What are beta blockers. How do beta blockers work. What conditions can beta blockers treat. Who should avoid taking beta blockers. What are the potential side effects of beta blockers. How do beta blockers interact with other medications. When should you seek medical attention while taking beta blockers.

Understanding Beta Blockers: Mechanism of Action and Types

Beta blockers are a class of prescription medications that primarily work by slowing down the heart rate. They achieve this effect by blocking the action of stress hormones like adrenaline on beta receptors in the body. These medications are typically administered in tablet form and can only be prescribed by qualified healthcare professionals.

Some commonly prescribed beta blockers include:

• Atenolol (Tenormin)
• Bisoprolol (Cardicor, Emcor)
• Carvedilol
• Labetalol (Trandate)
• Metoprolol (Betaloc, Lopresor)
• Propranolol (Inderal, Angilol)
• Sotalol

Are all beta blockers the same? No, there are several types of beta blockers, each with unique characteristics. The specific type prescribed depends on the individual’s health condition and other factors determined by their healthcare provider.

Medical Conditions Treated with Beta Blockers

Beta blockers are versatile medications used to treat various cardiovascular and other health conditions. Their primary applications include:

1. Angina (chest pain caused by narrowed heart arteries)
2. Heart failure
3. Atrial fibrillation (irregular heartbeat)
4. Heart attack recovery and prevention
5. High blood pressure (hypertension)

Can beta blockers be used for non-cardiac conditions? Yes, these medications have applications beyond heart-related issues. Less common uses include:

• Migraine prevention
• Hyperthyroidism (overactive thyroid) management
• Anxiety treatment
• Tremor control
• Glaucoma treatment (as eye drops)

Eligibility and Contraindications for Beta Blocker Use

While beta blockers are effective for many individuals, they are not suitable for everyone. Certain health conditions may preclude their use or require special consideration:

• Uncontrolled heart failure
• History of allergic reactions to beta blockers or similar medications
• Low blood pressure
• Certain heart rhythm disorders
• Metabolic acidosis
• Lung diseases, including asthma

Is it safe to take beta blockers during pregnancy or while breastfeeding? If you are trying to conceive, pregnant, or breastfeeding, it’s crucial to inform your doctor. They will assess the potential risks and benefits to determine the most appropriate course of action.

Important Precautions When Taking Beta Blockers

Can you stop taking beta blockers abruptly? No, it’s essential not to discontinue beta blocker use without consulting your healthcare provider. Sudden cessation can lead to a worsening of your health condition in some cases. Your doctor can provide guidance on safely adjusting or stopping the medication if necessary.

Potential Interactions Between Beta Blockers and Other Medications

Beta blockers can interact with various medications, potentially affecting their efficacy or increasing the risk of side effects. It’s crucial to inform your healthcare provider about all medications you’re taking, including over-the-counter drugs and supplements.

Some medications that may interact with beta blockers include:

• Other blood pressure medications
• Antiarrhythmic drugs (e.g., amiodarone, flecainide)
• Certain antidepressants
• Nitrates for chest pain
• Muscle relaxants (e.g., baclofen)
• Medications for enlarged prostate or Parkinson’s disease
• Asthma or COPD medications
• Diabetes medications, especially insulin
• Cold and allergy remedies
• Non-steroidal anti-inflammatory drugs (NSAIDs)

How do beta blockers affect diabetes management? Beta blockers may mask some symptoms of low blood sugar (hypoglycemia), making it more challenging for diabetic patients to recognize when their blood glucose levels drop. Close monitoring and potential adjustments to diabetes management may be necessary.

Common and Rare Side Effects of Beta Blockers

While many people tolerate beta blockers well, some may experience side effects. These effects are often mild and tend to diminish over time.

Common side effects of beta blockers include:

• Fatigue or dizziness
• Cold extremities (hands and feet)
• Sleep disturbances or nightmares
• Erectile dysfunction or other sexual difficulties
• Nausea

Are there any serious side effects associated with beta blockers? Yes, although rare, some individuals may experience more severe reactions. Seek immediate medical attention if you experience:

• Shortness of breath, especially during exercise
• Worsening cough
• Swelling in ankles or legs
• Irregular heartbeat
• Wheezing or chest tightness
• Yellowing of skin or eyes (jaundice)

It’s important to note that this list is not exhaustive. Always refer to the information leaflet provided with your medication and report any suspected side effects to your healthcare provider or through the appropriate reporting system, such as the Yellow Card Scheme in the UK.

Proper Administration and Dosage of Beta Blockers

The frequency of beta blocker administration can vary depending on the specific medication and individual patient needs. Some beta blockers are taken once daily, while others may require two to four doses per day.

What should you do if you miss a dose of your beta blocker? If you forget to take a dose, follow these guidelines:

• For once-daily medications: Take the missed dose as soon as you remember, unless it’s almost time for your next scheduled dose. In that case, skip the missed dose and continue with your regular schedule.
• For multiple daily doses: Take the missed dose if you remember within a few hours. If it’s close to your next scheduled dose, skip the missed one and continue as usual.

Never double up on doses to make up for a missed one. If you’re unsure about what to do, consult your pharmacist or healthcare provider for guidance.

Monitoring and Long-term Management with Beta Blockers

Regular monitoring is essential when taking beta blockers to ensure their effectiveness and minimize potential side effects. Your healthcare provider may recommend periodic check-ups to assess your response to the medication and make any necessary adjustments.

What aspects of your health will be monitored while on beta blockers?

• Blood pressure
• Heart rate
• Kidney function
• Liver function
• Blood sugar levels (especially for diabetic patients)

Can lifestyle changes complement beta blocker therapy? Absolutely. Adopting a heart-healthy lifestyle can enhance the effectiveness of beta blockers and improve overall cardiovascular health. Consider incorporating the following habits:

• Regular physical activity (consult your doctor about appropriate exercise levels)
• Balanced, nutritious diet low in saturated fats and sodium
• Stress management techniques (e.g., meditation, yoga)
• Smoking cessation
• Limiting alcohol consumption

Special Considerations for Elderly Patients

Older adults may be more sensitive to the effects of beta blockers and may require closer monitoring or dosage adjustments. Healthcare providers often start with lower doses and gradually increase as needed, carefully balancing the benefits and potential risks.

Beta Blockers in Emergency Situations

While beta blockers are primarily used for long-term management of various conditions, they can also play a crucial role in certain emergency situations.

In what emergency scenarios might beta blockers be administered?

• Acute heart attack: To reduce heart rate and blood pressure, potentially limiting damage to the heart muscle
• Severe hypertension: To quickly lower dangerously high blood pressure
• Acute aortic dissection: To reduce the force of blood flow through the aorta
• Thyroid storm: To manage symptoms of severe hyperthyroidism

It’s important to note that emergency use of beta blockers should only be under the direct supervision of medical professionals in appropriate healthcare settings.

Beta Blockers and Surgery

If you’re taking beta blockers and scheduled for surgery, it’s crucial to inform your surgical team. In many cases, beta blockers are continued through the perioperative period to maintain heart rate control and reduce the risk of cardiovascular complications.

However, the decision to continue or temporarily stop beta blockers before surgery depends on various factors, including the type of surgery, your overall health, and the specific beta blocker you’re taking. Your healthcare team will provide guidance on how to manage your medication in the lead-up to and following your procedure.

Future Developments and Research in Beta Blocker Therapy

The field of beta blocker therapy continues to evolve, with ongoing research exploring new applications and refining existing treatments. Some areas of current interest include:

• Development of more selective beta blockers with fewer side effects
• Exploration of beta blockers in cancer treatment and prevention
• Investigation of potential neuroprotective effects in conditions like Alzheimer’s disease
• Use of beta blockers in managing post-traumatic stress disorder (PTSD)
• Combination therapies incorporating beta blockers with other medications for enhanced efficacy

How might future developments in beta blocker therapy impact patient care? As research progresses, we may see more personalized approaches to beta blocker use, with treatments tailored to individual genetic profiles and specific health conditions. This could lead to improved outcomes and reduced side effects for patients requiring these medications.

The Role of Pharmacogenomics in Beta Blocker Therapy

Pharmacogenomics, the study of how an individual’s genetic makeup affects their response to medications, is an exciting area of research in beta blocker therapy. This field holds promise for optimizing treatment by helping healthcare providers select the most effective beta blocker and dosage based on a patient’s genetic profile.

What potential benefits could pharmacogenomic testing offer for beta blocker therapy?

• Improved prediction of treatment response
• Reduced risk of adverse reactions
• More precise dosing recommendations
• Enhanced overall treatment efficacy

While pharmacogenomic testing for beta blocker therapy is not yet standard practice, ongoing research may lead to its broader implementation in the future, potentially revolutionizing how these medications are prescribed and managed.

Beta blockers – NHS

Beta blockers work mainly by slowing down the heart. They do this by blocking the action of hormones like adrenaline.

Beta blockers usually come as tablets.

They are prescription-only medicines, which means they can only be prescribed by a GP or another suitably qualified healthcare professional.

Commonly used beta blockers include:

• atenolol (also called Tenormin)
• bisoprolol (also called Cardicor or Emcor)
• carvedilol
• labetalol (also called Trandate)
• metoprolol (also called Betaloc or Lopresor)
• propranolol (also called Inderal or Angilol)
• sotalol

Uses for beta blockers

Beta blockers may be used to treat:

• angina – chest pain caused by narrowing of the arteries supplying the heart
• heart failure – failure of the heart to pump enough blood around the body
• atrial fibrillation – irregular heartbeat
• heart attack – an emergency where the blood supply to the heart is suddenly blocked
• high blood pressure – when other medicines have been tried, or in addition to other medicines

Less commonly, beta blockers are used to prevent migraine or treat:

• an overactive thyroid (hyperthyroidism)
• anxiety 
• tremor
• glaucoma – as eyedrops

There are several types of beta blocker, and each one has its own characteristics. The type prescribed for you will depend on your health condition.

Who can take beta blockers

Beta blockers are not suitable for everyone. Tell your doctor if you have:

• uncontrolled heart failure
• had an allergic reaction to a beta blocker or any other medicine in the past
• low blood pressure or certain conditions that affect the rhythm of your heart
• metabolic acidosis – when there’s too much acid in your blood
• lung disease or asthma

Tell your doctor if you’re trying to get pregnant, are already pregnant or breastfeeding.

It’s important not to stop taking beta blockers without seeking your doctor’s advice. In some cases, suddenly stopping the medicine may make your health condition worse.

Cautions with other medicines

There are some medicines that may interfere with the way that beta blockers work, including beta blocker eyedrops.

Tell your doctor if you’re taking:

• other medicines for high blood pressure. The combination with beta blockers can sometimes lower your blood pressure too much. This may make you feel dizzy or faint
• other medicines for an irregular heartbeat such as amiodarone or flecainide
• other medicines that can lower your blood pressure. These include some antidepressants, nitrates (for chest pain), baclofen (a muscle relaxant), medicines for an enlarged prostate gland like tamsulosin, or Parkinson’s disease medicines such as levodopa
• medicines for asthma or chronic obstructive pulmonary disease (COPD)
• medicines for diabetes, particularly insulin – beta blockers may make it more difficult to recognise the warning signs of low blood sugar
• medicines to treat nose or sinus congestion, or other cold remedies (including those you can buy in the pharmacy)
• medicines for allergies, such as ephedrine, noradrenaline or adrenaline
• non-steroidal anti-inflammatory medicines (NSAIDs), such as ibuprofen. These medicines may increase your blood pressure, so it’s best to keep them to a minimum

Side effects of beta blockers

Most people taking beta blockers have either no or very mild side effects that become less troublesome with time.

Contact your GP if you’re having symptoms that bother you or last more than a few days.

Side effects commonly reported by people taking beta blockers include:

• feeling tired, dizzy or lightheaded (these can be signs of a slow heart rate)
• cold fingers or toes (beta blockers may affect the blood supply to your hands and feet)
• difficulties sleeping or nightmares
• difficulty getting an erection or other difficulties with sex
• feeling sick

It happens rarely, but some people have serious side effects when taking beta blockers.

Tell a doctor straight away if you have:

• shortness of breath and a cough that gets worse when you exercise (like walking up stairs), swollen ankles or legs, or an irregular heartbeat – these can be signs of heart problems
• shortness of breath, wheezing and tightening of your chest – these can be signs of lung problems
• yellowish skin or the whites of your eyes turn yellow, although this may be less obvious on brown or black skin – these can be signs of liver problems

These are not all the side effects of beta blockers. For a full list, see the leaflet inside your medicine packet.

You can report suspected side effects using the Yellow Card Scheme – find out more on the Yellow Card website.

For more information on the side effects of beta blockers, read about the specific medicine you take in our Medicines A to Z.

Missed or extra doses

Depending on your beta blocker, you can take it up to 4 times a day. Some must be taken once a day, others between 2 and 3 times a day. Check the information included with your medicine.

What if I forget to take it?

If you forget to take a dose of your beta blocker, take it as soon as you remember, unless it is nearly time for your next dose. In this case, just leave out the missed dose and take your next dose as normal.

Never take 2 doses at the same time. Never take an extra dose to make up for a forgotten one.

If you often forget doses, it may help to set an alarm to remind you. You could also ask your pharmacist for advice on other ways to help you remember to take your medicine.

What if I take too much?

If you take more than your prescribed dose, beta blockers can slow down your heart rate and make it difficult to breathe. It can also cause dizziness and trembling.

The amount of beta blocker that can lead to an overdose varies from person to person.

Call your doctor, contact 111 or go to A&E straight away if you take too much of your beta blocker.

Page last reviewed: 02 December 2022
Next review due: 02 December 2025

Beta Blockers – StatPearls – NCBI Bookshelf

Continuing Education Activity

Beta-blockers, as a class of drugs, are primarily used to treat cardiovascular diseases and other conditions. Beta-blockers are indicated and have FDA approval for the treatment of tachycardia, hypertension, myocardial infarction, congestive heart failure, cardiac arrhythmias, coronary artery disease, hyperthyroidism, essential tremor, aortic dissection, portal hypertension, glaucoma, migraine prophylaxis, and other conditions. They are also used to treat less common conditions such as long QT syndrome and hypertrophic obstructive cardiomyopathy. This activity outlines the indications, mechanism of action, safe administration, adverse effects, contraindications, toxicology, and monitoring of the broad array of physiological possibilities when using beta-blockers in the clinical setting.

Objectives:

• Summarize the mechanism of action of the beta-blocker class of medications, including the difference between selective and non-selective agents.

• Identify the indications for beta-blocker therapy.

• Review the adverse events, contraindications, toxicities, and interactions of beta-blockers.

• Outline the importance of improving care coordination among the interprofessional team to improve outcomes for patients using beta-blockers for indicated conditions.

Access free multiple choice questions on this topic.

Indications

Beta-blockers, as a class of drugs, are primarily used to treat cardiovascular diseases and other conditions.[1]

Beta receptors exist in three distinct forms: beta-1 (B1), beta-2 (B2), and beta-3 (B3). Beta-1 receptors located primarily in the heart mediate cardiac activity. Beta-2 receptors, with their diverse location in many organ systems, control various aspects of metabolic activity and induce smooth muscle relaxation. Beta-3 receptors induce the breakdown of fat cells and are less clinically relevant at present. Blockade of these receptors by beta-blocking medicines is used to treat a broad range of illnesses.[1] Beta-blockers, as a class of medications, are essential drugs and are first-line treatments in many acute and chronic conditions.

Beta-blockers are indicated and have FDA approval for the treatment of tachycardia, hypertension, myocardial infarction, congestive heart failure, cardiac arrhythmias, coronary artery disease, hyperthyroidism, essential tremor, aortic dissection, portal hypertension, glaucoma, migraine prophylaxis, and other conditions. They are also used to treat less common conditions such as long QT syndrome and hypertrophic obstructive cardiomyopathy. Beta-blockers are available for administration in three primary forms: oral, intravenous, and ophthalmic, and the route of administration often depends on the acuity of the illness (parenteral use in arrhythmias), disease type (topical use in glaucoma), and chronicity of the disease. 

Congestive heart failure patients are treated with beta-blockers if they are in a compensated state. Specifically, the beta-blockers bisoprolol, carvedilol, and metoprolol succinate are the agents chosen. Metoprolol tartrate is not indicated for heart failure and is instead used for other conditions such as atrial fibrillation. 

Athletes and musicians may use beta-blockers for their anxiolytic effect as well as their inhibitory effects on the sympathetic nervous system. They are not FDA approved for the treatment of anxiety-related disorders; however, they have a potent anxiolytic effect. Combined with a reduction in tremors, they may lead to improved stage performance. An example of a beta blocker that is commonly prescribed for anxiety or stage fright is propranolol; it may reduce some peripheral symptoms of anxiety, such as tachycardia, sweating, and general tension. [2]

Certain beta blockers are also used specifically in inpatient units rather than for outpatient prescriptions. A common example is esmolol, which is typically used either in the intensive care unit or a cardiac inpatient unit. It is generally used for refractory tachycardia, such as atrial fibrillation, and is titrable given its short onset of action and short half-life. It may also play a role in refractory ventricular tachycardia, which is also known as electrical storm. 

Mechanism of Action

The catecholamines, epinephrine, and norepinephrine bind to B1 receptors and increase cardiac automaticity as well as conduction velocity. B1 receptors also induce renin release, and this leads to an increase in blood pressure. In contrast, binding to B2 receptors causes relaxation of the smooth muscles along with increased metabolic effects such as glycogenolysis.

Beta-blockers vary in their specificity towards different receptors, and accordingly, the effects produced depend on the type of receptor(s) blocked as well as the organ system involved. Some beta-blockers also bind to alpha receptors to some degree, allowing them to induce a different clinical outcome when used in specific settings.

Once beta-blockers bind to the B1 and B2 receptors, they inhibit these effects. Therefore, the chronotropic and inotropic effects on the heart undergo inhibition, and the heart rate slows down as a result. Beta-blockers also decrease blood pressure via several mechanisms, including decreased renin and reduced cardiac output. The negative chronotropic and inotropic effects lead to a decreased oxygen demand; that is how angina improves after beta-blocker usage. These medications also prolong the atrial refractory periods and have a potent antiarrhythmic effect.

Beta-blockers classify as either non-selective or beta-1 selective. There are also beta-blocking drugs that affect both beta-2 and/or beta-3 selectively; neither has a known clinical purpose to date. Non-selective agents bind to both beta-1 and beta-2 receptors and induce antagonizing effects via both receptors. Examples include propranolol, carvedilol, sotalol, and labetalol. Beta-1 receptor-selective blockers like atenolol, bisoprolol, metoprolol, and esmolol only bind to the beta-1 receptors; therefore, they are cardio-selective.[3][4][5]

Beta-blockers lower the secretion of melatonin and hence may cause insomnia and sleep changes in some patients.[6]

Alpha-1 receptors induce vasoconstriction and increased cardiac chronotropy; this means agonism at the alpha-1 receptors leads to higher blood pressure and an increased heart rate. In contrast, antagonism at the alpha-1 receptor leads to vasodilation and negative chronotropic, which leads to lower blood pressure and decreased heart rate. Some beta-blockers, such as carvedilol, labetalol, and bucindolol, have additional alpha-1 receptor blockage activity in addition to their non-selective beta receptor blockage. This property is clinically useful because beta-blockers that block the alpha-1 receptor have a more pronounced clinical effect on treating hypertension. [7]

Administration

Beta-blockers are available in oral, intravenous, or ophthalmic forms and are also injectable intramuscularly.

Dosages are available in various ranges, depending on the specific medication. Outpatient prescriptions may include once-a-day dosing for longer-acting beta-blockers, such as metoprolol succinate. However, most beta blockers are often dosed at least twice per day. Certain beta-blockers, such as propranolol, with a half-life of approximately 4 hours, are dosed up to 3 or 4 times a day, depending on the indication and dose.

Adverse Effects

Beta receptors are found all over the body and induce a broad range of physiologic effects. The blockade of these receptors with beta-blocker medications can lead to many adverse effects. Bradycardia and hypotension are two adverse effects that may commonly occur. Fatigue, dizziness, nausea, and constipation are also widely reported. Some patients report sexual dysfunction and erectile dysfunction.

Less commonly, bronchospasm presents in patients on beta-blockers. Asthmatic patients are at a higher risk.[8] Patients with Raynaud syndrome are also at risk of exacerbation. Beta-blockers can induce hyperglycemia and mask the hemodynamic signs usually seen in a hypoglycemic patient, such as tachycardia.

Some patients report insomnia, sleep changes, and nightmares while using beta-blockers. This effect is more pronounced with beta-blockers that cross the blood-brain barrier. Some patients can experience fatigue or weight gain while on beta blockers. Managing these adverse events involves discontinuing the medication. Certain beta blockers are more likely to induce weight gain or fatigue. 

Carvedilol may increase edema in some patients.[9]

Sotalol blocks the potassium channels in the heart and thereby induces QT prolongation. It increases the risk of torsades de pointes.[10]

All beta-blockers, especially in patients with cardiac risk factors, carry a risk of heart block.

Contraindications

Traditionally, beta-blockers have been contraindicated in asthmatic patients. However, recommendations have aligned for allowing cardio-selective beta-blockers, also known as beta-1 selective, in asthmatics but not non-selective beta-blockers. Non-selective beta-blockers should not be used in patients with asthma.

Patients who have either acute or chronic bradycardia and/or hypotension have relatively contraindication to beta-blocker usage. 

Specific beta-blockers are contraindicated depending on the patient’s past medical history. Patients diagnosed with long QT syndrome or who have had torsades de pointes in the past should not use the drug sotalol. Patients with the Raynaud phenomenon should avoid beta-blockers due to the risk of exacerbation.[11][10]

Monitoring

The patient’s heart rate and blood pressure require monitoring while using beta-blockers. When using sotalol, the clinician must monitor the QTc interval as sotalol has QT-prolonging effects. [12] Other side effects, such as fatigue and weight gain, can also occur with outpatient beta-blocker use. 

Toxicity

The antidote for beta-blocker overdose is glucagon. It is especially useful in beta-blocker-induced cardiotoxicity. The second line of treatment is cardiac pacing if glucagon fails, and this may include transcutaneous pacing or transvenous pacing. 

Potential acute toxicity can be mitigated by using extended-release formulations as a preventative strategy, which will delay peak toxicity.[13]

Enhancing Healthcare Team Outcomes

Beta-blockers are a broad class of medications that are used for various clinical benefits but also carry the potential for adverse effects. They are prescribed by clinicians (MDs, DOs, NPs, or PAs) in both outpatient and inpatient settings, largely for the treatment of cardiovascular-related illnesses. While a patient is admitted to an inpatient ward, monitoring the clinical effects and potential adverse effects is an interprofessional task. This is crucial because excessively high serum levels can have serious or even fatal consequences.

Nurses will generally be the first caregivers to take note of any unwanted effects, such as a change in vital signs. In contrast, outpatient settings differ in that the pharmacist may be the closest line of healthcare contact for a patient. The pharmacist will dispense the medication, perform medication reconciliation, verify dosing, and also advise other interprofessional team members and the patient of any potential adverse effects. It is also imperative to take note of any patients who are currently on beta-blockers as it provides a clinical context for potential symptoms. Many clinical trials have been conducted on beta-blockers and shown to prolong life in patients with cardiovascular disease.[14][15][16] [Level 2]

The interprofessional healthcare team needs to prescribe, manage, and monitor the use of beta-blockers safely and effectively. [Level 5]

Review Questions

• Access free multiple choice questions on this topic.

• Comment on this article.

References

1.

do Vale GT, Ceron CS, Gonzaga NA, Simplicio JA, Padovan JC. Three Generations of β-blockers: History, Class Differences and Clinical Applicability. Curr Hypertens Rev. 2019;15(1):22-31. [PubMed: 30227820]

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Steenen SA, van Wijk AJ, van der Heijden GJ, van Westrhenen R, de Lange J, de Jongh A. Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis. J Psychopharmacol. 2016 Feb;30(2):128-39. [PMC free article: PMC4724794] [PubMed: 26487439]

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Gorre F, Vandekerckhove H. Beta-blockers: focus on mechanism of action. Which beta-blocker, when and why? Acta Cardiol. 2010 Oct;65(5):565-70. [PubMed: 21125979]

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Rehsia NS, Dhalla NS. Mechanisms of the beneficial effects of beta-adrenoceptor antagonists in congestive heart failure. Exp Clin Cardiol. 2010 Winter;15(4):e86-95. [PMC free article: PMC3016066] [PubMed: 21264074]

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Machackova J, Sanganalmath SK, Elimban V, Dhalla NS. β-adrenergic blockade attenuates cardiac dysfunction and myofibrillar remodelling in congestive heart failure. J Cell Mol Med. 2011 Mar;15(3):545-54. [PMC free article: PMC3922376] [PubMed: 20082655]

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Fares A. Night-time exogenous melatonin administration may be a beneficial treatment for sleeping disorders in beta blocker patients. J Cardiovasc Dis Res. 2011 Jul;2(3):153-5. [PMC free article: PMC3195193] [PubMed: 22022142]

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Weir MR. Beta-blockers in the treatment of hypertension: are there clinically relevant differences? Postgrad Med. 2009 May;121(3):90-8. [PubMed: 19491545]

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Marques de Mello L, Cruz ÁA. A proposed scheme to cope with comorbidities in asthma. Pulm Pharmacol Ther. 2018 Oct;52:41-51. [PubMed: 30149069]

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Soma K, Yao A, Saito A, Inaba T, Ishikawa Y, Hirata Y, Komuro I. Regular Treatment Strategy with a Large Amount of Carvedilol for Heart Failure Improves Biventricular Systolic Failure in a Patient with Repaired Tetralogy of Fallot. Int Heart J. 2018 Sep 26;59(5):1169-1173. [PubMed: 30101848]

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Etchegoyen CV, Keller GA, Mrad S, Cheng S, Di Girolamo G. Drug-induced QT Interval Prolongation in the Intensive Care Unit. Curr Clin Pharmacol. 2017;12(4):210-222. [PubMed: 29473523]

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De Vecchis R, Ariano C, Di Biase G, Noutsias M. Acquired drug-induced long QTc: new insights coming from a retrospective study. Eur J Clin Pharmacol. 2018 Dec;74(12):1645-1651. [PubMed: 30112668]

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Farzam K, Tivakaran VS. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Feb 12, 2023. QT Prolonging Drugs. [PubMed: 30521285]

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Graudins A, Lee HM, Druda D. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies. Br J Clin Pharmacol. 2016 Mar;81(3):453-61. [PMC free article: PMC4767195] [PubMed: 26344579]

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Hoedemaker NP, Roolvink V, de Winter RJ, van Royen N, Fuster V, García-Ruiz JM, Er F, Gassanov N, Hanada K, Okumura K, Ibáñez B, van ‘t Hof AW, Damman P. Early intravenous beta-blockers in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: A patient-pooled meta-analysis of randomized clinical trials. Eur Heart J Acute Cardiovasc Care. 2020 Aug;9(5):469-477. [PMC free article: PMC7672673] [PubMed: 30759994]

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Suissa S, Ernst P. Beta-Blockers in COPD: A Methodological Review of the Observational Studies. COPD. 2018 Oct;15(5):520-525. [PubMed: 30822238]

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Jensen MT. Resting heart rate and relation to disease and longevity: past, present and future. Scand J Clin Lab Invest. 2019 Feb-Apr;79(1-2):108-116. [PubMed: 30761923]

Disclosure: Khashayar Farzam declares no relevant financial relationships with ineligible companies.

Disclosure: Arif Jan declares no relevant financial relationships with ineligible companies.

Beta-blockers – mechanism of action and features of drugs

Dossier KS

Savely Barger (MOSCOW),

cardiologist, candidate of medical sciences. In the 1980s, he was one of the first scientists in the USSR to develop a technique for diagnostic transesophageal pacing. Author of manuals on cardiology and electrocardiography. He is the author of several popular books on various problems of modern medicine.

It is safe to say that beta-blockers are first-line drugs for the treatment of many diseases of the cardiovascular system.

Here are some clinical examples.

Patient B., 60 years old, suffered an acute myocardial infarction 4 years ago. At present, the characteristic squeezing pains behind the sternum with slight physical exertion are disturbing (at a slow pace of walking, it is possible to walk no more than 1000 meters without pain). Along with other drugs, he receives bisoprolol 5 mg in the morning and evening.

Patient R., 35 years old. At the appointment, he complains of constant headaches in the occipital region. Blood pressure 180/105 mm Hg. Art. Bisoprolol therapy is carried out at a daily dosage of 5 mg.

Patient L., aged 42, , complained of interruptions in the work of the heart, a feeling of “fading” of the heart. During daily ECG recording, frequent ventricular extrasystoles, episodes of “jogging” of ventricular tachycardia were diagnosed. Treatment: sotalol at a dosage of 40 mg twice a day.

Patient S., aged 57, , is concerned about shortness of breath at rest, attacks of cardiac asthma, decreased performance, edema in the lower extremities is noted, which worsens in the evening. An ultrasound examination of the heart revealed diastolic dysfunction of the left ventricle. Therapy: metoprolol 100 mg twice a day.

In such diverse patients: coronary heart disease, hypertension, paroxysmal ventricular tachycardia, heart failure – drug treatment is carried out with drugs of the same class – beta-blockers.

Beta-adrenergic receptors and mechanisms of action of beta-blockers

There are beta ₁ -adrenergic receptors located mainly in the heart, intestines, kidney tissue, in adipose tissue, limitedly in the bronchi. Beta ₂ -adrenergic receptors are located in the smooth muscles of blood vessels and bronchi, in the gastrointestinal tract, in the pancreas, and to a limited extent in the heart and coronary vessels. No tissue contains exclusively beta ₁ – or beta ₂ -adrenergic receptors. In the heart, the ratio of beta ₁ – and beta ₂ -adrenergic receptors is approximately 7:3.

Table 1. Main indications for the use of beta-blockers

The mechanism of action of beta-blockers is based on their structure, similar to catecholamines. Beta-blockers act as competitive antagonists of catecholamines (epinephrine and norepinephrine). The therapeutic effect depends on the ratio of the concentration of the drug and catecholamines in the blood.

Blockade of beta ₁ -adrenergic receptors leads to a decrease in heart rate, contractility and contraction rate of the heart muscle, while reducing myocardial oxygen demand.

• Beta-blockers cause depression of the 4th phase of diastolic depolarization of the cells of the conduction system of the heart, which determines their antiarrhythmic effect. Beta-blockers reduce the flow of impulses through the atrioventricular node and reduce the speed of impulse conduction.
• Beta-blockers reduce the activity of the renin-angiotensin system by reducing the release of renin from juxtaglomerular cells.
• Beta-blockers affect the sympathetic activity of vasoconstrictor nerves. The appointment of beta-blockers without internal sympathomimetic activity leads to a decrease in cardiac output, peripheral resistance increases, but returns to normal with prolonged use.
• Beta-blockers inhibit catecholamine-induced cardiomyocyte apoptosis.
• Beta-blockers stimulate the endothelial arginine/nitroxide system in endothelial cells, i.e., turn on the main biochemical mechanism for expanding vascular capillaries.
• Beta-blockers block part of the calcium channels of the cells and reduce the calcium content in the cells of the heart muscle. This is probably associated with a decrease in the strength of heart contractions, a negative inotropic effect.

Non-cardiac indications for the use of beta-blockers

• anxiety conditions
• alcoholic delirium
• juxtaglomerular hyperplasia
• insulinoma
• glaucoma
• migraine (attack prevention)
• narcolepsy
• thyrotoxicosis (treatment of rhythm disorders)
• portal hypertension

Table 2. Properties of beta-blockers: useful and side effects, contraindications

Clinical pharmacology

Treatment with beta-blockers must be carried out in effective therapeutic dosages, the dose of the drug is titrated upon reaching the target heart rate in the range of 50–60 min ^-1.

Only when the target heart rate is reached, one can judge the effectiveness or inefficiency of the drug in relation to the condition for which the drug is prescribed: angina, hypertension, arrhythmia.

For example, when treating hypertension with a beta-blocker, systolic blood pressure of 150–160 mm Hg is maintained. Art. If at the same time the heart rate does not decrease less than 70 minutes ^-1. , one should think not about the inefficiency of the beta-blocker and its replacement, but about increasing the daily dose until a heart rate of 60 min ^{-1 is reached.} .

An increase in the duration of the PQ interval on the electrocardiogram, the development of 1st degree AV block when taking a beta-blocker cannot be a reason for its cancellation. However, the development of AV block II and III degree, especially in combination with the development of syncope (Morgagni-Adams-Stokes syndrome), serves as an unconditional basis for the abolition of beta-blockers.

The cardioprotective effect of beta-blockers is more typical for lipophilic drugs than for hydrophilic ones. The ability of lipophilic beta-blockers to accumulate in tissues and increase vagus activity is important. Lipophilic beta-blockers penetrate the blood-brain barrier better and may have greater CNS side effects.

Cardioprotective doses of beta-blockers have been established in randomized clinical trials, i.e. doses, the use of which statistically significantly reduces the risk of death from cardiac causes, reduces the incidence of cardiac complications (myocardial infarction, severe arrhythmias), and increases life expectancy. Cardioprotective doses may differ from dosages at which control of hypertension and angina pectoris is achieved. If possible, beta-blockers should be prescribed at a cardioprotective dose that is higher than the average therapeutic doses.

It should also be taken into account that not all beta-blockers showed cardioprotective effects in randomized trials, only lipophilic metoprolol, propranolol, timolol and amphiphilic bisoprolol and carvediol are able to increase life expectancy.

An increase in the dose of beta-blockers above the cardioprotective dose is unjustified, since it does not lead to a positive result, increasing the risk of side effects.

Chronic obstructive pulmonary disease and bronchial asthma

If beta-blockers cause bronchospasm, then beta-agonists (such as beta ₂ -agonist salbutamol) can cause an attack of angina. The use of selective beta-blockers helps: cardioselective beta ₁ -blockers of bisoprolol and metoprolol in patients with coronary artery disease or hypertension in combination with chronic obstructive pulmonary disease (COPD) and bronchial asthma. In this case, it is necessary to take into account the function of external respiration (RF). In patients with mild impairment of respiratory function (forced expiratory volume more than 1.5 l), the use of cardioselective beta-blockers is acceptable.

In case of moderate and severe chronic bronchitis and bronchial asthma, one should refrain from prescribing beta-blockers, including cardioselective ones.

When choosing treatment tactics in patients with hypertension, angina pectoris or heart failure in combination with COPD, the priority is the treatment of cardiovascular pathology. In this case, it is necessary to individually assess whether it is possible to neglect the functional state of the bronchopulmonary system and vice versa – stop bronchospasm with beta-agonists.

Diabetes mellitus

When treating patients with diabetes mellitus taking beta-blockers, one should be prepared for the more frequent development of hypoglycemic conditions, while the clinical symptoms of hypoglycemia change. Beta-blockers largely eliminate the symptoms of hypoglycemia: tachycardia, tremor, hunger. Insulin-dependent diabetes with a tendency to hypoglycemia is a relative contraindication to the appointment of beta-blockers.

Peripheral vascular disease

If beta-blockers are used for peripheral vascular pathology, then cardioselective atenolol and metoprolol are safer.

Atenolol does not worsen the course of peripheral vascular disease, while captopril increases the rate of amputations.

Nevertheless, peripheral vascular diseases, including Raynaud’s disease, are included in the relative contraindications for prescribing beta-blockers.

Heart failure

While beta-blockers are widely used in the treatment of heart failure, they should not be prescribed for class IV failure with decompensation. Severe cardiomegaly is a contraindication to beta-blockers. Beta-blockers are not recommended when the ejection fraction is less than 20%.

Heart blocks and arrhythmias

Bradycardia with heart rate less than 60 min ^-1 (initial heart rate before prescribing drugs), atrioventricular blockade, especially of the second or more degree, is a contraindication to the use of beta-blockers.

Personal experience

Probably, each doctor has his own pharmacotherapeutic reference book, reflecting his personal clinical experience with drugs, addictions and negative attitudes. The success of the drug in one to three to ten of the first patients ensures that the doctor is addicted to it for many years, and the literature data strengthens the opinion about its effectiveness. Here is a list of some modern beta-blockers for which I have my own clinical experience.

Propranolol

The first of the beta-blockers that I began to use in my practice. It seems that in the mid-70s of the last century, propranolol was almost the only beta-blocker in the world, and certainly the only one in the USSR. The drug is still one of the most commonly prescribed beta-blockers, has more indications for use compared to other beta-blockers. However, I cannot consider its current use justified, since other beta-blockers have much less pronounced side effects.

Propranolol can be recommended in the complex therapy of coronary heart disease, it is also effective in lowering blood pressure in hypertension. When prescribing propranolol, there is a risk of developing orthostatic collapse. Propranolol is prescribed with caution in heart failure, with an ejection fraction of less than 35%, the drug is contraindicated.

I have observed that propranolol is effective in the treatment of mitral valve prolapse: dosages of 20–40 mg per day are sufficient to eliminate or significantly reduce leaflet prolapse (usually anterior) from grade 3 or 4 to grade 1 or none.

Bisoprolol

The cardioprotective effect of beta-blockers is achieved at a dosage that provides a heart rate of 50-60 per minute.

Highly selective beta ₁ is a blocker that has been shown to reduce mortality from myocardial infarction by 32%. A dose of 10 mg of bisoprolol is equivalent to 100 mg of atenolol, the drug is prescribed in a daily dosage of 5 to 20 mg. Bisoprolol can be confidently prescribed for a combination of hypertension (reduces arterial hypertension), coronary heart disease (reduces myocardial oxygen demand, reduces the frequency of angina attacks) and heart failure (reduces afterload).

Metoprolol

The drug belongs to beta ₁ cardioselective beta-blockers. In patients with COPD, metoprolol at a dose of up to 150 mg / day causes less pronounced bronchospasm compared with equivalent doses of non-selective beta-blockers. Bronchospasm when taking metoprolol is effectively stopped by beta2-agonists.

Metoprolol effectively reduces the frequency of ventricular tachycardia in acute myocardial infarction and has a pronounced cardioprotective effect, reducing the death rate of cardiac patients in randomized trials by 36%.

At present, beta-blockers should be considered as first-line drugs in the treatment of coronary heart disease, hypertension, and heart failure. The excellent compatibility of beta-blockers with diuretics, calcium channel blockers, ACE inhibitors, of course, is an additional argument in their appointment.

types, mode of action and uses

1. Action of beta-blockers
2. Discovery history
3. Classification of beta-blockers
4. Applications

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Cardiac activity is completely subordinated to adrenaline release, which speeds up the pulse, increases blood pressure and heart rate. Beta-blockers help slow down the process to protect the heart from the long-term effects of epinephrine and norepinephrine (catecholamines).

Action of beta-blockers

Beta-blockers stop the transmission of certain nerve impulses. When a nerve is stimulated, the ends of some nerves release a chemical (a neurotransmitter) called norepinephrine. This chemical then stimulates beta-adrenergic receptors. There are two different types: beta1 (β1)-adrenergic receptors, which affect the strength and frequency of heart contractions, as well as blood pressure. Beta2 (β2)-adrenergic receptors cause relaxation of the smooth muscles of the bronchi, uterus and blood vessels.

In the body, beta-blockers inhibit the action of the stress hormone adrenaline and the messenger substance norepinephrine. This leads to a decrease in heart rate. The heart muscle requires less oxygen and relaxes, which is especially important for patients with chronic heart failure or coronary heart disease.

Physicians commonly combine beta-blockers with other active ingredients to lower blood pressure, and their arousal-suppressing effect makes them the #1 drug in the fight against cardiac arrhythmias. Beta-blockers are available in the form of tablets, only a small part is for intravenous use.

Discovery history

In 1948, the American Raymond Ahlquist established the importance of the participation of norepinephrine in the transmission of nerve impulses. By this time, two types of adrenergic receptors were also known: alpha, which are most often present in the contractile tissues (smooth muscles) of the brain and liver, and beta, concentrated in the endocrine and external secretion glands, heart and kidneys.

In 1958, pharmacologist James Black from Scotland got a job as a young specialist at ICI Pharmaceuticals, choosing the most promising area – pharmacotherapy to improve myocardial blood supply. Thanks to Black at 19In 1968, the first beta-blocker, Propranolol, rolled off the assembly line. For his discovery and development, James Black was awarded the Nobel Prize in Physiology or Medicine in 1988.

Over the entire history, about a hundred drugs have been synthesized, 30 of them are used in modern practice. The last revolutionary drug of the new generation, Nebivolol, was developed in 2001. It combines the developments of previous generations with a small addition – a vasodilating effect.

Classification of beta-blockers

• Selective / non-selective. Non-selective equally affect both types of β1 / β2 receptors. Selective ones are directed only to β1 receptors.

• Lipophilic or fat soluble. It is better to overcome the blood-brain barrier between the circulatory and central nervous system, the drug is excreted by the liver, because of this, it should be carefully used by people suffering from liver failure. Absorption – 70–90%.

• Hydrophilic, or water-soluble, are metabolized in the liver for an order of magnitude longer, which means a prolonged effect of action. Excreted by the kidneys. Absorption – 30-50%.

• Amphiphilic blockers are lipid and water soluble. Absorption of the drug – 40-60%. It is equally well excreted by both the liver and the kidneys.

Applications:

• hypertension. Beta-blockers prevent the negative effects of the sympathetic nervous system on the heart. The need for oxygen decreases, blood pressure stabilizes;

• heart failure. Studies have shown that the use of beta-blockers reduces the risk of death from heart failure by 30% and the risk of severe conditions requiring hospitalization by 40%. Among patients with chronic or long-term heart failure, the risk of sudden death is reduced by 38%. Beta-blockers that are useful for heart failure include carvedilol, bisoprolol, nebivolol, and long-acting metoprolol;

• acute myocardial infarction or heart attack. Beta-blockers such as carvedilol and netoprolol may reduce the risk of heart attack and death. The drugs are especially useful for high-risk patients who have prolonged cardiac ischemia or left ventricular dysfunction;

• chronic stable angina. Patients with this disease experience a lack of blood supply (ischemia) to the heart muscles, resulting in chest pain, especially during exercise. Beta-blockers reduce myocardial oxygen demand and heart rate. A special form of angina called “Prinzmetal’s angina” should not be treated with non-selective beta-blockers, since the components can aggravate the condition;

• cardiac arrhythmias or arrhythmias. Some beta-blockers can be used to treat arrhythmias, such as Sotalol, Esmolol, and Propranolol. Beta-blockers are recommended in cases of arrhythmias involving the ventricles to reduce the risk of cardiac death from ventricular arrhythmias. Beta-blockers are also effective in treating an inherited arrhythmia called “Long Interval Syndrome”;

• glaucoma. This condition, in which pressure builds up in the eye due to fluid buildup, is a common cause of vision loss among older adults. Eye drops containing beta-blockers reduce fluid production and normalize eye pressure;

• anxiety. Drugs neutralize the effect of stress hormones on the psychological state. As a result, the frequency of physical manifestations of anxiety, tremor, sweating is significantly reduced. Many public figures take beta-blockers before performances to relieve emotional stress. However, in case of clinical manifestation of anxiety, it is necessary to consult with a specialized doctor;

• overactive thyroid.