Water Conservation Drugs

Question 1

What are the receptors that Vasopressin act on?
What is the results of Vasopressin binding to the receptors?
What is another MOA of Vasopressin?

Answer 1

V1a
V2

renal conservation of water

Vasopressin also induces the release of Factor VIII
and von Willebrand’s factor

Question 2

What is the results of V1a binding of Vasopressin?

Answer 2

vasoconstriction including in the kidney (low dose)

Question 3

What is the results of V2 binding of Vasopressin?

Answer 3

V2: increase NKCC in TAL
-> increase medullary osmolality

V2: increase expression and apical localization of aquaporin-2
-> increase permeability of collecting duct to water

Question 4

Which receptor is Desmopressin specific too?

What is the MOA of Desmopressin?

Answer 4

V2
Desmopressin is similar toVasopressin

Mechanism of action:
Less vasoconstricting action than vasopressin
Same action on water permeability than vasopressin

Question 5

What is the therapeutic use of Desmopressin?

Answer 5

To decrease urine production:

• Central DI (deficiency of ADH secretion)
• Nocturnal enuresis (bedwetting)

To help reduce bleeding:

• von Willebrand’s disease (vWF deficiency)
• Hemophilia A (factor VIII deficiency)

Question 6

What is the side effects and toxicity of desmopressin?

Answer 6

V1 effects:
pallor, vasoconstriction, nausea, cramp;
coronary vasoconstriction

V2 effects:
water intoxication, hyponatremia

Question 7

Which areas of the nephron does Vasopressin affect?

Answer 7

1) entire collecting duct
2) inner medullary collecting duct
3) EnAC in the CCD

Question 8

How does vasopressin act on the entirety of the CD?

Answer 8

1)Increase in water permeability along the whole CD (effect on AQP2) which enables osmotic equilibration between CD lumen and surrounding interstitium.

Question 9

How does vasopressin act on the IMCD?

Answer 9

2)Increase in urea permeability (effect on UT-A1), occurring only in the terminal part of the IMCD, and enabling urea diffusion in the inner medullary interstitium, where it contributes to papillary hyperosmolality and thus to more intense driving force for water reabsorption.

Question 10

How does vasopressin act on ENAC?

Answer 10

3)Stimulation of sodium reabsorption (through ENaC) which secondarily drives additional water reabsorption.

Question 11

What is the MOA of NSAIDS?

Answer 11

NSAIDs inhibit renal cyclooxygenase responsible for the production of prostaglandins

Question 12

What does prostagladins do to vasopressin?

Answer 12

prostaglandins antagonize the action of vasopressin

	- increase of phosphodiesterase?
 		- inhibit AVP binding to its receptors?

Question 13

How doe NSAIDS(indomethacin) increase the actionof vasopressin?

Answer 13

NSAIDs (indomethacin)
inhibit the production of prostaglandins
and increase the action of vasopressin

Question 14

What is the MOA of demeclocycline?

Answer 14

inhibits protein synthesis by binding with the 30S and possibly the 50S ribosomal subunit(s) of susceptible bacteria.

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.

Question 15

What is the therapeutic use of Demeclocycline?

Answer 15

treatment of chronic syndrome of inappropriate secretion of antidiuretic hormone

rarely used as antibiotic

Question 16

What are the side effects and toxcity of demeclocycline?

Answer 16

nausea, skin photosensitivity

nephrotoxicity, irreversible renal failure

Question 17

What are vaptans?

Answer 17

Vaptans are vasopressin-receptor antagonists.

-> loss of free water

Question 18

What are the names of the vaptans?

Answer 18

conivaptan

tolvaptan

Question 19

What is the MOA of Conivaptan?

Answer 19

vasopressin V1a/V2-receptor antagonist.

Question 20

What is the MOA of Tolvaptan?

Answer 20

selective vasopressinV2-receptor antagonist

Question 21

What happens when there simultaneous blockade of V1 and V2?

Answer 21

blockade of V1a- and V2-receptors would theoretically yield advantages over V2-receptor antagonism, by inhibiting V1a-mediated arterial vasoconstriction and myocardial remodeling, but V1a stimulation in the collecting duct antagonize the action of the V2.

Question 22

What are the therapeutic use of vaptans?

Answer 22

Approved to treat certain forms of hyponatremia

Question 23

What are the side effects of vaptans?

Answer 23

severe hypernatremia and nephrogenic diabetes insipidus (control sodium!)

Dry mouth and thirst

Question 24

What are side effects specific to tolvaptan?

Answer 24

Tolvaptan can cause hypotensions

Question 25

What is the caution when using vaptans?

Answer 25

Too rapid raise in plasma sodium concentrations can cause osmotic demyelination syndrome (ODS) which can lead to coma or death.

Question 26

What are early symptoms ODS?

Answer 26

include difficulty speaking or swallowing, drowsiness, confusion, mood changes, seizures and difficulty controlling body movements with muscle weakness in the arms and legs.