G7iii / 21B09 / 19B14: Outline the classification and effects of beta-blocking drugs with examples (50% marks). Compare and contrast the pharmacokinetics of metoprolol with esmolol (50% marks)

21B09: Exam Report

Outline the classification and effects of beta-blocking drugs, including examples (50% marks). Compare and contrast the pharmacokinetics of metoprolol with esmolol (50% marks)

59% of candidates passed this question.

This was a two-part question with marks and thus timing of the answers given as a percentage. There are generally many ways to classify drugs within the same class. These are usually well described in the relevant recommended pharmacological texts. Receptor distribution throughout the body and the effect of the drug-receptor interaction are useful ways to organise systemic pharmacodynamic responses, as opposed to a list of organ systems with associated vague statements of interaction.

19B14: Exam Report

Outline the classification and effects of beta-blocking drugs with examples (505 of marks). Compare and contrast the pharmacokinetics of metoprolol with esmolol (50% of marks).

47% of candidates passed this question.

Beta-blocking drugs were generally well classified. Selectivity, membrane stabilising activity and ISA should have been mentioned. Many candidates omitted or poorly answered the ‘effects’ of beta blockers. Candidates who performed well answering the pharmacokinetics of metoprolol and esmolol provided a table of the two drugs. Superficial statements such as “hepatic metabolism and renal excretion” attracted minimal marks. The mechanism of action of beta blockers was not requested.

G7iii / 21B09 / 19B14: Outline the classification and effects of beta-blocking drugs with examples (50% marks). Compare and contrast the pharmacokinetics of metoprolol with esmolol (50% marks)

Definition

Β blockers are antagonists of the effects of catecholamines at β adrenoreceptors

Chemical

  • All are derivatives of β agonist ISOPRENALINE
  • Benzene ring substitutions determine whether drug will be an agonist/antagonist
  • Levorotary more potent

Classification

Competitive antagonists – all are competitive antagonists & occupy β receptor to cause no activation

  • Selectivity:
    • Non-selective: β1 & β2 → PROPANOLOL
    • Selective: β1 = cardioselective → METOPROLOL, ATENOLOL, ESMOLOL
  • Intrinsic sympathomimetic activity – ∴ classified as partial agonist, better tolerated with poor LV function → LABETALOL
  • Membrane stabilising activity → PROPANOLOL, LABETAOLOL have MSA effects similar to Class IA antiarrythmics
  • Other → SOTALOL which exhibits K channel blocking activity

PK

A

Metoprolol

50% OBA

Esmolol

IV only

Comparison

LIPID SOLUBILITY: Metoprolol > esmolol

PK

D

Metoprolol

10% PPB

Esmolol

55% PPB

Vd 3.5L/kg

Comparison

Both have very high lipid solubility and cross BBB

PK

M

Metoprolol

Hepatic; 60% 1st pass metabolism

Inactive metabolites

Esmolol

Plasma hydrolysis by RBC esterase

Comparison

Esterase metabolism governs esmolol’s very short t1/2

PK

E

Metoprolol

Metabolites cleared in urine

<10% unchanged

t ½ B 6hrs

Esmolol

Renal <1% unchanged

T ½ 10mins

Comparison

Half life of metoprolol is much longer and usually has bd dosing