Adrenergic Vasoactives

This covers the pharmacology of specific catecholamines and sympathomimetics. The synthesis of endogenous catecholamines is covered under adrenal hormones, whilst specifics of catecholamine receptor function is covered under adrenoreceptors.

Adrenergic drugs:

  • Act via:
    • Dopamine receptors (D)
    • Adrenoreceptors (α and β)
  • Can be:
    • Direct-acting
      Stimulate the receptor.
    • Indirect-acting
      Stimulate the release of noradrenaline to cause effects.
  • Classified as either:
    • Naturally-occurring catecholamines
    • Synthetic catecholamines
    • Synthetic sympathomimetics
      Drugs which act on adrenoreceptors but are not classified as catecholamines due to their chemical structure.

Comparison of Naturally Occurring Vasoactives

Properties Adrenaline Noradrenaline Dopamine
Uses Cardiac arrest, anaphylaxis, inotropy, chronotropy, adjunct in local anaesthetics SVR HR, ↑ CO, ↑ UO
Dosing 0.05-2µg/kg/min 0.05-1.5µg/kg/min 1-50µg/kg/min. Increase by 1-4µg/kg/min ~10 minutely until desired response.
Presentation A clear, colourless solution typically at 0.1-1mg/ml Clear, colourless, light-sensitive solution. Sodium metabisulfite as excipient. Clear, colourless solution with 200mg or 800mg in water
Absorption Variable ETT and SC absorption IV only IV only
Metabolism t1/2 2min. Metabolised by mitochondrial MAO and COMT within liver, kidney, and blood to VMA and metadrenaline. t1/2 2min. Metabolised by mitochondrial MAO and COMT in liver, kidney, and blood to VMA and normetadrenaline. t1/2 3 min. 25% of dose converted to noradrenaline. Remainder is metabolised by MAO and COMT similar to nor/adrenaline.
Elimination Urinary excretion of metabolites Pulmonary uptake of up to 25%. Urinary excretion of metabolites Renal, t1/2β 3 minutes
Mechanism of action β>α at lower doses. At high doses α1 effects dominate. α>>β D1 dominates at ≤5µg/kg/min.
β1 dominate at 2-10µg/kg/min.
α dominates >10µg/kg/min
Respiratory MV, bronchodilation MV, bronchodilation
CVS ↑ Inotropy, ↑ HR, ↑ SVR and PVR, ↑ BP, ↑ CO, ↑ myocardial O2 consumption. Coronary vasodilation. Arrhythmogenic. SVR, venoconstriction and ↑ preload, ↑ Myocardial O2 consumption, ↑ Coronary flow. Reflex ↓ in HR. Receptor affinity ↓ in acidosis. ↑ Extravasation of peripheral veins due to constriction and ischaemia of vein wall. ↑ Inotropy, ↑ HR, ↑ CO, coronary vasodilation. At high doses, ↑ SVR and PVR, ↑ VR, tachyarrhythmias.
CNS ↑ Pain threshold, ↑ MAC Inhibits prolactin. Nausea.
MSK Necrosis with extravasation Necrosis with extravasation Necrosis with extravasation
Renal ↓ RBF and ↑ in sphincter tone ↓ RBF No evidence for renoprotective effects despite ↑ RBF at low doses
Metabolic BMR, ↑ lipolysis, ↑ gluconeogenesis and BSL, ↑ Lactate. Initially ↑ insulin secretion (β), then ↓ (α)
GU ↓ Uterine blood flow and foetal bradycardia
GIT Mesenteric vasodilation

Comparison of Synthetic Adrenergic Vasoactives

Properties Dobutamine Isoprenaline Ephedrine Metaraminol Phenylephrine
Uses Stress testing, increasing CO Severe bradycardia SVR without ↓ in HR SVR SVR
Dosing 5-15µg/kg/min Infusion from 0.5-10µg/min 3-6mg bolus Bolus 0.5-2mg Bolus start at 50-100mcg
Presentation Racemic mixture of 250mg dobutamine in 20ml water Clear solution at 1mg/ml Clear, colourless solution in 30mg/ml ampoule Clear, colourless solution in ampoule at 10mg/ml, typically reconstituted to 0.5mg/ml Clear, colourless solution at 100mcg/ml
Absorption IV IV IV or IM IV IV
Metabolism t1/2 2-5 min. COMT to inactive metabolites. Hepatic by COMT Hepatic (not metabolised by MAO and COMT), giving a longer (10-60 minute) duration of action and a t1/2β of 3-6 hours Some uptake into adrenergic nerve endings Hepatic by MAO
Elimination Urinary excretion of unchanged drug and metabolites 50% unchanged in urine Renal of metabolites, t1/2β 2-3 hours
Mechanism of action β1>>β2, D2 β1>β2 ↑ NA release (indirect α1) and direct α and β agonism Direct and indirect (via ↑ NA release) α1 agonism Direct α1
Respiratory Bronchodilation Potent bronchodilation Bronchodilation
CVS HR, CO, contractility, and automaticity. Β2 effects may ↓ SVR and BP, particularly if ↓ preload. HR and ↑ CO, modest ↑ inotropy. ↓ SVR due to β2 effects but BP usually unchanged due to ↑ CO. Direct and indirect (via NA release) ↑ in HR, BP, and CO. Arrhythmogenic. SVR/PVR, reflex bradycardia. Indirect ↑ in coronary flow. SVR and BP, potential reflex bradycardia. Not arrhythmogenic.
CNS Tremor MAC, mydriasis.
Renal ↑ RBF and ↑ urinary output with no improvement in renal function ↓ RBF ↓ RBF ↓ RBF
GU ↓ Uterine blood flow ↓ Uterine blood flow

Structure-Activity Relationships of Sympathomimetics

Catecholamines consist of:

  • A catechol ring
    A benzene ring with two hydroxyl groups in the 3 and 4 position.
    • Losing one hydroxyl group
      • Increases lipid solubility and decreases the potency 10-fold
      • Prevents metabolism by COMT, prolonging duration of action
    • Losing both hydroxyl groups decreases the potency 100-fold
      • Changing the hydroxyl groups to the 3 and 5 position increases beta-2 selectivity when there is also a large substitution present on the amine group
  • An ethylamine tail
    Consists of:
    • Beta carbon
      The first carbon.
      • Adding a hydroxyl group decreases lipid solubility and CNS penetration
      • Adding any group increases alpha and beta selectivity
    • Alpha carbon
      The second carbon.
      • Adding a group prevents metabolism by MAO, prolonging duration of action
      • Methylation increases indirect activity
    • Amine group
      The terminal nitrogen.
      • Addition of a methyl group generally increases beta selectivity
        As the chain length increases, so does the beta selectivity.


  • Dopamine is the prototypical catecholamine, to which others are compared


  • Noradrenaline has a hydroxyl group added to the beta carbon, increasing its alpha selectivity


  • Adrenaline is similar to noradrenaline with an additional hydroxyl group on the beta carbon
  • Adrenaline also has a methyl group added to the terminal amine, increasing beta selectivity


  • Metaraminol has an additional hydroxyl group on the beta carbon
  • Metaraminol has only one hydroxyl group on the phenol ring, so:
    • It is no longer classified as a catecholamine
    • It is not metabolised by COMT, prolonging its duration of action
    • It has reduced potency, requiring administration in higher doses
  • Metaraminol has an additional methyl group on the alpha carbon, preventing metabolism by MAO and further prolonging its duration of action


  • Like metaraminol, ephedrine has a hydroxyl group on the beta carbon and a methyl group on the alpha carbon
  • Ephedrine has no hydroxyl groups on the phenol ring, further reducing its potency and increasing its elimination half-life
  • Ephedrine has a methyl group on the amine, increasing its beta selectivity


  1. Brandis K. The Physiology Viva: Questions & Answers. 2003.
  2. Chambers D, Huang C, Matthews G. Basic Physiology for Anaesthetists. Cambridge University Press. 2015.
  3. Yartsev A. Deranged Physiology - Structure of Synthetic Catecholamines
  4. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
Last updated 2021-09-14

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