G7i / 22B13: Compare and contrast the pharmacology of EPHEDRINE and METARAMINOL

22B13: Exam Report

Compare and contrast the pharmacology of EPHEDRINE and METARAMINOL

27% of candidates passed this question.

The ‘compare and contrast’ pharmacology question indicates the use of a standardised structure that incorporates pharmaceutics, pharmacokinetics and pharmacodynamics.

The best answers provided excellent detail, ie. precise descriptions of mechanisms of action and emphasised noteworthy areas of contrast between the two drugs.

Highlighting opportunities for use and areas of caution/drug limitations.

Overall, most candidates seemed to have a sufficient knowledge of metaraminol but details surrounding
ephedrine were often lacking.

G7i / 22B13: Compare and contrast the pharmacology of EPHEDRINE and METARAMINOL

Metaraminol

Ephedrine

Metaraminol

Synthetic catecholamines

Ephedrine

Synthetic Non-catecholamines

Pharmaceutics

Class

Metaraminol

  • Synthetic catecholamine

Ephedrine

  • Indirect / direct acting

Receptors

Metaraminol

  • α1 (mostly)>>  β1

Ephedrine

  • α1  +  β1

Use

Metaraminol

  • Refractory hypotension

Ephedrine

  • Hypotension in general, spinal or epidural anaesthesia
  • Nocturnal enuresis
  • Narcolepsy
  • Diabetic autonomic neuropathy
  • Hiccups
  • Nasal decongestant

Presentation

Metaraminol

  • CCS 10mg/mL

Ephedrine

  • 15/30/60mg tabs
  • Elixir
  • Nasal drops
  • CSI 30mg/mL ephedrine (racemic with 4 isomers – L isomer is active) – diluted in 0.9% NaCl

Dose

Metaraminol

  • Infusion 0up to 10mg/hr
  • Bolus 0.5-1mg

Ephedrine

  • 3-7.5mg (max 9mg) slowly, repeated  3-4 minutely to a max of 30mg titrated to effect

Pharmacodynamics

MoA

Metaraminol

  • α1 GqPCR  → IP3  → ↑Ca2+ = vasoconstriction
  • Indirect (release of NA from nerve terminals)

Ephedrine

  • Direct stimulation of adrenoceptors
  • Indirect (release ae of NA from nerve terminals)

CNS Effects

Metaraminol

  • ↓CBF

Ephedrine

  • Stimulant
  • ↑ cerebral blood flow
  • Mydriasis
  • Local anaesthetic properties

Respiratory Effects

Metaraminol

  • ↑ MV

Ephedrine

  • Marked bronchodilation

CVS Effects

Metaraminol

  • ↑ SVR/PVR
  • Indirect effect on CoroBF

Ephedrine

  • Similar effects of adrenaline but more prolonged

Alimentary Effects

Metaraminol

  • ↑ GI tone + motility
  • ↑ Mesenteric bloodflow

Ephedrine

  • Splanchnic vasoconstriction

Genitourinary Effects

Metaraminol

↓ Renal bloodflow

Ephedrine

  • ↓ Renal bloodflow
  • ↓ Uterine tone
  • Urinary retention

Metabolic & Other Effects

Metaraminol

  • Skin necrosis

Ephedrine

  • ↑ GNG
  • ↑ BMR (stimulates O2 uptake and thermogenesis)

Pharmacokinetics

A

Metaraminol

  • IV

Ephedrine

  • IV
  • PO rapidly and completely absorbed
  • IM
  • Subcut

D

Metaraminol

  • 45% PPB
  • Does not cross BBB

Ephedrine

  • Rapidly and extensively distributed throughout the body
  • Accumulation in kidneys, liver, kidneys, spleen and brain
  • Vd 4L/kg
  • Crosses placenta/breast milk
  • Mild effect on uterine artery compared with other a-agonists.  Commonly used to treat maternal arterial hypotension & restore uterine perfusion pressure

M

Metaraminol

  • Not a MAO/COMT substitute

Ephedrine

  • NOT metabolised by MOA or COMT
  • Small amt metabolised by liver to Noradrenaline (major metabolite)

E

Metaraminol

  • 15-75% excreted unchanged in urine, remainder as metabolite
  • t1/2 2min

Ephedrine

  • 40% excreted renally unchanged
  • t1/2  6 hours

A/E

Metaraminol

  • Reflex bradycardiac
  • Headache
  • Dizziness
  • Tremor
  • N+V

Ephedrine

  • Insomnia
  • Tremor
  • Headachy
  • Arrythmias
  • Nausea
  • Vomiting
  • Chest pain
  • Acute hypertensive crisis if administered with MAOIs, beta blockers

Author: Erin Maylin