G7i / 19B18: Compare and contrast the pharmacology of metaraminol and noradrenaline

19B18: Exam Report

Compare and contrast the pharmacology of metaraminol and noradrenaline.

71% of candidates passed this question.

Marks were distributed across pharmaceutics, uses, dose & administration, mechanism of action, Pharmacokinetcs and Pharmacodynamics. Common omissions were doses/rates of infusion, effects other than on heart/SVR (e.g. splanchnic, renal blood flow), indirect effect of metaraminol, receptor effect of noradrenaline other than alpha 1 and tachyphylaxis.

G7i / 19B18: Compare and contrast the pharmacology of metaraminol and noradrenaline

Metaraminol

Noradrenaline

Chemical

Metaraminol

synthetic non-catecholamine with direct & indirect sympathomimetic effects but predominant α-adrenoreceptor activity

Noradrenaline

Endogenous catecholamine neurotransmitter released from postganglionic sympathetic n. endings

Also accounts for 20% adrenal medulla secretions

Use

Metaraminol

hypotension

Noradrenaline

to ↑SVR

Presentation

Metaraminol

clear solution 10mg/mL

Noradrenaline

Clear, colourless solution 1mg/mL

Brown ampoule → prevent light oxidation

Must be diluted in D5W to provide sufficient acidity to prevent oxidation

1 pH D5W = 4, pH 0.9% NaCl = 6

Metaraminol commonly comes in pre-formed syringes 0.5mg/ml

Dose

Metaraminol

0.5 – 1mg bolus or as an infusion 1 – 10mg/hr

Noradrenaline

Infusion 1 – 20mcg/min

Metaraminol used during intubation and sedation procedures, easy to administer peripherally

Route

Metaraminol

IV

Noradrenaline

central vein

Obvious advantage of peripheral administration w M

Onset

Metaraminol

1-2mins

Noradrenaline

immediate: tachyphylaxis with prolonged infusions

Both confer tachyphylaxis

MoA

Metaraminol

Indirect: taken up by postganglionic symp. nerve endings

Displaces NA

NA released

Mostly affects α1 adrenoreceptors

α1 → Gq → stimulates Phospholipase C → ↑IP3 & DAG → open Ca2+ channel → VC of smooth m. of vessels

 Direct

CVS – ↑SVR

Regional BF – ↓CBF & ↓renal BF

Noradrenaline

α1 = α2 > β1 > β2

Potent α agonist

Equal β1 cf. adrenaline

Little β2 activity

α1 → Gq → stimulates Phospholipase C → ↑IP3 & DAG → ↑Ca2+

Smooth m. vasoconstriction

Cardiac: weak +ve inotropy

Metabolic: ↑BSL

 α2 → Gi → inhibits AC → ↓cAMP → ↓Ca2+

CNS: ↓symp. outflow

Peripheries: inhibits NA release from nerve terminals

Platelets: ↓plat. aggregation

 β1 → GS → ↑AC →↑cAMP → ↑Ca2+

Heart: +ve inotropy, +ve chronotropy, +ve dromotropy

Renal: ↑renin, ↑AII

Metabolic: ↑lipolysis, ↑FFAs

PD

Metaraminol

CVS – increased SBP & DBP, reflex bradycardia, increase CA blood flow

Noradrenaline

CVS

Intense VC all vascular beds = ↑↑SVR

↑HR

↑FoC

Reflex ↓HR

Renal, hepatic, cerebral & skeletal m. BF all ↓

RESP

Small ↑MV

METABOLIC

↑BSL

↑FFA

RENAL

↑Renin

PK

Metaraminol

A

(limited data)

D

doesn’t cross BBB. 45% PPB

M

not a MAO/COMT substitute

E

Noradrenaline

A

IV administration

D

25% uptake via 1 lung passage

M

rapid metabolism t½ = 2 mins

MAO/COMT pathway

E

metabolites conjugated to glucuronic acid for renal excretion

Adverse Effects

Metaraminol

Reflex ↓HR

Headache

Dizziness

Tremor

Nausea &vomiting

LV failure

Noradrenaline

Extravasation → necrosis

Headache

Anxiety

 NB CAUTION:  Patients taking MAO inhibitors

 PREGNANCY = ↑contraction of pregnant uterus, foetal bradycardia & asphyxia