Vasopressin

also known as: Arginine vasopressin, AVP, Antidiuretic hormone, ADH, Vasostrict, Pitressin

Vasostrict — the endogenous antidiuretic hormone as an ICU vasopressor. FDA-approved April 2014 for adults with vasodilatory shock (post-cardiotomy, sepsis) who remain hypotensive despite fluids and catecholamines. Works through V1a receptors on vascular smooth muscle — a receptor axis pharmacologically distinct from catecholamine receptors, preserving its vasopressor effect when adrenergic receptors are desensitised.

A cyclic nonapeptide (Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2 with a disulfide bridge between Cys1 and Cys6) identical in sequence to the endogenous human antidiuretic hormone. Three receptors: V1a (vascular smooth muscle — vasoconstriction), V1b / V3 (anterior pituitary — ACTH release), and V2 (renal collecting duct — aquaporin-2 insertion, water reabsorption). Par Pharmaceutical's Vasostrict® received FDA NDA approval on 17 April 2014 (NDA 204485) via the 505(b)(2) pathway — the first and, at the time, only vasopressin injection USP with an approved NDA. Indication: vasodilatory shock (e.g., post-cardiotomy, septic) refractory to fluids and catecholamines. Dosing: 0.01–0.07 U/min for septic shock; 0.03–0.1 U/min for post-cardiotomy shock, titrated up in 0.005 U/min increments.

Mechanism of action

Endogenous agonist at three G-protein-coupled receptors. V1a receptors on vascular smooth muscle couple to Gq / phospholipase C / IP3 / calcium release, producing vasoconstriction — the pharmacologic basis of the vasopressor indication. V2 receptors on renal collecting duct principal cells couple to Gs / adenylate cyclase / cAMP / protein kinase A, driving aquaporin-2 insertion and water reabsorption. V1b / V3 receptors in anterior pituitary corticotrophs potentiate CRH-driven ACTH release. In vasodilatory shock, endogenous vasopressin is relatively deficient (the "vasopressin-deficiency" hypothesis) and sensitivity to catecholamines is reduced by receptor desensitisation; exogenous vasopressin engages an independent vasoconstrictor pathway to restore mean arterial pressure. Clinical dosing is titrated well below anti-diuretic thresholds but V2-mediated free-water retention and hyponatremia remain concerns at prolonged infusion.

Primary uses

Vasodilatory shock unresponsive to fluids and catecholamines (FDA-approved)
Septic shock as adjunct / catecholamine-sparing agent (Surviving Sepsis Campaign guideline)
Post-cardiotomy vasodilatory shock
Cardiac arrest (previously in ACLS algorithms; removed 2015)

Typical dosing

0.01–0.1 units/minute (continuous IV infusion) continuous infusion (intravenous)

Septic shock: start 0.01 U/min, titrate up to 0.07 U/min max. Post-cardiotomy shock: start 0.03 U/min, titrate up to 0.1 U/min max. After 8 hours of target MAP without catecholamines, taper by 0.005 U/min every hour. Contraindicated with 8-L-arginine hypersensitivity. Watch for skin / digital / mesenteric ischemia and hyponatremia from V2-mediated free-water retention.

Regulatory status

FDA-approved April 17, 2014 (Vasostrict®, Par Pharmaceutical Companies, NDA 204485) under the 505(b)(2) pathway. Indication: increasing blood pressure in adults with vasodilatory shock (e.g., post-cardiotomy or sepsis) who remain hypotensive despite fluids and catecholamines. Additional premixed formulations approved subsequently (40 units/100 mL, etc.). The older Pitressin® vasopressin product predated modern NDA requirements and had been marketed under a DESI-era grandfather status until the 2014 Vasostrict approval.

References

[fda-pi] Vasostrict® (vasopressin injection) Prescribing Information. Par Pharmaceutical Companies, Inc. Initial US approval April 2014.
[clinical-trial] Russell JA, Walley KR, Singer J, et al. "Vasopressin versus norepinephrine infusion in patients with septic shock (VASST)." N Engl J Med, 2008;358(9):877-887.
[guideline] Evans L, Rhodes A, Alhazzani W, et al. "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021." Crit Care Med, 2021;49(11):e1063-e1143.

Related peptides

Terlipressin

Terlivaz — the first and only FDA-approved drug for hepatorenal syndrome (HRS). FDA-approved September 2022 (Mallinckrodt) for adults with HRS with rapid reduction in kidney function, after a multi-decade regulatory history including four prior Complete Response Letters and the successful CONFIRM Phase 3 trial (NEJM 2021).

Desmopressin

DDAVP — the classic V2-selective vasopressin analog. FDA-approved February 1978 for central diabetes insipidus; decades of label expansion added primary nocturnal enuresis, nocturia (Noctiva / Nocdurna), and hemostatic use in mild hemophilia A and type 1 von Willebrand disease. WHO Essential Medicines List.

Angiotensin II

Giapreza — the first new vasopressor class approved in decades. FDA-approved December 2017 (La Jolla Pharmaceutical) for catecholamine-resistant septic / distributive shock based on the ATHOS-3 trial (NEJM 2017, n=321). Engages a third vasoconstrictor pathway (RAAS / AT1) independent of catecholamines and vasopressin — useful when both of those axes are desensitised.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.