Diuretics: Study Notes Oct 2025

• Purpose: Increase urine output by blocking sodium (Na⁺) reabsorption; water follows sodium.

• Main Classes:

  1. Carbonic Anhydrase Inhibitors

  2. Loop Diuretics

  3. Thiazide Diuretics

  4. Potassium-Sparing Diuretics

2. Carbonic Anhydrase Inhibitors

• Prototype: Acetazolamide

• Site: Proximal Tubule

• Mechanism: Inhibits carbonic anhydrase → reduces Na⁺ & HCO₃⁻ reabsorption → mild diuresis, metabolic acidosis

• Indications: Altitude sickness, glaucoma, intracranial hypertension, adjunct in hypervolemia with alkalosis

• Complications: Metabolic acidosis

3. Loop Diuretics

• Prototypes: Furosemide, Torsemide, Bumetanide

• Site: Thick Ascending Limb of Loop of Henle

• Mechanism: Blocks NKCC2 → Na⁺, K⁺, Cl⁻ loss; disrupts Ca²⁺/Mg²⁺ reabsorption

• Effect: Powerful diuresis, distal Na⁺ delivery ↑ → K⁺/H⁺ excretion

• Indications: Hypervolemia (CHF, pulmonary edema, cirrhosis), hyperkalemia

• Complications: Hypovolemia, hypokalemia, metabolic alkalosis, hypocalcemia, hypomagnesemia, hyperuricemia, ototoxicity

4. Thiazide Diuretics

• Prototypes: Hydrochlorothiazide, Chlorthalidone, Metolazone

• Site: Early Distal Tubule

• Mechanism: Blocks Na⁺-Cl⁻ cotransporter → Na⁺/water loss; Ca²⁺ reabsorption ↑

• Effect: Moderate diuresis, distal Na⁺ delivery ↑ → K⁺/H⁺ excretion

• Indications: Hypertension, hypervolemia adjunct, hypercalciuria, osteoporosis

• Complications: Hyponatremia, hypokalemia, metabolic alkalosis, hyperuricemia, hypercalcemia, hypotension

5. Potassium-Sparing Diuretics

• Site: Late Distal Tubule / Collecting Duct

• Subtypes:

  • Aldosterone Antagonists: Spironolactone, Eplerenone → block aldosterone → ↓ ENaC → K⁺ retention

  • Direct ENaC Blockers: Amiloride, Triamterene → block ENaC directly

• Effect: Weak diuresis, conserves K⁺ and H⁺

• Indications: Adjunct for hypervolemia with hypokalemia, hyperaldosteronism, CHF, cirrhosis

• Complications: Hyperkalemia, metabolic acidosis, hyponatremia; spironolactone → gynecomastia

6. Clinical Approach

1. Assess Volume Status:

   • Hypervolemia → JVD, edema, crackles → avoid fluids

   • Hypovolemia → dry mucosa, hypotension, tachycardia → diuretic may be indicated

2. Choose & Titrate Diuretic:

   • Loop diuretics for first-line hypervolemia

   • Use threshold and ceiling doses; IV → PO = 1:2

3. Add Adjuncts:

   • Persistent hypervolemia + hypernatremia → add thiazide

   • Persistent hypervolemia + hypokalemia → add K⁺-sparing

   • Persistent alkalosis → add acetazolamide

4. Monitor: Daily weights, electrolytes (Na⁺, K⁺, Mg²⁺, Ca²⁺), creatinine, volume status

7. Summary Table

Class	Site	Mechanism	Effect	Indications	Key Complications
Carbonic Anhydrase Inhibitor	Proximal Tubule	Inhibits CA	Mild Na⁺/H₂O loss, HCO₃⁻ loss	Altitude sickness, glaucoma, adjunct	Metabolic acidosis
Loop	Thick Ascending Limb	Blocks NKCC2	Powerful Na⁺/H₂O loss, K⁺/H⁺ excretion	Hypervolemia (1st line), hyperkalemia	Hypovolemia, hypokalemia, metabolic alkalosis, ototoxicity
Thiazide	Early Distal Tubule	Blocks Na⁺-Cl⁻ cotransporter	Moderate Na⁺/H₂O loss, Ca²⁺ retention	Hypertension, hypercalciuria, adjunct	Hyponatremia, hypokalemia, hyperuricemia, hypercalcemia
K⁺-Sparing	Collecting Duct	Blocks ENaC / Aldosterone	Weak diuresis, K⁺ retention	Adjunct for hypokalemia, CHF, cirrhosis	Hyperkalemia, metabolic acidosis, gynecomastia