Antihistamines are a class of medication primarily used to relieve allergy symptoms, such as sneezing, itching, and runny nose. While generally safe when taken as directed, certain older types can produce psychoactive effects when misused in excessively high doses. These effects are symptoms of drug toxicity, carrying severe and potentially fatal risks. The ability of an antihistamine to cause intoxication depends on its chemical structure and interaction with the central nervous system, dividing these medicines into two distinct categories.
The Difference Between First and Second Generation Antihistamines
The potential for an antihistamine to cause intoxication is directly linked to its generation.
First-Generation Antihistamines
First-generation antihistamines, such as diphenhydramine (Benadryl), are older compounds. These molecules are lipophilic (fat-soluble), allowing them to easily permeate the blood-brain barrier (BBB) and enter the central nervous system (CNS). Their action within the brain causes the well-known side effect of drowsiness and, at higher doses, the psychoactive state.
Second-Generation Antihistamines
Second-generation antihistamines, such as loratadine and fexofenadine, are newer drugs engineered to minimize CNS effects. These compounds are less lipophilic and are actively pumped out of the brain by transporter proteins. They primarily block histamine receptors in the periphery of the body, treating allergy symptoms without causing the same level of sedation or potential for recreational abuse.
How Anticholinergic Effects Cause a Psychoactive State
The psychoactive state induced by high doses of first-generation antihistamines is caused by their potent anticholinergic activity. While designed to block histamine receptors, these drugs also block muscarinic acetylcholine receptors in the brain. Acetylcholine is a major neurotransmitter involved in memory, learning, and attention.
Blocking its action in the central nervous system disrupts normal brain function, leading to a state medically referred to as delirium. This experience is characterized by profound confusion, disorientation, and extreme restlessness or agitation. Individuals may experience vivid, often frightening hallucinations. These effects are a manifestation of acute drug poisoning that severely impairs cognitive function.
Immediate Risks of High-Dose Antihistamine Use
Misusing first-generation antihistamines in high doses introduces severe, life-threatening health hazards.
Cardiovascular Risks
One significant danger is cardiovascular toxicity, as large amounts of the drug interfere with the heart’s electrical signaling. This interference can lead to a rapid heart rate (tachycardia), irregular heart rhythms (arrhythmias), and potentially cardiac arrest.
Systemic and Neurological Effects
The severe anticholinergic effects cause systemic physical symptoms, including extreme dry mouth, blurred vision, and hyperthermia (dangerously high body temperature) due to impaired sweating. Acute toxicity can trigger seizures, resulting from central nervous system overstimulation. Following these severe episodes, the individual may progress to profound drowsiness, loss of consciousness, and coma. Any sign of an overdose, such as severe agitation, confusion, or a rapid heart rate, requires immediate medical intervention, including calling emergency services.