2002B08 Outline the pharmacological effects of vasopressin.

 

List:

·     PC

·     PK

·     PD

 

Pharmaceutics: (not sure if would score marks)

Structure

·  Nonapeptide

Production

·  Supraoptic and paraventricular hypothalamic nuclei
(or synthetic)

 

Pharmacokinetics: (not sure if would score marks)

Administration

·  Hypotension: bolus 1-10 units, infusion 0.1-1 units/minute

·  Arrest: bolus 40 units

Time course

·  Onset <1 min

·  Duration 20-40 minutes for vascular effect, hours for renal effect

Absorption

·  Minimal (digested by peptidases)

Distribution

·  Plasma protein binding 10-40%

Metabolism

·  Peptidases in liver, kidneys; then recycled

·  t1/2β 10-20 minutes

Excretion

·  Some renal excretion

 

Pharmacodynamics:

Mechanism of action

·  Oxytocin receptor: Gq G protein coupled receptor

·  ↑IP3/Ca2+, ↑DAG

V1

·  Vascular smooth muscle

·  Generalised vasoconstriction -> ↑SVR > ↑PVR

V2

·  Late distal tubule and collecting duct

o Insertion of aquaporin-2 into apical membrane; endothelium

·  Endothelium

o Release of vWF

V3

·  Anterior pituitary

·  ↑ACTH -> ↑cortisol

Use

·  Cardiac arrest (alternative to adrenaline)

·  2nd line for vasoplegia (e.g. sepsis, post-cardiopulmonary bypass)

Side effects

·  Mild ↑PVR

·  Oxytocin-like effects