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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.Irbesartan¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸  Irbesartan is a nonpeptide angiotensin II antagonist that selectively blocks the binding of angiotensin II to the AT1  receptor. In the renin-angiotensin system, angiotensin I is converted by angiotensin-converting enzyme (ACE) to form angiotensin II. Angiotensin II stimulates the adrenal cortex to synthesize and secrete aldosterone, which decreases the excretion of sodium and increases the excretion of potassium. Angiotensin II also acts as a vasoconstrictor in vascular smooth muscle. Irbesartan, by blocking the binding of angiotensin II to the AT1  receptor, promotes vasodilation and decreases the effects of aldosterone. The negative feedback regulation of angiotensin II on renin secretion also is inhibited, but the resulting rise in plasma renin concentrations and consequent rise in angiotensin II plasma concentrations do not counteract the blood pressure–lowering effect that occurs. 
     
   
  
   
    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.Irbesartan¿¡ ´ëÇÑ Pharmacology Á¤º¸  Irbesartan is a specific competitive antagonist of AT1  receptors with a much greater affinity (more than 8500-fold) for the AT1  receptor than for the AT2  receptor and no agonist activity. 
     
   
  
   
    Metabolism 
    
      Hydrochlorothiazide¿¡ ´ëÇÑ Metabolism Á¤º¸  # Phase_1_Metabolizing_Enzyme:Not AvailableIrbesartan¿¡ ´ëÇÑ Metabolism Á¤º¸  # Phase_1_Metabolizing_Enzyme:Cytochrome P450 2C9 (CYP2C9) 
     
   
  
   
    Protein Binding 
    
      Hydrochlorothiazide¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸  67.9%Irbesartan¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸  90% bound to serum proteins (primarily albumin and a1-acid glycoprotein) with negligible binding to cellular components of blood. 
     
   
  
   
    Half-life 
    
      Hydrochlorothiazide¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸  5.6 and 14.8 hoursIrbesartan¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸  11-15 hours 
     
   
  
   
    Absorption 
    
      Hydrochlorothiazide¿¡ ´ëÇÑ Absorption Á¤º¸  50-60%Irbesartan¿¡ ´ëÇÑ Absorption Á¤º¸  Rapid and complete with an average absolute bioavailability of 60-80%. Food has no affect on bioavailability. 
     
   
  
   
    Pharmacokinetics 
    
      HydrochlorothiazideÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á  
	ÀÌ´¢È¿°ú ¹ßÇö½Ã°£ : °æ±¸ : 2½Ã°£ À̳»
	 ÃÖ´ëÈ¿°ú ¹ßÇö½Ã°£ : 4½Ã°£ 
	 ÀÛ¿ëÁö¼Ó½Ã°£ : 6-12½Ã°£
	 Èí¼ö : °æ±¸ : 60-80%
	 ¼Ò½Ç : ¹Ìº¯Èü·Î ½Å¹è¼³µÈ´Ù.
  
IrbesartanÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á  
ÃÖ°íÇ÷Áß³óµµ µµ´Þ½Ã°£ : 1.5 -2 ½Ã°£
 Ç×°íÇ÷¾Ð È¿°ú ¹ßÇö - Åõ¿© ½ÃÀÛ ÈÄ 2ÁÖ À̳»
 Ç×°íÇ÷¾Ð ÃÖ´ë È¿°ú - Åõ¿© ½ÃÀÛ ÈÄ 2-6ÁÖ »çÀÌ
 »ýü³»ÀÌ¿ë·ü : 60-80%
 ºÐÆ÷¿ëÀû : 53-93 L 
 ¹Ý°¨±â : 11-15 ½Ã°£
 ´ë»ç : CYP2C9¿¡ ÀÇÇØ ´ë»çµÊ
 ¼Ò½Ç : 78% ´ëº¯, 22% ´¢¹è¼³
   
 
	 
	 
	
     
   
  
   
    Biotransformation 
    
      Hydrochlorothiazide¿¡ ´ëÇÑ Biotransformation Á¤º¸  Hydrochlorothiazide is not metabolized.Irbesartan¿¡ ´ëÇÑ Biotransformation Á¤º¸  Hepatic. Irbesartan is metabolized via glucuronide conjugation and oxidation. In vitro studies of irbesartan oxidation by cytochrome P450 isoenzymes indicated irbesartan was oxidized primarily by 2C9; metabolism by 3A4 was negligible. 
     
   
  
   
    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.Irbesartan¿¡ ´ëÇÑ Toxicity Á¤º¸  Hypotension and tachycardia; bradycardia might also occur from overdose, LD50 =mg/kg(orally in rat) 
     
   
  
   
    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 effectIrbesartan¿¡ ´ëÇÑ Drug_Interactions Á¤º¸  Amiloride	Increased risk of hyperkaliemiaDrospirenone	Increased risk of hyperkaliemiaSpironolactone	Increased risk of hyperkaliemiaPotassium	Increased risk of hyperkaliemiaLithium	The ARB increases serum levels of lithiumTriamterene	Increased risk of hyperkaliemia 
     
   
  
   
    CYP450  Drug Interaction 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] Irbesartan¿¡ ´ëÇÑ P450 table SUBSTRATES  
CYP 2C9  
NSAIDs:  
diclofenac 
ibuprofen 
piroxicam 
Oral Hypoglycemic Agents:  
tolbutamide 
glipizide 
Angiotensin II Blockers:  
NOT candesartan 
**irbesartan**  
losartan 
NOT valsartan 
celecoxib 
fluvastatin naproxen 
phenytoin 
sulfamethoxazole 
tamoxifen 
tolbutamide 
torsemide 
warfarin 
INHIBITORS  
CYP 2C9  
amiodarone 
fluconazole 
isoniazid 
INDUCERS  
CYP 2C9  
rifampin 
secobarbital 
 
     
   
  
   
    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.Irbesartan¿¡ ´ëÇÑ Food Interaction Á¤º¸  Take without regard to meals. 
     
   
  
   
    Drug Target 
    
      
      [Drug Target]  
     
   
  
   
    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]Irbesartan¿¡ ´ëÇÑ Description Á¤º¸  Irbesartan is an angiotensin II receptor antagonist used mainly for the treatment of hypertension. 
     
   
  
   
    Dosage Form 
    
      Irbesartan¿¡ ´ëÇÑ Dosage_Form Á¤º¸  Tablet	Oral 
     
   
  
   
    Drug Category 
    
      Hydrochlorothiazide¿¡ ´ëÇÑ Drug_Category Á¤º¸  Antihypertensive AgentsDiureticsSodium Chloride Symporter InhibitorsIrbesartan¿¡ ´ëÇÑ Drug_Category Á¤º¸  Angiotensin II Receptor AntagonistsAngiotensin II Type 1 Receptor BlockersAntihypertensive Agents 
     
   
  
   
    Smiles String Canonical 
    
      Hydrochlorothiazide¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸  NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1Irbesartan¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸  CCCCC1=NC2(CCCC2)C(=O)N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1 
     
   
  
   
    Smiles String Isomeric 
    
      Hydrochlorothiazide¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸  NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1Irbesartan¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸  CCCCC1=NC2(CCCC2)C(=O)N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1 
     
   
  
   
    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/h9H2Irbesartan¿¡ ´ëÇÑ InChI_Identifier Á¤º¸  InChI=1/C25H28N6O/c1-2-3-10-22-26-25(15-6-7-16-25)24(32)31(22)17-18-11-13-19(14-12-18)20-8-4-5-9-21(20)23-27-29-30-28-23/h4-5,8-9,11-14H,2-3,6-7,10,15-17H2,1H3,(H,27,28,29,30)/f/h29H 
     
   
  
   
    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-sulfonamideIrbesartan¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸  2-butyl-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]-1,3-diazaspiro[4.4]non-1-en-4-one 
     
   
    
 
	  
	   
	
	  
       
	    
	      
	        
            
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