G7iii / 22A05: Write short notes on the pharmacology of labetalol and esmolol, highlighting their differences

22A05: Exam Report

Write short notes on the pharmacology of labetalol and esmolol, highlighting their differences

32% of candidates passed this question.

Overall, this question was poorly answered. Most answers demonstrated limited knowledge about the major differences between the two drugs’ including the target receptors and subsequent effects.

Antiarrhythmic effects were often omitted in answers, and scant or incorrect details provided about the metabolism and overall pharmacokinetics of the drugs. Generic vague statements about pharmacokinetic properties of medications do not attract marks.

Better scoring answers demonstrated a factual knowledge about both individual drugs and specific details related to any differences influencing the potential application of these differences.

A table superficially listing aspects of both drugs would not be of a passing standard. Many answers demonstrated significant incorrect facts.

G7iii / 22A05: Write short notes on the pharmacology of labetalol and esmolol, highlighting their differences

Labetalol

Esmolol

Class

Labetalol

  • Mixed α1 & β antagonist

Esmolol

  • Cardioselective β1 antagonist
  • (class II antiarrhythmic)

Use

Labetalol

  • Hypertension (all grades)
  • Acute MI
  • Hypotensive anaesthesia

Esmolol

  • Perioperative hypotension
  • Acute supraventricular arrhythmias (AF/flutter)
  • Hypotensive anaesthesia

Presentation

Labetalol

  • Clear solution for injection

  • Tablets

Esmolol

  • Clear solution for injection

Route

Labetalol

  • IV
  • PO

Esmolol

  • IV only

Dose

Labetalol

  • IV 20-40mg boluses as needed, can be run as infusion

Esmolol

  • 50-150mcg/kg/min infusion depending on effect

Onset

Labetalol

  • 5-30 minutes

Esmolol

  • 6-10 minutes

Duration

Labetalol

  • 50 minutes

Esmolol

  • 20 minutes (ultrashort acting)

MoA

Labetalol

  • α:β effects 1:3 (PO), 1:7 (IV)
  • β1 antagonism: ↓ adenylyl cyclase → ↓ cAMP → ↓ Ca2+ → -ve inotropy, -ve chronotropy
  • α1 antagonism: ↓ PLC → ↓ IP3 & DAG  → ↓Ca2+ → vasodilation
  • Intrinsic sympathomimetic β2 activity → vasodilation
  • ⇨ ↓BP

Esmolol

  • β1 effects only, cardioselective
  • β1 antagonism: ↓adenylyl cyclase → ↓ cAMP → ↓ Ca2+ → -ve inotropy, -ve chronotropy
  • No intrinsic sympathomimetic activity
  • ⇨ ↓BP

PD

Labetalol

CVS

  • ↓SBP and DBP
  • ↓HR + CO
  • ↓SVR
  • ↓Coronary vascular resistance

CNS

  • No effect on cerebral blood flow; autoregulation maintained

Renal

  • ↓ Renal vascular resistance → ↑RBF (GFR unchanged)
  • ↓ Renin activity → ↓Angiotensin II

Esmolol

CVS

  • ↓ BP
  • ↓ HR (dose-dependent)
  • ↓ Slows AV conduction
  • Obtunds reflex response to intubation

Absorption

Labetalol

  • Rapidly absorbed but significant first pass metabolism – OBA 10-80%

Esmolol

  • IV only

Distribution

Labetalol

  • PPB 50%, Vd 2.5-15L/kg

Esmolol

  • PPB 50%, Vd 3.4L/kg

Metabolism

Labetalol

  • Hepatic → inactive metabolites

Esmolol

  • By esterases in RBCs → inactive and weakly active metabolites

Elimination

Labetalol

  • Renal excretion of metabolites

Esmolol

  • Renal excretion of metabolites

Side Effects

Labetalol

  • α > β
  • α – dizziness, formication, nasal congestion
  • β – asthma, heart failure, nightmares, Raynaud’s

Esmolol

Β1 side effects

  • Hypotension, bradycardia
  • Bronchospasm
  • N+V
  • CNS disturbances

Author: Emily Little