Propranolol is a widely prescribed beta-blocker used to manage conditions such as hypertension, angina, and anxiety symptoms. Ingesting doses far exceeding the therapeutic range can lead to beta-blocker toxicity. This article explains the physiological process that occurs during a propranolol overdose. If you or someone you know is experiencing a medical emergency, call 988, 911, or your local emergency services immediately.
The Physiological Mechanism of Beta-Blocker Toxicity
Propranolol is a non-selective beta-adrenergic receptor antagonist that blocks beta-1 receptors in the heart and beta-2 receptors in the lungs and peripheral vasculature. In an overdose, this massive blockade impairs the sympathetic nervous system’s ability to stimulate the heart. This leads to a profound reduction in heart rate (bradycardia) and lowers the heart muscle’s contractility.
Propranolol is highly lipophilic, meaning it readily dissolves in fats and easily crosses the blood-brain barrier. High concentrations in the central nervous system (CNS) cause direct toxicity, which can manifest as delirium or seizures. Propranolol also possesses membrane-stabilizing activity, inhibiting fast sodium channels within the heart muscle.
This sodium channel blockade causes cardiovascular instability, often resulting in a widening of the QRS complex and promoting ventricular dysrhythmias. The combination of reduced heart rate, poor contractility, and sodium channel inhibition leads to a drop in blood pressure and inadequate perfusion of vital organs. Metabolic pathways are also affected, as the inhibition of glycogenolysis leads to hypoglycemia.
Acute Physical Manifestations of Overdose
The immediate physical manifestations of a propranolol overdose result from the body’s inability to maintain adequate circulation. The patient rapidly develops hypotension and profound bradycardia, with the heart rate often dropping below 40 beats per minute. This systemic collapse causes insufficient blood flow to the brain, initially presenting as lightheadedness, dizziness, and mental confusion.
The experience involves intense systemic distress, but the primary outcome is typically not sharp, localized pain. Instead, the patient experiences a severe sensation of air hunger (dyspnea), which may be due to reduced heart output or bronchospasm caused by beta-2 receptor blockade. This feeling of suffocation and fatigue represents the body’s acute reaction to insufficient oxygen delivery.
As cerebral perfusion worsens, the central nervous system deteriorates. Confusion progresses to stupor, followed by a rapid loss of consciousness. The direct CNS toxicity from the drug’s lipophilicity can also trigger generalized seizures before the patient becomes unconscious. Because circulatory and neurological collapse often occur quickly, prolonged conscious suffering is typically prevented by the onset of coma.
Emergency Medical Management
Upon arrival at a medical facility, management focuses on securing the airway and aggressively supporting the cardiovascular system. Initial supportive measures involve administering intravenous fluids to combat severe hypotension and managing the airway, often requiring intubation. Gastrointestinal decontamination with activated charcoal is considered if the ingestion occurred recently, aiming to limit drug absorption.
Specific antidotal therapy often begins with high-dose glucagon, which bypasses blocked beta-receptors to increase cyclic adenosine monophosphate (cAMP) inside heart cells. Glucagon is administered as an initial intravenous bolus, typically 5 to 10 mg, followed by a continuous infusion if effective, improving heart rate and contractility. Atropine is also administered to counteract profound bradycardia, though it is often ineffective alone in severe toxicity.
If primary therapies fail, clinicians may escalate treatment to high-dose insulin euglycemia therapy, which acts as a powerful inotrope. Vasopressors, such as norepinephrine or epinephrine, are used to constrict blood vessels and increase systemic vascular resistance to maintain blood pressure. In refractory cases, invasive procedures like temporary transvenous cardiac pacing or intravenous lipid emulsion therapy may be employed.