Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack (

secondary prevention Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...

). They are also widely used to treat

high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

, although they are no longer the first choice for initial treatment of most patients. Beta blockers are

competitive antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of recep ...

s that block the receptor sites for the

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...

catecholamines

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

(adrenaline) and norepinephrine (noradrenaline) on adrenergic beta receptors, of the

sympathetic nervous system The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...

, which mediates the fight-or-flight response. Some block activation of all types of

β-adrenergic receptor The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...

s 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

and lead to stress responses, especially when they are stimulated by

(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 Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

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 A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

and total cardiovascular events, they are not as effective as diuretics, medications inhibiting the renin–angiotensin system (e.g.,

ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...

s), or

calcium channel blockers Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

Medical uses

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 * Congestive heart failure * Essential tremor * Glaucoma (as eye drops, they decrease intraocular pressure by lowering aqueous humor secretion) *

Hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

, although they are generally not preferred as an initial treatment * Hyperthyroidism *

Migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

prophylaxis *

Mitral valve prolapse Mitral valve prolapse (MVP) is a valvular heart disease characterized by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. It is the primary form of myxomatous degeneration of the valve. There ar ...

* Myocardial infarction * Phaeochromocytoma, in conjunction with α-blocker * Postural orthostatic tachycardia syndrome * Symptomatic control ( tachycardia,

tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fa ...

) in anxiety and hyperthyroidism * Theophylline overdose Beta blockers have also been used for: * Acute aortic dissection * Hypertrophic obstructive

cardiomyopathy Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...

Long QT syndrome Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainting, d ...

Marfan syndrome Marfan syndrome (MFS) is a multi-systemic genetic disorder that affects the connective tissue. Those with the condition tend to be tall and thin, with long arms, legs, fingers, and toes. They also typically have exceptionally flexible joints a ...

(treatment with propranolol slows progression of aortic dilation and its complications) * Prevention of variceal bleeding in

portal hypertension Portal hypertension is abnormally increased portal venous pressure – blood pressure in the portal vein and its branches, that drain from most of the intestine to the liver. Portal hypertension is defined as a hepatic venous pressure gradient gr ...

* 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

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 Carvedilol, sold under the brand name Coreg among others, is a medication used to treat high blood pressure, congestive heart failure (CHF), and left ventricular dysfunction in people who are otherwise stable. For high blood pressure, it is gen ...

, and sustained-release metoprolol are specifically indicated as adjuncts to standard

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 the extracellular volume and increasing the oxygen-carrying capacity of the blood. Heart failure characteristically involves increased catecholamine activity on the heart, which is responsible for several 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 a 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.

Anxiety

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 Dance is a performing art form consisting of sequences of movement, either improvised or purposefully selected. This movement has aesthetic and often symbolic value. Dance can be categorized and described by its choreography, by its repertoire ...

have been known to use beta blockers to avoid

performance anxiety Stage fright or performance anxiety is the anxiety, fear, or persistent phobia which may be aroused in an individual by the requirement to perform in front of an audience, real or imagined, whether actually or potentially (for example, when perf ...

, 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".

Surgery

Low certainty evidence indicates that the use of beta blockers around the time of cardiac surgery may decrease the risk of

heart dysrhythmias Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

and atrial fibrillation. Starting them around the time of other types of surgery, however, may worsen outcomes. For non-cardiac surgery, the use of beta blockers to prevent adverse effects may reduce the risk of atrial fibrillation and myocardial infarctions (very low certainty evidence), however, there is moderate certainty evidence that this approach may increase the risk of hypotension. Low-certainty evidence suggests that beta blockers used perioperatively in non-cardiac surgeries may increase the risk of bradycardia.

Performance-enhancing use

Because they promote lower heart rates and reduce tremors, beta blockers have been used in professional sports where high accuracy is required, including

archery Archery is the sport, practice, or skill of using a bow to shoot arrows.Paterson ''Encyclopaedia of Archery'' p. 17 The word comes from the Latin ''arcus'', meaning bow. Historically, archery has been used for hunting and combat. In m ...

, shooting, golf and

snooker Snooker (pronounced , ) is a cue sports, cue sport played on a Billiard table#Snooker and English billiards tables, rectangular table covered with a green cloth called baize, with six Billiard table#Pockets 2, pockets, one at each corner and o ...

. Beta blockers are banned in some sports by the International Olympic Committee. In the

2008 Summer Olympics The 2008 Summer Olympics (), officially the Games of the XXIX Olympiad () and also known as Beijing 2008 (), were an international multisport event held from 8 to 24 August 2008, in Beijing, China. A total of 10,942 athletes from 204 Na ...

, 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. Classical musicians have commonly used beta blockers since the 1970s to reduce stage fright.

Adverse effects

Adverse drug reactions associated with the use of beta blockers include: nausea, diarrhea, bronchospasm, dyspnea, cold extremities, exacerbation of Raynaud's syndrome,

bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...

, hypotension,

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

, heart block,

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

, dizziness, alopecia (hair loss), abnormal vision,

hallucinations A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinatio ...

, insomnia,

nightmare A nightmare, also known as a bad dream, Retrieved 11 July 2016. is an unpleasant dream that can cause a strong emotional response from the mind, typically fear but also despair, anxiety or great sadness. The dream may contain situations of d ...

s, sexual dysfunction,

erectile dysfunction Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of male ...

and/or alteration of glucose and lipid metabolism. Mixed α₁/β-antagonist therapy is also commonly associated with orthostatic hypotension.

Carvedilol Carvedilol, sold under the brand name Coreg among others, is a medication used to treat high blood pressure, congestive heart failure (CHF), and left ventricular dysfunction in people who are otherwise stable. For high blood pressure, it is gen ...

therapy is commonly associated with

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...

. Due to the high penetration across the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...

, 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 Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...

. This causes hyponatremia and hyperkalemia. Hypoglycemia can occur with beta blockade because β2-adrenoceptors normally stimulate

glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one o ...

breakdown (glycogenolysis) in the liver and pancreatic release of the hormone

glucagon Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...

, 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 Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...

, reduces coronary blood flow, left

ventricular function A ventricle is one of two large chambers toward the bottom of the heart that collect and expel blood towards the peripheral beds within the body and lungs. The blood pumped by a ventricle is supplied by an atrium (heart), atrium, an adjacent chamb ...

, and

cardiac output In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: t ...

and tissue perfusion by means of leaving the alpha-adrenergic system stimulation unopposed. 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 Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests tha ...

drugs to administer during hypertensive crisis resulting from stimulant overdose are vasodilators such as

nitroglycerin Nitroglycerin (NG), (alternative spelling of nitroglycerine) also known as trinitroglycerin (TNG), nitro, glyceryl trinitrate (GTN), or 1,2,3-trinitroxypropane, is a dense, colorless, oily, explosive liquid most commonly produced by nitrating g ...

, diuretics such as furosemide, and alpha blockers such as phentolamine.

Contraindications

Contraindications for beta blockers include: * Abrupt discontinuations * Acute bronchospasm *

Acute heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

* Asthma * AV block *

Bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...

* Bronchitis *

Cardiogenic shock Cardiogenic shock (CS) is a medical emergency resulting from inadequate blood flow due to the dysfunction of the ventricles of the heart.Textbooks of Internal MedicinHarrison's Principles of Internal Medicine 16th Edition, The McGraw-Hill Compan ...

* Cerebrovascular disease * Chronic obstructive pulmonary disease (COPD) * Diabetes mellitus *

Emphysema Emphysema, or pulmonary emphysema, is a lower respiratory tract disease, characterised by air-filled spaces ( pneumatoses) in the lungs, that can vary in size and may be very large. The spaces are caused by the breakdown of the walls of the alve ...

* Hypersensitivity to beta blockers * Hypotension * Kidney failure * Hepatic disease *

Myopathy In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...

* Pheochromocytoma * Psoriasis *

Stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

* Vasospastic angina * Wolff–Parkinson–White syndrome

Asthma

The 2007 National Heart, Lung, and Blood Institute (

NHLBI The National Heart, Lung, and Blood Institute (NHLBI) is the third largest Institute of the National Institutes of Health, located in Bethesda, Maryland, United States. It is tasked with allocating about $3.6 billion in FY 2020 in tax revenue to ...

) asthma guidelines recommend against the use of non-selective beta blockers in asthmatics, while allowing for the use of cardio selective beta blockers. Cardio selective beta blocker (β1 blockers), if really required, can be prescribed at the least possible dose to those with mild to moderate respiratory symptoms.

β2-agonist Beta2-adrenergic agonists, also known as adrenergic β2 receptor agonists, are a class of drugs that act on the β2 adrenergic receptor. Like other β adrenergic agonists, they cause smooth muscle relaxation. β2 adrenergic agonists' effect ...

s 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.

Diabetes mellitus

Epinephrine signals early warning of the upcoming hypoglycemia. Beta blockers' inhibition on epinephrine's effect can somewhat exacerbate hypoglycemia by interfering with

glycogenolysis Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase. Mechanism The ...

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.

Hyperthyroidism

Abrupt withdrawal can result in a thyroid storm.

Bradycardia or AV block

Unless a pacemaker is present, beta blockers can severely depress conduction in the AV node, resulting in a reduction of heart rate and cardiac output. One should be very cautious with the use of beta blockers in tachycardia patients with Wolff-Parkinson-White Syndrome, as it can result in life-threatening arrhythmia in certain patients. By slowing the conduction through the AV node, preferential conduction through the accessory pathway is favored. If the patient happens to develop atrial flutter, this could lead to a 1:1 conduction with very fast ventricular rate, or worse, ventricular fibrillation in the case of atrial fibrillation.

Toxicity

Glucagon Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...

, used in the treatment of overdose, increases the strength of heart contractions, increases intracellular

cAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...

, and decreases renal vascular resistance. It is, therefore, useful in patients with beta blocker cardiotoxicity.

Cardiac pacing An artificial cardiac pacemaker (or artificial pacemaker, so as not to be confused with the natural cardiac pacemaker) or pacemaker is a medical device that generates electrical impulses delivered by electrodes to the chambers of the heart eith ...

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 Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic (SAMA: short acting muscarinic antagonist) medication which opens up the medium and large airways in the lungs. It is used to treat the symptoms ...

, which are safer than

beta agonists Beta adrenergic agonists or beta agonists are medications that relax muscles of the airways, causing widening of the airways and resulting in easier breathing. They are a class of sympathomimetic agents, each acting upon the beta adrenoceptors. ...

in patients with

cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...

. Other antidotes for beta blocker poisoning are

salbutamol Salbutamol, also known as albuterol and sold under the brand name Ventolin among others, is a medication that opens up the medium and large airways in the lungs. It is a short-acting β2 adrenergic receptor agonist which works by causing rel ...

and isoprenaline.

β-receptor antagonism

Stimulation of β₁ receptors by epinephrine and norepinephrine induces a positive chronotropic and

inotropic An inotrope is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular contraction. The term ''inotro ...

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 Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

relaxation, induces tremor in

skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

, and increases

in the liver and

. 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

, 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 Sotalol, sold under the brand name Betapace among others, is a medication used to treat and prevent abnormal heart rhythms. It is only recommended in those with significant abnormal heart rhythms due to potentially serious side effects. Evidence ...

, 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 Oxprenolol (brand names Trasacor, Trasicor, Coretal, Laracor, Slow-Pren, Captol, Corbeton, Slow-Trasicor, Tevacor, Trasitensin, Trasidex) is a non-selective beta blocker with some intrinsic sympathomimetic activity. It is used for the treatment o ...

pindolol Pindolol, sold under the brand name Visken among others, is a nonselective beta blocker which is used in the treatment of hypertension.Drugs.coInternational brand names for pindolol Page accessed Sept 4, 2015 It is also an antagonist of the se ...

penbutolol Penbutolol (brand names Levatol, Levatolol, Lobeta, Paginol, Hostabloc, Betapressin) is a medication in the class of beta blockers, used in the treatment of high blood pressure.FDPenbutolol labelLast updated Dec 2010 Penbutolol is able to bind to ...

, labetalol and

acebutolol Acebutolol, sold under the brand names Sectral among others, is a beta blocker for the treatment of hypertension and arrhythmias. Acebutolol is a cardioselective beta-1 blocker and has intrinsic sympathetic activity. It is commonly used in the ...

) exhibit intrinsic sympathomimetic activity (ISA). These agents are capable of exerting low-level

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

activity at the β-adrenergic receptor while simultaneously acting as a receptor site

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

. These agents, therefore, may be useful in individuals exhibiting excessive

with sustained beta blocker therapy. Agents with ISA should not be used for patients with any kind of angina as it can aggravate or after myocardial infarctions. They may also be less effective than other beta blockers in the management of

angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by ischemia, insufficient blood flow to the Cardiac muscle, heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typical ...

and

tachyarrhythmia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...

α₁-receptor antagonism

Some beta blockers (e.g., labetalol and

) exhibit mixed antagonism of both β- and α₁-

adrenergic receptor The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...

s, which provides additional arteriolar vasodilating action.

Examples

Nonselective agents

Nonselective beta blockers display both β₁ and β₂ antagonism. * Propranolol *

Bucindolol Bucindolol is a non-selective beta blocker with additional weak alpha-blocking properties and some intrinsic sympathomimetic activity. It was under review by the FDA in the United States for the treatment of heart failure in 2009, but was reject ...

(has additional α₁-blocking activity) *

Carteolol Carteolol is a non-selective beta blocker used to treat glaucoma. It has been found to act as a serotonin 5-HT1A and 5-HT1B receptor antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. ...

(has additional α₁-blocking activity) * Labetalol (has intrinsic sympathomimetic activity and additional α₁-blocking activity) * Nadolol *

Oxprenolol Oxprenolol (brand names Trasacor, Trasicor, Coretal, Laracor, Slow-Pren, Captol, Corbeton, Slow-Trasicor, Tevacor, Trasitensin, Trasidex) is a non-selective beta blocker with some intrinsic sympathomimetic activity. It is used for the treatment o ...

(has intrinsic sympathomimetic activity) *

Penbutolol Penbutolol (brand names Levatol, Levatolol, Lobeta, Paginol, Hostabloc, Betapressin) is a medication in the class of beta blockers, used in the treatment of high blood pressure.FDPenbutolol labelLast updated Dec 2010 Penbutolol is able to bind to ...

(has intrinsic sympathomimetic activity) *

Pindolol Pindolol, sold under the brand name Visken among others, is a nonselective beta blocker which is used in the treatment of hypertension.Drugs.coInternational brand names for pindolol Page accessed Sept 4, 2015 It is also an antagonist of the se ...

(has intrinsic sympathomimetic activity) *

(not considered a "typical beta blocker") *

Timolol Timolol is a beta blocker medication used either by mouth or as eye drops. As eye drops it is used to treat increased pressure inside the eye such as in ocular hypertension and glaucoma. By mouth it is used for high blood pressure, chest pai ...

β₁-selective agents

β₁-selective beta blockers are also known as cardioselective beta blockers. Pharmacologically, the beta-blockade of the B1 receptors in the heart will act on

. The function of cAMP as a second messenger in the cardiac cell is that it phosphorylates the LTCC and the ryanodine receptor to increase intracellular calcium levels and cause contraction. Beta-blockade of the B1 receptor will inhibit cAMP from phosphorylating, and it will decrease the ionotrophic and chronotropic effect. Note that drugs may be cardioselective, or act on B1 receptors in the heart only, but still have instrinsic sympathomimetic activity. *

Acebutolol Acebutolol, sold under the brand names Sectral among others, is a beta blocker for the treatment of hypertension and arrhythmias. Acebutolol is a cardioselective beta-1 blocker and has intrinsic sympathetic activity. It is commonly used in the ...

(has intrinsic sympathomimetic activity, ISA) * Atenolol *

Betaxolol Betaxolol is a selective beta1 receptor blocker used in the treatment of hypertension and angina. Being selective for beta1 receptors, it typically has fewer systemic side effects than non-selective beta-blockers, for example, not causing bronc ...

* Bisoprolol *

Celiprolol Celiprolol is a medication in the class of beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack af ...

(has intrinsic sympathomimetic activity) * Metoprolol *

Nebivolol Nebivolol is a beta blocker used to treat high blood pressure and heart failure. As with other β-blockers, it is generally a less preferred treatment for high blood pressure. It may be used by itself or with other blood pressure medication. I ...

Esmolol Esmolol, sold under the brand name Brevibloc, is a cardio selective beta1 receptor blocker with rapid onset, a very short duration of action, and no significant intrinsic sympathomimetic or membrane stabilising activity at therapeutic dosages. ...

Nebivolol and Bisoprolol are the most β₁ cardioselective beta blockers.

β₂-selective agents

* Butaxamine *

ICI-118,551 ICI-118,551 is a selective β2 adrenergic receptor (adrenoreceptor) antagonist or beta blocker. ICI binds to the β2 subtype with at least 100 times greater affinity than β1 or β3, the two other known subtypes of the beta adrenoceptor. The c ...

β₃-selective agents

* SR 59230A

β₁ selective antagonist and β₃ agonist agents

Comparative information

Pharmacological differences

* Agents with intrinsic sympathomimetic action (ISA) ** Acebutolol, pindolol, labetalol, mepindolol, oxprenolol, celiprolol, penbutolol * 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

Indication differences

* Agents specifically labeled for cardiac arrhythmia **

sotalol Sotalol, sold under the brand name Betapace among others, is a medication used to treat and prevent abnormal heart rhythms. It is only recommended in those with significant abnormal heart rhythms due to potentially serious side effects. Evidence ...

landiolol Landiolol (INN) is an ultra short-acting, β1-superselective intravenous adrenergic antagonist, which decreases the heart rate effectively with less negative effect on blood pressure or myocardial contractility. In comparison to other beta blo ...

(Japan) * Agents specifically labeled for congestive heart failure ** Bisoprolol,

, sustained-release metoprolol * Agents specifically labeled for glaucoma **

carteolol Carteolol is a non-selective beta blocker used to treat glaucoma. It has been found to act as a serotonin 5-HT1A and 5-HT1B receptor antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. ...

levobunolol Levobunolol (trade names AKBeta, Betagan, Vistagan, among others) is a non-selective beta blocker. It is used topically in the form of eye drops to manage ocular hypertension (high pressure in the eye) and open-angle glaucoma. Contraindications ...

timolol Timolol is a beta blocker medication used either by mouth or as eye drops. As eye drops it is used to treat increased pressure inside the eye such as in ocular hypertension and glaucoma. By mouth it is used for high blood pressure, chest pai ...

metipranolol Metipranolol (OptiPranolol, Betanol, Disorat, Trimepranol) is a non-selective beta blocker used in eye drops to treat glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. Th ...

* Agents specifically labeled for myocardial infarction ** Atenolol, metoprolol (immediate release), propranolol (immediate release),

(after left ventricular dysfunction), bisoprolol (preventive treatment before and primary treatment after heart attacks) * Agents specifically labeled for migraine prophylaxis **

, propranolol Propranolol is the only agent indicated for the control of tremor, portal hypertension, and esophageal variceal bleeding, and used in conjunction with α-blocker therapy in phaeochromocytoma.

Other effects

Beta blockers, due to their antagonism at beta-1 adrenergic receptors, inhibit both the synthesis of new

melatonin Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle. In vertebrates ...

and its secretion by the

pineal gland The pineal gland, conarium, or epiphysis cerebri, is a small endocrine gland in the brain of most vertebrates. The pineal gland produces melatonin, a serotonin-derived hormone which modulates sleep, sleep patterns in both circadian rhythm, circ ...

. 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 Schizoid personality disorder (, often abbreviated as SzPD or ScPD) is a personality disorder characterized by a Asociality, lack of interest in social relationships, a tendency toward a solitary or sheltered lifestyle, secretiveness, emotion ...

. However, there is limited evidence supporting the efficacy of supplemental beta blocker use in addition to antipsychotic drugs for treating schizophrenia. Contrast agents are not contraindicated in those receiving beta blockers.

References

External links

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.")

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. A condensed version of the 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) * {{DEFAULTSORT:Beta Blocker Scottish inventions

Medical uses

Congestive heart failure

Anxiety

Surgery

Performance-enhancing use

Adverse effects

Contraindications

Asthma

Diabetes mellitus

Hyperthyroidism

Bradycardia or AV block

Toxicity

β-receptor antagonism

Intrinsic sympathomimetic activity

α1-receptor antagonism

Examples

Nonselective agents

β1-selective agents

β2-selective agents

β3-selective agents

β1 selective antagonist and β3 agonist agents

Comparative information

Pharmacological differences

Indication differences

Other effects

See also

References

External links

α₁-receptor antagonism

β₁-selective agents

β₂-selective agents

β₃-selective agents

β₁ selective antagonist and β₃ agonist agents