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                    ÇÁ¶óÀÚÀÌÁ¤  [Acebutolol HCl , Hydrochlorothiazide]  
                    
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    | Mechanism of Action | 
    
       Acebutolol¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Acebutolol is a selective ¥â1-receptor antagonist. Activation of ¥â1-receptors by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen. Acebutolol blocks these receptors which reverses the effects of epinephrine, lowering the heart rate and blood pressure. In addition, beta blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels.
  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. 
     | 
   
  
   
    | Pharmacology | 
     
       Acebutolol¿¡ ´ëÇÑ Pharmacology Á¤º¸ Acebutolol is a cardioselective, beta-adrenoreceptor blocking agent, which possesses mild intrinsic sympathomimetic activity (ISA) in its therapeutically effective dose range. In general, beta-blockers reduce the work the heart has to do and allow it to beat more regularly. Acebutolol has less antagonistic effects on peripheral vascular ©¬2-receptors at rest and after epinephrine stimulation than nonselective beta-antagonists. Low doses of acebutolol produce less evidence of bronchoconstriction than nonselective agents like propranolol but more than atenolol.
  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. 
     | 
   
  
   
    | Metabolism | 
    
       Acebutolol¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 2D6 (CYP2D6)
  Hydrochlorothiazide¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Not Available 
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    | Protein Binding | 
    
       Acebutolol¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 26%
  Hydrochlorothiazide¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 67.9% 
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    | Half-life | 
    
       Acebutolol¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ The plasma elimination half-life is approximately 3 to 4 hours. The half-life of its metabolite, diacetolol, is 8 to 13 hours.
  Hydrochlorothiazide¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 5.6 and 14.8 hours 
     | 
   
  
   
    | Absorption | 
    
       Acebutolol¿¡ ´ëÇÑ Absorption Á¤º¸ Well absorbed from the Gl tract with an absolute bioavailability of approximately 40% for the parent compound. In
  Hydrochlorothiazide¿¡ ´ëÇÑ Absorption Á¤º¸ 50-60% 
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       Acebutolol HClÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
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	 HydrochlorothiazideÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
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    | Biotransformation | 
    
       Acebutolol¿¡ ´ëÇÑ Biotransformation Á¤º¸ Subject to extensive first-pass hepatic biotransformation (primarily to diacetolol).
  Hydrochlorothiazide¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hydrochlorothiazide is not metabolized. 
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    | Toxicity | 
    
       Acebutolol¿¡ ´ëÇÑ Toxicity Á¤º¸ Symptoms of overdose include extreme bradycardia, advanced atrioventricular block, intraventricular conduction defects, hypotension, severe congestive heart failure, seizures, and in susceptible patients, bronchospasm, and hypoglycemia.
  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. 
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    | Drug Interactions | 
    
       Acebutolol¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Acetohexamide	Decreased in symptoms of hypoglycemia and increase in time required for the body to compensate for hypoglycemiaChlorpropamide	Decreased in symptoms of hypoglycemia and increase in time required for the body to compensate for hypoglycemiaDisopyramide	Decreased in symptoms of hypoglycemia and increase in time required for the body to compensate for hypoglycemiaGliclazide	Decreased in symptoms of hypoglycemia and increase in time required for the body to compensate for hypoglycemiaGlipizide	Decreased in symptoms of hypoglycemia and increase in time required for the body to compensate for hypoglycemiaGlibenclamide	Decreased in symptoms of hypoglycemia and increase in time required for the body to compensate for hypoglycemiaLidocaine	Decreased in symptoms of hypoglycemia and increase in time required for the body to compensate for hypoglycemiaRepaglinide	Decreased in symptoms of hypoglycemia and increase in time required for the body to compensate for hypoglycemiaTolazamide	Decreased in symptoms of hypoglycemia and increase in time required for the body to compensate for hypoglycemiaTolbutamide	Decreased in symptoms of hypoglycemia and increase in time required for the body to compensate for hypoglycemiaClonidine	Increased hypertension when clonidine stoppedDihydroergotamine	Ischemia with risk of gangreneErgotamine	Ischemia with risk of gangreneMethysergide	Ischemia with risk of gangreneEpinephrine	Hypertension, then bradycardiaIbuprofen	Risk of inhibition of renal prostaglandinsIndomethacin	Risk of inhibition of renal prostaglandinsPiroxicam	Risk of inhibition of renal prostaglandinsPrazosin	Risk of hypotension at the beginning of therapyVerapamil	Increased effect of both drugsIsoproterenol	AntagonismSalmeterol	AntagonismTerbutaline	AntagonismDihydroergotoxine	Ischemia with risk of gangreneErgonovine	Ischemia with risk of gangreneFenoterol	AntagonismGlisoxepide	The beta-blocker decreases the symptoms of hypoglycemiaOrciprenaline	AntagonismPirbuterol	AntagonismFenoterol	AntagonismInsulin-aspart	The beta-blocker decreases the symptoms of hypoglycemiaInsulin-detemir	The beta-blocker decreases the symptoms of hypoglycemiaInsulin-glargine	The beta-blocker decreases the symptoms of hypoglycemiaInsulin-glulisine	The beta-blocker decreases the symptoms of hypoglycemiaInsulin-lispro	The beta-blocker decreases the symptoms of hypoglycemiaLidocaine	The beta-blocker increases the effect and toxicity of lidocainePirbuterol	AntagonismOrciprenaline	Antagonsim
  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 
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    CYP450  Drug Interaction | 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] 
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    | Food Interaction | 
    
       Acebutolol¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take without regard to meals; absorption rate and maximal concentration are slightly reduced but the extent of absorption is not affected.
  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. 
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    | Drug Target | 
    
      
      [Drug Target]
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    | Description | 
    
       Acebutolol¿¡ ´ëÇÑ Description Á¤º¸ A cardioselective beta-adrenergic antagonist with little effect on the bronchial receptors. The drug has stabilizing and quinidine-like effects on cardiac rhythm as well as weak inherent sympathomimetic action. [PubChem]
  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] 
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    | Drug Category | 
    
       Acebutolol¿¡ ´ëÇÑ Drug_Category Á¤º¸ Adrenergic beta-AntagonistsAnti-Arrhythmia AgentsAntihypertensive Agents
  Hydrochlorothiazide¿¡ ´ëÇÑ Drug_Category Á¤º¸ Antihypertensive AgentsDiureticsSodium Chloride Symporter Inhibitors 
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    | Smiles String Canonical | 
    
       Acebutolol¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CCCC(=O)NC1=CC(C(C)=O)=C(OCC(O)CNC(C)C)C=C1
  Hydrochlorothiazide¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1 
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    | Smiles String Isomeric | 
    
       Acebutolol¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CCCC(=O)NC1=CC(C(C)=O)=C(OC[C@H](O)CNC(C)C)C=C1
  Hydrochlorothiazide¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1 
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    | InChI Identifier | 
    
       Acebutolol¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C18H28N2O4/c1-5-6-18(23)20-14-7-8-17(16(9-14)13(4)21)24-11-15(22)10-19-12(2)3/h7-9,12,15,19,22H,5-6,10-11H2,1-4H3,(H,20,23)/f/h20H
  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 
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    | Chemical IUPAC Name | 
    
       Acebutolol¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ N-[3-acetyl-4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]butanamide
  Hydrochlorothiazide¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 6-chloro-1,1-dioxo-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide 
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    | Drug-Induced Toxicity Related Proteins | 
    
      ACEBUTOLOL ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:CYP2D6 Drug:Acebutolol Toxicity:Increased beta-blockade.  [¹Ù·Î°¡±â] 
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                          ÀüÈ: 02-3486-1061 ¤Ó À̸ÞÀÏ: webmaster@druginfo.co.kr
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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. ACEBUTOLOL[Composite Activity](Score)  I(Marginal)  3(Active)  0[Alkaline Phosphatase Increase](Activity Score)  M(Number of Rpts)  ¡Ã4(Index value)  3.9[SGOT Increase](Activity Score)  I(Number of Rpts)  ¡Ã4(Index value)  2.6[SGPT Increase](Activity Score)  M(Number of Rpts)  ¡Ã4(Index value)  3.3[LDH Increase](Activity Score)  M(Number of Rpts)  ¡Ã4(Index value)  3.3[GGT Increase](Activity Score)  I(Number of Rpts)  <4(Index value)  0HYDROCHLORO[GGT Increase][Composite Activity](Score)  NA(Marginal)  0(Active)  0[Alkaline Phosphatase Increase](Activity Score)  NA(Number of Rpts)  NA(Index value)  NA[SGOT Increase](Activity Score)  NA(Number of Rpts)  NA(Index value)  NA[SGPT Increase](Activity Score)  NA(Number of Rpts)  NA(Index value)  NA[LDH Increase](Activity Score)  NA(Number of Rpts)  NA(Index value)  NA[GGT Increase](Activity Score)  NA(Number of Rpts)  NA(Index value)  NAHYDROCHLOROTHIAZIDE[GGT Increase][Composite Activity](Score)  NA(Marginal)  0(Active)  0[Alkaline Phosphatase Increase](Activity Score)  NA(Number of Rpts)  NA(Index value)  NA[SGOT Increase](Activity Score)  NA(Number of Rpts)  NA(Index value)  NA[SGPT Increase](Activity Score)  NA(Number of Rpts)  NA(Index value)  NA[LDH Increase](Activity Score)  NA(Number of Rpts)  NA(Index value)  NA[GGT Increase](Activity Score)  NA(Number of Rpts)  NA(Index value)  NA
 
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