20A10: Exam Report

Compare and contrast the pharmacology of noradrenaline and vasopressin.

49% of candidates passed this question.

These are both level 1 drugs regularly used in intensive care. Significant depth and detail of each drug were expected. Overall knowledge was deemed to be superficial and lacked integration. Better answers identified key points of difference and overlap in areas such as structure, pharmaceutics, parmacokinetics, pharmacodynamics, mechanism of action, adverse effects and contraindications. A tabular list of individual drug pharmacological properties alongside each other did not score as well as answers which highlighted key areas of difference and similarities.

G7i / 20A10: Compare and contrast the pharmacology of noradrenaline and vasopressin

Noradrenaline

Vasopressin

Chemical

Noradrenaline

Endogenous catecholamine neurotransmitter released from postganglionic sympathetic n. endings

Also accounts for 20% adrenal medulla secretions

Vasopressin

Synthetic peptide hormone

Use

Noradrenaline

to ↑SVR

Vasopressin

  1. Cranial DI (ineffective for Renal DI)
  2. Platelet dysfunction (F VIII & vWF deficiency)
  3. Oesophageal variceal bleeding
  4. NA sparing in Septic Shock

Used synergistically in vasoplegia

Presentation

Noradrenaline

Clear, colourless solution 1mg/mL

Brown ampoule → prevent light oxidation

Must be diluted in D5W to provide sufficient acidity to prevent oxidation

1 pH D5W = 4, pH 0.9% NaCl = 6

Vasopressin

Clear colourless vial

20U/mL

Both need time to draw up as require reconstitution with crystalloid and infusion

Dose

Noradrenaline

Infusion 1 – 20mcg/min

Vasopressin

0.01 – 0.1 units/min

Route

Noradrenaline

central vein

Vasopressin

CVC

Both require CVC

Onset

Noradrenaline

immediate: tachyphylaxis with prolonged infusions

Vasopressin

Fast

MoA

Noradrenaline

α1 = α2 > β1 > β2

Potent α agonist

Equal β1 cf. adrenaline

Little β2 activity

α1 Gq stimulates Phospholipase C → ↑IP3 & DAG → ↑Ca2+

Smooth m. vasoconstriction

Cardiac: weak +ve inotropy

Metabolic: ↑BSL

 α2 Gi inhibits AC → ↓cAMP → ↓Ca2+

CNS: ↓symp. outflow

Peripheries: inhibits NA release from nerve terminals

Platelets: ↓plat. aggregation

 β1 GS → ↑AC →↑cAMP → ↑Ca2+

Heart: +ve inotropy, +ve chronotropy, +ve dromotropy

Renal: ↑renin, ↑AII

Metabolic: ↑lipolysis, ↑FFAs

Vasopressin

Vasopressin receptor agonist (all GPCR)

  • V1 – vascular smooth m.
  • Gq – intense VC
  • V2 – BASOLATERAL MEMBRANE of distal tubules & collecting duct → ↑H2O reabsorption

V2 – endothelial cells → ↑vWF release

Noradrenaline being a catecholamine has theoretical inotropy

Noradrenaline has more metabolic effects

PD

Noradrenaline

CVS

Intense VC all vascular beds = ↑↑SVR

↑HR

↑FoC

Reflex ↓HR

Renal, hepatic, cerebral & skeletal

Resp

Small ↑MV

Metbolic

↑BSL

↑FFA

Renal

↑Renin

Vasopressin

CVS

  • ↑SVR
  • ↑Circulating vol
  • ↑CO
  • CA vc & ↑afterload = ↓Myocardial O delivery

GI

  • Marked splanchnic VC
  • ↑Glycogenolysis

Haem

  • ↑platelet aggregation
  • ↑vWF, ↑F VIII

Renal

↑H2O reabsorption

Comments

Both confer intense VC

 

Vasopressin associated with restricted myocardial BF and avoided in IHD

 

Vasopressin able to constrict splanchnic vessel preferentially

PK

Noradrenaline

A

IV administration

D

25% uptake via 1 lung passage

M

rapid metabolism t½ = 2 mins

E

metabolites conjugated to glucuronic

Vasopressin

A

0% OBA

D

30% PPB. VD 0.2L/kg

M

65% unchanged by kidneys

35% liver + kidney peptidases

E

Renally

t½ B 30 mins  

Comments

Both rapidly metabolized with quick offset following cessation of infusion

Adverse Effects

Noradrenaline

Extravasation → necrosis

Headache

Anxiety

NB CAUTION:  Patients taking MAO inhibitors

 

PREGNANCY = ↑contraction of pregnant uterus, foetal bradycardia & asphyxia

Vasopressin

  • Hyponatraemia
  • Hypertensive crisis