Link to Beta-blockers Teaching Resources
Link to Problems for Discussion



Non - selective
  • Acebutolol
  • Alprenolol
  • Atenolol
  • Bisoprolol
  • Esmolol
  • Metoprolol
  • Nadolol
  • Oxprenolol
  • Pindolol
  • Practolol
  • Propranolol
  • Sotalol
  • Timolol

β1-selective agents
  • Acebutolol (has intrinsic sympathomimetic activity)
  • Atenolol
  • Betaxolol
  • Bisoprolol
  • Celiprolol
  • Esmolol[52]
  • Metoprolol
  • Nebivolol (also increases nitric oxide release for vasodilation)
  • Signal ISA


Morbidity and mortality are due to cardiovascular collapse resulting from a combination of beta blockade and direct myocardial depression and impaired myocardial conduction. Seizures are a common and serious complication of poisoning with lipophilic beta-blockers such as propranolol and may precipitate cardiac complications.


Antagonism of beta-receptors can cause bradycardia and hypotension for all drugs in this class.
Propranolol and sotalol have the highest relative toxicity due to other pharmacological properties of these drugs: sodium channel blockade (propranolol) and potassium channel blockade (sotalol)
Within the drug class they differ according to a number of other features:
  • Cardioselectivity (beta 1 selectivity)
  • Intrinsic sympathomimetic activity (partial agonist activity)
  • Lipid solubility (CNS effects)
  • Renal/hepatic clearance
  • Class I/III antiarrhythmic effects

Cardioselectivity (beta 1 selectivity)
Though this may be important in determining adverse effects in therapeutic use, it does not have much influence in overdose, as selectivity is lost with high concentrations.

Intrinsic sympathomimetic activity (ISA) or partial agonist activity
Drugs with ISA may cause beta stimulation leading to tachycardia and hypertension. This partial agonist effect rarely leads to significant problems and probably protects to some extent from the more serious class I and III antiarrhythmic effects.

Lipid solubility
(CNS effects) Only lipid soluble drugs will lead to direct CNS effects, though CNS symptoms may occur secondary to cardiac effects and decreased perfusion. Lipid solubility alone will not lead to CNS effects and they may relate to Na+ channel blocking effects as they are particularly common with propranolol.

Renal/hepatic clearance
This is occasionally important in therapeutics but is largely irrelevant to overdose.

Class I/III antiarrhythmic effects
Some beta blocking drugs have significant effects on voltage gated ion channels (Na+, Ca++, K+). This leads to arrhythmias (ventricular tachycardia and heart block) and direct myocardial depression (see pharmacological properties). Other effects In addition to their cardiac effects, beta blocking drugs may also cause hypoglycaemia (by inhibiting glycogenolysis) and /or bronchospasm (in susceptible individuals.)



Most beta-blockers are rapidly absorbed from the small intestine, though water-soluble beta-blockers may have poor absorption. Peak concentrations of these drugs occur in therapeutic use within 1-2 hours. Propranolol and some other lipid soluble beta-blockers have a significant first pass effect with bioavailability being as low as 10%. The bioavailability increases in overdose because of saturation of first-pass metabolism.


All beta-blockers have moderate to large volumes of distribution, roughly proportional to their lipid solubility. Lipid solubility also determines the degree of CNS penetration.

Metabolism - Elimination

The half-life of most beta-blockers in therapeutic doses is less than 12 hours and about 4 hours for propranolol. There are no data on the half-life in overdose.




Cardiac effects

Hypotension occurs due to a combination of bradycardia (with or without heart block) and myocardial depression. Toxicity develops over the first few hours. Intractable hypotension with extreme bradycardia and/or asystole is the usual mode of death. Varying degrees of bradyarrhythmia may occur (sinus bradycardia, 1st to 3rd degree heart block, junctional or ventricular bradycardia, or asystole) and deterioration may occur rapidly and without warning. Vagal stimuli (gastric lavage, emesis, intubation) and seizures are precipitants for cardiac arrest. Atropine pretreatment should be used prior to any intervention that could enhance vagal tone. Other ECG changes including QRS and QT prolongation occur and are a measure of severity. A prolonged QRS interval (>100 ms) is predictive for seizures in propranolol poisoning (Reith et al 1996).

Central nervous system effects

Delirium, coma, and seizures all occur with lipophilic beta blocking drugs. Risk factors for seizures include
  • ingestion of more than 2 grams of propranolol (Reith et al 1996).
  • QRS width > 100 ms

Hypoglycaemia - hyperglycaemia

Beta blocking drugs may cause hypoglycaemia by inhibiting glycogenolysis. There are some reports of patients responding to glucose with "normal" blood glucose measurements. Therefore, it is worth giving a bolus of 50% glucose to any patient with CNS effects. Hyperglycaemia, due to a combination of glucagon treatment and impaired insulin release (due to beta blockade) may also occur. Bronchospasm and airways obstruction is likely to occur in individuals with underlying airway hyper-responsiveness. This occurs uncommonly as patients usually ingest their own medication.


Blood concentrations

These are unhelpful in management.


Repeated measures of the ECG, with continuous monitoring if available, serve as a measure of severity and along with the blood pressure are the best guides to the need for specific treatment. Electrolytes and blood glucose should be monitored.


There are a number of drugs that can lead to a patient presenting with profound hypotension and bradycardia. Correct diagnosis is important as these drugs have different specific treatments.


Propranolol is the only beta-blocker that frequently causes seizures. In one series, of those who ingested more than 2 g of propranolol, two thirds had a seizure. It also causes more severe cardiovascular effects and death more commonly than other widely used beta blocking drugs. Propranolol also appears to be over represented in beta-blocker poisoning when corrected for frequency of prescription (Reith et al 1996). This presumably relates to propranolol being taken by a younger age group for predominantly non-cardiac indications. Sotalol may frequently cause significant QT prolongation and torsade de pointes (occasionally reported with propranolol) as well as the usual manifestations of beta blockade. Other factors relate to
  • Intrinsic sympathomimetic activity (partial agonist activity)
  • Lipid solubility (CNS effects)

(see pharmacological properties).


The prognosis correlates best with the degree of heart block/bradycardia. Factors that increase the severity of the overdose are:



IV access with IV fluids (normal saline) should be secured as soon as possible. ECG monitoring in intensive care is indicated for all but the most trivial propranolol or sotalol poisonings. Glucose should be given to any patient with decreased consciousness or seizures regardless of a normal blood sugar.

GI Decontamination

Syrup of ipecac should not be used to decontaminate beta-blocker poisonings under any circumstances. Gastric lavage should be considered in large ingestions of propranolol or sotalol if patients present within one hour of ingestion. Atropine should be given prior to lavage and in any patient who is vomiting. Oral activated charcoal should be given to all patients ingesting any overdose of a beta-blocking drug who present within 2 hours.


There are a number of drugs that will antagonize some of the cardiac effects of beta-blockers. All these treatments may be used simultaneously, if this is required

This should be tried in all patients with bradycardia. It should be given prior to intubation, lavage, or any other procedure that might increase vagal tone and in patients who are nauseated or vomiting.

Glucagon had been used as antidote for beta-blocker poisoning in the past but its use has been largely superseded by insulin dextrose. The rationale for its use is that it increases cyclic AMP and activates myosin kinase independent of beta-receptors. The dose is 5 - 10 mg IV as a bolus and then an infusion titrated against heart rate and blood pressure (starting at 5 - 10 mg/hour).

This is a non-selective competitive beta agonist. Doses should also be titrated against cardiac parameters and the dose required may be ten or twenty fold larger than normally used. As both the agonist and antagonist are competing for the same receptors, much larger doses are needed to reach the same level of receptor occupancy. Dose requirements will fall rapidly as the beta-blocking drug is metabolised.
Patients who require inotropics support should be commenced on
**Dextrose & Insulin**
This should be implemented in patients not responding to isoprenaline

Treatment of specific complications

Glucose should be given regardless of a normal blood sugar. Otherwise, they should be treated conventionally with benzodiazepines(eg diazepam). If seizures are refractory-use phenobarbitone.

Ventricular tachycardia (torsades de pointes) may occur with sotalol or occasionally propranolol. Conventional treatment is with magnesium, isoprenaline, or cardiac pacing. Magnesium has calcium channel blocking effects and is potentially hazardous as it may further impair cardiac conduction and contractility. It should be used with great caution if at all. Isoprenaline or cardiac pacing to achieve a heart rate of 120-140 bpm is the safest option.

Elimination enhancement

The drugs that are water soluble are predominantly renally cleared. Among these drugs, only sotalol has significant "antiarrhythmic" effects and frequently causes life threatening poisoning. Thus, haemodialysis is unlikely to be useful except perhaps for sotalol in patients with life threatening toxicity and impaired renal function.


Occasional late complications/deterioration have been reported generally in patients who have had significant poisoning. It is likely that these relate to too rapid withdrawal of treatment. Long term sequelae have not been reported and no follow up is required after resolution of the clinical signs - ECG findings unless the patient has been profoundly hypotensive.


Lip GY, Ferner RE. Poisoning with anti-hypertensive drugs: beta-adrenoceptor blocker drugs. J Hum Hypertens 1995; 9(4):213-221.
Love JN, Howell JM, Litovitz TL, Klein-Schwartz W. Acute beta blocker overdose: factors associated with the development of cardiovascular morbidity. J Toxicol Clin Toxicol 2000; 38(3):275-281.
Pentel PR, Salerno DM. Cardiac drug toxicity: digitalis glycosides and calcium-channel and beta-blocking agents. Med J Aust 1990; 152(2):88-94.
Reith DM, Dawson AH, Whyte IM, Buckley NA, Sayer GP. Relative toxicity of beta blockers in overdose. J Toxicol Clin Toxicol 1996; 34(3):273-278.
Albertson TE, Dawson A, de Latorre F, Hoffman RS, Hollander JE, Jaeger A, Kerns WR 2nd,Martin TG,Ross MP;American Heart Association;International Liaison Committee on Resuscitation.AnnEmergMed.
TOX-ACLS: toxicologic-oriented advanced cardiac life support 2001 Apr;37(4 Suppl):S78-90
O'grady J, Anderson S, Pringle D.Successful treatment of severe atenolol overdose with calcium chloride.CJEM. 2001 Jul;3(3):224-7.
Kerns W. Management of beta-adrenergic blocker and calcium channel antagonist toxicity. Emerg Med Clin North Am 2007, May;25(2):309-31; abstract viii.