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Á¾ÇÕ°¨±â¾à(Drugs to Relieve Common Cold)
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OTHER COLD PREPARATIONS / R05X
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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.
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.
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.
Pseudoephedrine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Pseudoephedrine acts directly on both alpha- and, to a lesser degree, beta-adrenergic receptors. Through direct action on alpha-adrenergic receptors in the mucosa of the respiratory tract, pseudoephedrine produces vasoconstriction. Pseudoephedrine relaxes bronchial smooth muscle by stimulating beta2-adrenergic receptors. Like ephedrine, pseudoephedrine releasing norepinephrine from its storage sites, an indirect effect.
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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.
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.
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.
Pseudoephedrine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Pseudoephedrine is a sympathomimetic agent, structurally similar to ephedrine, used to relieve nasal and sinus congestion and reduce air-travel-related otalgia in adults. The salts pseudoephedrine hydrochloride and pseudoephedrine sulfate are found in many over-the-counter preparations either as single-ingredient preparations, or more commonly in combination with antihistamines and/or paracetamol/ibuprofen. Unlike antihistamines, which modify the systemic histamine-mediated allergic response, pseudoephedrine only serves to relieve nasal congestion commonly associated with colds or allergies. The advantage of oral pseudoephedrine over topical nasal preparations, such as oxymetazoline, is that it does not cause rebound congestion (rhinitis medicamentosa).
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| Metabolism |
Acetaminophen¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 1A2 (CYP1A2)Cytochrome P450 2E1 (CYP2E1)
Chlorpheniramine¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 3A4 (CYP3A4)Cytochrome P450 2D6 (CYP2D6)
Pseudoephedrine¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Monoamine oxidase type A (MAO-A)
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| Absorption |
Acetaminophen¿¡ ´ëÇÑ Absorption Á¤º¸ Rapid and almost complete
Chlorpheniramine¿¡ ´ëÇÑ Absorption Á¤º¸ Well absorbed in the gastrointestinal tract.
Guaifenesin¿¡ ´ëÇÑ Absorption Á¤º¸ Rapidly absorbed from the GI tract
Pseudoephedrine¿¡ ´ëÇÑ Absorption Á¤º¸ Pseudoephedrine is readily and almost completely absorbed from the GI tract and there is no evidence of first-pass metabolism.
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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.
Chlorpheniramine¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50 = 306 mg/kg in humans, mild reproductive toxin to women of childbearing age.
Guaifenesin¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50 1510 mg/kg (rat, oral)
Pseudoephedrine¿¡ ´ëÇÑ Toxicity Á¤º¸ Common adverse reactions include nervousness, restlessness, and insomnia. Rare adverse reactions include difficult/painful urination, dizziness/lightheadedness, heart palpitations, headache, increased sweating, nausea/vomiting, trembling, troubled breathing, unusual paleness, and weakness.
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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
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
Guaifenesin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available
Pseudoephedrine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Alseroxylon Increased arterial pressureIsocarboxazid Increased arterial pressureLinezolid Possible increase of arterial pressureMethyldopa Increased arterial pressureBromocriptine The sympathomimetic increases the toxicity of bromocriptineTranylcypromine Increased arterial pressureMidodrine Increased arterial pressureMoclobemide Moclobemide increases the sympathomimetic effectPargyline Increased arterial pressurePhenelzine Increased arterial pressureRasagiline Increased arterial pressureReserpine Increased arterial pressureTrimipramine The tricyclic increases the sympathomimetic effectProtriptyline The tricyclic increases the sympathomimetic effectNortriptyline The tricyclic increases the sympathomimetic effectAmitriptyline The tricyclic increases the sympathomimetic effectAmoxapine The tricyclic increases the sympathomimetic effectClomipramine The tricyclic increases the sympathomimetic effectImipramine The tricyclic increases the sympathomimetic effectDesipramine The tricyclic increases the sympathomimetic effectDoxepin The tricyclic increases the sympathomimetic effectDeserpidine Increased arterial pressureGuanethidine The agent decreases the effect of guanethidine
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CYP450 Drug Interaction |
[CYP450 TableÁ÷Á¢Á¶È¸] Chlorpheniramine¿¡ ´ëÇÑ P450 table Acetaminophen¿¡ ´ëÇÑ P450 table
SUBSTRATES
CYP 2E1
**acetaminophen**
chlorzoxazone
ethanol
INHIBITORS
CYP 2E1
disulfiram
INDUCERS
CYP 2E1
ethanol
isoniazid
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 |
Acetaminophen¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take without regard to meals.Avoid alcohol (may increase risk of hepatotoxicity).
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.
Pseudoephedrine¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take without regard to meals.
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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]
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]
Guaifenesin¿¡ ´ëÇÑ Description Á¤º¸ An expectorant that also has some muscle relaxing action. It is used in many cough preparations. [PubChem]
Pseudoephedrine¿¡ ´ëÇÑ Description Á¤º¸ An alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used in the treatment of several disorders including asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists. [PubChem]
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| Drug Category |
Acetaminophen¿¡ ´ëÇÑ Drug_Category Á¤º¸ Analgesics, Non-NarcoticAntipyretics
Chlorpheniramine¿¡ ´ëÇÑ Drug_Category Á¤º¸ Anti-Allergic AgentsAntihistaminesAntipruriticsHistamine H1 Antagonists
Guaifenesin¿¡ ´ëÇÑ Drug_Category Á¤º¸ Expectorants
Pseudoephedrine¿¡ ´ëÇÑ Drug_Category Á¤º¸ Adrenergic AgentsBronchodilator AgentsCentral Nervous System AgentsNasal DecongestantsSympathomimeticsVasoconstrictor Agents
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| Smiles String Canonical |
Acetaminophen¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CC(=O)NC1=CC=C(O)C=C1
Chlorpheniramine¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CN(C)CCC(C1=CC=C(Cl)C=C1)C1=CC=CC=N1
Guaifenesin¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ COC1=CC=CC=C1OCC(O)CO
Pseudoephedrine¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CNC(C)C(O)C1=CC=CC=C1
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| Smiles String Isomeric |
Acetaminophen¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CC(=O)NC1=CC=C(O)C=C1
Chlorpheniramine¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CN(C)CC[C@H](C1=CC=C(Cl)C=C1)C1=CC=CC=N1
Guaifenesin¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ COC1=CC=CC=C1OC[C@H](O)CO
Pseudoephedrine¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CN[C@@H](C)[C@@H](O)C1=CC=CC=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
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
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
Pseudoephedrine¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C10H15NO/c1-8(11-2)10(12)9-6-4-3-5-7-9/h3-8,10-12H,1-2H3/t8-,10+/m0/s1
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| Chemical IUPAC Name |
Acetaminophen¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ N-(4-hydroxyphenyl)acetamide
Chlorpheniramine¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 3-(4-chlorophenyl)-N,N-dimethyl-3-pyridin-2-ylpropan-1-amine
Guaifenesin¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 3-(2-methoxyphenoxy)propane-1,2-diol
Pseudoephedrine¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ (1S,2S)-2-methylamino-1-phenylpropan-1-ol
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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] 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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