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 A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...

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, 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 r ...

s that block the receptor sites for the endogenous

catecholamine A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a su ...

s epinephrine (adrenaline) and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...

(noradrenaline) on adrenergic beta receptors, of the sympathetic nervous system, which mediates the

fight-or-flight response The fight-or-flight or the fight-flight-or-freeze response (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first des ...

. 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 The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...

muscles,

smooth muscles 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 ...

airway The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to ...

arteries An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pu ...

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...

s, 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 Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance an ...

and

pronethalol Pronethalol (also known as nethalide or compound 38,174; trade name Alderlin) was an early non-selective beta blocker clinical candidate. It was the first beta blocker to be developed by James Black and associates at Imperial Chemical Industri ...

; it revolutionized the medical management of

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

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 A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting m ...

of studies which mostly used

atenolol Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of mi ...

have shown that although beta blockers are more effective than

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...

in preventing stroke and total cardiovascular events, they are not as effective as

diuretics A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics i ...

, medications inhibiting the

renin–angiotensin system The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance. When renal blood flow is reduced, ...

(e.g., ACE inhibitors), or calcium channel blockers.

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

(contraindicated for

Prinzmetal's angina Variant angina, also known as Prinzmetal angina, vasospastic angina, angina inversa, coronary vessel spasm, or coronary artery vasospasm, is a syndrome typically consisting of angina (cardiac chest pain). Variant angina differs from stable angina ...

) * Atrial fibrillation *

Cardiac arrhythmia 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 ...

Congestive 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, ...

Essential tremor Essential tremor (ET), also called benign tremor, familial tremor, and idiopathic tremor, is a medical condition characterized by involuntary rhythmic contractions and relaxations ( oscillations or twitching movements) of certain muscle groups in ...

Glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...

(as eye drops, they decrease

intraocular pressure Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Most tonometers are calibrated t ...

by lowering

aqueous humor The aqueous humour is a transparent water-like fluid similar to plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the posteri ...

secretion) * Hypertension, although they are generally not preferred as an initial treatment *

Hyperthyroidism Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidis ...

* Migraine

prophylaxis 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 ...

* Mitral valve prolapse *

Myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...

Phaeochromocytoma Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...

, in conjunction with α-blocker *

Postural orthostatic tachycardia syndrome Postural orthostatic tachycardia syndrome (POTS) is a condition characterized by an abnormally large increase in heart rate upon standing. Symptoms may include lightheadedness, brain fog, blurred vision, weakness, fatigue, headaches, heart p ...

* Symptomatic control (

tachycardia 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 ( ...

, tremor) in

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

and

hyperthyroidism Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidis ...

Theophylline Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...

overdose Beta blockers have also been used for: * Acute

aortic dissection Aortic dissection (AD) occurs when an injury to the innermost layer of the aorta allows blood to flow between the layers of the aortic wall, forcing the layers apart. In most cases, this is associated with a sudden onset of severe chest or ...

* Hypertrophic obstructive cardiomyopathy * Long QT syndrome * Marfan syndrome (treatment with

slows progression of aortic dilation and its complications) * Prevention of variceal bleeding in portal hypertension * Possible mitigation of

hyperhidrosis Hyperhidrosis is a condition characterized by abnormally increased sweating, in excess of that required for regulation of body temperature. Although primarily a benign physical burden, hyperhidrosis can deteriorate quality of life from a psycholog ...

Social Social organisms, including human(s), live collectively in interacting populations. This interaction is considered social whether they are aware of it or not, and whether the exchange is voluntary or not. Etymology The word "social" derives from ...

and other

anxiety disorders Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...

* 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 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, ...

, 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 Bisoprolol, sold under the brand name Zebeta among others, is a beta blocker medication used for heart diseases. This includes tachyarrhythmias, high blood pressure, chest pain from not enough blood flow to the heart, and heart failure. It is ...

, carvedilol, and sustained-release

metoprolol Metoprolol, sold under the brand name Lopressor, among others, is a selective β1 receptor blocker medication. It is used to treat high blood pressure, chest pain due to poor blood flow to the heart, and a number of conditions involving an a ...

are specifically indicated as adjuncts to standard ACE inhibitor and

diuretic A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics i ...

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

at the kidneys. Beta blockers cause a decrease in

renin Renin (etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the r ...

secretion, which in turn reduces the heart oxygen demand by lowering the

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

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 An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...

use by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

. However, many controlled trials in the past 25 years indicate beta blockers are effective in

, though the mechanism of action is not known. The physiological symptoms of the

fight-or-flight The fight-or-flight or the fight-flight-or-freeze response (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first des ...

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 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 ...

, and tremor during both

audition An audition is a sample performance by an actor, singer, musician, dancer or other performer. It typically involves the performer displaying their talent through a previously memorized and rehearsed solo piece or by performing a work or piece giv ...

s and public performances. The application to stage fright was first recognized in ''

The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal and one of the oldest of its kind. It is also the world's highest-impact academic journal. It was founded in England in 1823. The journal publishes original research articles, ...

'' in 1976, and by 1987, a survey conducted by the

International Conference of Symphony Orchestra Musicians The International Conference of Symphony and Opera Musicians (ICSOis a Players' Conference of the American Federation of Musicians (AF In 1962, members of US and Canadian orchestras began to meet and discuss ways they could communicate with each o ...

, 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 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,

shooting Shooting is the act or process of discharging a projectile from a ranged weapon (such as a gun, bow, crossbow, slingshot, or blowpipe). Even the acts of launching flame, artillery, darts, harpoons, grenades, rockets, and guided missiles ...

golf Golf is a club-and-ball sport in which players use various clubs to hit balls into a series of holes on a course in as few strokes as possible. Golf, unlike most ball games, cannot and does not use a standardized playing area, and coping ...

and snooker. Beta blockers are banned in some sports by the

International Olympic Committee The International Olympic Committee (IOC; french: link=no, Comité international olympique, ''CIO'') is a non-governmental sports organisation based in Lausanne, Switzerland. It is constituted in the form of an association under the Swiss ...

. In the 2008 Summer Olympics, 50-metre pistol silver medalist and 10-metre air pistol bronze medalist

Kim Jong-su Kim Jong-su ( or ; born January 1, 1977) is a North Korean sport shooter who competed at the 2004 Summer Olympics in Athens and 2008 Summer Olympics in Beijing. In Athens, he won the bronze medal in the 50 metre pistol competition, and fi ...

tested positive for

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 reaction An adverse drug reaction (ADR) is a harmful, unintended result caused by taking medication. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs. The meaning of this term ...

s associated with the use of beta blockers include:

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

bronchospasm Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release (degranulation) of substances from mast cells or basophils under the influence of anaphylatoxins. It causes di ...

dyspnea Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...

, cold extremities, exacerbation of

Raynaud's syndrome Raynaud syndrome, also known as Raynaud's phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries cau ...

, bradycardia,

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

, heart failure,

heart block Heart block (HB) is a disorder in the heart's rhythm due to a fault in the natural pacemaker. This is caused by an obstruction – a block – in the electrical conduction system of the heart. Sometimes a disorder can be inherited. Despite the se ...

, fatigue,

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

alopecia Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scar ...

(hair loss), abnormal vision, hallucinations,

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

, nightmares,

sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction a ...

, erectile dysfunction and/or alteration of

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...

and

lipid metabolism Lipid metabolism is the synthesis and degradation of lipids in cells, involving the breakdown or storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes. In anim ...

. Mixed α₁/β-antagonist therapy is also commonly associated with

orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...

. Carvedilol therapy is commonly associated with edema. Due to the high penetration across the blood–brain barrier, lipophilic beta blockers, such as

and

, 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 In the kidney, the macula densa is an area of closely packed specialized cells lining the wall of the distal tubule, at the point where the thick ascending limb of the Loop of Henle meets the distal convoluted tubule. The macula densa is the t ...

, inhibits renin release, thus decreasing the release of aldosterone. This causes

hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be a ...

and

hyperkalemia Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasi ...

Hypoglycemia Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose bel ...

can occur with beta blockade because β2-adrenoceptors normally stimulate glycogen breakdown (glycogenolysis) in the liver and pancreatic release of the

hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...

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 Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

, while

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

and

angiotensin II receptor antagonist Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals tha ...

s (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. Beta blockers with lipophilic properties and CNS penetration such as

and

labetalol Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less pref ...

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 Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction ...

such as nitroglycerin,

such as

furosemide Furosemide is a loop diuretic medication used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It may also be used for the treatment of high blood pressure. It can be taken by injection into a vein or by m ...

, and

alpha blockers Alpha (uppercase , lowercase ; grc, ἄλφα, ''álpha'', or ell, άλφα, álfa) is the first letter of the Greek alphabet. In the system of Greek numerals, it has a value of one. Alpha is derived from the Phoenician letter aleph , whi ...

such as

phentolamine Phentolamine, sold under the brand name Regitine among others, is a reversible nonselective α- adrenergic antagonist. Mechanism Its primary action is vasodilation due to α1 blockade. Non-selective α-blockers can cause a much more pronounced ...

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, ...

Asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...

AV block Atrioventricular block (AV block) is a type of heart block that occurs when the electrical signal traveling from the atria, or the upper chambers of the heart, to ventricles, or the lower chambers of the heart, is impaired. Normally, the sinoa ...

* Bradycardia *

Bronchitis Bronchitis is inflammation of the bronchi (large and medium-sized airways) in the lungs that causes coughing. Bronchitis usually begins as an infection in the nose, ears, throat, or sinuses. The infection then makes its way down to the bronchi. ...

* Cardiogenic shock *

Cerebrovascular disease Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. Th ...

* Chronic obstructive pulmonary disease (COPD) *

Diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

* Emphysema *

Hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune ...

to beta blockers *

Hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

Kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

Hepatic disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the si ...

* Myopathy *

Pheochromocytoma Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...

Psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...

* Stroke *

Vasospastic angina Variant angina, also known as Prinzmetal angina, vasospastic angina, angina inversa, coronary vessel spasm, or coronary artery vasospasm, is a syndrome typically consisting of angina (cardiac chest pain). Variant angina differs from stable angina ...

Wolff–Parkinson–White syndrome Wolff–Parkinson–White syndrome (WPWS) is a disorder due to a specific type of problem with the electrical system of the heart. About 60% of people with the electrical problem developed symptoms, which may include an abnormally fast heartbeat, ...

Asthma

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 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-agonists can somewhat mitigate β-Blocker-induced

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 Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose bel ...

. Beta blockers' inhibition on epinephrine's effect can somewhat exacerbate hypoglycemia by interfering with glycogenolysis and mask signs of hypoglycemia such as tachycardia, palpitations,

diaphoresis Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distribu ...

, 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 The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...

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, used in the treatment of overdose, increases the strength of heart contractions, increases intracellular cAMP, and decreases renal

vascular resistance Vascular resistance is the resistance that must be overcome to push blood through the circulatory system and create flow. The resistance offered by the systemic circulation is known as the systemic vascular resistance (SVR) or may sometimes be cal ...

. 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 Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous sys ...

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 Isoprenaline, or isoproterenol (brand name: Isoprenaline Macure), is a medication used for the treatment of bradycardia (slow heart rate), heart block, and rarely for asthma. It is a non-selective β adrenoceptor agonist that is the isopropyla ...

β-receptor antagonism

Stimulation of β₁ receptors by epinephrine and norepinephrine induces a positive

chronotropic Chronotropic effects (from ''chrono-'', meaning time, and ''tropos'', "a turn") are those that change the heart rate. Chronotropic drugs may change the heart rate and rhythm by affecting the electrical conduction system of the heart and the ner ...

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

release. Stimulation of β₂ receptors induces smooth muscle relaxation, induces tremor in skeletal muscle, and increases glycogenolysis in the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

and skeletal muscle. Stimulation of β₃ receptors induces

lipolysis Lipolysis is the metabolic pathway through which lipid triglycerides are hydrolyzed into a glycerol and free fatty acids. It is used to mobilize stored energy during fasting or exercise, and usually occurs in fat adipocytes. The most important ...

. 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 The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

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

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 The sinoatrial node (also known as the sinuatrial node, SA node or sinus node) is an oval shaped region of special cardiac muscle in the upper back wall of the right atrium made up of cells known as pacemaker cells. The sinus node is approxima ...

function and

atrioventricular node The atrioventricular node or AV node electrically connects the heart's atria and ventricles to coordinate beating in the top of the heart; it is part of the electrical conduction system of the heart. The AV node lies at the lower back section of t ...

conduction, and prolonged

atrial The atrium ( la, ātrium, , entry hall) is one of two upper chambers in the heart that receives blood from the circulatory system. The blood in the atria is pumped into the heart ventricles through the atrioventricular valves. There are two at ...

refractory periods. Sotalol, in particular, has additional antiarrhythmic properties and prolongs

action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

duration through

potassium channel Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of c ...

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 In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonis ...

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 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 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.,

and carvedilol) exhibit mixed antagonism of both β- and α₁- adrenergic receptors, which provides additional arteriolar vasodilating action.

Examples

Nonselective agents

Nonselective beta blockers display both β₁ and β₂ antagonism. *

Propranolol Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance an ...

* Bucindolol (has additional α₁-blocking activity) * Carteolol * Carvedilol (has additional α₁-blocking activity) *

Labetalol Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less pref ...

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

Nadolol Nadolol, sold under the brand name Corgard among others, is a medication used to treat high blood pressure, heart pain, atrial fibrillation, and some inherited arrhythmic syndromes. It has also been used to prevent migraine headaches and compl ...

* Oxprenolol (has intrinsic sympathomimetic activity) * Penbutolol (has intrinsic sympathomimetic activity) * Pindolol (has intrinsic sympathomimetic activity) * Sotalol (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 pa ...

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 cAMP. 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 (has intrinsic sympathomimetic activity, ISA) *

Atenolol Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of mi ...

* Betaxolol *

* Celiprolol (has intrinsic sympathomimetic activity) *

Metoprolol Metoprolol, sold under the brand name Lopressor, among others, is a selective β1 receptor blocker medication. It is used to treat high blood pressure, chest pain due to poor blood flow to the heart, and a number of conditions involving an a ...

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. It ...

* Esmolol Nebivolol and Bisoprolol are the most β₁ cardioselective beta blockers.

β₂-selective agents

Butaxamine Butaxamine (INN, also known as butoxamine) is a β2-selective beta blocker. Its primary use is in experimental situations in which blockade of β2 receptors is necessary to determine the activity of the drug (i.e. if the β2 receptor is comple ...

* ICI-118,551

β₃-selective agents

SR 59230A SR 59230A is a selective antagonist of the beta-3 adrenergic receptor, but was subsequently shown to also act at α1 adrenoceptors at high doses. It has been shown to block the hyperthermia produced by MDMA 3,4-Methylenedioxymethamphetamine ...

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 Membrane stabilizing effects involve the inhibition or total abolishing of action potentials from being propagated across the membrane. This phenomenon is common in nerve tissues as they are the carrier of impulses from the periphery to the central ...

** Carvedilol, propranolol > oxprenolol > labetalol, metoprolol, timolol

Indication differences

* Agents specifically labeled for cardiac arrhythmia ** Esmolol, sotalol, landiolol (Japan) * Agents specifically labeled for congestive heart failure **

, carvedilol, sustained-release metoprolol * Agents specifically labeled for glaucoma ** Betaxolol, carteolol, levobunolol,

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 pa ...

, metipranolol * Agents specifically labeled for myocardial infarction **

(immediate release),

, carvedilol (after left ventricular dysfunction),

bisoprolol Bisoprolol, sold under the brand name Zebeta among others, is a beta blocker medication used for heart diseases. This includes tachyarrhythmias, high blood pressure, chest pain from not enough blood flow to the heart, and heart failure. It is ...

(preventive treatment before and primary treatment after heart attacks) * Agents specifically labeled for migraine prophylaxis **

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 Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...

Other effects

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,

) may be due to this effect. Some pre-clinical and clinical research suggests that some beta blockers may be beneficial for cancer treatment. However, other studies do not show a correlation between cancer survival and beta blocker usage. Also, a 2017 meta-analysis failed to show any benefit for the use of beta blockers in breast cancer. Beta blockers have also been used for the treatment of schizoid personality disorder. However, there is limited evidence supporting the efficacy of supplemental beta blocker use in addition to antipsychotic drugs for treating schizophrenia.

Contrast agent A contrast agent (or contrast medium) is a substance used to increase the contrast of structures or fluids within the body in medical imaging. Contrast agents absorb or alter external electromagnetism or ultrasound, which is different from radiop ...

s 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 ''The New York Times'' (''the Times'', ''NYT'', or the Gray Lady) is a daily newspaper based in New York City with a worldwide readership reported in 2020 to comprise a declining 840,000 paid print subscribers, and a growing 6 million paid d ...

'', 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 ''The Atlantic'' is an American magazine and multi-platform publisher. It features articles in the fields of politics, foreign affairs, business and the economy, culture and the arts, technology, and science. It was founded in 1857 in Boston, ...

'', August 20, 2008. (Discusses the use of propranolol by a North Korean pistol shooter in the 2008 Olympics) * {{DEFAULTSORT:Beta Blocker Scottish inventions