acetaminophen /əˌsiː.təˈmɪn.ə.fɪn/ n. (international nonproprietary name paracetamol; brand names include Tylenol, Panadol, Calpol)

Definition. A widely used non-opioid analgesic (pain-relieving) and antipyretic (fever-reducing) drug. It is one of the most common over-the-counter medications worldwide and is used for the symptomatic relief of mild to moderate pain and the reduction of fever.

Etymology. Both names derive from the chemical name para-acetylaminophenol (N-acetyl-para-aminophenol): acet-amino-phen and par-acetam-ol are each contractions of the same parent compound. “Acetaminophen” is standard in the United States, Canada, and Japan; “paracetamol” predominates in most other countries.

Drug class. Analgesic and antipyretic. Although sometimes grouped loosely with mild analgesics, it is not a typical non-steroidal anti-inflammatory drug (NSAID): at usual doses it has little clinically significant anti-inflammatory action and does not share the gastric, renal, or antiplatelet effects characteristic of NSAIDs.

Mechanism of action. Its precise mechanism remains incompletely understood. It is thought to act predominantly within the central nervous system, with proposed contributions from inhibition of cyclooxygenase activity in the brain, modulation of the serotonergic and endocannabinoid systems, and the action of an active metabolite (AM404). Unlike NSAIDs, it exerts only weak peripheral cyclooxygenase inhibition.

Indications. Headache, musculoskeletal and dental pain, dysmenorrhea, post-operative pain (often as part of multimodal analgesia), osteoarthritis, and the reduction of fever in adults and children. It is frequently combined with opioids or other agents in fixed-dose combination products.

Routes of administration. Available orally (tablets, capsules, liquids, dispersible forms), rectally (suppositories), and intravenously.

Pharmacokinetics. Rapidly absorbed from the gastrointestinal tract and metabolized primarily in the liver by glucuronidation and sulfation. A small fraction is oxidized by cytochrome P450 (chiefly CYP2E1) to the reactive metabolite NAPQI (N-acetyl-p-benzoquinone imine), which is normally neutralized by hepatic glutathione.

Toxicity. At therapeutic doses it is generally well tolerated. In overdose, hepatic glutathione becomes depleted, allowing NAPQI to accumulate and cause potentially fatal hepatocellular necrosis (acute liver failure). Risk is increased by exceeding the recommended maximum daily dose, chronic alcohol use, malnutrition, and inadvertent “double-dosing” from multiple combination products. The specific antidote is N-acetylcysteine (NAC), most effective when given early.

Adverse effects. Uncommon at recommended doses; rare reports include hypersensitivity and serious skin reactions (e.g., Stevens–Johnson syndrome). The principal safety concern is dose-related hepatotoxicity.

Cautions. Caution and dose limitation are advised in hepatic impairment, chronic high alcohol intake, and low body weight. Patients should be counselled not to exceed the recommended dose and to check for acetaminophen content in other combination medicines.

Related terms. analgesic; antipyretic; NAPQI; N-acetylcysteine; hepatotoxicity; NSAID (distinct drug class).

See also. ibuprofen; paracetamol poisoning; multimodal analgesia.

Disclaimer. This glossary entry is provided for general informational and educational purposes only. It does not constitute medical advice, diagnosis, treatment, or a prescribing or dosing recommendation, and it is not a substitute for consultation with a qualified healthcare professional. Drug indications, dosages, contraindications, and safety information vary by individual and by jurisdiction and may change over time. No therapeutic outcome is guaranteed. Do not start, stop, exceed, or alter any medication without the guidance of a licensed physician or pharmacist who has evaluated your specific situation. In cases of known or suspected overdose, seek emergency medical care immediately. Neither the author nor the publisher assumes liability for any action taken on the basis of this content.