Back To Search Results

Bisoprolol

Editor: Nada F. Alrashidi Updated: 8/17/2023 10:54:05 AM

Indications

Bisoprolol is a cardioselective beta1-blocker (B1-blocker). Selective B1-blockers are used to treat multiple heart diseases, such as congestive heart failure, without having the unwanted effect of the B2 receptor blocking, which can affect various systems in the body.[1]

  • Bisoprolol is FDA-approved for the management of hypertension. Clinicians must recognize that according to ACC/AHA guidelines, bisoprolol or other beta blockers are not the first-line treatment for hypertension unless the patient has ischemic heart disease or HFrEF.[2]
  • Bisoprolol is used in the treatment plan for compensated heart failure. According to 2022 AHA/ACC/HFSA guidelines, specific beta-blockers (bisoprolol, metoprolol succinate, and carvedilol) are included in guideline-directed medical therapy(GDMT) for heart failure with reduced ejection fraction(HFrEF). Bisoprolol is recommended to reduce mortality and hospitalizations in patients with HFrEF.[3]
  • Selective B1- blockers are used as the first-line treatment for chronic stable angina.[4] According to the 2020 International Society of Hypertension practice guidelines, cardioselective beta-blockers such as bisoprolol should be used (with or without calcium channel blockers) in patients with coronary artery disease.[5]
  • The use of bisoprolol correlates with decreased morbidity and mortality post-MI.[6] Bisoprolol reduces the risk of stroke and coronary artery disease in patients with heart disease.[7]
  • Non-FDA-approved uses of bisoprolol include the treatment of migraine, arrhythmia, and tremors; as an anxiolytic for some athletes and musicians.[8][9]
  • A fixed-dose combination of bisoprolol and hydrochlorothiazide is approved by FDA for managing hypertension.[10]

Mechanism of Action

Register For Free And Read The Full Article
Get the answers you need instantly with the StatPearls Clinical Decision Support tool. StatPearls spent the last decade developing the largest and most updated Point-of Care resource ever developed. Earn CME/CE by searching and reading articles.
  • Dropdown arrow Search engine and full access to all medical articles
  • Dropdown arrow 10 free questions in your specialty
  • Dropdown arrow Free CME/CE Activities
  • Dropdown arrow Free daily question in your email
  • Dropdown arrow Save favorite articles to your dashboard
  • Dropdown arrow Emails offering discounts

Learn more about a Subscription to StatPearls Point-of-Care

Mechanism of Action

Selective B1 blocker drugs have negative inotropic and chronotropic effects; they decrease heart contractions and heart rate. As a net result, bisoprolol reduces the oxygen consumption of myocardial cells. B1 receptors are also present in the juxtaglomerular cells. By blocking these receptors, bisoprolol leads to a decrease in the release of renin; as a result, this decrease in renin blocks the activation of the renin-angiotensin system.[11]

B1 adrenergic receptors are present in cardiac myocyte cells and juxtaglomerular cells. They couple with the G-stimulatory protein receptor (Gs receptor) and become stimulated by either norepinephrine or circulating catecholamine. Activation of B1 receptors in cardiac myocytes leads to positive chronotropic and inotropic effects; therefore, the net result will be increased heart rate, contraction, and the strength of myocyte contraction by activating Gs receptors (by the exchange of GTP to GDP). Eventually, this activity increases intracellular calcium concentration and promotes heart cell contraction.[12][13][14]

Activation of B1 receptors on juxtaglomerular cells leads to activating the renin-angiotensin system. Releasing renin increases the production of angiotensin I, which is eventually converted by an angiotensin-converting enzyme (ACE) to angiotensin II.

B2 receptors are present in multiple body organs and are activated by epinephrine, leading to different manifestations according to the location involved. In peripheral vessels, it causes vasodilation and decreases peripheral resistance, opposing the effect of alpha-1 receptors, which cause vasoconstriction in the peripheral vessels. On the bronchioles, it leads to extensive bronchodilation. In addition, B2 receptor activation in the liver and the muscles activates glycogenolysis and glucagon release, increasing blood sugar levels.

Non-selective beta-blocker drugs block both the B1 and B2 receptors, decreasing cardiac output and decreasing renin release from the kidney. And B2 receptor blockage leads to additional manifestations—vasoconstriction of the peripheral vessels. Blocking B2 receptors causes bronchial muscle contraction in the lung, leading to bronchospasm in patients with COPD or asthma. It also leads to decrease glycogenolysis and glucagon release, which may lead to hypoglycemia.[9][15]

Pharmacokinetics 

Absorption: Bisporolol is well absorbed, and the bioavailability of bisoprolol is approximately 80%. The time to peak plasma concentration is approximately 2 to 4 hours. Steady-state plasma concentration is achieved in 5 days.[16]

Distribution: Bisoprolol has low lipophilicity; penetration the through the blood-brain barrier is minimal. The volume of distribution of about 3.5 L/kg.[17]

Metabolism: Bisoprolol is primarily metabolized by the CYP3A4 and CYP2D6(minor). First-pass metabolism of bisoprolol is low.[18]

Excretion: Bisoprolol is eliminated by  50% renal excretion (unchanged drug) and 50% by hepatic metabolism to pharmacologically inactive metabolites excreted by the kidneys. Tubular secretion plays an important role in the renal elimination of bisoprolol. Excretion through feces is approximately 2%. Bisoprolol fumarate has a long half-life that extends from 9 to 12 hours.[19][20]

Administration

Cardioselective agents are either administered orally or intravenously. Bisoprolol fumarate is administered orally as 5 or 10 mg tablets once daily.

Hypertension: The dose of bisoprolol fumarate should be tailored to the patient's individualized needs. The usual starting dose is 5 mg once daily. If the 5 mg dose does not produce the desired antihypertensive effect,  the dose should be gradually increased to 10 mg and then, if needed, to 20 mg once daily.[21]

Heart Failure With Reduced Ejection Fraction: The initial dose is 1.25 mg once daily, while the target dose is 10 mg once daily. To optimize GDMT, the dose should be titrated every 1 to 2 weeks based on symptoms, vital signs, and volume status. Bisoprolol should be started once acute decompensated heart failure is stabilized, and the patient does not require vasopressors or inotropes.[3]

Atrial Fibrillation: According to AHA/ACC/HRS guidelines, the dose of bisoprolol for rate control is 2.5 mg to 10 mg PO once daily.[22][23]

Coronary Artery Disease: According to AHA/ACC/ASH guidelines, beta-blockers without intrinsic sympathomimetic activity, such as bisoprolol, should be used for CAD. The dose of bisoprolol is 5 to 10 mg once daily. The drug should not be used for variant angina (Prinzmetal angina).[24]

Specific Populations

Hepatic Impairment: According to the manufacturer's prescribing information in patients with hepatitis or cirrhosis, the initial daily dose should be 2.5 mg and, if needed, titrated upward slowly.

Renal Impairment: According to the manufacturer's prescribing information, in patients with creatinine clearance less than 40 ml/min starting dose should be 2.5 mg per day, and titrate upwards slowly. Since limited data suggest that bisoprolol fumarate is not dialyzable, dose adjustment is unnecessary for dialysis patients.

Older Patients: The dose needs to be adjusted in older patients only if there is significant hepatic or renal dysfunction.

Pediatric Patients: Product labeling has no information on pediatric experience with bisoprolol fumarate; there are no approved indications for pediatric patients.

Pregnancy Considerations: Bisoprolol is a former FDA category C medicine and should be used only if there are no other alternatives to its therapy. According to the ACOG (American College of Obstetricians and Gynecologists), labetalol might be preferred over bisoprolol to treat gestational hypertension.[25][26]

Breastfeeding Considerations: The excretion of beta blockers in breast milk is primarily determined by plasma protein binding (PPB). Low plasma protein binding is associated with increased excretion in breast milk. Bisoprolol has low PPB (30%), a long half-life, and a potential risk of accumulation in infants. In addition, there is minimal clinical experience in using bisoprolol during breastfeeding; consequently, other drugs are preferred, particularly if nursing a newborn or preterm infant.[27]

Adverse Effects

A common adverse effect of cardiovascular blockers is bradycardia, decreasing heart rate and strength of contraction due to its negative chronotropic and inotropic effects. Bisoprolol also decreases cardiac output; therefore, it decreases exercise capacity. Blocking beta receptors on the SA and AV node always carries a risk of heart block. It correlates less frequently with exacerbating peripheral diseases such as the Raynaud phenomenon, bronchoconstriction, and hypoglycemia than non-selective beta-blockers.[28]

Other commonly encountered adverse effects include nausea, vomiting, and constipation. Hypoglycemia is a dangerous adverse effect in people with diabetes using beta-blockers. The drug blocks the typical signs of hypoglycemia, such as tachycardia, delaying the body's normal response to hypoglycemia, possibly leading to fear of complications.[29] 

Bradycardia, fatigue, asthenia, diarrhea, and sinusitis are dose-related among all adverse events. Beta-blockers, including bisoprolol, are implicated in drug-induced psoriasis and the worsening of pre-existing psoriasis.[30][31][32] 

Neuropsychiatric adverse events such as insomnia may be caused by bisoprolol, but a recent study by AHA found no association between bisoprolol use and depression.[33]

Drug-Drug Interactions

  • Abrupt discontinuation of clonidine while taking bisoprolol results in a catecholamine surge and can lead to rebound hypertension. Bisoprolol should be stopped several days before the discontinuation of clonidine.[34]
  • Concomitant use of bisoprolol with calcium channel blockers such as verapamil and diltiazem may worsen the myocardial function and result in hypotension, bradycardia, and AV block.[35]
  • Strong CYP3A4 induces, like rifampin, increases the clearance of bisoprolol, resulting in a short elimination half-life of bisoprolol.[36]
  • Concomitant administration of cholinesterase inhibitors like donepezil with bisoprolol can increase the risk for bradycardia, falls, and syncope.[37]
  • Concomitant use of bisoprolol with digoxin delays AV conduction and can increase the risk of bradycardia.[38]

Contraindications

Cardioselective beta-blockers are contraindicated in patients with marked sinus bradycardia, cardiogenic shock, and complete heart block (third-degree AV block).[39] Patients with second-degree AV block should be monitored carefully. In addition, patients with a history of recent fluid retention should not use beta-blockers without the concomitant use of diuretics.[40] 

New studies suggest that cardioselective beta-blockers are contraindicated in patients with severe asthma or COPD, while it is entirely safe in patients with mild to moderate diseases.[41] 

In patients with diabetes, beta blockers may mask hypoglycemia, so careful monitoring is necessary.[42] Bisoprolol should not be abruptly withdrawn as doing so can cause rebound hypertension and tachycardia. In addition, some patients have developed or exacerbated existing angina pectoris, myocardial infarction, or ventricular arrhythmia when cessed therapy abruptly. Gradual reduction of the dose is recommended.[43]

Monitoring

The essential components to monitor at every visit in patients on the cardioselective beta-blocker are blood pressure and heart rate to detect and prevent bradycardia and hypotension. The cardiac electricity level should be monitored to avoid any degree of heart block. Renal function tests and complete blood counts are not indicated for regular monitoring but are necessary when there is a suspicion of toxicity or if the physician is concerned about the therapeutic level of the medicine.[28] 

The blood sugar level is regularly monitored in diabetic patients to prevent beta blocker-masked hypoglycemic episodes. Monitoring of lactate level is mandatory in a patient suspected of ingesting a high dose of beta-blockers due to the chance of having mesenteric ischemia.[44] 

In case of maternal exposure to bisoprolol, monitor the newborn baby's HR, blood glucose, and respiratory rate for 48 hours after birth.[25] Beta-blockers can worsen myasthenia gravis. Monitor for worsening of ptosis, diplopia, and muscle weakness.[45]

Toxicity

The toxicity of cardio-selective beta-blockers occurs after ingesting a high dose of the drug, either intentionally or unintentionally. Toxicity can be asymptomatic in some patients, but treatment is always required. Patients in such cases usually present with bradycardia and hypotension. In addition, selective beta-blockers in high doses lose their selectivity, causing patients to demonstrate signs of respiratory distress, congestive heart failure, and neurological manifestations, such as confusion and mental retardation, hypoglycemia, and hyperkalemia.

The beta-blocker overdose treatment protocol includes several medicines based on the signs and symptoms of clinical toxicity.[46][47]

  • Sympathomimetic agents (IV atropine or isoproterenol) are used in patients who experience bradycardia.
  • To antagonize beta-blocker-induced hypotension, the clinician should administer intravenous glucagon and fluid. Epinephrine may be ineffective in anaphylaxis induced by beta blockers. Glucagon stimulates heart contraction by glucagon receptors, which are not blocked by beta-blockers.[48]
  • To reverse the bronchospasm induced by beta-blockers, isoproterenol, and aminophylline can be used.
  • Depending on the patient's hemodynamic stability, hypoglycemia can be addressed by administering glucose orally or IV.
  • The patient needs to be monitored carefully in case of a heart block and should be treated with isoproterenol infusion or transvenous cardiac pacemaker insertion.[49]
  • Congestion and impaired perfusion status should be accurately determined in acute decompensated heart failure due to severe overdose. Digitalis, diuretics, inotropic agents, and vasopressors should be used according to hemodynamic status.[50]

Enhancing Healthcare Team Outcomes

Clinicians prescribe bisoprolol for hypertension, Heart failure with reduced ejection fraction, and coronary artery disease. Bisoprolol can mask the symptoms of hypoglycemia in diabetes; drug interactions can lead to bradycardia and AV block. In addition, abrupt withdrawal of bisoprolol can be life-threatening as it can cause life-threatening tachycardia, rebound hypertension, and in some cases, angina.

With careful monitoring of the patient's heart rate, blood pressure, temperature, and renal function, the clinician must know the possible adverse drug reactions and their appropriate management. The cardiologist's role is crucial in managing coronary artery disease. Arrhythmias refractory to bisoprolol therapy may require EP consultation. Patient care delivered by heart failure specialists is associated with lower mortality rates.[51]

Pharmacists must be aware of the required doses of the drug for each patient and perform medication reconciliation. Nurses can counsel the patients regarding administration and, along with the pharmacist, counsel the patient on potential adverse effects. Pharmacists and nurses must report any issues with the therapy regimen to the prescribing clinician for corrective action. Bisoprolol toxicity from accidental overdose is also possible in a patient with hypertension, so it is essential to know how to antagonize the drug's effect using high-dose glucagon. A study demonstrated that inpatient services delivered by medical toxicologists are associated with reduced length of stay and mortality in poisoning and overdose.[52] 

A psychiatrist consultation is required if the overdose of bisoprolol is intentional. An interprofessional team approach delivered by physicians, advanced practice practitioners, cardiologists, pulmonologists (for patients with asthma), pharmacists, specialty-trained nursing staff, and toxicologists can achieve optimal patient outcomes related to bisoprolol therapy.

References


[1]

Minushkina LO. [Bisoprolol: opportunities in the treatment of hypertension]. Kardiologiia. 2012:52(6):80-5     [PubMed PMID: 22839675]


[2]

Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright JT Jr. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension (Dallas, Tex. : 1979). 2018 Jun:71(6):e13-e115. doi: 10.1161/HYP.0000000000000065. Epub 2017 Nov 13     [PubMed PMID: 29133356]

Level 1 (high-level) evidence

[3]

Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2022 May 3:79(17):e263-e421. doi: 10.1016/j.jacc.2021.12.012. Epub 2022 Apr 1     [PubMed PMID: 35379503]

Level 1 (high-level) evidence

[4]

Wee Y, Burns K, Bett N. Medical management of chronic stable angina. Australian prescriber. 2015 Aug:38(4):131-6     [PubMed PMID: 26648642]


[5]

Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, Ramirez A, Schlaich M, Stergiou GS, Tomaszewski M, Wainford RD, Williams B, Schutte AE. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension (Dallas, Tex. : 1979). 2020 Jun:75(6):1334-1357. doi: 10.1161/HYPERTENSIONAHA.120.15026. Epub 2020 May 6     [PubMed PMID: 32370572]

Level 1 (high-level) evidence

[6]

Poldermans D, Boersma E, Bax JJ, Thomson IR, Paelinck B, van de Ven LL, Scheffer MG, Trocino G, Vigna C, Baars HF, van Urk H, Roelandt JR, Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. Bisoprolol reduces cardiac death and myocardial infarction in high-risk patients as long as 2 years after successful major vascular surgery. European heart journal. 2001 Aug:22(15):1353-8     [PubMed PMID: 11465968]

Level 1 (high-level) evidence

[7]

Cruickshank JM. Beta-blockers and heart failure. Indian heart journal. 2010 Mar-Apr:62(2):101-10     [PubMed PMID: 21180298]


[8]

Ladage D, Schwinger RH, Brixius K. Cardio-selective beta-blocker: pharmacological evidence and their influence on exercise capacity. Cardiovascular therapeutics. 2013 Apr:31(2):76-83. doi: 10.1111/j.1755-5922.2011.00306.x. Epub 2012 Jan 26     [PubMed PMID: 22279967]

Level 3 (low-level) evidence

[9]

do Vale GT, Ceron CS, Gonzaga NA, Simplicio JA, Padovan JC. Three Generations of β-blockers: History, Class Differences and Clinical Applicability. Current hypertension reviews. 2019:15(1):22-31. doi: 10.2174/1573402114666180918102735. Epub     [PubMed PMID: 30227820]


[10]

Papadopoulos DP, Papademetriou V. Low-dose fixed combination of bisoprolol/hydrochlorothiazide as first line for hypertension: a review of the rationale and clinical evidence. Angiology. 2009 Oct-Nov:60(5):601-7. doi: 10.1177/0003319708324926. Epub 2008 Nov 21     [PubMed PMID: 19028769]

Level 3 (low-level) evidence

[11]

Johns TE, Lopez LM. Bisoprolol: is this just another beta-blocker for hypertension or angina? The Annals of pharmacotherapy. 1995 Apr:29(4):403-14     [PubMed PMID: 7633020]


[12]

Galougahi KK, Liu CC, Bundgaard H, Rasmussen HH. β-Adrenergic regulation of the cardiac Na+-K+ ATPase mediated by oxidative signaling. Trends in cardiovascular medicine. 2012 May:22(4):83-7. doi: 10.1016/j.tcm.2012.06.017. Epub     [PubMed PMID: 23040838]


[13]

Kamp TJ, Hell JW. Regulation of cardiac L-type calcium channels by protein kinase A and protein kinase C. Circulation research. 2000 Dec 8:87(12):1095-102     [PubMed PMID: 11110765]


[14]

Kushnir A, Marks AR. The ryanodine receptor in cardiac physiology and disease. Advances in pharmacology (San Diego, Calif.). 2010:59():1-30. doi: 10.1016/S1054-3589(10)59001-X. Epub     [PubMed PMID: 20933197]

Level 3 (low-level) evidence

[15]

Ram CV. Beta-blockers in hypertension. The American journal of cardiology. 2010 Dec 15:106(12):1819-25. doi: 10.1016/j.amjcard.2010.08.023. Epub 2010 Nov 2     [PubMed PMID: 21126627]

Level 1 (high-level) evidence

[16]

Ishida K, Horie A, Nishimura M, Taguchi M, Fujii N, Nozawa T, Inoue H, Hashimoto Y. Variability of bioavailability and intestinal absorption characteristics of bisoprolol. Drug metabolism and pharmacokinetics. 2013:28(6):491-6     [PubMed PMID: 23719964]


[17]

Chan SW, Chu TTW, Ho CS, Kong APS, Tomlinson B, Zeng W. Influence of CYP2D6 and CYP3A5 Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Bisoprolol in Hypertensive Chinese Patients. Frontiers in medicine. 2021:8():683498. doi: 10.3389/fmed.2021.683498. Epub 2021 Sep 9     [PubMed PMID: 34568359]


[18]

Ågesen FN, Weeke PE, Tfelt-Hansen P, Tfelt-Hansen J, for ESCAPE‐NET. Pharmacokinetic variability of beta-adrenergic blocking agents used in cardiology. Pharmacology research & perspectives. 2019 Aug:7(4):e00496. doi: 10.1002/prp2.496. Epub 2019 Jul 12     [PubMed PMID: 31338197]

Level 3 (low-level) evidence

[19]

Li GF, Wang K, Chen R, Zhao HR, Yang J, Zheng QS. Simulation of the pharmacokinetics of bisoprolol in healthy adults and patients with impaired renal function using whole-body physiologically based pharmacokinetic modeling. Acta pharmacologica Sinica. 2012 Nov:33(11):1359-71. doi: 10.1038/aps.2012.103. Epub 2012 Oct 22     [PubMed PMID: 23085739]


[20]

Abeel M, Gupta A, Constance C. Concomitant Treatment of Hypertensive Patients with Bisoprolol and Perindopril in Routine Clinical Practice: A Post Hoc Analysis of the CONFIDENCE II, PROTECT I, and PROTECT III Observational Studies. Advances in therapy. 2022 Jan:39(1):391-404. doi: 10.1007/s12325-021-01958-6. Epub 2021 Nov 10     [PubMed PMID: 34755324]

Level 3 (low-level) evidence

[21]

Bonelli J, Staribacher H. Haemodynamic effects of bisoprolol in patients with coronary heart disease: influence of various bisoprolol plasma concentrations. Journal of cardiovascular pharmacology. 1986:8 Suppl 11():S83-6     [PubMed PMID: 2439805]


[22]

January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW, ACC/AHA Task Force Members. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014 Dec 2:130(23):e199-267. doi: 10.1161/CIR.0000000000000041. Epub 2014 Mar 28     [PubMed PMID: 24682347]

Level 1 (high-level) evidence

[23]

Muresan L, Cismaru G, Muresan C, Rosu R, Gusetu G, Puiu M, Mada RO, Martins RP. Beta-blockers for the treatment of arrhythmias: Bisoprolol - a systematic review. Annales pharmaceutiques francaises. 2022 Sep:80(5):617-634. doi: 10.1016/j.pharma.2022.01.007. Epub 2022 Jan 31     [PubMed PMID: 35093388]

Level 1 (high-level) evidence

[24]

Rosendorff C, Lackland DT, Allison M, Aronow WS, Black HR, Blumenthal RS, Cannon CP, de Lemos JA, Elliott WJ, Findeiss L, Gersh BJ, Gore JM, Levy D, Long JB, O'Connor CM, O'Gara PT, Ogedegbe G, Oparil S, White WB, American Heart Association, American College of Cardiology, and American Society of Hypertension. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. Circulation. 2015 May 12:131(19):e435-70. doi: 10.1161/CIR.0000000000000207. Epub 2015 Mar 31     [PubMed PMID: 25829340]


[25]

Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomström-Lundqvist C, Cífková R, De Bonis M, Iung B, Johnson MR, Kintscher U, Kranke P, Lang IM, Morais J, Pieper PG, Presbitero P, Price S, Rosano GMC, Seeland U, Simoncini T, Swan L, Warnes CA, ESC Scientific Document Group. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. European heart journal. 2018 Sep 7:39(34):3165-3241. doi: 10.1093/eurheartj/ehy340. Epub     [PubMed PMID: 30165544]


[26]

. ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstetrics and gynecology. 2019 Jan:133(1):1. doi: 10.1097/AOG.0000000000003018. Epub     [PubMed PMID: 30575675]


[27]

. Bisoprolol. Drugs and Lactation Database (LactMed®). 2006:():     [PubMed PMID: 30000203]


[28]

Tucker WD, Sankar P, Theetha Kariyanna P. Selective Beta-1 Blockers. StatPearls. 2023 Jan:():     [PubMed PMID: 29763157]


[29]

Fonseca VA. Effects of beta-blockers on glucose and lipid metabolism. Current medical research and opinion. 2010 Mar:26(3):615-29. doi: 10.1185/03007990903533681. Epub     [PubMed PMID: 20067434]

Level 3 (low-level) evidence

[30]

Milavec-Puretić V, Mance M, Ceović R, Lipozenčić J. Drug induced psoriasis. Acta dermatovenerologica Croatica : ADC. 2011:19(1):39-42     [PubMed PMID: 21489366]


[31]

Awad VM, Sakhamuru S, Kambampati S, Wasim S, Malik BH. Mechanisms of Beta-Blocker Induced Psoriasis, and Psoriasis De Novo at the Cellular Level. Cureus. 2020 Jul 2:12(7):e8964. doi: 10.7759/cureus.8964. Epub 2020 Jul 2     [PubMed PMID: 32766006]


[32]

Waqar S, Sarkar PK. Exacerbation of psoriasis with beta-blocker therapy. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2009 Jul 7:181(1-2):60. doi: 10.1503/cmaj.081433. Epub     [PubMed PMID: 19581619]

Level 3 (low-level) evidence

[33]

Scheer FA, Morris CJ, Garcia JI, Smales C, Kelly EE, Marks J, Malhotra A, Shea SA. Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. Sleep. 2012 Oct 1:35(10):1395-402     [PubMed PMID: 23024438]

Level 1 (high-level) evidence

[34]

Handler J. Adverse effects using combined rate-slowing antihypertensive agents. Journal of clinical hypertension (Greenwich, Conn.). 2011 Jul:13(7):529-32. doi: 10.1111/j.1751-7176.2011.00486.x. Epub 2011 Jun 20     [PubMed PMID: 21762367]

Level 3 (low-level) evidence

[35]

Saedder EA, Thomsen AH, Hasselstrøm JB, Jornil JR. Heart insufficiency after combination of verapamil and metoprolol: A fatal case report and literature review. Clinical case reports. 2019 Nov:7(11):2042-2048. doi: 10.1002/ccr3.2393. Epub 2019 Sep 19     [PubMed PMID: 31788248]

Level 3 (low-level) evidence

[36]

Liu W, Yan T, Chen K, Yang L, Benet LZ, Zhai S. Predicting Interactions between Rifampin and Antihypertensive Drugs Using the Biopharmaceutics Drug Disposition Classification System. Pharmacotherapy. 2020 Apr:40(4):274-290. doi: 10.1002/phar.2380. Epub 2020 Mar 26     [PubMed PMID: 32100890]


[37]

Hernandez RK, Farwell W, Cantor MD, Lawler EV. Cholinesterase inhibitors and incidence of bradycardia in patients with dementia in the veterans affairs new England healthcare system. Journal of the American Geriatrics Society. 2009 Nov:57(11):1997-2003. doi: 10.1111/j.1532-5415.2009.02488.x. Epub 2009 Sep 28     [PubMed PMID: 19793162]

Level 2 (mid-level) evidence

[38]

MacLeod-Glover N, Mink M, Yarema M, Chuang R. Digoxin toxicity: Case for retiring its use in elderly patients? Canadian family physician Medecin de famille canadien. 2016 Mar:62(3):223-8     [PubMed PMID: 26975913]

Level 3 (low-level) evidence

[39]

Osmonov D, Erdinler I, Ozcan KS, Altay S, Turkkan C, Yildirim E, Hasdemir H, Alper AT, Cakmak N, Satilmis S, Gurkan K. Management of patients with drug-induced atrioventricular block. Pacing and clinical electrophysiology : PACE. 2012 Jul:35(7):804-10. doi: 10.1111/j.1540-8159.2012.03410.x. Epub 2012 Apr 24     [PubMed PMID: 22530749]


[40]

Cowie MR. Recent developments in the management of heart failure. The Practitioner. 2012 Jun:256(1752):25-9, 3     [PubMed PMID: 22916582]


[41]

Salpeter SR, Ormiston TM, Salpeter EE. Cardioselective beta-blockers in patients with reactive airway disease: a meta-analysis. Annals of internal medicine. 2002 Nov 5:137(9):715-25     [PubMed PMID: 12416945]

Level 1 (high-level) evidence

[42]

Momčilović S, Jovanović A, Radojković D, Nikolić VN, Janković SM, Pešić M, Milovanović JR. Population pharmacokinetic analysis of bisoprolol in type 2 diabetic patients with hypertension. European journal of clinical pharmacology. 2020 Nov:76(11):1539-1546. doi: 10.1007/s00228-020-02937-6. Epub 2020 Jun 25     [PubMed PMID: 32583355]


[43]

Koracevic G, Micic S, Stojanovic M. By Discontinuing Beta-Blockers Before an Exercise Test, We may Precipitate a Rebound Phenomenon. Current vascular pharmacology. 2021:19(6):624-633. doi: 10.2174/1570161119666210302152322. Epub     [PubMed PMID: 33653252]


[44]

Bala M, Catena F, Kashuk J, De Simone B, Gomes CA, Weber D, Sartelli M, Coccolini F, Kluger Y, Abu-Zidan FM, Picetti E, Ansaloni L, Augustin G, Biffl WL, Ceresoli M, Chiara O, Chiarugi M, Coimbra R, Cui Y, Damaskos D, Di Saverio S, Galante JM, Khokha V, Kirkpatrick AW, Inaba K, Leppäniemi A, Litvin A, Peitzman AB, Shelat VG, Sugrue M, Tolonen M, Rizoli S, Sall I, Beka SG, Di Carlo I, Ten Broek R, Mircea C, Tebala G, Pisano M, van Goor H, Maier RV, Jeekel H, Civil I, Hecker A, Tan E, Soreide K, Lee MJ, Wani I, Bonavina L, Malangoni MA, Koike K, Velmahos GC, Fraga GP, Fette A, de'Angelis N, Balogh ZJ, Scalea TM, Sganga G, Kelly MD, Khan J, Stahel PF, Moore EE. Acute mesenteric ischemia: updated guidelines of the World Society of Emergency Surgery. World journal of emergency surgery : WJES. 2022 Oct 19:17(1):54. doi: 10.1186/s13017-022-00443-x. Epub 2022 Oct 19     [PubMed PMID: 36261857]


[45]

Trillenberg P, Katalinic A, Thern J, Graf T. The risk of worsening of myasthenia by cardiovascular medication as reflected by reporting frequency. European journal of neurology. 2021 Sep:28(9):2965-2970. doi: 10.1111/ene.14996. Epub 2021 Jul 9     [PubMed PMID: 34184370]


[46]

Shepherd G. Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2006 Oct 1:63(19):1828-35     [PubMed PMID: 16990629]


[47]

Lauterbach M. Clinical toxicology of beta-blocker overdose in adults. Basic & clinical pharmacology & toxicology. 2019 Aug:125(2):178-186. doi: 10.1111/bcpt.13231. Epub 2019 Apr 15     [PubMed PMID: 30916882]


[48]

Murakami Y, Kaneko S, Yokoyama H, Ishizaki H, Sekino M, Murata H, Hara T. Successful treatment of severe adrenaline-resistant anaphylactic shock with glucagon in a patient taking a beta-blocker: a case report. JA clinical reports. 2021 Dec 15:7(1):86. doi: 10.1186/s40981-021-00490-4. Epub 2021 Dec 15     [PubMed PMID: 34907487]

Level 3 (low-level) evidence

[49]

Tjong FVY, de Ruijter UW, Beurskens NEG, Knops RE. A comprehensive scoping review on transvenous temporary pacing therapy. Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation. 2019 Oct:27(10):462-473. doi: 10.1007/s12471-019-01307-x. Epub     [PubMed PMID: 31392624]

Level 2 (mid-level) evidence

[50]

Raj L, Maidman SD, Adhyaru BB. Inpatient management of acute decompensated heart failure. Postgraduate medical journal. 2020 Jan:96(1131):33-42. doi: 10.1136/postgradmedj-2019-136742. Epub 2019 Sep 12     [PubMed PMID: 31515438]


[51]

Sims DB, Kim Y, Kalininskiy A, Yanamandala M, Josephs J, Rivas-Lasarte M, Ahmed N, Assa A, Jahufar F, Kumar S, Sun E, Rahgozar K, Ali SZ, Zhang M, Patel S, Edwards P, Saeed O, Shin JJ, Murthy S, Patel S, Shah A, Jorde UP. Full-Time Cardiac Intensive Care Unit Staffing by Heart Failure Specialists and its Association with Mortality Rates. Journal of cardiac failure. 2022 Mar:28(3):394-402. doi: 10.1016/j.cardfail.2021.09.013. Epub 2021 Oct 9     [PubMed PMID: 34634449]


[52]

Curry SC, Brooks DE, Skolnik AB, Gerkin RD, Glenn S. Effect of a medical toxicology admitting service on length of stay, cost, and mortality among inpatients discharged with poisoning-related diagnoses. Journal of medical toxicology : official journal of the American College of Medical Toxicology. 2015 Mar:11(1):65-72. doi: 10.1007/s13181-014-0418-z. Epub     [PubMed PMID: 25127915]

Level 2 (mid-level) evidence