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                    ÇØ¼Ò¹Î¿¡½º½Ã·´  HAISOMIN-S SYR.[Chlorpheniramine Maleate , Dextromethorphan HBr , Guaifenesin , Phenylephrine HCl]  
                    
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    | µ¶¼ºÁ¤º¸ | 
    Chlorpheniramine¿¡ ´ëÇÑ µ¶¼ºÁ¤º¸ : Á¤º¸º¸±â 
Dextromethorphan¿¡ ´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 | 
    
       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.
  Dextromethorphan¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Dextromethorphan is an opioid-like drug that binds to and acts as antagonist to the NMDA glutamatergic receptor, it is an agonist to the opioid sigma 1 and sigma 2 receptors, it is also an alpha3/beta4 nicotinic receptor antagonist and targets the serotonin reuptake pump. Dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan.
  Guaifenesin¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Guaifenesin may act as an irritant to gastric vagal receptors, and recruit efferent parasympathetic reflexes that cause glandular exocytosis of a less viscous mucus mixture. Cough may be provoked. This combination may flush tenacious, congealed mucopurulent material from obstructed small airways and lead to a temporary improvement in dyspnea or the work of breathing.
  Phenylephrine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Phenylephrine produces its ophthalmic and systemic actions by acting on alpha 1 adrenergic receptors in the pupillary dilator muscle and the vascular smooth musle, resulting in contraction of the dilator muscle and contraction of the smooth muscle in the arterioles of the conjunctiva and peripheral vasoconstriction. Phenylephrine decreases nasal congestion by acting on alpha 1 adrenergic receptors in the arterioles of the nasal mucosa to produce constriction. 
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    | Pharmacology | 
     
       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.
  Dextromethorphan¿¡ ´ëÇÑ Pharmacology Á¤º¸ Dextromethorphan suppresses the cough reflex by a direct action on the cough center in the medulla of the brain. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist and acts as a non-competitive channel blocker. It is one of the widely used antitussives, and is also used to study the involvement of glutamate receptors in neurotoxicity.
  Guaifenesin¿¡ ´ëÇÑ Pharmacology Á¤º¸ Guaifenesin is an expectorant which increases the output of phlegm (sputum) and bronchial secretions by reducing adhesiveness and surface tension. The increased flow of less viscous secretions promotes ciliary action and changes a dry, unproductive cough to one that is more productive and less frequent. By reducing the viscosity and adhesiveness of secretions, guaifenesin increases the efficacy of the mucociliary mechanism in removing accumulated secretions from the upper and lower airway.
  Phenylephrine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Phenylephrine is a powerful vasoconstrictor. It is used as a mydriatic, nasal decongestant, and cardiotonic agent. Phenylephrine is a postsynaptic alpha-receptor stimulant with little effect on the beta receptors of the heart. Parenteral administration of Phenylephrine causes a rise in systolic and diastolic pressures, cardiac output is slightly decreased and peripheral resistance is considerably increased, most vascular beds are constricted; renal, splanchnic, cutaneous, and limb blood flows are reduced but coronary blood flow is increased. Pulmonary vessels are constricted, and pulmonary arterial pressure is raised. This alpha receptor sympathetic agonist is also used locally because its vasoconstrictor and mydriatic action. 
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    | Metabolism | 
    
       Chlorpheniramine¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 3A4 (CYP3A4)Cytochrome P450 2D6 (CYP2D6)
  Dextromethorphan¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 2D6 (CYP2D6)
  Phenylephrine¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Monoamine oxidase type A (MAO-A) 
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    | Protein Binding | 
    
       Chlorpheniramine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 72%
  Phenylephrine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 95% binding-plasma proteins 
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    | Half-life | 
    
       Chlorpheniramine¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 21-27 hours
  Dextromethorphan¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 3-6 hours
  Guaifenesin¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 1 hour
  Phenylephrine¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 2.1 to 3.4 hours 
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    | Absorption | 
    
       Chlorpheniramine¿¡ ´ëÇÑ Absorption Á¤º¸ Well absorbed in the gastrointestinal tract.
  Dextromethorphan¿¡ ´ëÇÑ Absorption Á¤º¸ Rapidly absorbed from the gastrointestinal tract.
  Guaifenesin¿¡ ´ëÇÑ Absorption Á¤º¸ Rapidly absorbed from the GI tract
  Phenylephrine¿¡ ´ëÇÑ Absorption Á¤º¸ Reduced bioavailability (compared to pseudoephedrine) following oral administration due to significant first-pass metabolism. 
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    | Pharmacokinetics | 
    
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    | Biotransformation | 
    
       Chlorpheniramine¿¡ ´ëÇÑ Biotransformation Á¤º¸ Primarily hepatic via Cytochrome P450 (CYP450) enzymes.
  Dextromethorphan¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic. Rapidly and extensively metabolized to dextrorphan (active metabolite). One well known metabolic catalyst involved is a specific cytochrome P450 enzyme known as 2D6, or CYP2D6.
  Guaifenesin¿¡ ´ëÇÑ Biotransformation Á¤º¸ Rapidly hydrolyzed (60% within seven hours) and then excreted in the urine, with beta-(2-methoxyphenoxy)-lactic acid as its major urinary metabolite.
  Phenylephrine¿¡ ´ëÇÑ Biotransformation Á¤º¸ Oral phenylephrine is extensively metabolised by monoamine oxidase, an enzyme which is present in the stomach and liver. 
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    | Toxicity | 
    
       Chlorpheniramine¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50 = 306 mg/kg in humans, mild reproductive toxin to women of childbearing age.
  Dextromethorphan¿¡ ´ëÇÑ Toxicity Á¤º¸ Not Available
  Guaifenesin¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50 1510 mg/kg (rat, oral)
  Phenylephrine¿¡ ´ëÇÑ Toxicity Á¤º¸ Not Available 
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    | Drug Interactions | 
    
       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
  Dextromethorphan¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Dihydroquinidine barbiturate	Quinidine increases the toxicity of dextromethorphanQuinidine	Quinidine increases the toxicity of dextromethorphanQuinidine barbiturate	Quinidine increases the toxicity of dextromethorphanFluoxetine	Combination associated with possible serotoninergic syndromeIsocarboxazid	Possible severe adverse reactionMemantine	Increased risk of CNS adverse effectsMoclobemide	Increased CNS toxicityParoxetine	Combination associated with possible serotoninergic syndromePhenelzine	Possible severe adverse reactionRasagiline	Possible severe adverse reactionSelegiline	Combination associated with possible serotoninergic syndromeSibutramine	Combination associated with possible serotoninergic syndromeTerbinafine	Terbinafine increases dextromethorphan levelsTranylcypromine	Possible severe adverse reaction
  Guaifenesin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available
  Phenylephrine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Alseroxylon	Increased arterial pressureIsocarboxazid	Increased arterial pressureDeserpidine	Increased arterial pressureGuanethidine	The agent decreases the effect of guanethidineRasagiline	Increased arterial pressureMethyldopa	Increased arterial pressureMidodrine	Increased arterial pressurePargyline	Increased arterial pressurePhenelzine	Increased arterial pressureReserpine	Increased arterial pressureTranylcypromine	Increased arterial pressureOxytocin	Possible marked increase of arterial pressureMethylergonovine	Possible marked increase of arterial pressureLinezolid	Possible increase of arterial pressureErgonovine	Possible marked increase of arterial pressureTrimipramine	The tricyclic increases the sympathomimetic effectProtriptyline	The tricyclic increases the sympathomimetic effectNortriptyline	The tricyclic increases the sympathomimetic effectClomipramine	The tricyclic increases the sympathomimetic effectAmitriptyline	The tricyclic increases the sympathomimetic effectAmoxapine	The tricyclic increases the sympathomimetic effectDesipramine	The tricyclic increases the sympathomimetic effectDoxepin	The tricyclic increases the sympathomimetic effectImipramine	The tricyclic increases the sympathomimetic effectMoclobemide	Moclobemide increases the sympathomimetic effect 
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    CYP450  Drug Interaction | 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] Dextromethorphan¿¡ ´ëÇÑ P450 table 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 
  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 
 
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    | Food Interaction | 
    
       Chlorpheniramine¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take with food.Avoid alcohol.
  Guaifenesin¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take with a full glass of water.Take without regard to meals.
  Phenylephrine¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take without regard to meals. 
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    | Drug Target | 
    
      
      [Drug Target]
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    | SNP Á¤º¸ | 
    
      Name:Dextromethorphan (DB00514)
 Interacting Gene/Enzyme:Cytochrome P450 2D6 (Gene symbol = CYP2D6) Swissprot P10635
 SNP(s):CYP2D6*6 rs5030655 (T deletion, homozygote)
 Effect:Poor drug metabolizer, lower dose requirements
 Reference(s):Bradford LD, Gaedigk A, Leeder JS: High frequency of CYP2D6 poor and "intermediate" metabolizers in black populations: a review and preliminary data. Psychopharmacol Bull. 1998;34(4):797-804. [PubMed] 
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    | Description | 
    
       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]
  Dextromethorphan¿¡ ´ëÇÑ Description Á¤º¸ The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is one of the widely used antitussives, and is also used to study the involvement of glutamate receptors in neurotoxicity. [PubChem]
  Guaifenesin¿¡ ´ëÇÑ Description Á¤º¸ An expectorant that also has some muscle relaxing action. It is used in many cough preparations. [PubChem]
  Phenylephrine¿¡ ´ëÇÑ Description Á¤º¸ An alpha-adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent. [PubChem] 
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    | Dosage Form | 
    
       Chlorpheniramine¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Syrup	OralTablet	OralTablet, extended release	Oral
  Dextromethorphan¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Capsule	OralLiquid	OralLozenge	OralStrip	OralSuspension	OralSyrup	OralTablet	Oral
  Guaifenesin¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Liquid	OralSyrup	Oral
  Phenylephrine¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Liquid	IntramuscularLiquid	IntravenousLiquid	OphthalmicOintment	TopicalSolution	IntravenousSolution / drops	OphthalmicStrip	OralTablet	Oral 
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    | Drug Category | 
    
       Chlorpheniramine¿¡ ´ëÇÑ Drug_Category Á¤º¸ Anti-Allergic AgentsAntihistaminesAntipruriticsHistamine H1 Antagonists
  Dextromethorphan¿¡ ´ëÇÑ Drug_Category Á¤º¸ Analgesics, OpioidAntitussive AgentsExcitatory Amino Acid Antagonists
  Guaifenesin¿¡ ´ëÇÑ Drug_Category Á¤º¸ Expectorants
  Phenylephrine¿¡ ´ëÇÑ Drug_Category Á¤º¸ Adrenergic alpha-AgonistsCardiotonic AgentsMydriaticsNasal DecongestantsSympathomimeticsVasoconstrictor Agents 
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    | Smiles String Canonical | 
    
       Chlorpheniramine¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CN(C)CCC(C1=CC=C(Cl)C=C1)C1=CC=CC=N1
  Dextromethorphan¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ COC1=CC2=C(CC3C4CCCCC24CCN3C)C=C1
  Guaifenesin¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ COC1=CC=CC=C1OCC(O)CO
  Phenylephrine¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CNCC(O)C1=CC(O)=CC=C1 
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    | Smiles String Isomeric | 
    
       Chlorpheniramine¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CN(C)CC[C@H](C1=CC=C(Cl)C=C1)C1=CC=CC=N1
  Dextromethorphan¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ COC1=CC2=C(C[C@H]3[C@H]4CCCC[C@@]24CCN3C)C=C1
  Guaifenesin¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ COC1=CC=CC=C1OC[C@H](O)CO
  Phenylephrine¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CNC[C@H](O)C1=CC(O)=CC=C1 
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    | InChI Identifier | 
    
       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
  Dextromethorphan¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C18H25NO/c1-19-10-9-18-8-4-3-5-15(18)17(19)11-13-6-7-14(20-2)12-16(13)18/h6-7,12,15,17H,3-5,8-11H2,1-2H3/t15-,17+,18-/m1/s1
  Guaifenesin¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C10H14O4/c1-13-9-4-2-3-5-10(9)14-7-8(12)6-11/h2-5,8,11-12H,6-7H2,1H3
  Phenylephrine¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C9H13NO2/c1-10-6-9(12)7-3-2-4-8(11)5-7/h2-5,9-12H,6H2,1H3/t9-/m0/s1 
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    | Chemical IUPAC Name | 
    
       Chlorpheniramine¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 3-(4-chlorophenyl)-N,N-dimethyl-3-pyridin-2-ylpropan-1-amine
  Dextromethorphan¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ Not Available
  Guaifenesin¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 3-(2-methoxyphenoxy)propane-1,2-diol
  Phenylephrine¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 3-[(1R)-1-hydroxy-2-methylaminoethyl]phenol 
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    | Drug-Induced Toxicity Related Proteins | 
    
      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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