2021A06 Compare and contrast the pharmacology of metaraminol and adrenaline (epinephrine).

 

Physicochemical:

 

Adrenaline

Metaraminol

Structure

Structure-activity

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

CH3 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

 

Pharmacokinetic:

 

Adrenaline

Metaraminol

Administration

IV infusion: 1-30mcg/min

IV bolus: 1mg in cardiac arrest

IM bolus: 500mcg in anaphylaxis

IV bolus: 0.5-1mg (10-20mcg/kg) PRN

IV infusion: typically 0.5-5mg/h (20-200mcg/kg/h)

S/C or IM

Time course

Onset < 1min

Duration 5 mins

o Drug elimination rapid

o Receptor effects prolonged

Onset 1-2 min

Duration: stated 20-60mins, likely shorter

Absorption

Not orally bioavailable

Orally bioavailable, % unknown

Distribution

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

Metabolism

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

 

Pharmacodynamics:

 

Adrenaline

Metaraminol

Receptor activity

β1 > β2 > α1

Direct only (i.e. via adrenoceptors)

α1 >> β1

Direct and indirect

o   Displaces noradrenaline from vesicles

Use

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

Toxicity

Safer with noradrenaline reuptake inhibitors (NRI)

Tachyphylaxis slow: adrenoceptor downregulation

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

Tachyphylaxis rapid: catecholamine depletion

 

 

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