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

heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

after a first heart attack ( secondary prevention). They are also widely used to treat

high blood pressure Hypertension, also known as high blood pressure, 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 itself. It is, however, a major ri ...

, although they are no longer the first choice for initial treatment of most people. Beta blockers are competitive antagonists that block the receptor sites for the endogenous catecholamines epinephrine (adrenaline) and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

(noradrenaline) on adrenergic beta receptors, of the sympathetic nervous system, which mediates the fight-or-flight response. Beta-adrenergic receptors are found on cells of the

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

muscles, smooth muscles, airways, arteries,

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

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 thereby weaken the effects of stress hormones. Some beta blockers 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. In 1964, James Black synthesized the first clinically significant beta blockers—

propranolol Propranolol is a medication of the beta blocker class. It is used to treat hypertension, high blood pressure, some types of cardiac dysrhythmia, irregular heart rate, thyrotoxicosis, capillary hemangiomas, akathisia, performance anxiety, and ...

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 the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur betwee ...

of the 20th century. For the treatment of primary hypertension (high blood pressure), meta-analyses of studies which mostly used

atenolol Atenolol is a beta blocker medication primarily used to treat high blood pressure and angina, heart-associated chest pain. Although used to treat high blood pressure, it does not seem to improve mortality rate, mortality in those with the condi ...

have shown that although beta blockers are more effective than

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

in preventing

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

and total cardiovascular events, they are not as effective as diuretics, 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

Beta blockers are utilized in the treatment of various conditions related to the heart and vascular system, as well as several other medical conditions. Common heart-related conditions for which beta blockers are well-established include angina pectoris, acute coronary syndromes, hypertension, and arrhythmias such as atrial fibrillation and heart failure. They are also used in the management of other heart diseases, such as hypertrophic obstructive cardiomyopathy, mitral valve stenosis or prolapse, and dissecting aneurysm. Additionally, beta blockers find applications in vascular surgery, the treatment of anxiety states, cases of thyrotoxicosis, glaucoma, migraines, and esophageal varices.

Congestive heart failure

Although beta blockers were once contraindicated in congestive heart failure, as they have the potential to worsen the condition due to their effect of decreasing cardiac contractility, studies in the late 1990s showed their efficacy at reducing morbidity and mortality. Bisoprolol, carvedilol, and sustained-release metoprolol are specifically indicated as adjuncts to standard ACE inhibitor and diuretic therapy in congestive heart failure, although at doses typically much lower than those indicated for other conditions. Beta blockers are only indicated in cases of compensated, stable congestive heart failure; in cases of acute decompensated heart failure, beta blockers will cause a further decrease in ejection fraction, worsening the patient's current symptoms. Beta blockers are known primarily for their reductive effect on heart rate, although this is not the only mechanism of action of importance in congestive heart failure. Beta blockers, in addition to their sympatholytic β₁ activity in the heart, influence the

at the kidneys. Beta blockers cause a decrease in renin 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. A 2020 Cochrane review found minimal evidence to support the use of beta blockers in congestive heart failure in children, however did identify that from the data available, that they may be of benefit. Therapeutic administration of beta blockers for congestive heart failure ought to begin at very low doses ( 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.

Acute myocardial infarction

Beta blockers are indicated for the treatment of acute

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

s. During a myocardial infarction, systemic stress causes an increase in circulating catecholamines. This results an increase in heart rate and blood pressure, therefore increasing myocardial oxygen demand. Beta blockers competitively inhibit catecholamines acting on the β₁-adrenergic receptors, thus reducing these detrimental effects and resulting in reduced myocardial oxygen consumption and demand. A 2019 Cochrane review compared beta blockers with

or no intervention, it found that beta blockers probably reduced the short-term risk of reinfarction and the long-term risk of all-cause mortality and cardiovascular mortality. The review identified that beta blockers likely had little to no impact on short-term all-cause mortality and cardiovascular mortality.

Hypertension

Beta blockers are widely used for the treatment of hypertension. A 2014 Cochrane review found that in individuals with mild-to-moderate hypertension, non-selective beta blockers led to a reduction of -10/-7mmHg (systolic/diastolic) without increased rates of adverse events. At higher doses, it was found to increase the rate of adverse effects such as a reduction in heart rate, without a corresponding reduction in blood pressure. A 2017 Cochrane review on the use of beta blockers in hypertension found a modest reduction in cardiovascular disease but little to no change in mortality. It suggested that the effects of beta blockers are inferior to other anti-hypertensive medications.

Anxiety

Officially, beta blockers are not approved for anxiolytic 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 respo ...

. However, many controlled trials in the past 25 years indicate beta blockers are effective in anxiety disorders, though the mechanism of action is not known. The physiological symptoms of the fight-or-flight response (pounding heart, cold/clammy hands, increased respiration, sweating, etc.) are significantly reduced, thus enabling anxious individuals to concentrate on the task at hand. Musicians, public speakers, actors, and professional dancers have been known to use beta blockers to avoid performance anxiety, stage fright, and tremor during both auditions and public performances. The application to stage fright was first recognized in ''

The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal, founded in England in 1823. It is one of the world's highest-impact academic journals and also one of the oldest medical journals still in publication. The journal publishes ...

'' 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 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.

Other

A 2014 Cochrane review investigated the use of beta blockers in the maintenance of chronic type B thoracic aortic aneurysm in comparison to other anti hypertensive medications. The review found no suitable evidence to support the current guidelines recommending its use. A 2017 Cochrane review on the use of beta blockers to prevent aortic dissections in people with Marfan syndrome was unable to draw definitive conclusions due to lack of evidence. Adrenergic antagonists are mostly used for

cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...

. The adrenergic antagonists are widely used for lowering blood pressure and relieving

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

. These antagonists have a been proven to relieve the pain caused by

, and also the infarction size, which correlates with heart rate. There are few non-cardiovascular uses for adrenergic antagonists. Alpha-adrenergic antagonists are also used for treatment of ureteric stones,

pain Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...

and panic disorders, withdrawal, and

anesthesia Anesthesia (American English) or anaesthesia (British English) is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prev ...

. Beta blockers are used to treat acute cardiovascular

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect o ...

(e.g. in

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014.

) caused by sympathomimetics, for instance caused by

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

ephedrine Ephedrine is a central nervous system (CNS) stimulant and sympathomimetic agent that is often used to prevent hypotension, low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred ...

, and other drugs. Combined α₁ and beta blockers like labetalol and carvedilol may be more favorable for such purposes due to the possibility of "unopposed α-stimulation" with selective beta blockers.

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 and arrow, bow to shooting, shoot arrows.Paterson ''Encyclopaedia of Archery'' p. 17 The word comes from the Latin ''arcus'', meaning bow. Historically, archery has been used for hunting ...

, shooting,

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

and

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

. Beta blockers are banned in some sports by the

International Olympic Committee The International Olympic Committee (IOC; , CIO) is the international, non-governmental, sports governing body of the modern Olympic Games. Founded in 1894 by Pierre de Coubertin and Demetrios Vikelas, it is based i ...

. In the

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

, 50-metre pistol silver medalist and 10-metre air pistol bronze medalist Kim Jong-su 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 reactions 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. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

, diarrhea, bronchospasm, dyspnea, cold extremities, exacerbation of Raynaud's syndrome, bradycardia,

hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

, heart block,

fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...

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

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

, nightmares, sexual dysfunction,

erectile dysfunction Erectile dysfunction (ED), also referred to as impotence, is a form of sexual dysfunction in males characterized by the persistent or recurring inability to achieve or maintain a Human penis, penile erection with sufficient rigidity and durat ...

, alteration of

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

and lipid metabolism. Mixed α₁/β-antagonist therapy is also commonly associated with orthostatic hypotension. Carvedilol therapy is commonly associated with edema. Due to the high penetration across the blood–brain barrier, lipophilic beta blockers, such as

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 ...

. This causes

hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the Serum (blood), 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. Symp ...

and hyperkalemia.

Hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes 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 tria ...

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 Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

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 mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...

, while ACE inhibitors 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 Blood pressure (BP) is the pressure of Circulatory system, 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 ...

, 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 metoprolol and labetalol may be useful for treating CNS and cardiovascular toxicity from a methamphetamine overdose. The mixed alpha- and beta blocker labetalol is especially useful for treatment of concomitant tachycardia and hypertension induced by methamphetamine. The phenomenon of "unopposed alpha stimulation" has not been reported with the use of beta blockers for treatment of methamphetamine toxicity. Other appropriate antihypertensive drugs to administer during hypertensive crisis resulting from stimulant overdose are vasodilators such as nitroglycerin, diuretics such as furosemide, and

alpha blockers Alpha blockers, also known as α-blockers or α-adrenoreceptor antagonists, are a class of pharmacological agents that act as neutral antagonist, antagonists on Adrenergic receptor#.CE.B1 receptors, α-adrenergic receptors (Adrenergic receptor ...

such as phentolamine.

Contraindications and cautions

Absolute contraindications: * Bradycardia *

Hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

* Hypersensitivity to beta blockers * Cardiogenic shock * Second or third degree AV block Relative contraindications, or contraindications specific to certain beta-blockers: * Long QT syndrome: sotalol is contraindicated * History of torsades de pointes: sotalol is contraindicated Cautions: * Abrupt discontinuations * Acute bronchospasm * Acute

* Asthma: see below * Bronchitis *

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) * Emphysema * Kidney failure * Hepatic disease * Myopathy * Pheochromocytoma * Psoriasis * Raynaud phenomenon *

Stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

* Vasospastic angina * Wolff–Parkinson–White syndrome

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) can be prescribed at the least possible dose to those with mild to moderate respiratory symptoms. β2-agonists can somewhat mitigate β-blocker-induced bronchospasm where it exerts greater efficacy on reversing ''selective'' β-blocker-induced bronchospasm than the ''nonselective'' β-blocker-induced worsening asthma and/or COPD.

Diabetes mellitus

Epinephrine signals early warning of the upcoming

hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes 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 tria ...

. 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, and tremors. Diligent blood glucose level monitoring is necessary for a patient with diabetes mellitus on beta blockers.

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, used in the treatment of overdose, increases the strength of heart contractions, increases intracellular cAMP, and decreases renal vascular resistance. It is, therefore, useful in patients with beta blocker cardiotoxicity. Cardiac pacing is usually reserved for patients unresponsive to pharmacological therapy. People experiencing bronchospasm due to the β₂ receptor-blocking effects of nonselective beta blockers may be treated with

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

drugs, such as ipratropium, which are safer than beta agonists in patients with

. Other antidotes for beta blocker poisoning are salbutamol and isoprenaline.

Pharmacology

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 (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

for a more general description. Some beta blockers (e.g. oxprenolol, pindolol, penbutolol, labetalol and acebutolol) exhibit intrinsic sympathomimetic activity (ISA). These agents are capable of exerting low-level

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

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 main enemy or rival of the protagonist and is often depicted as a villain.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 Heart rate#Resting heart rate, normal resting rate. In general, a resting heart rate over 100 pulse, beats per minute is accepted as tachycardia in adults. Heart rates a ...

β-Adrenergic 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 cardiac cycle, rhythm by affecting the electrical conduction system of the hea ...

and inotropic effect on the heart and increases cardiac conduction velocity and automaticity. Stimulation of β₁ receptors on the kidney causes renin release. Stimulation of β₂ receptors induces smooth muscle relaxation, induces tremor in

skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

, and increases glycogenolysis in the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

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

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 function and

atrioventricular node The atrioventricular node (AV node, or Aschoff-Tawara 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 ...

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

action potential An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...

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.

α₁-Adrenergic receptor antagonism

Some beta blockers (e.g., labetalol and carvedilol) exhibit mixed antagonism of both β- and α₁- adrenergic receptors, which provides additional arteriolar vasodilating action.

Blood–brain barrier permeability

Beta blockers vary in their lipophilicity (fat solubility) and in turn in their ability to cross the blood–brain barrier and exert effects in the

. Beta blockers with greater blood–brain barrier permeability can have both neuropsychiatric therapeutic benefits and

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s, as well as adverse cognitive effects. Central nervous system-related side effects and risks of beta blockers may include

, depression, sleep disorders (namely

) and nightmares, visual hallucinations, delirium,

psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

, and falling. Conversely, central nervous system-related benefits of beta blockers may include prevention and treatment of migraine, essential tremor, akathisia,

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental disorder that develops from experiencing a Psychological trauma, traumatic event, such as sexual assault, domestic violence, child abuse, warfare and its associated traumas, natural disaster ...

, aggression, and

obsessive–compulsive disorder Obsessive–compulsive disorder (OCD) is a mental disorder in which an individual has intrusive thoughts (an ''obsession'') and feels the need to perform certain routines (''Compulsive behavior, compulsions'') repeatedly to relieve the dis ...

. Most beta blockers are lipophilic and can cross into the brain, but there are a number of exceptions. Highly lipophilic beta blockers include penbutolol, pindolol,

, and timolol, moderately lipophilic beta blockers include acebutolol, betaxolol, bisoprolol, carvedilol, metoprolol, and nebivolol, and low lipophilicity or hydrophilic beta blockers include

, carteolol, esmolol, labetalol, nadolol, and sotalol. It is thought that highly lipophilic beta blockers are able to readily cross into the brain, moderately lipophilic beta blockers are able to cross to a lesser degree, and low lipophilicity or hydrophilic beta blockers are minimally able to cross. More lipophilic beta-blockers are known to suppress melatonin release by 50-80%. The preceding beta blockers also vary in their intrinsic sympathomimetic activity and β₁-adrenergic receptor selectivity (or cardioselectivity), resulting in further differences in pharmacological profiles and suitability in different contexts between them.

Agents

Nonselective agents

Nonselective beta blockers display both β₁ and β₂ antagonism. *

Propranolol Propranolol is a medication of the beta blocker class. It is used to treat hypertension, high blood pressure, some types of cardiac dysrhythmia, irregular heart rate, thyrotoxicosis, capillary hemangiomas, akathisia, performance anxiety, and ...

* Bucindolol (has additional α₁-blocking activity) * Carteolol * Carvedilol (has additional α₁-blocking activity) * Labetalol (has intrinsic sympathomimetic activity and additional α₁-blocking activity) * Nadolol * Oxprenolol (has intrinsic sympathomimetic activity) * Penbutolol (has intrinsic sympathomimetic activity) * Pindolol (has intrinsic sympathomimetic activity) * Sotalol (not considered a "typical beta blocker") * Timolol

β₁-selective agents

β₁-selective beta blockers are also known as cardioselective beta blockers. Pharmacologically, the beta-blockade of the β₁ 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 β₁ receptor will inhibit cAMP from phosphorylating, and it will decrease the ionotrophic and chronotropic effect. Note that drugs may be cardioselective, or act on β₁ receptors in the heart only, but still have intrinsic sympathomimetic activity. * Acebutolol (has intrinsic sympathomimetic activity, ISA) *

Atenolol Atenolol is a beta blocker medication primarily used to treat high blood pressure and angina, heart-associated chest pain. Although used to treat high blood pressure, it does not seem to improve mortality rate, mortality in those with the condi ...

* Betaxolol * Bisoprolol * Celiprolol (has intrinsic sympathomimetic activity) * Metoprolol * Nebivolol * Esmolol Nebivolol and bisoprolol are the most β₁ cardioselective beta blockers.

β₂-selective agents

* Butaxamine * ICI-118,551

β₃-selective agents

* SR 59230A

β₁ selective antagonist and β₃ agonist agents

* Nebivolol

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 ** Esmolol, sotalol, landiolol (Japan) * Agents specifically labeled for congestive heart failure ** Bisoprolol, carvedilol, sustained-release metoprolol * Agents specifically labeled for glaucoma ** Betaxolol, carteolol, levobunolol, timolol, metipranolol * Agents specifically labeled for myocardial infarction **

, metoprolol (immediate release),

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

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 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 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 ''The New York Times'' (''NYT'') is an American daily newspaper based in New York City. ''The New York Times'' covers domestic, national, and international news, and publishes opinion pieces, investigative reports, and reviews. As one of ...

'', 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 British inventions Scottish inventions