• Clinical science

Beta blockers (Beta antagonists)

Summary

Beta blockers are a group of drugs that inhibit the sympathetic activation of β-adrenergic receptors. Cardioselective blockers (e.g., atenolol, bisoprolol) primarily block β1 receptors in the heart, causing decreased heart rate and cardiac contractility, slower AVN conduction, and decreased cardiac workload. Nonselective β blockers (e.g., pindolol, propranolol) inhibit all β receptors and may cause bronchoconstriction, peripheral vasoconstriction, and metabolic imbalances (e.g., hypo- and hyperglycemia, hypertriglyceridemia) in addition to cardiac effects. Cardioselective β blockers have a lower side effect profile and are preferred in the management of coronary heart disease, compensated heart failure, acute coronary syndrome, and in certain types of arrhythmias. Propranolol, a nonselective β blocker, is the first-line drug in the management of essential tremor, portal hypertension, migraine prophylaxis, and thyroid storm. Beta blockers are contraindicated in patients with symptomatic bradycardia, AV block, decompensated heart failure, and asthma. Initiation and cessation of β blocker therapy should always be gradual to avoid side effects or symptoms of withdrawal (rebound tachycardia, hypertension, acute cardiac death).

Overview

Nonselective beta blockers Cardioselective beta blockers (β1 selective) Nonselective beta blockers with additional α blocking action
With ISA (intrinsic sympathomimetic activity) Without ISA With ISA Without ISA
Agents
  • Acebutolol
  • Celiprolol
Specific effects
  • Selectively bind to and block β1 receptors, which are primarily found in the heart
  • Do not cause bronchoconstriction or vasoconstriction
  • Do not interfere with glycogenolysis; safe in diabetics
  • Cardioselectivity is dose-dependent

All cardioselective beta blockers begin with the letters A to M (B1 = first half of the alphabet). All non-cardioselective beta blockers with the exception of carvedilol begin with the letters N to Z.

References:[1][2][3][4][5]

Effects

Beta blockers competitively bind to and block β-adrenergic receptors, thereby inhibiting sympathetic (adrenergic and/or noradrenergic) stimulation of β receptors.

Types of β receptors Main site of action Effects of β adrenergic stimulation Effects of β adrenergic blockade
β1
  • Heart
    • Anti-ischemic effect
      • β1 blockadeheart rate and ↓ cardiac contractility↓ BP and ↓ oxygen consumption by the heartanti-ischemic effect
    • Antiarrhythmic effect
      • β1 blockade ↓ AVN conduction, ↑ AVN refractory time, and heart rate → anti-arrhythmic effect
    • Anti-remodeling effect
  • Kidneys: renin releaseangiotensin II conversion → ↓ H2O resorption↓ BP
β2
β3
  • Lipolysis with weight gain

Beta blockers competitively inhibit adrenergic substances (such as adrenaline, noradrenaline) at β receptors!
References:[7][8][9][10][11][6][12]

Side effects

General side effects

Inhibited receptor Affected system Adverse effects
Both β1 and β2 Cardiac

CNS

  • Drowsiness, sleep disorders, nightmares
  • Fatigue/lethargy
  • Depression, hallucinations
Cholesterol levels
Cutaneous
β2 Pulmonary
  • Bronchoconstriction (esp. patients with asthma and reactive airway disease)
Peripheral vasculature
Metabolic

Beta blocker withdrawal

Beta blocker overdose

References:[3][8][13][14][15][16][17][18][19][20][21][22][23][24][25]

We list the most important adverse effects. The selection is not exhaustive.

Indications

Cardiovascular indications

Specific indications for propranolol

Miscellaneous

Beta blockers should be introduced gradually with slow increases in dosage, and slowly tapered off and stopped when their use is no longer needed!
References:[26][27][28][29][30][31][32]

Contraindications

Absolute contraindications Relative contraindications

References:[33][34][35][36]

We list the most important contraindications. The selection is not exhaustive.

Pharmacokinetics

Lipophilic agents Hydrophilic agents Mixed
Properties
  • Undergo hepatic clearance
  • Penetrate the blood-brain-barrier → central/neurological adverse effects (esp. nightmares and insomnia)
  • Long-acting: most require a single dose per day
  • Undergo renal clearance
  • Do not cross the blood-brain-barrier
  • Short-acting: require multiple doses per day
Agents
  • 1. Le T, Bhushan V, Skelley N. First Aid for the USMLE Step 2 CK. McGraw-Hill Education; 2012.
  • 2. Nebivolol (bystolic), a novel Beta blocker for hypertension. Hilas O, Ezzo D. P T. 2009; 34(4): pp. 188–192. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697096/.
  • 3. Frishman WH. Clinical significance of beta 1-selectivity and intrinsic sympathomimetic activity in a beta-adrenergic blocking drug. Am J Cardiol. 1987; 59(13): pp. 33F–37F. pmid: 2883876.
  • 4. Gleiter CH, Deckert J. Adverse CNS-effects of beta-adrenoceptor blockers. Pharmacopsychiatry. 1996; 29(6): pp. 201–211. doi: 10.1055/s-2007-979572.
  • 5. Le T, Bhushan V,‎ Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017.
  • 6. Sambhara D, Aref AA. Glaucoma management: relative value and place in therapy of available drug treatments. Ther Adv Chronic Dis. 2013; 5(1): pp. 30–43. doi: 10.1177/2040622313511286.
  • 7. Klabunde RE. Beta-Adrenoceptor Agonists (β-agonists). http://cvpharmacology.com/cardiostimulatory/beta-agonist. Updated October 26, 2012. Accessed April 7, 2017.
  • 8. Barrueto F Jr, Traub SJ, Grayzel J. Beta Blocker Poisoning. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/beta-blocker-poisoning. Last updated April 29, 2016. Accessed April 7, 2017.
  • 9. Wax MB, Molinoff PB. Distribution and properties of beta-adrenergic receptors in human iris-ciliary body. Invest Ophthalmol Vis Sci. 1987; 28(3): pp. 420–430. pmid: 3030954.
  • 10. Poirier L, Tobe SW. Contemporary use of β-blockers: clinical relevance of subclassification. Can J Cardiol. 2014; 30(5 Suppl): pp. S9–S15. doi: 10.1016/j.cjca.2013.12.001.
  • 11. Pharmacology : MCQs. Beta-Adrenoceptor Antagonists (Beta-Blockers). https://sites.google.com/site/pharmacologymcqs/slelective-beta-blockers. Updated April 7, 2017. Accessed April 7, 2017.
  • 12. Gorre, Vanderckhove. Beta-blockers: focus on mechanism of action. Which beta-blocker, when and why?. Acta Cardiologica. 2010; 65(5): pp. 565–570. doi: 10.2143/AC.65.5.2056244.
  • 13. Kamaruzzaman S, Watt H, Carson C, Ebrahim S. The association between orthostatic hypotension and medication use in the British Women's Heart and Health Study. Age Ageing. 2009; 39(1): pp. 51–56. doi: 10.1093/ageing/afp192.
  • 14. Milazzo V, Di Stefano C, Servo S, et al. Drugs and Orthostatic Hypotension: Evidence from Literature. J Hypertens. 2012; 1: p. 104. doi: 10.4172/2167-1095.1000104.
  • 15. Koella WP. CNS-related (side-)effects of β-Blockers with special reference to mechanisms of action. Eur J Clin Pharmacol . 1985; 28(Suppl 1): p. 55. doi: 10.1007/BF00543711.
  • 16. Mcainsh J, Cruickshank JM. Beta-blockers and central nervous system side effects. Pharmacol Ther. 1990; 46(2): pp. 163–197. doi: 10.1016/0163-7258(90)90092-G.
  • 17. Wolinsky H. The effects of beta-adrenergic blocking agents on blood lipid levels. Clin Cardiol. 1987; 10: pp. 561–566. doi: 10.1002/clc.4960101010.
  • 18. Fogari R, Zoppi A, Corradi L, Preti P, Mugellini A, Lusardi P. Beta-blocker effects on plasma lipids during prolonged treatment of hypertensive patients with hypercholesterolemia. J Cardiovasc Pharmacol. 1999; 33(4): pp. 534–539. pmid: 10218722.
  • 19. Marshall AJ, Roberts CJ, Barritt DW. Raynaud's phenomenon as side effect of beta-blockers in hypertension. Br Med J. 1976; 1(6024): pp. 1498–1499. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1640736/.
  • 20. GPnotebook. beta blockers and hyperglycemia. http://www.gpnotebook.co.uk/simplepage.cfm?ID=x20121021135802605084. Updated April 7, 2017. Accessed April 7, 2017.
  • 21. Rivas-Echeverria C, Allegaert K, Wainstein DE, Goran K. Proceedings of the World Medical Conference, Prague, Czech Republic, September 26-28, 2011. WSEAS Press; 2011.
  • 22. Pearson Education. Nursing Process Focus: Clients Receiving Beta-Adrenergic Antagonist Therapy. http://media.pearsoncmg.com/intl/pec/mylab/adams_mynursing/nursing_charts/ch21/21_Clients_Receiving_Beta-Adrenergic_Antagonist_Therapy.pdf. Updated January 1, 2010. Accessed April 7, 2017.
  • 23. Kaplan NM. Withdrawal syndromes with antihypertensive therapy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/withdrawal-syndromes-with-antihypertensive-therapy. Last updated March 21, 2016. Accessed April 7, 2017.
  • 24. Bailey B. Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review. Journal of toxicology. Clinical toxicology. 2003; 41(5): pp. 595–602. pmid: 14514004.
  • 25. Boyd R, Ghosh A. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Glucagon for the treatment of symptomatic beta blocker overdose. Emerg Med J. 2003; 20(3): pp. 266–7. pmid: 12748150.
  • 26. Kannam JP, Aroesty JM, Gersh BJ. Beta blockers in the management of stable ischemic heart disease. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/beta-blockers-in-the-management-of-stable-ischemic-heart-disease. Last updated September 21, 2016. Accessed February 23, 2017.
  • 27. Langan R, Jones K. Common Questions About the Initial Management of Hypertension. Am Fam Physician. 2015; 91(3): pp. 172–177. url: http://www.aafp.org/afp/2015/0201/p172.html.
  • 28. Pflieger M, Winslow BT, Mills K, Dauber IM. Medical Management of Stable Coronary Artery Disease. Am Fam Physician. 2011; 83(7): pp. 819–826. url: http://www.aafp.org/afp/2011/0401/p819.html.
  • 29. Rosenson RS, Reeder GS, Kennedy HL. Acute myocardial infarction: Role of beta blocker therapy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/acute-myocardial-infarction-role-of-beta-blocker-therapy. Last updated June 15, 2016. Accessed April 8, 2017.
  • 30. Giardina EG. Therapeutic use and major side effects of sotalol. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/therapeutic-use-and-major-side-effects-of-sotalol. Last updated November 2, 2016. Accessed April 8, 2017.
  • 31. Drugs.com. Sotalol. https://www.drugs.com/pro/sotalol.html. Updated April 8, 2017. Accessed April 8, 2017.
  • 32. Hedera P, Cibulčík F, Davis TL. Pharmacotherapy of essential tremor. J Cent Nerv Syst Dis. 2013; 5: pp. 43–55. doi: 10.4137/JCNSD.S6561.
  • 33. Podymow T, August P. Update on the use of antihypertensive drugs in pregnancy. Hypertension. 2008; 51(4): pp. 960–969. doi: 10.1161/HYPERTENSIONAHA.106.075895.
  • 34. Kim GK, Del rosso JQ. Drug-provoked psoriasis: is it drug induced or drug aggravated?: understanding pathophysiology and clinical relevance. J Clin Aesthet Dermatol. 2010; 3(1): pp. 32–38. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921739/.
  • 35. Hong J, Bernstein D. A Review of Drugs That Induce or Exacerbate Psoriasis. Psoriasis Forum. 2012; 18(1). url: https://www.psoriasis.org/files/publications/forum/FORUM-SPRING-2012-drugs-that-induce-psoriasis.pdf.
  • 36. Ph A. Management of hypertension in pregnant and postpartum women. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/management-of-hypertension-in-pregnant-and-postpartum-women. Last updated April 4, 2017. Accessed April 8, 2017.
  • Lehtonen. Effect of beta blockers on blood lipid profile. American Heart Journal. 1985. pmid: 2859784.
  • Nickson. Beta-Blocker Overdose. https://litfl.com/beta-blocker-overdose/. Updated April 2, 2019. Accessed April 22, 2019.
  • Silvestri et al. Report of erectile dysfunction after therapy with beta-blockers is related to patient knowledge of side effects and is reversed by placebo. European Heart Journal. 2003: pp. 1928–1932. doi: 10.1016/j.ehj.2003.08.016.
  • Modi S, Lowder DM. Medications for migraine prophylaxis. Am Fam Physician. 2006; 73(1): pp. 72–78. pmid: 16417067.
  • Man in 't Veld. Haemodynamic consequences of intrinsic sympathomimetic activity and cardioselectivity in beta-blocker therapy for hypertension. European Heart Journal. 1986: pp. D:31–41. pmid: 6137381.
  • Jailon. Relevance of intrinsic sympathomimetic activity for beta blockers. 66. 1990; 9: pp. 21C–23C. pmid: 1977302.
  • Book. Carvedilol: A Nonselective Beta-blocking Agent With Antioxidant Properties. Congestive Heart Failure. ; 8(3): pp. 173–7. pmid: 12045386.
  • Klabunde RE. Beta-Adrenoceptor Antagonists (Beta-Blockers). http://cvpharmacology.com/cardioinhibitory/beta-blockers. Updated January 29, 2016. Accessed February 22, 2017.
  • Herold G. Internal Medicine. Cologne, Germany: Herold G; 2014.
last updated 05/17/2019
{{uncollapseSections(['hrbcSE', 'RrblSE', 'irbJSE', 'QrbuSE', 'jrb_SE', 'PrbWhE', 'pmcLg10'])}}