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. 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. 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. Riboflavin¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Binds to riboflavin hydrogenase, riboflavin kinase, and riboflavin synthase. Riboflavin is the precursor of flavin mononucleotide (FMN, riboflavin monophosphate) and flavin adenine dinucleotide (FAD). The antioxidant activity of riboflavin is principally derived from its role as a precursor of FAD and the role of this cofactor in the production of the antioxidant reduced glutathione. Reduced glutathione is the cofactor of the selenium-containing glutathione peroxidases among other things. The glutathione peroxidases are major antioxidant enzymes. Reduced glutathione is generated by the FAD-containing enzyme glutathione reductase. Thiamine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ It is thought that the mechanism of action of thiamine on endothelial cells is related to a reduction in intracellular protein glycation by redirecting the glycolytic flux.
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. 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. 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). Riboflavin¿¡ ´ëÇÑ Pharmacology Á¤º¸ Riboflavin or vitamin B2 is an easily absorbed, water-soluble micronutrient with a key role in maintaining human health. Like the other B vitamins, it supports energy production by aiding in the metabolising of fats, carbohydrates, and proteins. Vitamin B2 is also required for red blood cell formation and respiration, antibody production, and for regulating human growth and reproduction. It is essential for healthy skin, nails, hair growth and general good health, including regulating thyroid activity. Riboflavin also helps in the prevention or treatment of many types of eye disorders, including some cases of cataracts. Thiamine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Thiamine is a vitamin with antioxidant, erythropoietic, cognition-and mood-modulatory, antiatherosclerotic, putative ergogenic, and detoxification activities. Thiamine has been found to protect against lead-induced lipid peroxidation in rat liver and kidney. Thiamine deficiency results in selective neuronal death in animal models. The neuronal death is associated with increased free radical production, suggesting that oxidative stress may play an important early role in brain damage associated with thiamine deficiency. Thiamine plays a key role in intracellular glucose metabolism and it is thought that thiamine inhibits the effect of glucose and insulin on arterial smooth muscle cell proliferation. Inhibition of endothelial cell proliferation may also promote atherosclerosis. Endothelial cells in culture have been found to have a decreased proliferative rate and delayed migration in response to hyperglycemic conditions. Thiamine has been shown to inhibit this effect of glucose on endothelial cells.
Chlorpheniramine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 72% Pseudoephedrine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Pseudoephedrine does not bind to human plasma proteins over the concentration range of 50 to 2000 ng/mL Riboflavin¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 60% Thiamine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 90-94%
Acetaminophen¿¡ ´ëÇÑ Absorption Á¤º¸ Rapid and almost complete 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 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. Riboflavin¿¡ ´ëÇÑ Absorption Á¤º¸ Vitamin B2 is readily absorbed from the upper gastrointestinal tract. Thiamine¿¡ ´ëÇÑ Absorption Á¤º¸ Absorbed mainly from duodenum, by both active and passive processes
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. 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. Pseudoephedrine¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic. Riboflavin¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic. Thiamine¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic
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. Dextromethorphan¿¡ ´ëÇÑ Toxicity Á¤º¸ Not Available 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. Riboflavin¿¡ ´ëÇÑ Toxicity Á¤º¸ Not Available Thiamine¿¡ ´ëÇÑ Toxicity Á¤º¸ Thiamine toxicity is uncommon; as excesses are readily excreted, although long-term supplementation of amounts larger than 3 gram have been known to cause toxicity. Oral mouse LD50 = 8224 mg/kg, oral rat LD50 = 3710 mg/kg.
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 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 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 Riboflavin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available Thiamine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available
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.
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] 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] 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] Riboflavin¿¡ ´ëÇÑ Description Á¤º¸ Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as flavin mononucleotide and flavin-adenine dinucleotide. [PubChem] Thiamine¿¡ ´ëÇÑ Description Á¤º¸ 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2- hydroxyethyl)-4-methylthiazolium chloride. [PubChem]