Diuretics Part 2
Potassium-Sparing, Carbonic Anhydrase Inhibitors, Osmotic Agents, Vasopressin Antagonists
Four Classes — Targets and Primary Uses
MR Antagonists
Spironolactone / Eplerenone / Finerenone
- Block aldosterone at collecting duct
- Potassium-sparing natriuresis
- Heart failure, hyperaldosteronism
- Risk: hyperkalemia
- Spironolactone: gynecomastia (anti-androgen effect)
ENaC Blockers
Amiloride / Triamterene
- Block epithelial Na channel directly
- Aldosterone-independent K sparing
- Amiloride: lithium-induced diabetes insipidus
- Triamterene: prodrug, nephrolithiasis risk
- Risk: hyperkalemia
CA Inhibitors
Acetazolamide
- Block proximal tubule carbonic anhydrase
- Bicarbonate wasting → metabolic acidosis
- Altitude sickness prophylaxis
- Glaucoma (aqueous humor)
- Reverses diuretic-induced alkalosis
Osmotic / Vaptan
Mannitol / Tolvaptan
- Mannitol: osmotic water retention in lumen
- Elevated intracranial pressure, acute glaucoma
- Tolvaptan: V2 receptor block → aquaresis
- Euvolemic/hypervolemic hyponatremia
- Monitor: Na overcorrection risk
Mineralocorticoid Receptor Antagonist Comparison
| Feature |
Spironolactone |
Eplerenone |
Finerenone |
| Scaffold |
Steroidal |
Steroidal |
Nonsteroidal |
| MR selectivity |
Low (binds androgen, progesterone receptors) |
High (40x more selective than spironolactone) |
Highest (distinct scaffold) |
| Gynecomastia |
Common (dose-dependent) |
Rare |
Rare |
| Key indication |
Heart failure, resistant HTN, cirrhosis |
Post-MI heart failure (EPHESUS) |
Diabetic CKD (FIDELIO-DKD, FIGARO-DKD) |
Vaptan Safety
Sodium Overcorrection Risk
- Max correction: 10–12 mEq/L per 24 hours
- Osmotic demyelination: irreversible
- Highest risk: Na below 120 mEq/L for >48 hours
- Free water access required throughout
- Tolvaptan: hepatotoxicity warning beyond 30 days
Sequential Blockade
Combination Strategies
- Loop + metolazone: profound natriuresis, watch K/Mg
- Loop + MR antagonist: K-neutral combination in HF
- Loop + acetazolamide: correct contraction alkalosis
- ADVOR trial: acetazolamide accelerates decongestion
Mannitol Contraindications
Contraindicated in heart failure (initial volume expansion precipitates decompensation), anuric renal failure (drug accumulates, cannot be excreted), and disrupted blood-brain barrier (mannitol crosses into brain tissue and worsens edema by reversing the osmotic gradient).