VPEP Module 4 Infographic

Vascular Smooth Muscle

V1 Receptor — Vasoconstriction

Raises systemic vascular resistance
Used as vasopressor in septic shock and cardiac arrest
No tachycardia (unlike catecholamines)
Blocked by conivaptan (V1+V2 antagonist)

Renal Collecting Duct

V2 Receptor — Water Reabsorption

Inserts aquaporin-2 water channels → concentrated urine
Primary antidiuretic mechanism
Blocked by tolvaptan (selective) and conivaptan (dual)
Activated by desmopressin (no V1 activity)

Correction Rate Limit

Maximum safe correction of chronic hyponatremia: 8–10 mEq/L per 24 hours. Exceeding this risks osmotic demyelination syndrome — largely irreversible neurological injury.

Feature	Detail
Mechanism	Vasopressin secreted despite low osmolality → free water retained → dilutional hyponatremia
Volume status	Euvolemic (distinguishes from heart failure, cirrhosis)
Key lab finding	Urine osmolality >100 mOsm/kg despite low plasma osmolality; urine Na >40 mEq/L
Common causes	CNS disorders, pneumonia, small cell lung cancer, drugs (SSRIs, carbamazepine, thiazides)
Treatment ladder	Fluid restriction → vaptans or salt tablets → hypertonic saline (severe/symptomatic)

Feature

Detail

Mechanism

Vasopressin secreted despite low osmolality → free water retained → dilutional hyponatremia

Volume status

Euvolemic (distinguishes from heart failure, cirrhosis)

Key lab finding

Urine osmolality >100 mOsm/kg despite low plasma osmolality; urine Na >40 mEq/L

Common causes

CNS disorders, pneumonia, small cell lung cancer, drugs (SSRIs, carbamazepine, thiazides)

Treatment ladder

Fluid restriction → vaptans or salt tablets → hypertonic saline (severe/symptomatic)

Oral · Selective V2 Antagonist

Tolvaptan

Selective V2 blocker → aquaresis (free water excretion)
Approved: euvolemic and hypervolemic hyponatremia
Black box: hepatotoxicity — contraindicated in liver disease
Maximum 30 days of use
Initiate in hospital — monitor sodium rate
CYP3A4 inhibitor — drug interactions

Intravenous Only · Dual V1+V2 Antagonist

Conivaptan

Blocks V1 (vasodilation) + V2 (aquaresis)
Hospital use only — IV administration
Approved: euvolemic and hypervolemic hyponatremia
Caution if hypotensive (V1 blockade reduces vascular resistance)
Potent CYP3A4 inhibitor

Indication	Mechanism and Notes
Central diabetes insipidus	Replaces deficient vasopressin; V2 activation concentrates urine. Ineffective in nephrogenic diabetes insipidus (receptor absent or blocked)
Nocturnal enuresis	Reduces overnight urine volume; fluid restriction required after dosing to prevent hyponatremia
Mild hemophilia A / Type 1 von Willebrand disease	V2 activation on endothelial cells → Weibel-Palade body exocytosis → von Willebrand factor and factor VIII release. Tachyphylaxis with repeated doses within 24–48 hours

Indication

Mechanism and Notes

Central diabetes insipidus

Replaces deficient vasopressin; V2 activation concentrates urine. Ineffective in nephrogenic diabetes insipidus (receptor absent or blocked)

Nocturnal enuresis

Reduces overnight urine volume; fluid restriction required after dosing to prevent hyponatremia

Mild hemophilia A / Type 1 von Willebrand disease

V2 activation on endothelial cells → Weibel-Palade body exocytosis → von Willebrand factor and factor VIII release. Tachyphylaxis with repeated doses within 24–48 hours