Pharmacology of Diuretics: Loop Diuretics

Diuretics Pharmacology

Loop Diuretics

• Mechanism of action: Inhibit Na+/K+/2Cl- symporter in the thick ascending limb of the loop of Henle, reducing sodium reabsorption and increasing urine production.
• Examples: Furosemide, Bumetanide, Torsemide.
• Effects:
  • Increase urinary sodium and potassium excretion.
  • Reduce blood volume and blood pressure.
  • Increase urinary calcium excretion.
• Uses:
  • Edema (heart failure, liver disease, kidney disease).
  • Hypertension.
  • Pulmonary edema.

Thiazide Diuretics

• Mechanism of action: Inhibit Na+/Cl- symporter in the distal convoluted tubule, reducing sodium reabsorption and increasing urine production.
• Examples: Hydrochlorothiazide, Chlorthalidone, Indapamide.
• Effects:
  • Increase urinary sodium and potassium excretion.
  • Reduce blood volume and blood pressure.
  • Increase urinary calcium reabsorption.
• Uses:
  • Hypertension.
  • Edema (heart failure, liver disease, kidney disease).
  • Nephrogenic diabetes insipidus.

Potassium-sparing Diuretics

• Mechanism of action: Inhibit aldosterone's effects on the distal convoluted tubule, reducing sodium reabsorption and increasing potassium retention.
• Examples: Spironolactone, Eplerenone, Triamterene, Amiloride.
• Effects:
  • Increase urinary sodium excretion.
  • Reduce potassium excretion.
  • Reduce blood pressure.
• Uses:
  • Hypertension.
  • Heart failure.
  • Primary aldosteronism.

Osmotic Diuretics

• Mechanism of action: Increase osmotic pressure in the renal tubules, reducing water reabsorption and increasing urine production.
• Examples: Mannitol, Glycerin.
• Effects:
  • Increase urine production.
  • Reduce cerebral edema.
  • Reduce intraocular pressure.
• Uses:
  • Cerebral edema (head trauma, stroke).
  • Glaucoma.
  • Reversible oliguria.

Diuretic Resistance

• Definition: Decreased response to diuretic therapy, leading to inadequate natriuresis and diuresis.
• Causes:
  • Reduced diuretic delivery to the kidney.
  • Impaired diuretic secretion into the renal tubules.
  • Increased sodium reabsorption in the distal nephron.
  • Activation of the renin-angiotensin-aldosterone system.
• Management:
  • Increase diuretic dose.
  • Combine diuretics with different mechanisms of action.
  • Address underlying causes (e.g., heart failure, kidney disease).
  • Monitor electrolyte levels and adjust therapy accordingly.

Diuretics Pharmacology

Loop Diuretics

• Inhibit Na+/K+/2Cl- symporter in the thick ascending limb of the loop of Henle, reducing sodium reabsorption and increasing urine production.
• Examples: Furosemide, Bumetanide, Torsemide.
• Increase urinary sodium and potassium excretion.
• Reduce blood volume and blood pressure.
• Increase urinary calcium excretion.
• Uses: edema (heart failure, liver disease, kidney disease), hypertension, pulmonary edema.

Thiazide Diuretics

• Inhibit Na+/Cl- symporter in the distal convoluted tubule, reducing sodium reabsorption and increasing urine production.
• Examples: Hydrochlorothiazide, Chlorthalidone, Indapamide.
• Increase urinary sodium and potassium excretion.
• Reduce blood volume and blood pressure.
• Increase urinary calcium reabsorption.
• Uses: hypertension, edema (heart failure, liver disease, kidney disease), nephrogenic diabetes insipidus.

Potassium-sparing Diuretics

• Inhibit aldosterone's effects on the distal convoluted tubule, reducing sodium reabsorption and increasing potassium retention.
• Examples: Spironolactone, Eplerenone, Triamterene, Amiloride.
• Increase urinary sodium excretion.
• Reduce potassium excretion.
• Reduce blood pressure.
• Uses: hypertension, heart failure, primary aldosteronism.

Osmotic Diuretics

• Increase osmotic pressure in the renal tubules, reducing water reabsorption and increasing urine production.
• Examples: Mannitol, Glycerin.
• Increase urine production.
• Reduce cerebral edema.
• Reduce intraocular pressure.
• Uses: cerebral edema (head trauma, stroke), glaucoma, reversible oliguria.

Diuretic Resistance

• Definition: Decreased response to diuretic therapy, leading to inadequate natriuresis and diuresis.
• Causes: reduced diuretic delivery to the kidney, impaired diuretic secretion into the renal tubules, increased sodium reabsorption in the distal nephron, activation of the renin-angiotensin-aldosterone system.
• Management: increase diuretic dose, combine diuretics with different mechanisms of action, address underlying causes (e.g., heart failure, kidney disease), monitor electrolyte levels and adjust therapy accordingly.