Management of “Autocorrection” During the Treatment of Hyponatremia (see Hyponatremia)
Pharmacology
Desmopressin Binds to Renal Collecting Duct Vasopressin V2 Receptors (Resulting in its “Antidiuretic” Activity), Inducing an Iatrogenic Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), Allowing from a More Controlled Increase in the Serum Sodium While Using Hypertonic (3%) Saline
Von Willebrand Disease Type 2B (see Von Willebrand Disease): desmopressin may induce platelet aggregation, thrombocytopenia, and possibly thrombosis
Pharmacology
Desmopressin (DDAVP = 1-Deamino-8-D-Arginine Vasopressin) is a Synthetic analogue of Human 8-Arginine Vasopressin (i.e. Antidiuretic Hormone, ADH)
Structure
Compared to Vasopressin, the First Amino Acid of Desmopressin Has Been Deaminated and the Arginine at the 8th Position is in the Dextro (Rather than the Levo) Configuration
Due to Their Structural Differences, Vasopressin and Desmopressin Exhibit Distinct Receptor Binding Abilities
Vasopressin Binds to Both the V1a and V2 Receptors
Desmopressin Binds to Only the V2 Receptors (Which Primarily Mediates the Antidiuretic Response), But Not the V1a Receptors
Effects of Desmopressin on Renal Collecting Duct V2 Receptors
Desmopressin Binds to Renal Collecting Duct V2 Receptors, Resulting in “Antidiuretic” Effects
Decreased Urine Volume
Increased Urine Osmolality
Effects of Desmopressin on Endothelial Cell V2 Receptors
Desmopressin Binds to Endothelial Cell V2 Receptors, Stimulating Von Willebrand Factor and tPA Release from Endothelial Cell Weibel Palade Bodies
Von Willebrand Factor and tPA are Normally Stored in Weibel Palade Bodies
Desmopressin Results in Increased Endothelial Cell Factor VIII Release (Via an Unknown Mechanism)
Desmopressin is More Potent Than Vasopressin in Increasing Plasma Factor VIII Activity
Effects of Desmopressin on Vasoconstriction/Blood Pressure and the Uterus
Compared to Vasopressin, Desmopressin Has Little Effect on Vasoconstriction/Blood Pressure or the Uterus (see Vasopressin)
Metabolism
Unclear
Not affected by hepatic microsomal P450 enzymes
Desmopressin is Degraded More Slowly Than Recombinant Vasopressin: requires less frequent administration
Administration
Intravenous Treatment of Uremic Platelet Dysfunction (see xxxx): 0.3 μg/kg
Alternatively, Subcutaneous Administration Can Be Used (Although it is Less Preferred)
Intravenous Management of “Autocorrection” During the Treatment of Hyponatremia (see Hyponatremia)
Proactive (Preventative) Strategy/Reactive Strategy: 1-2 μg q6-8hrs x 24-48 hrs
Rescue Strategy: 2 μg q6 hrs
Dose Adjustment
Hepatic: none
Renal
CrCl <50 mL/min: although use is contraindicated in manufacturer labeling, use of desmopressin in common in this population for the treatment of uremic platelet dysfunction
