| Beta blockers | |
|---|---|
| Drug class | |
 Skeletal formula ofpropranolol, the first clinically successful beta blocker. | |
| Class identifiers | |
| Synonyms | Beta-blockers, β-blockers, beta-adrenergic blocking agents, beta antagonists, beta-adrenergic antagonists, beta-adrenoreceptor antagonists, beta adrenergic receptor antagonists, BB |
| Use | Hypertension,arrhythmia, etc. |
| ATC code | C07 |
| Biological target | beta receptors |
| Clinical data | |
| Drugs.com | Drug Classes |
| Consumer Reports | Best Buy Drugs |
| WebMD | MedicineNet RxList |
| External links | |
| MeSH | D000319 |
| Legal status | |
| In Wikidata | |
Beta blockers, also spelledβ-blockers and also known asβ-adrenergic receptor antagonists, are a class of medications that are predominantly used to manage abnormal heart rhythms (arrhythmia), and to protect the heart from a secondheart attack after a first heart attack (secondary prevention).[1] They are also widely used to treathigh blood pressure, although they are no longer the first choice for initial treatment of most people.[2] There are additional uses as well, like treatment ofanxiety.[3][4]
Beta blockers arecompetitive antagonists that block the receptor sites for theendogenouscatecholaminesepinephrine (adrenaline) andnorepinephrine (noradrenaline) onadrenergic beta receptors, of thesympathetic nervous system, which mediates thefight-or-flight response.[5]: 152 [6]
β-Adrenergic receptors are found on cells of theheart 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 byepinephrine (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.[5]: 153 β1-Adrenergic receptors are located mainly in the heart and in the kidneys.[6]β2-Adrenergic receptors are located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle.[6]β3-Adrenergic receptors are located in fat cells.[7]
In 1964,James Black[8] synthesized the first clinically significant beta blockers—propranolol andpronethalol; it revolutionized the medical management ofangina pectoris[9] and is considered by many to be one of the most important contributions to clinical medicine andpharmacology of the 20th century.[10]
For the treatment of primary hypertension (high blood pressure),meta-analyses of studies which mostly usedatenolol have shown that although beta blockers are more effective thanplacebo in preventingstroke and total cardiovascular events, they are not as effective asdiuretics, medications inhibiting therenin–angiotensin system (e.g.,ACE inhibitors), orcalcium channel blockers.[11][12][13][14]
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.[15]
Although beta blockers were once contraindicated incongestive 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.[16][17][18]Bisoprolol,carvedilol, and sustained-releasemetoprolol are specifically indicated as adjuncts to standardACE inhibitor anddiuretic 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.[citation needed]
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.[19] Beta blockers, in addition to their sympatholytic β1 activity in the heart, influence therenin–angiotensin system at the kidneys. Beta blockers cause a decrease inrenin secretion, which in turn reduces the heart oxygen demand by lowering theextracellular 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.[20] Beta blockers counter this inappropriately high sympathetic activity, eventually leading to an improved ejection fraction, despite an initial reduction in ejection fraction.[citation needed]
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.[21] 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.[22]
Therapeutic administration of beta blockers for congestive heart failure ought to begin at very low doses (1⁄8 of target) with a gradual escalation of the dose. The heart of the patient must adjust to decreasing stimulation by catecholamines and find a new equilibrium at a lower adrenergic drive.[23]
Beta blockers are indicated for the treatment of acutemyocardial infarctions. During a myocardial infarction, systemic stress causes an increase in circulatingcatecholamines.[24][25] This results an increase in heart rate and blood pressure, therefore increasing myocardial oxygen demand.[25][24] 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.[24]
A 2019 Cochrane review compared beta blockers withplacebo or no intervention, it found that beta blockers probably reduced the short-term risk of reinfarction and the long-term risk ofall-cause mortality and cardiovascular mortality.[24] The review identified that beta blockers likely had little to no impact on short-term all-cause mortality and cardiovascular mortality.[24]
Beta blockers are widely used for the treatment of hypertension.[26]
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.[27] 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.[27]
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.[28] It suggested that the effects of beta blockers are inferior to other anti-hypertensive medications.[28]
Beta blockers are used to treatanxiety disorders includingperformance anxiety,panic disorder,generalized anxiety disorder, andspecific phobias.[29] They are not formally approved foranxiolytic use by the United StatesFood and Drug Administration.[30] However, many clinical studies have found beta blockers to be effective for anxiety, though the exactmechanism of action is unclear.[29][31] A 2025systematic review andmeta-analysis found widespread prescription of beta blockers, namelypropranolol, for treatment anxiety disorders, but found no evidence of a beneficial effect relative to placebo orbenzodiazepines in people withsocial phobia orpanic disorder.[3] However, thequality of evidence, including both numbers of studies and patients as well as quality and risk ofbias of those studies, was limited.[3] Findings were similar in a previous 2016 systematic review and meta-analysis.[4] Beta blockers that have been used to treat anxiety include propranolol,atenolol,pindolol,nadolol,betaxolol, andoxprenolol.[29][3]
It is thought that beta blockers do not directly treat psychological symptoms of anxiety, but can help control physical symptoms such aspalpitations, and this may interfere with a positive feedback loop to indirectly reduce psychological anxiety.[3] Highlylipophilic beta blockers like propranolol, which arecentrallypermeable, and highlyhydrophilic beta blockers like atenolol, which areperipherally selective, appear to have similar benefits on performance anxiety, suggesting that their anxiolytic effects are mediated peripherally.[29] However, there has been little in the way of direct comparisons between different types of beta blockers.[29] In any case, the physiological symptoms of thefight-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.[citation needed] Although it is thought that beta blockers may act via peripheral mechanisms, there are also findings frompreclinical research of central β-adrenergic receptors mediating anxiety.[32][33][34][35]
Musicians, public speakers, actors, and professionaldancers have been known to use beta blockers to avoidperformance anxiety,stage fright, and tremor during bothauditions and public performances. The application to stage fright was first recognized inThe Lancet in 1976, and by 1987, a survey conducted by theInternational 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.[36] 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".[36] Although beta blockers have been studied and found to improve performance anxiety in musicians, no data exist on treatment of performance anxiety in dancers.[37]
Low certainty evidence indicates that the use of beta blockers around the time of cardiac surgery may decrease the risk ofheart dysrhythmias andatrial fibrillation.[38] 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.[39] Low-certainty evidence suggests that beta blockers used perioperatively in non-cardiac surgeries may increase the risk of bradycardia.[39]
Beta blockers are frequently used to treatakathisia and may be considered afirst-line therapy for this indication.[29] Akathisia is a type ofextrapyramidal symptom often associated withantipsychotics used to treatpsychotic disorders likeschizophrenia.[29]Propranolol is the most-studied beta blocker for treatment of akathisia, whereas very limited data suggest thatmetoprolol may provide comparable benefits, andnadolol, which isperipherally selective, does not appear to be effective.[29]
A 2014 Cochrane review investigated the use of beta blockers in the maintenance of chronic type B thoracicaortic aneurysm in comparison to other anti hypertensive medications.[40] The review found no suitable evidence to support the current guidelines recommending its use.[40]
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.[41]
Adrenergic antagonists are mostly used forcardiovascular disease. The adrenergic antagonists are widely used for lowering blood pressure and relievinghypertension.[42] These antagonists have a been proven to relieve the pain caused bymyocardial infarction, and also the infarction size, which correlates with heart rate.[43]
There are few non-cardiovascular uses for adrenergic antagonists. Alpha-adrenergic antagonists are also used for treatment ofureteric stones,pain andpanic disorders,withdrawal, andanesthesia.[44][45]
Beta blockers are used to treat acute cardiovasculartoxicity (e.g. inoverdose) caused bysympathomimetics, for instance caused byamphetamine,methamphetamine,cocaine,ephedrine, and other drugs.[46] Combined α1 and beta blockers likelabetalol andcarvedilol may be more favorable for such purposes due to the possibility of "unopposed α-stimulation" with selective beta blockers likepropranolol andatenolol.[46][47]
Propranolol is the only agent indicated for the control of tremor, portal hypertension, and esophageal variceal bleeding, and used in conjunction with α-blocker therapy inphaeochromocytoma.[55]
Contraindications of beta blockers include the following:[56][57][58]
Relative contraindications, or contraindications specific to certain beta-blockers:
Cautions:
Contrast agents are not contraindicated in those receiving beta blockers.[59]
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.[60]: 182
Cardio selective beta blocker (β1 blockers) can be prescribed at the least possible dose to those with mild to moderate respiratory symptoms.[61][62]β2-agonists can somewhat mitigate β-blocker-inducedbronchospasm where it exerts greater efficacy on reversingselective β-blocker-induced bronchospasm than thenonselective β-blocker-induced worsening asthma and/or COPD.[61]
Epinephrine signals early warning of the upcominghypoglycemia.[63]
Beta blockers' inhibition on epinephrine's effect can somewhat exacerbate hypoglycemia by interfering withglycogenolysis 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.
Abrupt withdrawal can result in athyroid storm.[56]
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.[citation needed]
Adverse drug reactions associated with the use of beta blockers include:nausea,diarrhea,bronchospasm,dyspnea, cold extremities, exacerbation ofRaynaud's syndrome,bradycardia,hypotension,heart failure,heart block,fatigue,dizziness,alopecia (hair loss), abnormal vision,hallucinations,insomnia,nightmares,sexual dysfunction,erectile dysfunction, alteration ofglucose andlipid metabolism.[medical citation needed] Mixed α1/β-antagonist therapy is also commonly associated withorthostatic hypotension.
Carvedilol therapy is commonly associated withedema.[55][page needed]Due to the high penetration across theblood–brain barrier, lipophilic beta blockers, such aspropranolol andmetoprolol, are more likely than other less lipophilic beta blockers to cause sleep disturbances, such as insomnia, vivid dreams and nightmares.[64]
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 themacula densa, inhibits renin release, thus decreasing the release ofaldosterone. This causeshyponatremia andhyperkalemia.[citation needed]
Hypoglycemia can occur with beta blockade because β2-adrenoceptors normally stimulateglycogen breakdown (glycogenolysis) in the liver and pancreatic release of thehormoneglucagon, 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 inhypoglycemia unawareness. This is termedbeta blocker-induced hypoglycemia unawareness. Therefore, beta blockers are to be used cautiously in diabetics.[65]
A 2007 study revealed diuretics and beta blockers used for hypertension increase a patient's risk of developingdiabetes mellitus, whileACE inhibitors andangiotensin II receptor antagonists (angiotensin receptor blockers) actually decrease the risk of diabetes.[66] 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.[67]
Beta blockers must not be used in the treatment of selective alpha-adrenergic agonist overdose. The blockade of only beta receptors increasesblood pressure, reduces coronary blood flow, leftventricular function, andcardiac 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 asmetoprolol andlabetalol may be useful for treating CNS and cardiovascular toxicity from a methamphetamine overdose.[68] The mixedalpha- and beta blocker labetalol is especially useful for treatment of concomitant tachycardia and hypertension induced by methamphetamine.[69] The phenomenon of "unopposed alpha stimulation" has not been reported with the use of beta blockers for treatment of methamphetamine toxicity.[69] Other appropriateantihypertensive drugs to administer during hypertensive crisis resulting from stimulant overdose arevasodilators such asnitroglycerin,diuretics such asfurosemide, andalpha blockers such asphentolamine.[70]
Beta blockers were found to be associated withdepression in earlier studies.[29] Morelipophilic beta blockers, with greatercentral effects, were especially implicated.[29] However, subsequent more rigorous studies found no causal relationship of beta blockers with depression and regardless of lipid solubility.[29] A small and significant but inconsistent risk offatigue was found for non-selective beta blockers however.[29]
Beta blockers, due to their antagonism at β1 adrenergic receptors, inhibit both the synthesis of newmelatonin and its secretion by thepineal gland. Morelipophilic beta blockers, with greater ability to cross theblood–brain barrier, are known to be able to suppressmelatonin release by 50 to 80%.[71][72][73] The neuropsychiatric side effects of some beta blockers (e.g. sleep disruption,insomnia) may be related to this effect.[74]
Glucagon, used in the treatment ofoverdose,[75][76] increases the strength of heart contractions, increases intracellularcAMP, and decreases renalvascular resistance. It is, therefore, useful in patients with beta blocker cardiotoxicity.[77][78]Cardiac pacing is usually reserved for patients unresponsive topharmacological therapy.
People experiencing bronchospasm due to the β2 receptor-blocking effects of nonselective beta blockers may be treated withanticholinergic drugs, such asipratropium, which are safer thanbeta agonists in patients withcardiovascular disease. Other antidotes for beta blocker poisoning aresalbutamol andisoprenaline.
Beta blockers have a variety ofdrug interactions.[29] An example is that various beta blockers includingpropranolol,carvedilol,nebivolol,timolol, andmetoprolol aremetabolized by thecytochrome P450enzymeCYP2D6 and may be potentiated by CYP2D6inhibitors likefluoxetine,paroxetine,duloxetine, andbupropion.[29] This may increase the risk ofadverse effects likebradycardia andhypotension.[29]
| Beta blocker | Selectivity | Lipophilicity | ISATooltip Intrinsic sympathomimetic activity | MSATooltip Membrane-stabilizing activity | |||
|---|---|---|---|---|---|---|---|
| Acebutolol | β1 | Moderate | Yes/mild | ? | |||
| Atenolol | β1 | Low | No | No | |||
| Betaxolol | β1 | Moderate | Yes | ? | |||
| Bisoprolol | β1 | Moderate | No | No | |||
| Carteolol | β1, β2 | Low | Yes | ? | |||
| Carvedilol | β1, β2, α1 | High | No | Yes/high | |||
| Esmolol | β1 | Moderate | No | No | |||
| Labetalol | β1, β2, α1 | Moderate or higha | Yes | Yes | |||
| Metoprolol | β1 | Moderate | No | Yes | |||
| Nadolol | β1, β2 | Low | No | ? | |||
| Nebivolol | β1 | High | No | ? | |||
| Oxprenolol | β1, β2 | Moderate | Yes | Yes | |||
| Penbutolol | β1, β2 | High | Yes | ? | |||
| Pindolol | β1, β2 | Moderate | Yes/mild | ? | |||
| Practolol | β1 | Low | Yes | No | |||
| Propranolol | β1, β2 | High | No | Yes/high | |||
| Sotalol | β1, β2 | Low | No | No | |||
| Timolol | β1, β2 | Moderate | No | Yes | |||
| Acronyms: ISA =Intrinsic sympathomimetic activity (i.e.,partial agonist activity). MSA =Membrane-stabilizing activity (i.e.,sodium channel blockade orlocal anesthetic activity).Notes:Lipophilicity is defined as low =log P <1, moderate = log P 1–3, and high = log P >3 among other definitions.[29] It is a predictor ofblood–brain barrierpermeability andcentral effects.[29]Footnotes:a Althoughlabetalol has moderate or high lipophilicity, it appears to nonetheless beperipherally selective.Refs:[29][79][52][80][81][51][82] | |||||||
Beta blockers act asβ-adrenergic receptorantagonists. They may benon-selective, antagonizing both theβ1- andβ2-adrenergic receptors, or they may beselective for antagonism of the β1-adrenergic receptor (often referred to as "cardioselective"). Some beta blockers haveintrinsic sympathomimetic activity (ISA), otherwise known aspartial agonist activity at the β-adrenergic receptors with weaksympathomimetic effects.
Some beta blockers are not selective for the β-adrenergic receptor and have additionalα1-adrenergic receptor antagonism. Some beta blockers havemembrane-stabilizing activity, otherwise known assodium channel blockade orlocal anesthetic activity. Beta blockers vary in theirlipophilicity versushydrophilicity and hence in their capacity to cross theblood–brain barrier, with some havingcentral nervous system effects and others beingperipherally selective.
Stimulation of β1 receptors by epinephrine and norepinephrine induces a positivechronotropic andinotropic effect on the heart and increases cardiac conduction velocity and automaticity.[83] Stimulation of β1 receptors on the kidney causesrenin release.[84] Stimulation of β2 receptors inducessmooth muscle relaxation,[85] induces tremor inskeletal muscle,[86] and increasesglycogenolysis in theliver andskeletal muscle.[87] Stimulation of β3 receptors induceslipolysis.[88]
Beta blockers inhibit these normal epinephrine- and norepinephrine-mediatedsympathetic actions,[5] but have minimal effect on resting subjects.[citation needed]That is, they reduce the effect of excitement or physical exertion on heart rate and force of contraction,[89] and also tremor,[90] and breakdown of glycogen. Beta blockers can have a constricting effect on the bronchi of the lungs, possibly worsening or causing asthma symptoms.[91]
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.[92]
Accordingly, nonselective beta blockers are expected to have antihypertensive effects.[93] The primary antihypertensive mechanism of beta blockers is unclear, but may involve reduction in cardiac output (due to negative chronotropic and inotropic effects).[94] It may also be due to reduction in renin release from the kidneys, and acentral nervous system effect to reduce sympathetic activity (for those beta blockers that do cross theblood–brain barrier, e.g. propranolol).[citation needed]
Antianginal effects result from negative chronotropic and inotropic effects, which decrease cardiac workload and oxygen demand. Negativechronotropic 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.[citation needed]
The antiarrhythmic effects of beta blockers arise from sympathetic nervous system blockade—resulting in depression ofsinus node function andatrioventricular node conduction, and prolongedatrialrefractory periods.Sotalol, in particular, has additional antiarrhythmic properties and prolongsaction potential duration throughpotassium channel blockade.
Blockade of the sympathetic nervous system on renin release leads to reduced aldosterone via therenin–angiotensin–aldosterone system, with a resultant decrease in blood pressure due to decreased sodium and water retention.
Some beta blockers (e.g.,labetalol andcarvedilol) exhibit mixed antagonism of both β- and α1-adrenergic receptors, which provides additionalarteriolar vasodilating action.[95][96]
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). Seepartial agonist for a more general description.[citation needed]
Some beta blockers (e.g.oxprenolol,pindolol,penbutolol,labetalol andacebutolol) exhibit intrinsic sympathomimetic activity (ISA). These agents are capable of exerting low-levelagonist activity at the β-adrenergic receptor while simultaneously acting as a receptor siteantagonist. These agents, therefore, may be useful in individuals exhibiting excessivebradycardia with sustained beta blocker therapy.[citation needed]
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 ofangina andtachyarrhythmia.[55]
Beta blockers vary in theirlipophilicity (fat solubility) and in turn in their ability to cross theblood–brain barrier and exert effects in thecentral nervous system.[79] Beta blockers with greater blood–brain barrierpermeability can have bothneuropsychiatric therapeutic benefits andside effects, as well as adversecognitive effects.[79] Central nervous system-related side effects and risks of beta blockers may includefatigue,depression,sleep disorders (namelyinsomnia) andnightmares,visual hallucinations,delirium,psychosis,Parkinson's disease, andfalling.[79] Conversely, central nervous system-related benefits of beta blockers may include prevention and treatment ofmigraine,essential tremor,akathisia,anxiety,post-traumatic stress disorder,aggression, andobsessive–compulsive disorder.[79]
Most beta blockers are lipophilic and can cross into the brain, but there are a number of exceptions.[79] Highly lipophilic beta blockers includepenbutolol,pindolol,propranolol, andtimolol, moderately lipophilic beta blockers includeacebutolol,betaxolol,bisoprolol,carvedilol,metoprolol, andnebivolol, and low lipophilicity or hydrophilic beta blockers includeatenolol,carteolol,esmolol,labetalol,nadolol, andsotalol.[79] 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.[79] The preceding beta blockers also vary in theirintrinsic sympathomimetic activity andβ1-adrenergic receptorselectivity (or cardioselectivity), resulting in further differences in pharmacological profiles and suitability in different contexts between them.[79]
Thebrain-to-blood ratios of certain beta blockers in humans have been characterized and have been found to be 50:1 foroxprenolol, 15:1 to 33:1 forpropranolol, 16:1 foralprenolol, 12:1 formetoprolol, and 0.2:1 foratenolol.[97][98] The blood-to-brain ratios of various other beta blockers, for instanceacebutolol,bevantolol,nadolol,pindolol, andtimolol, appear to be unknown.[97]
Theadrenergic receptors were discoveredHenry Hallett Dale in 1906 and theα- andβ-adrenergic receptors were differentiated byRaymond P. Ahlquist in 1948.[99] In 1967, the β-adrenergic receptors were further differentiated into theβ1- andβ2-adrenergic receptors by Alonzo M. Lands.[99]
The first beta blocker to be developed wasdichloroisoprenaline, based onstructural modification of theβ-adrenergic receptor agonistisoprenaline (isoproterenol).[100][101][102] It was described by C. E. Powell and I. H. Slater in 1958.[100][101][99][102] However, dichloroisoprenaline had significantpartial agonism andsympathomimetic activity and hence was not a pureantagonist.[100][101]James Black and John Stephenson describedpronethalol (nethalide; ICI-38,174; Alderlin) as a purely antagonistic beta blocker in 1962.[100][101][103] But pronethalol suffered fromoff-target activity and associatedside effects andtoxicity.[100][101] As such, it did not enter widespread use and was soon discontinued.[101]
In 1964, Black and colleagues published onpropranolol (ICI-45,520; Inderal), which did not have the problems of earlier beta blockers.[100][101][104] It was introduced for medical use under the brand name Inderal the same year and became the first widely used beta blocker.[100][101] Since the introduction of propranolol, there have been three generations of beta blockers with different pharmacological properties, with numerous beta blockers having been developed and introduced for medical use.[100]
Because they promote lower heart rates and reduce tremors, beta blockers have been used in professional sports where high accuracy is required, includingarchery,shooting,golf[105] andsnooker.[105] Beta blockers are banned in some sports by theInternational Olympic Committee.[106] In the2008 Summer Olympics,50-metre pistol silver medalist and10-metre air pistol bronze medalistKim Jong-su tested positive forpropranolol and was stripped of his medals.[107]
For similar reasons, beta blockers have also been used by surgeons.[108] Classical musicians have commonly used beta blockers since the 1970s to reducestage fright.[109]
Beta blockers have been researched for treatment of a variety ofpsychiatric disorders besidesanxiety disorders.[29] These includedepression,mania,acute stress disorder,post-traumatic stress disorder (PTSD),schizophrenia,aggression, andagitation.[29]
Beta blockers have also been used for the treatment ofschizoid personality disorder.[110] However, there is limited evidence supporting the efficacy of supplemental beta blocker use in addition to antipsychotic drugs for treating schizophrenia.[111][112]
Somepreclinical andclinical research suggests that some beta blockers may be beneficial forcancer treatment.[113][114] However, other studies do not show a correlation between cancer survival and beta blocker use.[115][116] Also, a 2017meta-analysis failed to show any benefit for the use of beta blockers inbreast cancer.[117]
Nonselective beta blockers display both β1 and β2 antagonism.[51]
β1-selective beta blockers are also known as cardioselective beta blockers.[51] Pharmacologically, the beta-blockade of the β1 receptors in the heart will act oncAMP. The function of cAMP as a second messenger in the cardiac cell is that it phosphorylates theLTCC and theryanodine 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.
Nebivolol and bisoprolol are the most β1 cardioselective beta blockers.[123]
{{cite journal}}: CS1 maint: DOI inactive as of July 2025 (link)beta blockers dilation of blood vessels.
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