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Toxicology – Acetaminophen (Paracetamol) Toxicity
Source
Acetaminophen is a commonly used over-the-counter medication for pain relief and fever reduction. It is available as a single agent and is frequently combined with other drugs, including opioids and “cold and flu” preparations. In adults, doses below 4 grams per day are generally considered safe.
Typical Presentation
Patients may present after intentional or accidental overdose. Early on, individuals often appear well, which can make diagnosis challenging without a clear history.
Clinical Features
In the initial phase, symptoms may be minimal or limited to mild nausea and vomiting. Within 24–48 hours, laboratory abnormalities begin to appear, including elevated liver enzymes (ALT, AST) and prolonged coagulation times (PT/PTT). As toxicity progresses, patients may develop altered mental status, metabolic acidosis, liver failure, and kidney injury. Severe cases can lead to encephalopathy and death.
Mechanism of Action
Acetaminophen is metabolized primarily through glucuronidation and sulfation. A smaller portion is metabolized via the cytochrome P450 system, producing a toxic metabolite (NAPQI). Under normal conditions, NAPQI is neutralized by glutathione. In overdose, glutathione stores are depleted, allowing NAPQI to accumulate and cause liver cell damage.
Management
An acetaminophen level should be measured approximately 4 hours after ingestion and interpreted using the Rumack-Matthew nomogram. If levels fall within the treatment range, N-acetylcysteine (NAC) should be administered. NAC acts as a glutathione substitute and helps detoxify the harmful metabolite. It is most effective when given early but can still be beneficial later in the course. NAC is available in both oral and intravenous forms. Severe liver failure may require liver transplantation.
Key Points
Source
Acetaminophen is a commonly used over-the-counter medication for pain relief and fever reduction. It is available as a single agent and is frequently combined with other drugs, including opioids and “cold and flu” preparations. In adults, doses below 4 grams per day are generally considered safe.
Typical Presentation
Patients may present after intentional or accidental overdose. Early on, individuals often appear well, which can make diagnosis challenging without a clear history.
Clinical Features
In the initial phase, symptoms may be minimal or limited to mild nausea and vomiting. Within 24–48 hours, laboratory abnormalities begin to appear, including elevated liver enzymes (ALT, AST) and prolonged coagulation times (PT/PTT). As toxicity progresses, patients may develop altered mental status, metabolic acidosis, liver failure, and kidney injury. Severe cases can lead to encephalopathy and death.
Mechanism of Action
Acetaminophen is metabolized primarily through glucuronidation and sulfation. A smaller portion is metabolized via the cytochrome P450 system, producing a toxic metabolite (NAPQI). Under normal conditions, NAPQI is neutralized by glutathione. In overdose, glutathione stores are depleted, allowing NAPQI to accumulate and cause liver cell damage.
Management
An acetaminophen level should be measured approximately 4 hours after ingestion and interpreted using the Rumack-Matthew nomogram. If levels fall within the treatment range, N-acetylcysteine (NAC) should be administered. NAC acts as a glutathione substitute and helps detoxify the harmful metabolite. It is most effective when given early but can still be beneficial later in the course. NAC is available in both oral and intravenous forms. Severe liver failure may require liver transplantation.
Key Points
- Early stages may be asymptomatic despite significant toxicity.
- Always consider acetaminophen exposure in mixed or unknown overdoses.
- The nomogram is not reliable for chronic ingestion or certain extended-release formulations.
- Toxic doses are generally ≥7.5 g in adults and ≥140 mg/kg in children.
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