35 : Acetaminophen

By the late 1800s, both phenacetin and acetanilide were used as analgesics and antipyretics, but their acceptance was limited by significant side effects including methemoglobinemia. N-acetyl-p-aminophenol (APAP) is a major metabolite of phenacetin and acetanilide, and is responsible for, both analgesia and antipyresis. APAP was synthesized in 1878 and has a low risk of causing methemoglobinemia. N-acetyl-paminophenol is referred to as acetaminophen (N-acetyl-paraaminophenol) in the United States, Canada, Japan, and several other countries and as paracetamol (para-acetylaminophenol) in most other areas of the globe. Both terms are abbreviations of the chemical name. APAP was first used clinically in the United States and the United Kingdom in the mid 1950s, but its widespread acceptance was delayed until the 1970s because of concerns of the toxicities of its precursors. APAP has since proved to be a remarkably safe xenobiotic at appropriate dosage, which has led to its popularity. APAP is available in a myriad of single-agent dose formulations and delivery systems, and in a variety of combinations with opioids, other analgesics, sedatives, decongestants, expectorants, and antihistamines. The diversity and wide availability of APAP products dictate that APAP toxicity be considered not only after identified ingestions but also after exposure to unknown or multiple xenobiotics in settings of intentional overdose, abuse, and therapeutic misadventures.