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Namespace Prefixes

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Statements

Subject Item
n2:DB00316
rdf:type
n3:Drug
n3:description
Acetaminophen, also known as paracetamol, is commonly used for its analgesic and antipyretic effects. Its therapeutic effects are similar to salicylates, but it lacks anti-inflammatory, antiplatelet, and gastric ulcerative effects.
n3:dosage
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n3:generalReferences
# Kis B, Snipes JA, Busija DW: Acetaminophen and the cyclooxygenase-3 puzzle: sorting out facts, fictions, and uncertainties. J Pharmacol Exp Ther. 2005 Oct;315(1):1-7. Epub 2005 May 6. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/15879007 # Aronoff DM, Oates JA, Boutaud O: New insights into the mechanism of action of acetaminophen: Its clinical pharmacologic characteristics reflect its inhibition of the two prostaglandin H2 synthases. Clin Pharmacol Ther. 2006 Jan;79(1):9-19. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/16413237 # Bertolini A, Ferrari A, Ottani A, Guerzoni S, Tacchi R, Leone S: Paracetamol: new vistas of an old drug. CNS Drug Rev. 2006 Fall-Winter;12(3-4):250-75. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/17227290 # Graham GG, Scott KF: Mechanism of action of paracetamol. Am J Ther. 2005 Jan-Feb;12(1):46-55. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/15662292 # Ohki S, Ogino N, Yamamoto S, Hayaishi O: Prostaglandin hydroperoxidase, an integral part of prostaglandin endoperoxide synthetase from bovine vesicular gland microsomes. J Biol Chem. 1979 Feb 10;254(3):829-36. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/104998 # Bertolini A, Ferrari A, Ottani A, Guerzoni S, Tacchi R, Leone S: Paracetamol: new vistas of an old drug. CNS Drug Rev. 2006 Fall-Winter;12(3-4):250-75. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/17227290 # Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, Simmons DL: COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13926-31. Epub 2002 Sep 19. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/12242329 # Adjei AA, Gaedigk A, Simon SD, Weinshilboum RM, Leeder JS: Interindividual variability in acetaminophen sulfation by human fetal liver: implications for pharmacogenetic investigations of drug-induced birth defects. Birth Defects Res A Clin Mol Teratol. 2008 Mar;82(3):155-65. doi: 10.1002/bdra.20535. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/18232020 # Hazai E, Vereczkey L, Monostory K: Reduction of toxic metabolite formation of acetaminophen. Biochem Biophys Res Commun. 2002 Mar 8;291(4):1089-94. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11866476
n3:group
approved
n3:halfLife
1 to 4 hours
n3:indication
For temporary relief of fever, minor aches, and pains.
n3:manufacturer
n21:271B518A-363D-11E5-9242-09173F13E4C5 n21:271B518B-363D-11E5-9242-09173F13E4C5 n21:271B5188-363D-11E5-9242-09173F13E4C5 n21:271B5189-363D-11E5-9242-09173F13E4C5 n21:271B5186-363D-11E5-9242-09173F13E4C5 n21:271B5187-363D-11E5-9242-09173F13E4C5 n21:271B5184-363D-11E5-9242-09173F13E4C5 n21:271B5185-363D-11E5-9242-09173F13E4C5 n21:271B5182-363D-11E5-9242-09173F13E4C5 n21:271B5183-363D-11E5-9242-09173F13E4C5 n21:271B5181-363D-11E5-9242-09173F13E4C5
owl:sameAs
n20:DB00316 n30:DB00316
dcterms:title
Acetaminophen
adms:identifier
n9:Acetaminophen n12:D00217 n13:50580-508-20 n14:C06804 n15:1906 n16:DB00316 n17:26197 n18:2386 n27:46506142 n28:PA448015 n29:1983
n3:mechanismOfAction
Acetaminophen is thought to act primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 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. The antipyretic properties of acetaminophen are likely due to direct effects on the heat-regulating centres of the hypothalamus resulting in peripheral vasodilation, sweating and hence heat dissipation.
n3:packager
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n3:patent
n25:RE39221
n3:routeOfElimination
Approximately 80% of acetaminophen is excreted in the urine after conjugation and about 3% is excreted unchanged.
n3:synonym
Tylenol N-acetyl-p-aminophenol p-acetamidophenol p-acetaminophenol Acetaminophen 4-(Acetylamino)phenol Paracetamol Acetaminofen p-Acetylaminophenol 4'-hydroxyacetanilide APAP p-hydroxyacetanilide p-hydroxyphenolacetamide Acetaminophene Panadol Acenol 4-acetamidophenol Paracetamolum
n3: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 glucuronic acid and, to a lesser extent, sulfuric acid. Conjugates are then excreted by the kidneys. Only a small portion is excreted in unchanged in urine or oxidized via the hepatic cytochrome P450 enzyme system (CYP2E1). Metabolism via CYP2E1 produces a toxic metabolite, N-acetyl-p-benzoquinoneimine (NAPQI). The toxic effects of acetaminophen are due to NAPQI, not acetaminophen itself nor any of the major metabolites. At therapeutic doses, NAPQI reacts with the sulfhydryl group of glutathione to produce a non-toxic conjugate that is excreted by the kidneys. High doses of acetaminophen may cause glutathione depletion, accumulation of NAPQI and hepatic necrosis. The maximum daily dose of acetaminophen is 4 g. Liver failure has been observed at doses as low as 6 g per day. As such, the maximum daily and single dose of acetaminophen is currently being reviewed in some countries. N-acetyl-cysteine, a precursor of glutathione, may be administered in the event of acetaminophen toxicity.
n5:hasAHFSCode
n6:28-08-92
n3:foodInteraction
Avoid alcohol (may increase risk of hepatotoxicity). Take without regard to meals.
n3:mixture
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n3:proteinBinding
25%
n3:synthesisReference
Jeffrey L. Finnan, Rudolph E. Lisa, Douglass N. Schmidt, "Process for preparing spray dried acetaminophen powder and the powder prepared thereby." U.S. Patent US4710519, issued October, 1975.
n31:hasConcept
n32:M0000115
foaf:page
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n3:IUPAC-Name
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n3:InChI
n11:271B5274-363D-11E5-9242-09173F13E4C5
n3:Molecular-Formula
n11:271B5273-363D-11E5-9242-09173F13E4C5
n3:Molecular-Weight
n11:271B5270-363D-11E5-9242-09173F13E4C5
n3:Monoisotopic-Weight
n11:271B5271-363D-11E5-9242-09173F13E4C5
n3:SMILES
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n3:Water-Solubility
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n3:logP
n11:271B5286-363D-11E5-9242-09173F13E4C5 n11:271B526A-363D-11E5-9242-09173F13E4C5 n11:271B526D-363D-11E5-9242-09173F13E4C5
n3:logS
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n3:pKa
n11:271B5288-363D-11E5-9242-09173F13E4C5
n5:hasATCCode
n26:N02BE01
n3:H-Bond-Acceptor-Count
n11:271B527A-363D-11E5-9242-09173F13E4C5
n3:H-Bond-Donor-Count
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n3:InChIKey
n11:271B5275-363D-11E5-9242-09173F13E4C5
n3:Polar-Surface-Area--PSA-
n11:271B5276-363D-11E5-9242-09173F13E4C5
n3:Polarizability
n11:271B5278-363D-11E5-9242-09173F13E4C5
n3:Refractivity
n11:271B5277-363D-11E5-9242-09173F13E4C5
n3:Rotatable-Bond-Count
n11:271B5279-363D-11E5-9242-09173F13E4C5
n3:absorption
Rapid and almost complete
n3:affectedOrganism
Humans and other mammals
n3:casRegistryNumber
103-90-2
n3:category
n3:containedIn
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n3:Bioavailability
n11:271B5280-363D-11E5-9242-09173F13E4C5
n3:Ghose-Filter
n11:271B5282-363D-11E5-9242-09173F13E4C5
n3:MDDR-Like-Rule
n11:271B5283-363D-11E5-9242-09173F13E4C5
n3:Melting-Point
n11:271B5285-363D-11E5-9242-09173F13E4C5
n3:Number-of-Rings
n11:271B527F-363D-11E5-9242-09173F13E4C5
n3:Physiological-Charge
n11:271B527E-363D-11E5-9242-09173F13E4C5
n3:Rule-of-Five
n11:271B5281-363D-11E5-9242-09173F13E4C5
n3:Traditional-IUPAC-Name
n11:271B526F-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-acidic-
n11:271B527C-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-basic-
n11:271B527D-363D-11E5-9242-09173F13E4C5