β-Blocker and calcium channel blocker poisoning have significant morbidity, and their hallmark is bradycardia and hypotension.
If standard Pediatric Advance Life Support (PALS) protocols do not restore adequate cardiovascular function, stepwise administration of glucagon, hyperinsulinemia-euglycemia (HIE) therapy, and lipid emulsion should be considered.
Administration of specific anti-digoxin Fab antibody fragments is a highly effective treatment for digoxin poisoning.
Consider naloxone if PALS protocols fail to reverse clonidine toxicity.
β-ADRENERGIC BLOCKING AGENTS
In 2016, the American Association of Poison Control Centers documented 3076 single substance β-blocker exposures in children younger than 5 years and 832 in 6- to 19-year-olds.1 Those producing the greatest morbidity were metoprolol, atenolol, and propranolol. β1- and β2-receptor antagonism, intrinsic sympathomimetic activity, and membrane-stabilizing activity are responsible for the clinical effects of these drugs. α-Antagonist activity is seen with labetalol and carvedilol. β-Adrenergic blocking agents account for almost 60% of pediatric emergency department visits due to the ingestion of an adult prescription medication by a child.2
The pharmacologic effects of β-blocking drugs are mediated through modulation of intercellular signals and calcium secondary to inhibited adrenergic activation.3 β1-Antagonism produces decreased cardiac contractility and conduction. β2-Antagonism produces increased smooth muscle tone, which may manifest as bronchospasm, increased peripheral vascular tone, and increased gut motility. Although many β-blockers are β1-selective at therapeutic doses, these drugs have both β1- and β2-effects in overdose.
Intrinsic sympathomimetic properties of some β-blockers produce agonist–antagonist activity, which may blunt the bradycardic response in some patients.2,4 Drugs with intrinsic sympathomimetic activity include acebutolol, carteolol, oxprenolol, penbutolol, and pindolol. The membrane-stabilizing activity characteristic of some β-blockers is a quinidine-like effect, resulting in inhibition of fast sodium channels, decreased contractility, and ventricular arryhythmias.5 This effect is additive to the β1-toxic effects.
β-Blockers with increased intrinsic sympathomimetic activity and decreased membrane-stabilizing properties demonstrate less toxicity than those with increased membrane-stabilizing properties.5–8 Drugs with significant membrane-stabilizing properties include propranolol, acebutolol, and oxprenolol.9
Sotalol is a β-blocker that has class III antiarrhythmic properties.10 In overdose, it may prolong the QT interval, resulting in ventricular arrhythmias, including torsades de pointes. Each β-blocker may have only some of the described activities, and the clinical manifestations may vary.
The absorption, distribution, and elimination of β-blockers vary with the drug. Extended-release formulations can have a marked delay of onset of toxic effects. Conversely, standard release β-blockers are rapidly absorbed, with 30% to 90% bioavailability. Only penbutolol and propranolol exhibit high lipid solubility and thus can cross the blood–brain barrier. Protein binding ranges from 10% (timolol) to 98% (carvedilol). Most are metabolized in the liver by the cytochrome P-450 2D6 isoenzyme. The elimination half-life varies from 2 to 24 ...