Describe the pharmacology of vasopressin (70% of marks) and its analogues (30% of
marks).
A pharmacology answer template outlining pharmacokinetics and dynamics was required. Candidates failed to score marks for describing the physiology of vasopressin secretion. A number of answers demonstrated limited knowledge about its indications for use and its potential adverse effects.
The table below gives a good breakdown of the pharmacology of vasopressin, for 70%:
| Class | Vasopressor |
| Chemistry | Pituitary hormone |
| Routes of administration | IV |
| Absorption | Basically zero oral availability due to destruction by intestinal peptidases, such as trypsin |
| Solubility | pKa = 10.26, good water solubility |
| Distribution | VOD = 0.14 to 0.2 L/kg; protein binding ~ 30% |
| Target receptor | Vasopressin binds to V1 receptors (vasoconstrictor effect) and V2 receptors (antidiuretic effect). |
| Metabolism | 35% is metabolised by endothelial peptidases in the liver |
| Elimination | 65% is excreted unchanged by the kidney; half-life 17-35 minutes |
| Time course of action | 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. |
| Clinical effects | Vasoconstriction, redistribution of splanchnic blood flow, increased platelet aggregation, decreased urine output, increased circulating Factor VIII and von Willebrand factor |
| Single best reference for further information | TGA PI document |
To write about vasopressin analogue pharmacology in 3 minutes, for 30 % of the mark, would surely have to be an unsatisfyingly short discussion which lacks all the normal structure of a pharmacology answer. You'd really be limited to just explaining how they are different to vasopressin. The examiners clearly must have recognised this in Question 22 from the first paper of 2013, where they only asked the candidates to "list the vasopressin analogues and their uses". Unfortunately, here we need to probably do more. That would have to look something like this:
Sharman, Andrew, and James Low. "Vasopressin and its role in critical care." Continuing Education in Anaesthesia Critical Care & Pain 8.4 (2008): 134-137.
Avni, Tomer, et al. "Vasopressors for the Treatment of Septic Shock: Systematic Review and Meta-Analysis." PloS one 10.8 (2015): e0129305.
Robertson, Gary L., and Alan Harris. "Clinical use of vasopressin analogues." Hospital Practice 24.10 (1989): 114-139.
Morelli, Andrea, et al. "Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study." Crit Care 13.4 (2009): R130.
Mannucci, Pier Mannuccio. "Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years." Blood 90.7 (1997): 2515-2521.
Kim, R. J., et al. "Vasopressin and desmopressin in central diabetes insipidus: adverse effects and clinical considerations." Pediatric endocrinology reviews: PER 2 (2004): 115-123.
Franchini, Massimo. "The use of desmopressin as a hemostatic agent: a concise review." American journal of hematology 82.8 (2007): 731-735.