Drugs for Water Conservation

Question 1

MOA of ADH (Vasopressin)?

Answer 1

MOA:
1. V1a: vasoconstriction in vasculature and in the kidney
•Vasoconstriction of kidney → ↓ GFR → ↓ urine output
2. V2: increase NKCC in TAL
•→ increase medullary osmolality (tip of loop of Henle)
3. V2: increase expression and apical insertion of aquaporin-2
•→ increase permeability of collecting duct to water
4. V2: induces release of Factor VIII and von Willebrand’s factor.
Ultimately = conserve water in kidney

Question 2

What is Desmopressin (DDAVP)? MOA?

Answer 2

Similar to vasopressin but more specific to V2 receptor.

Less vasoconstriction.

Question 3

What are the uses of DDAVP?

Answer 3

1. To decrease urine production/increase concentration:
   •Central DI (deficiency of ADH secretion)
   •Nocturnal enuresis (bedwetting)
2. To help reduce bleeding:
   •von Willebrand’s disease (vWF deficiency)
   •Hemophilia A (factor VIII deficiency)

Question 4

What are the SE of DDAVP?

Answer 4

V1 effects: Pallor, vasoconstriction, nausea, cramp; Coronary vasoconstriction
V2 effects: Water intoxication, hyponatremia

Question 5

How do NSAIDS enhance the antidiuretic response to vasopressin?

Answer 5

MOA: Inhibit renal cyclooxygenase responsible for the production of prostaglandins.
•Prostaglandins usually antagonize vasopressin (possibly d/t increase in cAMP which inhibits AVP binding to its receptors).
***Know-Indomethacin increases the action of vasopressin

Question 6

What is Demeclocycline? MOA? Use?

Answer 6

Antibiotic
MOA: Inhibits the action of vasopressin by interfering with the vasopressin-aquaporin signaling cascade.
•Inhibition of vasopressin binding to its receptor V2, and/or inhibition of cAMP protein kinases.
Use: SIADH

Question 7

What are Vaptans? Examples? MOA? Use?

Answer 7

Vasopressin antagonists.
Examples: Conivaptan and Tolvaptan
MOA:
•Conivaptan is a vasopressin V1a/V2-receptor antagonist.
•Tolvaptan is a selective vasopressin V2-receptor antagonist
Use: Hyponatremia

Question 8

What are some major SE of Vaptans?

Answer 8

1. Severe hypernatremia and nephrogenic diabetes insipidus (be careful and control Na+)
2. Tolvaptan can cause liver damage and its use is limited to 30 days.

Question 9

What is the big caution w/ Vaptans?

Answer 9

Too rapid a rise in plasma sodium concentrations can cause osmotic demyelination syndrome (ODS) in the brain, which can lead to coma or death.
Early symptoms of ODS include difficulty speaking or swallowing, drowsiness, confusion, mood changes, seizures and difficulty controlling body movements with muscle weakness in the arms and legs.