Side effects of Diphenhydramine Hydrochloride

Diphenhydramine Hydrochloride is the hydrochloride form of diphenhydramine, an ethanolamine and first-generation histamine antagonist with antiallergic activity, commonly used to treat allergies, mosquito and other insect bites, bee stings, and certain types of rashes. It is an over-the-counter drug with antiparkinsonian, antitussive, antiemetic, sedative, and hypnotic properties, and is therefore also used to treat and prevent dystonia, cough, insomnia, itching, urticaria, vertigo, and motion sickness.

Mechanism of Action

Diphenhydramine Hydrochloride prevents the effects of histamine on bronchial smooth muscle, capillaries, and gastrointestinal (GI) smooth muscle by competitively blocking H1 receptors. This prevents histamine-induced bronchoconstriction, vasodilation, increased capillary permeability, and spasm of GI smooth muscle.

Side Effects

Common side effects of Diphenhydramine Hydrochloride include: drowsiness, dry mouth, frequent urination, dizziness, headache, nausea, vomiting, anorexia, constipation, increased chest tightness and nervousness. Use with caution in younger children, who may experience periods of excitement, hallucinations, ataxia, muscle twitching, fever, convulsions, and even cardiopulmonary failure and death. Serious adverse reactions include anaphylaxis/anaphylactoid reactions, QT interval prolongation, anemia, hemolysis, thrombocytopenia, agranulocytosis, leukopenia, pancytopenia, arrhythmias, seizures, toxic psychosis, acute labyrinthitis, and heat stroke.

Several case reports of deaths in children under three years of age from accidental ingestion of Diphenhydramine Hydrochloride have been reported. Estimated doses range from 100 to 500 mg, and toxic symptoms are not necessarily dose-related. Each child initially experienced muscle twitching, which then progressed to convulsions, hyperthermia, cardiopulmonary failure, and death. Symptoms develop within one to four hours of ingestion, and death occurs within two to eighteen hours. Treatment includes gastric lavage, control of seizures with barbiturates, and ventilator assistance as needed. However, adverse synergistic sedative effects are recognized when diphenhydramine is administered with barbiturates.

Cardiac arrhythmias have only been mentioned in two cases. Our patient presented with arrhythmias, which we presumed were due to hypoxia caused by the combined sedative effects of diphenhydramine and sodium phenobarbital. Because of the arrhythmias, he was treated with assisted ventilation to improve myocardial oxygenation. Our patient responded within five hours, with resolution of the pattern of bundle branch block, but the extent and duration of cardiac enzyme changes suggest that he had severe but reversible cardiac injury. Our current treatment regimen is aggressive symptomatic and supportive care, including gastric lavage, termination of seizures with phenytoin or parabens, hypothermia, and assisted ventilation for cardiopulmonary depression.

In addition, dizziness or loss of balance is the most common side effect when diphenhydramine hydrochloride is used as a sleep aid.

References:

[1] Diphenhydramine Hydrochloride[J]. Definitions, 2020, 52 1. DOI:10.32388/wh8us3.

[2] M.D. HAROLD E. HESTAND  M. D D W T. Diphenhydramine hydrochloride intoxication[J]. Journal of Pediatrics, 1977, 90 6: Pages 1017-1018. DOI:10.1016/S0022-3476(77)80586-6.

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