Synthesis: Synthesized in the Hypothalamus (specifically the Supraoptic and Paraventricular nuclei).
Storage/Secretion: Transported to and secreted by the Posterior Pituitary (Neurohypophysis).
Mechanism of Action:
V1 Receptors: Located on vascular smooth muscle → Gq pathway → Vasoconstriction (↑ BP).
V2 Receptors: Located on principal cells of the renal collecting duct → Gs pathway → Insertion of Aquaporin-2 channels into the apical membrane → ↑ Water Reabsorption.
Desmopressin
Mechanism of Action
Synthetic Analog of ADH: Selective agonist for V2 receptors (Kidney) with minimal V1 receptor (Vascular) activity.
Antidiuretic Effect: Inserts Aquaporin-2 channels in collecting duct → ↑ water reabsorption.
Hematologic Effect: Stimulates release of von Willebrand Factor (vWF) and Factor VIII from endothelial Weibel-Palade bodies.
Clinical Indications
Central Diabetes Insipidus: First-line Tx (Intranasal, oral, or IV).
von Willebrand Disease (vWD): Specifically Type 1 (mild). Increases circulating vWF levels to promote clotting.
Hemophilia A: Useful for mild cases (increases Factor VIII).
Nocturnal Enuresis: Used for primary bedwetting in children (oral formulation preferred).
Diagnostic Use: Water deprivation test to distinguish Central vs. Nephrogenic DI.
Adverse Effects
Hyponatremia: Risk of dilutional hyponatremia and water intoxication (seizures, headache).
Flushing, headache (mild vasodilatory effects).
High-Yield Associations
Unlike Vasopressin, Desmopressin causes minimal vasoconstriction (due to high V2 > V1 specificity).
Tachyphylaxis (rapidly diminishing response) can occur with frequent use in Hemophilia/vWD due to depletion of stored vWF/Factor VIII.