β-blockers in the Cardiovascular section of the 2023 CICM Primary Syllabus Pharmacopeia appear as "Beta Blockers – not listed above" in the sweaty depths of the crowded "Level 3" section. The "listed above" are only esmolol and labetalol. Others are either missing or reshuffled, for example (understandably) sotalol appears apart in the antiarrhythmic section, and (weirdly) carvedilol is listed even deeper below as a "Mixed Antagonist".
| Class | Beta blocker |
|---|---|
| Chemistry |
All are aryloxypropanolamines
|
| Routes of administration |
Oral only, for all of them, except labetalol metoprolol and sotalol (which are both IV and oral) and esmolol (which is IV only) |
| Absorption |
Absorption is excellent for all of them except esmolol (0%) and atenolol (50%), but bioavailability is extremely poor even for the well absorbed ones due to high first pass metabolism.
|
| Solubility |
All have a high-ish pKa, in the 8-10 range; many are highly lipid soluble (propanolol is highest). Protein binding varies from 3% (atenolol) to 98% (nebivolol)
|
| Distribution |
Atenolol has the smallest VOD (0.3-0.6 L/kg) and labetalol has the largest (3-16 L/kg)
|
| Metabolism |
All undergo hepatic metabolism with minimal renal involvement except for atenolol (100% renally cleared as unchanged drug) and bisoprolol (50% renally cleared)
|
| Elimination |
Half-lives range from 3-4hrs (metoprolol) to 10-30 hrs (nebivolol)
|
| Time course of action |
Clinical effect is much longer than half life, and is completely unrelated to it; eg. for metoprolol, ~ 24 hrs
|
| Target receptor |
All of these drugs bind to the β1 and β2 receptors with varying degrees of affinity. . |
| Mechanism of action |
By binding to Gs-protein coupled β1 and β2 receptors, block cAMP synthesis |
| Clinical effects |
β1 effects: decreased heart rate, decreased contractility, decreased blood pressure, lower myocardial oxygen demand and increased diastolic coronary filling, and decreased arrhythmogenicity. β2 effects: increased peripheral vascular resistance, bronchospasm, decreased insulin release, increased bladder and uterine tone Some penetrate the blood brain barrier and exert an anxiolytic effect. Some have a membrane-stabilising (sodium channel blocker) effect. |
| Literature reference | |
| CICM details of understanding | Level 3 |
| Mentioned around Deranged Physiology | |
| Related SAQs |
Question 12 from the second paper of 2023 (metoprolol, briefly) Question 5 from the first paper of 2022 (labetalol vs. esmolol) Question 14 from the second paper of 2019 (metoprolol vs esmolol) Question 10 from the first paper of 2013 (carvedilol and spironolactone, weirdly) Question 4(p.2) from the first paper of 2010 (metoprolol and GTN) |