Outline the classification and effects of beta-blocking drugs, including examples (50% marks).
Compare and contrast the pharmacokinetics of metoprolol with esmolol (50% marks).
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.
"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 Goodman & Gillman.
| According to selectivity | According to membrane stabilising effects | According to intrinsic sympathomimetic activity |
|
Non-selective
β1-selective
Combined α- and β-blocker effect
|
Stabilising
Non-stabilising
|
ISA
Non-ISA
|
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 |
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.
