2017B07 Compare and contrast the pharmacology of ephedrine and noradrenaline.

 

List:

·      Table of ephedrine vs noradrenaline

·      Pharmacokinetics

·      Pharmacodynamics

 

Physicochemical:

 

Noradrenaline

Ephedrine

Structure

Structure-activity

· Catecholamine: direct, potent, sensitive to COMT

· OH on β-carbon: direct, alpha

· No substitution on α-carbon: MAO sensitive

· Smaller amine: α>β

· Non-catecholamine: resistant to COMT

· OH on β-carbon: direct, alpha

· CH3 substitution on α-carbon: indirect, MAO resistant

· Larger amine: β>α

 

Pharmacokinetic:

 

Noradrenaline

Ephedrine

Administration

· IV infusion 1-30mcg/min

· 3-6mg q2min, max 15mg

· IV, IM, PO

Time course

· Onset < 1min

· Duration 5 mins

o Drug elimination rapid

o Receptor effects prolonged

· Onset 1-2 min

· Duration 1 hour

Absorption

· Oral bioav nil

· Oral bioav 85%

Distribution

· Should not cross blood-brain barrier

· Should not cross BBB

Metabolism

· By COMT and MAO -> VMA

· By COMT only -> normetadrenaline

· t1/2β 2 mins

· Minimal

Excretion

· Metabolites -> urine

· Unchanged in urine

· t1/2β 3-6 hours

 

Pharmacodynamics:

 

Noradrenaline

Ephedrine

Receptor activity

· α1 > β1 >> β2

· Direct

· β1 ≥ α1

· Direct and indirect

Use

· Vasodilatory shock: sepsis, anaphylaxis, post-CPB

· Myocardial ischaemia with GTN

· Hypotension especially if also bradycardic

· Previously preferred in pregnancy, but increases neonatal [lactate]

Toxicity

· Safer with noradrenaline reuptake inhibitors (NRI)

· Extravasation -> necrosis hence CVC only

· Tachyphylaxis slow: adrenoceptor downregulation

· Dangerous with NRI (indirect -> ↑↑NAd rel.)

· Peripheral IV injection safe

· IM injection safe

· Tachyphylaxis rapid: NAd depletion

 

 

 

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