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
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].
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MBBS CCPU (RCE, Biliary, DVT, E-FAST, AAA) Rob is an Emergency Medicine Advanced Trainee based in Melbourne, Australia. He has special interests in medical education, ECG interpretation, and the use of diagnostic and procedural ultrasound in the undifferentiated and unwell patient.

Follow him on twitter: @rob_buttner | ECG Library |

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