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[Acetaminophen]
> [Acetaminophen] CAS number/103-90-2 ATC code/N02BE01 PubChem/1983 DrugBank/APRD00252 Formula/C8H9NO2 Mol. mass/151.17 g/mol Bioavailability/almost 100% Metabolism/90 to 95% Hepatic Excretion/Renal Pregnancy cat./
A(AU) B(US) safe Legal status/
Unscheduled(AU) GSL(UK) OTC(US) Routes/Oral, rectal, intravenous Solubility/1.4 g/100 ml or 14 mg/mL (20 °C)
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Acetaminophen¿¡ ´ëÇÑ µ¶¼ºÁ¤º¸ : Á¤º¸º¸±â
Ãâó: ±¹¸³µ¶¼º°úÇпø µ¶¼º¹°ÁúÁ¤º¸DB : http://www.nitr.go.kr/nitr/contents/m134200/view.do |
| Mechanism of Action |
Acetaminophen¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ 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.
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| Pharmacology |
Acetaminophen¿¡ ´ëÇÑ Pharmacology Á¤º¸ 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.
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| Metabolism |
Acetaminophen¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 1A2 (CYP1A2)Cytochrome P450 2E1 (CYP2E1)
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| Half-life |
Acetaminophen¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 1 to 4 hours
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| Absorption |
Acetaminophen¿¡ ´ëÇÑ Absorption Á¤º¸ Rapid and almost complete
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| Pharmacokinetics |
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| Biotransformation |
Acetaminophen¿¡ ´ëÇÑ Biotransformation Á¤º¸ 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.
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| Toxicity |
Acetaminophen¿¡ ´ëÇÑ Toxicity Á¤º¸ 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.
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| Drug Interactions |
Acetaminophen¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Anisindione Acetaminophen increases the anticoagulant effectWarfarin Acetaminophen increases the anticoagulant effectImatinib Increased hepatic toxicity of both agentsIsoniazid Risk of hepatotoxicityDicumarol Acetaminophen increases the anticoagulant effectDicumarol Increases the anticoagulant effectAcenocoumarol Increases the anticoagulant effect
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CYP450 Drug Interaction |
[CYP450 TableÁ÷Á¢Á¶È¸] Acetaminophen¿¡ ´ëÇÑ P450 table
SUBSTRATES
CYP 2E1
**acetaminophen**
chlorzoxazone
ethanol
INHIBITORS
CYP 2E1
disulfiram
INDUCERS
CYP 2E1
ethanol
isoniazid
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| Food Interaction |
Acetaminophen¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take without regard to meals.Avoid alcohol (may increase risk of hepatotoxicity).
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| Drug Target |
[Drug Target]
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| Description |
Acetaminophen¿¡ ´ëÇÑ Description Á¤º¸ 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]
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| Drug Category |
Acetaminophen¿¡ ´ëÇÑ Drug_Category Á¤º¸ Analgesics, Non-NarcoticAntipyretics
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| Smiles String Canonical |
Acetaminophen¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CC(=O)NC1=CC=C(O)C=C1
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| Smiles String Isomeric |
Acetaminophen¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CC(=O)NC1=CC=C(O)C=C1
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| InChI Identifier |
Acetaminophen¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C8H9NO2/c1-6(10)9-7-2-4-8(11)5-3-7/h2-5,11H,1H3,(H,9,10)/f/h9H
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| Chemical IUPAC Name |
Acetaminophen¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ N-(4-hydroxyphenyl)acetamide
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| Drug-Induced Toxicity Related Proteins |
ACETAMINOPHEN ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:Alpha-2A adrenergic receptor Drug:acetaminophen Toxicity:hepatic injury . [¹Ù·Î°¡±â] Replated Protein:Myeloperoxidase Drug:acetaminophen Toxicity:respiratory burst. [¹Ù·Î°¡±â] Replated Protein:Glucose-6-phosphate 1-dehydrogenase Drug:acetaminophen Toxicity:drug-induced hemolysis. [¹Ù·Î°¡±â] Replated Protein:Ornithine decarboxylase Drug:acetaminophen Toxicity:hepatotoxicity. [¹Ù·Î°¡±â] Replated Protein:Lactate dehydrogenase Drug:acetaminophen Toxicity:hepatotoxicity. [¹Ù·Î°¡±â] Replated Protein:Transcription factor AP-1(JUN) Drug:acetaminophen Toxicity:hepatotoxicity. [¹Ù·Î°¡±â] Replated Protein:Haptoglobin Drug:acetaminophen Toxicity:drug-induced hemolysis. [¹Ù·Î°¡±â] Replated Protein:Alanine aminotransferase Drug:acetaminophen Toxicity:hepatotoxicity. [¹Ù·Î°¡±â] Replated Protein:Beta-glucuronidase Drug:acetaminophen Toxicity:hepatotoxin-induced effects. [¹Ù·Î°¡±â] Replated Protein:CYP2E1 Drug:Acetaminophen Toxicity:idiosyncratic hepatotoxicity. [¹Ù·Î°¡±â] Replated Protein:Cytochrome P450 2E1 Drug:acetaminophen Toxicity:hepatotoxicity. [¹Ù·Î°¡±â] Replated Protein:Sulfotransferase family cytosolic Drug:acetaminophen Toxicity:chronic hypoxia. [¹Ù·Î°¡±â] Replated Protein:Cytochrome P450 3A4 Drug:acetaminophen Toxicity:hepatotoxicity. [¹Ù·Î°¡±â] Replated Protein:Caspase recruitment domain-containing protein Drug:acetaminophen Toxicity:hepatotoxicity. [¹Ù·Î°¡±â] Replated Protein:Cytochrome P450 1A2 Drug:acetaminophen Toxicity:hepatotoxicity. [¹Ù·Î°¡±â] ACETAMINOPHEN (APAP) ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:Cytochrome P450 Drug:acetaminophen (APAP) Toxicity:renal functional changes, strain-dependent histopathological changes. [¹Ù·Î°¡±â]
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The database contains the following fields: The generic name of each chemical For module A10 (liver enzyme composite module): Overall activity category for each compound (A for active, M for marginally active, or I for inactive) based on the number of active and marginally active scores for each compound at the five individual endpoints (see research article for full description of method) Number of endpoints at which each compound is marginally active (M) Number of endpoints at which each compound is active (A) For modules A11 to A15 (alkaline phosphatase increased, SGOT increased, SGPT increased, LDH increased, and GGT increased, respectively): Overall activity category for each compound (A for active, M for marginally active, or I for inactive) based on the RI and ADR values (see the research article for full description of method) Number of ADR reports for each compound, given as <4 or ¡Ã4 Reporting Index value for each compound, except where no shipping units were available (NSU) Group 1 comprises of compounds for which ADR data were available for the first five years of marketing, so when no ADR reports were listed during this period the compounds were evaluated as inactive. Group 2 comprises of compounds for which a 'steady state' period of ADR data were available (1992-1996). In cases where no ADR reports were filed during this period, the compounds were scored as 'NA' (data not available) since they may have had one or more ADR reports during their first five years of marketing which should not be negated by a lack of ADR reports during the steady-state period. ACETAMINOPHEN[Composite Activity](Score) A(Marginal) 3(Active) 2[Alkaline Phosphatase Increase](Activity Score) M(Number of Rpts) ¡Ã4(Index value) NSU[SGOT Increase](Activity Score) A(Number of Rpts) ¡Ã4(Index value) NSU[SGPT Increase](Activity Score) A(Number of Rpts) ¡Ã4(Index value) NSU[LDH Increase](Activity Score) M(Number of Rpts) ¡Ã4(Index value) NSU[GGT Increase](Activity Score) M(Number of Rpts) ¡Ã4(Index value) NSU
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