bisoprolol

File:000859lg Zebeta 5 MG Oral Tablet.jpg

Bisoprolol is used for prevention of cardiovascular events following a heart attack in patients with risk factors for disease progression,{{cite journal | vauthors = Bangalore S, Makani H, Radford M, Thakur K, Toklu B, Katz SD, DiNicolantonio JJ, Devereaux PJ, Alexander KP, Wetterslev J, Messerli FH | display-authors = 6 | title = Clinical outcomes with β-blockers for myocardial infarction: a meta-analysis of randomized trials | journal = The American Journal of Medicine | volume = 127 | issue = 10 | pages = 939–953 | date = October 2014 | pmid = 24927909 | doi = 10.1016/j.amjmed.2014.05.032 | doi-access = free }} in the management of congestive heart failure with reduced ejection fraction,{{cite journal | author = CIBIS-II Investigators | title = The cardiac insufficiency bisoprolol study II (CIBIS-II): a randomised trial. | journal = The Lancet | date = January 1999 | volume = 353 | issue = 9146 | pages = 9–13 | doi = 10.1016/S0140-6736(98)11181-9 | s2cid = 10083527 }}> and as a second-line agent for hypertension.{{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 }}

Bisoprolol may be beneficial in the treatment of high blood pressure, but it is not recommended as a first-line antihypertensive agent. It can be an adjunct to first-line antihypertensive agents in patients with accompanying comorbidities, for example, congestive heart failure, where selected beta blockers can be added in patients who remain mildly to moderately symptomatic despite appropriate doses of an angiotensin-converting-enzyme inhibitor.{{Cite web |title=Clinical information for Hypertension I Heart Foundation |url=https://heartfoundation-prod.azurewebsites.net/bundles/for-professionals/hypertension |access-date=13 May 2023 |website=heartfoundation-prod.azurewebsites.net |archive-date=13 September 2022 |archive-url=https://web.archive.org/web/20220913121141/https://heartfoundation-prod.azurewebsites.net/Bundles/For-Professionals/Hypertension |url-status=dead }}

In cardiac ischemia, the drug is used to reduce the activity of the heart muscle, thereby reducing its oxygen and nutrient demands and allowing its reduced blood supply to still transport sufficient amounts of oxygen and nutrients to meet its needs.{{cite journal | author = CIBIS Investigators and Committees | title = A randomized trial of beta-blockade in heart failure. The Cardiac Insufficiency Bisoprolol Study (CIBIS). | journal = Circulation | volume = 90 | issue = 4 | pages = 1765–1773 | date = October 1994 | pmid = 7923660 | doi = 10.1161/01.cir.90.4.1765 | doi-access = free }}{{cite journal | vauthors = Konishi M, Haraguchi G, Kimura S, Inagaki H, Kawabata M, Hachiya H, Hirao K, Isobe M | display-authors = 6 | title = Comparative effects of carvedilol vs bisoprolol for severe congestive heart failure | journal = Circulation Journal | volume = 74 | issue = 6 | pages = 1127–1134 | date = June 2010 | pmid = 20354334 | doi = 10.1253/circj.cj-09-0989 | doi-access = free }}{{cite journal | vauthors = Castagno D, Jhund PS, McMurray JJ, Lewsey JD, Erdmann E, Zannad F, Remme WJ, Lopez-Sendon JL, Lechat P, Follath F, Höglund C, Mareev V, Sadowski Z, Seabra-Gomes RJ, Dargie HJ | display-authors = 6 | title = Improved survival with bisoprolol in patients with heart failure and renal impairment: an analysis of the cardiac insufficiency bisoprolol study II (CIBIS-II) trial | journal = European Journal of Heart Failure | volume = 12 | issue = 6 | pages = 607–616 | date = June 2010 | pmid = 20354032 | doi = 10.1093/eurjhf/hfq038 | s2cid = 205048092 | doi-access = free | hdl = 2318/134969 | hdl-access = free }}

An overdose of bisoprolol can lead to fatigue, hypotension, hypoglycemia, bronchospasms, and bradycardia. Bronchospasms and hypoglycemia occur because at high doses, the drug can be an antagonist for β₂ adrenergic receptors located in the lungs and liver. Bronchospasm occurs due to the blockage of β₂ receptors in the lungs. Hypoglycemia occurs due to decreased stimulation of glycogenolysis and gluconeogenesis in the liver via β₂ receptors.{{cite journal | vauthors = Hauck RW, Schulz C, Emslander HP, Böhm M | title = Pharmacological actions of the selective and non-selective beta-adrenoceptor antagonists celiprolol, bisoprolol and propranolol on human bronchi | journal = British Journal of Pharmacology | volume = 113 | issue = 3 | pages = 1043–1049 | date = November 1994 | pmid = 7858847 | pmc = 1510470 | doi = 10.1111/j.1476-5381.1994.tb17098.x }}

There have been no reported cases of clinically evident drug-induced liver injury associated with bisoprolol.{{cite book|pmid=31643790 |date=2012 |title=Bisoprolol }}

Non-selective beta-blockers should be avoided in people with asthma or bronchospasm as they may cause exacerbations and worsening of symptoms.{{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 }}{{cite journal | vauthors = Morales DR, Lipworth BJ, Donnan PT, Jackson C, Guthrie B | title = Respiratory effect of beta-blockers in people with asthma and cardiovascular disease: population-based nested case control study | journal = BMC Medicine | volume = 15 | issue = 1 | pages = 18 | date = January 2017 | pmid = 28126029 | pmc = 5270217 | doi = 10.1186/s12916-017-0781-0 | doi-access = free }}{{cite journal | vauthors = Bennett M, Chang CL, Tatley M, Savage R, Hancox RJ | title = The safety of cardioselective β1-blockers in asthma: literature review and search of global pharmacovigilance safety reports | journal = ERJ Open Research | volume = 7 | issue = 1 | pages = | date = January 2021 | pmid = 33681344 | pmc = 7917232 | doi = 10.1183/23120541.00801-2020 | url = }} β₁ selective beta-blockers like bisoprolol have not been shown to cause an increase in asthma exacerbations, and may be cautiously tried in those with controlled, mild-to-moderate asthma with cardiac comorbidities.

A 2014 meta-analysis found that unlike non-selective beta-blockers, β₁ selective beta-blockers (bisoprolol) showed only a small impact on lung function, with patients remaining responsive to salbutamol (β₂ -agonist) rescue therapy and endorses the use of bisoprolol in select patients with controlled asthma.{{cite journal | vauthors = Loth DW, Brusselle GG, Lahousse L, Hofman A, Leufkens HG, Stricker BH | title = β-Adrenoceptor blockers and pulmonary function in the general population: the Rotterdam Study | journal = British Journal of Clinical Pharmacology | volume = 77 | issue = 1 | pages = 190–200 | date = January 2014 | pmid = 23772842 | doi = 10.1111/bcp.12181 | pmc = 3895360 }} This was supported by a 2020 clinical trial where bisoprolol had no significant impact on bronchodilation post salbutamol administration.{{cite journal | vauthors = Bennett MR, Chang CL, Tuffery C, Hopping S, Hancox RJ | title = The impact of regular bisoprolol on the response to salbutamol in asthma: A double-blind randomized placebo-controlled crossover trial | journal = Respirology | volume = 26 | issue = 3 | pages = 225–232 | date = March 2021 | pmid = 33043552 | doi = 10.1111/resp.13955 | s2cid = 222301890 }}

Bisoprolol is cardioprotective because it selectively and competitively blocks catecholamine (adrenaline) stimulation of β₁ adrenergic receptors (adrenoreceptors), which are mainly found in the heart muscle cells and heart conduction tissue (cardiospecific), but also found in juxtaglomerular cells in the kidney. Normally, adrenaline and noradrenaline stimulation of the β₁ adrenoreceptor activates a signalling cascade (Gs protein and cAMP) which ultimately leads to increased myocardial contractility and increased heart rate of the heart muscle and heart pacemaker, respectively.{{cite journal | vauthors = Bristow MR, Hershberger RE, Port JD, Minobe W, Rasmussen R | title = Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium | journal = Molecular Pharmacology | volume = 35 | issue = 3 | pages = 295–303 | date = March 1989 | doi = 10.1016/S0026-895X(25)11117-6 | pmid = 2564629 }}

Bisoprolol competitively blocks the activation of this cascade, so decreases the adrenergic tone/stimulation of the heart muscle and pacemaker cells. Decreased adrenergic tone shows less contractility of heart muscle and lowered heart rate of pacemakers.{{cite journal | vauthors = Leopold G, Pabst J, Ungethüm W, Bühring KU | title = Basic pharmacokinetics of bisoprolol, a new highly beta 1-selective adrenoceptor antagonist | journal = Journal of Clinical Pharmacology | volume = 26 | issue = 8 | pages = 616–621 | year = 1986 | pmid = 2878941 | doi = 10.1002/j.1552-4604.1986.tb02959.x | s2cid = 42159046 }}{{cite journal | vauthors = Leopold G, Ungethüm W, Pabst J, Simane Z, Bühring KU, Wiemann H | title = Pharmacodynamic profile of bisoprolol, a new beta 1-selective adrenoceptor antagonist | journal = British Journal of Clinical Pharmacology | volume = 22 | issue = 3 | pages = 293–300 | date = September 1986 | pmid = 2876722 | pmc = 1401121 | doi = 10.1111/j.1365-2125.1986.tb02890.x }}

Bisoprolol β₁-selectivity is especially important in comparison to other nonselective beta blockers. The effects of the drug are limited to areas containing β₁ adrenoreceptors, which are mainly the heart and part of the kidney. Bisoprolol, whilst β₁ adrenoceptor selective can help patients to avoid certain side-effects associated with non-selective beta-blocker activity at additional adrenoceptors (α₁ and β₂), it does not signify its superiority in treating beta-blocker indicated cardiac conditions such as heart failure but could prove beneficial to patients with specific comorbidities.{{cite journal | vauthors = Taniguchi T, Ohtani T, Mizote I, Kanzaki M, Ichibori Y, Minamiguchi H, Asano Y, Sakata Y, Komuro I | display-authors = 6 | title = Switching from carvedilol to bisoprolol ameliorates adverse effects in heart failure patients with dizziness or hypotension | journal = Journal of Cardiology | volume = 61 | issue = 6 | pages = 417–422 | date = June 2013 | pmid = 23548374 | doi = 10.1016/j.jjcc.2013.01.009 | doi-access = free }}{{cite journal | vauthors = Düngen HD, Apostolovic S, Inkrot S, Tahirovic E, Töpper A, Mehrhof F, Prettin C, Putnikovic B, Neskovic AN, Krotin M, Sakac D, Lainscak M, Edelmann F, Wachter R, Rau T, Eschenhagen T, Doehner W, Anker SD, Waagstein F, Herrmann-Lingen C, Gelbrich G, Dietz R | display-authors = 6 | title = Titration to target dose of bisoprolol vs. carvedilol in elderly patients with heart failure: the CIBIS-ELD trial | journal = European Journal of Heart Failure | volume = 13 | issue = 6 | pages = 670–680 | date = June 2011 | pmid = 21429992 | pmc = 3101867 | doi = 10.1093/eurjhf/hfr020 }}

Bisoprolol has a higher degree of β₁-selectivity compared to atenolol, metoprolol and betaxolol.{{cite journal | vauthors = Muresan L, Cismaru G, Muresan C, Rosu R, Gusetu G, Puiu M, Mada RO, Martins RP | display-authors = 6 | title = Beta-blockers for the treatment of arrhythmias: Bisoprolol - a systematic review | journal = Annales Pharmaceutiques Françaises | volume = 80 | issue = 5 | pages = 617–634 | date = September 2022 | pmid = 35093388 | doi = 10.1016/j.pharma.2022.01.007 | s2cid = 246428722 | url = https://hal.archives-ouvertes.fr/hal-03719705/file/Muresan%20et%20al-2022-Beta%20blockers%20for%20the%20treatment%20of%20arrhythmias.pdf | access-date = 26 October 2023 | archive-date = 19 April 2024 | archive-url = https://web.archive.org/web/20240419035547/https://hal.archives-ouvertes.fr/hal-03719705/file/Muresan%20et%20al-2022-Beta%20blockers%20for%20the%20treatment%20of%20arrhythmias.pdf | url-status = live }} With a selectivity ranging from being 11 to 15 times more selective for β₁ over β₂.{{cite journal | vauthors = Haeusler G, Schliep HJ, Schelling P, Becker KH, Klockow M, Minck KO, Enenkel HJ, Schulze E, Bergmann R, Schmitges CJ | display-authors = 6 | title = High beta 1-selectivity and favourable pharmacokinetics as the outstanding properties of bisoprolol | journal = Journal of Cardiovascular Pharmacology | volume = 8 | issue = Suppl 11 | pages = S2-15 | year = 1986 | pmid = 2439793 | doi = 10.1097/00005344-198511001-00002 | s2cid = 24617470 }}{{cite journal | vauthors = Harting J, Becker KH, Bergmann R, Bourgois R, Enenkel HJ, Fuchs A, Jonas R, Lettenbaur H, Minck KO, Schelling P | display-authors = 6 | title = Pharmacodynamic profile of the selective beta 1-adrenoceptor antagonist bisoprolol | journal = Arzneimittel-Forschung | volume = 36 | issue = 2 | pages = 200–208 | date = February 1986 | pmid = 2870720 }}{{cite journal | vauthors = Kaumann AJ, Lemoine H | title = Direct labelling of myocardial beta 1-adrenoceptors. Comparison of binding affinity of 3H-(-)-bisoprolol with its blocking potency | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 331 | issue = 1 | pages = 27–39 | date = October 1985 | pmid = 2866449 | doi = 10.1007/bf00498849 | s2cid = 22328991 }}{{cite journal | vauthors = Klockow M, Greiner HE, Haase A, Schmitges CJ, Seyfried C | title = Studies on the receptor profile of bisoprolol | journal = Arzneimittel-Forschung | volume = 36 | issue = 2 | pages = 197–200 | date = February 1986 | pmid = 2870719 }}{{cite journal | vauthors = Manalan AS, Besch HR, Watanabe AM | title = Characterization of [3H](+/-)carazolol binding to beta-adrenergic receptors. Application to study of beta-adrenergic receptor subtypes in canine ventricular myocardium and lung | journal = Circulation Research | volume = 49 | issue = 2 | pages = 326–336 | date = August 1981 | pmid = 6113900 | doi = 10.1161/01.res.49.2.326 | doi-access = free }}{{cite journal | vauthors = Schliep HJ, Schulze E, Harting J, Haeusler G | title = Antagonistic effects of bisoprolol on several beta-adrenoceptor-mediated actions in anaesthetized cats | journal = European Journal of Pharmacology | volume = 123 | issue = 2 | pages = 253–261 | date = April 1986 | pmid = 3011461 | doi = 10.1016/0014-2999(86)90666-7 }}{{cite journal | vauthors = Schliep HJ, Harting J | title = Beta 1-selectivity of bisoprolol, a new beta-adrenoceptor antagonist, in anesthetized dogs and guinea pigs | journal = Journal of Cardiovascular Pharmacology | volume = 6 | issue = 6 | pages = 1156–1160 | year = 1984 | pmid = 6084774 | doi = 10.1097/00005344-198406060-00024 | doi-access = free }}{{cite journal | vauthors = Schnabel P, Maack C, Mies F, Tyroller S, Scheer A, Böhm M | title = Binding properties of beta-blockers at recombinant beta1-, beta2-, and beta3-adrenoceptors | journal = Journal of Cardiovascular Pharmacology | volume = 36 | issue = 4 | pages = 466–471 | date = October 2000 | pmid = 11026647 | doi = 10.1097/00005344-200010000-00008 | doi-access = free }}{{cite journal | vauthors = Smith C, Teitler M | title = Beta-blocker selectivity at cloned human beta 1- and beta 2-adrenergic receptors | journal = Cardiovascular Drugs and Therapy | volume = 13 | issue = 2 | pages = 123–126 | date = April 1999 | pmid = 10372227 | doi = 10.1023/A:1007784109255 | s2cid = 12639448 }}{{cite journal | vauthors = Wellstein A, Palm D, Belz GG | title = Affinity and selectivity of beta-adrenoceptor antagonists in vitro | journal = Journal of Cardiovascular Pharmacology | volume = 8 | issue = Suppl 11 | pages = S36–S40 | year = 1986 | pmid = 2439796 | doi = 10.1097/00005344-198511001-00006 | s2cid = 30987576 }} However, nebivolol is approximately 3.5 times more β₁-selective.{{cite journal | vauthors = Bundkirchen A, Brixius K, Bölck B, Nguyen Q, Schwinger RH | title = Beta 1-adrenoceptor selectivity of nebivolol and bisoprolol. A comparison of [3H]CGP 12.177 and [125I]iodocyanopindolol binding studies | journal = European Journal of Pharmacology | volume = 460 | issue = 1 | pages = 19–26 | date = January 2003 | pmid = 12535855 | doi = 10.1016/S0014-2999(02)02875-3 }}{{cite journal | vauthors = Nuttall SL, Routledge HC, Kendall MJ | title = A comparison of the beta1-selectivity of three beta1-selective beta-blockers | journal = Journal of Clinical Pharmacy and Therapeutics | volume = 28 | issue = 3 | pages = 179–186 | date = June 2003 | pmid = 12795776 | doi = 10.1046/j.1365-2710.2003.00477.x | s2cid = 58760796 }}

Bisoprolol inhibits renin secretion by about 65% and tachycardia by about 30%.

After ingestion, bisoprolol is absorbed and has a high bioavailability of approximately 90% with a plasma half-life of 10–12 hours. Typically, half the circulating bisoprolol is metabolized by the liver, the rest passing unchanged through the kidneys before elimination; less than 2% may be excreted in the feces.

Bisoprolol is soluble in both lipids and water. It is classified as a beta blocker with moderate lipophilicity and hence intermediate potential for crossing the blood–brain barrier.{{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 (Kaunas) | volume = 57 | issue = 2 | date = February 2021 | page = 155 | pmid = 33572109 | pmc = 7914867 | doi = 10.3390/medicina57020155 | url = | doi-access = free }} This in turn may result in fewer effects in the central nervous system as well as a lower risk of neuropsychiatric side effects than highly lipophilic beta blockers like propranolol but greater such effects than beta blockers with low lipophilicity like atenolol.

The plasma protein binding of bisoprolol is approximately 35%, the volume of distribution is 3.5 L/kg and the total clearance is approximately 15 L/h. Bisoprolol is eliminated from the body in two ways - 50% of the substance is converted in the liver to inactive metabolites, which are then excreted in the kidneys. The remaining 50% is eliminated unchanged via the kidneys.{{Cite web |title=Bisoprolol |url=https://go.drugbank.com/drugs/DB00612 |access-date=17 August 2022 |website=go.drugbank.com |archive-date=17 August 2022 |archive-url=https://web.archive.org/web/20220817143701/https://go.drugbank.com/drugs/DB00612 |url-status=live }} Since elimination is equal in liver and kidney, no dose adjustment is required in patients with hepatic or renal impairment.

The pharmacokinetics of bisoprolol are linear and independent of age.

In patients with chronic heart failure, the plasma level of bisoprolol is higher and the half-life is longer than in healthy subjects when compared across studies. There is a lack of evidence directly comparing bisoprolol pharmacokinetics between healthy subjects and chronic heart failure subjects.{{cite journal | vauthors = Kirch W, Rose I, Demers HG, Leopold G, Pabst J, Ohnhaus EE | title = Pharmacokinetics of bisoprolol during repeated oral administration to healthy volunteers and patients with kidney or liver disease | journal = Clinical Pharmacokinetics | volume = 13 | issue = 2 | pages = 110–117 | date = August 1987 | pmid = 2887325 | doi = 10.2165/00003088-198713020-00003 | s2cid = 25105692 }}{{cite journal | vauthors = Cvan Trobec K, Grabnar I, Kerec Kos M, Vovk T, Trontelj J, Anker SD, Rosano G, Lainscak M | display-authors = 6 | title = Bisoprolol pharmacokinetics and body composition in patients with chronic heart failure: a longitudinal study | journal = European Journal of Clinical Pharmacology | volume = 72 | issue = 7 | pages = 813–822 | date = July 2016 | pmid = 26996442 | doi = 10.1007/s00228-016-2041-1 | s2cid = 14146663 }}

{{Reflist}}

{{Beta blockers}}

{{Merck Serono|state=autocollapse}}

{{Portal bar | Medicine}}

{{Authority control}}

Category:Beta blockers

Category:N-isopropyl-phenoxypropanolamines

Category:Peripherally selective drugs

Category:Drugs developed by Merck

Category:World Health Organization essential medicines

Category:Wikipedia medicine articles ready to translate