Outline the classification and effects of beta-blocking drugs with examples (50% of marks). Compare and contrast the pharmacokinetics of metoprolol with esmolol (50% of marks).
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.
No classification of beta-blockers could possibly incorporate "selectivity, membrane stabilising activity and ISA" all into a single taxonomy, so where the college examiners asked to "outline", what they really mean was "give us three separate classification systems". Thus:
| 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
|
With this anagram-like exercise behind us, the rest of the question can be answered by the reptilian hindbrain, requiring nothing more than the direct recall of stored information.
| Name | Metoprolol | Esmolol |
| Class | Beta blocker | Beta blocker |
| 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 metabolized in blood by hydrolysis of its methyl ester linkag |
| Elimination | minimal renal excretion; half-life 3-4 hrs | minimal renal excretion; half-life 9 min |
| Time course of action | Clinical effects persist for longer than the half life would suggest, because they are mainly determined by drug-receptor affinity | Rapid onset and offset of effect |
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