||This article's lead section may not adequately summarize key points of its contents. (July 2014)|
|Use||Hypertension, arrhythmia, etc.|
|Biological target||beta receptors|
Beta blockers (β-blockers, beta-adrenergic blocking agents, beta antagonists, beta-adrenergic antagonists, beta-adrenoreceptor antagonists, or beta adrenergic receptor antagonists) are a class of drugs that target the beta receptor. 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 1962, Sir James Black  found the first clinically significant beta blockers—propranolol and pronethalol; the discovery 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.
Beta blockers block the action of endogenous catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) in particular, on β-adrenergic receptors, part of the sympathetic nervous system, which mediates the fight-or-flight response. Three types of beta receptors are known, 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.
- 1 Medical uses
- 2 Efficacy
- 3 Off label uses
- 4 Adverse effects
- 5 β-Receptor antagonism
- 6 Intrinsic sympathomimetic activity
- 7 α1-Receptor antagonism
- 8 Other effects
- 9 Examples
- 10 Comparative information
- 11 See also
- 12 References
- 13 External links
Large differences exist in the pharmacology of agents within the class, thus not all beta blockers are used for all indications listed below. All beta blockers are approved for the treatment of hypertension. Other US Food and Drug Administration-approved uses are specific to each beta blocker and include stable and unstable angina pectoris, atrial arrhythmias including atrial fibrillation, prevention of bleeding by esophageal varices, coronary artery disease, asymptomatic and symptomatic heart failure, migraine prophylaxis, and secondary prevention of myocardial infarction.
Indications for beta blockers also may include:
- Essential tremor
- Mitral valve prolapse, mitral stenosis
- Phaeochromocytoma, in conjunction with α-blocker
- Postural orthostatic tachycardia syndrome
- Symptomatic control (tachycardia, tremor) in anxiety and hyperthyroidism
- Theophylline overdose
Congestive heart failure
Although beta blockers were once contraindicated in congestive heart failure, as they have the potential to worsen the condition, 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. An ACE inhibitor in combination with a beta-blocker is first-line therapy for chronic heart failure.
A 2001 meta analysis found beta-blocker therapy was associated with clinically meaningful reductions in mortality and morbidity in people with stable congestive heart failure.  Both elderly and non-elderly people with chronic heart failure benefit from beta-blocker therapy. A 2012 meta analysis in people with heart failure with reduced ejection fraction also found a mortality benefit for the different beta blockers in current use bisoprolol, carvedilol, and metoprolol in comparison with placebo or standard treatment. The benefits of β blockers in those people were mainly due to a class effect, as no statistical evidence from current trials supported the superiority of any single agent over the others.
Secondary prevention of heart infarction
Compared with placebo, beta-blockers may be more effective at reducing mortality in people when started within days or weeks of a heart attack, and in people with left ventricular dysfunction, with a minimum of 12 weeks' duration. According to clinical evidence it was low-quality evidence. They are used in combination with antiplatelets and statins.
Stable angina pectoris
In patients with angina pectoris, there is a lack of blood supply (ischemia) to the heart muscles which leads to chest pain, especially during exertion. Beta-blockers could reduce rate of death and the rate of angina pectoris, in patients with stable angina, compared with no treatment, but they were no more effective than calcium channel blockers. But quality of trials was considered generally moderate to poor, leaving the potential for bias, particularly in those trials that had no treatment as a comparator.
Unstable angina pectoris / acute coronary syndrome
Non-selective β blockers showed a statistically significant reduction over placebo with respect to all-cause mortality and vascular events in six studies. They were maybe more efficient than β1 blockers. β1 blockers studied were atenolol, betaxolol, bisoprolol, metoprolol and nebivolol and β1+2 blockers were bucindolol, carvedilol, propranolol and timolol.
For treatment of hypertension, beta-blockers lead to modest reductions in cardiovascular disease (primarily decrease in stroke). They have no significant effects on total mortality against placebo, diuretics and renin angiotensin system inhibitors, but a higher risk compared to calcium channel blockers. These effects of beta-blockers are inferior to those of other antihypertensive drugs, but the quality of this evidence is low, implying that the true effect of beta-blockers may be substantially different from this estimate. First-line beta-blockers appear to be less effective at reducing adverse cardiovascular outcomes than first-line thiazide diuretics, particularly in older individuals. In diabetic people with hypertension, there was no increased risk of myocardial infarction, stroke, cardiovascular mortality and total mortality for beta blockers compared with control antihypertensive therapy, but beta-blockers increased cardiovascular mortality compared to renin-angiotensin blockade therapy.
β blockers are used for rate control in atrial fibrillation. There are fewer hospitalisations and adverse events against rhythm control. With rate control there were fewer embolic events in patients with heart failure, but no significant differences on all-cause and cardiovascular mortality.
Beta-blockers (metoprolol) are efficient for rhythm control; they reduced significantly atrial fibrillation recurrence after conversion. Number needed to threat 9.
Sotalol is used for rhythm control after conversion of atrial fibrillation. Several class IA, IC and III drugs, as well as class II (beta-blockers), are moderately effective in maintaining sinus rhythm after conversion of atrial fibrillation. However, they increase adverse events, including pro-arrhythmia, and some of them (disopyramide, quinidine and sotalol) may increase mortality. For sotalol numbers needed to harm were 166. Possible benefits on clinically relevant outcomes (stroke, embolisms, heart failure) remain to be established.
Prevention of bleeding esophageal varices
Non-selective beta-blockers are used as a first-line treatment for primary prevention in people with medium- to high-risk esophageal varices. This is a complication of chronic liver disease and portal hypertension.
Off label uses
Beta blockers have also been used for:
- Acute aortic dissection although there is no evidence from trials.
- Marfan syndrome (treatment with propranolol slows progression of aortic dilatation and its complications)
Prevention of perioperative death in non-cardiac surgery
Perioperative β-blockade is recommended by US 2009 and 2011 and European 2009 guidelines as class 1 recommendation. But a 2013 meta analysis found a statistically significant 27% increase in mortality. β-blockade reduced non-fatal myocardial infarction but increased stroke and hypo-tension risk. The DECREASE family of studies was considered insecure because of misconduct by Prof Don Poldermans and was withhold from meta analysis. It contradicted this meta-analysis. Prof Don Poldermans was also the chairman of the ESC committee that drafted the guidelines. By following the guideline UK doctors might have caused as many as 10,000 deaths each year. In a joint statement, both the ACCF/AHA and ESC have indicated their intention to update the 2009 guidelines for perioperative cardiac care, and recommend that beta blocker initiation prior to surgery not be routine practice, but should be decided on a case-by-case basis. Just 48 hours after publishing an article alleging that Don Poldermans‘ scientific misconduct led to the deaths of some 800,000 Europeans over the past five years by tainting clinical guidelines, the European Heart Journal retracted the paper.
Hypertrophic obstructive cardiomyopathy
Beta-blocking drugs are recommended for the treatment of symptoms (angina or dyspnea) in adult patients with obstructive or nonobstructive hypertrophic cardiomyopathy but should be used with caution in patients with sinus bradycardia or severe conduction disease.
Anxiety and performance enhancement
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.
Beta-blockers are often used in primary medical management of physical symptoms of anxiety but placebo-controlled evidence of efficacy in acute treatment of patients with generalised anxiety disorder is minimal. The beta blocker propranolol had a lack of efficacy in the acute treatment of patients with panic disorder in one trial. The beta-blocker atenolol was not efficacious in generalised social anxiety disorder, although a number of small single-dose placebo-controlled cross-over studies together suggest that beta-blockers can be beneficial in reducing anxiety symptoms in individuals with ‘performance anxiety’ (for example, when speaking in public), which overlaps with mild non-generalised social anxiety disorder.
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, like 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."
Since 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. A recent, high-profile transgression took place in the 2008 Summer Olympics, where 50 metre pistol silver medallist and 10 metre air pistol bronze medallist Kim Jong-su tested positive for propranolol and was stripped of his medals.
Adverse drug reactions (ADRs) 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 and 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, however 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 hepatic glycogen breakdown (glycogenolysis) and pancreatic release of 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 tachycardia that serves as a warning sign for insulin-induced hypoglycemia may be masked. 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, 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 cocaine, amphetamine, or other alpha-adrenergic stimulant overdose. The blockade of only beta receptors increases hypertension, reduces coronary blood flow, left ventricular function, and cardiac output and tissue perfusion by means of leaving the alpha-adrenergic system stimulation unopposed. The appropriate antihypertensive drugs to administer during hypertensive crisis resulting from stimulant abuse 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. But cardioselective beta-blockers given in mild to moderate reversible airway disease or COPD do not produce adverse respiratory effects. Given their demonstrated benefit in conditions such as heart failure, cardiac arrhythmias and hypertension, these agents should not be withheld from such patients. Long-term safety still needs to be established.
Recent cocaine use is considered a contraindication for beta blockers, because of concern for precipitating coronary vasoconstriction due to unopposed α-receptor stimulation. The 2004 guidelines by the American College of Cardiology/American Heart Association recommend against the use of beta blockers in cocaine-induced ST elevation myocardial infarction because of the risk of coronary vasospasm. But the current management of cocaine-associated chest pain and acute coronary syndromes, is anecdotally derived and based on studies written more than 2 decades ago that involved only a few patients. In a trial of cocaine associated chest pain patients were given the combined α- and β-blocker labetolol or diltiazem; it was found that both medications were associated with a similar and statistically significant decrease in blood pressure and heart rate, with no adverse outcomes. Currently, calcium channel blockers combined with nitroglycerin are recommended for the treatment of cocaine associated chest pain patients with ST-segment elevation or depression.
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.
Patients experiencing bronchospasm due to the β2 receptor-blocking effects of non-selective 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 the breakdown of glycogen 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 excitement/physical exertion on heart rate and force of contraction, and also tremor and breakdown of glycogen, but increase dilation of blood vessels and constriction of bronchi.
Therefore, 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 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.
- Carteolol (has intrinsic sympathomimetic activity)
- Carvedilol (has additional α-blocking activity)
- Labetalol (has additional α-blocking activity)
- Oxprenolol (has intrinsic sympathomimetic activity)
- Penbutolol (has intrinsic sympathomimetic activity)
- Pindolol (has intrinsic sympathomimetic activity)
- Eucommia bark (herb)
Also known as cardioselective
- Acebutolol (has intrinsic sympathomimetic activity)
- Nebivolol (also increases nitric oxide release for vasodilation)
- Butaxamine (weak α-adrenergic agonist activity): No common clinical applications, but used in experiments.
- ICI-118,551: Highly selective β2-adrenergic receptor antagonist—no known clinical applications, but used in experiments due to its strong receptor specificity.
- SR 59230A (has additional α-blocking activity): Used in experiments.
- Agents with intrinsic sympathomimetic action (ISA)
- Acebutolol, carteolol, celiprolol, mepindolol, oxprenolol, pindolol
- Agents with greater aqueous solubility (hydrophilic beta blockers)
- Atenolol, celiprolol, nadolol, sotalol
- Agents with membrane stabilizing effect
- Acebutolol, propranolol
- Agents specifically indicated for cardiac arrhythmia
- Esmolol, sotalol, landiolol
- Agents specifically indicated for congestive heart failure
- Agents specifically indicated for glaucoma
- Agents specifically indicated for myocardial infarction
- Agents specifically indicated for migraine prophylaxis
- Timolol, propranolol
- 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 31101. PMID 10381708.
- Cruickshank JM (August 2010). "Beta blockers in hypertension". Lancet 376 (9739): 415; author reply 415–6. doi:10.1016/S0140-6736(10)61217-2. PMID 20692524.
- "Sir James Black inventor of beta-blockers passes away". Retrieved 2010-09-06.
- van der Vring JA (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): 447–454. 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 325477. PMID 9456487.
- Frishman W.H.; 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 V.P.; Peterson A.M. (2006). Pharmacotherapeutics for advanced practice: a practical approach. Lippincott Williams & Wilkins. p. 205. ISBN 978-0-7817-5784-3. Retrieved 2010-09-07.
- Frishman W.H.; 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.
- Helfand, Mark. "Drug Class Review: Beta Adrenergic Blockers Final Report Update 4 Drug Class Reviews Update 3: September 2007".
- Zesiewicz, TA; Elble, RJ; Louis, ED; Gronseth, GS; Ondo, WG; Dewey RB, Jr; Okun, MS; Sullivan, KL; Weiner, WJ (Nov 8, 2011). "Evidence-based guideline update: treatment of essential tremor: report of the Quality Standards subcommittee of the American Academy of Neurology.". Neurology 77 (19): 1752–5. PMID 22013182.
- Burr, J; Azuara-Blanco, A; Avenell, A; Tuulonen, A (Sep 12, 2012). "Medical versus surgical interventions for open angle glaucoma.". The Cochrane database of systematic reviews 9: CD004399. PMID 22972069.
- Vass, C; Hirn, C; Sycha, T; Findl, O; Bauer, P; Schmetterer, L (Oct 17, 2007). "Medical interventions for primary open angle glaucoma and ocular hypertension.". The Cochrane database of systematic reviews (4): CD003167. PMID 17943780.
- Desai, PA; Tafreshi, J; Pai, RG (May 2011). "Beta-blocker therapy for valvular disorders.". The Journal of heart valve disease 20 (3): 241–53. PMID 21714412.
- Hjalmarson A, Goldstein S, Fagerberg B et al. (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): 1295–1302. doi:10.1001/jama.283.10.1295. PMID 10714728.
- Leizorovicz A, Lechat P, Cucherat M, Bugnard F (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". Am. Heart J. 143 (2): 301–307. doi:10.1067/mhj.2002.120768. PMID 11835035.
- Packer M, Fowler MB, Roecker EB et al. (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): 2194–2199. doi:10.1161/01.CIR.0000035653.72855.BF. PMID 12390947.
- Brophy, JM; Joseph, L; Rouleau, JL (Apr 3, 2001). "Beta-blockers in congestive heart failure. A Bayesian meta-analysis.". Annals of internal medicine 134 (7): 550–60. PMID 11281737.
- Dulin, Brian R.; Haas, Steven J.; Abraham, William T.; Krum, Henry. "Do elderly systolic heart failure patients benefit from beta blockers to the same extent as the non-elderly? Meta-analysis of >12,000 patients in large-scale clinical trials". The American Journal of Cardiology 95 (7): 896–898. doi:10.1016/j.amjcard.2004.11.052.Dare analysis009732
- Chatterjee, S.; Biondi-Zoccai, G.; Abbate, A.; D'Ascenzo, F.; Castagno, D.; Van Tassell, B.; Mukherjee, D.; Lichstein, E. (16 January 2013). "Benefits of blockers in patients with heart failure and reduced ejection fraction: network meta-analysis". BMJ 346 (jan16 1): f55–f55. doi:10.1136/bmj.f55.
- Skinner, Jane (31 August 2011). "Secondary prevention of ischaemic cardiac events". Clinical Evidence.
- "Fact sheet: Medication for long-term treatment of CAD". PubMedHealth.
- Shu, DF. "Long-term beta blockers for stable angina: systematic review and meta-analysis Shu DF, Dong BR, Lin XF, Wu TX, Liu GJ". Dare. Retrieved 2 May 2014.http://cpr.sagepub.com/content/19/3/330.abstract
- de Peuter, OR; Lussana, F; Peters, RJ; Büller, HR; Kamphuisen, PW (Oct 2009). "A systematic review of selective and non-selective beta blockers for prevention of vascular events in patients with acute coronary syndrome or heart failure.". The Netherlands journal of medicine 67 (9): 284–94. PMID 19841485.A systematic review of selective and non-selective beta blockers for prevention of vascular events in patients with acute coronary syndrome or heart failure
- Wiysonge, CS; Bradley, HA; Volmink, J; Mayosi, BM; Mbewu, A; Opie, LH (Nov 14, 2012). "Beta-blockers for hypertension.". The Cochrane database of systematic reviews 11: CD002003. PMID 23152211.
- Chen, JM; Heran, BS; Perez, MI; Wright, JM (Jan 20, 2010). "Blood pressure lowering efficacy of beta-blockers as second-line therapy for primary hypertension.". The Cochrane database of systematic reviews (1): CD007185. PMID 20091622.
- Balamuthusamy, S. "Comparative analysis of beta-blockers with other antihypertensive agents on cardiovascular outcomes in hypertensive patients with diabetes mellitus: a systematic review and meta-analysis". Dare.
- Kumana, Cyrus R.; Cheung, Bernard M. Y.; Cheung, Giselle T. Y.; Ovedal, Tori; Pederson, Bjorn; Lauder, Ian J. (2005). "Rhythm vs. rate control of atrial fibrillation meta-analysed by number needed to treat". British Journal of Clinical Pharmacology 60 (4): 347–354. doi:10.1111/j.1365-2125.2005.02449.x.Rhythm vs. rate control of atrial fibrillation meta-analysed by number needed to treat
- Caldeira, Daniel; David, Cláudio; Sampaio, Cristina. "Rate versus rhythm control in atrial fibrillation and clinical outcomes: Updated systematic review and meta-analysis of randomized controlled trials". Archives of Cardiovascular Diseases 105 (4): 226–238. doi:10.1016/j.acvd.2011.11.005.
- Lafuente-Lafuente, C; Longas-Tejero, MA; Bergmann, JF; Belmin, J (May 16, 2012). "Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation.". The Cochrane database of systematic reviews 5: CD005049. PMID 22592700.
- Linde, K; Rossnagel, K (2004). "Propranolol for migraine prophylaxis.". The Cochrane database of systematic reviews (2): CD003225. PMID 15106196.
- "Migraine August 2013". Nice.
- Gluud, LL; Krag, A (Aug 15, 2012). "Banding ligation versus beta-blockers for primary prevention in esophageal varices in adults.". The Cochrane database of systematic reviews 8: CD004544. PMID 22895942.
- Chan, KK; Lai, P; Wright, JM (Feb 26, 2014). "First-line beta-blockers versus other antihypertensive medications for chronic type B aortic dissection.". The Cochrane database of systematic reviews 2: CD010426. PMID 24570114.
- Thakur, V; Rankin, KN; Hartling, L; Mackie, AS (Aug 2013). "A systematic review of the pharmacological management of aortic root dilation in Marfan syndrome.". Cardiology in the young 23 (4): 568–81. PMID 23083542.
- Fleisher, LA; Beckman, JA; Brown, KA; Calkins, H; Chaikof, EL; Fleischmann, KE; Freeman, WK; Froehlich, JB; Kasper, EK; Kersten, JR; Riegel, B; Robb, JF (Nov 24, 2009). "2009 ACCF/AHA focused update on perioperative beta blockade incorporated into the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American college of cardiology foundation/American heart association task force on practice guidelines.". Circulation 120 (21): e169–276. PMID 19884473.
- Poldermans, D.; Bax, J. J.; Boersma, E.; De Hert, S.; Eeckhout, E.; Fowkes, G.; Gorenek, B.; Hennerici, M. G.; Iung, B.; Kelm, M.; Kjeldsen, K. P.; Kristensen, S. D.; Lopez-Sendon, J.; Pelosi, P.; Philippe, F.; Pierard, L.; Ponikowski, P.; Schmid, J.-P.; Sellevold, O. F. M.; Sicari, R.; Van den Berghe, G.; Vermassen, F.; Hoeks, S. E.; Vanhorebeek, I.; Vahanian, A.; Auricchio, A.; Bax, J. J.; Ceconi, C.; Dean, V.; Filippatos, G.; Funck-Brentano, C.; Hobbs, R.; Kearney, P.; McDonagh, T.; McGregor, K.; Popescu, B. A.; Reiner, Z.; Sechtem, U.; Sirnes, P. A.; Tendera, M.; Vardas, P.; Widimsky, P.; De Caterina, R.; Agewall, S.; Al Attar, N.; Andreotti, F.; Anker, S. D.; Baron-Esquivias, G.; Berkenboom, G.; Chapoutot, L.; Cifkova, R.; Faggiano, P.; Gibbs, S.; Hansen, H. S.; Iserin, L.; Israel, C. W.; Kornowski, R.; Eizagaechevarria, N. M.; Pepi, M.; Piepoli, M.; Priebe, H. J.; Scherer, M.; Stepinska, J.; Taggart, D.; Tubaro, M. (27 August 2009). "Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery: The Task Force for Preoperative Cardiac Risk Assessment and Perioperative Cardiac Management in Non-cardiac Surgery of the European Society of Cardiology (ESC) and endorsed by the European Society of Anaesthesiology (ESA)". European Heart Journal 30 (22): 2769–2812. doi:10.1093/eurheartj/ehp337.
- Bouri, S.; Shun-Shin, M. J.; Cole, G. D.; Mayet, J.; Francis, D. P. (31 July 2013). "Meta-analysis of secure randomised controlled trials of -blockade to prevent perioperative death in non-cardiac surgery". Heart 100 (6): 456–464. doi:10.1136/heartjnl-2013-304262.
- "Joint Statement: issued by the American College of Cardiology, American Heart Association and the European Society of Cardiology 05 Aug 2013". ESC. Retrieved 5 May 2014.
- "quickest-withdrawal-ever-journal-yanks-paper-alleging-800k-deaths-from-poldermans-affair January 20, 2014". retractionwatch. Retrieved 5 May 2014.
- Gersh, BJ; Maron, BJ; Bonow, RO; Dearani, JA; Fifer, MA; Link, MS; Naidu, SS; Nishimura, RA; Ommen, SR; Rakowski, H; Seidman, CE; Towbin, JA; Udelson, JE; Yancy, CW; American College of Cardiology Foundation/American Heart Association Task Force on Practice, Guidelines (Dec 13, 2011). "2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.". Journal of the American College of Cardiology 58 (25): e212–60. PMID 22075469.
- Schneier FR (2006). "Clinical practice. Social anxiety disorder". N. Engl. J. Med. 355 (10): 1029–1036. doi:10.1056/NEJMcp060145. PMID 16957148.
- Tyrer, Peter (1992). "Anxiolytics not acting at the benzodiazepine receptor: Beta blockers". Progress in Neuro-Psychopharmacology and Biological Psychiatry 16 (1): 17–26. doi:10.1016/0278-5846(92)90004-X. PMID 1348368.
- Baldwin, D. S.; Anderson, I. M.; Nutt, D. J.; Allgulander, C.; Bandelow, B.; den Boer, J. A.; Christmas, D. M.; Davies, S.; Fineberg, N.; Lidbetter, N.; Malizia, A.; McCrone, P.; Nabarro, D.; O'Neill, C.; Scott, J.; van der Wee, N.; Wittchen, H.-U. (8 April 2014). "Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: A revision of the 2005 guidelines from the British Association for Psychopharmacology". Journal of Psychopharmacology 28 (5): 403–439. doi:10.1177/0269881114525674.
- Blair Tindall. "Better Playing Through Chemistry", The New York Times, 17 October 2004. Retrieved 3 July 2011.
- World Anti-Doping Agency (2005-09-19). "The Worl Anti-Doping Code: The 2006 Prohibited List International Standard". World Anti-Doping Agency. Retrieved 2006-12-13.
- Elman MJ, Sugar J, Fiscella R, et al. (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.
- Editor Rossi S, ed. (2006). Australian Medicines Handbook. Adelaide: Australian Medicines Handbook.
- Cruickshank JM (2010). "Beta-blockers and heart failure". Indian Heart J 62 (2): 101–10. PMID 21180298.
- Beta-Adrenoceptor Antagonists (Beta-Blockers); http://www.cvpharmacology.com/cardioinhibitory/beta-blockers.htm
- Elliott WJ, Meyer PM (2007). "Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis". Lancet 369 (9557): 201–207. doi:10.1016/S0140-6736(07)60108-1. PMID 17240286.
- Mayor S (2006). "NICE removes beta blockers as first line treatment for hypertension". BMJ 333 (7557): 8–8. doi:10.1136/bmj.333.7557.8-a. PMC 1488775. PMID 16809680.
- eMedicine - Toxicity, Cocaine : Article by Carlos J Roldan
- eMedicine - Toxicity, Amphetamine : Article by Neal Handly
- Salpeter, SR. "Cardioselective beta-blockers for reversible airway disease 9 November 2011". cochrane summaries.
- Finkel, Jonathan B.; Marhefka, Gregary D. "Rethinking Cocaine-Associated Chest Pain and Acute Coronary Syndromes". Mayo Clinic Proceedings 86 (12): 1198–1207. doi:10.4065/mcp.2011.0338.Rethinking Cocaine-Associated Chest Pain and Acute Coronary Syndromes
- Antman, EM; Anbe, DT; Armstrong, PW; Bates, ER; Green, LA; Hand, M; Hochman, JS; Krumholz, HM; Kushner, FG; Lamas, GA; Mullany, CJ; Ornato, JP; Pearle, DL; Sloan, MA; Smith SC, Jr; Alpert, JS; Anderson, JL; Faxon, DP; Fuster, V; Gibbons, RJ; Gregoratos, G; Halperin, JL; Hiratzka, LF; Hunt, SA; Jacobs, AK; Ornato, JP (Aug 4, 2004). "ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction).". Journal of the American College of Cardiology 44 (3): E1–E211. PMID 15358047.
- Weinstein RS, Cole S, Knaster HB, Dahlbert T (February 1985). "Beta blocker overdose with propranolol and with atenolol". Ann Emerg Med 14 (2): 161–163. doi:10.1016/S0196-0644(85)81081-7. PMID 2857542.
- "Toxicity, Beta-blocker: Treatment & Medication - eMedicine Emergency Medicine". Retrieved 2009-03-06.
- Beta-Adrenergic Blocker Poisoning; http://www.courses.ahc.umn.edu/pharmacy/6124/handouts/Beta%20blockers.pdf
- 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, J. Larry; Loscalzo, Joseph (2010). Harrison's Nephrology and Acid-Base Disorders. McGraw-Hill Companies. p. 215. ISBN 0-07-166339-8. Retrieved 2010-09-08.
- O'Donnell, John M.; Nácul, Flávio E. (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, Ira B.; Northridge, Mary E., 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.
- Manger, William Muir; Gifford, Ray Wallace (2001). 100 Questions and Answers about Hypertension. Blackwell Science. p. 106. ISBN 0-632-04481-0. Retrieved 2010-09-10.
- Rothfeld, Glenn S.; Romaine, Deborah S. (2005). The Encyclopedia of Men's Health. Amaranth. p. 48. ISBN 0-8160-5177-1. Retrieved 2010-10-23.
- 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.
- Stoschitzky K, Sakotnik A, Lercher P et al. (1999). "Influence of beta-blockers on melatonin release". Eur. J. Clin. Pharmacol. 55 (2): 111–115. doi:10.1007/s002280050604. PMID 10335905.
- Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 15. ISBN 1-59541-101-1.
- Greenway, F; Liu, Z; Yu, Y; Gupta, A (2011). "A clinical trial testing the safety and efficacy of a standardized Eucommia ulmoides Oliver bark extract to treat hypertension". Alternative medicine review 16 (4): 338–47. PMID 22214253.
- Umehara S, Goyagi T, Nishikawa T, Tobe Y, Masaki Y (2010). "Esmolol and landiolol, selective beta1-adrenoreceptor antagonists, provide neuroprotection against spinal cord ischemia and reperfusion in rats". Anesthesia and Analgesia 21 (3): 1133–7. doi:10.1213/ANE.0b013e3181cdb06b. PMID 20103544.
- 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, 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)