Acetaminophen Toxicity

Excerpt

Acetaminophen toxicity is prevalent, primarily due to the drug's widespread availability and the common perception of its safety. In the United States, acetaminophen toxicity is the leading cause of liver failure. Over 60 million Americans use acetaminophen weekly, often unknowingly, due to its presence in various combination products, particularly those containing opioids and diphenhydramine. Acetaminophen, also known as N-acetyl-para-aminophenol or paracetamol, functions as an antipyretic and analgesic with a mechanism distinct from nonsteroidal anti-inflammatory medications. Although its mode of action, specifically the selective inhibition of cyclooxygenase in the brain, is not fully understood, acetaminophen effectively alleviates fever and pain. In addition, it may inhibit prostaglandin synthesis in the central nervous system and directly affect the hypothalamus to produce an antipyretic effect.

If left untreated, acetaminophen toxicity can lead to both fatal and non-fatal hepatic necrosis. Timely intervention is essential in preventing fulminant liver failure and the need for liver transplantation. Activated charcoal should be administered within the first hour and N-acetylcysteine within the first 8 hours. The most reliable predictor of toxicity is correlating the time of ingestion with the serum acetaminophen concentration using the Revised Rumack-Matthew nomogram. Patients whose levels fall above the treatment line at 4 hours require N-acetylcysteine. A striking 50% of cases result from unintentional overdoses, highlighting a crucial need for healthcare professionals to properly educate patients regarding the proper dosing of acetaminophen and its presence in prescribed and over-the-counter preparations.