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                    ÄÚÀ̵§Á¤  COIDEN TAB.[Caffeine anhydrous , Chlorpheniramine Maleate , Dipotassium glycyrrhizinate , Phenylpropanolamine HCl]  
                    
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[Drugbank ÀÇ ¼ººÐÁ¤º¸¿¶÷] [Caffeine][Chlorpheniramine][Phenylpropanolamine]
      
      
      
      
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    Chlorpheniramine¿¡ ´ëÇÑ µ¶¼ºÁ¤º¸ : Á¤º¸º¸±â 
Potassium¿¡ ´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 | 
    
       Caffeine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Caffeine stimulates medullary, vagal, vasomotor, and respiratory centers, promoting bradycardia, vasoconstriction, and increased respiratory rate. This action was previously believed to be due primarily to increased intracellular cyclic 3¡Ç,5¡Ç-adenosine monophosphate (cyclic AMP) following inhibition of phosphodiesterase, the enzyme that degrades cyclic AMP. It is now thought that xanthines such as caffeine act as agonists at adenosine-receptors within the plasma membrane of virtually every cell. As adenosine acts as an autocoid, inhibiting the release of neurotransmitters from presynaptic sites but augmenting the actions of norepinephrine or angiotensin, antagonism of adenosine receptors promotes neurotransmitter release. This explains the stimulatory effects of caffeine. Blockade of the adenosine A1 receptor in the heart leads to the accelerated, pronounced "pounding" of the heart upon caffeine intake.
  Chlorpheniramine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.
  Phenylpropanolamine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Phenylpropanolamine acts directly on alpha- and, to a lesser degree, beta-adrenergic receptors in the mucosa of the respiratory tract. Stimulation of alpha-adrenergic receptors produces vasoconstriction, reduces tissue hyperemia, edema, and nasal congestion, and increases nasal airway patency. PPA indirectly stimulates beta-receptors, producing tachycardia and a positive inotropic effect. 
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    | Pharmacology | 
     
       Caffeine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Caffeine, a naturally occurring xanthine derivative like theobromine and the bronchodilator theophylline, is used as a CNS stimulant, mild diuretic, and respiratory stimulant (in neonates with apnea of prematurity). Often combined with analgesics or with ergot alkaloids, caffeine is used to treat migraine and other headache types. Over the counter, caffeine is available to treat drowsiness or mild water-weight gain.
  Chlorpheniramine¿¡ ´ëÇÑ Pharmacology Á¤º¸ In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine, is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.
  Phenylpropanolamine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Phenylpropanolamine (PPA), a sympathomimetic agent structurally similar to pseudoephedrine, is used to treat nasal congestion. Phenylpropanolamine is found in appetite suppressant formulations and with guaifenesinin in cough-cold formulations. In 2000, the FDA requested that all drug companies discontinue marketing products containing phenylpropanolamine, due to an increased risk of hemorrhagic stroke in women who used phenylpropanolamine. 
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    | Metabolism | 
    
       Caffeine¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 1A2 (CYP1A2)
  Chlorpheniramine¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 3A4 (CYP3A4)Cytochrome P450 2D6 (CYP2D6)
  Phenylpropanolamine¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Monoamine oxidase type A (MAO-A) 
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    | Protein Binding | 
    
       Caffeine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Low (25 to 36%).
  Chlorpheniramine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 72%
  Phenylpropanolamine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Not Available 
     | 
   
  
   
    | Half-life | 
    
       Caffeine¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 3 to 7 hours in adults, 65 to 130 hours in neonates
  Chlorpheniramine¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 21-27 hours
  Phenylpropanolamine¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 2.1 to 3.4 hours. 
     | 
   
  
   
    | Absorption | 
    
       Caffeine¿¡ ´ëÇÑ Absorption Á¤º¸ Readily absorbed after oral or parenteral administration. The peak plasma level for caffeine range from 6-10mg/L and the mean time to reach peak concentration ranged from 30 minutes to 2 hours.
  Chlorpheniramine¿¡ ´ëÇÑ Absorption Á¤º¸ Well absorbed in the gastrointestinal tract.
  Phenylpropanolamine¿¡ ´ëÇÑ Absorption Á¤º¸ Reduced bioavailability (about 38%) from gastrointestinal tract because of first pass metabolism by monoamine oxidase in the stomach and liver. 
     | 
   
  
   
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       Phenylpropanolamine HClÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
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	 -  »ýü³»ÀÌ¿ë·ü : °ÅÀÇ 100%
 
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	 -  ¹Ý°¨±â : 4.6-6.6 ½Ã°£ 
 
	 -  ¼Ò½Ç : ÁÖ·Î ¹Ìº¯Èü·Î¼(80-90%) ´¢¸¦ ÅëÇØ ¹è¼³µÊ
  
 Caffeine anhydrousÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
	-  Èí¼ö : °æ±¸ : ½Å¼ÓÇϰÔ, ¿ÏÀüÈ÷ Èí¼öµÊ (99%)
 
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 -  ½Å»ý¾Æ : 0.92 L/kg
		
 -  ¼ºÀÎ : 0.58 L/kg
		
  
 	 -  ´Ü¹é°áÇÕ : 15-35%
	
 -  ´ë»ç : ¼ºÀÎ : °ÅÀÇ ´ëºÎºÐÀÌ °£¿¡¼ ´ë»çµÇ¸ç, Å»¸ÞƿȵǾî paraxanthine (72%), theobromine (20%), theophylline (8%)À¸·Î ´ë»çµÊ
	
 
  -  ¹Ý°¨±â : 
   		
		-  ¹Ì¼÷¾Æ : 65-103 ½Ã°£
	   	
 -  ¿Ï¼÷¾Æ : 82½Ã°£
   		
 -  3-4°³¿ù ¿µ¾Æ : 14.4 ½Ã°£
   		
 -  5-6°³¿ù ¿µ¾Æ : 2.6 ½Ã°£
   		
 -  ¼ºÀÎ : 3-7.5 ½Ã°£ (Æò±Õ 4.9 ½Ã°£)
   		
 -  ÀӽźΠ: 18½Ã°£±îÁö
		
  
	
  -  Ç÷ÁßÃÖ°í³óµµ µµ´Þ½Ã°£ : 15-45ºÐ
	
 
  -  ¼Ò½Ç : 
   	
		-  ¼ºÀÎ : ¹Ìº¯Èü·Î ½Å¹è¼³µÇ´Â ¾çÀº 0.5-3.5%
   		
 -  ½Å»ý¾Æ : °ÅÀÇ ´ëºÎºÐ ¹Ìº¯Èü·Î ½Å¹è¼³µÊ
		
   Chlorpheniramine MaleateÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
	- ´Ü¹é°áÇÕ : 69-72%
	
 - ´ë»ç : °£´ë»ç
	
 - ¹Ý°¨±â : 20-24 ½Ã°£
	
 - ¼Ò½Ç : ´ë»çü, ¾à¹°(3-4%)ÀÌ ½Å¹è¼³µÇ¸ç, 48½Ã°£³»¿¡ ÀüüÀÇ 35%°¡ ¼Ò½ÇµÈ´Ù.
  
       | 
   
  
   
    | Biotransformation | 
    
       Caffeine¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic cytochrome P450 1A2 (CYP 1A2) is involved in caffeine biotransformation. About 80% of a dose of caffeine is metabolized to paraxanthine (1,7-dimethylxanthine), 10% to theobromine (3,7-dimethylxanthine), and 4% to theophylline (1,3-dimethylxanthine).
  Chlorpheniramine¿¡ ´ëÇÑ Biotransformation Á¤º¸ Primarily hepatic via Cytochrome P450 (CYP450) enzymes.
  Phenylpropanolamine¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic 
     | 
   
  
   
    | Toxicity | 
    
       Caffeine¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50=127 mg/kg (orally in mice)
  Chlorpheniramine¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50 = 306 mg/kg in humans, mild reproductive toxin to women of childbearing age.
  Phenylpropanolamine¿¡ ´ëÇÑ Toxicity Á¤º¸ May induce ventricular extrasystoles and short paroxysms of ventricular tachycardia, a sensation of fullness in the head and tingling of the extremities; LD50=1490mg/kg (orally in rat) 
     | 
   
  
   
    | Drug Interactions | 
    
       Caffeine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available
  Chlorpheniramine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Donepezil	Possible antagonism of actionGalantamine	Possible antagonism of actionRivastigmine	Possible antagonism of actionEthotoin	The antihistamine increases the effect of hydantoinFosphenytoin	The antihistamine increases the effect of hydantoinMephenytoin	The antihistamine increases the effect of hydantoinPhenytoin	The antihistamine increases the effect of hydantoin
  Phenylpropanolamine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Acetophenazine	Decreased anorexic effect, may increase psychotic symptomsChlorpromazine	Decreased anorexic effect, may increase psychotic symptomsEthopropazine	Decreased anorexic effect, may increase psychotic symptomsFluphenazine	Decreased anorexic effect, may increase psychotic symptomsMethotrimeprazine	Decreased anorexic effect, may increase psychotic symptomsGuanethidine	The agent decreases the effect of guanethidineMesoridazine	Decreased anorexic effect, may increase psychotic symptomsThioridazine	Decreased anorexic effect, may increase psychotic symptomsMethdilazine	Decreased anorexic effect, may increase psychotic symptomsTrimeprazine	Decreased anorexic effect, may increase psychotic symptomsPropericiazine	Decreased anorexic effect, may increase psychotic symptomsPerphenazine	Decreased anorexic effect, may increase psychotic symptomsProchlorperazine	Decreased anorexic effect, may increase psychotic symptomsPromazine	Decreased anorexic effect, may increase psychotic symptomsPromethazine	Decreased anorexic effect, may increase psychotic symptomsPropiomazine	Decreased anorexic effect, may increase psychotic symptomsThiethylperazine	Decreased anorexic effect, may increase psychotic symptomsTrifluoperazine	Decreased anorexic effect, may increase psychotic symptomsTriflupromazine	Decreased anorexic effect, may increase psychotic symptomsMoclobemide	Moclobemide increases the sympathomimetic effectAmitriptyline	The tricyclic increases the sympathomimetic effectAmoxapine	The tricyclic increases the sympathomimetic effectBromocriptine	The sympathomimetic increases the toxicity of bromocriptineClomipramine	The tricyclic increases the sympathomimetic effectDesipramine	The tricyclic increases the sympathomimetic effectDoxepin	The tricyclic increases the sympathomimetic effectImipramine	The tricyclic increases the sympathomimetic effectNortriptyline	The tricyclic increases the sympathomimetic effectProtriptyline	The tricyclic increases the sympathomimetic effectTrimipramine	The tricyclic increases the sympathomimetic effectVenlafaxine	Risk of serotoninergic syndromeFluvoxamine	Risk of serotoninergic syndromeParoxetine	Risk of serotoninergic syndromeFluoxetine	Risk of serotoninergic syndromeAlseroxylon	Increased arterial pressureDeserpidine	Increased arterial pressureIsocarboxazid	Increased arterial pressureLinezolid	Possible increase of arterial pressureTranylcypromine	Increased arterial pressureRasagiline	Increased arterial pressureReserpine	Increased arterial pressurePhenelzine	Increased arterial pressurePargyline	Increased arterial pressureMethyldopa	Increased arterial pressureMidodrine	Increased arterial pressure 
     | 
   
  
   
    CYP450  Drug Interaction | 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] Chlorpheniramine¿¡ ´ëÇÑ P450 table
  SUBSTRATES 
CYP 2D6 
Beta Blockers: 
S-metoprolol 
propafenone 
timolol 
Antidepressants: 
amitriptyline 
clomipramine 
desipramine 
imipramine 
paroxetine 
Antipsychotics: 
haloperidol 
risperidone 
thioridazine 
aripiprazole 
codeine 
dextromethorphan 
duloxetine 
flecainide 
mexiletine 
ondansetron 
tamoxifen 
tramadol 
venlafaxine 
 INHIBITORS 
CYP 2D6 
amiodarone 
buproprion 
**chlorpheniramine** 
cimetidine 
clomipramine 
duloxetine 
fluoxetine 
haloperidol 
methadone 
mibefradil 
paroxetine 
quinidine 
ritonavir 
 INDUCERS 
CYP 2D6 
N/A 
 
     | 
   
  
   
    | Food Interaction | 
    
       Chlorpheniramine¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take with food.Avoid alcohol.
  Phenylpropanolamine¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take without regard to meals.Limit caffeine intake. 
     | 
   
  
   
    | Drug Target | 
    
      
      [Drug Target]
     | 
   
  
   
    | SNP Á¤º¸ | 
    
      Name:Caffeine (DB00201)
 Interacting Gene/Enzyme:Cytochrome P450 1A2 (Gene symbol = CYP1A2) Swissprot P05177
 SNP(s):rs762551 (C allele)
 Effect:Myocardial infarction
 Reference(s):Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H: Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA. 2006 Mar 8;295(10):1135-41. [PubMed] 
     | 
   
  
   
    | Description | 
    
       Caffeine¿¡ ´ëÇÑ Description Á¤º¸ A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine&
  Chlorpheniramine¿¡ ´ëÇÑ Description Á¤º¸ A histamine H1 antagonist used in allergic reactions, hay fever, rhinitis, urticaria, and asthma. It has also been used in veterinary applications. One of the most widely used of the classical antihistaminics, it generally causes less drowsiness and sedation than promethazine. [PubChem]
  Phenylpropanolamine¿¡ ´ëÇÑ Description Á¤º¸ Phenylpropanolamine has been withdrawn in Canada. In November 2000, the Food and Drug Administration (FDA) issued a public health advisory against the use of the drug. 
     | 
   
  
   
    | Dosage Form | 
    
       Caffeine¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Capsule	OralElixir	OralLiquid	OralPill	OralSolution	OralSolution / drops	OralSuppository	RectalSuspension	OralSyrup	OralTablet	OralTablet, extended release	Oral
  Chlorpheniramine¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Syrup	OralTablet	OralTablet, extended release	Oral
  Phenylpropanolamine¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Not Available 
     | 
   
  
   
    | Drug Category | 
    
       Caffeine¿¡ ´ëÇÑ Drug_Category Á¤º¸ Anorexigenic AgentsCentral Nervous System StimulantsPhosphodiesterase Inhibitors
  Chlorpheniramine¿¡ ´ëÇÑ Drug_Category Á¤º¸ Anti-Allergic AgentsAntihistaminesAntipruriticsHistamine H1 Antagonists
  Phenylpropanolamine¿¡ ´ëÇÑ Drug_Category Á¤º¸ Adrenergic alpha-AgonistsAppetite DepressantsNasal DecongestantsSympathomimetics 
     | 
   
  
   
    | Smiles String Canonical | 
    
       Caffeine¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CN1C=NC2=C1C(=O)N(C)C(=O)N2C
  Chlorpheniramine¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CN(C)CCC(C1=CC=C(Cl)C=C1)C1=CC=CC=N1
  Phenylpropanolamine¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CC(N)C(O)C1=CC=CC=C1 
     | 
   
  
   
    | Smiles String Isomeric | 
    
       Caffeine¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CN1C=NC2=C1C(=O)N(C)C(=O)N2C
  Chlorpheniramine¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CN(C)CC[C@H](C1=CC=C(Cl)C=C1)C1=CC=CC=N1
  Phenylpropanolamine¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ C[C@@H](N)[C@@H](O)C1=CC=CC=C1 
     | 
   
  
   
    | InChI Identifier | 
    
       Caffeine¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C8H10N4O2/c1-10-4-9-6-5(10)7(13)12(3)8(14)11(6)2/h4H,1-3H3
  Chlorpheniramine¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C16H19ClN2/c1-19(2)12-10-15(16-5-3-4-11-18-16)13-6-8-14(17)9-7-13/h3-9,11,15H,10,12H2,1-2H3
  Phenylpropanolamine¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C9H13NO/c1-7(10)9(11)8-5-3-2-4-6-8/h2-7,9,11H,10H2,1H3/t7-,9-/m1/s1 
     | 
   
  
   
    | Chemical IUPAC Name | 
    
       Caffeine¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 1,3,7-trimethylpurine-2,6-dione
  Chlorpheniramine¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 3-(4-chlorophenyl)-N,N-dimethyl-3-pyridin-2-ylpropan-1-amine
  Phenylpropanolamine¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ (1S,2R)-2-amino-1-phenylpropan-1-ol 
     | 
   
  
   
    | Drug-Induced Toxicity Related Proteins | 
    
      CAFFEINE ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:Metallothionein Drug:caffeine Toxicity:hepatotoxicity.  [¹Ù·Î°¡±â] MALEATE ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:Intercellular adhesion molecule 1  Drug:maleate Toxicity:hepatic injury.  [¹Ù·Î°¡±â] 
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