Pharmacology · Year 2 · from Pharmacology

Case 2: Anticholinergic Toxicity (Diphenhydramine Overdose)

Clinical Scenario

A 19-year-old female is brought to the emergency department by her roommate after intentionally ingesting multiple diphenhydramine tablets.

Patient Demographics

  • Age: 19 years
  • Sex: Female
  • Weight: 58 kg

Chief Complaint

Confusion, agitation, and "seeing things" after intentional overdose

History of Present Illness

The patient's roommate found an empty bottle of diphenhydramine (original 100 tablets of 25 mg) and a suicide note approximately 4 hours ago. The patient is now agitated, confused, picking at invisible objects, and talking to people who are not present. She appears flushed and has not urinated despite IV fluids.

Physical Examination

  • Vital Signs: BP 145/92 mmHg, HR 128 bpm, RR 20, T 39.2C
  • General: Agitated, mumbling incoherently, picking at clothing and air
  • HEENT: Mydriasis (7 mm bilaterally, sluggishly reactive), dry mucous membranes
  • Cardiovascular: Tachycardic, regular rhythm
  • Abdominal: Distended bladder palpable, absent bowel sounds
  • Neurological: Disoriented to place and time, visual hallucinations, hyperreflexia
  • Skin: Flushed, dry, hot to touch

Workup and Results

TestResultReference Range
ECGSinus tachycardia, QRS 102 ms, QTc 485 msQRS <100 ms, QTc <450 ms
Urine drug screenNegative-
Creatinine0.9 mg/dL0.6-1.2 mg/dL
Glucose138 mg/dL70-100 mg/dL
CK450 U/L30-170 U/L

Bladder scan: 650 mL residual

Diagnosis

Anticholinergic toxicity from diphenhydramine overdose - "Hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter"

Autonomic Pharmacology Principles Illustrated

  1. Muscarinic blockade: Diphenhydramine competitively blocks muscarinic receptors throughout the body.
  2. Central effects: Crosses blood-brain barrier causing delirium, hallucinations, seizures.
  3. Peripheral effects: Mydriasis, tachycardia (loss of vagal tone), urinary retention, decreased secretions, ileus.
  4. Hyperthermia: Loss of sweating (sympathetic cholinergic pathway) impairs thermoregulation.
  5. QT prolongation: Diphenhydramine also blocks cardiac potassium channels (off-target effect).

Treatment

  1. Supportive care: Primary approach
  2. Cooling measures: Ice packs, cooling blankets for hyperthermia
  3. Benzodiazepines: Lorazepam 2 mg IV for agitation and seizure prevention
  4. Foley catheter: For urinary retention
  5. Activated charcoal: If within 1-2 hours and airway protected
  6. Physostigmine: Consider 1-2 mg IV slowly for severe, refractory agitation ONLY if no QRS widening (risk of seizures and asystole)
  7. Psychiatric consultation after medical stabilization

Clinical Image

Chemical structure of atropine, a prototypical muscarinic antagonist. Diphenhydramine and many other drugs produce anticholinergic toxicity through the same mechanism of muscarinic receptor blockade.

Image Source: Wikimedia Commons License: Public Domain URL: https://commons.wikimedia.org/wiki/File:Atropine.svg


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