2021A Question 6

Compare and contrast the pharmacology of metaraminol and adrenaline (epinephrine).

Examiner Report

55% of candidates achieved a pass in this question.

The main domains assessed in this question were:

  • Structure and classification
  • Mechanism of action
  • Pharmacokinetics
  • Pharmacodynamics – with particular emphasis on cardiovascular system effects

Both metaraminol and adrenaline (epinephrine) are drugs commonly used by anaesthetists and therefore it was expected that candidates should have a thorough knowledge of their pharmacology to pass. Many candidates utilised a table format and this lent itself well to a comparison of the two drugs across the required domains

Common problems included:

  • Lack of detail regarding mechanism of action (including adrenoreceptor selectivity)
  • Little pharmacokinetic information provided
  • Superficial mention of the cardiovascular effects of the drugs
  • No mention of effects on other body systems

The intracellular details of G-protein coupled receptor activation was not required and did not receive marks.

Model Answer


Adrenaline Metaraminol

- Catecholamine: Direct, potent, sensitive to COMT

- OH on β-carbon: Direct, alpha

- No substitution on α-carbon: MAO sensitive

- Larger amine: Β>α

- Non-catecholamine: Resistant to COMT

- OH on β-carbon: Direct, alpha

- NH2 substitution on α-carbon: Indirect, MAO resistant

- Smaller amine: Α>β

Presentation 1mg in 1mL or 10mL (concentrated ++++) 10mg in 1mL (concentrated++)
Tissue necrosis High risk – CVC only Low risk – PIVC ok


Adrenaline Metaraminol

- IV infusion: 1-30μg/min

- IV bolus: 1mg in cardiac arrest

- IM bolus: 500μg in anaphylaxis

- IV bolus: 0.5-1mg (10-20μg/kg) PRN

- IV infusion: Typically 0.5-5mg/h (20-200μg/kg/h)

- S/C or IM

Time course

- Onset ≤1min

- Duration 5 mins

 - Drug elimination rapid

 - Receptor effects prolonged

- Onset 1-2 min

- Duration: Stated 20-60mins, likely shorter

Absorption Not orally bioavailable Orally bioavailable, % unknown

- VD 0.1-0.2L/kg

- 12% protein bound

- Should not cross blood-brain barrier

- Poorly studied in humans

- 45% protein bound

- VD 4L/kg

- Should not cross BBB


- By COMT and MAO → VMA

- By COMT only → Normetadrenaline

- t1/2β 2 mins

- Poorly studied in humans; likely slow

- Not susceptible to MAO or COMT

- t1/2β 6 hours

Excretion Metabolites → Urine Unknown


Adrenaline Metaraminol
Receptor activity

- β1 > β2 > α1

- Direct

- α1 >> β1

- Direct

- Indirect (displaces noradrenaline from vesicles)


- Anaphylaxis (↑ CO, ↑ SVR, stabilize mast cells)

- Cardiogenic shock (↑ CO)

- Cardiac arrest (↑ SVR → Vital organ perfusion)

- Additive with local anaesthetic (↑ duration, ↓ LAST)

- Peri-operative hypotension – GA and neuraxial

- Unclear if equivalent to phenylephrine in obstetrics


- Safer with noradrenaline reuptake inhibitors (NRI)

- Tachyphylaxis slow: Adrenoceptor downregulation

- Dangerous with NRI e.g. MAOi (↑↑ NAd release)

- Tachyphylaxis rapid: Catecholamine depletion

Last updated 2021-08-23

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