Vasopressin (Vasostrict)

Benefits

About Vasopressin (Vasostrict)

Vasopressin, also known as arginine vasopressin (AVP) or antidiuretic hormone (ADH), is a cyclic nonapeptide (Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2) with a disulfide bridge between the two cysteine residues at positions 1 and 6. It is synthesized as a preprohormone in magnocellular neurons of the hypothalamic supraoptic and paraventricular nuclei, then transported along axons to the posterior pituitary gland where it is stored in secretory granules and released in response to increased plasma osmolality, hypovolemia, or hypotension. Vasopressin was first isolated and synthesized by Vincent du Vigneaud in 1954, earning him the Nobel Prize in Chemistry in 1955. The synthetic form used clinically is 8-L-arginine vasopressin, identical to the endogenous human hormone. Vasostrict, the branded injectable formulation manufactured by Endo International (now Par Pharmaceutical), received FDA approval in 2014 for the treatment of vasodilatory shock in patients who remain hypotensive despite fluid resuscitation and catecholamines. The hormone exerts its physiological effects through three distinct G protein-coupled receptor subtypes: V1a receptors on vascular smooth muscle mediate vasoconstriction via the Gq/phospholipase C/IP3/calcium pathway; V2 receptors on renal collecting duct principal cells promote water reabsorption via Gs/cAMP-mediated insertion of aquaporin-2 channels into the apical membrane; and V1b (V3) receptors in the anterior pituitary stimulate ACTH secretion. Additional effects include platelet aggregation, hepatic glycogenolysis, and release of von Willebrand factor and Factor VIII from vascular endothelium (via V2 receptors). Clinically, vasopressin is primarily used in three major settings: vasodilatory shock (septic, postcardiotomy, or other distributive shock) as a catecholamine-sparing vasopressor, central diabetes insipidus (as replacement therapy for ADH deficiency), and acute variceal hemorrhage in the GI tract (to reduce splanchnic blood flow). The landmark VASST trial (2008) and VANISH trial (2016) established its role as an adjunctive vasopressor in septic shock. Vasopressin is also included in the Advanced Cardiovascular Life Support (ACLS) algorithm as an alternative to epinephrine in cardiac arrest, though recent guidelines have de-emphasized this indication.

Who Should Consider Vasopressin (Vasostrict)

• ICU patients with vasodilatory or septic shock refractory to fluids and catecholamines
• Patients with central diabetes insipidus (ADH deficiency)
• Patients with acute variceal or GI hemorrhage requiring splanchnic vasoconstriction
• Postcardiotomy shock patients requiring catecholamine-sparing vasopressor support
• Cardiac arrest patients (ACLS protocol — alternative to epinephrine)

How Vasopressin (Vasostrict) Works

Vasopressin exerts its effects through three distinct G protein-coupled receptor subtypes with differing tissue distributions and signaling cascades. V1a receptors, expressed on vascular smooth muscle, hepatocytes, platelets, and myometrium, couple to Gq proteins that activate phospholipase C, generating inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 triggers calcium release from the sarcoplasmic reticulum, causing smooth muscle contraction and vasoconstriction — the primary mechanism underlying its vasopressor effect in shock states. At the vascular level, vasopressin also potentiates the vasoconstrictive effects of catecholamines and inhibits nitric oxide-mediated vasodilation, which is particularly relevant in septic shock where pathological NO overproduction drives refractory hypotension. V2 receptors, located on the basolateral membrane of renal collecting duct principal cells, couple to Gs proteins that activate adenylyl cyclase, increasing intracellular cAMP. This triggers protein kinase A-mediated phosphorylation and translocation of aquaporin-2 (AQP2) water channels to the apical membrane, dramatically increasing water permeability and enabling osmotic water reabsorption from the tubular lumen. This is the antidiuretic mechanism. V2 receptors on vascular endothelium also mediate release of von Willebrand factor multimers and coagulation Factor VIII from Weibel-Palade bodies. V1b (V3) receptors in anterior pituitary corticotrophs activate the Gq/PLC pathway to stimulate ACTH release, contributing to the stress hormone response. Vasopressin acts synergistically with CRH at this level to amplify the hypothalamic-pituitary-adrenal axis response during physiological stress.

What to Expect

Dosing Protocol

Note: Vasopressin (arginine vasopressin, AVP, antidiuretic hormone/ADH) is an endogenous nonapeptide hormone synthesized in the supraoptic and paraventricular nuclei of the hypothalamus and released from the posterior pituitary. It is FDA-approved as Vasostrict for the treatment of vasodilatory shock in adults. Vasopressin is administered exclusively by continuous intravenous infusion in critical care settings; the dosing tiers shown reflect standard ICU infusion rates in units per minute (U/min). The typical starting dose is 0.01-0.04 U/min, titrated to hemodynamic response. It is NOT a peptide for self-administration or wellness use. All vasopressin therapy must occur under direct physician supervision with continuous hemodynamic monitoring. Premixed ready-to-use formulations are available and preferred to reduce medication errors. Vasopressin should be tapered gradually rather than discontinued abruptly to avoid rebound hypotension and transient diabetes insipidus.

How to Inject Vasopressin (Vasostrict)

Vasopressin is administered exclusively by continuous intravenous infusion in monitored critical care settings. The concentrated solution (20 units/mL) must be diluted prior to infusion: typically 25-50 units diluted in 250-500 mL of 0.9% normal saline or 5% dextrose in water (D5W) to achieve a final concentration of 0.1 U/mL. Premixed ready-to-use formulations (0.2, 0.4, or 0.6 U/mL) are commercially available and preferred to minimize dilution errors. For vasodilatory shock, the recommended infusion rate is 0.01 to 0.07 U/min (0.6-4.2 U/hr), titrated to the target mean arterial pressure. The infusion should NOT be administered as a bolus. A dedicated central venous line is recommended, though peripheral IV administration is acceptable for short durations. When discontinuing, the infusion rate should be tapered gradually (decrease by 0.005 U/min every 15-30 minutes) rather than stopped abruptly. Continuous arterial blood pressure monitoring, urine output measurement, and serial electrolyte panels (particularly serum sodium) are mandatory during vasopressin infusion.

Cycling Protocol

Pharmacokinetics

Side Effects

The most clinically significant adverse effects of vasopressin relate to excessive vasoconstriction and end-organ ischemia. Cardiac effects include decreased cardiac output, bradycardia, and tachyarrhythmias; myocardial ischemia can occur, particularly in patients with coronary artery disease. Peripheral ischemia may manifest as digital (finger/toe) ischemia, skin necrosis, or gangrene, especially with higher infusion rates or prolonged use. Mesenteric ischemia is a serious concern and can present as abdominal pain, ileus, or bowel necrosis. Hyponatremia results from excessive water retention mediated by V2 receptor activation. Transient diabetes insipidus (polyuria, dilute urine, hypernatremia) can develop after abrupt discontinuation due to V2 receptor downregulation, occurring in approximately 1.5% of patients. Other reported effects include nausea, vomiting, abdominal cramping, headache, vertigo, and bronchospasm. Extravasation at the IV site can cause local tissue necrosis.

Contraindications

Drug Interactions

Storage & Stability

Molecular Profile

Related Peptides

Oxytocin

Sexual Health

Somatostatin (SST-14 and SST-28)

Metabolic

Octreotide (Sandostatin)

Metabolic

References

1. Vasopressin versus norepinephrine infusion in patients with septic shock (VASST Trial)Clinical Trial
2. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical TrialClinical Trial
3. Vasopressin in Vasodilatory Shock (NEJM Review)Review
4. Vasostrict (vasopressin injection) FDA Prescribing InformationFDA Label