DDAVP

Desmopressin (1-deamino-8-D-arginine vasopressin) is a synthetic analog of arginine vasopressin (ADH) with selective agonism at V2 receptors (minimal V1 activity), making it more potent antidiuretic effect with fewer vasopressor/pressor side effects compared to natural ADH. It has a longer half-life than endogenous ADH.

Mechanism: V2 receptor activation on the basolateral membrane of renal collecting duct principal cells triggers Gs-protein-coupled activation of adenylate cyclase, increasing cAMP, which promotes insertion of aquaporin-2 water channels into the apical membrane, increasing water reabsorption and producing concentrated urine.

Clinical uses: 1. Central diabetes insipidus - distinguishes from nephrogenic DI (water deprivation test: DDAVP administration corrects central DI by increasing urine osmolality, but has no effect in nephrogenic DI since the kidney is unresponsive to ADH). 2. Primary nocturnal enuresis in children. 3. Mild hemophilia A and von Willebrand disease - DDAVP stimulates release of von Willebrand factor and Factor VIII from endothelial cell Weibel-Palade bodies, temporarily increasing plasma levels (useful for minor bleeding/procedures, not severe hemophilia A). 4. Can be used in the workup/treatment of some platelet function disorders.

Adverse effects: Hyponatremia and water intoxication (due to excessive free water retention) - caution in patients at risk of SIADH-like effects; headache; facial flushing; rarely tachyphylaxis with repeated dosing (depletes vWF stores over consecutive days).

High-yield board associations: DDAVP is used diagnostically to differentiate central DI from nephrogenic DI. It's also a good example illustrating structure-activity relationship in peptide hormone analogs (selective receptor agonism).