Editing Beta blocker (section)

== 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 β<sub>1</sub> 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|df = mdy-all}}</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 | pages = 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=9781259584732}}</ref>

==== Acute myocardial infarction ====

Beta blockers are indicated for the treatment of acute [[myocardial infarction]]s. During a myocardial infarction, systemic stress causes an increase in circulating [[catecholamine]]s.<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 | pages = 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= http://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 β<sub>1</sub>-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 = http://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 | pages = 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 | pages = 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 ===
Officially, beta blockers are not approved for [[anxiolytic]] use by the U.S. [[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 controlled trials in the past 25 years indicate beta blockers are effective in [[anxiety disorders]], though the mechanism of action is not known.<ref>{{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> 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}}

Musicians, public speakers, actors, and professional [[dancers]] have been known to use beta blockers to avoid [[performance anxiety]], [[stage fright]], and tremor during both [[Audition (performing arts)|audition]]s 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"/>

=== 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 | pages = 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 | pages = 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 ===
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 | pages = 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 | pages = 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 a been proven to relieve the pain caused by [[myocardial infarction]], and also the infarction size, which correlates with heart rate.<ref>{{cite book|author=John Malcolm 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, Conn|isbn=978-1-60795-108-7}}</ref>

There are few non-cardiovascular uses for adrenergic antagonists. Alpha-adrenergic antagonists are also used for treatment of [[ureteral stones|ureteric stones]], [[pain disorder|pain]] and [[panic disorder]]s, [[drug withdrawal|withdrawal]], and [[anesthesia]].<ref name="pmid27908918">{{cite journal | vauthors = Hollingsworth JM, Canales BK, Rogers MA, Sukumar S, Yan P, Kuntz GM, Dahm P | title = Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis | journal = BMJ | volume = 355 | pages = i6112 | date = December 2016 | pmid = 27908918 | pmc = 5131734 | doi = 10.1136/bmj.i6112 }}</ref><ref name="pmid25849473">{{cite journal | vauthors = Giovannitti JA, Thoms SM, Crawford JJ | title = Alpha-2 adrenergic receptor agonists: a review of current clinical applications | journal = Anesth Prog | volume = 62 | issue = 1 | pages = 31–9 | date = 2015 | pmid = 25849473 | pmc = 4389556 | doi = 10.2344/0003-3006-62.1.31 | url = }}</ref>

Beta blockers are used to treat acute cardiovascular [[toxicity]] (e.g. in [[overdose]]) caused by [[sympathomimetic]]s, 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 α<sub>1</sub> 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.<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>