Contributor: Ruben Marrero-Vasquez, PharmD

Educational Pearls:

ACEP and FDA have both issued warnings about the viral Tik Tok Benadryl (diphenhydramine) challenge where individuals voluntarily overdose on diphenhydramine which can cause fatal toxicity
Diphenhydramine is typically dosed at 0.5-1 mg/kg in pediatric patients Q4-6 PRN and carries a fatal dose of 20-40 mg/kg but anywhere from 3-5x recommended dose does can cause toxicity
Diphenhydramine toxicity causes both central and peripheral anticholinergic toxicity
- Central anticholinergic toxicity symptoms: delirium, agitation, combativeness, confusion, restlessness, hallucinations, ataxia, tremor and seizures
- Peripheral anticholinergic toxicity symptoms: tachycardia, dry flushed skin, dry mucus membranes, thick secretions, dilation of pupils, urinary retention, and decreased bowel sounds
Pneumatic to help you remember anticholinergic toxidrome:
- Red as a beet
- Dry as a bone
- Blind as a bat
- Mad as a hatter
- Hot as a hare
- Full as a flask
Management typically only requires supportive care, agitation from central anticholinergic delirium can be hardest aspect to treat, IV benzodiapines are first line treatment to control and may require large doses to prevent rhabdomyolysis and hyperthermia
Diphenhydramine toxicity has been associated with blockade of sodium and potentially potassium channels increasing risk of arrhythmia and seizures. Cardiac changes can include: QRS widening, myocardial depression, QT prolongation and torasades-type ventricular tachycardia.
- Wide QRS complexes indicate delayed ventricular depolarization caused by sodium channel blockade, bolus of sodium bicarbonate can be used dosed 1-2 mEq/kg followed by continuous infusion
- Prolonged QT: restoration of low serum potassium and magnesium to high normal range
Benzodiazipines should be used as first line therapy for toxin induced seizures
- Don't use fosphenytoin or phenytoin sodium channel blockers as they can worsen cardiac conduction

References

Olson KR, Anderson IB, Benowitz NL, Blanc PD, Clark RF, Kearney TE, Kim-Katz SY, Wu AH. Diphenhydramine. In: Poisoning & Drug Overdose. 7th ed.McGraw Hll; 2018: 544-545.
FDA Warns About Serious Problems With High Doses Of The Allergy Medicine Diphenhydramine (Benadryl).(09/24/2020). CDC website. Accessed December 01, 2020. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-problems-high-doses-allergy-medicine-diphenhydramine-benadryl.
Su M, Goldman M. Anticholinergic Poisoning. UpToDate. https://www.uptodate.com/contents/anticholinergic-poisoning?search=diphenhydramine overdose&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1. Published October 6, 2020. Accessed December 26, 2020.

Summarized by Mason Tuttle

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