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

· Table of ephedrine vs noradrenaline

· Pharmacokinetics

· Pharmacodynamics

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

	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 · t_1/2_β 2 mins	· Minimal
Excretion	· Metabolites -> urine	· Unchanged in urine · t_1/2_β 3-6 hours

	Noradrenaline	Ephedrine
Receptor activity	· α₁ > β₁ >> β₂ · Direct only (i.e. via adrenoceptors)	· β1 ≥ α₁ · Direct and indirect o Displaces noradrenaline from its vesicles o Noradrenaline reuptake inhibitor
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