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Beta Blocker

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Beta Blocker, Beta-Blocker, Beta Adrenergic Antagonist, Beta Adrenoceptor Blocking Drug, Atenolol, Timolol, Nadolol

  1. Sir James Black won 1988 Nobel Prize for Propranolol
  2. Synthesized Propranolol first in the 1960's
  3. Revolutionized cardiovascular medicine
  • Indications
  1. Hypertension
  2. Atrial Fibrillation Rate Control
  3. Coronary Artery Disease without prior Myocardial Infarction
    1. Consider to reduce Anginal symptoms and improve Exercise tolerance
  4. Myocardial Infarction without Congestive Heart Failure
    1. Continue for at least 2-3 years after Myocardial Infarction
  5. Stable Congestive Heart Failure (Carvedilol, Metoprolol, Bisoprolol)
    1. Continue Beta Blocker indefinately
  6. Arrhythmia refractory to other modality
    1. Recurrent Ventricular Tachycardia
    2. Recurrent Ventricular Fibrillation
  7. Migraine Prophylaxis
  • Contraindications
  1. Reactive Airway Disease and Obstructive Lung Disease (Asthma, COPD)
    1. Cardioselective Beta Blockers (e.g. Metoprolol) are not contraindicated
    2. Avoid non-selective Beta Blockers (Carvedilol, Propranolol)
    3. See Bronchospasm under adverse effects below
  2. Acute Congestive Heart Failure exascerbation
  3. Concurrent Calcium Channel Blocker use
  • Precautions
  1. Abrupt discontinuation is associated with exacerbation of Angina and risk of MI (FDA black box warning)
  2. Taper over one to two weeks
  1. Beta Adrenergic Receptor Antagonist
  2. Inhibits effects of circulating Catecholamines
  3. Blocks Beta Adrenergic Receptors
    1. Beta-1 Adrenergic Receptors
      1. Cardiac muscle (primarily contraction)
      2. Allow calcium entry into cells (cAMP mediated)
      3. Inotropic and chronotropic effects
    2. Beta-2 Adrenergic Receptors
      1. Smooth muscle and Bronchioles
    3. Beta-3 Adrenergic Receptors
      1. Lipolysis
  1. General Cardiac Effects
    1. Negative Inotrope
      1. Reduces Myocardial Contractility
    2. Negative Chronotrope
      1. Reduces Heart Rate
    3. Reduces Blood Pressure
    4. Reduces Myocardial Oxygen Demand
  2. Antiarrhythmic effects
    1. Seen with non-selective Beta Blockers (Propranolol)
    2. Controls Catecholamine stimulated arrhythmias
      1. Recurrent Ventricular Tachycardia
      2. Recurrent Ventricular Fibrillation
    3. Controls Myocardial Ischemia related arrhythmias
    4. Reduces AV Nodal Conduction
      1. Slows ventricular response
        1. Atrial Fibrillation
        2. Atrial Flutter
        3. Paroxysmal Supraventricular Tachycardia
      2. Quinidine-like effect on action potential
        1. Seen with Propranolol
  3. Myocardial protection
    1. Reduces Myocardial Infarction size
    2. Prevents re-infarction after Thrombolytic
  • Mechanism
  • Non-Selective effects (non-cardiovascular effects)
  1. Beta 2 Adrenergic Receptor blockade
    1. Results in bronchoconstriction
      1. Beta 2 Adrenergic Receptors affect Bronchiole and smooth muscles
    2. Non-Selective Beta Blockers (e.g. Propranolol)
    3. Selective Beta Blockers lose selectivity at high dose and in Overdose
      1. High dose Metoprolol (over 200 mg/day)
      2. High dose Esmolol (over 300 ug/kg/min)
  2. Beta 3 Adrenergic Receptor blockade
    1. Lipolysis inhibited
  • Adverse Effects
  1. SA and AV nodal blockade
    1. Avoid in over age 75 unless secondary indication
    2. Do not use with Calcium Channel Blockers
  2. Hypotension or Orthostasis
  3. Congestive Heart Failure
    1. Treat with vasodilators and Diuretics with inotropes
  4. Bradycardia
    1. Treat with Atropine, Transcutaneous pacing, Dopamine
  5. Bronchospasm
    1. Treat with Sympathomimetics and Aminophylline
    2. Unlikely to occur in cardioselective Beta Blockers at standard doses
      1. Study looked at Atenolol, Metoprolol, bisoprolol
      2. First dose may lower FEV1 (responds to Albuterol)
      3. Continuous use does not impair lung function
      4. Salpeter (2002) Ann Intern Med 137:715-25 [PubMed]
  6. Major Depression exacerbation
  7. Fatigue
  • Drug Interactions
  • Decreased Heart Rate and AV Conduction
  • Preparations
  • Cardioselective (Beta-1 Selective Adrenergic Blockade)
  1. Atenolol (Tenormin)
    1. Despite daily dosing, duration of activity is not a a full 24 hours
      1. Consider dividing dosing into twice daily (e.g. 50 mg twice daily)
    2. Not as effective as other Beta Blockers in cardiovascular disease prevention (especially with Hypertension present)
      1. Consider Metoprolol, Bisoprolol, Carvedilol or Nadolol instead
      2. Carlberg (2004) Lancet 364:1684-9 [PubMed]
    3. Dosing
      1. Regular: 50 mg PO daily (MAX: 100 mg/day)
      2. IV (Acute MI): 5 mg IV over 5 min, repeat in 10 min
  2. Bisoprolol
    1. Most cardioselective of Beta Blockers
  3. Metoprolol (Lopressor, Toprol XL)
    1. Preferred Beta Blocker for Hypertension, Myocardial Infarction, Atrial Fibrillation Rate Control
    2. Metoprolol Succinate (Toprol XL) is preferred over Metoprolol Tartrate (Lopressor)
  4. Esmolol Hydrochloride (Brevibloc)
    1. Intravenous very short acting Beta Blocker used in Emergent Hypertension Management
  5. Nebivolol (Bystolic)
    1. Third generation Beta Blocker with vasodilatory properties (nitric oxide release)
  6. Other cardioselective Beta Blockers
    1. Betaxolol
    2. Acebutolol
  • Preparations
  • Nonselective (Beta-1 and Beta-2 Adrenergic Blockade)
  1. Timolol (Blocadren)
    1. Dose: 10 mg PO bid (MAX 60 mg/day)
  2. Nadolol (Corgard)
    1. Dose: 40 mg PO qd (MAX 320 mg/day)
  3. Propranolol (Inderal)
    1. Used for Essential Tremor, symptomatic Hyperthyroidism, Migraine Prophylaxis, symptomatic Palpitations
  4. Timolol
    1. Typically used topically for Open Angle Glaucoma
  5. Sotalol
    1. Primarily used as Antiarrhythmic
  6. Other non-selective Beta Blockers
    1. Carteolol
    2. Oxprenolol
    3. Penbutolol
  • Preparations
  • Combined Alpha-1, Beta-1 and Beta-2 Adrenergic Blockade
  1. Labetalol
    1. Used in Hypertension in Pregnancy, Resistant Hypertension, CVA Blood Pressure Control
  2. Carvedilol (Coreg)
    1. Third generation Beta Blocker with vasodilatory properties (alpha blocker)
    2. Used in Congestive Heart Failure
  • References
  1. (2012) Presc Lett 19(12): 67-8
  2. Yen (2015) Crit Dec Emerg Med 29(10): 18-23