DESCRIPTION

The beta-receptor blocking drugs (beta-blockers) are used in the treatment of hypertension, angina, myocardial infarction, cardiac dysrhythmia, cardiomyopathy, migraine headache, thyrotoxicosis, and topical use in glaucoma.

FORMS AND USES

• Pharmaceutical preparations of these substances include acebutolol, alprenolol, atenolol, betaxolol, Betoptic Ophthalmic, bisoprolol, Brevibloc, bucindolol, bufetolol, carteolol, Cartrol, esmolol, Inderal, Inderide (also contains hydrochlorothiazide), Kerlone, labetolol, Levatol, Lopressor, Lopressor HCT (also contains hydrochlorothiazide), Metipranolol, metoprolol, nadolol, oxprenolol, penbutolol, pindolol, practolol, propranolol, Sectral, Tenoretic (also contains chlorthalidone), Tenormin, Timolide (also contains hydrochlorothiazide), timolol, Timoptic, Toprol XL, Visken, Zebeta, and Ziac (also contains hydrochlorothiazide).
• Representative daily dosage
  • Atenolol. Oral, 50 to 100 mg (200 mg maximum); intravenous, 5 to 10 mg.
  • Betoptic Ophthalmic Solution. Ocular, 2 to 4 drops.
  • Labetolol. Oral, 200 to 800 mg (2,400 mg maximum).
  • Metoprolol. Oral, 100 to 400 mg.
  • Propranolol. Oral, 40 to 320 mg; intravenous, 1 to 10 mg.
  • Timolol. Oral, 10 to 60 mg.
  • Timoptic. Ocular, 2 drops.

PATHOPHYSIOLOGY

• beta-blocking agents are competitive antagonists at beta-₁, beta-₂, or both types of adrenergic receptors.
• Some agents also exhibit partial beta-receptor agonist or antagonist activity.

EPIDEMIOLOGY

• Poisoning is uncommon.
• Toxic effects following exposure are typically mild to moderate, with death occurring in cases involving coingestants or large overdose.

CAUSES

• Toxic ingestion is usually intentional.
• Child neglect or abuse should be considered if the patient is less than 1 year of age, suicide attempt if the patient is over 6 years of age.

RISK FACTORS

• Patients with reactive airways disease may develop bronchospasm even at therapeutic doses.
• Elderly patients and those with underlying cardiovascular disease may be intolerant of even mild hypotension.
• Seizures and hypoglycemia are more common in children, particularly with propranolol.

DRUG AND DISEASE INTERACTIONS

• Coingestion of calcium channel blocker or digitalis may worsen bradycardia, dysrhythmias, and hypotension.
• Coingestion of other antihypertensives may worsen hypotension.

PREGNANCY AND LACTATION

• Acebutolol, metoprolol, and pindolol. US FDA Pregnancy Category B. Animal studies indicate no fetal risk and there are no controlled human studies, or animal studies show an adverse fetal effect but well-controlled studies in pregnant women do not.
• Atenolol, betaxolol, bisoprolol, carteolol, esmolol, labetolol, nadolol, penbutolol, propranolol, and timolol. US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• RISK FACTORS
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

DIFFERENTIAL DIAGNOSIS

• Toxicologic causes of bradycardia or heart block include calcium channel blockers, digitalis, class I antidysrhythmics, and clonidine.
• Nontoxicologic causes include ischemic heart disease and severe electrolyte abnormalities.

SIGNS AND SYMPTOMS

• Hypotension and bradycardia are common; life-threatening dysrhythmia may occur in severe cases.
• Bronchospasm, seizures, and hypoglycemia may occur.

Vital Signs

Bradycardia and hypotension are common.

Cardiovascular

May include severe bradycardia, atrioventricular blocks, intraventricular conduction delays, ventricular dysrhythmias, and congestive heart failure.

Pulmonary

• Bronchospasm is possible.
• Respiratory depression is possible in patients with hemodynamic instability.
• Pulmonary edema and acute respiratory distress syndrome may occur after a severe overdose.

Neurologic

• Seizures, most commonly after propranolol overdose
• CNS depression, coma (complicates profound hypotension)

Endocrine

Hypoglycemia, most commonly in children and diabetics after propranolol overdose.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• ECG and continuous monitoring to detect dysrhythmia or ischemia
• Serum electrolytes, glucose, BUN, and creatinine to detect other causes of dysrhythmia or cause of drug accumulation

Recommended Tests

• Serum creatine kinase in patients with prolonged seizures or coma to detect rhabdomyolysis
• Serum acetaminophen and aspirin levels in an overdose setting to detect occult ingestion
• Lumbar puncture, bacterial cultures, and other tests in patients with altered mental status of unknown etiology
• Chest radiography in patients with pulmonary symptoms or coma

Not Recommended Tests

beta-blocker levels are not clinically useful.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • Cardiovascular
  • Pulmonary
  • Neurologic
  • Endocrine
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests
  • Not Recommended Tests

DIRECTING PATIENT COURSE

Treatment should focus on supportive care with appropriate airway management.

Dose and time of exposure should be determined for all substances involved.

The health-care professional should call the poison control center when:

• Bradycardia, hypotension, altered mental status, or other severe effects are present.
• Toxic effects are not consistent with beta-blocker poisoning.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• More than one daily dose of medication was ingested.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management is warranted if:

• Patient has ingested sustained-release preparation.
• Patient has toxic effects (hypotension, seizures, pulmonary edema, or dysrhythmia) other than mild bradycardia.

DECONTAMINATION

Out of Hospital

Emesis should not be induced; coma or seizures may develop abruptly.

In Hospital

• Gastric lavage in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients presenting within 1 hour of substantial ingestion or if severe effects are present
• One dose of activated charcoal (1-2 g/kg) without a cathartic if a substantial ingestion has occurred within previous few hours
• Whole-bowel irrigation with a polyethylene glycol solution may be useful following ingestion of sustained-release preparation

ANTIDOTES

Glucagon

• Indications. Bradycardia and hypotension induced by beta-receptor blocker; animal studies suggest that glucagon primarily affects heart rate without having a dramatic effect on blood pressure.
• Contraindication. Hypersensitivity to glucagon.

Method of administration. Intravenous bolus of 50 to 150 µg/kg (5-10 mg in an adult) followed by an infusion of 2 to 10 mg/h, titrated to effect.

Potential adverse effects. Frequent occurrence of vomiting and hyperglycemia. Acidosis may result from phenol diluent in some glucagon preparations. Check label and assure that saline is substituted for phenol diluent.

ADJUNCTIVE TREATMENT

• Hypotension
  • Primary treatment is correction of dysrhythmia.
  • If needed, patient may be infused with 10 to 20 ml/kg 0.9% saline and vasopressor such as dopamine.
• Intraaortic balloon pump has been used for hemodynamic support in overdoses unresponsive to drug therapy.
• Hemodialysis may increase elimination of acebutolol, atenolol, and nadolol, but is not expected to be useful for other beta-blockers.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
  • Glucagon
• ADJUNCTIVE TREATMENT

PATIENT MONITORING

• Continuous cardiac and hemodynamic monitoring
• Serum glucose in diabetics and children
• Pulmonary status in patients with reactive airways disease

EXPECTED COURSE AND PROGNOSIS

• Most patients do well with gastrointestinal decontamination and supportive care. Factors producing greatest risk for complications include:
  • Advanced age
  • Underlying disease (especially cardiovascular)
  • Coingestion of other myocardial depressant (calcium channel blockers, digitalis, clonidine, etc.)
  • Massive ingestion of sustained release product

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Patients who have ingested an immediate-release formulation and are asymptomatic other than mild bradycardia may be discharged after gastric decontamination, a 6-hour observation period, and psychiatric evaluation, if needed.
• From the hospital. Patients may be discharged following gastrointestinal decontamination, resolution of cardiac effects, and psychiatric evaluation, if needed.

PATIENT EDUCATION

• Patients should be instructed carefully on the use and dosage of ophthalmic preparations.
• Patients should be warned to avoid simultaneous use of beta-blockers and other agents with similar effects (calcium channel blocker, digitalis) when possible.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS
• PATIENT EDUCATION

DIAGNOSIS

• Ophthalmic drops can cause serious toxicity, particularly in the elderly.
• Sustained-release products may not produce toxic effects for several hours after overdose.

TREATMENT

Multiple modes of treatment (pressors, glucagon, isoproterenol, etc.) are often needed simultaneously in patients with severe effects.

Section Outline:

• DIAGNOSIS
• TREATMENT

Poisoning by drugs primarily affecting the autonomic nervous system: sympatholytics (adrenergics).

See Also: SECTION II, Hypotension chapter; SECTION III, Glucagon chapter.

RECOMMENDED READING

Love JN. Beta blocker toxicity: a clinical diagnosis. Am J Emerg Med 1994;12:356-375.

Taboulett P, Cariou A, Bordeaux A, et al. Pathophysiology and management of self-poisoning with beta blockers. J Toxicol Clin Toxicol 1993;31:531-551.

Author: Katherine M. Hurlbut

Reviewer: Richard C. Dart