Dr. Lajoie is a medical doctor, specializing in Internal Medicine, and a Chiropractic Physician. She has 40 years of experience as a Chiropractor and over 20 years as a medical doctor. As a Diplomate of the Chiropractic Board of Examiners, she is also a Certified Chiropractic Sports Physician. She has worked extensively in the private sector, then for over five years with the Veterans Healthcare System. Integrating traditional with complementary forms of treatment, Dr. Lajoie has specialized in pain management and musculoskeletal disorders. She is licensed to practice in Florida, Massachusetts, and Montana. Additionally, she has two doctorates in theology, a Doctorate in Biblical Studies, and a Doctorate in Ministry.


Topic Overview

Beta-blockers are essential in the treatment of many cardiovascular diseases, including congestive heart failure, myocardial infarction, and tachyarrhythmias. Beta-blockers are also used for migraine prophylaxis, performance anxiety, glaucoma, and various other conditions. They have notable side effects, contraindications, and warnings associated with their use. Pharmacists should be aware of these when determining the appropriateness of beta-blocker therapy. Additionally, pharmacists should note any potential drug interactions when beta-blocker therapy is initiated. This course will review the pharmacologic characteristics of beta-blockers, identify indications for beta-blocker therapy, and highlight adverse reactions, contraindications, warnings, and interactions associated with beta-blocker therapy. Finally, the management of beta-blocker overdose will be discussed.

Accreditation Statement:

image LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.


Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist  0669-0000-22-045-H01-P

Pharmacy Technician  0669-0000-22-046-H01-T

Credits: 2 hours of continuing education credit


Type of Activity: Knowledge


Media: Internet Fee Information: $6.99


Estimated time to complete activity: 2 hours, including Course Test and course evaluation


Release Date: October 18, 2022 Expiration Date: October 18, 2025


Target Audience: This educational activity is for pharmacists


How to Earn Credit: From October 18, 2022, through October 18, 2025, participants must:


Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “educational activity;” and

Complete the Post-test and Evaluation form. The Post-test will be graded automatically. Following successful completion of the Post-test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Learning Objectives: Upon completion of this educational activity, participants should be able to:


Describe the mechanism of action of beta-blockers, including differentiating between nonselective and beta-1 selective agents

Identify indications for beta-blockers, including labeled and off-label uses

Discuss side effects, interactions, warnings, and contraindications of beta-blocker therapy

Review the management of beta-blocker overdose




The following individuals were involved in the development of this activity: Marilyn Lajoie, MD, DC, CCSP, Susan DePasquale, MSN, PMHNP-BC, Amanda Mayer, PharmD, and Jeff Goldberg, PharmD, BCPP. There are no financial relationships relevant to this activity to report or disclose by any of the individuals involved in the development of this activity.


ⓒ LLC 2022: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of LLC.



Beta-blockers are essential in the treatment of many cardiovascular diseases, including congestive heart failure, myocardial infarction, and tachyarrhythmias. Beta-blockers are also used for migraine prophylaxis, performance anxiety, glaucoma, and various other conditions. They have notable side effects, contraindications, and warnings associated with their use. Pharmacists should be aware of these when determining the appropriateness of beta-blocker therapy. Additionally, pharmacists should note any potential drug interactions when beta-blocker therapy is initiated. This course will review the pharmacologic characteristics of beta-blockers, identify indications for beta-blocker therapy, and highlight adverse reactions, contraindications, warnings, and interactions associated with beta-blocker therapy. Finally, the management of beta-blocker overdose will be discussed.


History of Beta-blockers


The first commercially marketed beta-blocker was propranolol, which was introduced in 1964 under the trade name InderalⓇ, and approved by the FDA in 1967.1,2 Propranolol’s effectiveness for the treatment of angina pectoris was quickly recognized, and not long after, its therapeutic effects on hypertension and arrhythmias were discovered.1 Its inventor, physician, and scientist Sir James Black, was said to have revolutionized the management of angina with this discovery, earning him the Nobel Prize in 1988.1,2 The discovery of how this beta-adrenergic receptor antagonist caused changes in the cardiovascular system is complex, but as a class, beta-blockers produce their therapeutic effects on the sympathetic branch of the autonomic nervous system.2


Clinical Pharmacology


The sympathetic nervous system regulates bodily functions by activating adrenergic receptors. These receptors include beta-adrenergic receptors in the heart that regulate cardiac contractility.3 Sympathetic nerve impulses are transmitted by catecholamines norepinephrine and epinephrine.3

These endogenous substances bind to alpha and beta-adrenergic receptors in the heart, lungs, liver, vascular smooth muscle, and many other areas within the body.3 Catecholamine-receptor binding is referred to as the “second messenger effect,” which initiates a specific cellular activity producing a measurable physiological response.3 For example, when epinephrine binds to adrenergic receptors in the heart, the physiological responses are increases in heart rate, the speed of impulse conduction through the AV nodal system, and the force of the contraction of the myocardium.3


There are three beta (ß) receptor subtypes: ß1, ß2, and ß3.3 A ligand, or signaling molecule, can be produced either endogenously, or in the case of a beta-blocker, synthetically. While all subtypes of beta-adrenergic receptors are G-coupled protein receptors (GCRPs), which lead to an increase in cyclic AMP, the type of response secondary to beta receptor stimulation is determined by the ligand, as well as the type and location of the receptor.3 ß1 receptors are located primarily in the heart and also the kidney.3,4 Within the heart, they mediate cardiac activity, with activation leading to increased heart rate, increased contractility, and increased AV node transmission.4 In the kidney, activation results in renin release.4 ß2 receptors are located in the lungs and peripheral vascular smooth muscle and, to a lesser extent, the heart. Upon activation, vasodilation and bronchodilation result.3,4 In hepatic tissue, activation leads to glycogenolysis.4 Finally, ß3 receptors are located in adipose tissue and the bladder detrusor muscle, and activation of these receptors causes relaxation of the bladder detrusor and thermogenesis resulting from fat breakdown.3


Mechanism of Action


Beta-blockers are a heterogeneous group of medications whose primary mechanism of action is to block adrenergic stimulation of beta-adrenergic receptors located in various parts of the body.3 Beta-1 receptor blockade results in decreased cardiac contractility, decreased heart rate and decreased cardiac conduction times.5 Beta-2 receptor blockade results in vasoconstriction.6 Beta-blockers differ in their receptor specificity, intrinsic

sympathomimetic activity (ISA), membrane stabilizing activity, and lipid solubility, all of which help determine the overall effects of each medication.


Beta Receptor Specificity


Beta-blockers are typically classified as either non-selective or beta-1 selective.5 Non-selective agents bind ß1 and ß2 adrenoceptors.5 Beta-1 selective agents are considered cardioselective.5 The dose of the beta-blocker can cause changes in this relative selectivity, particularly when dosages are high.5 Additionally, some beta-blockers can also bind to alpha-adrenergic receptors. There can be variability in the selectivity of beta-blockers which is relative and not total. Cardioselective beta-blockers include acebutolol, atenolol, betaxolol, bisoprolol, metoprolol, and nebivolol.


Intrinsic Sympathomimetic Activity


Some beta-blockers are not full antagonists and are actually partial agonists. Upon binding to a beta-adrenoreceptor, they simultaneously partially activate the receptor and prevent catecholamines from binding and completely activating the receptor.7,8 As a result, normal or enhanced sympathetic activity is prevented.7,8 The amount of beta stimulation is low grade while at rest, but when sympathetic activity is high, it acts as a typical beta-blocker.8 This is known as intrinsic sympathomimetic activity (ISA).7,8 Beta-blockers that possess ISA do not lower resting heart rate or have as strong of an effect on cardiac output as other beta-blockers without ISA.9 Acebutolol, penbutolol, and pindolol have ISA.7


Membrane Stabilizing Activity


Certain beta-blockers have membrane stabilizing activity that decreases the responsiveness of the myocardium (stabilizing it) to an action potential and prevents cardiac arrhythmias.8 It is at very high concentrations that membrane stabilizing activity occurs; otherwise, it is not of much clinical significance.8 However, if an excessive amount of a beta-blocker that has membrane stabilizing activity is ingested, e.g., in a deliberate overdose, this

effect can lead to serious ventricular arrhythmias. Carvedilol and propranolol are the two most used beta-blockers that have membrane stabilizing activity.8


Lipid Solubility


A drug that has high lipid solubility can easily move across cell membranes. Lipid solubility in a beta-blocker allows the drug to enter the central nervous system (CNS) by crossing the blood-brain barrier, which can lead to an increase in CNS adverse effects.10,11 Beta-blockers with high lipid solubility include carvedilol and propranolol.8,11 Beta-blockers with moderate lipid solubility include metoprolol, labetalol, timolol, and pindolol.11 Bisoprolol has low to medium lipid solubility.11 Beta-blockers identified to have low lipid solubility are atenolol, betaxolol, acebutolol, esmolol, nadolol, and sotalol.11,12


Serotonin Receptor Activity


Some beta-blockers, including propranolol, can bind to serotonin receptors. This activity is a proposed mechanism of action as to why some beta-blockers have been effectively used as prophylactic treatments for migraine headaches. In a review by Danesh and Gottschalk (2019), a comparison was made between beta-blocker efficacy and that of other migraine prophylactic medications.13 It was determined that most often, the dosage of beta-blockers prescribed is too low, but when the optimal dose is given, the results show a favorable comparison with the other migraine medications.13 The review also states that metoprolol and nadolol do not have a high affinity for serotonin receptors, yet they are still effective for treating migraines.13


Pharmacological Profile of Beta-blockers


Beta-blockers are available for use as systemic and ophthalmic preparations. Beta-blockers encompass several therapeutic categories, with many of these agents falling under several different therapeutic categories. This section will briefly compare the pharmacologic and pharmacokinetic properties of the beta-blockers. Important information specific to a beta-

blocker will be mentioned, and clinicians are encouraged to review current drug information regarding beta-blockers continuously.




Beta-blockers vary in their pharmacokinetic profiles.11,12 Most beta- blockers undergo hepatic metabolism, except for nadolol and sotalol, which are not metabolized, esmolol, which is metabolized by red blood cell esterases, and atenolol which is only metabolized to a limited extent. Beta-blockers are generally eliminated renally, and carvedilol, acebutolol, and unmetabolized atenolol are also partially eliminated in the feces. Half-life properties, metabolism, and elimination of beta-blockers vary and will be included in the dosing section.11,12


Labeled Uses


Beta-blockers are primarily used to treat cardiovascular diseases.12 Labeled uses of systemic beta-blockers include angina pectoris, hypertension (alone or with other drugs), management of ventricular arrhythmias, management of hemodynamically stable patients with known or suspected MI to reduce morbidity and mortality, treatment of mild to moderate heart failure, and glaucoma (using ophthalmic preparations). Below are descriptions of the roles beta-blockers play for certain disease states.


Angina Pectoris


Angina pectoris, also known as stable angina, is transient pain or pressure in the chest caused by myocardial ischemia.14 Myocardial ischemia is a result of an imbalance between myocardial oxygen demand and supply. For most patients, angina pectoris is typically caused by atherosclerotic heart disease.14 Angina pectoris is common, with approximately 10 million Americans suffering from the disease.14

Improving the quality of life via a reduction in angina symptoms and preventing cardiovascular events (such as MI and death) are the primary goals of angina treatment.14 Beta-blockers decrease myocardial oxygen demand by decreasing heart rate, myocardial contractility, and stress on the left ventricle. It has been conclusively shown that beta-blockers improve exercise capacity, reduce the number of angina attacks, reduce exercise-induced ST segment depression, and reduce the need for sublingual nitroglycerin.15-17


All beta-blockers are effective as a treatment for chronic angina, but ß1 selective agents are preferred because the non-selective beta-blockers do not have any comparative advantages, and they have an increased risk of adverse effects.16 Selection of beta-blocker can be determined by the following: patient’s comorbidities, frequency of dosing, and prescriber experience. Beta- blockers are preferred as initial therapy in the absence of contraindications. The treatment goals when using beta-blockers for angina pectoris are to reduce the frequency and severity of anginal attacks, improve exercise tolerance, attain a resting heart rate of 50-60 bpm, decrease blood pressure and heart rate during exercise, and use the lowest effective dose to avoid adverse effects. Beta-blockers should not be used in patients who have Prinzmetal angina (vasospastic angina), as use could lead to coronary vasospasm secondary to unopposed alpha activity.18


Atrial Fibrillation


Atrial fibrillation is the most common arrhythmia that is characterized by ectopic atrial activity and an irregular, often rapid ventricular response.19 Beta-blockers are a preferred agent for attaining rate control in patients who have atrial fibrillation.19 Intravenous beta-blockers, such as metoprolol, propranolol, and esmolol, are useful for achieving acute control of ventricular rate.19 Oral beta-blockers can then be used for chronic rate control, with metoprolol succinate, atenolol, and nadolol being once-daily options that are helpful for compliance.19

Congestive Heart Failure


Heart failure (HF) is a common cardiovascular condition caused by structural or functional impairment leading the ventricle to be unable to fill with and eject blood appropriately.20 In late-stage severe heart failure, any level of physical activity is difficult and tiring, and the patient will be dyspneic even while at rest. Three agents--bisoprolol, carvedilol, and metoprolol succinate--have demonstrated efficacy in the management of heart failure with reduced ejection fraction.20 Treatment with these beta-blockers can lessen the symptoms of HF, improve the patient’s clinical status, reduce the risk of death, and reduce the combined risk of death or hospitalization.24 Beta- blocker therapy should be started at low doses and should be titrated up until the target dose is reached, unless not tolerated (signs of bradycardia or hypotension occur).20




Hypertension is a leading cause of death and significantly increases the risk of developing atherosclerosis, heart disease, kidney disease, stroke, and retinal damage.21,22 Blood pressure control is critically important for preventing hypertensive complications. Lifestyle changes like smoking cessation and weight loss can significantly lower blood pressure, but many people who have hypertension require treatment with antihypertensive medication.


Treatment of hypertension is a labeled use for beta-blockers, but they are not a first or second-line choice as they may not be as effective as other classes in preventing stroke or cardiovascular events for patients with hypertension.21,22 In addition, the beta-blockers are less effective for African American patients, and their use increases the risk of glucose intolerance, the development of new-onset diabetes, fatigue, and sexual dysfunction.21 Current guidelines recommend angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), a thiazide diuretic, or a calcium channel blocker, alone or in combination as the primary treatment for hypertension. Beta-blockers can be added to the treatment regimen if there

is a separate indication for these medications or if therapies and lifestyle modifications have not reduced blood pressure to the target level.21,22


Myocardial Infarction


Treatment with a beta-blocker is considered standard care for patients who have had an acute ST-segment elevation myocardial infarction (STEMI).23 Beta-blockers decrease oxygen demand, decrease the risk for ventricular fibrillation, have a positive effect on ventricular remodeling, decrease automaticity, reduce infarct size, and decrease the risk of mortality.24


Ventricular Arrhythmias


Beta-blockers have been successfully used to prevent ventricular arrhythmias in patients who are having an acute coronary syndrome.25 This is particularly well-researched in the arrhythmias of ventricular tachycardia and/or ventricular fibrillation.25


Glaucoma and Ocular Hypertension


Beta-blockers, such as timolol and betaxolol, may be used to reduce intraocular pressure, which may be useful in patients with ocular hypertension and glaucoma. These beta blockers work by blocking the sympathetic nerve endings in the ciliary epithelium, which causes a fall in aqueous humor production.26


Off-Label Uses


Outside of managing cardiovascular conditions, systemic beta-blockers are used off-label to treat a variety of conditions, including Marfan syndrome, migraines, anxiety, agitation, and thyrotoxicosis.

Beta-blocker Dosage Forms, Metabolism, and Half-lives


The table below describes dosage forms, metabolism, and half-life of beta-blockers within the context of the labeled use of specific medication brands. Package inserts should be referenced for specific dosing of each medication. Beta-blockers can be administered orally, intravenously, or ophthalmically depending on the agent.11,12


Noncardioselective Agents


t½: 10-24 hrs

Angina and hypertension Available orally.

Not metabolized. Renally eliminated as an unchanged drug.


t½: 3-6 hrs (IR), 8-

10 hrs (ER)

Acute myocardial infarction, angina, atrial fibrillation, atrial flutter, hemangioma, hypertension, idiopathic hypertrophic subaortic stenosis, migraine prophylaxis, paroxysmal supraventricular tachycardia, pheochromocytoma, reduction of cardiovascular mortality, tremor
 Available orally (IR, ER, and oral solution) and IV
 Immediate-release tablets should be taken on an empty stomach. Extended-release capsules may be taken with or without food and should not be crushed.
 Hepatic metabolism. Renal elimination.


t½: 1-4 hrs

Hypertension, migraine prophylaxis, myocardial infarction prophylaxis, ocular hypertension, open- angle glaucoma, reduction of cardiovascular mortality

Available orally and ophthalmically Hepatic metabolism. Renal elimination.


t½: 12 hrs

Atrial fibrillation, atrial flutter, ventricular tachycardia Available as IV solution, oral tablet, or oral solution

Not metabolized. Renal elimination.



Cardioselective Agents


t½: 6-7 hrs

Acute myocardial infarction (STEMI), angina, hypertension, myocardial infarction prophylaxis, reduction of cardiovascular mortality
 Available orally
 Little to no hepatic metabolism. Absorbed portion eliminated by renal excretion with the rest of the dose excreted as unchanged drug in the feces
BetaxololHypertension, ocular hypertension,open-angle
t½: approx. 15 hrsglaucoma 
 Available orally and ophthalmically 
 Hepatic metabolism. Renal elimination. 


t½: 9-12 hrs

Hypertension Available orally

Hepatic metabolism. Renal elimination.

EsmololAtrial fibrillation, atrial flutter, paroxysmal
t½: approx. 9 minsupraventricular tachycardia, perioperative
 hypertension, postoperative hypertension
 Available as IV solution

Infusion into small veins or through a butterfly catheter should be avoided as it can cause thrombophlebitis


Red blood cell esterase metabolism. Renal elimination.

Metoprolol tartrate, immediate-release Metoprolol succinate, extended-release t½: 3-7 hrs

Acute myocardial infarction (STEMI), angina, cardiomyopathy, heart failure, hypertension, reduction of cardiovascular mortality


Available as IV solution or oral tablet Hepatic metabolism. Renal elimination.


t½: 12 hrs in extensive metabolizers, 19 hours in poor metabolizers

Hypertension Available orally

Hepatic metabolism. Renal and feces elimination.


Agents with alpha-1 antagonist activity


t½: 5-11 hrs

Acute myocardial infarction, cardiomyopathy, heart failure, hypertension, reduction of cardiovascular mortality


Available orally (IR and ER)


Hepatic metabolism. Excreted in the bile and feces.


t½: 6-8 hrs



Available as IV solution and orally


Hepatic metabolism. Excreted in the urine and feces.

Agents with intrinsic sympathomimetic activity (ISA)


t½: 3-4 hrs

Hypertension and premature ventricular contractions Available orally

Hepatic metabolism. Excreted in urine and bile and via direct passage through the intestinal wall.


t½: 3-4 hrs

Hypertension Available orally

Hepatic metabolism. Renal elimination.


Contraindications and Warnings


Absolute contraindications to beta-blockers as a class include symptomatic bradycardia, cardiogenic shock, and atrioventricular block.12 Beta-blockers should be used with caution in asthma or bronchospastic disease and diabetes mellitus. The use of beta-blockers in patients who have asthma, COPD, or diabetes mellitus is discussed here in greater detail.


Patients with Asthma or COPD


While the use of beta-blockers is safe for most patients, these agents should be used cautiously in patients with asthma and COPD.27 These drugs, particularly the non-selective beta-blockers, can precipitate bronchial obstructions, increase airway reactivity, cause exacerbations, and cause resistance to the beta-agonist drugs (such as albuterol) that are used to treat asthma and COPD. Clinicians should avoid the use of non-selective ß1 and ß2 antagonists (like propranolol) in patients who have severe or decompensated bronchospastic disease.27 Cardioselective beta-blockers and beta-blockers with ISA can be used for patients who have mild to moderate asthma or COPD, and there is evidence that these drugs are safe for this population.28,29

Clinicians tend to avoid the use of beta-blockers completely or use the smallest effective dose because receptor selectivity of the beta-blockers is not absolute, and the use of selective beta-blockers is not risk-free when given to patients who have asthma or bronchospastic disease.30


Diabetes Mellitus


The prescribing information about beta-blockers notes these drugs should be used cautiously if a patient has diabetes, as hypoglycemia caused by beta-blockers is well documented.29-33 Blockade of ß2 receptors can prevent catecholamines from increasing blood glucose in an individual who is hypoglycemic and can blunt the signs and symptoms of hypoglycemia (such as diaphoresis and tachycardia), putting patients at risk for severe hypoglycemia and preventing self-treatment.33


Beta-blockers can be and are used in diabetic patients. To do so safely, the following points should be kept in mind:31-33


Beta-blockers can cause hypoglycemia.

These drugs have been used safely for diabetic patients.

There should be a case-by-case assessment of the risks and benefits of using beta-blockers for diabetic patients.

Diabetic patients who are prescribed a beta-blocker should be closely monitored, taught about the signs and symptoms of hypoglycemia, and informed that the signs and symptoms of hypoglycemia might be blunted by beta-blockers.


Withdrawal Warning


Prescribing information for beta-blockers contains a US boxed warning that states that abrupt discontinuation of a beta-blocker has been reported to exacerbate angina pectoris and can cause severe hypertension and acute myocardial infarction.34 This effect is thought to be due to the upregulation of beta receptors during beta-blocker therapy and increased receptor sensitivity to catecholamines.35 Prescribing information and authoritative sources

recommend that discontinuation of beta-blocker therapy should be over a 1- to 2-week period, especially if the patient has ischemic heart disease.34


Adverse Reactions


Bradycardia, depression, exacerbation of heart failure, fatigue, hypotension, dizziness, dyspnea, headache, sexual dysfunction, and gastrointestinal distress are some of the most reported adverse effects associated with beta-blocker therapy. In addition to these adverse events, labetalol may lead to floppy iris syndrome. The use of beta-blockers may also be associated with hyperkalemia, severe mesenteric ischemia, myasthenia gravis, Prinzmetal angina, psoriasis, and peripheral vascular disease.


Drug Interactions


Drugs that affect blood pressure, heart rate, or the cardiac conduction system should be used cautiously when the patient is taking a beta-blocker. Local and general anesthetics should also be used with caution in patients taking beta-blockers due to the risk of prolonged hypotension. Patients taking certain antidepressants and a beta-blocker can be at risk for adverse events such as bradycardia, hypotension, and falls, particularly in antidepressant drugs, which are inhibitors of cytochrome P450 2D6 liver enzymes (CYP2D6).36 This inhibition would potentiate the plasma levels of the beta- blocker, increasing the beta-blocker effects. Clinicians should always consult a reliable source for drug interactions before administering a drug to a patient currently taking a beta-blocker.


Specific Populations




The use of beta-blockers during pregnancy is controversial as beta- blockers can cross the placenta.37 Beta-blockers are not associated with teratogenicity, but some beta-blockers have been associated with low birth weight, fetal bradycardia, hypoglycemia, and other adverse effects in

neonates.38-40 The prescribing information typically states that these drugs are not recommended for use during pregnancy, but that the risk to the fetus from uncontrolled maternal hypertension must be considered. Labetalol is considered an appropriate choice for treating chronic hypertension in pregnant women.38




Beta-blockers can be excreted in breast milk, but the amount is largely determined by their protein binding, with low protein binding leading to larger amounts in breast milk.39 There is a low risk for the accumulation of beta- blockers such as propranolol, metoprolol, and labetalol in breast milk, and these three are most compatible with breastfeeding. Caution should be used with atenolol, nadolol, and sotalol as they are excreted in higher amounts in breast milk and may lead to the infant experiencing hypotension, bradycardia, and tachypnea.37,41


Renal Impairment


In patients with renal disease, beta-blockers that are not renally eliminated, such as labetalol, metoprolol, pindolol, and propranolol, are preferred.42-45 Dosing may need to be adjusted if other beta-blockers are chosen for therapy in patients with impaired renal function.44,45


Hepatic Impairment


Beta-blockers that are not hepatically eliminated, such as atenolol and nadolol, are preferred in patients with hepatic impairment.46 Dosing may need to be adjusted if other beta-blockers are chosen for therapy.47


Beta-Blocker Poisoning


While the use of beta-blockers is generally considered safe when taken as prescribed, cases of overdose or poisoning can result in significant

morbidity and mortality. Pharmacists should be aware of the signs and symptoms of beta-blocker poisoning as well as management strategies.48


Beta-blocker overdose causes excessive blockade of beta-adrenergic receptors, with receptor selectivity diminishing after overdose.49 Overall, the toxicity following beta-blocker overdose will depend on both the agent and dose ingested.69 Beta-blockers that have membrane stabilizing activity appear to be particularly dangerous and are more likely to cause arrhythmias.49,50


Beta-Blocker Overdose: Signs, Symptoms, and Treatment


The majority of patients who overdose on beta-blockers will display symptoms within 2 to 6 hours; however, if sustained release formulations were ingested, signs and symptoms may be delayed up to 24 hours.49 Bradycardia and hypotension are the most common signs of beta-blocker overdose, with the risk of seizures also being possible.49 An overdose of sotalol can cause QT prolongation and torsade de pointes.51 Bronchospasm and hypoglycemia can also result from beta-blocker overdose and may complicate its management.49


Initial management of overdose includes stabilizing the patient and ensuring adequate oxygenation and circulation. Asymptomatic patients can often be observed and discharged unless other concerns remain, the overdose was intentional. or they took a sustained release formulation.49 If it is suspected that the beta-blocker was ingested within the last hour, gastric lavage and activated charcoal are options for treatment, depending on the situation. IV access should be established, and continuous ECG monitoring started. Mildly symptomatic patients can receive boluses of an IV isotonic crystalloid for hypotension and atropine for bradycardia. In many cases, these patients will require additional therapies that have been found to be beneficial in case reports, such as intravenous calcium salts, vasopressors, high-dose insulin, and lipid emulsion therapy.48,52

Intravenous Glucagon


Glucagon is recognized as a first-line therapy for beta-blocker toxicity and acts as a cardiac stimulant to help treat bradycardia. Glucagon bypasses the beta receptors and increases cAMP. High doses of glucagon are recommended, with an initial dose of 50-150 mcg/kg in adults being administered over one to two minutes. A transient effect should occur within approximately 5 minutes, and if a benefit is seen, the initial dose should be followed by a continuous infusion at a rate of 2-5 mg/hour. If no benefit is seen, the dose may need to be increased. While high-dose glucagon may be initially effective, the dose can be tapered down when the patient starts to improve.52




Beta-blockers are a diverse class of medications primarily used to manage cardiovascular conditions. They also have demonstrated efficacy for a multitude of other conditions. Non-selective agents block ß1 and ß2 adrenoceptors. Beta-1 selective blockers are relatively selective for ß1 adrenoceptors and are thus more cardioselective. While these medications share the same basic mechanisms of action, they have different properties, which makes knowledge of this class important for pharmacists who manage or review patient therapies.

Course Test


Beta-blockers produce their therapeutic effect on which branch of the autonomic nervous system?





The primary mechanism of action of beta-blockers is to prevent which of the following from binding to beta receptors?



amino acids


True or False: There are beta-adrenergic receptors in the heart, lungs, liver, vascular smooth muscle, and many other areas of the body.



Which of the following beta-blockers is highly lipid soluble?





Compared to nonselective beta-blockers, cardioselective beta- blockers and beta-blockers with ISA can be used for patients who have which of the following diseases?


symptomatic bradycardia.

cardiogenic shock.

mild to moderate asthma or COPD.

decompensated heart failure.

Which of the following is an appropriate step in the management of beta-blocker overdose in a mildly symptomatic patient?

Immediate use of glucagon and vasopressors

Initially stabilizing the patient and ensuring adequate oxygenation and circulation

Beginning a lipid emulsion infusion at a rate of 2.5 mL/kg/min

Avoiding high-dose insulin therapy in patients who are hyperglycemic

Which of the following conditions are considered to be absolute contraindications to the use of beta-blockers?

Heart conduction abnormalities

Symptomatic bradycardia


Diabetes mellitus

True or False: Abrupt discontinuation of a beta-blocker can lead to severe hypertension and myocardial infarction.



Patients taking a drug that inhibits cytochrome P450 2D6 liver enzymes (CYP2D6) and a beta blocker concurrently are at risk for which of the following adverse effects?

exertional angina



a hemostatic event

A patient who has asthma or COPD should particularly avoid which of the following beta-blockers?

all beta-blockers.

cardioselective (blockade of ß1 adrenoceptors) beta-blockers.

beta-blockers with intrinsic sympathomimetic activity.

non-selective (blockade of both ß1 and ß2 adrenoceptors) beta- blockers.



Stapleton MP. Sir James Black and propranolol. The role of the basic sciences in the history of cardiovascular pharmacology. Tex Heart Inst

J. 1997;24(4):336-42. PMID: 9456487; PMCID: PMC325477.

Srinivasan AV. Propranolol: A 50-Year Historical Perspective. Ann Indian Acad Neurol. 2019 Jan-Mar;22(1):21-26. doi: 10.4103/aian.AIAN_201_18. PMID: 30692755; PMCID: PMC6327687.

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. doi: 10.2174/1573402114666180918102735. PMID: 30227820.

Motiejunaite J, Amar L, Vidal-Petiot E. Adrenergic receptors and cardiovascular effects of catecholamines. Ann Endocrinol (Paris). 2021;82(3-4):193-197. doi:10.1016/j.ando.2020.03.012

Ladage D, Schwinger RH, Brixius K. Cardio-selective beta-blocker: pharmacological evidence and their influence on exercise capacity. Cardiovasc Ther. 2013;31(2):76-83. doi:10.1111/j.1755- 5922.2011.00306.x

Khouri C, Jouve T, Blaise S, Carpentier P, Cracowski JL, Roustit M. Peripheral vasoconstriction induced by β-adrenoceptor blockers: a systematic review and a network meta-analysis. Br J Clin Pharmacol. 2016 Aug;82(2):549-60. doi: 10.1111/bcp.12980. Epub 2016 May 31. PMID: 27085011; PMCID: PMC4972171.

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