Beta blocker

{{Short description|Medication class with multiple uses}} {{Use mdy dates|date=November 2016}} {{Infobox drug class | Name = Beta blockers | Synonyms = Beta-blockers, β-blockers, beta-adrenergic blocking agents, beta antagonists, beta-adrenergic antagonists, beta-adrenoreceptor antagonists, beta adrenergic receptor antagonists, BB | Image = Propranolol structure.svg | ImageClass = skin-invert-image | Width = 225px | Alt = Propranolol | Use = Hypertension, arrhythmia, etc. | Caption = Skeletal formula of propranolol, the first clinically successful beta blocker. | Biological_target = beta receptors | ATC_prefix = C07 | MeshID = D000319 | Drugs.com = {{Drugs.com|drug-class|cardioselective-beta-blockers}} | Consumer_Reports = beta_blockers | medicinenet = beta_blockers | rxlist = 90349 }}

'''Beta blockers''', also spelled '''β-blockers''' and also sometimes known as '''β-adrenergic receptor antagonists''', are a class of medications predominantly used to manage abnormal heart rhythms (arrhythmia) and to protect the heart from a second heart attack after the first one (secondary prevention).<ref name="pmid10381708">{{cite journal | vauthors = Freemantle N, Cleland J, Young P, Mason J, Harrison J | title = beta Blockade after myocardial infarction: systematic review and meta regression analysis | journal = BMJ | volume = 318 | issue = 7200 | pages = 1730–1737 | date = June 1999 | pmid = 10381708 | pmc = 31101 | doi = 10.1136/bmj.318.7200.1730 }}</ref> They are also used widely to treat high blood pressure, though they are no longer the first choice for initial treatment of most people.<ref name="pmid24352797">{{cite journal | vauthors = James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC, Svetkey LP, Taler SJ, Townsend RR, Wright JT, Narva AS, Ortiz E | display-authors = 6 | title = 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8) | journal = JAMA | volume = 311 | issue = 5 | pages = 507–520 | date = February 2014 | pmid = 24352797 | doi = 10.1001/jama.2013.284427 | doi-access = free }}</ref> They can also be used to treat anxiety – a notable example being the situational use of propranolol to help dampen the physical symptoms of performance anxiety.<ref name="ArcherWilesKessler2025" /><ref name="SteenenvanWijkvanderHeijden2016" />

Beta blockers are competitive antagonists that block the receptor sites for the endogenous catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) on adrenergic beta receptors, of the sympathetic nervous system, which mediates the fight-or-flight response.<ref name="Frishman_2005">{{Cite book | chapter = Beta-Adrenergic Blockers | chapter-url = https://books.google.com/books?id=y3R1Vd3NHqcC&q=mode+of+action+of+beta+blockers&pg=PA152 | title = Current Cardiovascular Drugs | veditors = Frishman WH, Cheng-Lai A, Nawarskas J | year = 2005 | publisher = Current Science Group | access-date = 2010-09-07 | isbn = 978-1-57340-221-7 }}</ref>{{rp|152}}<ref name="Barranger_2006">{{Cite book | vauthors = Barranger K, Vivian E, Peterson AM | chapter = Hypertension | chapter-url = https://books.google.com/books?id=EaP1yJz4fkEC&pg=PA205 | title = Pharmacotherapeutics for advanced practice: a practical approach | veditors = Arcangelo VP, Peterson AM | year = 2006 | publisher = Lippincott Williams & Wilkins | page = 205 | access-date = 2010-09-07 | isbn = 978-0-7817-5784-3 }}</ref>

β-adrenergic receptors are found on cells of the heart muscles, smooth muscles, airways, arteries, kidneys, and other tissues that are part of the sympathetic nervous system and lead to stress responses, especially when they are stimulated by epinephrine (adrenaline). Beta blockers interfere with the binding to the receptor of epinephrine and other stress hormones and thereby weaken the effects of stress hormones.

Some beta blockers block activation of all types of β-adrenergic receptors and others are selective for one of the three known types of beta receptors, designated β₁, β₂, and β₃ receptors.<ref name="Frishman_2005" />{{rp|153}} β₁-Adrenergic receptors are located mainly in the heart and in the kidneys.<ref name="Barranger_2006" /> β₂-Adrenergic receptors are located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle.<ref name="Barranger_2006" /> β₃-Adrenergic receptors are located in fat cells.<ref name="pmid7609752">{{cite journal |display-authors=6 |vauthors=Clément K, Vaisse C, Manning BS, Basdevant A, Guy-Grand B, Ruiz J, Silver KD, Shuldiner AR, Froguel P, Strosberg AD |date=August 1995 |title=Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity |journal=The New England Journal of Medicine |volume=333 |issue=6 |pages=352–354 |doi=10.1056/NEJM199508103330605 |pmid=7609752 |doi-access=free}}</ref>

In 1964, James Black<ref name="telegraph">{{cite news|url=https://www.telegraph.co.uk/news/obituaries/medicine-obituaries/7507080/Sir-James-Black-OM.html|title=Sir James Black, OM|date=23 March 2010|newspaper=The Telegraph|access-date=25 March 2010|url-status=live|archive-url=https://web.archive.org/web/20100327031442/http://www.telegraph.co.uk/news/obituaries/medicine-obituaries/7507080/Sir-James-Black-OM.html|archive-date=March 27, 2010}}</ref> synthesized the first clinically significant beta blockers—propranolol and pronethalol; it revolutionized the medical management of angina pectoris<ref name="pmid10378820">{{cite journal | vauthors = van der Vring JA, Daniëls MC, Holwerda NJ, Withagen PJ, Schelling A, Cleophas TJ, Hendriks MG | title = Combination of calcium channel blockers and beta blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. The Netherlands Working Group on Cardiovascular Research (WCN) | journal = Angiology | volume = 50 | issue = 6 | pages = 447–454 | date = June 1999 | pmid = 10378820 | doi = 10.1177/000331979905000602 | s2cid = 21885509 }}</ref> and is considered by many to be one of the most important contributions to clinical medicine and pharmacology of the 20th century.<ref name="pmid9456487">{{cite journal | vauthors = Stapleton MP | title = Sir James Black and propranolol. The role of the basic sciences in the history of cardiovascular pharmacology | journal = Texas Heart Institute Journal | volume = 24 | issue = 4 | pages = 336–342 | year = 1997 | pmid = 9456487 | pmc = 325477 }}</ref>

For the treatment of primary hypertension (high blood pressure), meta-analyses of studies which mostly used atenolol have shown that although beta blockers are more effective than placebo in preventing stroke and total cardiovascular events, they are not as effective as diuretics, medications inhibiting the renin–angiotensin system (e.g., ACE inhibitors), or calcium channel blockers.<ref>{{cite journal | vauthors = Wiysonge CS, Bradley HA, Volmink J, Mayosi BM, Opie LH | title = Beta-blockers for hypertension | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | article-number = CD002003 | date = January 2017 | pmid = 28107561 | pmc = 5369873 | doi = 10.1002/14651858.CD002003.pub5 }}</ref><ref>{{Cite journal |last1=Reinhart |first1=Marcia |last2=Puil |first2=Lorri |last3=Salzwedel |first3=Douglas M. |last4=Wright |first4=James M. |date=2023-07-13 |title=First-line diuretics versus other classes of antihypertensive drugs for hypertension |journal=The Cochrane Database of Systematic Reviews |volume=2023 |issue=7 |article-number=CD008161 |doi=10.1002/14651858.CD008161.pub3 |issn=1469-493X |pmc=10339786 |pmid=37439548}}</ref><ref>{{cite journal | vauthors = Zhu J, Chen N, Zhou M, Guo J, Zhu C, Zhou J, Ma M, He L | display-authors = 6 | title = Calcium channel blockers versus other classes of drugs for hypertension | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | article-number = CD003654 | date = January 2022 | pmid = 35000192 | pmc = 8742884 | doi = 10.1002/14651858.CD003654.pub6 }}</ref><ref>{{cite journal | vauthors = Wiysonge CS, Bradley HA, Volmink J, Mayosi BM, Opie LH | title = Beta-blockers for hypertension | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | article-number = CD002003 | date = January 2017 | pmid = 28107561 | pmc = 5369873 | doi = 10.1002/14651858.cd002003.pub5 }}</ref>

==Medical uses== Beta blockers are utilized in the treatment of various conditions related to the heart and vascular system, as well as several other medical conditions. Common heart-related conditions for which beta blockers are well-established include angina pectoris, acute coronary syndromes, hypertension, and arrhythmias such as atrial fibrillation and heart failure. They are also used in the management of other heart diseases, such as hypertrophic obstructive cardiomyopathy, mitral valve stenosis or prolapse, and dissecting aneurysm. Additionally, beta blockers find applications in vascular surgery, the treatment of anxiety states, cases of thyrotoxicosis, glaucoma, migraines, and esophageal varices.<ref name="Opie 2009 p.">{{cite book | vauthors = Opie LH | title=Drugs for the Heart | publisher=Saunders | publication-place=Philadelphia | date=2009 | isbn=978-1-4160-6158-8 | pages=6–18}}</ref>

===Congestive heart failure=== Although beta blockers were once contraindicated in congestive heart failure, as they have the potential to worsen the condition due to their effect of decreasing cardiac contractility, studies in the late 1990s showed their efficacy at reducing morbidity and mortality.<ref name="pmid10714728">{{cite journal | vauthors = Hjalmarson A, Goldstein S, Fagerberg B, Wedel H, Waagstein F, Kjekshus J, Wikstrand J, El Allaf D, Vítovec J, Aldershvile J, Halinen M, Dietz R, Neuhaus KL, Jánosi A, Thorgeirsson G, Dunselman PH, Gullestad L, Kuch J, Herlitz J, Rickenbacher P, Ball S, Gottlieb S, Deedwania P | display-authors = 6 | title = Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group | journal = JAMA | volume = 283 | issue = 10 | pages = 1295–1302 | date = March 2000 | pmid = 10714728 | doi = 10.1001/jama.283.10.1295 | doi-access = free }}</ref><ref name="pmid11835035">{{cite journal | vauthors = Leizorovicz A, Lechat P, Cucherat M, Bugnard F | title = Bisoprolol for the treatment of chronic heart failure: a meta-analysis on individual data of two placebo-controlled studies—CIBIS and CIBIS II. Cardiac Insufficiency Bisoprolol Study | journal = American Heart Journal | volume = 143 | issue = 2 | pages = 301–307 | date = February 2002 | pmid = 11835035 | doi = 10.1067/mhj.2002.120768 }}</ref><ref name="pmid12390947">{{cite journal | vauthors = Packer M, Fowler MB, Roecker EB, Coats AJ, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Staiger C, Holcslaw TL, Amann-Zalan I, DeMets DL | display-authors = 6 | title = Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study | journal = Circulation | volume = 106 | issue = 17 | pages = 2194–2199 | date = October 2002 | pmid = 12390947 | doi = 10.1161/01.CIR.0000035653.72855.BF | doi-access = free }}</ref> Bisoprolol, carvedilol, and sustained-release metoprolol are specifically indicated as adjuncts to standard ACE inhibitor and diuretic therapy in congestive heart failure, although at doses typically much lower than those indicated for other conditions. Beta blockers are only indicated in cases of compensated, stable congestive heart failure; in cases of acute decompensated heart failure, beta blockers will cause a further decrease in ejection fraction, worsening the patient's current symptoms.{{citation needed|date=September 2023}}

Beta blockers are known primarily for their reductive effect on heart rate, although this is not the only mechanism of action of importance in congestive heart failure.<ref>{{Cite journal | vauthors = Fletcher P |title=Beta blockers in heart failure |journal=Australian Prescriber |year=2000 |volume=23 |issue=6 |pages=120–123 |url=https://www.nps.org.au/australian-prescriber/articles/beta-blockers-in-heart-failure |language=en |doi=10.18773/austprescr.2000.138|doi-access=free }}</ref> Beta blockers, in addition to their sympatholytic β₁ activity in the heart, influence the renin–angiotensin system at the kidneys. Beta blockers cause a decrease in renin secretion, which in turn reduces the heart oxygen demand by lowering the extracellular volume and increasing the oxygen-carrying capacity of the blood. Heart failure characteristically involves increased catecholamine activity on the heart, which is responsible for several deleterious effects, including increased oxygen demand, propagation of inflammatory mediators, and abnormal cardiac tissue remodeling, all of which decrease the efficiency of cardiac contraction and contribute to the low ejection fraction.<ref>{{cite web|title = Use of beta-blockers and ivabradine in heart failure with reduced ejection fraction|url = http://www.uptodate.com/contents/use-of-beta-blockers-and-ivabradine-in-heart-failure-with-reduced-ejection-fraction|website = www.uptodate.com|access-date = 2015-12-11|url-status = live|archive-url = https://web.archive.org/web/20151222081646/http://www.uptodate.com/contents/use-of-beta-blockers-and-ivabradine-in-heart-failure-with-reduced-ejection-fraction|archive-date = December 22, 2015}}</ref> Beta blockers counter this inappropriately high sympathetic activity, eventually leading to an improved ejection fraction, despite an initial reduction in ejection fraction.{{citation needed|date=October 2023}}

Trials have shown beta blockers reduce the absolute risk of death by 4.5% over a 13-month period. In addition to reducing the risk of mortality, the numbers of hospital visits and hospitalizations were also reduced in the trials.<ref name="pmid12173717">{{cite journal | vauthors = Pritchett AM, Redfield MM | title = Beta-blockers: new standard therapy for heart failure | journal = Mayo Clinic Proceedings | volume = 77 | issue = 8 | pages = 839–845; quiz 845–46 | date = August 2002 | pmid = 12173717 | doi = 10.4065/77.8.839 | doi-access = free }}</ref> A 2020 Cochrane review found minimal evidence to support the use of beta blockers in congestive heart failure in children, however did identify that from the data available, that they may be of benefit.<ref>{{cite journal | vauthors = Alabed S, Sabouni A, Al Dakhoul S, Bdaiwi Y | title = Beta-blockers for congestive heart failure in children | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 7 | article-number = CD007037 | date = July 2020 | pmid = 32700759 | pmc = 7389334 | doi = 10.1002/14651858.CD007037.pub4 | collaboration = Cochrane Heart Group }}</ref>

Therapeutic administration of beta blockers for congestive heart failure ought to begin at very low doses ({{frac|1|8}} of target) with a gradual escalation of the dose. The heart of the patient must adjust to decreasing stimulation by catecholamines and find a new equilibrium at a lower adrenergic drive.<ref>{{Cite book|title=Goodman & Gilman's: The Pharmacological Basic of Therapeutics|publisher=McGraw-Hill|year=2018|isbn=978-1-259-58473-2}}</ref>

====Acute myocardial infarction==== Beta blockers are indicated for the treatment of acute myocardial infarctions. During a myocardial infarction, systemic stress causes an increase in circulating catecholamines.<ref name="Safi_2019">{{cite journal | vauthors = Safi S, Sethi NJ, Nielsen EE, Feinberg J, Jakobsen JC, Gluud C | title = Beta-blockers for suspected or diagnosed acute myocardial infarction | journal = The Cochrane Database of Systematic Reviews | volume = 12 | issue = 12 | article-number = CD012484 | date = December 2019 | pmid = 31845756 | pmc = 6915833 | doi = 10.1002/14651858.CD012484.pub2 | collaboration = Cochrane Heart Group }}</ref><ref name="Farzam_2023">{{cite book | vauthors = Farzam K, Jan A | chapter = Beta Blockers |date=2023 |chapter-url= https://www.ncbi.nlm.nih.gov/books/NBK532906/ | title = StatPearls |access-date=2023-10-31 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30422501 }}</ref> This results an increase in heart rate and blood pressure, therefore increasing myocardial oxygen demand.<ref name="Farzam_2023" /><ref name="Safi_2019" /> Beta blockers competitively inhibit catecholamines acting on the β₁-adrenergic receptors, thus reducing these detrimental effects and resulting in reduced myocardial oxygen consumption and demand.<ref name="Safi_2019" />

A 2019 Cochrane review compared beta blockers with placebo or no intervention, it found that beta blockers probably reduced the short-term risk of reinfarction and the long-term risk of all-cause mortality and cardiovascular mortality.<ref name="Safi_2019" /> The review identified that beta blockers likely had little to no impact on short-term all-cause mortality and cardiovascular mortality.<ref name="Safi_2019" />

===Hypertension=== Beta blockers are widely used for the treatment of hypertension.<ref>{{cite book | vauthors = Iqbal AH, Jamal SF | chapter = Essential Hypertension |date=2023 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK539859/ | title = StatPearls |access-date=2023-10-31 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30969681 }}</ref>

A 2014 Cochrane review found that in individuals with mild-to-moderate hypertension, non-selective beta blockers led to a reduction of -10/-7mmHg (systolic/diastolic) without increased rates of adverse events.<ref name="Wong_2014">{{cite journal | vauthors = Wong GW, Wright JM | title = Blood pressure lowering efficacy of nonselective beta-blockers for primary hypertension | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 2 | article-number = CD007452 | date = February 2014 | pmid = 24585007 | pmc = 10603273 | doi = 10.1002/14651858.CD007452.pub2 | collaboration = Cochrane Hypertension Group }}</ref> At higher doses, it was found to increase the rate of adverse effects such as a reduction in heart rate, without a corresponding reduction in blood pressure.<ref name="Wong_2014" />

A 2017 Cochrane review on the use of beta blockers in hypertension found a modest reduction in cardiovascular disease but little to no change in mortality.<ref name="Wiysonge_2017">{{cite journal | vauthors = Wiysonge CS, Bradley HA, Volmink J, Mayosi BM, Opie LH | title = Beta-blockers for hypertension | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | article-number = CD002003 | date = January 2017 | pmid = 28107561 | pmc = 5369873 | doi = 10.1002/14651858.CD002003.pub5 | collaboration = Cochrane Hypertension Group }}.</ref> It suggested that the effects of beta blockers are inferior to other anti-hypertensive medications.<ref name="Wiysonge_2017" />

===Anxiety=== {{See also|Propranolol#Anxiety and related disorders}}

Beta blockers are used to treat anxiety disorders including performance anxiety, panic disorder, generalized anxiety disorder, and specific phobias.<ref name="BoyceBalloneCerta2021" /> They are not formally approved for anxiolytic use by the United States Food and Drug Administration.<ref name="pmid16957148">{{cite journal | vauthors = Schneier FR | title = Clinical practice. Social anxiety disorder | journal = The New England Journal of Medicine | volume = 355 | issue = 10 | pages = 1029–1036 | date = September 2006 | pmid = 16957148 | doi = 10.1056/NEJMcp060145 }}</ref> However, many clinical studies have found beta blockers to be effective for anxiety, though the exact mechanism of action is unclear.<ref name="BoyceBalloneCerta2021" /><ref name="Tyrer1992">{{cite journal | vauthors = Tyrer P | title = Anxiolytics not acting at the benzodiazepine receptor: beta blockers | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 16 | issue = 1 | pages = 17–26 | date = January 1992 | pmid = 1348368 | doi = 10.1016/0278-5846(92)90004-X | s2cid = 24742562 }}</ref> A 2025 systematic review and meta-analysis found widespread prescription of beta blockers, namely propranolol, for the treatment of anxiety disorders, but found no evidence of a beneficial effect relative to placebo or benzodiazepines in people with social phobia or panic disorder.<ref name="ArcherWilesKessler2025">{{cite journal | vauthors = Archer C, Wiles N, Kessler D, Turner K, Caldwell DM | title = Beta-blockers for the treatment of anxiety disorders: A systematic review and meta-analysis | journal = J Affect Disord | volume = 368 | issue = | pages = 90–99 | date = January 2025 | pmid = 39271062 | doi = 10.1016/j.jad.2024.09.068 | url = | doi-access = free }}</ref> However, the quality of evidence, including both numbers of studies and patients as well as quality and risk of bias of those studies, was limited.<ref name="ArcherWilesKessler2025" /> Findings were similar in a previous 2016 systematic review and meta-analysis.<ref name="SteenenvanWijkvanderHeijden2016">{{cite journal | vauthors = Steenen SA, van Wijk AJ, van der Heijden GJ, van Westrhenen R, de Lange J, de Jongh A | title = Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis | journal = J Psychopharmacol | volume = 30 | issue = 2 | pages = 128–139 | date = February 2016 | pmid = 26487439 | pmc = 4724794 | doi = 10.1177/0269881115612236 | url = }}</ref> Beta blockers that have been used to treat anxiety include propranolol, atenolol, pindolol, nadolol, betaxolol, and oxprenolol.<ref name="BoyceBalloneCerta2021" /><ref name="ArcherWilesKessler2025" />

It is thought that beta blockers do not directly treat psychological symptoms of anxiety, but can help control physical symptoms such as palpitations, and this may interfere with a positive feedback loop to indirectly reduce psychological anxiety.<ref name="ArcherWilesKessler2025" /> Highly lipophilic beta blockers like propranolol, which are centrally permeable, and highly hydrophilic beta blockers like atenolol, which are peripherally selective, appear to have similar benefits on performance anxiety, suggesting that their anxiolytic effects are mediated peripherally.<ref name="BoyceBalloneCerta2021">{{cite journal | vauthors = Boyce TG, Ballone NT, Certa KM, Becker MA | title = The Use of β-Adrenergic Receptor Antagonists in Psychiatry: A Review | journal = J Acad Consult Liaison Psychiatry | volume = 62 | issue = 4 | pages = 404–412 | date = 2021 | pmid = 34210401 | doi = 10.1016/j.jaclp.2020.12.009 | url = }}</ref> However, there has been little in the way of direct comparisons between different types of beta blockers.<ref name="BoyceBalloneCerta2021" /> In any case, the physiological symptoms of the fight-or-flight response (pounding heart, cold/clammy hands, increased respiration, sweating, etc.) are significantly reduced, thus enabling anxious individuals to concentrate on the task at hand.{{citation needed|date=October 2023}} Although it is thought that beta blockers may act via peripheral mechanisms, there are also findings from preclinical research of central β-adrenergic receptors mediating anxiety.<ref name="SorberaDulsatRosa2011">{{cite journal | last1=Sorbera | first1=L.A. | last2=Dulsat | first2=C. | last3=Rosa | first3=E. | title=Therapeutic targets for anxiety disorders | journal=Drugs of the Future | volume=36 | issue=6 | date=2011 | issn=0377-8282 | doi=10.1358/dof.2011.036.06.1653891 | page=473 | url=http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=1653891&p_IsPs=N | access-date=22 June 2025}}</ref><ref name="FuLiZhao2008">{{cite journal | vauthors = Fu A, Li X, Zhao B | title = Role of beta1-adrenoceptor in the basolateral amygdala of rats with anxiety-like behavior | journal = Brain Res | volume = 1211 | issue = | pages = 85–92 | date = May 2008 | pmid = 18423428 | doi = 10.1016/j.brainres.2008.03.013 | url = }}</ref><ref name="McCallSiudaBhatti2017">{{cite journal | vauthors = McCall JG, Siuda ER, Bhatti DL, Lawson LA, McElligott ZA, Stuber GD, Bruchas MR | title = Locus coeruleus to basolateral amygdala noradrenergic projections promote anxiety-like behavior | journal = eLife | volume = 6 | issue = | date = July 2017 | article-number = e18247 | pmid = 28708061 | pmc = 5550275 | doi = 10.7554/eLife.18247 | doi-access = free | url = }}</ref><ref name="LeiLamLi2022">{{cite journal | vauthors = Lei Z, Lam Y, Li C, Fu Z, Ramkrishnan AS, Liu S, Li Y | title = β2-Adrenoceptors in the Medial Prefrontal Cortex Excitatory Neurons Regulate Anxiety-like Behavior in Mice | journal = Int J Mol Sci | volume = 23 | issue = 10 | date = May 2022 | page = 5578 | pmid = 35628393 | pmc = 9145949 | doi = 10.3390/ijms23105578 | doi-access = free | url = }}</ref>

Musicians, public speakers, actors, models and adult performers, athletes, and professional dancers have been known to use beta blockers to avoid performance anxiety, stage fright, and tremor during both auditions and public performances. The application to stage fright was first recognized in ''The Lancet'' in 1976, and by 1987, a survey conducted by the International Conference of Symphony Orchestra Musicians, representing the 51 largest orchestras in the United States, revealed 27% of its musicians had used beta blockers and 70% obtained them from friends, not physicians.<ref name="nyt2004">{{cite news | vauthors = Tindall B |url=https://www.nytimes.com/2004/10/17/arts/music/better-playing-through-chemistry.html |title=Better Playing Through Chemistry |archive-url=https://web.archive.org/web/20150826190339/https://www.nytimes.com/2004/10/17/arts/music/better-playing-through-chemistry.html |archive-date=August 26, 2015 |work=The New York Times |date=October 17, 2004}}</ref> Beta blockers are inexpensive, said to be relatively safe, and on one hand, seem to improve musicians' performances on a technical level, while some, such as Barry Green, the author of "The Inner Game of Music" and Don Greene, a former Olympic diving coach who teaches Juilliard students to overcome their stage fright naturally, say the performances may be perceived as "soulless and inauthentic".<ref name="nyt2004"/> Although beta blockers have been studied and found to improve performance anxiety in musicians, no data exist on treatment of performance anxiety in dancers.<ref name="Harris2001">{{cite journal | last=Harris | first=David Alan | title=Using Beta-blockers to Control Stage Fright: A Dancer's Dilemma | journal=Medical Problems of Performing Artists | volume=16 | issue=2 | date=1 June 2001 | issn=0885-1158 | doi=10.21091/mppa.2001.2012 | pages=72–76 | url=https://www.ingentaconnect.com/content/10.21091/mppa.2001.2012 | access-date=10 July 2025| url-access=subscription }}</ref>

===Surgery=== Low certainty evidence indicates that the use of beta blockers around the time of cardiac surgery may decrease the risk of heart dysrhythmias and atrial fibrillation.<ref>{{cite journal | vauthors = Blessberger H, Lewis SR, Pritchard MW, Fawcett LJ, Domanovits H, Schlager O, Wildner B, Kammler J, Steinwender C | display-authors = 6 | title = Perioperative beta-blockers for preventing surgery-related mortality and morbidity in adults undergoing cardiac surgery | journal = The Cochrane Database of Systematic Reviews | volume = 9 | issue = 9 | article-number = CD013435 | date = September 2019 | pmid = 31544227 | pmc = 6755267 | doi = 10.1002/14651858.CD013435 }}</ref> Starting them around the time of other types of surgery, however, may worsen outcomes. For non-cardiac surgery, the use of beta blockers to prevent adverse effects may reduce the risk of atrial fibrillation and myocardial infarctions (very low certainty evidence), however, there is moderate certainty evidence that this approach may increase the risk of hypotension.<ref name="Blessberger_2019">{{cite journal | vauthors = Blessberger H, Lewis SR, Pritchard MW, Fawcett LJ, Domanovits H, Schlager O, Wildner B, Kammler J, Steinwender C | display-authors = 6 | title = Perioperative beta-blockers for preventing surgery-related mortality and morbidity in adults undergoing non-cardiac surgery | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 9 | article-number = CD013438 | date = September 2019 | pmid = 31556094 | pmc = 6761481 | doi = 10.1002/14651858.CD013438 }}</ref> Low-certainty evidence suggests that beta blockers used perioperatively in non-cardiac surgeries may increase the risk of bradycardia.<ref name="Blessberger_2019" />

===Other uses=== Beta blockers are frequently used to treat akathisia and may be considered a first-line therapy for this indication.<ref name="BoyceBalloneCerta2021" /> Akathisia is a type of extrapyramidal symptom often associated with antipsychotics used to treat psychotic disorders like schizophrenia.<ref name="BoyceBalloneCerta2021" /> Propranolol is the most-studied beta blocker for treatment of akathisia, whereas very limited data suggest that metoprolol may provide comparable benefits, and nadolol, which is peripherally selective, does not appear to be effective.<ref name="BoyceBalloneCerta2021" />

A 2014 Cochrane review investigated the use of beta blockers in the maintenance of chronic type B thoracic aortic aneurysm in comparison to other anti hypertensive medications.<ref name="Chan_2014">{{cite journal | vauthors = Chan KK, Lai P, Wright JM | title = First-line beta-blockers versus other antihypertensive medications for chronic type B aortic dissection | journal = The Cochrane Database of Systematic Reviews | issue = 2 | article-number = CD010426 | date = February 2014 | volume = 2014 | pmid = 24570114 | doi = 10.1002/14651858.CD010426.pub2 | collaboration = Cochrane Hypertension Group | pmc = 10726980 }}</ref> The review found no suitable evidence to support the current guidelines recommending its use.<ref name="Chan_2014" />

A 2017 Cochrane review on the use of beta blockers to prevent aortic dissections in people with Marfan syndrome was unable to draw definitive conclusions due to lack of evidence.<ref>{{cite journal | vauthors = Koo HK, Lawrence KA, Musini VM | title = Beta-blockers for preventing aortic dissection in Marfan syndrome | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 11 | article-number = CD011103 | date = November 2017 | pmid = 29110304 | pmc = 6486285 | doi = 10.1002/14651858.CD011103.pub2 | collaboration = Cochrane Heart Group }}</ref>

Adrenergic antagonists are mostly used for cardiovascular disease. The adrenergic antagonists are widely used for lowering blood pressure and relieving hypertension.<ref>[http://hyper.ahajournals.org/content/hypertensionaha/early/2015/11/30/HYPERTENSIONAHA.115.06467.full.pdf Effects of β-Blockers With and Without Vasodilating Properties on Central Blood Pressure], Pucci, G., Ranalli, M. G., Battista, F., & Schillaci, G. (2015). Effects of β-Blockers With and Without Vasodilating Properties on Central Blood Pressure. Hypertension, HYPERTENSIONAHA-115.</ref> These antagonists have been proven to relieve the pain caused by myocardial infarction, and also the infarction size, which correlates with heart rate.<ref>{{cite book|author=Cruickshank|title=The Modern Role of Beta-Blockers in Cardiovascular Medicine|url=https://books.google.com/books?id=QH0kZ7jjfOQC|year=2010|publisher=PMPH-USA|location=Shelton, Connecticut|isbn=978-1-60795-108-7|first=John Malcolm}}</ref>

Beta blockers are used to treat acute cardiovascular toxicity (e.g. in overdose) caused by sympathomimetics, for instance caused by amphetamine, methamphetamine, cocaine, ephedrine, and other drugs.<ref name="RichardsAlbertsonDerlet2015">{{cite journal | vauthors = Richards JR, Albertson TE, Derlet RW, Lange RA, Olson KR, Horowitz BZ | title = Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review | journal = Drug Alcohol Depend | volume = 150 | issue = | pages = 1–13 | date = May 2015 | pmid = 25724076 | doi = 10.1016/j.drugalcdep.2015.01.040 | url = }}</ref> Combined α₁ and beta blockers like labetalol and carvedilol may be more favorable for such purposes due to the possibility of "unopposed α-stimulation" with selective beta blockers like propranolol and atenolol.<ref name="RichardsAlbertsonDerlet2015" /><ref name="RichardsHollanderRamoska2017">{{cite journal | vauthors = Richards JR, Hollander JE, Ramoska EA, Fareed FN, Sand IC, Izquierdo Gómez MM, Lange RA | title = β-Blockers, Cocaine, and the Unopposed α-Stimulation Phenomenon | journal = J Cardiovasc Pharmacol Ther | volume = 22 | issue = 3 | pages = 239–249 | date = May 2017 | pmid = 28399647 | doi = 10.1177/1074248416681644 | url = }}</ref>

===Indication differences=== * Agents specifically labeled for cardiac arrhythmia ** Esmolol,<ref name="Esmolol package insert">{{Cite web |title=DailyMed – BREVIBLOC- esmolol hydrochloride injection |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=595cc3d5-1306-4828-aefa-5595219ffd62 |access-date=2022-11-09 | work = DailyMed | publisher = U.S. National Library of Medicine }}</ref> sotalol,<ref>{{Cite web |title=DailyMed – BETAPACE- sotalol hydrochloride tablet BETAPACE AF- sotalol hydrochloride tablet |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=afce2787-8899-4098-87c8-f1e8dd19e6dd |access-date=2022-11-09 | work = DailyMed | publisher = U.S. National Library of Medicine }}</ref> landiolol (Japan)<ref>{{cite web|title=Announcement of Approval of Additional Indications for Onoact 50 for Injection, Short-Acting Selective ß1 Blocker|url=http://www.evaluategroup.com/Universal/View.aspx?type=Story&id=103244|website=www.evaluategroup.com|publisher=Evaluate Ltd.|access-date=18 October 2017|archive-date=August 28, 2021|archive-url=https://web.archive.org/web/20210828002945/https://www.evaluate.com/}}</ref> * Agents specifically labeled for congestive heart failure<ref name="PharmLetter BB Table" /> ** Bisoprolol, carvedilol, sustained-release metoprolol * Agents specifically labeled for glaucoma ** Betaxolol,<ref name="Aronson2008" /> carteolol,<ref name="Aronson2008" /> levobunolol,<ref name="Aronson2008" /> timolol,<ref name="Aronson2008" /> metipranolol<ref>{{cite web|title=Metiprapanol – metipranolol solution/ drops|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=699ce415-0798-4244-b5ec-bcdb383b50b3| work = DailyMed | publisher = U.S. National Library of Medicine – NIH|access-date=18 October 2017|url-status=live|archive-url=https://web.archive.org/web/20171018133648/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=699ce415-0798-4244-b5ec-bcdb383b50b3|archive-date=October 18, 2017}}</ref> * Agents specifically labeled for myocardial infarction<ref name="PharmLetter BB Table" /> ** Atenolol, metoprolol (immediate release), propranolol (immediate release), timolol, carvedilol (after left ventricular dysfunction), bisoprolol (preventive treatment before and primary treatment after heart attacks) * Agents specifically labeled for migraine prophylaxis<ref name="PL Chart Migraine">{{cite web|title=Drugs to Prevent Migraine in Adults|url=https://pharmacist.therapeuticresearch.com/Content/Segments/PRL/2012/Jul/Drugs-to-Prevent-Migraine-in-Adults-4513|website=pharmacist.therapeuticresearch.com|publisher=Therapeutic Research Center|access-date=30 April 2017|url-status=live|archive-url=https://web.archive.org/web/20171018133956/https://pharmacist.therapeuticresearch.com/Content/Segments/PRL/2012/Jul/Drugs-to-Prevent-Migraine-in-Adults-4513|archive-date=October 18, 2017}}</ref> ** Timolol, propranolol

Propranolol is the only agent indicated for the control of tremor, portal hypertension, and esophageal variceal bleeding, and used in conjunction with α-blocker therapy in phaeochromocytoma.<ref name="Rossi"/>

==Contraindications== Contraindications of beta blockers include the following:<ref name="Wyeth Propranolol" /><ref name="NaikFreudenberger2007">{{cite journal | vauthors = Naik SD, Freudenberger RS | title = Beta-blocker contraindications: are there patients or situations where use is inappropriate? | journal = Curr Heart Fail Rep | volume = 4 | issue = 2 | pages = 93–98 | date = June 2007 | pmid = 17521501 | doi = 10.1007/s11897-007-0006-5 | url = }}</ref><ref name="KoraćevićStojanovićKostić2021">{{cite journal | vauthors = Koraćević G, Stojanović M, Kostić T, Lović D, Zdravković M, Koraćević M, Pavlović D, Mićić S | title = Contraindications Differ Widely Among Beta Blockers and Ought to be Cited for an Individual Drug, Not for the Entire Class | journal = Curr Pharm Des | volume = 27 | issue = 40 | pages = 4125–4132 | date = 2021 | pmid = 34279195 | doi = 10.2174/1381612827666210716162130 | url = }}</ref>

{{div col|colwidth=30em}}Absolute contraindications:

* Bradycardia<ref name="Wyeth Propranolol" /> * Hypotension * Hypersensitivity to beta blockers<ref name="Wyeth Propranolol" /> * Cardiogenic shock<ref name="Wyeth Propranolol" /> * Second or third degree AV block

Relative contraindications, or contraindications specific to certain beta-blockers:

* Long QT syndrome: sotalol is contraindicated * History of torsades de pointes: sotalol is contraindicated

Cautions:

* Abrupt discontinuations * Acute bronchospasm<ref name="Wyeth Propranolol">{{Cite web| author = Wyeth |title=Propranolol hydrochloride |url= https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/016418s078lbl.pdf |access-date=2020-09-03 }}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref> * Acute heart failure<ref name="Wyeth Propranolol" /> * Asthma: see below * Bronchitis<ref name="Wyeth Propranolol" /> * Cerebrovascular disease * Chronic obstructive pulmonary disease (COPD) * Emphysema<ref name="Wyeth Propranolol" /> * Kidney failure * Hepatic disease * Myopathy * Pheochromocytoma * Psoriasis * Raynaud phenomenon * Stroke * Vasospastic angina * Wolff–Parkinson–White syndrome<ref name="Wyeth Propranolol" />{{div col end}}

Contrast agents are not contraindicated in those receiving beta blockers.<ref>{{cite journal | vauthors = Boehm I, Morelli J, Nairz K, Silva Hasembank Keller P, Heverhagen JT | title = Beta blockers and intravenous roentgen contrast materials: Which risks do exist? | journal = European Journal of Internal Medicine | volume = 35 | pages = e17–e18 | date = November 2016 | pmid = 27531627 | doi = 10.1016/j.ejim.2016.08.003 }}</ref>

===Asthma=== The 2007 National Heart, Lung, and Blood Institute (NHLBI) asthma guidelines recommend against the use of non-selective beta blockers in asthmatics, while allowing for the use of cardio selective beta blockers.<ref name="NHLBI Asthma 07">{{cite journal | title = Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma–Summary Report 2007 | journal = The Journal of Allergy and Clinical Immunology | volume = 120 | issue = 5 | pages = S94–S138 | year = 2007 | url = https://www.jacionline.org/article/S0091-6749(07)01823-4/fulltext | doi = 10.1016/j.jaci.2007.09.029 | access-date = 2017-12-09 | archive-url = https://web.archive.org/web/20210828002833/https://www.jacionline.org/article/S0091-6749%2807%2901823-4/fulltext | doi-access = free | archive-date = August 28, 2021 | url-access = subscription }}</ref>{{rp|182}}

Cardio selective beta blocker (β₁ blockers) can be prescribed at the least possible dose to those with mild to moderate respiratory symptoms.<ref name="Morales Jackson Lipworth Donnan 2014 pp. 779–786"/><ref name="Salpeter Ormiston Salpeter p=715">{{cite journal | vauthors = Salpeter SR, Ormiston TM, Salpeter EE | title = Cardioselective beta-blockers in patients with reactive airway disease: a meta-analysis | journal = Annals of Internal Medicine | volume = 137 | issue = 9 | pages = 715–725 | date = November 2002 | pmid = 12416945 | doi = 10.7326/0003-4819-137-9-200211050-00035 | publisher = American College of Physicians | doi-access = free }}</ref> β2-agonists can somewhat mitigate β-blocker-induced bronchospasm where it exerts greater efficacy on reversing ''selective'' β-blocker-induced bronchospasm than the ''nonselective'' β-blocker-induced worsening asthma and/or COPD.<ref name="Morales Jackson Lipworth Donnan 2014 pp. 779–786">{{cite journal | vauthors = Morales DR, Jackson C, Lipworth BJ, Donnan PT, Guthrie B | title = Adverse respiratory effect of acute β-blocker exposure in asthma: a systematic review and meta-analysis of randomized controlled trials | journal = Chest | volume = 145 | issue = 4 | pages = 779–786 | date = April 2014 | pmid = 24202435 | doi = 10.1378/chest.13-1235 | publisher = Elsevier BV }}</ref>

===Diabetes mellitus=== Epinephrine signals early warning of the upcoming hypoglycemia.<ref name="Sprague Arbeláez 2011 pp. 463–475">{{cite journal | vauthors = Sprague JE, Arbeláez AM | title = Glucose counterregulatory responses to hypoglycemia | journal = Pediatric Endocrinology Reviews | volume = 9 | issue = 1 | pages = 463–475 | date = September 2011 | pmid = 22783644 | pmc = 3755377 }}</ref>

Beta blockers' inhibition on epinephrine's effect can somewhat exacerbate hypoglycemia by interfering with glycogenolysis and mask signs of hypoglycemia such as tachycardia, palpitations, diaphoresis, and tremors. Diligent blood glucose level monitoring is necessary for a patient with diabetes mellitus on beta blockers.

===Hyperthyroidism=== Abrupt withdrawal can result in a thyroid storm.<ref name="Wyeth Propranolol" />

===Bradycardia or AV block=== Unless a pacemaker is present, beta blockers can severely depress conduction in the AV node, resulting in a reduction of heart rate and cardiac output. One should be very cautious with the use of beta blockers in tachycardia patients with Wolff-Parkinson-White Syndrome, as it can result in life-threatening arrhythmia in certain patients. By slowing the conduction through the AV node, preferential conduction through the accessory pathway is favored. If the patient happens to develop atrial flutter, this could lead to a 1:1 conduction with very fast ventricular rate, or worse, ventricular fibrillation in the case of atrial fibrillation.{{citation needed|date=October 2023}}

==Adverse effects== Adverse drug reactions <!-- (ADRs) --> associated with the use of beta blockers include nausea, diarrhea, bronchospasm, dyspnea, cold extremities, exacerbation of Raynaud's syndrome, bradycardia, hypotension, heart failure, heart block, fatigue, dizziness, alopecia (hair loss), abnormal vision, hallucinations, insomnia, nightmares, sexual dysfunction, erectile dysfunction, alteration of glucose and lipid metabolism.{{Medical citation needed|date=June 2023}} Mixed α₁/β-antagonist therapy is also commonly associated with orthostatic hypotension.

Carvedilol therapy is commonly associated with edema.<ref name="Rossi"/>{{Page needed|date=June 2023}} Due to the high penetration across the blood–brain barrier, lipophilic beta blockers, such as propranolol and metoprolol, are more likely than other less lipophilic beta blockers to cause sleep disturbances, such as insomnia, vivid dreams and nightmares.<ref name="pmid21180298">{{cite journal | vauthors = Cruickshank JM | title = Beta-blockers and heart failure | journal = Indian Heart Journal | volume = 62 | issue = 2 | pages = 101–110 | year = 2010 | pmid = 21180298 }}</ref>

Adverse effects associated with β₂-adrenergic receptor antagonist activity (bronchospasm, peripheral vasoconstriction, alteration of glucose and lipid metabolism) are less common with β₁-selective (often termed "cardioselective") agents, but receptor selectivity diminishes at higher doses. Beta blockade, especially of the beta-1 receptor at the macula densa, inhibits renin release, thus decreasing the release of aldosterone. This causes hyponatremia and hyperkalemia.{{citation needed|date=October 2023}}

Hypoglycemia can occur with beta blockade because β₂-adrenoceptors normally stimulate glycogen breakdown (glycogenolysis) in the liver and pancreatic release of the hormone glucagon, which work together to increase plasma glucose. Therefore, blocking β₂-adrenoceptors lowers plasma glucose. β₁-blockers have fewer metabolic side effects in diabetic patients; however, the fast heart rate that serves as a warning sign for insulin-induced low blood sugar may be masked, resulting in hypoglycemia unawareness. This is termed beta blocker-induced hypoglycemia unawareness. Therefore, beta blockers are to be used cautiously in diabetics.<ref>Beta-Adrenoceptor Antagonists (Beta-Blockers); {{cite web |url=http://www.cvpharmacology.com/cardioinhibitory/beta-blockers.htm | work = CV Pharmacology | title = Beta-Adrenoceptor Antagonists (Beta-Blockers) |access-date=2011-08-08 |url-status=live |archive-url=https://web.archive.org/web/20110808021353/http://www.cvpharmacology.com/cardioinhibitory/beta-blockers.htm |archive-date=August 8, 2011 }}</ref>

A 2007 study revealed diuretics and beta blockers used for hypertension increase a patient's risk of developing diabetes mellitus, while ACE inhibitors and angiotensin II receptor antagonists (angiotensin receptor blockers) actually decrease the risk of diabetes.<ref name="pmid17240286">{{cite journal | vauthors = Elliott WJ, Meyer PM | title = Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis | journal = Lancet | volume = 369 | issue = 9557 | pages = 201–207 | date = January 2007 | pmid = 17240286 | doi = 10.1016/S0140-6736(07)60108-1 | s2cid = 37044384 }}</ref> Clinical guidelines in Great Britain, but not in the United States, call for avoiding diuretics and beta blockers as first-line treatment of hypertension due to the risk of diabetes.<ref name="pmid16809680">{{cite journal | vauthors = Mayor S | title = NICE removes beta blockers as first line treatment for hypertension | journal = BMJ | volume = 333 | issue = 7557 | page = 8 | date = July 2006 | pmid = 16809680 | pmc = 1488775 | doi = 10.1136/bmj.333.7557.8-a }}</ref>

Beta blockers must not be used in the treatment of selective alpha-adrenergic agonist overdose. The blockade of only beta receptors increases blood pressure, reduces coronary blood flow, left ventricular function, and cardiac output and tissue perfusion by means of leaving the alpha-adrenergic system stimulation unopposed.{{medical citation needed|date=July 2015}} Beta blockers with lipophilic properties and CNS penetration such as metoprolol and labetalol may be useful for treating CNS and cardiovascular toxicity from a methamphetamine overdose.<ref name="Medscape meth toxicity">{{cite web | url = http://emedicine.medscape.com/article/820918-overview#showall | title = Methamphetamine Toxicity: Treatment & Management | vauthors = Richards JR, Derlet RW, Albertson TE | work = Medscape | publisher = WebMD | access-date = April 20, 2016 | url-status = live | archive-url = https://web.archive.org/web/20160409114830/http://emedicine.medscape.com/article/820918-overview#showall | archive-date = April 9, 2016 }}</ref> The mixed alpha- and beta blocker labetalol is especially useful for treatment of concomitant tachycardia and hypertension induced by methamphetamine.<ref name="Richards 2015 review">{{cite journal | vauthors = Richards JR, Albertson TE, Derlet RW, Lange RA, Olson KR, Horowitz BZ | title = Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review | journal = Drug and Alcohol Dependence | volume = 150 | pages = 1–13 | date = May 2015 | pmid = 25724076 | doi = 10.1016/j.drugalcdep.2015.01.040 }}</ref> The phenomenon of "unopposed alpha stimulation" has not been reported with the use of beta blockers for treatment of methamphetamine toxicity.<ref name="Richards 2015 review" /> Other appropriate antihypertensive drugs to administer during hypertensive crisis resulting from stimulant overdose are vasodilators such as nitroglycerin, diuretics such as furosemide, and alpha blockers such as phentolamine.<ref name="Toxicity, Amphetamine;eMedicine">{{cite web |url=http://www.emedicine.com/EMERG/topic23.htm |title=Toxicity, Amphetamine | vauthors = Handly M | work =Medscape |date=16 December 2016 |url-status=live |archive-url=https://web.archive.org/web/20071013053706/http://www.emedicine.com/emerg/topic23.htm |archive-date=October 13, 2007 }}</ref>

Beta blockers were found to be associated with depression in earlier studies.<ref name="BoyceBalloneCerta2021" /> More lipophilic beta blockers, with greater central effects, were especially implicated.<ref name="BoyceBalloneCerta2021" /> However, subsequent more rigorous studies found no causal relationship of beta blockers with depression and regardless of lipid solubility.<ref name="BoyceBalloneCerta2021" /> A small and significant but inconsistent risk of fatigue was found for non-selective beta blockers however.<ref name="BoyceBalloneCerta2021" />

Beta blockers, due to their antagonism at β₁ adrenergic receptors, inhibit both the synthesis of new melatonin and its secretion by the pineal gland. More lipophilic beta blockers, with greater ability to cross the blood–brain barrier, are known to be able to suppress melatonin release by 50 to 80%.<ref name="StoschitzkySakotnikLercher1999">{{Cite journal |last1=Stoschitzky |first1=K. |last2=Sakotnik |first2=A. |last3=Lercher |first3=P. |last4=Zweiker |first4=R. |last5=Maier |first5=R. |last6=Liebmann |first6=P. |last7=Lindner |first7=W. |date=April 1999 |title=Influence of beta-blockers on melatonin release |journal=European Journal of Clinical Pharmacology |volume=55 |issue=2 |pages=111–115 |doi=10.1007/s002280050604 |issn=0031-6970 |pmid=10335905|s2cid=32317760 }}</ref><ref name="TikhomirovaZybinaKozhevnikova2022">{{Cite journal |last1=Tikhomirova |first1=O. V. |last2=Zybina |first2=N. N. |last3=Kozhevnikova |first3=V. V. |date=2022-05-01 |title=Effects of Prolonged Use of β-Adrenoblockers on Melatonin Secretion, Sleep Quality, and Vascular Brain Damage |journal=Neuroscience and Behavioral Physiology |language=en |volume=52 |issue=4 |pages=500–504 |doi=10.1007/s11055-022-01270-y |s2cid=250708105 |issn=1573-899X}}</ref><ref name="GehrmanAnafi2021">{{Cite journal |last1=Gehrman |first1=Philip R. |last2=Anafi |first2=Ron C. |date=October 2021 |title=Treatment of a patient with a circadian sleep-wake disorder using a combination of melatonin and metoprolol |journal=Journal of Clinical Sleep Medicine |language=en |volume=17 |issue=10 |pages=2121–2124 |doi=10.5664/jcsm.9410 |issn=1550-9389 |pmc=8494102 |pmid=34032203}}</ref> The neuropsychiatric side effects of some beta blockers (e.g. sleep disruption, insomnia) may be related to this effect.<ref name="Fares2011">{{cite journal | vauthors = Fares A | title = Night-time exogenous melatonin administration may be a beneficial treatment for sleeping disorders in beta blocker patients | journal = Journal of Cardiovascular Disease Research | volume = 2 | issue = 3 | pages = 153–155 | date = July 2011 | pmid = 22022142 | pmc = 3195193 | doi = 10.4103/0975-3583.85261 | doi-broken-date = July 1, 2025 | doi-access = free }}</ref>

==Overdose== Glucagon, used in the treatment of overdose,<ref name="pmid2857542">{{cite journal | vauthors = Weinstein RS, Cole S, Knaster HB, Dahlbert T | title = Beta blocker overdose with propranolol and with atenolol | journal = Annals of Emergency Medicine | volume = 14 | issue = 2 | pages = 161–163 | date = February 1985 | pmid = 2857542 | doi = 10.1016/S0196-0644(85)81081-7 }}</ref><ref name="urlToxicity, Beta-blocker: Treatment & Medication - eMedicine Emergency Medicine">{{cite web |url=http://emedicine.medscape.com/article/813342-treatment |title=Toxicity, Beta-blocker: Treatment & Medication – eMedicine Emergency Medicine |access-date=2009-03-06 |url-status=live |archive-url=https://web.archive.org/web/20090317113942/http://emedicine.medscape.com/article/813342-treatment |archive-date=March 17, 2009 }}</ref> increases the strength of heart contractions, increases intracellular cAMP, and decreases renal vascular resistance. It is, therefore, useful in patients with beta blocker cardiotoxicity.<ref>{{cite web |url=http://www.courses.ahc.umn.edu/pharmacy/6124/handouts/Beta%20blockers.pdf |title=Beta-Adrenergic Blocker Poisoning |author=John Gualtier |website=Courses.ahc.umn.edu |access-date=2017-03-28 |archive-url=https://web.archive.org/web/20160303210046/http://www.courses.ahc.umn.edu/pharmacy/6124/handouts/Beta%20blockers.pdf |archive-date=March 3, 2016 }}</ref><ref>USMLE WORLD 2009 Step1, Pharmacology, Q85</ref> Cardiac pacing is usually reserved for patients unresponsive to pharmacological therapy.

People experiencing bronchospasm due to the β₂ receptor-blocking effects of nonselective beta blockers may be treated with anticholinergic drugs, such as ipratropium, which are safer than beta agonists in patients with cardiovascular disease. Other antidotes for beta blocker poisoning are salbutamol and isoprenaline.

==Interactions== {{See also|Propranolol#Interactions|Atenolol#Interactions}}

Beta blockers have a variety of drug interactions.<ref name="BoyceBalloneCerta2021" /> An example is that various beta blockers including propranolol, carvedilol, nebivolol, timolol, and metoprolol are metabolized by the cytochrome P450 enzyme CYP2D6 and may be potentiated by CYP2D6 inhibitors like fluoxetine, paroxetine, duloxetine, and bupropion.<ref name="BoyceBalloneCerta2021" /> This may increase the risk of adverse effects like bradycardia and hypotension.<ref name="BoyceBalloneCerta2021" />

==Pharmacology== {| class="wikitable floatright" style="font-size:small;" |+ {{Nowrap|Comparison of pharmacological properties of beta blockers}} |- ! Beta blocker !! Selectivity !! Lipophilicity<br />(log P]) !! {{Abbrlink|ISA|Intrinsic sympathomimetic activity}} || {{Abbrlink|MSA|Membrane-stabilizing activity}} |- | Acebutolol || β₁ || 1–3 || Yes/mild || ? |- | Atenolol || β₁ || <1 || No || No |- | Betaxolol || β₁ || 1–3 || Yes || ? |- | Bisoprolol || β₁ || 1–3 || No || No |- | Carteolol || β₁, β₂ || <1 || Yes || ? |- | Carvedilol || β₁, β₂, α₁ || >3 || No || Yes/high |- | Esmolol || β₁ || 1–3 || No || No |- | Labetalol || β₁, β₂, α₁ || >1<ref group="bb">Labetalol appears to be peripherally selective.</ref>|| Yes || Yes |- | Metoprolol || β₁ || 1–3 || No || Yes |- | Nadolol || β₁, β₂ || <1 || No || ? |- | Nebivolol || β₁ || >3 || No || ? |- | Oxprenolol || β₁, β₂ || 1–3 || Yes || Yes |- | Penbutolol || β₁, β₂ || >3 || Yes || ? |- | Pindolol || β₁, β₂ || 1–3 || Yes/mild || ? |- | Practolol || β₁ || <1 || Yes || No |- | Propranolol || β₁, β₂ || >3 || No || Yes/high |- | Sotalol || β₁, β₂ || <1 || No || No |- | Timolol || β₁, β₂ || 1–3 || No || Yes |- class="sortbottom" | colspan="8" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" |<references group="bb"/>'''Refs:''' <ref name="BoyceBalloneCerta2021" /><ref name="CojocariuMaștaleruSascău2021" /><ref name="Aronson2008">{{cite journal | vauthors = Aronson JK | title = Changing beta-blockers in heart failure: when is a class not a class? | journal = The British Journal of General Practice | volume = 58 | issue = 551 | pages = 387–389 | date = June 2008 | pmid = 18505613 | pmc = 2418988 | doi = 10.3399/bjgp08X299317 }}</ref><ref name="ZipurskyMacdonaldLuo2017">{{cite journal | vauthors = Zipursky JS, Macdonald EM, Luo J, Gomes T, Mamdani MM, Paterson JM, Juurlink DN | title = Lipophilic β-Blockers and Suicide in the Elderly | journal = Journal of Clinical Psychopharmacology | volume = 37 | issue = 3 | pages = 381–384 | date = June 2017 | pmid = 28338548 | doi = 10.1097/JCP.0000000000000695 | s2cid = 23355130 }}</ref><ref name="BB in HTN Meta-analyses">{{cite journal | vauthors = Larochelle P, Tobe SW, Lacourcière Y | title = β-Blockers in hypertension: studies and meta-analyses over the years | journal = The Canadian Journal of Cardiology | volume = 30 | issue = 5 Suppl | pages = S16–S22 | date = May 2014 | pmid = 24750978 | doi = 10.1016/j.cjca.2014.02.012 | doi-access = free }}</ref><ref name="PharmLetter BB Table" /><ref name="Mannhold2005">{{cite journal | vauthors = Mannhold R | title = The impact of lipophilicity in drug research: a case report on beta-blockers | journal = Mini Rev Med Chem | volume = 5 | issue = 2 | pages = 197–205 | date = February 2005 | pmid = 15720289 | doi = 10.2174/1389557053402701 | url = }}</ref>

|}

Beta blockers act as β-adrenergic receptor antagonists. They may be non-selective, antagonizing both the β₁- and β₂-adrenergic receptors, or they may be selective for antagonism of the β₁-adrenergic receptor (often referred to as "cardioselective"). Some beta blockers have intrinsic sympathomimetic activity (ISA), otherwise known as partial agonist activity at the β-adrenergic receptors with weak sympathomimetic effects.

Some beta blockers are not selective for the β-adrenergic receptor and have additional α₁-adrenergic receptor antagonism. Some beta blockers have membrane-stabilizing activity, otherwise known as sodium channel blockade or local anesthetic activity. Beta blockers vary in their lipophilicity versus hydrophilicity and hence in their capacity to cross the blood–brain barrier, with some having central nervous system effects and others being peripherally selective.

===β-Adrenergic receptor antagonism=== Stimulation of β₁ receptors by epinephrine and norepinephrine induces a positive chronotropic and inotropic effect on the heart and increases cardiac conduction velocity and automaticity.<ref>{{cite book | vauthors = Michel MC, Insel PA | chapter = Adrenergic Receptors in Clinical Medicine |title= The Adrenergic Receptors in the 21st Century | veditors = Perez DM |year= 2006 |publisher= Humana Press |isbn= 978-1-58829-423-4 |page= 135 | chapter-url= https://books.google.com/books?id=QNpIsKwp8PUC&q=%CE%B21+receptors+positive+chronotropic+inotropic+effect&pg=PA135 |access-date= 2010-09-08 }}{{Dead link|date=October 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Stimulation of β₁ receptors on the kidney causes renin release.<ref>{{cite book |title=Harrison's Nephrology and Acid-Base Disorders | vauthors = Jameson JL, Loscalzo J |year=2010 |publisher=McGraw-Hill Companies |isbn=978-0-07-166339-7 |page= 215 |url=https://books.google.com/books?id=zVQZpJnQM_AC&q=%CE%B21+receptors+kidneys+renin&pg=PA215 |access-date=2010-09-08}}</ref> Stimulation of β₂ receptors induces smooth muscle relaxation,<ref>{{cite book | vauthors = Lewis KP, Gonzalez RM, Balonov K | chapter = Vasoactive Amines and Inotropic Agents |title= Surgical Intensive Care Medicine| veditors = O'Donnell JM, Nácul FE |year= 2009 |publisher= Springer |isbn= 978-0-387-77892-1 |page= 47 | chapter-url= https://books.google.com/books?id=Bih5AXq_0uMC&q=b2+receptors+smooth+muscle+relaxation&pg=PA47 |access-date= 2010-09-08}}</ref> induces tremor in skeletal muscle,<ref name="pmid1968452">{{cite journal | vauthors = Ahrens RC | title = Skeletal muscle tremor and the influence of adrenergic drugs | journal = The Journal of Asthma | volume = 27 | issue = 1 | pages = 11–20 | year = 1990 | pmid = 1968452 | doi = 10.3109/02770909009073289 }}</ref> and increases glycogenolysis in the liver and skeletal muscle.<ref>{{cite book |title=Sport and exercise pharmacology | vauthors = Reents S |year=2000 |publisher=Human Kinetics |isbn=978-0-87322-937-1 |page= 19|url=https://books.google.com/books?id=8ysOZlGnkC0C&q=beta+blocker+stimulation+glycogenolysis&pg=PA19 |access-date=2010-09-10}}</ref> Stimulation of β₃ receptors induces lipolysis.<ref>{{cite book |title=Anatomy and Physiology | vauthors = Martini FH |year= 2005 |publisher= Pearson Education |isbn=978-0-8053-5947-3 |page=394 |url=https://books.google.com/books?id=0e08PrEMQJoC&q=beta+3+stimulating+lipolysis&pg=PA394 |access-date= 2010-09-10}}</ref>

Beta blockers inhibit these normal epinephrine- and norepinephrine-mediated sympathetic actions,<ref name="Frishman_2005" /> but have minimal effect on resting subjects.{{citation needed|date=September 2010}} That is, they reduce the effect of excitement or physical exertion on heart rate and force of contraction,<ref>{{cite book | chapter = Beta-Blockers |title=Encyclopedia of Heart Diseases | vauthors = Khan MI |year=2006 |publisher=Elsevier |isbn=978-0-12-406061-6 |page=160 | chapter-url=https://books.google.com/books?id=xco9aJ_Y9XIC&q=beta+blockers+effects+on+heart+rate&pg=PA160 |access-date= 2010-09-10}}</ref> and also tremor,<ref>{{cite book |title=Improving Oral Health for the Elderly: An Interdisciplinary Approach | veditors = Lamster IB, Northridge ME |editor2-link=Mary Northridge | name-list-style = vanc |year=2008 |publisher= Springer|location=New York |isbn=978-0-387-74337-0 |page= 87|url=https://books.google.com/books?id=qs2v9Sm-dVoC&q=beta+blockers+reduce+tremor&pg=PA87 |access-date=2010-10-23}}</ref> and breakdown of glycogen. Beta blockers can have a constricting effect on the bronchi of the lungs, possibly worsening or causing asthma symptoms.<ref>{{cite book | chapter = Beta Antagonist (Blocker) Medications | vauthors = Rothfeld GS, Romaine DS |title= The Encyclopedia of Men's Health | chapter-url = https://books.google.com/books?id=AyPacn1o4nIC&q=beta+blockers+opening+of+bronchi&pg=PA48 |access-date= 2010-10-23 |year= 2005 |publisher= Amaranth |isbn= 978-0-8160-5177-9 |page=48}}</ref>

Since β₂ adrenergic receptors can cause vascular smooth muscle dilation, beta blockers may cause some vasoconstriction. However, this effect tends to be small because the activity of β₂ receptors is overshadowed by the more dominant vasoconstricting α₁ receptors. By far the greatest effect of beta blockers remains in the heart. Newer, third-generation beta blockers can cause vasodilation through blockade of alpha-adrenergic receptors.<ref>{{cite book |title=100 Questions and Answers about Hypertension | vauthors = Manger WM, Gifford RW |year=2001 |publisher=Blackwell Science |isbn=978-0-632-04481-8 |page= [https://archive.org/details/100questionsansw0000mang/page/106 106]|url=https://archive.org/details/100questionsansw0000mang |url-access=registration |quote=beta blockers dilation of blood vessels. |access-date=2010-09-10}}</ref>

Accordingly, nonselective beta blockers are expected to have antihypertensive effects.<ref>{{cite book | chapter = Hypertension: Epidemiology, Pathophysiology, Diagnosis and Treatment | vauthors = Hurst J | veditors = Schlant RC | title= Hurst's the Heart| chapter-url= https://books.google.com/books?id=eWQAJDrVV7gC&q=beta+blockers+antihypertensive&pg=PA1564|access-date= 2010-10-07|volume= 2|year= 1997|publisher= Blackwell Science. |isbn= 978-0-07-912951-2|page=1564}}</ref> The primary antihypertensive mechanism of beta blockers is unclear, but may involve reduction in cardiac output (due to negative chronotropic and inotropic effects).<ref>{{cite book | vauthors = Reid JL |title= Lecture notes on clinical pharmacology|url= https://books.google.com/books?id=dsEmlotDt2wC&q=beta+blockers+antihypertensive+effect+reduction+of+cardiac+output&pg=PA76|access-date= 2011-03-11|volume= 6|year= 2001|publisher= Blackwell Science. |isbn= 978-0-632-05077-2|page=76}}</ref> It may also be due to reduction in renin release from the kidneys, and a central nervous system effect to reduce sympathetic activity (for those beta blockers that do cross the blood–brain barrier, e.g. propranolol).{{citation needed|date=October 2023}}

Antianginal effects result from negative chronotropic and inotropic effects, which decrease cardiac workload and oxygen demand. Negative chronotropic properties of beta blockers allow the lifesaving property of heart rate control. Beta blockers are readily titrated to optimal rate control in many pathologic states.{{citation needed|date=October 2023}}

The antiarrhythmic effects of beta blockers arise from sympathetic nervous system blockade—resulting in depression of sinus node function and atrioventricular node conduction, and prolonged atrial refractory periods. Sotalol, in particular, has additional antiarrhythmic properties and prolongs action potential duration through potassium channel blockade.

Blockade of the sympathetic nervous system on renin release leads to reduced aldosterone via the renin–angiotensin–aldosterone system, with a resultant decrease in blood pressure due to decreased sodium and water retention.

===α₁-Adrenergic receptor antagonism=== Some beta blockers (e.g., labetalol and carvedilol) exhibit mixed antagonism of both β- and α₁-adrenergic receptors, which provides additional arteriolar vasodilating action.<ref>{{cite web |title=Labetalol Hydrochloride Monograph for Professionals |url=https://www.drugs.com/monograph/labetalol-hydrochloride.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=3 March 2019}}</ref><ref>{{cite web|url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020297s029lbl.pdf|archive-url = https://web.archive.org/web/20160304085017/http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020297s029lbl.pdf|archive-date = March 4, 2016|title = Coreg – Food and Drug Administration}}</ref>

===Intrinsic sympathomimetic activity=== Also referred to as intrinsic sympathomimetic effect, this term is used particularly with beta blockers that can show both agonism and antagonism at a given beta receptor, depending on the concentration of the agent (beta blocker) and the concentration of the antagonized agent (usually an endogenous compound, such as norepinephrine). See partial agonist for a more general description.{{citation needed|date=October 2023}}

Some beta blockers (e.g. oxprenolol, pindolol, penbutolol, labetalol and acebutolol) exhibit intrinsic sympathomimetic activity (ISA). These agents are capable of exerting low-level agonist activity at the β-adrenergic receptor while simultaneously acting as a receptor site antagonist. These agents, therefore, may be useful in individuals exhibiting excessive bradycardia with sustained beta blocker therapy.{{citation needed|date=October 2023}}

Agents with ISA should not be used for patients with any kind of angina as it can aggravate or after myocardial infarctions. They may also be less effective than other beta blockers in the management of angina and tachyarrhythmia.<ref name="Rossi">{{cite book | editor= Rossi S | title=Australian Medicines Handbook |year=2006 |location=Adelaide |publisher=Australian Medicines Handbook| title-link=Australian Medicines Handbook }}</ref>

===Blood–brain barrier permeability=== Beta blockers vary in their lipophilicity (fat solubility) and in turn in their ability to cross the blood–brain barrier and exert effects in the central nervous system.<ref name="CojocariuMaștaleruSascău2021">{{cite journal | vauthors = Cojocariu SA, Maștaleru A, Sascău RA, Stătescu C, Mitu F, Leon-Constantin MM | title = Neuropsychiatric Consequences of Lipophilic Beta-Blockers | journal = Medicina | volume = 57 | issue = 2 | date = February 2021 | page = 155 | pmid = 33572109 | pmc = 7914867 | doi = 10.3390/medicina57020155 | doi-access = free }}</ref> Beta blockers with greater blood–brain barrier permeability can have both neuropsychiatric therapeutic benefits and side effects, as well as adverse cognitive effects.<ref name="CojocariuMaștaleruSascău2021" /> Central nervous system-related side effects and risks of beta blockers may include fatigue, depression, sleep disorders (namely insomnia) and nightmares, visual hallucinations, delirium, psychosis, Parkinson's disease, and falling.<ref name="CojocariuMaștaleruSascău2021" /> Conversely, central nervous system-related benefits of beta blockers may include prevention and treatment of migraine, essential tremor, akathisia, anxiety, post-traumatic stress disorder, aggression, and obsessive–compulsive disorder.<ref name="CojocariuMaștaleruSascău2021" />

Most beta blockers are lipophilic and can cross into the brain, but there are a number of exceptions.<ref name="CojocariuMaștaleruSascău2021" /> Highly lipophilic beta blockers include penbutolol, pindolol, propranolol, and timolol, moderately lipophilic beta blockers include acebutolol, betaxolol, bisoprolol, carvedilol, metoprolol, and nebivolol, and low lipophilicity or hydrophilic beta blockers include atenolol, carteolol, esmolol, labetalol, nadolol, and sotalol.<ref name="CojocariuMaștaleruSascău2021" /> It is thought that highly lipophilic beta blockers are able to readily cross into the brain, moderately lipophilic beta blockers are able to cross to a lesser degree, and low lipophilicity or hydrophilic beta blockers are minimally able to cross.<ref name="CojocariuMaștaleruSascău2021" /> The preceding beta blockers also vary in their intrinsic sympathomimetic activity and β₁-adrenergic receptor selectivity (or cardioselectivity), resulting in further differences in pharmacological profiles and suitability in different contexts between them.<ref name="CojocariuMaștaleruSascău2021" />

The brain-to-blood ratios of certain beta blockers in humans have been characterized and have been found to be 50:1 for oxprenolol, 15:1 to 33:1 for propranolol, 16:1 for alprenolol, 12:1 for metoprolol, and 0.2:1 for atenolol.<ref name="Drayer1987">{{cite journal | vauthors = Drayer DE | title = Lipophilicity, hydrophilicity, and the central nervous system side effects of beta blockers | journal = Pharmacotherapy | volume = 7 | issue = 4 | pages = 87–91 | date = 1987 | pmid = 2891122 | doi = 10.1002/j.1875-9114.1987.tb04029.x | url = }}</ref><ref name="HeelBrogdenSpeight1979">{{cite journal | vauthors = Heel RC, Brogden RN, Speight TM, Avery GS | title = Atenolol: a review of its pharmacological properties and therapeutic efficacy in angina pectoris and hypertension | journal = Drugs | volume = 17 | issue = 6 | pages = 425–460 | date = June 1979 | pmid = 38096 | doi = 10.2165/00003495-197917060-00001 | url = }}</ref> The blood-to-brain ratios of various other beta blockers, for instance acebutolol, bevantolol, nadolol, pindolol, and timolol, appear to be unknown.<ref name="Drayer1987" />

==History== {{Main|Discovery and development of beta-blockers}}

thumb|upright=1.6|class=skin-invert-image|Beta blockers development timeline.

The adrenergic receptors were discovered Henry Hallett Dale in 1906 and the α- and β-adrenergic receptors were differentiated by Raymond P. Ahlquist in 1948.<ref name="OliverMayorD'Ocon2019" /> In 1967, the β-adrenergic receptors were further differentiated into the β₁- and β₂-adrenergic receptors by Alonzo M. Lands.<ref name="OliverMayorD'Ocon2019" />

The first beta blocker to be developed was dichloroisoprenaline, based on structural modification of the β-adrenergic receptor agonist isoprenaline (isoproterenol).<ref name="doValeCeronGonzaga2019">{{cite journal | vauthors = do Vale GT, Ceron CS, Gonzaga NA, Simplicio JA, Padovan JC | title = Three Generations of β-blockers: History, Class Differences and Clinical Applicability | journal = Curr Hypertens Rev | volume = 15 | issue = 1 | pages = 22–31 | date = 2019 | pmid = 30227820 | doi = 10.2174/1573402114666180918102735 | url = }}</ref><ref name="Stapleton1997">{{cite journal | vauthors = Stapleton MP | title = Sir James Black and propranolol. The role of the basic sciences in the history of cardiovascular pharmacology | journal = Tex Heart Inst J | volume = 24 | issue = 4 | pages = 336–342 | date = 1997 | pmid = 9456487 | pmc = 325477 | doi = | url = }}</ref><ref name="PowellSlater1958">{{cite journal | vauthors = Powell CE, Slater IH | title = Blocking of inhibitory adrenergic receptors by a dichloro analog of isoproterenol | journal = J Pharmacol Exp Ther | volume = 122 | issue = 4 | pages = 480–488 | date = April 1958 | pmid = 13539775 | doi = 10.1016/S0022-3565(25)12002-8| url = }}</ref> It was described by C. E. Powell and I. H. Slater in 1958.<ref name="doValeCeronGonzaga2019" /><ref name="Stapleton1997" /><ref name="OliverMayorD'Ocon2019">{{cite journal | vauthors = Oliver E, Mayor F, D'Ocon P | title = Beta-blockers: Historical Perspective and Mechanisms of Action | journal = Rev Esp Cardiol (Engl Ed) | volume = 72 | issue = 10 | pages = 853–862 | date = October 2019 | pmid = 31178382 | doi = 10.1016/j.rec.2019.04.006 | url = }}</ref><ref name="PowellSlater1958" /> However, dichloroisoprenaline had significant partial agonism and sympathomimetic activity and hence was not a pure antagonist.<ref name="doValeCeronGonzaga2019" /><ref name="Stapleton1997" /> James Black and John Stephenson described pronethalol (nethalide; ICI-38,174; Alderlin) as a purely antagonistic beta blocker in 1962.<ref name="doValeCeronGonzaga2019" /><ref name="Stapleton1997" /><ref name="BlackStephenson1962">{{cite journal | vauthors = Black JW, Stephenson JS | title = Pharmacology of a new adrenergic beta-receptor-blocking compound (Nethalide) | journal = Lancet | volume = 2 | issue = 7251 | pages = 311–314 | date = August 1962 | pmid = 13869657 | doi = 10.1016/s0140-6736(62)90103-4 | url = }}</ref> But pronethalol suffered from off-target activity and associated side effects and toxicity.<ref name="doValeCeronGonzaga2019" /><ref name="Stapleton1997" /> As such, it did not enter widespread use and was soon discontinued.<ref name="Stapleton1997" />

In 1964, Black and colleagues published on propranolol (ICI-45,520; Inderal), which did not have the problems of earlier beta blockers.<ref name="doValeCeronGonzaga2019" /><ref name="Stapleton1997" /><ref name="BlackCrowtherShanks1964">{{cite journal | vauthors = Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC | title = A new adrenergic: beta-receptor antagonist | journal = Lancet | volume = 1 | issue = 7342 | pages = 1080–1081 | date = May 1964 | pmid = 14132613 | doi = 10.1016/s0140-6736(64)91275-9 | url = }}</ref> It was introduced for medical use under the brand name Inderal the same year and became the first widely used beta blocker.<ref name="doValeCeronGonzaga2019" /><ref name="Stapleton1997" /> Since the introduction of propranolol, there have been three generations of beta blockers with different pharmacological properties, with numerous beta blockers having been developed and introduced for medical use.<ref name="doValeCeronGonzaga2019" />

==Society and culture== ===Performance-enhancing use=== Because they promote lower heart rates and reduce tremors, beta blockers have been used in professional sports where high accuracy is required, including archery, shooting, golf<ref name="ogrady">{{cite news |author=Glover |url=https://www.independent.co.uk/sport/golf-ogrady-says-players-use-betablockers-drugs-helped-win-majors-1368307.html |title=Golf: O'Grady says players use beta-blockers: Drugs 'helped win majors' |newspaper=The Independent |access-date=2017-03-28 |url-status=live |archive-url=https://web.archive.org/web/20150925223906/http://www.independent.co.uk/sport/golf-ogrady-says-players-use-betablockers-drugs-helped-win-majors-1368307.html |archive-date=September 25, 2015 |first=Tim}}</ref> and snooker.<ref name="ogrady"/> Beta blockers are banned in some sports by the International Olympic Committee.<ref name="ref4">{{cite web | author=World Anti-Doping Agency | title=The World Anti-Doping Code: The 2006 Prohibited List International Standard | url=https://www.wada-ama.org/sites/default/files/resources/files/WADA_Prohibited_List_2006_EN.pdf | date=September 19, 2005 | publisher=World Anti-Doping Agency | access-date=2017-02-10 | url-status=live | archive-url=https://web.archive.org/web/20170211160033/https://www.wada-ama.org/sites/default/files/resources/files/WADA_Prohibited_List_2006_EN.pdf | archive-date=February 11, 2017 }}</ref> In the 2008 Summer Olympics, 50-metre pistol silver medalist and 10-metre air pistol bronze medalist Kim Jong-su tested positive for propranolol and was stripped of his medals.<ref name="Guardian NK Doping">{{Cite news| vauthors = Scott M |title=Olympics: North Korea's Kim Jong-su loses medals after positive drugs test |url= https://www.theguardian.com/sport/2008/aug/15/olympics2008.drugsinsport|newspaper=The Guardian|publisher=Guardian News and Media Limited|access-date=7 March 2018|language=en|date=15 August 2008}}</ref>

For similar reasons, beta blockers have also been used by surgeons.<ref>{{cite journal | vauthors = Elman MJ, Sugar J, Fiscella R, Deutsch TA, Noth J, Nyberg M, Packo K, Anderson RJ | display-authors = 6 | title = The effect of propranolol versus placebo on resident surgical performance | journal = Transactions of the American Ophthalmological Society | volume = 96 | pages = 283–91; discussion 291–4 | year = 1998 | pmid = 10360293 | pmc = 1298399 }}</ref> Classical musicians have commonly used beta blockers since the 1970s to reduce stage fright.<ref>{{cite news|date=August 16, 2013|title=Musicians Use Beta Blockers as Performance-Enabling Drugs|publisher=WQXR|url=https://www.wqxr.org/story/312920-musicians-use-beta-blockers-relieve-stage-fright/|access-date=March 11, 2021}}</ref>

==Research== ===Psychiatric disorders=== Beta blockers have been researched for treatment of a variety of psychiatric disorders besides anxiety disorders.<ref name="BoyceBalloneCerta2021" /> These include depression, mania, acute stress disorder, post-traumatic stress disorder (PTSD), schizophrenia, aggression, and agitation.<ref name="BoyceBalloneCerta2021" />

Beta blockers have also been used for the treatment of schizoid personality disorder.<ref>{{cite book | vauthors = Joseph S | date = 1997 | chapter =Chapter 3, Schizoid Personality Disorder. | title = Personality Disorders: New Symptom-Focused Drug Therapy. | publisher = Psychology Press | pages = 45–56 | isbn = 978-0-7890-0134-4}}</ref> However, there is limited evidence supporting the efficacy of supplemental beta blocker use in addition to antipsychotic drugs for treating schizophrenia.<ref>{{Cite journal |last1=Cheine |first1=M. |last2=Ahonen |first2=J. |last3=Wahlbeck |first3=K. |date=2001 |title=Beta-blocker supplementation of standard drug treatment for schizophrenia |journal=The Cochrane Database of Systematic Reviews |volume=2010 |issue=3 |article-number=CD000234 |doi=10.1002/14651858.CD000234 |issn=1469-493X |pmid=11686955}}</ref><ref>{{Cite journal | vauthors = Shek E, Bardhan S, Cheine MV, Ahonen J, Wahlbeck | collaboration = Cochrane Schizophrenia Group | title = Beta-blocker supplementation of standard drug treatment for schizophrenia. | journal = Cochrane Database of Systematic Reviews | date = September 1996 | volume = 2010 | issue = 7 |url=https://www.cochrane.org/CD000234/SCHIZ_beta-blocker-supplementation-of-standard-drug-treatment-for-people-with-schizophrenia | doi = 10.1002/14651858.CD000234 |s2cid=1627733 | url-access = subscription }}</ref>

===Cancer treatment=== Some preclinical and clinical research suggests that some beta blockers may be beneficial for cancer treatment.<ref>{{cite journal | vauthors = Choy C, Raytis JL, Smith DD, Duenas M, Neman J, Jandial R, Lew MW | title = Inhibition of β2-adrenergic receptor reduces triple-negative breast cancer brain metastases: The potential benefit of perioperative β-blockade | journal = Oncology Reports | volume = 35 | issue = 6 | pages = 3135–3142 | date = June 2016 | pmid = 27035124 | pmc = 4869944 | doi = 10.3892/or.2016.4710 }}</ref><ref>{{cite journal | vauthors = Kokolus KM, Zhang Y, Sivik JM, Schmeck C, Zhu J, Repasky EA, Drabick JJ, Schell TD | display-authors = 6 | title = Beta blocker use correlates with better overall survival in metastatic melanoma patients and improves the efficacy of immunotherapies in mice | journal = Oncoimmunology | volume = 7 | issue = 3 | article-number = e1405205 | year = 2018 | pmid = 29399407 | pmc = 5790362 | doi = 10.1080/2162402X.2017.1405205 }}</ref> However, other studies do not show a correlation between cancer survival and beta blocker use.<ref>{{cite journal | vauthors = Livingstone E, Hollestein LM, van Herk-Sukel MP, van de Poll-Franse L, Nijsten T, Schadendorf D, de Vries E | title = β-Blocker use and all-cause mortality of melanoma patients: results from a population-based Dutch cohort study | journal = European Journal of Cancer | volume = 49 | issue = 18 | pages = 3863–3871 | date = December 2013 | pmid = 23942335 | doi = 10.1016/j.ejca.2013.07.141 }}</ref><ref>{{cite journal | vauthors = Cardwell CR, Coleman HG, Murray LJ, O'Sullivan JM, Powe DG | title = Beta-blocker usage and prostate cancer survival: a nested case-control study in the UK Clinical Practice Research Datalink cohort | journal = Cancer Epidemiology | volume = 38 | issue = 3 | pages = 279–285 | date = June 2014 | pmid = 24786858 | doi = 10.1016/j.canep.2014.03.011 }}</ref> Also, a 2017 meta-analysis failed to show any benefit for the use of beta blockers in breast cancer.<ref>{{cite journal | vauthors = Kim HY, Jung YJ, Lee SH, Jung HJ, Pak K | title = Is Beta-Blocker Use Beneficial in Breast Cancer? A Meta-Analysis | journal = Oncology | volume = 92 | issue = 5 | pages = 264–268 | year = 2017 | pmid = 28132057 | doi = 10.1159/000455143 | s2cid = 5463335 }}</ref>

==List of beta blockers== [[File:Dichloroisoprenaline structure.svg|thumb|upright=0.7|class=skin-invert-image|Dichloroisoprenaline, the first beta blocker.]]

===Nonselective agents=== Nonselective beta blockers display both β₁ and β₂ antagonism.<ref name="PharmLetter BB Table">{{cite web|title=Comparison of Oral Beta-Blockers|url=https://pharmacist.therapeuticresearch.com/Content/Segments/PRL/2012/Dec/Comparison-of-Oral-Beta-Blockers-5052|website=pharmacist.therapeuticresearch.com|publisher=Therapeutic Research Center|access-date=30 April 2017|url-status=live|archive-url=https://web.archive.org/web/20171018134059/https://pharmacist.therapeuticresearch.com/Content/Segments/PRL/2012/Dec/Comparison-of-Oral-Beta-Blockers-5052|archive-date=October 18, 2017}}</ref>

* Propranolol<ref name="PharmLetter BB Table" /> * Bucindolol (has additional α₁-blocking activity)<ref>{{cite journal | vauthors = Rosendorff C | title = Beta-blocking agents with vasodilator activity | journal = Journal of Hypertension Supplement | volume = 11 | issue = 4 | pages = S37–S40 | date = June 1993 | pmid = 8104240 | doi = 10.1097/00004872-199306003-00009 }}</ref> * Carteolol<ref>{{cite web|title=CARTEOLOL|url=https://pubchem.ncbi.nlm.nih.gov/compound/carteolol|website=pubchem.ncbi.nlm.nih.gov|publisher=U.S. National Library of Medicine|access-date=18 October 2017|language=en|url-status=live|archive-url=https://web.archive.org/web/20171018134213/https://pubchem.ncbi.nlm.nih.gov/compound/carteolol|archive-date=October 18, 2017}}</ref> * Carvedilol (has additional α₁-blocking activity)<ref name="PharmLetter BB Table" /> * Labetalol (has intrinsic sympathomimetic activity and additional α₁-blocking activity)<ref name="PharmLetter BB Table" /> * Nadolol<ref name="PharmLetter BB Table" /> * Oxprenolol (has intrinsic sympathomimetic activity)<ref name="oxprenolol">{{cite web|title=oxprenolol|url=https://pubchem.ncbi.nlm.nih.gov/compound/4631|website=pubchem.ncbi.nlm.nih.gov|publisher=U.S. National Library of Medicine|access-date=18 October 2017|language=en|url-status=live|archive-url=https://web.archive.org/web/20171018133859/https://pubchem.ncbi.nlm.nih.gov/compound/4631|archive-date=October 18, 2017}}</ref> * Penbutolol (has intrinsic sympathomimetic activity)<ref name="PharmLetter BB Table" /> * Pindolol (has intrinsic sympathomimetic activity)<ref name="PharmLetter BB Table" /> * Sotalol (not considered a "typical beta blocker")<ref name="PharmLetter BB Table" /> * Timolol<ref name="PharmLetter BB Table" />

===β₁-selective agents=== β₁-selective beta blockers are also known as cardioselective beta blockers.<ref name="PharmLetter BB Table" /> Pharmacologically, the beta-blockade of the β₁ receptors in the heart will act on cAMP. The function of cAMP as a second messenger in the cardiac cell is that it phosphorylates the LTCC and the ryanodine receptor to increase intracellular calcium levels and cause contraction. Beta-blockade of the β₁ receptor will inhibit cAMP from phosphorylating, and it will decrease the ionotrophic and chronotropic effect. Note that drugs may be cardioselective, or act on β₁ receptors in the heart only, but still have intrinsic sympathomimetic activity.

* Acebutolol (has intrinsic sympathomimetic activity, ISA)<ref name="PharmLetter BB Table" /> * Atenolol<ref name="PharmLetter BB Table" /> * Betaxolol<ref name="PharmLetter BB Table" /> * Bisoprolol<ref name="PharmLetter BB Table" /> * Celiprolol (has intrinsic sympathomimetic activity)<ref name="Celiprolol">{{cite web|title=Celiprolol|url=https://pubchem.ncbi.nlm.nih.gov/compound/2663|website=pubchem.ncbi.nlm.nih.gov|publisher=U.S. National Library of Medicine|access-date=18 October 2017|language=en|url-status=live|archive-url=https://web.archive.org/web/20171018133611/https://pubchem.ncbi.nlm.nih.gov/compound/2663|archive-date=October 18, 2017}}</ref> * Metoprolol<ref name="PharmLetter BB Table" /> * Nebivolol<ref name="PharmLetter BB Table" /> * Esmolol<ref name="VolzZang">{{cite journal | vauthors = Volz-Zang C, Eckrich B, Jahn P, Schneidrowski B, Schulte B, Palm D | title = Esmolol, an ultrashort-acting, selective beta 1-adrenoceptor antagonist: pharmacodynamic and pharmacokinetic properties | journal = European Journal of Clinical Pharmacology | volume = 46 | issue = 5 | pages = 399–404 | year = 1994 | pmid = 7957532 | doi = 10.1007/BF00191900 | s2cid = 12809602 }}</ref> Nebivolol and bisoprolol are the most β₁ cardioselective beta blockers.<ref>{{cite journal | vauthors = Sinha SS, Gurm HS | title = The double jeopardy of chronic obstructive pulmonary disease and myocardial infarction | journal = Open Heart | volume = 1 | issue = 1 | article-number = e000010 | date = February 2014 | pmid = 25332777 | pmc = 4189253 | doi = 10.1136/openhrt-2013-000010 }}</ref>

===β₂-selective agents=== Due to their limited indications, β₂-selective agents are rarely used in the clinical setting.<ref name="Abosamak">{{cite book |last1=Abosamak |first1=NourEldin R. |last2=Patel |first2=Preeti |last3=Shahin |first3=Mohamed H. |title=StatPearls |date=2025 |publisher=StatPearls Publishing |url=https://www.ncbi.nlm.nih.gov/books/NBK559069/ |chapter=Beta2-Receptor Agonists and Antagonists}}</ref> * Butaxamine<ref>{{cite web|title=Butaxamine|url=https://pubchem.ncbi.nlm.nih.gov/compound/18026|website=pubchem.ncbi.nlm.nih.gov|publisher=U.S. National Library of Medicine|access-date=18 October 2017|language=en|url-status=live|archive-url=https://web.archive.org/web/20171018134215/https://pubchem.ncbi.nlm.nih.gov/compound/18026|archive-date=October 18, 2017}}</ref> * ICI-118,551<ref>{{cite web|title=ICI 118551|url=https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI%3A73289|website=ChEBI|language=en}}</ref>

===β₃-selective agents=== * SR 59230A<ref>{{cite web|title=SR 59230A|url=https://pubchem.ncbi.nlm.nih.gov/compound/9888075|website=pubchem.ncbi.nlm.nih.gov|publisher=U.S. National Library of Medicine|access-date=18 October 2017|language=en|url-status=live|archive-url=https://web.archive.org/web/20171018134222/https://pubchem.ncbi.nlm.nih.gov/compound/9888075|archive-date=October 18, 2017}}</ref>

===β₁ selective antagonist and β₃ agonist agents=== * Nebivolol<ref name="PharmLetter BB Table" />

==See also== * Adrenergic antagonist * Adrenergic receptor * Alpha blocker * Discovery and development of beta-blockers * Sympathetic nervous system

==References== {{Reflist}}

==External links== * [https://www.musiciansway.com/blog/2010/03/musicians-and-beta-blockers/ "Musicians and beta-blockers"] by Gerald Klickstein, March 11, 2010 (A blog post that considers "whether beta-blockers are safe, effective, and appropriate for performers to use") * [https://www.nytimes.com/2004/10/17/arts/music/17tind.html "Better Playing Through Chemistry"] by Blair Tindall, ''The New York Times'', October 17, 2004. (Discusses the use of beta blockers among professional musicians) ** [https://www.sfgate.com/health/article/Using-chemistry-to-create-better-music-Legal-2687828.php "Musicians using beta blockers"] by Blair Tindall. A condensed version of the above article. * [https://www.theatlantic.com/doc/200808u/beta-blockers "In Defense of the Beta Blocker"] by Carl Elliott, ''The Atlantic'', August 20, 2008. (Discusses the use of propranolol by a North Korean pistol shooter in the 2008 Olympics) * {{MeshName|beta-Adrenergic+Blockers}}

{{Beta blockers}} {{Major Drug Groups}} {{Endothelial antihypertensives}} {{Antiglaucoma preparations and miotics}} {{Anxiolytics}} {{Adrenergic receptor modulators}} {{Authority control}}

{{DEFAULTSORT:Beta Blocker}} Category:Beta blockers Category:British inventions Category:Scottish inventions