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- Ariella Nadler, MD*
- Daniel M. Fein, MD*
- *Albert Einstein College of Medicine/Children’s Hospital at Montefiore, Bronx, NY
AUTHOR DISCLOSURE
Drs Nadler and Fein have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.
Acetaminophen (N-acetyl-para-aminophenol) is one of the most prevalent medications on the market today, available for purchase in multiple different formulations: as an individual product (eg, Tylenol® [Johnson & Johnson Consumer Inc, Fort Washington, PA]), as a component in over-the-counter cold remedies (eg, DayQuil™/Nyquil™ [Procter & Gamble, Cincinnati, OH], Alka-Seltzer Plus® [Bayer Corp, Whippany, NJ], and Dimetapp® Cold & Flu [Pfizer Inc, New York, NY]), and in combination with an opiate (eg, acetaminophen-codeine and Percocet® [Endo Pharmaceuticals Inc, Malvern, PA]). Being so widely available both over the counter and by prescription, it is a common cause of both accidental and intentional ingestions. As a class, analgesics (including acetaminophen) are the most commonly ingested medication, and in 2015, products containing acetaminophen were the reason for approximately 45,000 calls to poison control centers throughout the United States related to children.
Acetaminophen toxicity occurs via its metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which ultimately leads to oxidative hepatic injury. In therapeutic doses, acetaminophen produces only minimal amounts of NAPQI because it is metabolized in hepatocytes via UDP-glucuronosyl transferase (UGT) and sulfotransferase (SULT) mainly to compounds that are readily excreted in the urine. In addition, any NAPQI that is produced is conjugated by glutathione into a nontoxic compound in the liver. However, with an overdose, the UGT and SULT metabolic pathways are saturated and glutathione stores become exhausted, resulting in free NAPQI and its oxidative injury to the liver.
Clinical signs and symptoms of acetaminophen toxicity can be thought of as occurring in 4 distinct stages: the first 24 hours …
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