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| Related FDA Approved Drug |
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| Mechanism of Action |
Hydrochlorothiazide¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ As a diuretic, hydrochlorothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like hydrochlorothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of hydrochlorothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.
Metoprolol¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Like betaxolol and atenolol, metoprolol competes with adrenergic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart and vascular smooth muscle. Beta(1)-receptor blockade results in a decrease in heart rate, cardiac output, and blood pressure.
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| Pharmacology |
Hydrochlorothiazide¿¡ ´ëÇÑ Pharmacology Á¤º¸ Thiazides such as hydrochlorothiazide promote water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.
Metoprolol¿¡ ´ëÇÑ Pharmacology Á¤º¸ Metoprolol, a competitive, beta1-selective (cardioselective) adrenergic antagonist, is similar to atenolol in its moderate lipid solubility, lack of intrinsic sympathomimetic activity (ISA), and weak membrane stabilizing activity (MSA).
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| Metabolism |
Hydrochlorothiazide¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Not Available
Metoprolol¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 2D6 (CYP2D6)
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| Protein Binding |
Hydrochlorothiazide¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 67.9%
Metoprolol¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 12%
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| Half-life |
Hydrochlorothiazide¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 5.6 and 14.8 hours
Metoprolol¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 3-7 hours
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| Absorption |
Hydrochlorothiazide¿¡ ´ëÇÑ Absorption Á¤º¸ 50-60%
Metoprolol¿¡ ´ëÇÑ Absorption Á¤º¸ Rapid and complete, 50%
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HydrochlorothiazideÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á
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Metoprolol TartrateÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á
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| Biotransformation |
Hydrochlorothiazide¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hydrochlorothiazide is not metabolized.
Metoprolol¿¡ ´ëÇÑ Biotransformation Á¤º¸ Primarily hepatic
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| Toxicity |
Hydrochlorothiazide¿¡ ´ëÇÑ Toxicity Á¤º¸ The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in the mouse and rat.
Metoprolol¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50=5500 mg/kg (orally in rats), toxic effects include bradycardia, hypotension, bronchospasm, and cardiac failure. LD50=2090 mg/kg (orally in mice)
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| Drug Interactions |
Hydrochlorothiazide¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Amantadine The diuretic increases the adverse effect of amantadineDeslanoside Possible electrolyte variations and arrhythmiasDigitoxin Possible electrolyte variations and arrhythmiasDigoxin Possible electrolyte variations and arrhythmiasLithium The thiazide diuretic increases serum levels of lithiumDofetilide Increased risk of cardiotoxicity and arrhythmiasDiazoxide Significant hyperglycemic effect
Metoprolol¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Acetohexamide The beta-blocker decreases the symptoms of hypoglycemiaChlorpropamide The beta-blocker decreases the symptoms of hypoglycemiaCimetidine Cimetidine increases the effect of the beta-blockerClonidine Increased hypertension when clonidine stoppedDisopyramide The beta-blocker increases toxicity of disopyramideGliclazide The beta-blocker decreases the symptoms of hypoglycemiaGlipizide The beta-blocker decreases the symptoms of hypoglycemiaGlisoxepide The beta-blocker decreases the symptoms of hypoglycemiaGlibenclamide The beta-blocker decreases the symptoms of hypoglycemiaGlycodiazine The beta-blocker decreases the symptoms of hypoglycemiaInsulin The beta-blocker decreases the symptoms of hypoglycemiaLidocaine The beta-blocker increases the effect and toxicity of lidocainePropafenone Propafenone increases the effect of beta-blockerRepaglinide The beta-blocker decreases the symptoms of hypoglycemiaRifampin Rifampin decreases the effect of the metabolized beta-blockerTelithromycin Telithromycin may possibly increase metoprolol effectTolazamide The beta-blocker decreases the symptoms of hypoglycemiaTolbutamide The beta-blocker decreases the symptoms of hypoglycemiaAmobarbital The barbiturate decreases the effect of metabolized beta-blockerAprobarbital The barbiturate decreases the effect of metabolized beta-blockerButalbital The barbiturate decreases the effect of metabolized beta-blockerButabarbital The barbiturate decreases the effect of metabolized beta-blockerButethal The barbiturate decreases the effect of metabolized beta-blockerDihydroquinidine barbiturate The barbiturate decreases the effect of metabolized beta-blockerHeptabarbital The barbiturate decreases the effect of metabolized beta-blockerHexobarbital The barbiturate decreases the effect of metabolized beta-blockerMethohexital The barbiturate decreases the effect of metabolized beta-blockerMethylphenobarbital The barbiturate decreases the effect of metabolized beta-blockerPentobarbital The barbiturate decreases the effect of metabolized beta-blockerPhenobarbital The barbiturate decreases the effect of metabolized beta-blockerPrimidone The barbiturate decreases the effect of metabolized beta-blockerQuinidine barbiturate The barbiturate decreases the effect of metabolized beta-blockerSecobarbital The barbiturate decreases the effect of metabolized beta-blockerTalbutal The barbiturate decreases the effect of metabolized beta-blockerCitalopram The SSRI increases the effect of the beta-blockerEscitalopram The SSRI increases the effect of the beta-blockerFluoxetine The SSRI increases the effect of the beta-blockerSertraline The SSRI increases the effect of the beta-blockerParoxetine The SSRI increases the effect of the beta-blockerDihydroergotamine Ischemia with risk of gangreneDihydroergotoxine Ischemia with risk of gangreneErgonovine Ischemia with risk of gangreneErgotamine Ischemia with risk of gangreneMethysergide Ischemia with risk of gangreneVerapamil Increased effect of both drugsHydralazine Increased effect of both drugsDiltiazem Increased risk of bradycardiaEpinephrine Hypertension, then bradycardiaFenoterol AntagonismFormoterol AntagonismIsoproterenol AntagonismOrciprenaline AntagonismPirbuterol AntagonismPrazosin Risk of hypotension at the beginning of therapyProcaterol AntagonismSalbutamol AntagonismSalmeterol AntagonismTerbutaline AntagonismIbuprofen Risk of inhibition of renal prostaglandinsIndomethacin Risk of inhibition of renal prostaglandinsPiroxicam Risk of inhibition of renal prostaglandins
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CYP450 Drug Interaction |
[CYP450 TableÁ÷Á¢Á¶È¸]
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| Food Interaction |
Hydrochlorothiazide¿¡ ´ëÇÑ Food Interaction Á¤º¸ Avoid alcohol.Avoid excess salt/sodium unless otherwise instructed by your physician.Take with food.Increase potassium intake; add a banana or orange juice; unless instructed otherwise.Avoid natural licorice.Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication.
Metoprolol¿¡ ´ëÇÑ Food Interaction Á¤º¸ Avoid alcohol.Take with food.Avoid natural licorice.
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| Drug Target |
[Drug Target]
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| SNP Á¤º¸ |
Name:Metoprolol (DB00264)
Interacting Gene/Enzyme:Beta-1 adrenergic receptor (Gene symbol = ADRB1) Swissprot P08588
SNP(s):rs1801253 (C Allele) rs1801252 (A Allele)
Effect:Improved response to blood pressure medication
Reference(s):Johnson JA, Zineh I, Puckett BJ, McGorray SP, Yarandi HN, Pauly DF: Beta 1-adrenergic receptor polymorphisms and antihypertensive response to metoprolol. Clin Pharmacol Ther. 2003 Jul;74(1):44-52. [PubMed]
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| Description |
Hydrochlorothiazide¿¡ ´ëÇÑ Description Á¤º¸ A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. [PubChem]
Metoprolol¿¡ ´ëÇÑ Description Á¤º¸ A selective adrenergic beta-1-blocking agent with no stimulatory action. It&
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| Dosage Form |
Metoprolol¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Liquid IntravenousSolution IntravenousTablet OralTablet, extended release Oral
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| Drug Category |
Hydrochlorothiazide¿¡ ´ëÇÑ Drug_Category Á¤º¸ Antihypertensive AgentsDiureticsSodium Chloride Symporter Inhibitors
Metoprolol¿¡ ´ëÇÑ Drug_Category Á¤º¸ Adrenergic AgentsAdrenergic beta-AntagonistsAnti-Arrhythmia AgentsAntiarrhythmic AgentsAntihypertensive AgentsSympatholytics
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| Smiles String Canonical |
Hydrochlorothiazide¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1
Metoprolol¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ COCCC1=CC=C(OCC(O)CNC(C)C)C=C1
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| Smiles String Isomeric |
Hydrochlorothiazide¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1
Metoprolol¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ COCCC1=CC=C(OC[C@H](O)CNC(C)C)C=C1
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| InChI Identifier |
Hydrochlorothiazide¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C7H8ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-2,10-11H,3H2,(H2,9,12,13)/f/h9H2
Metoprolol¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C15H25NO3/c1-12(2)16-10-14(17)11-19-15-6-4-13(5-7-15)8-9-18-3/h4-7,12,14,16-17H,8-11H2,1-3H3
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| Chemical IUPAC Name |
Hydrochlorothiazide¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 6-chloro-1,1-dioxo-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide
Metoprolol¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 1-[4-(2-methoxyethyl)phenoxy]-3-(propan-2-ylamino)propan-2-ol
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| Drug-Induced Toxicity Related Proteins |
METOPROLOL ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:CYP2D6 Drug:Metoprolol Toxicity:Increased beta-blockade. [¹Ù·Î°¡±â]
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The database contains the following fields: The generic name of each chemical For module A10 (liver enzyme composite module): Overall activity category for each compound (A for active, M for marginally active, or I for inactive) based on the number of active and marginally active scores for each compound at the five individual endpoints (see research article for full description of method) Number of endpoints at which each compound is marginally active (M) Number of endpoints at which each compound is active (A) For modules A11 to A15 (alkaline phosphatase increased, SGOT increased, SGPT increased, LDH increased, and GGT increased, respectively): Overall activity category for each compound (A for active, M for marginally active, or I for inactive) based on the RI and ADR values (see the research article for full description of method) Number of ADR reports for each compound, given as <4 or ¡Ã4 Reporting Index value for each compound, except where no shipping units were available (NSU) Group 1 comprises of compounds for which ADR data were available for the first five years of marketing, so when no ADR reports were listed during this period the compounds were evaluated as inactive. Group 2 comprises of compounds for which a 'steady state' period of ADR data were available (1992-1996). In cases where no ADR reports were filed during this period, the compounds were scored as 'NA' (data not available) since they may have had one or more ADR reports during their first five years of marketing which should not be negated by a lack of ADR reports during the steady-state period. METOPROLOL[GGT Increase][Composite Activity](Score) I(Marginal) 0(Active) 0[Alkaline Phosphatase Increase](Activity Score) I(Number of Rpts) ¡Ã4(Index value) 0.4[SGOT Increase](Activity Score) I(Number of Rpts) ¡Ã4(Index value) 0.5[SGPT Increase](Activity Score) I(Number of Rpts) ¡Ã4(Index value) 0.5[LDH Increase](Activity Score) I(Number of Rpts) <4(Index value) 0.3[GGT Increase](Activity Score) I(Number of Rpts) <4(Index value) 0
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