Adrenergic Vasoactives

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

Adrenergic drugs:

  • Act via:
    • Dopamine (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 Commonly Used Adrenergic Agents

Properties Noradrenaline Adrenaline Phenylephrine Metaraminol Ephedrine
Class Natural Catecholamine Natural Catecholamine Sympathomimetic phenylethylamine derivative Synthetic sympathomimetic Synthetic sympathomimetic
Uses SVR Cardiac arrest, anaphylaxis, inotropy, chronotropy, adjunct in local anaesthetics SVR SVR SVR without ↓ in HR
Dosing Start at 0.05µg/kg/min Infusion starts at: 0.01µg/kg/min Bolus start at 50-100mcg Bolus 0.5-2mg 3-6mg bolus
Presentation Clear, colourless, light-sensitive solution. Sodium metabisulfite as excipient. A clear, colourless solution typically at 0.1-1mg/ml Clear, colourless solution at 100mcg/ml Clear, colourless solution in ampoule at 10mg/ml, typically reconstituted to 0.5mg/ml Clear, colourless solution in 30mg/ml ampoule
Absorption IV only Variable ETT and SC absorption IM onset 15 minutes, duration up to 1 hour IV only IV or IM
Metabolism t1/2 2min. Metabolised by mitochondrial MAO and COMT in liver, kidney, and blood to VMA and metadrenaline. t1/2 2min. Metabolised by mitochondrial MAO and COMT within liver, kidney, and blood to VMA and metadrenaline. Hepatic by MAO Some uptake into adrenergic nerve endings Hepatic (not metabolised by MAO and COMT), giving a longer (10-60 minute) duration of action and a t1/2β of 3-6 hours
Elimination Pulmonary uptake of up to 25%. Urinary excretion of metabolites Urinary excretion of metabolites Renal of metabolites, t1/2β 2-3 hours 50% unchanged in urine
Mechanism of action α>>β β>α at lower doses. At high doses α1 effects dominate. Direct α1 Direct α1 ↑ NA release (indirect α1) and direct α and β agonism
Respiratory MV, bronchodilation MV, bronchodilation Bronchodilation
CVS SVR, ↑ Myocardial O2 consumption, ↑ Coronary flow. ↑ Inotropy, ↑ HR, ↑ SVR and PVR, ↑ BP, ↑ CO, ↑ myocardial O2 consumption. Coronary vasodilation. Arrythmogenic. SVR and BP, potential reflex bradycardia. Not arrythmogenic. SVR/PVR, reflex bradycardia. Indirect ↑ in coronary flow. Direct and indirect (via NA release) ↑ in HR, BP, and CO. Arrhythmogenic.
CNS ↑ Pain threshold, ↑ MAC MAC, mydriasis.
MSK Necrosis with extravasation Necrosis with extravasation
Renal ↓ RBF ↓ RBF and ↑ in sphincter tone ↓ RBF ↓ RBF ↓ RBF
Metabolic BMR, ↑ lipolysis, ↑ gluconeogenesis and BSL, ↑ Lactate. Initally ↑ insulin secretion (β), then ↓ (α)
GU ↓ Uterine blood flow and foetal bradycardia ↓ Uterine blood flow ↓ Uterine blood flow

Comparison of Less Common Adrenergic Agents

Properties Dopamine Isoprenaline Dobutamine
Class Natural Catecholamine Synthetic Catecholamine Synthetic Catecholamine
Uses Haemodynamic support Severe bradycardia Stress testing, increasing CO
Dosing Start 1µg/kg/min Infusion from 0.5-10µg/min 0.5-20µg/kg/min
Route IV IV IV
Presentation Clear, colourless solution with 200mg or 800mg in water Clear solution at 1mg/ml 250mg dobutamine in 20ml water
Metabolism t1/2 3 min. 25% of dose converted to noradrenaline. Remainder is metabolised by MAO and COMT similar to nor/adrenaline. Hepatic by COMT t1/2 2 min. COMT to inactive metabolites.
Elimination Renal, t1/2β 3 minutes Urinary excetion of unchanged drug and metabolites
Mechanism of action D1, D2; β>α at lower dose β1>>β2, D2
Respiratory Potent bronchodilation Bronchodilation
CVS ↑ Inotropy, ↑ HR, ↑ CO, coronary vasodilation. At high doses, ↑ SVR and PVR, ↑ VR. SVR, potential reflex bradycardia. Not arrythmogenic. HR, CO, contractility, and automaticity. Β2 effects may ↓ SVR and BP.
CNS Inhibits prolactin. Nausea. Stimulant Tremor
MSK Necrosis with extravasation
Renal ↑ RBF and ↑ urinary output with no improvement in renal function
GIT Mesenteric vasodilation

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 selectiviy
    • 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 2017-10-08

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