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    | 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.
  Chlorzoxazone¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Chlorzoxazone inhibits degranulation of mast cells, subsequently preventing the release of histamine and slow-reacting substance of anaphylaxis (SRS-A), mediators of type I allergic reactions. Chlorzoxazone also may reduce the release of inflammatory leukotrienes. Chlorzoxazone may act by inhibiting calcium influx. 
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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.
  Chlorzoxazone¿¡ ´ëÇÑ Pharmacology Á¤º¸ Chlorzoxazone, a synthetic compound, inhibits antigen-induced bronchospasms and, hence, is used to treat asthma and allergic rhinitis. Chlorzoxazone is used as an ophthalmic solution to treat conjunctivitis and is taken orally to treat systemic mastocytosis and ulcerative colitis. Chlorzoxazone is also a centrally-acting agent for painful musculoskeletal conditions. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex a.c. involved in producing and maintaining skeletal muscle spasm of varied etiology. The clinical result is a reduction of the skeletal muscle spasm with relief of pain and increased mobility of the involved muscles. 
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    | Metabolism | 
    
       Acetaminophen¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 1A2 (CYP1A2)Cytochrome P450 2E1 (CYP2E1)
  Chlorzoxazone¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 2E1 (CYP2E1)Cytochrome P450 2C19 (CYP2C19)Cytochrome P450 1A2 (CYP1A2)Cytochrome P450 2A6 (CYP2A6)Cytochrome P450 1A1 (CYP1A1)Cytochrome P450 2D6 (CYP2D6) 
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    | Protein Binding | 
    
       Chlorzoxazone¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 13-18% 
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    | Half-life | 
    
       Acetaminophen¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 1 to 4 hours
  Chlorzoxazone¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ Not Available 
     | 
   
  
   
    | Absorption | 
    
       Acetaminophen¿¡ ´ëÇÑ Absorption Á¤º¸ Rapid and almost complete
  Chlorzoxazone¿¡ ´ëÇÑ Absorption Á¤º¸ Not Available 
     | 
   
  
   
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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.
  Chlorzoxazone¿¡ ´ëÇÑ Biotransformation Á¤º¸ Chlorzoxazone is rapidly metabolized in the liver and is excreted in the urine, primarily in a conjugated form as the glucuronide. 
     | 
   
  
   
    | 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.
  Chlorzoxazone¿¡ ´ëÇÑ Toxicity Á¤º¸ Oral, mouse: LD50 = 440 mg/kg; Oral, rat: LD50 = 763 mg/kg; Symptoms of overdose include diarrhea, dizziness, drowsiness, headache, light-headedness, nausea, and vomiting. 
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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
  Chlorzoxazone¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Disulfiram	Disulfiram increases chlorzoxazone levels 
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    CYP450  Drug Interaction | 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] Chlorzoxazone¿¡ ´ëÇÑ P450 table Acetaminophen¿¡ ´ëÇÑ P450 table
  SUBSTRATES 
CYP 2E1 
**acetaminophen** 
chlorzoxazone 
ethanol 
 INHIBITORS 
CYP 2E1 
disulfiram 
 INDUCERS 
CYP 2E1 
ethanol 
isoniazid 
  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).
  Chlorzoxazone¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take without regard to meals.Avoid alcohol. 
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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]
  Chlorzoxazone¿¡ ´ëÇÑ Description Á¤º¸ A centrally acting central muscle relaxant with sedative properties. It is claimed to inhibit muscle spasm by exerting an effect primarily at the level of the spinal cord and subcortical areas of the brain. (From Martindale, The Extra Pharmacopoea, 30th ed, p1202) 
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    | Dosage Form | 
    
       Acetaminophen¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Capsule	OralElixir	OralLiquid	OralSolution	OralSolution / drops	OralSuppository	RectalSuspension	OralSyrup	OralTablet	OralTablet, effervescent	OralTablet, extended release	Oral
  Chlorzoxazone¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Capsule	Oral 
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    | Drug Category | 
    
       Acetaminophen¿¡ ´ëÇÑ Drug_Category Á¤º¸ Analgesics, Non-NarcoticAntipyretics
  Chlorzoxazone¿¡ ´ëÇÑ Drug_Category Á¤º¸ Muscle Relaxants, Central 
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    | Smiles String Canonical | 
    
       Acetaminophen¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CC(=O)NC1=CC=C(O)C=C1
  Chlorzoxazone¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ ClC1=CC2=C(OC(=O)N2)C=C1 
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    | Smiles String Isomeric | 
    
       Acetaminophen¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CC(=O)NC1=CC=C(O)C=C1
  Chlorzoxazone¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ ClC1=CC2=C(OC(=O)N2)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
  Chlorzoxazone¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C7H4ClNO2/c8-4-1-2-6-5(3-4)9-7(10)11-6/h1-3H,(H,9,10)/f/h9H 
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    | Chemical IUPAC Name | 
    
       Acetaminophen¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ N-(4-hydroxyphenyl)acetamide
  Chlorzoxazone¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 5-chloro-3H-1,3-benzoxazol-2-one 
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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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                          ÀüÈ: 02-3486-1061 ¤Ó À̸ÞÀÏ: webmaster@druginfo.co.kr
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