Beta blocker

Beta blocker

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Encyclopedia
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...

 used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

 (heart attack), and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

. As beta adrenergic receptor antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

s, they diminish the effects of epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

 (adrenaline) and other stress hormones. In 1958 the first beta blocker, dichloroisoproterenol, was synthesised by Eli Lilly Laboratories, but it was Sir James W. Black
James W. Black
Sir James Whyte Black, OM, FRS, FRSE, FRCP was a Scottish doctor and pharmacologist. He spent his career both as researcher and as an academic at several universities. Black established the physiology department at the University of Glasgow, where he became interested in the effects of adrenaline...

 in 1962, who found the first clinically significant use of beta blockers with propranolol and pronethalol
Pronethalol
Pronethalol was an early non-selective beta blocker clinical candidate. It was never used clinically due to carcinogenicity in mice, which was thought to result from formation of a carcinogenic naphthalene epoxide metabolite....

; 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
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...

 of the 20th century.

Beta blockers block the action of endogenous
Endogenous
Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...

 catecholamine
Catecholamine
Catecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...

s epinephrine (adrenaline) and norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

 (noradrenaline) in particular, on β-adrenergic receptor
Adrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....

s, part of the sympathetic nervous system
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...

 which mediates the "fight or flight
Fight-or-flight response
The fight-or-flight response was first described by Walter Bradford Cannon....

" response. There are three known types of beta receptor, designated β1, β2 and β3 receptors. β1-adrenergic receptors
Beta-1 adrenergic receptor
The beta-1 adrenergic receptor , also known as ADRB1, is a beta-adrenergic receptor, and also denotes the human gene encoding it...

 are located mainly in the heart and in the kidneys. β2-adrenergic receptors
Beta-2 adrenergic receptor
The beta-2 adrenergic receptor , also known as ADRB2, is a beta-adrenergic receptor, and also denotes the human gene encoding it.-Gene:The gene is intronless...

 are located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle. β3-adrenergic receptors
Beta-3 adrenergic receptor
The beta-3 adrenergic receptor , also known as ADRB3, is an beta-adrenergic receptor, and also denotes the human gene encoding it.-Function:Actions of the β3 receptor include:*Enhancement of lipolysis in adipose tissue....

 are located in fat cells.

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
  • Atrial fibrillation
    Atrial fibrillation
    Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...

  • Cardiac arrhythmia
  • Congestive heart failure
    Congestive heart failure
    Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...

  • Essential tremor
    Essential tremor
    Essential tremor is a slowly progressive neurological disorder whose most recognizable feature is a tremor of the arms that is apparent during voluntary movements such as eating and writing...

  • Glaucoma
    Glaucoma
    Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...

  • Hypertension
    Hypertension
    Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

  • Migraine
    Migraine
    Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...

     prophylaxis
  • Mitral valve prolapse
    Mitral valve prolapse
    Mitral valve prolapse is a valvular heart disease characterized by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. There are various types of MVP, broadly classified as classic and nonclassic. In its nonclassic form, MVP carries a low risk of...

  • Myocardial infarction
    Myocardial infarction
    Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

  • Phaeochromocytoma, in conjunction with α-blocker
    Alpha blocker
    Alpha-1 blockers constitute a variety of drugs which block α1-adrenergic receptors in arteries and smooth muscles.-Pharmacology:...

  • Postural orthostatic tachycardia syndrome
    Postural orthostatic tachycardia syndrome
    Postural orthostatic tachycardia syndrome is a condition of dysautonomia, more specifically orthostatic intolerance, in which a change from the supine position to an upright position causes an abnormally large increase in heart rate, called tachycardia...

  • Symptomatic control (tachycardia
    Tachycardia
    Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

    , tremor
    Tremor
    A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...

    ) in anxiety
    Anxiety
    Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

     and hyperthyroidism
    Hyperthyroidism
    Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...



Beta blockers have also been used in the following conditions:
  • Acute aortic dissection
    Aortic dissection
    Aortic dissection occurs when a tear in the inner wall of the aorta causes blood to flow between the layers of the wall of the aorta and force the layers apart. The dissection typically extends anterograde, but can extend retrograde from the site of the intimal tear. Aortic dissection is a medical...

  • Hypertrophic obstructive cardiomyopathy
    Cardiomyopathy
    Cardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both. Cardiomyopathy can often go undetected, making it especially dangerous to...

  • Marfan syndrome
    Marfan syndrome
    Marfan syndrome is a genetic disorder of the connective tissue. People with Marfan's tend to be unusually tall, with long limbs and long, thin fingers....

     (treatment with propranolol slows progression of aortic dilation and its complications)
  • Prevention of variceal bleeding in portal hypertension
    Portal hypertension
    In medicine, portal hypertension is hypertension in the portal vein and its tributaries.It is often defined as a portal pressure gradient of 10 mmHg or greater.-Causes:Causes can be divided into prehepatic, intrahepatic, and posthepatic...

  • Possible mitigation of hyperhidrosis
    Hyperhidrosis
    Hyperhidrosis is the condition characterized by abnormally increased perspiration, in excess of that required for regulation of body temperature.-Classification:Hyperhidrosis can either be generalized or localized to specific parts of the body...

  • Social anxiety disorder
    Social anxiety disorder
    Social anxiety disorder , also known as social phobia, is an anxiety disorder characterized by intense fear in social situations causing considerable distress and impaired ability to function in at least some parts of daily life...

     and other anxiety disorders

Congestive heart failure


Although beta blockers were once contraindicated in congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...

, as they have the potential to worsen the condition, studies in the late 1990s showed their efficacy at reducing morbidity and mortality in congestive heart failure.
Bisoprolol
Bisoprolol
Bisoprolol is a drug belonging to the group of beta blockers, a class of drugs used primarily in cardiovascular diseases. More specifically, it is a selective type β1 adrenergic receptor blocker. The FDA approved Duramed Pharmaceutical's application for Zebeta Oral Tablets as a new molecular...

, carvedilol
Carvedilol
Carvedilol is a non-selective beta blocker/alpha-1 blocker indicated in the treatment of mild to moderate congestive heart failure . It is marketed under various trade names including Carvil , Coreg , Dilatrend , Eucardic , and Carloc as a generic drug ., and as a...

 and sustained-release metoprolol
Metoprolol
Metoprolol is a selective β1 receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. The active substance metoprolol is employed either as metoprolol succinate or metoprolol tartrate...

 are specifically indicated as adjuncts to standard ACE inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...

 and diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...

 therapy in congestive heart failure.

Beta blockers are primarily known for their reductive effect on heart rate, although this is not the only mechanism of action of importance in congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...

 . Beta blockers, in addition to their sympatholytic B1 activity in the heart, influence the renin/angiotensin system at the kidneys. Beta blockers cause a decrease in renin secretion, which in turn reduce the heart oxygen demand by lowering extracellular volume and increasing the oxygen carrying capacity of blood. Beta blockers sympatholytic activity reduce heart rate, thereby increasing the ejection fraction of the heart despite an initial reduction in ejection fraction.

Trials have shown that beta blockers reduce the absolute risk of death by 4.5% over a 13 month period. As well as reducing the risk of mortality, the number of hospital visits and hospitalizations were also reduced in the trials.

Anxiety and performance enhancement


There is clear evidence from many controlled trials in the past 25 years that beta blockers are effective in anxiety disorders, though the mechanism of action is not known. Some people have used beta blockers for performance enhancement, and especially to combat performance anxiety. In particular, musicians, public speakers, actors, and professional dancers, have been known to use beta blockers to avoid stage fright
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, whether actually or potentially . In the context of public speaking, this fear is termed glossophobia, one of the most common...

 and tremor during public performance and especially auditions.

The application to stage fright was first recognized in The Lancet
The Lancet
The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...

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
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

, revealed that 27 percent of its musicians had used beta blockers and that 70 percent 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 say the performance may be perceived as "soulless and inauthentic".

The physiological symptoms of the fight/flight response associated with 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, whether actually or potentially . In the context of public speaking, this fear is termed glossophobia, one of the most common...

 and panic
Panic
Panic is a sudden sensation of fear which is so strong as to dominate or prevent reason and logical thinking, replacing it with overwhelming feelings of anxiety and frantic agitation consistent with an animalistic fight-or-flight reaction...

 (pounding heart, cold/clammy hands, increased respiration, sweating, etc.) are significantly reduced, thus enabling anxious individuals to concentrate on the task at hand. Stutterers
Stuttering
Stuttering , also known as stammering , is a speech disorder in which the flow of speech is disrupted by involuntary repetitions and prolongations of sounds, syllables, words or phrases, and involuntary silent pauses or blocks in which the stutterer is unable to produce sounds...

 also use beta blockers to avoid fight/flight responses, hence reducing the tendency to stutter. Officially, beta blockers are not approved for anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...

 use by the U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

.

Since they promote a lower heart rate and reduce tremor, beta blockers have been used by some Olympic
Olympic Games
The Olympic Games is a major international event featuring summer and winter sports, in which thousands of athletes participate in a variety of competitions. The Olympic Games have come to be regarded as the world’s foremost sports competition where more than 200 nations participate...

 marksmen
Marksman
A marksman is a person who is skilled in precision, or a sharpshooter shooting, using projectile weapons, such as with a rifle but most commonly with a sniper rifle, to shoot at long range targets...

 to enhance performance, though beta blockers are banned by the International Olympic Committee
International Olympic Committee
The International Olympic Committee is an international corporation based in Lausanne, Switzerland, created by Pierre de Coubertin on 23 June 1894 with Demetrios Vikelas as its first president...

 (IOC). Although they have no recognisable benefit to most sports, it is acknowledged that they are beneficial to sports such as archery
Target archery
Modern competitive archery is governed by the World Archery Federation, abbreviated WA . Olympic rules are derived from WA rules. WA is the International Olympic Committee's recognized governing body for all of archery.Currently 142 nations are represented by WA archery governing bodies...

 and shooting
Shooting sports
A shooting sport is a competitive sport involving tests of proficiency using various types of guns such as firearms and airguns . Hunting is also a shooting sport, and indeed shooting live pigeons was an Olympic event...

. A recent, high-profile transgression took place in the 2008 Summer Olympics
2008 Summer Olympics
The 2008 Summer Olympics, officially known as the Games of the XXIX Olympiad, was a major international multi-sport event that took place in Beijing, China, from August 8 to August 24, 2008. A total of 11,028 athletes from 204 National Olympic Committees competed in 28 sports and 302 events...

, where 50 metre pistol
Shooting at the 2008 Summer Olympics – Men's 50 metre pistol
-Qualification round:DQ Disqualified – Q Qualified for final-Final:DQ Disqualified...

 silver medallist and 10 metre air pistol
Shooting at the 2008 Summer Olympics – Men's 10 metre air pistol
-Qualification round:The qualification round was held between 12:00 and 13:45 China Standard Time , with all shooters fitting into a single relay.DQ Disqualified – Q Qualified for final-Final:...

 bronze medallist Kim Jong-su tested positive for propranolol and was stripped of his medal.

Preventing PTSD


Posttraumatic stress disorder (PTSD) is theorized to be the result of neurological patterns caused by adrenaline and fear in the brain. By administering beta blockers immediately following a traumatic event, as well as over the next couple weeks, the formation of PTSD has been reduced in clinical studies.

Adverse effects


Adverse drug reaction
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...

s (ADRs) associated with the use of beta blockers include: nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

, diarrhoea, bronchospasm
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 of substances from mast cells or basophils under the influence of anaphylatoxins...

, dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...

, cold extremities, exacerbation of Raynaud's syndrome, bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...

, hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...

, heart failure, heart block
Heart block
A heart block can be a blockage at any level of the electrical conduction system of the heart .* Blocks that occur within the sinoatrial node are described as SA nodal blocks....

, fatigue, dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....

, alopecia
Alopecia
Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...

 (hair loss), abnormal vision, hallucinations, insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

, nightmares, sexual dysfunction
Sexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....

, erectile dysfunction
Erectile dysfunction
Erectile dysfunction is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual performance....

 and/or alteration of glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 and lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

 metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

. Mixed α1/β-antagonist therapy is also commonly associated with orthostatic hypotension
Orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...

. Carvedilol
Carvedilol
Carvedilol is a non-selective beta blocker/alpha-1 blocker indicated in the treatment of mild to moderate congestive heart failure . It is marketed under various trade names including Carvil , Coreg , Dilatrend , Eucardic , and Carloc as a generic drug ., and as a...

 therapy is commonly associated with edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...

.

Central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 (CNS) adverse effects (hallucinations, insomnia, nightmares) are more common in agents with greater lipid solubility, which are able to cross the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

 into the CNS. Similarly, CNS adverse effects are less common in agents with greater aqueous solubility (listed below).

Adverse effects associated with β2-adrenergic receptor antagonist activity (bronchospasm, peripheral vasoconstriction, alteration of glucose and lipid metabolism) are less common with β1-selective (often termed "cardioselective") agents, however receptor selectivity diminishes at higher doses. Beta blockade, especially of the beta-1 receptor at the macula densa inhibits renin release, thus decreasing the release of aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...

. This causes hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...

 and hyperkalemia
Hyperkalemia
Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...

.

Hypoglycemia can occur with beta-blockade because β2-adrenoceptors normally stimulate hepatic glycogen breakdown (glycogenolysis) and pancreatic release of glucagon, which work together to increase plasma glucose. Therefore, blocking β2-adrenoceptors lowers plasma glucose. β1-blockers have fewer metabolic side effects in diabetic patients; however, the tachycardia which serves as a warning sign for insulin-induced hypoglycemia may be masked. Therefore, beta-blockers are to be used cautiously in diabetics.

A 2007 study revealed that diuretics and beta-blockers used for hypertension increase a patient's risk of developing diabetes while ACE inhibitors and Angiotensin II receptor antagonist
Angiotensin II receptor antagonist
Angiotensin II receptor antagonists, also known as angiotensin receptor blockers , AT1-receptor antagonists or sartans, are a group of pharmaceuticals which modulate the renin-angiotensin-aldosterone system...

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 cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

, amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...

, or other alpha adrenergic stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...

 overdose. The blockade of only beta receptors increases hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, reduces coronary blood flow, left ventricular function, and cardiac output
Cardiac output
Cardiac output is the volume of blood being pumped by the heart, in particular by a left or right ventricle in the time interval of one minute. CO may be measured in many ways, for example dm3/min...

 and tissue perfusion by means of leaving the alpha adrenergic system stimulation unopposed. The appropriate antihypertensive
Antihypertensive
The antihypertensives are a class of drugs that are used to treat hypertension . Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from...

 drugs to administer during hypertensive crisis resulting from stimulant abuse are vasodilators like nitroglycerin, diuretics like furosemide
Furosemide
Furosemide or frusemide is a loop diuretic used in the treatment of congestive heart failure and edema. It is most commonly marketed by Sanofi-Aventis under the brand name Lasix...

 and alpha blockers like phentolamine
Phentolamine
Phentolamine is a reversible nonselective alpha-adrenergic antagonist. -Mechanism:Its primary action is vasodilation due to α1 blockade....

.

Contraindications


They are contraindicative to patients with asthma as stated in the BNF 2011. Beta blockers should also be avoided in patients with history of cocaine use or in cocaine-induced tachycardia or MI.

Toxicity


Glucagon
Glucagon
Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...

 has been used in the treatment of overdose.
Glucagon has a positive inotropic action on the heart and decreases renal vascular resistance. It is therefore useful in patients with beta-blocker cardiotoxicity. Glucagon is the specific antidote for beta-blocker poisoning, because it increases intracellular cAMP and cardiac contractility.
Cardiac pacing should be reserved for patients unresponsive to pharmacological therapy.

Patients who experience bronchospasm due to the B2 blocking effects of non-selective beta-blockers may be treated with anticholinergic drugs such as Ipratropium
Ipratropium
Ipratropium bromide is an anticholinergic drug used for the treatment of chronic obstructive pulmonary disease and acute asthma. It blocks the muscarinic acetylcholine receptors in the smooth muscles of the bronchi in the lungs, opening the bronchi...

, which are safer than beta agonists in patients with cardiovascular disease.

β-Receptor antagonism


Stimulation of β1 receptors by epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

 induces a positive chronotropic
Chronotropic
Chronotropic effects are those that change the heart rate.Chronotropic drugs may change the heart rate by affecting the nerves controlling the heart, or by changing the rhythm produced by the sinoatrial node...

 and inotropic effect on the heart and increases cardiac conduction velocity and automaticity.
Stimulation of β1 receptors on the kidney causes renin
Renin
Renin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...

 release. Stimulation of β2 receptors induces smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...

 relaxation, induces tremor in skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...

, and increases glycogenolysis
Glycogenolysis
Glycogenolysis is the conversion of glycogen polymers to glucose monomers. Glycogen is catabolized by removal of a glucose monomer through cleavage with inorganic phosphate to produce glucose-1-phosphate...

 in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 and skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...

. Stimulation of β3 receptors induces lipolysis
Lipolysis
Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into free fatty acids followed by further degradation into acetyl units by beta oxidation. The process produces Ketones, which are found in large quantities in ketosis, a metabolic state that occurs when the liver...

.

Beta blockers inhibit these normal epinephrine-mediated sympathetic
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...

 actions, but have minimal effect on resting subjects.
That is, they reduce excitement/physical exertion on heart rate and force of contraction, and also tremor and breakdown of glycogen, but increase dilation of blood vessels and constriction of bronchi.

It is therefore expected that non-selective beta blockers have an antihypertensive
Antihypertensive
The antihypertensives are a class of drugs that are used to treat hypertension . Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from...

 effect. The primary antihypertensive mechanism of betablockers is unclear but it may involve reduction in cardiac output (due to negative chronotropic and inotropic effects). It may also be due to reduction in renin
Renin
Renin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...

 release from the kidneys, and a central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 effect to reduce sympathetic activity (for those β-blockers that do cross the blood-brain barrier, e.g. Propranolol).

Antianginal effects result from negative chronotropic
Chronotropic
Chronotropic effects are those that change the heart rate.Chronotropic drugs may change the heart rate by affecting the nerves controlling the heart, or by changing the rhythm produced by the sinoatrial node...

 and inotropic effects, which decrease cardiac workload and oxygen demand. Negative chronotropic
Chronotropic
Chronotropic effects are those that change the heart rate.Chronotropic drugs may change the heart rate by affecting the nerves controlling the heart, or by changing the rhythm produced by the sinoatrial node...

 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
Atrioventricular node
The atrioventricular node is a part of the electrical control system of the heart that coordinates heart rate. It electrically connects atrial and ventricular chambers...

 conduction, and prolonged atrial
Atrium (anatomy)
In anatomy, the atrium , sometimes called auricle , refers to a chamber or space. For example, the term is used for a portion of the lateral ventricle in the brain and the blood collection chamber of the heart...

 refractory periods. Sotalol
Sotalol
Sotalol is a drug used in individuals with rhythm disturbances of the heart, and to treat hypertension in some individuals. It is a non-selective competitive β-adrenergic receptor blocker that also exhibits Class III antiarrhythmic properties by its inhibition of potassium channels...

, in particular, has additional antiarrhythmic properties and prolongs action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...

 duration through potassium channel
Potassium channel
In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...

 blockade.

Blockade of the sympathetic nervous system on renin release leads to reduced aldosterone via the renin angiotensin aldosterone system
Renin-angiotensin system
The renin-angiotensin system or the renin-angiotensin-aldosterone system is a hormone system that regulates blood pressure and water balance....

 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
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

). See partial agonist
Partial agonist
Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...

 for a more general description.

Some beta blockers (e.g. oxprenolol
Oxprenolol
Oxprenolol is a non-selective beta blocker with some intrinsic sympathomimetic activity...

, pindolol
Pindolol
Pindolol is a beta blocker....

, penbutolol
Penbutolol
Penbutolol is a medication in the class of beta blockers, used in the treatment of high blood pressure.-External links:*...

 and acebutolol
Acebutolol
Acebutolol is a beta blocker for the treatment of hypertension and arrhythmias.-Pharmacology:Acebutolol is a cardioselective beta blocker with ISA...

) 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
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

. These agents, therefore, may be useful in individuals exhibiting excessive bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...

 with sustained beta blocker therapy.

Agents with ISA are not used in post-myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

 as they have not been demonstrated to be beneficial. They may also be less effective than other beta blockers in the management of angina and tachyarrhythmia.

α1-Receptor antagonism


Some beta blockers (e.g. labetalol
Labetalol
Labetalol is a mixed alpha/beta adrenergic antagonist, which is used to treat high blood pressure.-Indications:...

 and carvedilol
Carvedilol
Carvedilol is a non-selective beta blocker/alpha-1 blocker indicated in the treatment of mild to moderate congestive heart failure . It is marketed under various trade names including Carvil , Coreg , Dilatrend , Eucardic , and Carloc as a generic drug ., and as a...

) exhibit mixed antagonism of both β- and α1-adrenergic receptor
Adrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....

s, which provides additional arteriolar
Arteriole
An arteriole is a small diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillaries.Arterioles have muscular walls and are the primary site of vascular resistance...

 vasodilating action.

Other effects


Beta blockers decrease nocturnal melatonin
Melatonin
Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...

 release, perhaps partly accounting for sleep disturbance caused by some agents.

They can also be used to treat glaucoma because they decrease intraocular pressure
Intraocular pressure
Intraocular pressure 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 from glaucoma...

 by lowering aqueous humor secretion.

Examples of beta blockers



Non-selective agents

  • Alprenolol
    Alprenolol
    Alprenolol, or alfeprol, alpheprol, and alprenololum , is a non-selective beta blocker as well as 5-HT1A receptor antagonist, used in the treatment of angina pectoris...

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

  • Carteolol
    Carteolol
    Carteolol is a non-selective beta blocker used to treat glaucoma....

  • Carvedilol
    Carvedilol
    Carvedilol is a non-selective beta blocker/alpha-1 blocker indicated in the treatment of mild to moderate congestive heart failure . It is marketed under various trade names including Carvil , Coreg , Dilatrend , Eucardic , and Carloc as a generic drug ., and as a...

     (has additional α-blocking activity)
  • Labetalol
    Labetalol
    Labetalol is a mixed alpha/beta adrenergic antagonist, which is used to treat high blood pressure.-Indications:...

     (has additional α-blocking activity)
  • Nadolol
    Nadolol
    Nadolol is a non-selective beta blocker used in the treatment of high blood pressure, migraine headaches, and chest pain.-Pharmacology:...

  • Oxprenolol
    Oxprenolol
    Oxprenolol is a non-selective beta blocker with some intrinsic sympathomimetic activity...

  • Penbutolol
    Penbutolol
    Penbutolol is a medication in the class of beta blockers, used in the treatment of high blood pressure.-External links:*...

     (has intrinsic sympathomimetic activity)
  • Pindolol
    Pindolol
    Pindolol is a beta blocker....

     (has intrinsic sympathomimetic activity)
  • Propranolol
  • Sotalol
    Sotalol
    Sotalol is a drug used in individuals with rhythm disturbances of the heart, and to treat hypertension in some individuals. It is a non-selective competitive β-adrenergic receptor blocker that also exhibits Class III antiarrhythmic properties by its inhibition of potassium channels...

  • Timolol
    Timolol
    Timolol maleate is a non-selective beta-adrenergic receptor blocker.-Uses:In its oral form , it is used:* to treat high blood pressure* to prevent heart attacks* to prevent migraine headaches...

  • Eucommia
    Eucommia
    Eucommia is a small tree native to China. It is near threatened in the wild, but is widely cultivated in China for its bark, highly valued in herbology such as Traditional Chinese medicine .-Characteristics:...

     bark (herb)

β1-Selective agents

  • Acebutolol
    Acebutolol
    Acebutolol is a beta blocker for the treatment of hypertension and arrhythmias.-Pharmacology:Acebutolol is a cardioselective beta blocker with ISA...

     (has intrinsic sympathomimetic activity)
  • Atenolol
  • Betaxolol
    Betaxolol
    Betaxolol is a selective beta1 receptor blocker used in the treatment of hypertension and glaucoma. Being selective for beta1 receptors, it typically has fewer systemic side effects than non-selective beta-blockers, for example, not causing bronchospasm as timolol may...

  • Bisoprolol
    Bisoprolol
    Bisoprolol is a drug belonging to the group of beta blockers, a class of drugs used primarily in cardiovascular diseases. More specifically, it is a selective type β1 adrenergic receptor blocker. The FDA approved Duramed Pharmaceutical's application for Zebeta Oral Tablets as a new molecular...

  • Celiprolol
    Celiprolol
    Celiprolol is a medication in the class of beta blockers, used in the treatment of high blood pressure....

  • Esmolol
    Esmolol
    Esmolol is a cardioselective beta1 receptor blocker with rapid onset, a very short duration of action, and no significant intrinsic sympathomimetic or membrane stabilising activity at therapeutic dosages....

  • Metoprolol
    Metoprolol
    Metoprolol is a selective β1 receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. The active substance metoprolol is employed either as metoprolol succinate or metoprolol tartrate...

  • Nebivolol
    Nebivolol
    Nebivolol is a β1 receptor blocker with nitric oxide-potentiating vasodilatory effect used in treatment of hypertension and, in Europe, also for left ventricular failure...


β2-Selective agents

  • Butaxamine
    Butaxamine
    Butaxamine 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...

     (weak α-adrenergic agonist activity) - No common clinical applications, but used in experiments.
  • ICI-118,551 Highly selective β2-adrenergic receptor antagonist - No known clinical applications, but used in experiments due to its strong receptor specificity.

β3-Selective agents

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

     (has additional α-blocking activity) - Used in experiments.

Pharmacological differences

  • Agents with intrinsic sympathomimetic action (ISA)
    • Acebutolol, carteolol, celiprolol, mepindolol, oxprenolol, pindolol, labetalol.
  • Agents with greater aqueous solubility (hydrophilic beta blockers)
    • Atenolol, celiprolol, nadolol, sotalol
  • Agents with membrane stabilizing effect
    Membrane stabilizing effect
    Membrane stabilizing effects involve the inhibition or total abolishing of action potential 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 nervous system. Membrane stabilization is the...

    • Acebutolol, betaxolol, pindolol, propranolol
  • Agents with antioxidant
    Antioxidant
    An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...

     effect
    • Carvedilol, nebivolol

Indication differences

  • Agents specifically indicated for cardiac arrhythmia
    • Esmolol
      Esmolol
      Esmolol is a cardioselective beta1 receptor blocker with rapid onset, a very short duration of action, and no significant intrinsic sympathomimetic or membrane stabilising activity at therapeutic dosages....

      , sotalol
      Sotalol
      Sotalol is a drug used in individuals with rhythm disturbances of the heart, and to treat hypertension in some individuals. It is a non-selective competitive β-adrenergic receptor blocker that also exhibits Class III antiarrhythmic properties by its inhibition of potassium channels...

      , landiolol
      Landiolol
      Landiolol is a drug which acts as a highly cardioselective, ultra short-acting beta blocker. It is used as an anti-arrhythmic agent....

  • Agents specifically indicated for congestive heart failure
    • Bisoprolol
      Bisoprolol
      Bisoprolol is a drug belonging to the group of beta blockers, a class of drugs used primarily in cardiovascular diseases. More specifically, it is a selective type β1 adrenergic receptor blocker. The FDA approved Duramed Pharmaceutical's application for Zebeta Oral Tablets as a new molecular...

      , carvedilol
      Carvedilol
      Carvedilol is a non-selective beta blocker/alpha-1 blocker indicated in the treatment of mild to moderate congestive heart failure . It is marketed under various trade names including Carvil , Coreg , Dilatrend , Eucardic , and Carloc as a generic drug ., and as a...

      , sustained-release metoprolol
      Metoprolol
      Metoprolol is a selective β1 receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. The active substance metoprolol is employed either as metoprolol succinate or metoprolol tartrate...

      , nebivolol
      Nebivolol
      Nebivolol is a β1 receptor blocker with nitric oxide-potentiating vasodilatory effect used in treatment of hypertension and, in Europe, also for left ventricular failure...

  • Agents specifically indicated for glaucoma
    • Betaxolol
      Betaxolol
      Betaxolol is a selective beta1 receptor blocker used in the treatment of hypertension and glaucoma. Being selective for beta1 receptors, it typically has fewer systemic side effects than non-selective beta-blockers, for example, not causing bronchospasm as timolol may...

      , carteolol
      Carteolol
      Carteolol is a non-selective beta blocker used to treat glaucoma....

      , levobunolol
      Levobunolol
      Levobunolol is a non-selective beta blocker. It is used topically to manage glaucoma....

      , metipranolol
      Metipranolol
      Metipranolol is a non-selective beta blocker used in eye drops to treat glaucoma. It is rapidly metabolized into desacetylmetipranolol....

      , timolol
      Timolol
      Timolol maleate is a non-selective beta-adrenergic receptor blocker.-Uses:In its oral form , it is used:* to treat high blood pressure* to prevent heart attacks* to prevent migraine headaches...

  • Agents specifically indicated for myocardial infarction
    • Atenolol, metoprolol
      Metoprolol
      Metoprolol is a selective β1 receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. The active substance metoprolol is employed either as metoprolol succinate or metoprolol tartrate...

      , propranolol
  • Agents specifically indicated for migraine prophylaxis
    • Timolol
      Timolol
      Timolol maleate is a non-selective beta-adrenergic receptor blocker.-Uses:In its oral form , it is used:* to treat high blood pressure* to prevent heart attacks* to prevent migraine headaches...

      , propranolol


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

External links