2002B08 Outline the pharmacological effects of vasopressin.

Structure

·   Nonapeptide

Production

·   Supraoptic and paraventricular hypothalamic nuclei
(or synthetic)

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

·   t_1/2β 10-20 minutes

Excretion

·   Some renal excretion

Mechanism of action

·   Oxytocin receptor: G_q 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)

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

Side effects

·   Mild ↑PVR

·   Oxytocin-like effects