Question 22

Describe the actions of endogenous vasopressin. (60% of marks) List the vasopressin analogues and their uses. (40% of marks)

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College Answer

Overall the first section was not answered in sufficient detail. Aspects such as the  antidiuretic effects of vasopressin were often overlooked. Some candidates spent more time on outlining the clinical contexts in which vasopressin is used (which did not score marks), rather than the physiology (which did score marks). DDAVP was the most common analogue mentioned, with the others often being omitted (e.g. terlipressin, ornipressin, etc.). 

Discussion

"Describe the actions", they said. Not "spill everything you know about vasopressin the drug". Thus, the mechanisms of action of vasopressin are:

  • V1 effects:
    •  Gq-protein coupled receptors.
    • Found on vascular smooth muscle in these regional vascular beds:
      • Systemic arterial
      • Splanchnic
      • Renal
      • Coronary 
    • Mediate vasoconstriction
    • Similarly to alpha-1 receptors, they increase intracellular calcium by means of increasing cAMP concentrations.
    • Unlike catecholamine receptors, vasopressin receptors do not lose their affinity for vasopressin with changing pH.
  • V2 effects:
    • Gs-coupled receptors
    • They facilitate the insertion of aquaporins into the apical membrane of principle cells of the collecting tubule.
    • The result is water retention and increased concentration of the urine
  • V3 effects
    • Gq-coupled G-protein receptors
    • Increase intracellular calcium when activated.
    • Thought to be involved in ACTH release 
  • Oxytocin receptor effects
    • Activation of these receptors raises intracellular calcium (through phospholipase C) 
    • Mainly found on myometrium and vascular smooth muscle
    • Mediate vasodilation via nitric oxide synthase
    • Responsible for vascular selectivity of vasopressin

Vasopressin analogs were asked for as a list, along with their uses. Even though this was 40% of the mark, you'd not be wanting to waste any time here. 

  • Desmopressin (DDAVP):
    • Management of diabetes insipidus
    • Reversal of antiplatelet drug or uraemic antiplatelet effects
    • Slowing the rate of sodium correction in hypovolemic hyponatremia
  • Terlipressin
    • Management of variceal bleeding due to portal hypertension
    • Management of hepatorenal syndrome
  • Ornipressin
    • Potent vasopressor for subcutaneous use along with a local anaesthetic
  • Felypressin
    • Potent vasopressor for subcutaneous use along with a local anaesthetic

There's even more detail in the answer to Question 22 from the second Fellowship Exam paper of 2009 (in those days, pharmacology questions in the Fellowship Exam were commonplace)

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.

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.