Question 20

Compare and contrast the relevant pharmacology of intravenous adrenaline and vasopressin.

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College Answer

The major emphasis of this question and opportunity to score marks reside in “comparing the two drugs” in various aspects – pharmaceutics, indication, mechanism of action, pharmacodynamics, and pharmacokinetics. Although most of the candidates were able to list pharmaceutics, indications, kinetics and dynamics of both the drugs in reasonably structured and tabulated format, many failed to highlight the important commonalities and differences between the two. In mechanism of action, details of the receptor, their location and second messenger system were expected. In pharmacodynamics, similarities and differences in cardiovascular, respiratory, haematological, renal and metabolic effects were needed. There are additional neurological effects and genito-urinary (tocolysis and sphincter tone) of adrenaline which were rarely mentioned. There were frequent significant omissions or incorrect details in the pharmacokinetics sections of both drugs.


Name Vasopressin Adrenaline
Class Vasopressor Inodilator
Chemistry Cyclic peptide Endogenous catecholamine
Routes of administration IV IV, IM, subcutaneous, nebulised, topical, as eye drops and directly into the ETT during an arrest
Absorption Basically zero oral availabilty due to destruction by intestinal peptidases Basically zero oral availabilty due to destruction by brush border enzymes in the gut (COMT and MAO)
Solubility pKa = 10.26, good water solubility pKa of 9.69; minimal water slubility
Distribution VOD = 0.14 to 0.2 L/kg; protein binding ~ 30% VOD = 0.1-0.2 L/kg; 12% protein-bound
Target receptor Vasopressin binds to V1 receptors (vasoconstrictor effect) and V2 receptors (antidiuretic effect). All adrenoceptors, with some selectivity for beta-1 and beta-2 at lower doses
Metabolism 35% is metabolised by endothelial peptidases in the liver Metabolised rapidly and completely by COMT and MAO
Elimination 65% is excreted unchanged by the kidney; half-life 17-35 minutes Metabolites are renally excreted. Half-life is ~2 minutes
Time course of action Rapid onset of effect Very short acting, very rapid onset of effect
Mechanism of action Vasopressor effects are exerted by V1 receptors, which are Gq-protein coupled receptors. Similarly to alpha-1 receptors, they increase intracellular calcium by means of increasing cAMP concentrations.
V2 receptors are Gs-coupled receptors and produce the insertion of aquaporins into the apical membrane of principle cells of the collecting tubule.
Unlike catecholamine receptors, vasopressin receptors do not lose their affinity for vasopressin with changing pH.
By binding to the alpha-1 receptor, adrenaline increases the release of a secondary messenger (inositol triphosphate, IP3) which results in the release of calcium into the cytosol, and thus enhanced smooth muscle contractility. By binding to beta-1 and beta-2 receptors, it increases cAMP, whcih as a second messenger mediates the other cardiovascular clinical effects
Clinical effects Vasoconstriction, redistribution of splanchnic blood flow, increased platelet aggregation, decreased urine output, increased circulating Factor VIII and von Willebrand factor Increased cardiac contractility, increased heart rate, some peripheral vasodilation, decreased afterload, hyperglycaemia, hyperlactataemia, hypokalemia, increased arrhythmogenicity
Single best reference for further information TGA PI document TGA PI document


Cowley Jr, Allen W., and Jean-François Liard. "Cardiovascular actions of vasopressin." Vasopressin. Springer US, 1987. 389-433.

Holmes, Cheryl L., Donald W. Landry, and John T. Granton. "Science review: Vasopressin and the cardiovascular system part 1–receptor physiology." Critical care 7.6 (2003): 427.

Lemmens-Gruber R, Kamyar M. Vasopressin antagonists.Cell Mol Life Sci. 2006 Aug;63(15):1766-79.

Gorain, Bapi, et al. "Pharmacology of Adrenaline, Noradrenaline, and Their Receptors." Frontiers in Pharmacology of Neurotransmitters. Springer, Singapore, 2020. 107-142.

Stratton, JOHN R., et al. "Hemodynamic effects of epinephrine: concentration-effect study in humans." Journal of Applied Physiology 58.4 (1985): 1199-1206.