Symptoms, Diagnosis, and Management of Beta-Blocker Toxicity

Introduction

Beta-blockers belong to the class of drugs mainly used for treating high blood pressure, irregular heart rhythms, and recurrent heart attacks. Beta-blockers are used to manage high blood pressure when other medications like diuretics are ineffective for the treatment. These drugs have wide applications due to their effectiveness in managing various cardiac disorders, glaucoma, migraine, hyperthyroidism, and anxiety.

Over the years, beta-blocker overdose and toxicity increased due to widespread use and availability. Beta-blocker toxicity may cause cardiotoxicity and hypotension. Profound cardiotoxicity is observed when a beta-blocker overdose occurs in individuals who have already taken other medications like tricyclic antidepressants and calcium channel blockers. Depending on the beta-blocker involved and underlying health conditions (cardiac diseases), people show different toxicity levels after a drug overdose.

What Are Beta-Blockers?

Beta-blockers are a group of drugs that block the receptor sites for epinephrine, norepinephrine, and catecholamines on adrenergic beta receptors present in the sympathetic nervous system. Beta receptors are mainly found on cells of the smooth muscles, heart muscles, arteries, airways and kidneys, and other tissues that are a part of the sympathetic nervous system. These receptors induce stress responses when they are stimulated by epinephrine. Beta-blockers interfere with the binding of stress hormones and epinephrine to the receptors and reduce the effects of stress hormones.

Beta-blockers that are commonly used for therapeutic purposes are the following.

• Atenolol.

• Propranolol.

• Carvedilol.

• Metoprolol.

• Labetalol.

• Bisoprolol.

• Nebivolol.

• Acebutolol.

• Nadolol.

• Pindolol.

• Timolol.

• Esmolol.

• Sotalol.

• Betaxolol.

What Are the Uses of Beta-Blockers?

Beta-blockers are used to treat, improve and prevent various medical conditions.

It includes:

• Chest pain (angina).

• High blood pressure.

• Arrhythmia (irregular heart rhythm).

• Tremors.

• Heart attacks.

• Glaucoma.

• Hyperthyroidism.

• Pheochromocytoma.

• Anxiety disorders.

• Irregular heartbeat.

• Mitral valve prolapse.

What Is Beta-Blocker Toxicity?

Beta-blockers are one of the most commonly prescribed medications in the world. As a result, there is an increased chance of drug overdose and abuse, leading to toxic health effects. Beta-blocker toxicity may occur due to accidental ingestion of large doses of the drug or long-term exposure to drug doses more than needed. After ingestion, these drugs are readily absorbed within one to four hours. Toxicity involved with beta-blockers depends on the drug's ability to cross blood-brain barriers.

Highly lipophilic (lipid-soluble) beta-blockers like Propranolol easily cross the blood-brain barrier and induce central nervous system toxicity. In addition, excessive beta-blocker concentration in the body will result in reduced catecholamine (adrenaline) activity and altered stress response. Hypotension, hypoglycemia, bradycardia (heart rate lower than usual), hemodynamic instability, and decreased myocardial contraction are the significant side effects of beta-blocker toxicity.

What Are the Symptoms of Beta-Blocker Toxicity?

Beta-blocker overdose can slow down the heart rate and induce difficulties in breathing. The majority of the patients develop trembling and dizziness after overdose.

The common symptoms associated with beta-blocker overdose are the following.

1. Central Nervous System

• Weakness.

• Confusion.

• Seizures.

• Excessive sweating.

• Drowsiness.

• Nervousness.

• Altered consciousness.

• Coma.

2. Cardiovascular System

• Low blood pressure.

• Irregular heart rate.

• Heart failure.

• Rapid heartbeat.

• Lightheadedness.

• Shock.

3. Respiratory System

• Shortness of breath.

• Respiratory arrest.

• Breathing problems.

• Wheezing (asthmatic patients).

4. Visual System

• Double vision.

• Blurred vision.

How Can We Diagnose Beta-Blocker Toxicity?

Beta-blocker overdose mainly involves cardiac and central nervous system toxicity. Prolonged hypotension and bradycardia are the first clinical signs pointing toward an overdose. Beta-blocker overdose can be confirmed based on the patient's drug history and clinical features. Cardiotoxicity related to beta-blockers may cause altered levels of cardiac enzymes in the blood. Myocardial infarction can be ruled out by measuring the cardiac enzyme levels. Serum electrolyte levels can be measured to identify hypokalemia and resultant cardiac arrhythmias. An electrocardiogram (ECG) must be done in patients suspecting beta-blocker toxicity to diagnose and manage cardiac changes that may occur due to toxicity.

How Can We Manage Beta-Blocker Toxicity?

• Airway Management - Most beta-blockers can cross the blood-brain barrier and induce central nervous system toxicity, which may lead to respiratory arrest. Thus proper airway management must be done in patients with decreased consciousness and respiratory depression. Bronchodilators like Alhuterol and supplemental oxygen therapy can be given to reduce bronchospasm. In the case of deeply obtunded patients, the airway must be managed with a cuffed endotracheal tube.

• Gastrointestinal Decontamination - This includes charcoal administration, gastric lavage, and total bowel irrigation. Gastric lavage and decontamination are done in patients admitted into the hospital within a few hours (1 to 2 hours) after a fatal overdose. Activated charcoal can be used to reduce drug absorption and limit toxicity. Whole bowel irrigation can be done using polyethylene glycol-release preparation until the rectal effluent is clear.

• Glucagon - It is considered an essential agent in managing beta-blocker toxicity. Glucagon activates adenylyl cyclase (through a secondary mechanism) and increases cardiac inotropy and thus bypasses beta-blocker receptor blockage. It also helps to overcome hypoglycemia induced by excessive beta-blockers in the body through hepatic gluconeogenesis. An initial dose of 5 to 10 milligrams intravenously is given. Later on, the dosage can be altered based on the patient's response and efficacy.

• Intravenous Fluids - Fluid resuscitation is essential in managing hypotension and bradycardia induced due to beta-blocker toxicity.

• Benzodiazepines - They can be given to manage seizures associated with beta-blocker toxicity.

• Calcium Salts - Decreased intracellular calcium levels may occur due to beta-blocker toxicity. However, it can be somehow managed by giving intravenous calcium.

• Intralipid Therapy - It is used in cases of severe overdose with highly lipophilic beta-blockers like Propranolol, Nebivolol, and Carvedilol. Intralipid therapy will help to reduce the toxicity of lipophilic drugs by lowering the active drug dose in plasma.

• High Dose Insulin (Euglycemia) - It helps to increase cardiac contractility and glucose utilization.

Conclusion

Accidental or intentional ingestion of large doses of beta-blockers may cause toxic effects in the body. Neurotoxicity and cardiotoxicity are the dangerous effects induced by beta-blocker overdose. Prolonged hypotension, cardiac arrest, respiratory failure, and altered consciousness are the commonly observed conditions associated with beta-blocker toxicity. Therefore, early diagnosis and efficient medical treatment are essential to prevent hazardous adverse effects such as cardiac arrest and respiratory failure.