β-Blocker, Calcium Channel Blocker & Digoxin Toxicity
When the heart slows and pressure falls, the antidotes stack
β-blocker poisoning
Mechanism and features. Blocking β1 receptors slows the sinus node, depresses contractility, and delays AV conduction, producing bradycardia, hypotension, and heart block. Loss of β-adrenergic support for glycogenolysis and gluconeogenesis causes hypoglycemia, most often in children and treated with IV dextrose, and β2 blockade can precipitate bronchospasm in asthma or COPD. Lethargy is common. Most immediate-release overdoses become symptomatic within about 6 hours, whereas extended-release products and sotalol need longer observation.
Propranolol. Its high lipid solubility carries it into the brain, and its membrane-stabilizing effect blocks fast sodium channels. Overdose therefore adds delirium, seizures, coma, QRS widening, and ventricular arrhythmias, a picture resembling tricyclic poisoning. Sodium bicarbonate boluses treat the wide QRS, and benzodiazepines treat seizures.
Sotalol. Sotalol also blocks potassium channels (a class III effect), so overdose prolongs the QT and causes torsades de pointes. Treatment is IV magnesium, potassium repletion, and overdrive pacing or isoproterenol. Hydrophilic β-blockers (atenolol, sotalol, nadolol) can be removed by hemodialysis; propranolol cannot.
Calcium channel blocker poisoning
Verapamil and diltiazem. These nondihydropyridines block L-type calcium channels in the SA and AV nodes and in myocardium, causing sinus bradycardia, AV block, junctional rhythms, and profound cardiogenic and vasodilatory shock. Verapamil is the most lethal agent in overdose. Blocking L-type channels in pancreatic β-cells cuts insulin release, so hyperglycemia is typical, and its degree tracks severity. Mental status is often surprisingly preserved despite deep shock.
Dihydropyridines. Amlodipine and nifedipine act mainly on arteriolar smooth muscle, so overdose causes hypotension with reflex tachycardia; at high doses selectivity is lost and bradycardia can follow. Amlodipine's long half-life prolongs shock, and noncardiogenic pulmonary edema can occur.
| Feature | β-blocker | Verapamil or diltiazem | Dihydropyridine |
|---|---|---|---|
| Heart rate | Slow | Slow, AV block, junctional | Fast (reflex) early |
| Glucose | Low, especially children | High; tracks severity | May be high |
| Mental status | Depressed; seizures with propranolol | Often preserved | Often preserved |
| ECG extras | Wide QRS (propranolol), long QT (sotalol) | PR prolongation, heart block | Sinus tachycardia |
| Emphasized antidote | Glucagon | Calcium, high-dose insulin | Vasopressors, calcium |
Stepwise management of cardiotoxic shock
- Airway and decontaminationActivated charcoal (1 g/kg) for early presenters with a protected airway; whole-bowel irrigation with polyethylene glycol for sustained-release pills, with observation for at least 24 hours.
- Atropine and fluidsAtropine is often ineffective; give crystalloid boluses.
- IV calciumCalcium chloride 1 g via central line or calcium gluconate 3 g, repeated; follow ionized calcium.
- Glucagon and high-dose insulinGlucagon for β-blockers; insulin with dextrose for severe CCB or β-blocker poisoning.
- VasopressorsNorepinephrine or epinephrine titrated to perfusion.
- Rescue20% lipid emulsion for lipophilic drugs, transvenous pacing, or VA-ECMO.
| Agent | How it works | Practical points |
|---|---|---|
| Calcium | Raises extracellular calcium to drive influx through remaining channels | Helps BP and contractility most in CCB poisoning; repeat doses |
| Glucagon | Own Gs-coupled receptor activates adenylyl cyclase and raises cAMP, bypassing β-receptors | 3–10 mg IV bolus then infusion; vomiting is common, so protect the airway |
| High-dose insulin | Lets the stressed myocardium use glucose, improving contractility | Regular insulin 1 unit/kg bolus, then an infusion from about 1 unit/kg/h; dextrose to keep euglycemia; check glucose and potassium often; effect builds over 15–60 min, so start early |
| Lipid emulsion (20%) | Sequesters lipophilic drug in a plasma lipid phase | Refractory shock or arrest from propranolol or verapamil |
Digoxin toxicity
Mechanism. Digoxin inhibits the Na⁺/K⁺-ATPase; the resulting rise in intracellular sodium slows sodium-calcium exchange, so intracellular calcium and contractility increase. It also raises vagal tone, slowing the sinus and AV nodes. Toxicity reflects excess automaticity combined with depressed conduction.
Symptoms. Anorexia, nausea, vomiting, and abdominal pain come first, then fatigue, weakness, and confusion, especially in the elderly. Visual changes include blurring, halos, and yellow-green tinting (xanthopsia).
Arrhythmias. Frequent PVCs and bigeminy are the most common; atrial tachycardia with AV block, accelerated junctional rhythm, and bidirectional VT (also seen in catecholaminergic polymorphic VT) are highly suggestive; sinus bradycardia and AV block are frequent. Atrial fibrillation that becomes slow and regular suggests complete heart block with a junctional escape. Scooped ST segments (digoxin effect) indicate use, not toxicity.
| Feature | Acute ingestion | Chronic toxicity |
|---|---|---|
| Typical patient | Single large overdose | Elderly patient on maintenance therapy |
| Potassium | High; hyperkalemia predicts death | Normal or low; hypokalemia worsens toxicity |
| Serum level | Very high | May be only modestly raised |
| Precipitants | Intentional or accidental ingestion | Renal failure, hypokalemia, hypomagnesemia, verapamil, amiodarone, quinidine |
Why potassium matters. In acute poisoning the pump is inhibited, so potassium cannot re-enter cells; hyperkalemia is a marker of how much pump is poisoned. In chronic toxicity, hypokalemia (often from diuretics) increases digoxin binding to the pump and worsens toxicity. Amiodarone, verapamil, and quinidine raise digoxin levels by reducing its renal and P-glycoprotein-mediated clearance, so the digoxin dose is typically cut by about half when they are started.
Digoxin-specific Fab. Antibody fragments bind digoxin into a complex excreted by the kidney and usually reverse toxicity within an hour. Indications:
- Life-threatening arrhythmia (ventricular arrhythmia, symptomatic bradycardia, or high-grade AV block)
- Potassium above 5–5.5 mEq/L in acute poisoning
- Ingestion of 10 mg or more in an adult, or 4 mg or more in a child
- Steady-state level above 10 ng/mL
Digoxin has a huge volume of distribution and is not dialyzable. After Fab, measured levels rise because the assay detects bound drug, so post-Fab levels are ignored; watch for hypokalemia as potassium returns into cells.
Clonidine: the opioid mimic
Presentation. Clonidine is a central α2 agonist that reduces sympathetic outflow. Overdose causes CNS depression, miosis, bradycardia, hypotension (sometimes after a brief initial hypertension), hypothermia, and respiratory depression with apneic pauses, closely mimicking the opioid toxidrome, while opioid screens are negative.
Management. Care is supportive: airway and ventilation, atropine for symptomatic bradycardia, and fluids or vasopressors for hypotension. Naloxone helps inconsistently but is reasonable to try.
Swallowed imidazoline eye drops or nasal decongestants (tetrahydrozoline, oxymetazoline) produce the same syndrome in young children.