ADH, Desmopressin,ADH receptor antagonist

Question 1

ADH MOA

Answer 1

-ADH is released from the posterior pituitary
(“Posterior water jug”)

-the site of action - Collecting Duct
(“Collecting duct (CD)”)
——————————————————————————–
V1R activation

-ADH activates V1 receptor coupled to Gq activates PLC→ IP3 + DAG → increased intracellular Ca2+
(“V1 hole on the Q shaped green”)

• ADH activation of V1 on vascular smooth muscle causes vasoconstriction and increased BP
  (“Constricted golf club”)

V2R activation

• Renal

ADH activates V2 receptors coupled to Gs (activates adenylyl cyclase → increased cAMP)
(“V2 hole on the S shaped green”)

-ADH activation of V2 on the basolateral membrane of the CD causes translocation of aquaporin 2 to the apical membrane and reabsorption of free water
(“Translocation of pure water”)
* Extrarenal V2

• located on the vascular endothelium
  (“Endothelial tile”)

-ADH activation of V2 on vascular endothelium causes release of von Willebrand factor (vWF)
(“Von Wille brand pool table”)

-ADH activation of V2 on vascular endothelium causes release of factor VIII
(“8-ball”)

Question 2

Nephrogenic Diabetes Insipidus MOA

Answer 2

-occurs when the nephron does not respond appropriately to ADH

• lithium can cause drug-induced nephrogenic DI
  (“Lift-ium balloons”)

(“Ignoring water boy”)

Question 3

possible treatments of Nephrogenic Diabetes Insipidus

Answer 3

Thiazide diuretics
(“Chloro-thighs”)

Amiloride -a K+ sparing diuretic
(“Almond cart”)

• amiloride treats lithium induced DI

NSAIDs (e.g. indomethacin)
(“Fire extinguisher”)

Question 4

Central Diabetes Insipidus MOA

Answer 4

occurs when the pituitary does not release adequate amounts of ADH
(“Absent waterboys”)

Question 5

treatment of Central Diabetes Insipidus

Answer 5

-exogenous ADH adminstration
(“Waterboy entering exogenously”)

-Desmopressin acetate
(“Desert-mobile”)

• DDAVP- a long acting synthetic analog of ADH
• DDAVP has high specificity for the V2 receptor
  (“V-2 engine”)

Question 6

DDAVP can be used to treat …

Answer 6

-treats von Willebrand disease releases vWF from vascular endothelium

• can be associated with increased bruisability and muscosal bleeding
  (“Bruised with mucosal bleeding”)

-DDAVP treats hemophilia A
(“Missing 8-ball in “A” frame”)

• releases factor VIII from vascular endothelium
• can be associated with hemarthrosis and prolonged bleeding after minor procedures
  (“Bleeding knee joint”)

-DDAVP treats night enuresis
(“Wet mattress”)

• decreased urine production

-ADH is useful in the management of esophageal variceal bleeding
(“Bulging venous golf clubs”)

• constricts mesenteric arterioles→reduced portal pressure

(“Scratched von Wille brand felt”)

Question 7

DDAVP Side Effect

Answer 7

-can cause hyponatremia

(“Falling salty peanut shells”)

Question 8

SIADH MOA

Answer 8

-caused by the overproduction of ADH
(“Over-hydrating waterboy”)

Question 9

SIADH treatment

Answer 9

V2 ADH receptor antagonists “-vaptan” suffix
(“Vaporizer”)

Conivaptan
Tolvaptan
——————————————————————————–
Demeclocycline
(“Bicycle”)

• vaptans are first line