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 (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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