Question 7

Compare and contrast the pharmacology of noradrenaline and vasopressin

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College Answer

This was best answered using a table.

The main points expected for a pass were

  • Both are naturally occurring substances
  • Direct acting via receptors
  • Mechanisms by which both increase mean arterial pressure
  •  Metabolism
  • Uses in Intensive Care, septic shock, vasodilatory shock and diabetes insipidus.  
  • Side effects related to intense vasoconstriction and for vasopressin possible coronary ischaemia and sodium and water retention

Discussion

Name Vasopressin Noradrenaline
Class Vasopressor Vasopressor
Chemistry Cyclic peptide Endogenous catecholamine
Routes of administration IV IV
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 = 8.85; water-soluble
Distribution VOD = 0.14 to 0.2 L/kg; protein binding ~ 30% VOD = 0.12 L/kg, i.e. essentially confined to the circulating volume; 25% protein-bound
Target receptor Vasopressin binds to V1 receptors (vasoconstrictor effect) and V2 receptors (antidiuretic effect). Noradrenaline is highly selective for the alpha-1 receptor
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, noradrenaline 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.
Clinical effects Vasoconstriction, redistribution of splanchnic blood flow, increased platelet aggregation, decreased urine output, increased circulating Factor VIII and von Willebrand factor Increased peripheral resistance, increased afterload, increased blood pressure; redistribution of blood flow from splanchnic circulation and skeletal muscle.
Single best reference for further information TGA PI document TGA PI document

References

Sharman, Andrew, and James Low. "Vasopressin and its role in critical care." Continuing Education in Anaesthesia Critical Care & Pain 8.4 (2008): 134-137.

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

Chidambaram, Swathikan, et al. "Vasopressin vs noradrenaline: Have we found the perfect recipe to improve outcome in septic shock?." Journal of Critical Care 49 (2019): 99-104.