β-Adrenergic Receptor Antagonists (β Blockers)

Agents

Non-Selective Beta Blockers

  • Carteolol
  • Nadolol (Corgard, Anabet, Solgol, Corzide, Alti-Nadolol, Apo-Nadol, Novo-Nadolol) (see Nadolol, [[Nadolol]])
  • Penbutolol
  • Pindolol (Visken, Betapindol, Blockin L, Blocklin L, Calvisken, Cardilate, Decreten, Durapindol, Glauco-Visken, Pectobloc, Pinbetol, Prindolol, Pynastin)
  • Propafenone (Rhythmol) (see Propafenone, [[Propafenone]]): with additional Class 1C antiarrhythmic properties (inhibits sodium channels)
  • Propanolol (Inderal) (see Propanolol, [[Propanolol]])
  • Sotalol (Betapace, Betapace AF, Sotalex, Sotacor) (see Sotalol, [[Sotalol]]): with additional Class III antiarrhythmic properties (inhibits potassium channels)
  • Timolol (Blocadren, Timoptic) (see Timolol, [[Timolol]])

Cardioselective (β1-Selective) Beta Blockers

  • Acebutolol (Sectral, Prent) (see Acebutolol, [[Acebutolol]])
  • Atenolol (Tenormin) (see Atenolol, [[Atenolol]])
  • Betaxalol (Betoptic, Lokren, Kerlone) (see Betaxalol, [[Betaxalol]])
  • Bisoprolol (Concor, Zebeta) (see Bisoprolol, [[Bisoprolol]])
  • Esmolol (Brevibloc) (see Esmolol, [[Esmolol]])
  • Metoprolol (Lopressor) (see Metoprolol, [[Metoprolol]])
  • Nebivolol (Bystolic) (see Nebivolol, [[Nebivolol]])
  • Practolol: although structurally similar to propanolol, it is no longer used in humans (due to adverse effect of oculomucocutaneous syndrome)

Beta Blockers with Intrinsic Sympathomimetic Activity (β-Adrenergic Receptor Antagonism + Low Level β-Adrenergic Receptor Agonism)

  • Acebutolol (see Acebutolol, [[Acebutolol]])
  • Carteolol
  • Celiprolol
  • Mepindolol
  • Oxprenolol
  • Penbutolol
  • Pindolol (Visken, Betapindol, Blockin L, Blocklin L, Calvisken, Cardilate, Decreten, Durapindol, Glauco-Visken, Pectobloc, Pinbetol, Prindolol, Pynastin)

Beta Blockers with Alpha Blocking Activity

  • Carvedilol (Coreg) (see Carvedilol, [[Carvedilol]])
  • Labetalol (Normodyne, Trandate) (see Labetalol, [[Labetalol]])

Pharmacology

  • β-Adrenergic Receptor Antagonism
    • Inhibition of Atrioventricular Nodal Conduction
    • Vasodilation

Clinical Aspects

  • Retrospective Review of the Impact of Peri-Operative Beta Blocker Use on Inpatient Mortality (2005) MEDLINE]
    • Study: retrospective review of patients undergoing major non-cardiac surgery (n = 782,969 in 329 US hospitals)
    • Main Findings
      • Perioperative beta-blocker therapy was associated with a reduced risk of in-hospital death among high-risk, but not low-risk, patients undergoing major noncardiac surgery
        • RCRI score 0-1: treatment was associated with no benefit and possible harm
        • RCRI score 2: adjusted odds ratios for death in the hospital was 0.88 (95 percent confidence interval, 0.80 to 0.98)
        • RCRI score 3: adjusted odds ratios for death in the hospital was 0.71 (95 percent confidence interval, 0.63 to 0.80)
        • RCRI score 4 or more: adjusted odds ratios for death in the hospital was 0.58 (95 percent confidence interval, 0.50 to 0.67)
  • POISE Trial (2008) [MEDLINE]
    • Study: randomized, placebo-controlled trial (n = 8,351)
    • Main Findings
      • Initiation of extended-release metoprolol succinate increased mortality and strokes in non-cardiac surgery patients
  • Meta-Analysis of Studies Examining Peri-Operative Beta Blocker Use (Excluding DECREASE Series of Trials) (2014) [MEDLINE]
    • Study: meta-analysis of randomized controlled trials of β-blockade on perioperative mortality, non-fatal myocardial infarction, stroke and hypotension in non-cardiac surgery
      • Importantly excluded the discredited DECREASE trials (author of trials and discussant for development of the guidelines was notably dismissed for academic dishonesty)
    • Main Findings
      • Initiation of a course of β-blockers before surgery resulted in a 27% risk increase in 30-day all-cause mortality (p=0.04)
        • β-blockade decreased non-fatal myocardial infarction (RR 0.73, p=0.001), but increased stroke (RR 1.73, p=0.05) and hypotension (RR 1.51, p<0.00001)
        • The results were dominated by the large POISE trial
      • Separate analysis of the DECREASE trials contradict the meta-analysis related to mortality (p=0.05 for divergence)
      • Current guidelines (which are based on the DECREASE trials) need to be revised

Adverse Effects

Cardiac Adverse Effects

  • Bradycardia (see Bradycardia, [[Bradycardia]])
    • May especially occur when used in conjunction with other negative chronotropes which slow heart rate and atrioventricular nodal conduction (such as digoxin or calcium channel blockers)
  • Congestive Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]]): due to negative inotropy
    • May occur in some cases, especially when used in conjunction with other negative inotropes and chronotropes (such as calcium channel blockers)
  • Heart Block
  • Hypotension (see Hypotension, [[Hypotension]])
  • Masking of Hypoglycemia-Induced Tachycardia (see Hypoglycemia, [[Hypoglycemia]]): beta blockers may mask tachycardia (but not necessarily the diaphoresis or dizziness) which occur in hypoglycemia
  • Masking of Hyperthyroidism-Induced Tachycardia (see Hyperthyroidism, [[Hyperthyroidism]])
    • Abrupt withdrawal of beta blockers in this setting may precipitate thyroid storm
  • Paradoxical Increase in Blood Pressure in Pheochromocytoma (see Pheochromocytoma, [[Pheochromocytoma]]): when used alone and not in combination with alpha blockers, beta blockers may paradoxically increase blood pressure (due to attenuation of the beta receptor-mediated vasodilatation in skeletal muscle)
    • Therefore, in pheochromocytoma, beta blockers should only be initiated after alpha blockers have been initiated
  • Potentiation of the Hypertensive Response that Occurs with Clonidine Withdrawal (in Patients on Concomitant Clonidine and Beta Blockers)
    • In such cases, it is advised to withdraw the beta blocker at least several days before withdrawing the clonidine

Neurologic Adverse Effects

Pulmonary Adverse Effects

  • Bronchospasm/Exacerbation of Obstructive Airways Disease (see Obstructive Lung Disease, [[Obstructive Lung Disease]])
    • Bronchoprovocation Potential (in decreasing order)
      • Propanolol (Inderal) (see Propanolol, [[Propanolol]])
      • Timolol (see Timolol, [[Timolol]])
      • Nadolol (see Nadolol, [[Nadolol]])
      • Metoprolol (Lopressor) (see Metoprolol, [[Metoprolol]])
      • Atenolol (Tenormin) (see Atenolol, [[Atenolol]])
      • Pindolol (Visken, Betapindol, Blockin L, Blocklin L, Calvisken, Cardilate, Decreten, Durapindol, Glauco-Visken, Pectobloc, Pinbetol, Prindolol, Pynastin)
      • Labetalol (see Labetalol, [[Labetalol]])
  • Interstitial Pneumonitis (see Interstitial Lung Disease-Etiology, [[Interstitial Lung Disease-Etiology]])
    • Acebutolol (Sectral, Prent) (see Acebutolol, [[Acebutolol]])
    • Atenolol (Tenormin) (see Atenolol, [[Atenolol]])
    • Carvedilol (Coreg) (see Carvedilol, [[Carvedilol]])
    • Celiprolol
    • Labetalol (see Labetalol, [[Labetalol]])
    • Nadolol (see Nadolol, [[Nadolol]])
    • Pindolol (Visken, Betapindol, Blockin L, Blocklin L, Calvisken, Cardilate, Decreten, Durapindol, Glauco-Visken, Pectobloc, Pinbetol, Prindolol, Pynastin)
    • Practolol
    • Propanolol (see Propanolol, [[Propanolol]])
    • Timolol (see Timolol, [[Timolol]])
  • Organizing Pneumonia (see Cryptogenic Organizing Pneumonia, [[Cryptogenic Organizing Pneumonia]])
    • Acebutolol (Sectral, Prent) (see Acebutolol, [[Acebutolol]])
    • Betaxalol (Betoptic, Lokren, Kerlone) (see Betaxalol, [[Betaxalol]])
    • Oxprenolol
    • Sotalol (Betapace, Betapace AF, Sotalex, Sotacor) (see Sotalol, [[Sotalol]])
    • Timolol (Blocadren, Timoptic) (see Timolol, [[Timolol]])

Renal Adverse Effects

  • Hyperkalemia (see Hyperkalemia, [Hyperkalemia]): due to induced potassium release from cells

Rheumatologic Adverse Effects

  • Drug-Induced Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus, [[Systemic Lupus Erythematosus]])
    • Acebutolol (Sectral, Prent) (see Acebutolol, [[Acebutolol]]): case reports

Other Adverse Effects

  • Fatigue (see Fatigue, [[Fatigue]])

Beta Blocker Intoxication

Diagnosis

  • xxx

Clinical Manifestations

Cardiac Manifestations

Pulmonary Manifestations

Other Manifestations

Treatment

  • Glucagon
    • Dose: 3-10 mg IV, then 2-5 mg/hr drip
    • Enhances myocardial contractility and AV conduction
    • Increases heart rate
  • Nasogastric Lavage: indicated if performed within 1-2 hrs of ingestion
  • Charcoal
  • Hemodialysis
  • Cardiac Pacing
  • IV Fluid Resuscitation

Beta Blocker Withdrawal

Etiology

  • Patient Self-Discontinuation of Beta Blocker
  • Clinician Discontinuation of Beta Blocker During Hospitalization/Surgery

Clinical

Treatment

  • Avoid Abrupt Discontinuation of Beta Blockers: especially in peri-operative period

References

  • Acebutolol-induced pleuropulmonary lupus syndrome. Ann Intern Med 1981; 95: 326 [MEDLINE]
  • Atenolol-induced interstitial pneumonia. Ann Intern Med 1997; 148: 505-507 [MEDLINE]
  • Betaxolol and drug-induced lupus complicated by pericarditis and large pericardial effusion. West J Med 1997; 167: 106-109 [MEDLINE]
  • Adverse effects of a single dose of (+)-sotalol in patients with mild stable asthma. Br J Clin Pharmacol 1998; 46: 79-82 [MEDLINE]
  • Bronchiolitis obliterans with organizing pneumonia. Retrospective study of 19 cases. Rev Pneumol Clin 1998; 54: 136-143 [MEDLINE]
  • Perioperative beta-blocker therapy and mortality after major noncardiac surgery. N Engl J Med. 2005 Jul 28;353(4):349-61 [MEDLINE]
  • Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008 May 31;371(9627):1839-47. doi: 10.1016/S0140-6736(08)60601-7. Epub 2008 May 12 [MEDLINE]
  • Meta-analysis of secure randomised controlled trials of β-blockade to prevent perioperative death in non-cardiac surgery. Heart. 2014 Mar;100(6):456-64. doi: 10.1136/heartjnl-2013-304262. Epub 2013 Jul 31 [MEDLINE]