Diphenhydramine (DPH) is a first-generation antihistamine widely available over the counter under common brand names like Benadryl, Unisom, and Nytol. It is primarily used to treat allergy symptoms such as sneezing and itching. Because it readily crosses the blood-brain barrier, it also causes significant drowsiness, making it a popular ingredient in many non-prescription sleep aids. However, diphenhydramine carries a risk of severe toxicity when consumed in excessive amounts.
Defining the Toxic Threshold
Determining a single “fatal dose” for diphenhydramine is impossible because individual biological variation and immediate medical intervention play significant roles in outcomes. Toxicity is best understood as a range of exposure relative to body weight. For adults, doses exceeding 20 to 40 milligrams per kilogram (mg/kg) are commonly cited as potentially lethal.
A healthy adult who ingests a total amount exceeding 500 milligrams will likely require aggressive medical intervention. Ingestions greater than 1,000 milligrams (1 gram) carry a substantially greater risk of severe complications, including seizures, coma, and death.
The risk profile changes drastically for children, who are more sensitive to the drug’s effects. In children, ingestions of only 7.5 mg/kg are considered significant enough to warrant immediate evaluation. Fatalities have been documented following the ingestion of amounts as low as 11.6 mg/kg, highlighting that the life-threatening dose is dramatically lower for pediatric populations.
Physiological Effects of Severe Toxicity
Diphenhydramine toxicity results primarily from the drug’s potent anticholinergic properties, which block the neurotransmitter acetylcholine. This blockade leads to the classic set of symptoms known as the anticholinergic toxidrome. Peripherally, this causes hyperthermia, flushed and dry skin, significantly dilated pupils, and urinary retention.
The central nervous system (CNS) effects are often the most dangerous, manifesting as confusion, agitation, and profound delirium with vivid hallucinations. At higher doses, CNS toxicity can progress to seizures and a deep coma with respiratory depression.
Beyond the anticholinergic action, severe overdose also causes cardiotoxicity by blocking the heart’s sodium and potassium ion channels. This channel blockade can lead to dangerous cardiac rhythm disturbances, including a widened QRS complex and prolonged QT interval. These electrical abnormalities increase the risk of ventricular arrhythmias, which are a direct cause of death in severe diphenhydramine poisoning.
Immediate Emergency Procedures
If a diphenhydramine overdose is suspected, the immediate priority is to seek professional medical help without delay. Call your local emergency services (such as 911) or the national Poison Help hotline (1-800-222-1222). Quick action is necessary, as symptoms can progress rapidly to life-threatening cardiac or neurological events.
When speaking to emergency personnel or Poison Control, provide precise details: the estimated amount taken, the time of ingestion, and the age and weight of the affected person. Follow all instructions provided by the experts.
Do not attempt to induce vomiting or administer any other substances unless specifically instructed by a medical professional. Attempting home remedies wastes valuable time and increases the risk of complications if the person’s mental status declines. Emergency medical personnel will monitor the patient’s airway, breathing, and circulation until definitive hospital care can be provided.
Individual Factors Affecting Dose Sensitivity
The dose that causes severe harm varies significantly among individuals based on several underlying factors. Age is a major determinant of sensitivity, with both pediatric and elderly populations being at higher risk for toxicity at lower doses. Older adults, in particular, often have a reduced capacity to metabolize and excrete the drug, leading to higher drug concentrations in the bloodstream.
A person’s existing health conditions, especially the function of the liver and kidneys, also influence how the body handles the drug. Since the liver metabolizes diphenhydramine and the kidneys excrete its breakdown products, impairment in either organ can dramatically slow drug clearance, effectively lowering the toxic threshold.
Combining diphenhydramine with other substances significantly increases the potential for toxicity, a phenomenon known as polypharmacy. Co-ingestion with alcohol, opioids, or other central nervous system depressants compounds the sedative effects, increasing the risk of respiratory failure. Interactions with other anticholinergic medications or monoamine oxidase inhibitors (MAOIs) can also intensify the drug’s dangerous side effects.