Acetaminophen

Snapshot

  • A 20-year-old woman presents to the emergency department for ingestion of acetaminophen. She reports that she has had suicidal ideation and had ingested an unknown quantity of acetaminophen in an attempt to end her life. An hour later, she began feeling nauseous. She regretted the ingestion and came to the hospital. In the emergency room two hours after ingestion, she has vomited twice. Serum labs reveal no abnormalities. She is given activated charcoal since the ingestion was within four hours of presentation.

Introduction

  • Mechanism of action
    • central reversible inhibition of cyclooxygenase (COX)
      • inactivated peripherally
  • Clinical use
    • used as an antipyretic and analgesic
      • especially useful in the pediatric population to avoid a risk of Reye syndrome in children with viral infection
      • not used for inflammation
  • Toxicity
    • massive hepatic necrosis
      • pathogenesis
        • cytochrome P450 in the liver metabolizes acetaminophen into N-acetyl-p-benzoquinoneimine (NAPQI)
        • NAPQI depletes glutathione, which forms toxic byproducts that result in hepatic necrosis
        • chronic alcoholism induces cytochrome P450, thus exacerbating the toxicity 
      • clinical manifestations
        • immediately after ingestion, nausea, vomiting, malaise, and lethargy are common
          • early manifestations of overdose are nonspecific and are not reliable predictors of hepatotoxicity, so serum acetaminophen levels should be determined
        • liver enzymes may rise at 8-12 hours if patients severely overdose
        • 48-72 hours later, hepatitis progresses rapidly and patients may die from multi-organ failure, including acute renal failure
      • treatment
        • N-acetylcysteine (NAC) is the antidote for acetaminophen toxicity
          • replenishes glutathione 
          • useful for up to 24 hours after ingestion
        • activated charcoal if ingested within 4 hours
        • acetaminophen levels should be drawn 4 hours after ingestion or immediately if ingestion occurred more than 4 hours prior to evaluation 
    • minimal gastrointestinal irritation