Drug/Small Molecule:

acetaminophen

Overview

Generic Names:	APAP; Acetaminofen; Paracetamol; Paracetamolo; Paracetanol
IUPAC Name:	N-(4-hydroxyphenyl)acetamide
Trade Names:	Abenol; Abensanil; Acamol; Accu-Tap; Acephen; Aceta Elixir; Aceta Tablets; Acetagesic; Acetalgin; Actamin; Actimol; Algotropyl; Allay; Alpiny; Alpinyl; Alvedon; Amadil; Aminofen; Anacin; Anacin-3; Anaflon; Anapap; Anelix; Anhiba; Apacet; Apadon; Apamid; Apamide; Atasol; Banesin; Bayer Select; Bickie-mol; Bucet; Butapap; Calpol; Captin; Cetadol; Clixodyne; Co-Gesic; Conacetol; Dafalgan; Dapa; Dapa X-S; Darvocet; Datril; Dimindol; Dirox; Disprol; Dolene AP-65; Doliprane; Dolprone; Drixoral Plus; Dularin; Dymadon; Dypap; Elixodyne; Enelfa; Eneril; Eu-Med; Excedrin; Exdol; Febridol; Febrilix; Febrinol; Febro-Gesic; Febrolin; Fendon; Feverall; Fevor; Finimal; Gelocatil; Genapap; Genebs; Hedex; Homoolan; Hy-Phen; Injectapap; Janupap; Korum; Lestemp; Liquagesic; Liquiprin; Lonarid; Lyteca; Momentum; Multin; NAPA; Napafen; Napap; Naprinol; Nealgyl; Nebs; Neopap; Neotrend; Nobedon; Norco; Oraphen-PD; Ortensan; Pacemo; Painex; Paldesic; Panadol; Panaleve; Panasorb; Panets; Panex; Panofen; Papa-Deine; Paracet; Parapan; Paraspen; Parelan; Parmol; Pasolind; Pasolind N; Pedric; Phenaphen; Phenaphen Caplets; Phendon; Phrenilin; Phrenilin Forte; Prompt; Propacet 100; Proval #3; Pyrinazine; Redutemp; Rivalgyl; Robigesic; Rounox; SK-Apap; Salzone; Sedapap; Servigesic; Snaplets-FR; St. Joseph Fever Reducer; Suppap; Synalgos-Dc-A; Tabalgin; Talacen; Tapanol; Tapar; Tavist Allergy/Sinus/Headache; Temlo; Tempanal; Tempra; Tencon; Tibinide; Tibizide; Tisin; Tisiodrazida; Tizide; Tralgon; Triaprin; Tussapap; Tycolet; Tylenol; Ultracet; Valadol; Valgesic; Valorin; Valorin Extra; Wygesic
Brand Mixtures:	Amacodone (acetaminophen + hydrocodone bitartrate); Anexsia (acetaminophen + hydrocodone bitartrate); Anodynos (acetaminophen + hydrocodone bitartrate); Anolor (acetaminophen + butalbital + caffeine); Bancap (acetaminophen + hydrocodone bitartrate); CoGesic (acetaminophen + hydrocodone bitartrate); Dolacet (acetaminophen + hydrocodone bitartrate); Duradyne (acetaminophen + hydrocodone bitartrate); Endolor (acetaminophen + butalbital + caffeine); Esgic (acetaminophen + butalbital + caffeine); Fioricet (acetaminophen + butalbital + caffeine); Hydrocet (acetaminophen + hydrocodone bitartrate); Hydrogesic (acetaminophen + hydrocodone bitartrate); Lorcet (acetaminophen + hydrocodone bitartrate); Lortab (acetaminophen + hydrocodone bitartrate); Margesic (acetaminophen + hydrocodone bitartrate); Norcet (acetaminophen + hydrocodone bitartrate); Oxycet (acetaminophen + oxycodone hydrochloride); Percocet (acetaminophen + oxycodone hydrochloride); Roxicet (acetaminophen + oxycodone hydrochloride); Roxilox (acetaminophen + oxycodone hydrochloride); Stagesic (acetaminophen + hydrocodone bitartrate); TGesic (acetaminophen + hydrocodone bitartrate); Tylox (acetaminophen + oxycodone hydrochloride); Vicodin (acetaminophen + hydrocodone bitartrate); Zebutal (acetaminophen + butalbital + caffeine); Zydone (acetaminophen + hydrocodone bitartrate)
PharmGKB Accession Id:	PA448015

Description

Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [PubChem]

Indication

For temporary relief of fever and minor aches and pains.

ATC Therapeutic Category

• N02BE:Anilides

Pharmacology and Interactions

Mechanism Of Action

Acetaminophen is thought to act primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1 and COX-2, enzymes involved in prostaglandin (PG) synthesis. Unlike NSAIDs, acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, thus, has no peripheral anti-inflammatory affects. While aspirin acts as an irreversible inhibitor of COX and directly blocks the enzyme's active site, studies have found that acetaminophen indirectly blocks COX, and that this blockade is ineffective in the presence of peroxides. This might explain why acetaminophen is effective in the central nervous system and in endothelial cells but not in platelets and immune cells which have high levels of peroxides. Studies also report data suggesting that acetaminophen selectively blocks a variant of the COX enzyme that is different from the known variants COX-1 and COX-2. This enzyme is now referred to as COX-3. Its exact mechanism of action is still poorly understood, but future research may provide further insight into how it works.

Pharmacology

Acetaminophen (USAN) or Paracetamol (INN) is a popular analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains. It is a major ingredient in numerous cold and flu medications and many prescription analgesics. It is extremely safe in standard doses, but because of its wide availability, deliberate or accidental overdoses are not uncommon. Acetaminophen, unlike other common analgesics such as aspirin and ibuprofen, has no anti-inflammatory properties or effects on platelet function, and so it is not a member of the class of drugs known as non-steroidal anti-inflammatory drugs or NSAIDs. In normal doses acetaminophen does not irritate the lining of the stomach nor affect blood coagulation, the kidneys, or the fetal ductus arteriosus (as NSAIDs can). Like NSAIDs and unlike opioid analgesics, acetaminophen does not cause euphoria or alter mood in any way. Acetaminophen and NSAIDs have the benefit of being completely free of problems with addiction, dependence, tolerance and withdrawal. Acetaminophen is used on its own or in combination with pseudoephedrine, dextromethorphan, chlorpheniramine, diphenhydramine, doxylamine, codeine, hydrocodone, or oxycodone.

Food Interactions

Avoid alcohol (may increase risk of hepatotoxicity). Take without regard to meals.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Approximately 90 to 95% of a dose is metabolized in the liver via the cytochrome P450 enzyme pathways (primarily by conjugation with glucuronic acid, sulfuric acid, and cysteine). An intermediate metabolite is hepatotoxic and most likely nephrotoxic and can accumulate after the primary metabolic pathways have been saturated.

Protein Binding

25%

Absorption

Rapid and almost complete

Half Life

1 to 4 hours

Toxicity

Oral, mouse: LD₅₀ = 338 mg/kg; Oral, rat: LD₅₀ = 1944 mg/kg. Acetaminophen is metabolized primarily in the liver, where most of it is converted to inactive compounds by conjugation with sulfate and glucuronide, and then excreted by the kidneys. Only a small portion is metabolized via the hepatic cytochrome P450 enzyme system. The toxic effects of acetaminophen are due to a minor alkylating metabolite (N-acetyl-p-benzo-quinone imine), not acetaminophen itself nor any of the major metabolites. This toxic metabolite reacts with sulfhydryl groups. At usual doses, it is quickly detoxified by combining irreversibly with the sulfhydryl group of glutathione to produce a non-toxic conjugate that is eventually excreted by the kidneys. The toxic dose of paracetamol is highly variable. In adults, single doses above 10 grams or 140 mg/kg have a reasonable likelihood of causing toxicity. In adults, single doses of more than 25 grams have a high risk of lethality.

Chemical Properties

Chemical Formula:

C₈H₉NO₂

SMILES Code:

CC(=O)Nc1ccc(cc1)O

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

151.1626 / 151.0633

Curated Information

The following genes are in curated knowledge about this drug.

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Metabolizing Enzymes

• CYP1A2
• CYP2E1

Drug Targets

• PTGS2
• PTGS1

PharmGKB Curated Pathways

• Celecoxib Pathway

BioCarta Pathways†

• mechanism of acetaminophen activity and toxicity - (BioCarta via Pathway Interaction Database)

Curated Information

The following drugs are in curated knowledge about this drug.

	Drug	Relationship	Evidence
	acetylcysteine	CO	Publications
	tropisetron	PD	Publications
	warfarin		Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

acenocoumarol	Increases the anticoagulant effect
anisindione	Acetaminophen increases the anticoagulant effect
dicumarol	Increases the anticoagulant effect
imatinib	Increased hepatic toxicity of both agents
isoniazid	Risk of hepatotoxicity
warfarin	Acetaminophen increases the anticoagulant effect

Curated Information

The following diseases are in curated knowledge about this drug.

	Disease	Relationship	Evidence
	Adenomatous Polyposis Coli	PD PK	Pathways
	Arthritis, Rheumatoid	PD PK	Pathways
	Asthma	PD PK	Pathways
	Bradycardia	CO    PK	Publications
	Colonic Neoplasms	PD PK	Pathways
	Drug Toxicity	PK FA GN	Publications
	Dysmenorrhea	PD PK	Pathways
	Fever	PD PK	Pathways
	Gastroschisis	PK	Publications
	Inflammation	PD PK	Pathways
	Liver Failure, Acute	PK	Publications
	Osteoarthritis	PD PK	Pathways
	Pain	PD PK	Publications, Pathways
	Spondylitis, Ankylosing	PD PK	Pathways
	Toxic liver disease	PD PK FA GN	Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

1. Physicochemical determinants of human renal clearance

LinkOuts

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.