2017B Question 07

Compare and contrast the pharmacology of ephedrine and noradrenaline.

Examiner Report

61.2% of candidates achieved a pass in this question.

Candidates were required to compare the pharmacology of ephedrine and noradrenaline. It was difficult to score highly if a structure such as uses, pharmaceutics, pharmacodynamics, pharmacokinetics, side effects and interactions was not used.

Common errors included being vague with answers (e.g. “works at adrenoreceptors”), over-estimating the beta effects of ephedrine, only including cardiovascular effects of the drugs and not being aware of the clinical relevance of structural differences between the two medications. Some candidates answered the question using adrenaline instead of ephedrine and candidates are reminded to read short answer questions carefully.

Candidates who scored highly included the above (with correct information), and discussed clinically relevant and important points about the drugs that fall outside the above sections. Often candidates who scored well were able to discuss the differences in structure between the two medications and what the implications of these structural differences are.

Model Answer

Structure:

  • 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 1-30μg/min

- 3-6mg q2min, max 15mg

- IV, IM, PO

Time course

- Onset ≤1min

- Duration 5 mins

 - Drug elimination rapid

 - 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


Last updated 2021-08-23

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