Question 9

Outline the classification and effects of beta-blocking drugs, including examples (50% marks).

Compare and contrast the pharmacokinetics of metoprolol with esmolol (50% marks).

[Click here to toggle visibility of the answers]

College Answer

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.

Discussion

"There are generally many ways to classify drugs within the same class", the examiners cackle mockingly. No standard classification system seems to exist, and the "recommended pharmacological texts" each seem to take a different road here. Here's an example from Katsung. 

Three Different Classification of Beta-blockers
According to selectivity According to membrane stabilising effects According to intrinsic sympathomimetic activity

Non-selective

  • Propanolol

β1-selective

  • Atenolol
  • Metoprolol
  • Bisoprolol
  • Nebivolol
  • Esmolol
  • Sotalol

Combined α- and β-blocker effect

  • Carvedilol
  • Labetalol

Stabilising

  • Propanolol
  • Sotalol
  • Metoprolol

Non-stabilising

  • Atenolol
  • Bisoprolol
  • Nebivolol
  • Esmolol
  • Carvedilol
  • Labetalol

ISA

  • Labetalol
  • Acebutolol
  • Pindolol

Non-ISA

  • Propanolol
  • Atenolol
  • Metoprolol
  • Bisoprolol
  • Nebivolol
  • Esmolol
  • Sotalol
  • Carvedilol

Metoprolol vs esmolol:

Name Metoprolol Esmolol
Chemistry aryloxypropanolamine aryloxypropanolamine
Routes of administration Oral or IV IV
Absorption 50% oral bioavailability 0% oral bioavailability
Solubility pKa 9.7, poor lipid solubility pKa 9.5, minimal lipid solubility
Distribution VOD 2.8-4.8 L/kg; only 12% protein bound VOD 3.4 L/kg; 60% protein bound
Target receptor Selective β1 receptor blocker Highly selective β1 receptor blocker
Metabolism Mainly hepatic clearance Rapidly metabolised in blood by hydrolysis of methyl ester linkage
Elimination minimal renal excretion;
half-life 3-4 hrs
minimal renal excretion;
half-life 9 min
Time course of action 12-24 hrs Rapid onset and offset of effect

References

Oliver, Eduardo, Federico Mayor Jr, and Pilar D’Ocon. "Beta-blockers: Historical perspective and mechanisms of action." Revista Española de Cardiología (English Edition) 72.10 (2019): 853-862.

Gorre, Frauke, and Hans Vandekerckhove. "Beta-blockers: focus on mechanism of action Which beta-blocker, when and why?." Acta cardiologica 65.5 (2010): 565-570.

Johnsson, Gillis, and C-G. Regårdh. "Clinical pharmacokinetics of β-adrenoceptor blocking drugs." Clinical pharmacokinetics 1.4 (1976): 233-263.

Kendall, Martin J. "Clinical relevance of pharmacokinetic differences between beta blockers." The American journal of cardiology 80.9 (1997): 15J-19J.

McDevitt, D. G. "Comparison of pharmacokinetic properties of beta-adrenoceptor blocking drugs." European heart journal 8.suppl_M (1987): 9-14.