Pharmacology · Year 2 · from Pharmacology
Case 1: Acetaminophen Overdose
Clinical Scenario
A 22-year-old female is brought to the emergency department by her roommate after ingesting an unknown quantity of acetaminophen tablets in a suicide attempt approximately 6 hours ago.
Patient Demographics
- Age: 22 years
- Sex: Female
- Weight: 60 kg
Chief Complaint
Intentional overdose of acetaminophen 6 hours prior
History of Present Illness
The patient's roommate found an empty bottle of extra-strength acetaminophen (500 mg tablets, 100 count) and a suicide note. The patient admits to taking "the whole bottle" approximately 6 hours ago following a relationship breakup. She currently has mild nausea and vague abdominal discomfort but is otherwise asymptomatic. She has no other medical problems and takes no other medications.
Physical Examination
- Vital Signs: BP 118/72 mmHg, HR 82 bpm, RR 16, T 36.8C
- General: Alert, tearful, cooperative
- Abdominal: Mild right upper quadrant tenderness, no guarding or rebound
- Neurological: Intact, no asterixis
- Mental status: Appropriate, remorseful
Workup and Results
| Test | Result | Reference Range |
|---|---|---|
| Acetaminophen level (6 hours post) | 285 mcg/mL | <10 mcg/mL |
| AST | 42 U/L | 10-40 U/L |
| ALT | 38 U/L | 7-56 U/L |
| INR | 1.0 | 0.9-1.1 |
| Creatinine | 0.8 mg/dL | 0.6-1.2 mg/dL |
| Total bilirubin | 0.8 mg/dL | 0.1-1.2 mg/dL |
Rumack-Matthew nomogram: Level of 285 mcg/mL at 6 hours is well above the treatment line (150 mcg/mL at 4 hours)
Diagnosis
Acute acetaminophen overdose - estimated ingestion of 50 g (833 mg/kg), high risk for hepatotoxicity
CNS Pharmacology Principles Illustrated
- NAPQI formation: Acetaminophen is metabolized by CYP2E1 to toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI).
- Glutathione depletion: Normally, glutathione conjugates NAPQI. In overdose, glutathione is depleted, allowing NAPQI to bind cellular proteins.
- Zone 3 necrosis: Centrilobular hepatocyte necrosis due to highest CYP450 concentration in zone 3.
- N-acetylcysteine mechanism: NAC replenishes glutathione and provides alternative substrate for NAPQI detoxification.
- Timing critical: NAC is nearly 100% hepatoprotective if given within 8 hours.
Treatment
- N-acetylcysteine (NAC): Start immediately - IV protocol:
- Loading: 150 mg/kg in 200 mL D5W over 1 hour
- Second infusion: 50 mg/kg in 500 mL D5W over 4 hours
- Third infusion: 100 mg/kg in 1000 mL D5W over 16 hours
- Activated charcoal: 50 g PO if within 4 hours (may still have benefit at 6 hours)
- Serial labs: LFTs, INR, creatinine every 6-12 hours
- Monitor for hepatotoxicity: Peak liver injury typically 72-96 hours post-ingestion
- Psychiatric consultation once medically cleared
- Suicide precautions
Clinical Image
The Rumack-Matthew nomogram plots acetaminophen serum concentration against time since ingestion. Levels above the treatment line indicate risk of hepatotoxicity and need for N-acetylcysteine therapy.
Image Source: Wikimedia Commons License: Public Domain URL: https://commons.wikimedia.org/wiki/File:Rumack-Matthew_nomogram.svg