|Synonyms||β-blockers, beta-adrenergic blocking agents, beta antagonists, beta-adrenergic antagonists, beta-adrenoreceptor antagonists, beta adrenergic receptor antagonists|
|Use||Hypertension, arrhythmia, etc.|
|Biological target||beta receptors|
Beta blockers, also written β-blockers, are a class of medications that are predominately used to manage abnormal heart rhythms, and to protect the heart from a second heart attack (myocardial infarction) after a first heart attack (secondary prevention). They are also widely used to treat high blood pressure (hypertension), although they are no longer the first choice for initial treatment of most patients.
Beta blockers are competitive antagonists that block the receptor sites for the endogenous catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) on adrenergic beta receptors, of the sympathetic nervous system, which mediates the fight-or-flight response. Some block activation of all types of β-adrenergic receptors and others are selective for one of the three known types of beta receptors, designated β1, β2 and β3 receptors. β1-adrenergic receptors are located mainly in the heart and in the kidneys. β2-adrenergic receptors are located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle. β3-adrenergic receptors are located in fat cells.
Beta receptors are found on cells of the heart muscles, smooth muscles, airways, arteries, kidneys, and other tissues that are part of the sympathetic nervous system and lead to stress responses, especially when they are stimulated by epinephrine (adrenaline). Beta blockers interfere with the binding to the receptor of epinephrine and other stress hormones, and weaken the effects of stress hormones.
In 1964, James Black synthesized the first clinically significant beta blockers—propranolol and pronethalol; it revolutionized the medical management of angina pectoris and is considered by many to be one of the most important contributions to clinical medicine and pharmacology of the 20th century.
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.
- 1 Medical uses
- 2 Performance-enhancing use
- 3 Adverse effects
- 4 β-Receptor antagonism
- 5 Intrinsic sympathomimetic activity
- 6 α1-receptor antagonism
- 7 Examples
- 8 Comparative information
- 9 Other effects
- 10 See also
- 11 References
- 12 External links
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Large differences exist in the pharmacology of agents within the class, thus not all beta blockers are used for all indications listed below.
Indications for beta blockers include:
- Angina pectoris (contraindicated for Prinzmetal's angina)
- Atrial fibrillation
- Cardiac arrhythmia[vague]
- 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
Congestive heart failure
Although beta blockers were once contraindicated in congestive heart failure, as they have the potential to worsen the condition due to their effect of decreasing cardiac contractility, studies in the late 1990s showed their efficacy at reducing morbidity and mortality. 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.
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".
Because they promote lower heart rates and reduce tremors, beta blockers have been used in professional sports where high accuracy is required, including archery, shooting, golf and snooker. 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.
Adverse drug reactions 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.
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 patient's risk of developing diabetes mellitus, while ACE inhibitors and angiotensin II receptor antagonists (angiotensin receptor blockers) actually decrease the risk of diabetes. Clinical guidelines in Great Britain, but not in the United States, call for avoiding diuretics and beta blockers as first-line treatment of hypertension due to the risk of diabetes.
Beta blockers must not be used in the treatment of selective alpha-adrenergic agonist overdose. The blockade of only beta receptors increases blood pressure, reduces coronary blood flow, left ventricular function, and cardiac output and tissue perfusion by means of leaving the alpha-adrenergic system stimulation unopposed.[medical citation needed] 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.
Beta blockers are contraindicated in patients with asthma as stated in the British National Formulary 2011. 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.
They should also be avoided in patients with a history of cocaine use or in cocaine-induced tachycardia.
Beta blockers should not be used as a first-line treatment in the acute setting for cocaine-induced acute coronary syndrome (CIACS). No recent studies have been identified that show the benefit of beta blockers in reducing coronary vasospasm, or coronary vascular resistance, in patients with CIACS. In the multiple case studies identified, the use of beta blockers in CIACS resulted in detrimental outcomes, and the discontinuation of beta blockers used in the acute setting led to improvement in clinical course. The guidelines by the American College of Cardiology/American Heart Association also support this idea, and recommend against the use of beta blockers in cocaine-induced ST-segment elevation myocardial infarction (MI) because of the risk of coronary vasospasm. Though, in general, beta blockers improve mortality in patients who have suffered MI, it is unclear whether patients with CIACS will benefit from this mortality reduction because no studies assess the use of beta blockers in the long term, and because cocaine users may be prone to continue to abuse the substance, thus complicating the effect of drug therapy. Contrast media are not contraindicated in patients receiving beta blockers.
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.
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, breakdown of glycogen, and dilation of bronchi.
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.
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.
- Acebutolol (has intrinsic sympathomimetic activity, ISA)
- Celiprolol (has intrinsic sympathomimetic activity)
β1 selective antagonist and β3 agonist agents
- 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
- 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.
- Freemantle N, Cleland J, Young P, Mason J, Harrison J (June 1999). "beta Blockade after myocardial infarction: systematic review and meta regression analysis". BMJ. 318 (7200): 1730–7. doi:10.1136/bmj.318.7200.1730. PMC . PMID 10381708.
- 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.
- 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.
- 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.
- Frishman WH, Cheng-Lai A, Nawarskas J (2005). Current Cardiovascular Drugs. Current Science Group. p. 153. ISBN 978-1-57340-221-7. Retrieved 2010-09-07.
- Clément K, Vaisse C, Manning BS, Basdevant A, Guy-Grand B, Ruiz J, Silver KD, Shuldiner AR, Froguel P, Strosberg AD (August 1995). "Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity". The New England Journal of Medicine. 333 (6): 352–4. doi:10.1056/NEJM199508103330605. PMID 7609752.
- "Sir James Black, OM". The Telegraph. March 23, 2010. Archived from the original on March 27, 2010. Retrieved March 25, 2010.
- van der Vring JA, Daniëls MC, Holwerda NJ, Withagen PJ, Schelling A, Cleophas TJ, Hendriks MG (June 1999). "Combination of calcium channel blockers and beta blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. The Netherlands Working Group on Cardiovascular Research (WCN)". Angiology. 50 (6): 447–54. doi:10.1177/000331979905000602. PMID 10378820.
- 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 . PMID 9456487.
- 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 . PMID 28107561.
- Xue H, Lu Z, Tang WL, Pang LW, Wang GM, Wong GW, Wright JM (January 2015). "First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension". The Cochrane Database of Systematic Reviews. 1: CD008170. doi:10.1002/14651858.CD008170.pub2. PMID 25577154.
- 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. John Wiley & Sons. 1: CD002003. doi:10.1002/14651858.cd002003.pub5. PMID 28107561. Archived from the original on August 11, 2017.
- Cleophas, Ton (1995). Beta-blockers in hypertension and angina pectoris: different compounds, different strategies. Kluwer Academic Publishers. ISBN 0-7923-3516-3.
- Khan, M.I. Gabriel (2007). Cardia Drug Therapy. Humana Press. ISBN 1-59745-238-6.
- Meinertz T, Willems S (December 2008). "[Treatment of atrial fibrillation in every days practice]" [Treatment of atrial fibrillation in every day practice]. Der Internist. 49 (12): 1437–42, 1444–5. doi:10.1007/s00108-008-2152-6. PMID 19020848.
- Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 15. ISBN 1-59541-101-1.
- NICE Hypertension guidance Archived April 9, 2017, at the Wayback Machine. Last updated 2013
- 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" (PDF). 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.
- Blair Tindall. "Better Playing Through Chemistry Archived October 14, 2012, at the Wayback Machine.", The New York Times, October 17, 2004. Retrieved July 3, 2011.
- 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. PMID 29533470.
- 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.
- 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.
- 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 . 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.
- Beta-Adrenoceptor Antagonists (Beta-Blockers); "Archived copy". 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.
- 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 . 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.
- "Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma". NIH.
- Page RL, Utz KJ, Wolfel EE (December 2007). "Should beta-blockers be used in the treatment of cocaine-associated acute coronary syndrome?". The Annals of Pharmacotherapy. 41 (12): 2008–13. doi:10.1345/aph.1H643. PMID 17956961.
- 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?". European Journal of Internal Medicine. 35: e17–e18. doi:10.1016/j.ejim.2016.08.003. PMID 27531627.
- 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 (PDF) from the original 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 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 0-07-166339-8. Retrieved 2010-09-08.
- O'Donnell JM, Nácul FE (2009). Surgical Intensive Care Medicine. Springer. p. 47. ISBN 0-387-77892-6. 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 0-87322-937-1. Retrieved 2010-09-10.
- Martini, Frederic H. (2005). Anatomy and Physiology. Pearson Education. p. 394. ISBN 0-8053-5947-8. Retrieved 2010-09-10.
- 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 0-8160-5177-1. Retrieved 2010-10-23.
- Manger WM, Gifford RW (2001). 100 Questions and Answers about Hypertension. Blackwell Science. p. 106. ISBN 0-632-04481-0. Retrieved 2010-09-10.
- Hurst, J.W. (1997). Schlant, Robert C., ed. Hurst's the Heart. 2. Blackwell Science. p. 1564. ISBN 0-07-912951-X. Retrieved 2010-10-07.
- Reid, J.L. (2001). Lecture notes on clinical pharmacology. 6. Blackwell Science. p. 76. ISBN 0-632-05077-2. Retrieved 2011-03-11.
- "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.
- "Esmolol, an ultrashort-acting, selective beta 1-adrenoceptor antagonist: pharmacodynamic and pharmacokinetic properties". PMID 7957532.
- "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 hydrochloride". abcam.com. Abcam plc. Archived from the original on October 18, 2017. Retrieved October 18, 2017.
- "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.
- 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.
- 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. Archived from the original on October 18, 2017.
- 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 . PMID 18505613.
- "BREVIBLOC (esmolol hydrochloride)". Baxter Healthcare Corporation.
- "BETAPACE AF (sotalol HCl)". Bayer HealthCare Pharmaceuticals Inc.
- "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 . 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 . PMID 27035124.
- Kokolus KM, Zhang Y, Sivik JM, Schmeck C, Zhu J, Repasky EA, Drabick JJ, Schell TD. "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. PMID 29399407.
- Powe DG, Voss MJ, Zänker KS, Habashy HO, Green AR, Ellis IO, Entschladen F (November 2010). "Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival". Oncotarget. 1 (7): 628–38. doi:10.18632/oncotarget.101009. PMC . PMID 21317458.
- 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. "Is Beta-Blocker Use Beneficial in Breast Cancer? A Meta-Analysis". Oncology. 92 (5): 264–268. doi:10.1159/000455143. PMID 28132057.
- Sonny Joseph (1997). "Chapter 3, Schizoid Personality Disorder". Personality Disorders: New Symptom-Focused Drug Therapy. Psychology Press. pp. 45–56. ISBN 9780789001344.
- Musicians and beta-blockers by Gerald Klickstein, March 11, 2010 (A blog post that considers "whether beta-blockers are safe, effective, and appropriate for performers to use.")
- Better Playing Through Chemistry by Blair Tindall, The New York Times, October 17, 2004. (Discusses the use of beta blockers among professional musicians)
- Musicians using beta blockers by Blair Tindall. Condensed version of above article.
- In Defense of the Beta Blocker by Carl Elliott, The Atlantic, August 20, 2008. (Discusses the use of propranolol by a North Korean pistol shooter in the 2008 Olympics)
- beta-Adrenergic+Blockers at the US National Library of Medicine Medical Subject Headings (MeSH)