Diuretic classes and mechanisms

Diuretic Classes - The Nephron Hit List

• Proximal Convoluted Tubule (PCT): Carbonic Anhydrase Inhibitors (e.g., Acetazolamide)
• Thick Ascending Limb (TAL): Loop Diuretics (e.g., Furosemide)
  • Inhibit Na-K-2Cl cotransporter.
• Distal Convoluted Tubule (DCT): Thiazide Diuretics (e.g., Hydrochlorothiazide)
  • Inhibit Na-Cl cotransporter.
• Collecting Duct: K-Sparing Diuretics (e.g., Spironolactone, Amiloride)

⭐ Thiazides can cause hypercalcemia as they increase distal tubular reabsorption of Ca²⁺, making them useful for osteoporosis.

📌 Mnemonic (proximal to distal): Punch The Ticket, Chief!

Loop Diuretics - The Powerhouse Blockers

• MOA: Inhibit the Na⁺/K⁺/2Cl⁻ cotransporter in the thick ascending limb of the Loop of Henle.
• Drugs: Furosemide, Bumetanide, Torsemide. Ethacrynic acid (for sulfa allergy).
• Key Effects:
  • Most potent diuretic class; causes significant ↑ in Na⁺, K⁺, Cl⁻ excretion.
  • "Loops Lose Ca²⁺" → increases Ca²⁺ excretion.
• Uses: Edema (HF, cirrhosis), HTN with renal failure, hypercalcemia.
• Adverse Effects: Hypokalemia, ototoxicity, hyperuricemia (gout).
  • 📌 OHH DAANG! (Ototoxicity, Hypokalemia, Hypomagnesemia, Dehydration, Allergy, Nephritis, Gout).

⭐ Exam Favorite: Loops stimulate prostaglandin release, causing afferent arteriole vasodilation. NSAIDs can blunt their diuretic effect by inhibiting prostaglandins.

Thiazide Diuretics - The Gentle Squeezers

• Mechanism: Inhibit the Na⁺-Cl⁻ cotransporter (NCC) in the Distal Convoluted Tubule (DCT).
• Primary Effect: Modest increase in Na⁺, Cl⁻, and water excretion.
• Electrolyte Changes:
  • ↓ Serum: Na⁺, K⁺, Mg²⁺
  • ↑ Serum: Ca²⁺ (spares calcium), Uric acid, Glucose, Lipids
• Clinical Uses:
  • Hypertension (first-line therapy)
  • Edema (mild heart failure)
  • Nephrolithiasis (from idiopathic hypercalciuria)
  • Nephrogenic diabetes insipidus
• Adverse Effects: Hypokalemic metabolic alkalosis, hyponatremia, sulfa allergy.
  • 📌 Remember the "Hyper-GLUC" side effects: HyperGlycemia, HyperLipidemia, HyperUricemia, and HyperCalcemia.

⭐ Thiazides lose efficacy when GFR is < 30 mL/min (exception: metolazone).

K-Sparing Diuretics - The Potassium Keepers

• Mechanism: Act on collecting ducts to ↓Na+ reabsorption & ↓K+ secretion.
  • Aldosterone Antagonists: Spironolactone, Eplerenone.
  • ENaC Blockers: Amiloride, Triamterene.
• Primary Use: Often co-administered with thiazide or loop diuretics to mitigate hypokalemia. Also used in heart failure and hyperaldosteronism.
• Adverse Effects: ⚠️ Hyperkalemia (risk ↑ with ACEi/ARBs), metabolic acidosis.
• 📌 Mnemonic: The K+ STAys with Spironolactone, Triamterene, Amiloride.

⭐ Spironolactone's anti-androgen activity can lead to painful gynecomastia, a frequently tested side effect.

Other Diuretics - Niche Agents

• Carbonic Anhydrase Inhibitors (Acetazolamide)

  • Site: Proximal Convoluted Tubule (PCT).
  • Mechanism: Inhibits carbonic anhydrase → ↓ NaHCO₃ reabsorption → self-limited bicarbonate diuresis.
  • Uses: Glaucoma, metabolic alkalosis, altitude sickness.
  • Adverse Effect: Hyperchloremic metabolic acidosis. 📌 "ACID"-azolamide.

• Osmotic Diuretics (Mannitol)

  • Site: PCT, thin descending limb.
  • Mechanism: ↑ tubular fluid osmolarity, drawing water into the lumen.
  • Uses: ↓ intracranial and intraocular pressure.

⭐ Mannitol may cause pulmonary edema by rapidly expanding extracellular fluid volume before the onset of diuresis.

High‑Yield Points - ⚡ Biggest Takeaways

• Thiazides block the Na-Cl cotransporter in the DCT, causing hypercalcemia.
• Loop diuretics inhibit the Na-K-2Cl cotransporter in the thick ascending limb and are most potent; they cause hypocalcemia.
• K+-sparing diuretics (e.g., Spironolactone) are aldosterone antagonists in the collecting duct, risking hyperkalemia.
• Most diuretics cause hypokalemia, except for K+-sparing types.
• Acetazolamide inhibits carbonic anhydrase in the PCT; used for glaucoma and metabolic alkalosis.
• Mannitol is an osmotic diuretic used to decrease intracranial pressure.