Diuretics

Definition of Diuretics:

• Diuretics are medications that promote the excretion of water and electrolytes by the kidneys, increasing urine output.
• They are used in conditions like hypertension, heart failure, edema, and certain renal disorders.

Classes of Diuretics:

1. Thiazide Diuretics:

• Examples: Hydrochlorothiazide, Chlorthalidone, Indapamide.
• Mechanism:
  • Inhibit the sodium-chloride symporter in the distal convoluted tubule, reducing sodium and chloride reabsorption.
  • Result in increased excretion of sodium, chloride, potassium, and water.
• Uses: Hypertension, mild to moderate edema (e.g., in heart failure), nephrolithiasis prevention.
• Side Effects: Hypokalemia, hyponatremia, hypercalcemia, hyperlipidemia, hyperglycemia, hyperuricemia, hypotension.

2. Loop Diuretics:

• Examples: Furosemide, Bumetanide, Torsemide.
• Mechanism:
  • Inhibit the Na-K-2Cl symporter in the thick ascending limb of the loop of Henle, leading to significant excretion of sodium, chloride, potassium, calcium, and magnesium.
• Uses: Acute and chronic heart failure, pulmonary edema, renal dysfunction, hypercalcemia.
• Side Effects: Hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, ototoxicity (especially with high doses or rapid IV administration), dehydration, hypotension.

3. Potassium-Sparing Diuretics:

• Subclasses:
  1. Aldosterone Antagonists:
     • Examples: Spironolactone, Eplerenone.
     • Mechanism: Block aldosterone receptors in the collecting ducts, reducing sodium reabsorption and potassium excretion.
     • Uses: Heart failure, hypertension, primary hyperaldosteronism, add-on therapy in loop/thiazide diuretic regimens.
     • Side Effects: Hyperkalemia, gynecomastia (especially with spironolactone), menstrual irregularities, impotence.
  2. Epithelial Sodium Channel (ENaC) Blockers:
     • Examples: Amiloride, Triamterene.
     • Mechanism: Directly inhibit sodium reabsorption in the collecting ducts, reducing potassium excretion.
     • Uses: Hypertension, heart failure, adjunctive therapy with other diuretics.
     • Side Effects: Hyperkalemia, gastrointestinal disturbances, dizziness.

4. Carbonic Anhydrase Inhibitors:

• Examples: Acetazolamide, Methazolamide.
• Mechanism: Inhibit carbonic anhydrase in the proximal tubule, reducing bicarbonate reabsorption, leading to excretion of sodium, bicarbonate, potassium, and water.
• Uses: Glaucoma, metabolic alkalosis correction, altitude sickness prophylaxis, certain types of seizures.
• Side Effects: Metabolic acidosis, hypokalemia, paresthesia, kidney stones, diuresis.

5. Osmotic Diuretics:

• Examples: Mannitol, Glycerin.
• Mechanism: Increase osmolarity of the glomerular filtrate, preventing water reabsorption in the proximal tubule and descending limb of the loop of Henle.
• Uses: Cerebral edema, elevated intraocular pressure, acute renal failure prevention (during certain surgeries), osmotic therapy in certain poisonings.
• Side Effects: Fluid and electrolyte imbalance, dehydration, hyperosmolarity, pulmonary edema, renal dysfunction.

Clinical Considerations:

• Electrolyte Monitoring: Regular monitoring of potassium, sodium, magnesium, and calcium levels is essential, especially with loop and thiazide diuretics.
• Renal Function: Diuretics can affect renal perfusion; kidney function should be monitored.
• Blood Pressure Management: Diuretics are first-line for hypertension; choice depends on patient comorbidities.
• Combination Therapy: Often used in combination to balance electrolyte effects (e.g., thiazides with potassium-sparing diuretic).

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