|Other names||Beta-blocker, β-blockers, beta-adrenergic blocking agents, beta antagonists, beta-adrenergic antagonists, beta-adrenoreceptor antagonists, beta adrenergic receptor antagonists, BB|
|Uses||Abnormal heart rhythms, ischemic heart disease, heart failure, hypertension|
|Side effects||Tiredness, headache, trouble sleeping, nausea, sexual dysfunction|
|Interactions||Some calcium channel blockers|
|Subtypes||Cardioselective: Atenolol, bisoprolol, metoprolol, esmolol|
Non-cardioselective: Carvedilol, labetalol, propranolol, sotalol
Beta blockers (β-blockers) are a class of medication mainly used to manage abnormal heart rhythms, ischemic heart disease, and heart failure. They are also used to treat high blood pressure, though are no longer a first choice for initial treatment in most people. Other uses may include overactive thyroid, essential tremor, glaucoma, and migraines. Common agents in this class include atenolol, bisoprolol, carvedilol, and metoprolol. They can be taken by mouth, given intravenously, or used as eye drops.
Side effects may include tiredness, headache, trouble sleeping, nausea, and sexual dysfunction. They may cause complications in asthma, low blood pressure, and heart block. Lower doses may be required in those with liver problems and heart failure. They may also interact with certain calcium channel blockers. Beta blocker toxicity is associated with a high risk of a poor outcome.
Beta blockers work by binding to and blocking epinephrine (adrenaline) and norepinephrine (noradrenaline) from activating beta receptors, and thus decrease sympathetic nervous system activity. Some block activation at all β-adrenergic receptors while others are selective for β1- receptors. β1- receptors are located mainly in the heart and kidneys. β2-receptors are located in the smooth muscles of blood vessels and the airway. β3- receptors are located in fat cells.
The first medically useful beta blocker, propranolol, was made in 1964 by James Black. It is considered one of the most important contributions to pharmacology of the 20th century. Beta blockers are among the most widely used medications. Some are available as generic medication and are relatively inexpensive. Their use in particular sports is banned by the International Olympic Committee as they improve accuracy.
Nonselective beta blockers display both β1 and β2 antagonism.
- Bucindolol (has additional α1-blocking activity)
- Carvedilol (has additional α1-blocking activity)
- Labetalol (has additional α1-blocking activity)
- Oxprenolol (has intrinsic sympathomimetic activity)
- Penbutolol (has intrinsic sympathomimetic activity)
- Pindolol (has intrinsic sympathomimetic activity)
- Sotalol (not considered a "typical beta blocker")
β1-selective beta blockers are also known as cardioselective beta blockers.
β1 selective antagonist and β3 agonist
Large differences exist in the pharmacology of agents within the class, thus not all beta blockers are used for all indications listed below.
Uses for beta blockers include:
- Angina pectoris (contraindicated for Prinzmetal's angina)
- Atrial fibrillation
- Cardiac arrhythmia
- Congestive heart failure
- Essential tremor
- Glaucoma (as eye drops, they decrease intraocular pressure by lowering aqueous humor secretion.)
- Hypertension, although they are generally not preferred as an initial treatment.
- Migraine prophylaxis
- Mitral valve prolapse
- Myocardial infarction
- Phaeochromocytoma, in conjunction with α-blocker
- Postural orthostatic tachycardia syndrome
- Symptomatic control (tachycardia, tremor) in anxiety and hyperthyroidism
- Theophylline overdose
Beta blockers have also been used for:
- Acute aortic dissection
- Hypertrophic obstructive cardiomyopathy
- Long QT syndrome
- Marfan syndrome (treatment with propranolol slows progression of aortic dilation and its complications)
- Prevention of variceal bleeding in portal hypertension
- Possible mitigation of hyperhidrosis
- Social and other anxiety disorders
- Controversially, for reduction of perioperative mortality in non-cardiac surgery, but the best evidence suggests that they increase mortality when used this way
High blood pressure
For the treatment of primary hypertension, 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.
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. 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.
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. 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 extracellular volume and increasing the oxygen-carrying capacity of blood. Heart failure characteristically involves increased catecholamine activity on the heart, which is responsible for a number of 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. Beta blockers counter this inappropriately high sympathetic activity, eventually leading to an improved ejection fraction, despite an initial reduction in ejection fraction.
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.
Therapeutic administration of beta blockers for congestive heart failure ought to begin at very low doses (1/8 of target) with 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.
Officially, beta blockers are not approved for anxiolytic use by the U.S. Food and Drug Administration. 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. 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.
Musicians, public speakers, actors, 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. 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".
Beta blockers lower the heart rate and reduce tremors, and as a result have been used in professional sports where high accuracy is required. Such sports have included archery and shooting. Golf and snooker have been implicated as well. Beta blockers are banned by the International Olympic Committee. 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.
For similar reasons, beta blockers have also been used by surgeons.
Side effects 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 and/or alteration of glucose and lipid metabolism. Mixed α1/β-antagonist therapy is also commonly associated with orthostatic hypotension. Carvedilol therapy is commonly associated with edema. 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. Beta blockers do not appear to affect the rate of depression.
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.
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.
A 2007 study revealed diuretics and beta blockers used for hypertension increase a person's risk of developing diabetes mellitus, while ACE inhibitors and angiotensin II receptor antagonists (angiotensin receptor blockers) actually decrease the risk of diabetes. 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.
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. The mixed alpha- and beta blocker labetalol is especially useful for treatment of concomitant tachycardia and hypertension induced by methamphetamine. The phenomenon of "unopposed alpha stimulation" has not been reported with the use of beta blockers for treatment of methamphetamine toxicity. 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.
Contraindications for beta-blockers include:
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 cardioselective beta blockers.:182
Cardioselective beta-blocker (β1 blockers), if really required, can be prescribed at the least possible dose to those with mild to moderate respiratory symptoms. 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.
Beta-blockers' inhibition on epinephrine's effect can somewhat exacerbate hypoglycemia by interfering with glycogenesis 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-blocker.
Abrupt withdrawal can result in thyroid storm.
Bradycardia or AV block
Unless a pacemaker is present, beta-blockers can severely depress conduction in the AV node, resulting in reduction of heart rate and cardiac output. Usage of beta-blockers in tachycardic patients with Wolff-Parkinson-White Syndrome can result in severe bradycardia, necessitating treatment with a pacemaker.
Glucagon, used in the treatment of overdose, increases the strength of heart contractions, increases intracellular cAMP, and decreases renal vascular resistance. It is, therefore, useful in patients with beta blocker cardiotoxicity. 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.
Mechanism of action
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. Stimulation of β1 receptors on the kidney causes renin release. Stimulation of β2 receptors induces smooth muscle relaxation, induces tremor in skeletal muscle, and increases glycogenolysis in the liver and skeletal muscle. Stimulation of β3 receptors induces lipolysis.
Beta blockers inhibit these normal epinephrine- and norepinephrine-mediated sympathetic actions, but have minimal effect on resting subjects. That is, they reduce the effect of excitement or physical exertion on heart rate and force of contraction, and also tremor, and breakdown of glycogen. Beta blockers can have a constricting effect on the bronchi of the lungs, possibly worsening or causing asthma symptoms.
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.
Accordingly, nonselective beta blockers are expected to have antihypertensive effects. The primary antihypertensive mechanism of beta blockers is unclear, but may involve reduction in cardiac output (due to negative chronotropic and inotropic effects). 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).
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.
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.
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.
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.
Agents with ISA are not used after myocardial infarctions, as they have not been demonstrated to be beneficial. They may also be less effective than other beta blockers in the management of angina and tachyarrhythmia.
- Agents with intrinsic sympathomimetic action (ISA)
- Agents organized by lipid solubility (lipophilicity)
- High lipophilicity: propranolol, labetalol
- Intermediate lipophilicity: metoprolol, bisoprolol, carvedilol, acebutolol, timolol, pindolol
- Low lipophilicity (also known as hydrophilic beta blockers): atenolol, nadolol, and sotalol
- Agents with membrane stabilizing effect
- Carvedilol, propranolol > oxprenolol > labetalol, metoprolol, timolol
In 1964, the search to find an effective drug in myocardial infarction led Sir James Black and ICI, the company with which Black worked with, to develop propranolol, the first beta blocker with beneficial effects. Subsequent poorly designed trials failed to demonstrate benefits and beta blockers for myocardial infarction fell out of favour until the ISIS-1 trial, a landmark trial which looked at injecting beta blockers in myocardial infarction. Beta blockers were found to reduce cardiac rupture, leading to their estabishment in the use following an acute myocardial infarction.
Society and culture
Commonly used β-blockers are available as generic medication and are relatively inexpensive. Their use in certain precision sports is banned by the International Olympic Committee as they improve performance by reducing tremor and anxiety.
- Agents specifically labeled for cardiac arrhythmia
- Agents specifically labeled for congestive heart failure
- Agents specifically labeled for glaucoma
- Agents specifically labeled for myocardial infarction
- Agents specifically labeled for migraine prophylaxis
Beta blockers, due to their antagonism at beta-1 adrenergic receptors, inhibit both the synthesis of new melatonin and its secretion by the pineal gland. The neuropsychiatric side effects of some beta blockers (e.g. sleep disruption, insomnia) may be due to this effect.
Some pre-clinical and clinical research suggests that some beta blockers may be beneficial for cancer treatment. However, other studies do not show a correlation between cancer survival and beta blocker usage. Also, a 2017 meta-analysis failed to show any benefit for the use of beta blockers in breast cancer.
Beta blockers have also been used for the treatment of schizoid personality disorder. However, there is limited evidence supporting the efficacy of supplemental beta-blocker use in addition to antipsychotic drugs for treating schizophrenia.
Contrast media are not contraindicated in patients receiving beta blockers.
- "Generic Name Stems - Drug Information Portal - U.S. National Library of Medicine". druginfo.nlm.nih.gov. Retrieved 13 March 2021. CS1 maint: discouraged parameter (link)
- Hitchings, Andrew; Lonsdale, Dagan; Burrage, Daniel; Baker, Emma (2019). The Top 100 Drugs: Clinical Pharmacology and Practical Prescribing (2nd ed.). Elsevier. pp. 90–91. ISBN 978-0-7020-7442-4.
- Farzam, K; Jan, A (January 2021). "Beta Blockers". PMID 30422501. Cite journal requires
- 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 (February 2014). "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)". JAMA. 311 (5): 507–20. doi:10.1001/jama.2013.284427. PMID 24352797.
- "Beta blockers". nhs.uk. 17 October 2017. Archived from the original on 12 March 2021. Retrieved 12 March 2021.
- Marx, John A. Marx (2014). "Cardiovascular Drugs". Rosen's emergency medicine: concepts and clinical practice (8th ed.). Philadelphia, PA: Elsevier/Saunders. pp. Chapter 152. ISBN 1455706051.
- "List of Beta-adrenergic blocking agents (beta blockers) - Generics Only". Drugs.com. Retrieved 11 March 2021. CS1 maint: discouraged parameter (link)
- Arcangelo VP, Peterson AM (2006). Pharmacotherapeutics for advanced practice: a practical approach. Lippincott Williams & Wilkins. p. 205. ISBN 978-0-7817-5784-3. Retrieved 2010-09-07.
- Cruikshank, J. M. (2013). "4. History of beta blockers". In Chopra, H. K.; Nanda, Navin C. (eds.). Textbook of Cardiology: A Clinical and Historical Perspective. Jaypee Brothers Medical Publishers Pvt. Ltd. p. 15. ISBN 978-93-5090-081-9.
- Stapleton MP (1997). "Sir James Black and propranolol. The role of the basic sciences in the history of cardiovascular pharmacology". Texas Heart Institute Journal. 24 (4): 336–42. PMC 325477. PMID 9456487.
- World Anti-Doping Agency (September 19, 2005). "The World Anti-Doping Code: The 2006 Prohibited List International Standard" (PDF). World Anti-Doping Agency. Archived (PDF) from the original on February 11, 2017. Retrieved February 10, 2017.
- Heuberger, JAAC; Cohen, AF (April 2019). "Review of WADA Prohibited Substances: Limited Evidence for Performance-Enhancing Effects". Sports medicine (Auckland, N.Z.). 49 (4): 525–539. doi:10.1007/s40279-018-1014-1. PMID 30411235.
- "Comparison of Oral Beta-Blockers". pharmacist.therapeuticresearch.com. Therapeutic Research Center. Archived from the original on October 18, 2017. Retrieved April 30, 2017.
- Rosendorff C (June 1993). "Beta-blocking agents with vasodilator activity". Journal of Hypertension Supplement. 11 (4): S37–40. doi:10.1097/00004872-199306003-00009. PMID 8104240.
- "CARTEOLOL". pubchem.ncbi.nlm.nih.gov. U.S. National Library of Medicine. Archived from the original on October 18, 2017. Retrieved October 18, 2017.
- "oxprenolol". pubchem.ncbi.nlm.nih.gov. U.S. National Library of Medicine. Archived from the original on October 18, 2017. Retrieved October 18, 2017.
- "Celiprolol". pubchem.ncbi.nlm.nih.gov. U.S. National Library of Medicine. Archived from the original on October 18, 2017. Retrieved October 18, 2017.
- Volz-Zang C, Eckrich B, Jahn P, Schneidrowski B, Schulte B, Palm D (1994). "Esmolol, an ultrashort-acting, selective beta 1-adrenoceptor antagonist: pharmacodynamic and pharmacokinetic properties". European Journal of Clinical Pharmacology. 46 (5): 399–404. doi:10.1007/BF00191900. PMID 7957532. S2CID 12809602.
- "Butaxamine". pubchem.ncbi.nlm.nih.gov. U.S. National Library of Medicine. Archived from the original on October 18, 2017. Retrieved October 18, 2017.
- "ICI 118551 (CHEBI:73289)". www.ebi.ac.uk. Archived from the original on 12 March 2021. Retrieved 12 March 2021.
- "SR 59230A". pubchem.ncbi.nlm.nih.gov. U.S. National Library of Medicine. Archived from the original on October 18, 2017. Retrieved October 18, 2017.
- Cleophas, Ton (1995). Beta-blockers in hypertension and angina pectoris: different compounds, different strategies. Kluwer Academic Publishers. ISBN 978-0-7923-3516-0.
- Khan, M.I. Gabriel (2007). Cardia Drug Therapy. Humana Press. ISBN 978-1-59745-238-0.
- Katzung, Bertram (2018). Basic & Clinical Pharmacology. McGraw-Hill. ISBN 9781259641152.
- Meinertz T, Willems S (December 2008). "[Treatment of atrial fibrillation in every days [sic] practice]" [Treatment of atrial fibrillation in everyday practice]. Der Internist. 49 (12): 1437–42, 1444–5. doi:10.1007/s00108-008-2152-6. PMID 19020848.
- "Medications for Arrhythmia". www.heart.org. Retrieved 2019-08-10.
- "Beta Blocker Therapy". American College of Cardiology. Retrieved 2019-08-10.
- "Essential Tremor Medications". Cleveland Clinic. Retrieved 2019-08-10.
- Goodman & Gilman's: The Pharmacological Basic of Therapeutics. McGraw-Hill. 2018. ISBN 9781259584732.
- Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 15. ISBN 978-1-59541-101-3.
- NICE Hypertension guidance Archived April 9, 2017, at the Wayback Machine Last updated 2013
- "Preventive Treatment of Migraine in Adults". www.uptodate.com. Retrieved 2019-08-10.
- "Mitral Valve Prolapse". Mayo Clinic. March 6, 2018. Retrieved August 9, 2019.
- "Acute myocardial infarction: Role of beta blocker therapy". www.uptodate.com. Retrieved 2019-08-10.
- "Pheochromocytoma Medication: Alpha Blockers, Antihypertensives, BPH, Alpha Blocker, Vasodilators, Beta Blockers, Nonselective, Beta Blockers, Beta1 Selective, Antihypertensives, Other, Radiopharmaceuticals". emedicine.medscape.com. Retrieved 2019-08-10.
- "Vanderbilt Autonomic Dysfunction Center - Propranolol (Beta Blocker) - Vanderbilt Health Nashville, TN". ww2.mc.vanderbilt.edu. Retrieved 2019-08-10.
- "Theophylline Poisoning". www.uptodate.com. Retrieved 2019-08-10.
- Bouri, Sonia; Shun-Shin, Matthew James; Cole, Graham D; Mayet, Jamil; Francis, Darrel P (2014-03-15). "Meta-analysis of secure randomised controlled trials of β-blockade to prevent perioperative death in non-cardiac surgery". Heart. 100 (6): 456–464. doi:10.1136/heartjnl-2013-304262. ISSN 1355-6037. PMC 3932762. PMID 23904357.
- Blessberger H, Kammler J, Domanovits H, Schlager O, Wildner B, Azar D, Schillinger M, Wiesbauer F, Steinwender C (March 2018). "Perioperative beta-blockers for preventing surgery-related mortality and morbidity". The Cochrane Database of Systematic Reviews. 9 (9): CD004476. doi:10.1002/14651858.CD004476.pub3. PMC 6494407. PMID 29533470.
- Wiysonge CS, Bradley HA, Volmink J, Mayosi BM, Opie LH (January 2017). "Beta-blockers for hypertension". The Cochrane Database of Systematic Reviews. 1: CD002003. doi:10.1002/14651858.CD002003.pub5. PMC 5369873. PMID 28107561.
- Chen YJ, Li LJ, Tang WL, Song JY, Qiu R, Li Q, Xue H, Wright JM (November 2018). "First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension". The Cochrane Database of Systematic Reviews. 11: CD008170. doi:10.1002/14651858.CD008170.pub3. PMC 6516995. PMID 30480768.
- Chen N, Zhou M, Yang M, Guo J, Zhu C, Yang J, Wang Y, Yang X, He L (August 2010). "Calcium channel blockers versus other classes of drugs for hypertension". The Cochrane Database of Systematic Reviews (8): CD003654. doi:10.1002/14651858.CD003654.pub4. PMID 20687074.
- Wiysonge CS, Bradley HA, Volmink J, Mayosi BM, Opie LH (January 2017). "Beta-blockers for hypertension". The Cochrane Database of Systematic Reviews. 1: CD002003. doi:10.1002/14651858.cd002003.pub5. PMC 5369873. PMID 28107561.
- 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 (March 2000). "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". JAMA. 283 (10): 1295–302. doi:10.1001/jama.283.10.1295. PMID 10714728.
- Leizorovicz A, Lechat P, Cucherat M, Bugnard F (February 2002). "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". American Heart Journal. 143 (2): 301–7. doi:10.1067/mhj.2002.120768. PMID 11835035.
- 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 (October 2002). "Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study". Circulation. 106 (17): 2194–9. doi:10.1161/01.CIR.0000035653.72855.BF. PMID 12390947.
- "Use of beta blockers and ivabradine in heart failure with reduced ejection fraction". www.uptodate.com. Archived from the original on December 22, 2015. Retrieved December 11, 2015.
- Pritchett AM, Redfield MM (August 2002). "Beta-blockers: new standard therapy for heart failure". Mayo Clinic Proceedings. 77 (8): 839–45, quiz 845–6. doi:10.4065/77.8.839. PMID 12173717.
- Schneier FR (September 2006). "Clinical practice. Social anxiety disorder". The New England Journal of Medicine. 355 (10): 1029–36. doi:10.1056/NEJMcp060145. PMID 16957148.
- Tyrer P (January 1992). "Anxiolytics not acting at the benzodiazepine receptor: beta blockers". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 16 (1): 17–26. doi:10.1016/0278-5846(92)90004-X. PMID 1348368. S2CID 24742562.
- Tindall, Blair (October 17, 2004). "Better Playing Through Chemistry". The New York Times. Archived from the original on August 26, 2015.
- Fitch, Ken (June 2012). "Proscribed drugs at the Olympic Games: permitted use and misuse (doping) by athletes". Clinical Medicine. 12 (3): 257–260. doi:10.7861/clinmedicine.12-3-257. ISSN 1470-2118. PMID 22783779.
- Tim Glover. "Golf: O'Grady says players use beta-blockers: Drugs 'helped win majors'". The Independent. Archived from the original on September 25, 2015. Retrieved March 28, 2017.
- Scott, Matt (15 August 2008). "Olympics: North Korea's Kim Jong-su loses medals after positive drugs test". The Guardian. Guardian News and Media Limited. Retrieved 7 March 2018.
- Elman MJ, Sugar J, Fiscella R, Deutsch TA, Noth J, Nyberg M, Packo K, Anderson RJ (1998). "The effect of propranolol versus placebo on resident surgical performance". Transactions of the American Ophthalmological Society. 96: 283–91, discussion 291–4. PMC 1298399. PMID 10360293.
- Rossi S, ed. (2006). Australian Medicines Handbook. Adelaide: Australian Medicines Handbook.
- Cruickshank JM (2010). "Beta-blockers and heart failure". Indian Heart Journal. 62 (2): 101–10. PMID 21180298.
- "Do β-Blockers Cause Depression?". Hypertension: HYPERTENSIONAHA.120.16590. 15 Mar 2021. doi:10.1161/HYPERTENSIONAHA.120.16590.
- Beta-Adrenoceptor Antagonists (Beta-Blockers); "CV Pharmacology | Beta-Adrenoceptor Antagonists (Beta-Blockers)". Archived from the original on August 8, 2011. Retrieved August 8, 2011.
- Elliott WJ, Meyer PM (January 2007). "Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis". Lancet. 369 (9557): 201–7. doi:10.1016/S0140-6736(07)60108-1. PMID 17240286. S2CID 37044384.
- Mayor S (July 2006). "NICE removes beta blockers as first line treatment for hypertension". BMJ. 333 (7557): 8. doi:10.1136/bmj.333.7557.8-a. PMC 1488775. PMID 16809680.
- Richards JR, Derlet RW, Albertson TE. "Treatment & Management". Methamphetamine Toxicity. Medscape. WebMD. Archived from the original on April 9, 2016. Retrieved April 20, 2016.
- Richards JR, Albertson TE, Derlet RW, Lange RA, Olson KR, Horowitz BZ (May 2015). "Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review". Drug and Alcohol Dependence. 150: 1–13. doi:10.1016/j.drugalcdep.2015.01.040. PMID 25724076.
- Handly, Neal (December 16, 2016). "Toxicity, Amphetamine". Medscape. Archived from the original on October 13, 2007.
- Wyeth Pharmaceuticals Inc. "Propranolol hydrochloride" (PDF). Retrieved 2020-09-03.
- National Heart, Lung, and Blood Institute (2007). "Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma–Summary Report 2007". The Journal of Allergy and Clinical Immunology. 120 (5): S94–S138. doi:10.1016/j.jaci.2007.09.029. Retrieved 2017-12-09.CS1 maint: multiple names: authors list (link)
- Morales, Daniel R.; Jackson, Cathy; Lipworth, Brian J.; Donnan, Peter T.; Guthrie, Bruce (2014). "Adverse Respiratory Effect of Acute β-Blocker Exposure in Asthma". Chest. Elsevier BV. 145 (4): 779–786. doi:10.1378/chest.13-1235. ISSN 0012-3692. PMID 24202435.
- Salpeter, Shelley R.; Ormiston, Thomas M.; Salpeter, Edwin E. (2002-11-05). "Cardioselective β-Blockers in Patients with Reactive Airway Disease". Annals of Internal Medicine. American College of Physicians. 137 (9): 715–25. doi:10.7326/0003-4819-137-9-200211050-00035. ISSN 0003-4819. PMID 12416945.
- Sprague, JE; Arbeláez, AM (2011). "Glucose Counterregulatory Responses to Hypoglycemia". Pediatric Endocrinology Reviews : PER. 9 (1): 463–475. PMC 3755377. PMID 22783644.
- Weinstein RS, Cole S, Knaster HB, Dahlbert T (February 1985). "Beta blocker overdose with propranolol and with atenolol". Annals of Emergency Medicine. 14 (2): 161–3. doi:10.1016/S0196-0644(85)81081-7. PMID 2857542.
- "Toxicity, Beta-blocker: Treatment & Medication – eMedicine Emergency Medicine". Archived from the original on March 17, 2009. Retrieved March 6, 2009.
- John Gualtier. "Beta-Adrenergic Blocker Poisoning" (PDF). Courses.ahc.umn.edu. Archived from the original (PDF) on March 3, 2016. Retrieved March 28, 2017.
- USMLE WORLD 2009 Step1, Pharmacology, Q85
- Perez, Dianne M. (2006). The Adrenergic Receptors in the 21st Century. Humana Press. p. 135. ISBN 978-1-58829-423-4. Retrieved 2010-09-08.
- Jameson JL, Loscalzo J (2010). Harrison's Nephrology and Acid-Base Disorders. McGraw-Hill Companies. p. 215. ISBN 978-0-07-166339-7. Retrieved 2010-09-08.
- O'Donnell JM, Nácul FE (2009). Surgical Intensive Care Medicine. Springer. p. 47. ISBN 978-0-387-77892-1. Retrieved 2010-09-08.
- Ahrens RC (1990). "Skeletal muscle tremor and the influence of adrenergic drugs". The Journal of Asthma. 27 (1): 11–20. doi:10.3109/02770909009073289. PMID 1968452.
- Reents, Stan (2000). Sport and exercise pharmacology. Human Kinetics. p. 19. ISBN 978-0-87322-937-1. Retrieved 2010-09-10.
- Martini, Frederic H. (2005). Anatomy and Physiology. Pearson Education. p. 394. ISBN 978-0-8053-5947-3. Retrieved 2010-09-10.
- Frishman WH, Cheng-Lai A, Nawarskas J (2005). Current Cardiovascular Drugs. Current Science Group. p. 152. ISBN 978-1-57340-221-7. Retrieved 2010-09-07.
- Khan, M. I. Gabriel (2006). Encyclopedia of Heart Diseases. Elsevier. p. 160. ISBN 978-0-12-406061-6. Retrieved 2010-09-10.
- Lamster IB, Northridge ME, eds. (2008). Improving Oral Health for the Elderly: An Interdisciplinary Approach. New York: Springer. p. 87. ISBN 978-0-387-74337-0. Retrieved 2010-10-23.
- Rothfeld GS, Romaine DS (2005). The Encyclopedia of Men's Health. Amaranth. p. 48. ISBN 978-0-8160-5177-9. Retrieved 2010-10-23.
- Manger WM, Gifford RW (2001). 100 Questions and Answers about Hypertension. Blackwell Science. p. 106. ISBN 978-0-632-04481-8. Retrieved 2010-09-10.
beta blockers dilation of blood vessels.
- Hurst, J.W. (1997). Schlant, Robert C. (ed.). Hurst's the Heart. 2. Blackwell Science. p. 1564. ISBN 978-0-07-912951-2. Retrieved 2010-10-07.
- Reid, J.L. (2001). Lecture notes on clinical pharmacology. 6. Blackwell Science. p. 76. ISBN 978-0-632-05077-2. Retrieved 2011-03-11.
- Larochelle P, Tobe SW, Lacourcière Y (May 2014). "β-Blockers in hypertension: studies and meta-analyses over the years". The Canadian Journal of Cardiology. 30 (5 Suppl): S16–22. doi:10.1016/j.cjca.2014.02.012. PMID 24750978.
- Mulrow, edited by Detlev Ganten, Patrick J. (1990). Pharmacology of Antihypertensive Therapeutics. Berlin, Heidelberg: Springer Berlin Heidelberg. p. 523. ISBN 9783642742095.CS1 maint: extra text: authors list (link)
- Zipursky JS, Macdonald EM, Luo J, Gomes T, Mamdani MM, Paterson JM, Juurlink DN (June 2017). "Lipophilic β-Blockers and Suicide in the Elderly". Journal of Clinical Psychopharmacology. 37 (3): 381–384. doi:10.1097/JCP.0000000000000695. PMID 28338548. S2CID 23355130.
- Aronson JK (June 2008). "Changing beta-blockers in heart failure: when is a class not a class?". The British Journal of General Practice. 58 (551): 387–9. doi:10.3399/bjgp08X299317. PMC 2418988. PMID 18505613.
- Julian, Desmond G; Pocock, Stuart (2000). "19. Clinical Trials". In Silverman, Mark E.; Fleming, Peter R.; Hollman, Arthur; Julian, Desmond G.; Krikler, Dennis M. (eds.). British Cardiology in the 20th Century. Springer. p. 245. ISBN 978-1-4471-1199-3.
- "BREVIBLOC (esmolol hydrochloride)". Baxter Healthcare Corporation. Missing or empty
- "BETAPACE AF (sotalol HCl)". Bayer HealthCare Pharmaceuticals Inc. Missing or empty
- "Announcement of Approval of Additional Indications for Onoact 50 for Injection, Short-Acting Selective ß1 Blocker". www.evaluategroup.com. Evaluate Ltd. Retrieved 18 October 2017.
- "DailyMed - METIPRANOLOL- metipranolol solution/ drops". dailymed.nlm.nih.gov. NIH. Archived from the original on October 18, 2017. Retrieved October 18, 2017.
- "Drugs to Prevent Migraine in Adults". pharmacist.therapeuticresearch.com. Therapeutic Research Center. Archived from the original on October 18, 2017. Retrieved April 30, 2017.
- Fares A (July 2011). "Night-time exogenous melatonin administration may be a beneficial treatment for sleeping disorders in beta blocker patients". Journal of Cardiovascular Disease Research. 2 (3): 153–5. doi:10.4103/0975-3583.85261. PMC 3195193. PMID 22022142.
- Choy C, Raytis JL, Smith DD, Duenas M, Neman J, Jandial R, Lew MW (June 2016). "Inhibition of β2-adrenergic receptor reduces triple-negative breast cancer brain metastases: The potential benefit of perioperative β-blockade". Oncology Reports. 35 (6): 3135–42. doi:10.3892/or.2016.4710. PMC 4869944. PMID 27035124.
- Kokolus KM, Zhang Y, Sivik JM, Schmeck C, Zhu J, Repasky EA, Drabick JJ, Schell TD (2018). "Beta blocker use correlates with better overall survival in metastatic melanoma patients and improves the efficacy of immunotherapies in mice". Oncoimmunology. 7 (3): e1405205. doi:10.1080/2162402X.2017.1405205. PMC 5790362. PMID 29399407.
- Livingstone E, Hollestein LM, van Herk-Sukel MP, van de Poll-Franse L, Nijsten T, Schadendorf D, de Vries E (December 2013). "β-Blocker use and all-cause mortality of melanoma patients: results from a population-based Dutch cohort study". European Journal of Cancer. 49 (18): 3863–71. doi:10.1016/j.ejca.2013.07.141. PMID 23942335.
- Cardwell CR, Coleman HG, Murray LJ, O'Sullivan JM, Powe DG (June 2014). "Beta-blocker usage and prostate cancer survival: a nested case-control study in the UK Clinical Practice Research Datalink cohort". Cancer Epidemiology. 38 (3): 279–85. doi:10.1016/j.canep.2014.03.011. PMID 24786858.
- Kim HY, Jung YJ, Lee SH, Jung HJ, Pak K (2017). "Is Beta-Blocker Use Beneficial in Breast Cancer? A Meta-Analysis". Oncology. 92 (5): 264–268. doi:10.1159/000455143. PMID 28132057. S2CID 5463335.
- Sonny Joseph (1997). "Chapter 3, Schizoid Personality Disorder". Personality Disorders: New Symptom-Focused Drug Therapy. Psychology Press. pp. 45–56. ISBN 9780789001344.
- Shek, Elena; Bardhan, Sabyasachi; Cheine, Maxim V; Ahonen, Juha; Wahlbeck, Kristian. "Beta-blocker supplementation of standard drug treatment for people with schizophrenia". www.cochrane.org. doi:10.1002/14651858.CD000234. Retrieved 2019-08-09.
- Boehm I, Morelli J, Nairz K, Silva Hasembank Keller P, Heverhagen JT (November 2016). "Beta blockers and intravenous roentgen contrast materials: Which risks do exist?" (PDF). European Journal of Internal Medicine. 35: e17–e18. doi:10.1016/j.ejim.2016.08.003. PMID 27531627.