkalemia, nausea, lethargy, and mental confusion

Osmotic Diuretics (Mannitol, Urea)

• Mechanism of action: increase osmolarity of tubular fluid, resulting in osmotic diuresis
• Therapeutic uses: treatment of patients with increased intracranial pressure or acute renal failure due to shock, drug toxicities, and trauma
• Adverse effects: extracellular water expansion and dehydration, hyponatremia, and hypernatremia

Carbonic Anhydrase Inhibitors (Acetazolamide)

• Mechanism of action: inhibit carbonic anhydrase in the proximal tubular epithelium, decreasing ability to exchange Na+ for H+
• Result: mild diuresis, increased urinary pH, and hyperchloremic metabolic acidosis
• Therapeutic uses: treatment of glaucoma, mountain sickness, and idiopathic intracranial hypertension

Understand the mechanism of action of Thiazides, a type of low ceiling diuretic, and their therapeutic uses in treating hypertension, mild edema, and calcium nephrolithiasis. Learn about their adverse effects as well.