Write short notes on the pharmacology of labetalol and esmolol, highlighting their differences.
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.
The mind boggles at the byzantine complexity of SAQ writers' stem wording design, where "write short notes" but "highlighting the differences" was chosen instead of "compare and contrast" - presumably to achieve some sort of hidden educational effect. What influence this had on the answer structure is difficult to guess, but judging by the rest of the comments, it was none - the college still expected something about pharmacokinetics, receptors, effects, etc. In short, this generic table structure from the Part One Pharmacopoeia would have probably been just fine.
| Name | Labetalol | Esmolol |
| Class | Beta blocker | Beta blocker |
| Chemistry | aryloxypropanolamine; a racemic mixture of four stereoisomers, of which only one is active |
aryloxypropanolamine |
| Routes of administration | Oral or IV | IV |
| Absorption | 25% oral bioavailability | 0% oral bioavailability |
| Solubility | pKa 9.3, 50% fairly lipid-soluble | pKa 9.5, minimal lipid solubility |
| Distribution | VOD 3-16 L/kg; 50% protein bound | VOD 3.4 L/kg; 60% protein bound |
| Target receptor | Nonselective β1 and β2 receptor blocker, with some anti-α1 effects and some sodium channel blocker (membrane stabilising) effects | Highly selective β1 receptor blocker |
| Metabolism | Mainly hepatic clearance | rapidly metabolized in blood by hydrolysis of its methyl ester linkage |
| 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 |
| Mechanism of action | By binding to Gs-protein coupled β1 and β2 receptors, blocks cAMP synthesis | By binding to Gs-protein coupled β1 receptors, blocks cAMP synthesis |
| Clinical effects | β1 effects: decreased heart rate, decreased contractility, decreased blood pressure, lower myocardial oxygen demand and increased diastolci coronary fillng, and decreased arrhythmogenicity. β2 effects: increased peripheral vascular resistance, bronchospasm, decreased insulin release, increased bladder and uterine tone α1 effects: afterload reduction, vasodilation Membrane-stabilising (sodium channel blocker) effect |
β1 effects: decreased heart rate, decreased contractility, decreased blood pressure, lower myocardial oxygen demand and increased diastolic coronary filling, and decreased arrhythmogenicity. |
| Single best reference for further information | Oliver et al (2019) | Oliver et al (2019) |
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.
MacCarthy, E. Paul, and Saul S. Bloomfield. "Labetalol: a review of its pharmacology, pharmacokinetics, clinical uses and adverse effects." Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 3.4 (1983): 193-217.
Gorczynski, Richard J. "Basic pharmacology of esmolol." The American journal of cardiology 56.11 (1985): F3-F13.