Pharm 101: Noradrenaline

Class

Vasopressor
Endogenous catecholamine

Pharmacodynamics

• Sympathomimetic, direct alpha and beta adrenergic receptor agonist (alpha > beta)
• Adrenoceptor affinity:
  • Alpha 1 = alpha 2 > beta 1 >> beta 2
  • Predominately stimulates alpha 1 receptors causing vascular smooth muscle constriction
  • Alpha 2 (presynaptic) agonism inhibits noradrenaline release (negative feedback)
  • Some beta 1 receptor agonist activity results in positive inotropic effect at higher doses
• Cardiovascular effects:
  • Increased PVR
  • Increased SBP and DBP
  • Positive inotropy
  • Little chronotropy (compensatory baroreflex activation overcomes direct positive chronotropic effects)

Pharmacokinetics

• IV administration (preferably CVL)
• Onset of action 1-2 minutes
• Half-life 2 minutes
• Duration of action 5-10 minutes
• Metabolised by MAO and COMT within liver, kidney and blood to VMA and metadrenaline
• Elimination:
  • Pulmonary uptake of 25%
  • Urinary excretion of metabolites

Clinical uses

• Management of hypotension refractory to fluid resuscitation (primarily distributive shock such as septic shock, neurogenic shock and drug-induced)
• Vasopressor of choice for management of septic shock
• Infusion (central):
  • 6mg noradrenaline in 100ml of 5% dextrose (final concentration 60microg/ml)
  • 1ml/hour = 1microg/min
  • Starting dose 2-10microg/min, titrate to BP
  • Usual dose range 0.5-30microg/min

Adverse effects

• Hypertension
• Reflex bradycardia
• Arrhythmias
• Myocardial, mesenteric, renal or peripheral (digital) ischaemia
  • Can manifest as AMI, GI infarct, decreased urine output / creatinine clearance, or gangrene
• Extravasation may cause peripheral ischaemia and tissue necrosis
• Hypergylcaemia
• Increased afterload and beta effects may increase myocardial work and oxygen consumption

Precautions/contraindications

• Untreated hypovolaemic shock
• Hypersensitivity to sulphites
• Do not cease abruptly

Further reading

• Nickson C. Initial Management of Sepsis. LITFL

References

• Katzung BG. Basic & Clinical Pharmacology. 14e. 2018: 96-97
• Better Safe Care. Melbourne, Australia: Victorian Agency for Health Information; 2018. Noradrenaline (norepinephrine); 2018 Dec 05 [cited 2020 Aug 02].