2001A15 Compare and contrast the pharmacology of esmolol and propranolol.

 

List:

·      PC

·      PK

·      PD

 

Physicochemical:

 

Propranolol

Esmolol

Structure

Racemic

Achiral

 

Pharmacokinetic:

 

Propranolol

Esmolol

Admin

·  1-2 mins bolus q2 min

0.5mg/kg bolus

IV infusion 0.05-2mcg/kg/min

Time course

·  Onset 1-2 min (IV)

·  Duration 5 min (IV)

·  Onset 2-10 mins

·  Duration 10-30 mins

Absorption

·  Oral bioav 25%

·  Oral bioav 30%

Distribution

·  Plasma protein binding 95%

·  VD 3.5L/kg

·  High lipid solubility

·  Crosses blood-brain barrier effectively

·  Plasma protein binding 60%

·  VD 3.5L/kg

·  Moderate lipid solubility

Metabolism

·  Hepatic oxidative deamination then dealkylation or glucuronidation

·  Active 4-OH metabolite

·  t1/2β 3 hours

·  RBC esterase to acid and alcohol; acid is weak β-blocker

·  Cl 300mL/kg/min

·  t1/2β 10 mins

Excretion

·  <1% unchanged.

·  1% unchanged

 

Pharmacodynamic:

 

Propranolol

Esmolol

Receptor effects

S-propranolol:

·  β1 β2 non-selective

·  Membrane stabilizing activity (MSA)

·  No intrinsic sympathomimetic activity (ISA)

R-propranolol:

·  Inhibit peripheral conversion T4->T3 (inhibits deodinase)

·  β1 selective

·  No membrane-stabilising activity

·  No MSA

·  No ISA

Indications

·  Angina

·  HOCM

·  Thyrotoxicosis

·  Anxiety

·  Tremor

·  Intra-op hypertension

·  Ablate pressor response to laryngoscopy

Side effects and toxicity

·  CNS: drowsiness, fatigue, depression, insomnia, nightmares

·  CVS: AV block, worsen acute LV failure, worsen peripheral vascular disease

·  Resp: bronchoconstriction (↑risk if asthma)

·  Metabolic: ↓autonomic response to hypoglycaemia, ↑risk T2DM

·  Other: hair loss

·  MSA toxicity: as for local anaesthetic toxicity

o CNS: excitation (seizures) then inhibition (coma)

o CVS: hypotension, arrhythmia, arrest

·  Similar

·  Minimal CNS effects

·  No MSA effects

·  Long term effects not relevant – used for short periods in critical care only

 

 

 

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