Non-Adrenergic Vasoactives

Key non-adrenergic cardiovascular drugs include vasopressin (and its analogues, terlipressin and ornipressin), phosphodiesterase III inhibitors such as milrinone, and calcium sensitisers such as levosimendan.

Property Vasopressin (ADH) Milrinone Levosimendan
Class Natural nonapeptide Phosphodiesterase III inhibitor Calcium sensitiser and phosphodiesterase inhibitor
Uses Haemorrhage, DI, catecholamine-sparing vasopressor Refractory CCF and low CO states Severe acute heart failure 50μg/kg loading dose over 10 minutes (often omitted), followed by infusion titrated to haemodynamic effects, up to 75μg/kg/min
Dosing 5-10 units IV bolus, up to 4U/hr infusion Load 12-24mcg/kg over 10min, then infusion at 0.05-2mcg/kg/min
Presentation Clear solution Yellow solution at 1mg/ml 2.5mg/mL in 5ml & 10ml vials
Distribution 70% protein bound Very high protein binding >90%
Metabolism t1/2 10 minutes. Metabolised by tissue peptidases and renal elimination. t1/2 1-2.5 hours, prolonged in patients with cardiac or renal disease t1/2 1 hour. Hepatic to active metabolite with a t1/2 ~70 hours
Elimination 80% of drug is excreted unchanged, making it highly dependent on renal blood flow
Mechanism of action V2 receptors (kidney, platelets) are adenylate cyclase mediated. V1 (vascular smooth muscle) and V3 receptors (pituitary) are phospholipase C/inositol triphosphate mediated Inhibits phosphodiesterase breakdown of cAMP, increasing intracellular Ca2+ levels. Also increases speed of Ca2+ uptake into cardiac muscle, increasing lusitropy. Binds to troponin C increasing myofilament Ca2+ sensitivity. Also opens K+ channels causing vasodilation. It may also have some PD III inhibition effect.
CVS SVR through vasoconstriction Increased inotropy, increased lusitropy, decreased SVR and PVR (PVR decreases more than SVR). Increased dysrhythmias. Increased CO without increased O2 demand, vasodilation, prolonged QTc with risk of arrhythmia
GIT GIT smooth muscle contraction
Renal ↑ Aquaporin insertion into the apical membrane of collecting ducts which ↑ water reabsorption
Haematological ↑ Coagulation factor mobilisation and ↑ platelet aggregation
Metabolic Hyponatraemia


  1. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  2. Smith S, Scarth E, Sasada M. Drugs in Anaesthesia and Intensive Care. 4th Ed. Oxford University Press. 2011.
  3. Brunton L, Chabner BA, Knollman B. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 12th Ed. McGraw-Hill Education - Europe. 2011.
Last updated 2020-02-14

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