Beta blocker

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Beta blockers
Drug class
Skeletal formula of propranolol, the first clinically successful beta blocker
Class identifiers
Use Hypertension, arrhythmia, etc.
ATC code C07
Biological target beta receptors
Clinical data Drug Classes
Consumer Reports Best Buy Drugs
WebMD MedicineNet  RxList
External links
MeSH D000319

Beta blockers (also β-blockers, beta-adrenergic blocking agents, beta antagonists, beta-adrenergic antagonists, beta-adrenoreceptor antagonists, or beta adrenergic receptor antagonists) are a class of drugs that are particularly used to manage cardiac arrhythmias, and to protect the heart from a second heart attack (myocardial infarction) after a first heart attack (secondary prevention).[1] They are also widely used to treat hypertension, although they are no longer the first choice for initial treatment of most patients according to current guidelines (as of 2016).[2][3]

Beta blockers are competitive antagonists that block the receptor sites for the endogenous catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) on adrenergic beta receptors, of the sympathetic nervous system, which mediates the fight-or-flight response.[4][5] Some block activation of all types of β-adrenergic receptors and others are selective for one of the three known types of beta receptors, designated β1, β2 and β3 receptors.[6] β1-adrenergic receptors are located mainly in the heart and in the kidneys.[5] β2-adrenergic receptors are located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle.[5] β3-adrenergic receptors are located in fat cells.[7]

Beta receptors are found on cells of the heart muscles, smooth muscles, airways, arteries, kidneys, and other tissues that are part of the sympathetic nervous system and lead to stress responses, especially when they are stimulated by epinephrine (adrenaline). Beta blockers interfere with the binding to the receptor of epinephrine and other stress hormones, and weaken the effects of stress hormones.

In 1964, Sir James W. Black [8] synthesized the first clinically significant beta blockers—propranolol and pronethalol; it revolutionized the medical management of angina pectoris[9] and is considered by many to be one of the most important contributions to clinical medicine and pharmacology of the 20th century.[10]

For the treatment of primary hypertension, meta-analyses of studies which mostly used atenolol as the beta-blocker tested[11] have shown although beta-blockers are more effective than placebo in preventing stroke and total cardiovascular events, they are not as effective as diuretics, drugs inhibiting the renin-angiotensin system or calcium channel blockers.[11][12][13][14]

Medical uses[edit]

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:

Beta blockers have also been used for:

Congestive heart failure[edit]

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.[20][21][22] 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 what are indicated for other conditions. It should be noted that 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.[citation needed] Beta blockers, in addition to their sympatholytic β1 activity in the heart, influence the renin–angiotensin system at the kidneys. Beta blockers cause a decrease in renin secretion, which in turn reduces the heart oxygen demand by lowering extracellular volume and increasing the oxygen-carrying capacity of blood. Heart failure characteristically involves increased catecholamine activity on the heart, which is responsible for a number of 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.[23] 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.[24]


Officially, beta blockers are not approved for anxiolytic use by the U.S. Food and Drug Administration.[25] 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.[26] 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 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.[27] 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".[27]

Since they promote lower heart rates and reduce tremors, beta blockers have been used in professional sports where high accuracy is required, including archery, shooting, golf[28] and snooker.[28] Beta blockers are banned by the International Olympic Committee.[29] A recent, high-profile transgression took place in the 2008 Summer Olympics, where 50- metre pistol silver medallist and 10-metre air pistol bronze medallist Kim Jong-su tested positive for propranolol and was stripped of his medals.

For similar reasons, beta blockers have also been used by surgeons.[30]


The use of beta blockers around the time of cardiac surgery decreases the risk of heart dysrhythmias.[31] Starting them around the time of other types of surgery, however, worsens outcomes.[31]

Adverse effects[edit]

Adverse drug reactions associated with the use of beta blockers include: nausea, diarrhea, bronchospasm, dyspnea, cold extremities, exacerbation of Raynaud's syndrome, bradycardia, hypotension, heart failure, heart block, fatigue, dizziness, alopecia (hair loss), abnormal vision, hallucinations, insomnia, nightmares, sexual dysfunction, erectile dysfunction and/or alteration of glucose and lipid metabolism. Mixed α1/β-antagonist therapy is also commonly associated with orthostatic hypotension. Carvedilol therapy is commonly associated with edema.[32] Due to the high penetration across the blood–brain barrier, lipophilic beta blockers, such as propranolol and metoprolol, are more likely than other less lipophilic beta blockers to cause sleep disturbances, such as insomnia, vivid dreams and nightmares.[33]

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. This causes hyponatremia and hyperkalemia.

Hypoglycemia can occur with beta blockade because β2-adrenoceptors normally stimulate hepatic glycogen breakdown (glycogenolysis) and pancreatic release of glucagon, which work together to increase plasma glucose. Therefore, blocking β2-adrenoceptors lowers plasma glucose. β1-blockers have fewer metabolic side effects in diabetic patients; however, the tachycardia that serves as a warning sign for insulin-induced hypoglycemia may be masked. Therefore, beta blockers are to be used cautiously in diabetics.[34]

A 2007 study revealed diuretics and beta blockers used for hypertension increase a patient's risk of developing diabetes, while ACE inhibitors and angiotensin II receptor antagonists (angiotensin receptor blockers) actually decrease the risk of diabetes.[35] 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.[36]

Beta blockers must not be used in the treatment of selective alpha-adrenergic agonist overdose. The blockade of only beta receptors increases hypertension, reduces coronary blood flow, left ventricular function, and cardiac output and tissue perfusion by means of leaving the alpha-adrenergic system stimulation unopposed.[medical citation needed] 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.[37] The mixed alpha- and beta-blocker labetalol is especially useful for treatment of concomitant tachycardia and hypertension induced by methamphetamine.[38] The phenomenon of "unopposed alpha stimulation" has not been reported with the use of beta-blockers for treatment of methamphetamine toxicity.[38] 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 such as phentolamine.[39]


Beta blockers are contraindicated in patients with asthma as stated in the British National Formulary 2011.[citation needed] They should also be avoided in patients with a history of cocaine use or in cocaine-induced tachycardia.[citation needed]

Beta blockers should not be used as a first-line treatment in the acute setting for cocaine-induced acute coronary syndrome (CIACS). No recent studies have been identified that show the benefit of beta blockers in reducing coronary vasospasm, or coronary vascular resistance, in patients with CIACS. In the multiple case studies identified, the use of beta blockers in CIACS resulted in detrimental outcomes, and the discontinuation of beta blockers used in the acute setting led to improvement in clinical course.[citation needed] The guidelines by the American College of Cardiology/American Heart Association also support this idea, and recommend against the use of beta blockers in cocaine-induced ST-segment elevation myocardial infarction (MI) because of the risk of coronary vasospasm.[citation needed] Though, in general, beta blockers improve mortality in patients who have suffered MI, it is unclear whether patients with CIACS will benefit from this mortality reduction because no studies assess the use of beta blockers in the long term, and because cocaine users may be prone to continue to abuse the substance, thus complicating the effect of drug therapy.[40]


Glucagon, used in the treatment of overdose,[41][42] increases the strength of heart contractions, increases intracellular cAMP, and decreases renal vascular resistance. It is, therefore, useful in patients with beta-blocker cardiotoxicity.[43][44] Cardiac pacing is usually reserved for patients unresponsive to pharmacological therapy.

Patients experiencing bronchospasm due to the β2 receptor-blocking effects of nonselective beta blockers may be treated with anticholinergic drugs, such as ipratropium, which are safer than beta agonists in patients with cardiovascular disease. Other antidotes for beta-blocker poisoning are salbutamol and isoprenaline.

β-Receptor antagonism[edit]

Stimulation of β1 receptors by epinephrine and norepinephrine induces a positive chronotropic and inotropic effect on the heart and increases cardiac conduction velocity and automaticity.[45] Stimulation of β1 receptors on the kidney causes renin release.[46] Stimulation of β2 receptors induces smooth muscle relaxation,[47] induces tremor in skeletal muscle,[48] and increases glycogenolysis in the liver and skeletal muscle.[49] Stimulation of β3 receptors induces lipolysis.[50]

Beta blockers inhibit these normal epinephrine- and norepinephrine-mediated sympathetic actions,[4] but have minimal effect on resting subjects.[citation needed] That is, they reduce excitement/physical exertion on heart rate and force of contraction,[51] and also tremor,[52] breakdown of glycogen, and constriction of bronchi.[53]

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.[54]

Accordingly, nonselective beta blockers are expected to have antihypertensive effects.[55] The primary antihypertensive mechanism of beta blockers is unclear, but may involve reduction in cardiac output (due to negative chronotropic and inotropic effects).[56] It may also be due to reduction in renin release from the kidneys, and a central nervous system effect to reduce sympathetic activity (for those beta blockers that do cross the blood–brain barrier, e.g. propranolol).

Antianginal effects result from negative chronotropic and inotropic effects, which decrease cardiac workload and oxygen demand. Negative chronotropic properties of beta blockers allow the lifesaving property of heart rate control. Beta blockers are readily titrated to optimal rate control in many pathologic states.

The antiarrhythmic effects of beta blockers arise from sympathetic nervous system blockade—resulting in depression of sinus node function and atrioventricular node conduction, and prolonged atrial refractory periods. Sotalol, in particular, has additional antiarrhythmic properties and prolongs action potential duration through potassium channel blockade.

Blockade of the sympathetic nervous system on renin release leads to reduced aldosterone via the renin-angiotensin-aldosterone system, with a resultant decrease in blood pressure due to decreased sodium and water retention.

Intrinsic sympathomimetic activity[edit]

Also referred to as intrinsic sympathomimetic effect, this term is used particularly with beta blockers that can show both agonism and antagonism at a given beta receptor, depending on the concentration of the agent (beta blocker) and the concentration of the antagonized agent (usually an endogenous compound, such as norepinephrine). See partial agonist for a more general description.

Some beta blockers (e.g. oxprenolol, pindolol, penbutolol, labetalol and acebutolol) exhibit intrinsic sympathomimetic activity (ISA). These agents are capable of exerting low-level agonist activity at the β-adrenergic receptor while simultaneously acting as a receptor site antagonist. These agents, therefore, may be useful in individuals exhibiting excessive bradycardia with sustained beta blocker therapy.

Agents with ISA are not used after myocardial infarctions, as they have not been demonstrated to be beneficial. They may also be less effective than other beta blockers in the management of angina and tachyarrhythmia.[32]

α1-receptor antagonism[edit]

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

Other effects[edit]

Beta blockers decrease nocturnal melatonin release, perhaps partly accounting for sleep disturbances caused by some agents.[57]


Dichloroisoprenaline, the first beta blocker

Nonselective agents[edit]

β1-selective agents[edit]

Also known as cardioselective

β2-selective agents[edit]

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

β3-selective agents[edit]

  • SR 59230A (has additional α-blocking activity): Used in experiments

Comparative information[edit]

Pharmacological differences[edit]

  • Agents with intrinsic sympathomimetic action (ISA)
    • Acebutolol, carteolol, celiprolol, mepindolol, oxprenolol, pindolol
  • Agents with greater aqueous solubility (hydrophilic beta blockers)
    • Atenolol, celiprolol, nadolol, sotalol
  • Agents with membrane stabilizing effect

Indication differences[edit]

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.[32]

See also[edit]


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External links[edit]