What are the bioavailability and half-lives of beta blockers (beta-adrenergic blocking agents), and which intravenous (IV) formulations are available in Singapore?

Bioavailability and Half-Lives of Beta Blockers and IV Formulations in Singapore

Beta blockers have widely varying bioavailability (from 20% to 90%) and half-lives (from 1-2 hours to 15-24 hours), with esmolol and metoprolol being the most commonly available IV formulations in Singapore. 1

Pharmacokinetic Properties of Beta Blockers

Bioavailability

Beta blockers can be categorized based on their bioavailability:

• High Bioavailability (>70%):

  • Bisoprolol: 90%
  • Sotalol: 90%
  • Pindolol: 50-90%
  • Nebivolol: Variable but high
  • Betaxolol: 75-90%

• Moderate Bioavailability (40-70%):

  • Atenolol: 50-60%
  • Metoprolol: 40-60%
  • Celiprolol: 30-70%
  • Acebutolol: 35-50%

• Low Bioavailability (<40%):

  • Propranolol: 20-50% (due to high first-pass metabolism)
  • Carvedilol: 20-30%
  • Labetalol: 20-30%

Half-Lives

Beta blockers can be categorized based on their half-lives:

• Short Half-Life (<5 hours):

  • Esmolol: 9 minutes (ultra-short) 2
  • Propranolol: 3-5 hours
  • Metoprolol: 3-5 hours
  • Acebutolol: 2-4 hours
  • Labetalol: 3-10 hours

• Intermediate Half-Life (5-12 hours):

  • Bisoprolol: 9-12 hours
  • Atenolol: 5-8 hours
  • Metipranolol: 2.5-3 hours
  • Carvedilol: 6-7 hours

• Long Half-Life (>12 hours):

  • Nadolol: 10-15 hours
  • Sotalol: 5-9 hours
  • Nebivolol: 10-15 hours
  • Talinolol: 10-12 hours

IV Beta Blockers Available in Singapore

The most commonly available IV beta blockers in Singapore are:

1. Esmolol (IV) 2

   • Ultra-short acting (half-life ~9 minutes)
   • Cardioselective (beta-1 selective)
   • Dosing: 500 mcg/kg IV bolus over 1 minute, followed by infusion at 50-300 mcg/kg/min 1
   • Particularly useful for acute situations requiring rapid onset and offset of action

2. Metoprolol (IV) 3

   • Short-acting (half-life 3-5 hours)
   • Cardioselective (beta-1 selective)
   • Dosing: 2.5-5.0 mg IV bolus over 2 minutes, can repeat up to 3 doses at 10-minute intervals 1
   • Commonly used for rate control in supraventricular tachycardias

3. Propranolol (IV)

   • Non-selective beta blocker
   • Dosing: 1 mg IV over 1 minute, can repeat at 2-minute intervals up to 3 doses 1
   • Used for various indications including arrhythmias and aortic dissection

4. Labetalol (IV)

   • Combined alpha and beta blocker
   • Particularly useful in hypertensive emergencies
   • Has been used in aortic dissection and pregnancy-related hypertension 1

Clinical Considerations for IV Beta Blocker Selection

When selecting an IV beta blocker in Singapore, consider:

1. Duration of Action Required:

   • For short procedures or rapid titration: Esmolol (ultra-short acting)
   • For intermediate duration: Metoprolol
   • For longer effect: Propranolol

2. Selectivity Needs:

   • Cardioselective (fewer pulmonary effects): Esmolol, Metoprolol
   • Non-selective: Propranolol
   • Combined alpha/beta blockade: Labetalol

3. Comorbidities:

   • Reactive airway disease: Prefer cardioselective agents (Esmolol, Metoprolol) 2
   • Hepatic impairment: Caution with Metoprolol and Propranolol (hepatically metabolized) 4
   • Renal impairment: Caution with Atenolol (renally cleared) 1

4. Clinical Scenario:

   • Aortic dissection: Esmolol, Propranolol, or Labetalol 1
   • Supraventricular tachycardia: Esmolol or Metoprolol 1
   • Hypertensive emergencies in pregnancy: Labetalol preferred 1

Practical Considerations for IV Beta Blocker Use

• Monitoring: All IV beta blockers require close monitoring of heart rate, blood pressure, and ECG
• Contraindications: Avoid in cardiogenic shock, severe bradycardia, high-degree AV block without pacemaker, and decompensated heart failure 4
• Precautions: Use with caution in patients with bronchospastic disease, diabetes, and peripheral vascular disease

Common Pitfalls to Avoid

1. Abrupt Discontinuation: Never abruptly stop beta blockers as this can precipitate rebound hypertension, angina, or arrhythmias 4

2. Excessive Dosing: Start with lower doses in elderly patients, particularly women, who may require significantly lower doses for equivalent effect 4

3. Failure to Recognize Lipophilicity Differences: Lipophilic beta blockers (propranolol, metoprolol) have higher first-pass metabolism and greater CNS penetration than hydrophilic ones (atenolol) 5, 6

4. Overlooking Renal/Hepatic Function: Adjust dosing based on organ function - hydrophilic beta blockers require dose adjustment in renal impairment, while lipophilic ones need adjustment in hepatic impairment 7