Thiazide Diuretics: Mechanism of Action and Therapeutic Uses

Study Notes

Thiazides (Low Ceiling Diuretics)

Impair Na+ and Cl- reabsorption in the early distal tubule, increasing Ca reabsorption and K+ excretion.
Increase urinary excretion of Na+ (5%), Cl-, K+, and water, leading to reduced ECF volume, cardiac output, and blood pressure.
Therapeutic uses: Treatment of Hypertension, Mild Edema, and Calcium Nephrolithiasis.
Adverse effects: Hypokalemia, Hypokalemic metabolic alkalosis, Hyperuricemia, Hyperglycemia, and Hyperlipidemia.

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

Inhibit the apical Na+-K+-2Cl- cotransporter of 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, and Ototoxicity.

Potassium-Sparing Diuretics

Mechanism 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

Mechanism of action: Hydrophilic chemical substances that are filtered through the glomerulus, then undergo little or no reabsorption, resulting in a higher osmolarity of the tubular fluid and 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 until diuresis occurs.

Carbonic Anhydrase Inhibitors (Acetazolamide)

Mechanism of action: Inhibits carbonic anhydrase in the proximal tubular epithelium, decreasing the ability to exchange Na+ for H+ and resulting in a mild diuresis.
Therapeutic effects: Increased urinary pH and phosphate excretion by an unknown mechanism.
Adverse effects: Hyperchloremic metabolic acidosis and decreased diuretic efficacy following several days of therapy.

Description

Learn about the mechanism of action of thiazide diuretics, their pharmacological actions, therapeutic uses, and adverse effects. Understand how they affect sodium, potassium, and calcium levels in the body.