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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