Diuretics Lecture Notes

Introduction to Diuretics

• Definition: Medications that promote the elimination of sodium and water through urine.
• Importance: Used to manage fluid retention and hypertension.
• Types of diuretics: Loop, Thiazide, Potassium-sparing, Carbonic anhydrase inhibitors, Osmotic diuretics.

Anatomy of the Nephron

• Bowman’s capsule
• Proximal convoluted tubule (PCT)
  • Sodium Reabsorption: 65% occurs here.
  • Diuretic Example: Carbonic anhydrase inhibitors (inhibit bicarbonate reabsorption).
• Loop of Henle
  • Descending Limb: Primarily water reabsorption.
  • Ascending Limb: Sodium Reabsorption: 25% occurs here.
    • Diuretic Example: Loop diuretics (inhibit sodium/potassium/chloride co-transporter).
• Distal Convoluted Tubule (DCT)
  • Early DCT: Sodium reabsorption, about 5%.
    • Diuretic Example: Thiazide diuretics (inhibit sodium/chloride co-transporter).
  • Late DCT: Sodium reabsorption, about 5%.
    • Diuretic Example: Potassium-sparing diuretics (aldosterone antagonists).

Types of Diuretics

1. Carbonic Anhydrase Inhibitors

• Example: Acetazolamide
• Mechanism: Inhibit bicarbonate reabsorption, leading to loss of bicarbonate, sodium, and mild water loss.
• Indications: Altitude sickness, metabolic alkalosis, glaucoma.
• Adverse Effects: Metabolic acidosis, kidney stones, hyperammonemia.

2. Loop Diuretics

• Examples: Furosemide, Bumetanide, Torsemide.
• Mechanism: Inhibit sodium/potassium/chloride co-transporter in the ascending limb of the loop of Henle.
• Indications: Acute pulmonary edema, heart failure, hyperkalemia, hypercalcemia.
• Adverse Effects: Hypernatremia, hypovolemia, hypocalcemia, hypomagnesemia, hypokalemia, metabolic alkalosis, hyperuricemia, ototoxicity.

3. Thiazide Diuretics

• Examples: Hydrochlorothiazide, Chlorthalidone, Metolazone.
• Mechanism: Block sodium/chloride co-transporter in early DCT.
• Indications: Hypertension, nephrolithiasis (reduces calcium excretion).
• Adverse Effects: Hyponatremia, hypercalcemia, hypokalemia, metabolic alkalosis, hyperlipidemia, hyperglycemia, hyperuricemia.

4. Potassium-Sparing Diuretics

• Examples: Spironolactone, Eplerenone, Amiloride.
• Mechanism: Aldosterone antagonists (inhibit sodium reabsorption and potassium excretion) or ENaC blockers.
• Indications: Heart failure, hypertension, hyperaldosteronism (Conn's syndrome).
• Adverse Effects: Hyperkalemia, metabolic acidosis, gynecomastia, menstrual irregularities.

5. Osmotic Diuretics

• Examples: Mannitol, Urea.
• Mechanism: Increase osmotic pressure, pulling water into the renal tubules.
• Indications: Cerebral edema, acute glaucoma.
• Adverse Effects: Volume overload, dehydration, hypernatremia.

Mechanisms of Action

• Diuretics act at various sites in the nephron, altering the reabsorption of sodium, water, and other electrolytes.

Clinical Applications and Indications

• Manage fluid overload in conditions like heart failure, cirrhosis, kidney disease.
• Utilize specific diuretics based on the required effect and patient condition (e.g., Loop for rapid diuresis, Thiazides for hypertension).

Summary of Adverse Effects

• Loop Diuretics: Hypernatremia, hypovolemia, electrolyte imbalances, ototoxicity.
• Thiazide Diuretics: Similar effects, plus potential hypercalcemia.
• Potassium-Sparing Diuretics: Hyperkalemia, metabolic acidosis.
• Carbonic Anhydrase Inhibitors: Metabolic acidosis, hyperammonemia.

Case Studies and Application of Knowledge

• Acute Pulmonary Edema: Use Loop diuretics.
• Altitude Sickness: Acetazolamide.
• Cirrhosis with Ascites: Primarily use aldosterone antagonists (spironolactone).
• Kidney Stones: Use Thiazide diuretics to decrease urinary calcium excretion.