Presentation on short topic - Aquaretics

1. Aquaretics
Dr. Sahil Kumar
Department of Pharmacology
Maulana Azad Medical College

2. Outline
Definition
Aquaretic agents and their uses
Conclusion

3. Definition
An aquaretic is a drug that is used to promote
loss of water (aquaresis) whilst retaining
electrolytes.

4. Aquaretic agents
Vasopressin Receptor Antagonists
Demeclocycline
Lithium

5. Vasopressin Receptors

6. Structure of the Vasopressin V2 Receptor

7. Signal Transduction Via the V2 Receptor

8. Vasopressin (ADH) ↑ in…
SIADH – ADH release is not fully suppressed as it
would normally be in a setting of hypotonicity.
CHF – arterial under-distention & baroreceptor
unloading  secretion of ADH.
Cirrhosis – splanchnic vasodilatation  arterial
underfilling w/ non-osmotic release of ADH.

9. Treatments for SIADH
Water restriction
Salt +/- a loop diuretic
Saline
Drugs used:
• Urea
• Demeclocycline
• Lithium
• Vaptans

10. Vaptans:
Vasopressin Receptor Antagonists
Conivaptan
Tolvaptan
Lixivaptan
Satavaptan
Mozavaptan

11. Conivaptan
Approved for euvolemic hyponatremia.
Disadvantages:
• Non-selective (V2 & V1a)
• Potent CYP3A4 inhibition.
• IV formulation only.
A/E – Infusion site reactions, Hypotension,
polydipsia, polyuria.

12. Tolvaptan
Oral.
V2 selective.
Approved for hyponatremia associated with
congestive heart failure, cirrhosis, and SIADH.
?PCKD.
A/E – liver injury, potentially leading to liver
failure.

13. Lixivaptan
Oral.
V2 selective.
Phase III.
THE BALANCE (Treatment of HyponatrEmia
BAsed on LixivAptan in Nyha class III/IV
Cardiac patient Evaluation) study.

14. Satavaptan
Mozavaptan

15. Aquaretic agents – Vaptans, Demeclocycline, Li.
Vasopressin receptor antagonists can cause an
electrolyte-free aquaresis, reduce urine
osmolality, & raise serum Na
Main side effect is increased thirst.
Some Vaptans under development for SIADH,
CHF and Cirrhosis.
Conclusion