FRCA Notes

Vasopressin & Friends

  • Vasopressin (arginine vasopressin, ADH) is a naturally occurring hormone
  • It is synthesised by magnocellular neurones in the supraoptic hypothalamic nuclei
  • Released from axon terminals in the posterior pituitary, mainly in response to increased plasma osmolality due to high sodium
  • Reduced blood pressure (10% sensitivity)
  • Reduced blood volume
  • Reduced cardiac output
  • Standing up
  • IPPV
  • Physiological stress
  • Nausea and vomiting
  • Angiotensin II
  • Nicotine
  • Various drugs: TCA's, analgesics, AED's, morphine

V1 receptor

  • Gq - linked GPCR; phospholipase second messenger
  • Activation causes vasoconstriction, especially in the coronary and splanchnic vascular beds, but also in skin and smooth/skeletal muscle
  • Activation also causes platelet aggregation

V2 receptor

  • Gs - linked GPCR; adenylyl cyclase activation and increased cAMP
  • Opens aquaporin 2 channels in the renal collecting ducts, causing re-absorption of water and reduced urine output
  • Also causes vWF release

V3 receptor

  • Gq - linked GPCR; phospholipase second messenger
  • Primarily found in ACTH secreting cells of the anterior pituitary
  • Stimulation increases ACTH release

  • Under normal circumstances it is concerned with the regulation of plasma osmolarity
  • It is present in relatively small amounts and has little effect on blood pressure
  • Vasopressin levels rise linearly with increasing osmolarity

  • In hypovolaemic shock, there is little change in vasopressin levels until 10% of blood volume is lost
  • After this, vasopressin levels rise exponentially as part of homeostatic mechanisms to restore blood pressure

  • Secretion is suppressed by water intake and reduced plasma osmolality

  • Is not bound to plasma proteins
  • Has a short (<5min) half life

Desmopressin (ddAVP)

  • The normal L-arginine is replaced with unnatural D-arginine - slows enzymatic destruction
  • The cysteine terminal is deaminated - affects receptor affinity

Terlipressin

  • The normal L-arginine is replaced with lysine - slow enzymatic destruction
  • Glycine tail attached
  • It acts predominantly on V1 receptors

Oxytocin

  • Oxytocin has a similar chemical structure but little overlapping function
  • Prolonged oxytocin infusions can cause a dilutional hyponatraemia

Felypressin

  • A synthetic V1a receptor agonist
  • Added to prilocaine to add vasoconstricting properties to the solution

Vasoconstriction

  • Vasopressin is a second-line vasopressor on ICU, particularly in patients with pulmonary HTN as noradrenaline (1st line) causes increased PVR
  • Other use as a vasoconstrictor (e.g. cardiac arrest, distributive shock from sepsis, haemorrhagic shock) is not routine although may be used to reduce intensity of adrenergic therapy

  • Terlipressin can be used for variceal upper GI bleeding
  • It reduces portal venous pressure via splanchnic vasoconstriction and therefore reduces bleeding

Diabetes insipidus

  • Desmopressin can be used to treat diabetes insipidus

Thrombocytopaenia

  • Desmopressin may be used in cases of maternal thrombocytopaenia
  • It improves haemostasis by stimulating hepatic release of clotting factor VIII 111 and endothelial release of tissue plasminogen activator and von Willebrand factor