Aquaretics
Aquaretics
Short Answer Questions (5 Points Each)
1. What are aquaretics and how do they differ from traditional diuretics?
- Aquaretics promote free water excretion without electrolyte loss.
- They antagonize vasopressin (ADH) receptors, primarily V2.
- Diuretics cause natriuresis (salt and water loss), unlike aquaretics.
- Aquaretics preserve sodium and potassium balance.
- Useful in euvolemic/hypervolemic hyponatremia, not in hypovolemia.
2. Enumerate the indications for Tolvaptan use.
- Euvolemic hyponatremia (e.g., SIADH).
- Hypervolemic hyponatremia in heart failure.
- Cirrhotic hyponatremia (with caution).
- Autosomal Dominant Polycystic Kidney Disease (ADPKD).
- Off-label in selected cases of water-retention syndromes.
3. What precautions must be taken during aquaretic therapy?
- Monitor serum sodium frequently to avoid overcorrection.
- Avoid use in hypovolemic hyponatremia.
- Monitor liver function in long-term Tolvaptan (especially in ADPKD).
- Ensure adequate fluid intake to prevent dehydration.
- Hospitalization may be required during initiation.
4. Describe the mechanism of action of Tolvaptan.
- Tolvaptan selectively blocks V2 vasopressin receptors.
- V2 receptors regulate aquaporin-2 insertion in collecting ducts.
- Blocking V2 inhibits water reabsorption.
- Results in aquaresis: excretion of free water.
- Leads to gradual rise in serum sodium.
5. Compare Tolvaptan and Conivaptan.
- Tolvaptan is oral; Conivaptan is intravenous.
- Tolvaptan is selective for V2; Conivaptan blocks both V1A and V2.
- Tolvaptan used in chronic therapy (SIADH, ADPKD).
- Conivaptan used for acute correction in hospitalized patients.
- Hepatotoxicity is more relevant with Tolvaptan in long-term use.
6. What are the side effects and risks of aquaretic use?
- Overcorrection of sodium causing osmotic demyelination.
- Polyuria and dehydration symptoms.
- Elevated liver enzymes with long-term use.
- Thirst, dry mouth, and weakness.
- Potential drug interactions via CYP3A metabolism.
7. How is hyponatremia corrected using aquaretics safely?
- Start at low dose and titrate based on serum Na+.
- Sodium correction should not exceed 8–10 mmol/L per 24 hours.
- Monitor urine output to assess aquaresis.
- Replace water losses if polyuria is excessive.
- Consider holding drug if rapid correction occurs.
8. What is SIADH and how do aquaretics treat it?
- Syndrome of inappropriate antidiuretic hormone secretion.
- Results in water retention and hyponatremia.
- Aquaretics antagonize ADH effect on collecting ducts.
- Promote free water excretion without sodium loss.
- Normalize serum sodium and reduce water overload.
9. Explain the role of Tolvaptan in ADPKD.
- Slows cyst growth by reducing cAMP levels.
- Reduces rate of kidney volume expansion.
- Preserves renal function over time.
- Requires liver monitoring due to hepatotoxicity risk.
- Used in selected patients with rapid progression.
10. List contraindications of aquaretic therapy.
- Hypovolemic hyponatremia (risk of worsening volume loss).
- Anuria or severely impaired renal function.
- Inability to sense or respond to thirst.
- Concurrent strong CYP3A4 inhibitors (e.g., ketoconazole).
- History of liver injury with prior Tolvaptan use.
