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    | Mechanism of Action | 
    
       Diltiazem¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, dilitiazem, like verapamil, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue. 
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    | Pharmacology | 
     
       Diltiazem¿¡ ´ëÇÑ Pharmacology Á¤º¸ Diltiazem, a benzothiazepine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Diltiazem is similar to other peripheral vasodilators. Diltiazem inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload. 
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    | Metabolism | 
    
       Diltiazem¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 3A4 (CYP3A4)Cytochrome P450 2C19 (CYP2C19)Cytochrome P450 2D6 (CYP2D6) 
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    | Protein Binding | 
    
       Diltiazem¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 70%-80% 
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    | Half-life | 
    
       Diltiazem¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 3.0 - 4.5 hours 
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    | Absorption | 
    
       Diltiazem¿¡ ´ëÇÑ Absorption Á¤º¸ Diltiazem is well absorbed from the gastrointestinal tract but undergoes substantial hepatic first-pass effect. 
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    | Pharmacokinetics | 
    
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     | 
   
  
   
    | Biotransformation | 
    
       Diltiazem¿¡ ´ëÇÑ Biotransformation Á¤º¸ Diltiazem is metabolized by and acts as an inhibitor of the CYP3A4 enzyme. 
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    | Toxicity | 
    
       Diltiazem¿¡ ´ëÇÑ Toxicity Á¤º¸ LD50=740mg/kg (orally in mice) 
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    | Drug Interactions | 
    
       Diltiazem¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Amiodarone	Increased risk of cardiotoxicity and arrhythmiasAmlodipine	Increases the effect and toxicity of amlodipineAprepitant	This CYP3A4 inhibitor increases the effect and toxicity of aprepitantAtazanavir	Atazanavir increases the effect and toxicity of diltiazemAtenolol	Increased risk of bradycardiaAtorvastatin	Increases the effect and toxicity of atorvastatinBuspirone	The calcium channel blocker increases the effect and toxicity of buspironeCarbamazepine	Increases the effect of carbamazepineCerivastatin	Increases the effect and toxicity of the statinCilostazol	Increases the effect of cilostazolCisapride	Increases the levels of cisaprideCyclosporine	Increases the effect and toxicity of cyclosporineDihydroquinidine barbiturate	Increases the effect and toxicity of quinidineLovastatin	Increases the effect and toxicity of the statinMesoridazine	Increased risk of cardiotoxicity and arrhythmiasMetoprolol	Increased risk of bradycardiaMidazolam	The calcium channel blocker increases the effect and toxicity of the benzodiazepineMoricizine	Increased effect/toxicity of moricizinePindolol	Increased risk of bradycardiaPropranolol	Increased risk of bradycardiaQuinidine	Increases the effect and toxicity of quinidineQuinidine barbiturate	Increases the effect and toxicity of quinidineQuinupristin	This combination presents an increased risk of toxicityRanolazine	Increased levels of ranolazine- risk of toxicityRifampin	Rifampin decreases levels of diltiazemRitonavir	Ritonavir increases diltiazem levelsSimvastatin	Increases the effect and toicity of simvastatinSirolimus	Increases the effect and toxicity of sirolimusTacrolimus	Increases levels of tacrolimusTerfenadine	Increased risk of cardiotoxicity and arrhythmiasThioridazine	Increased risk of cardiotoxicity and arrhythmiasTriazolam	The calcium channel blocker increases the effect and toxicity of the benzodiazepine 
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    CYP450  Drug Interaction | 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] Diltiazem¿¡ ´ëÇÑ P450 table
  SUBSTRATES 
CYP 3A4/3A5/3A7 
Macrolide antibiotics: 
clarithromycin 
erythromycin 
NOT azithromycin 
telithromycin 
Anti-arrhythmics: 
quinidine 
Benzodiazepines: 
alprazolam 
diazepam 
midazolam 
triazolam 
Immune Modulators: 
cyclosporine 
tacrolimus (FK506) 
HIV Protease Inhibitors: 
indinavir 
ritonavir 
saquinavir 
Prokinetic: 
cisapride 
Antihistamines: 
astemizole 
chlorpheniramine 
Calcium Channel Blockers: 
amlodipine 
**diltiazem** 
felodipine 
nifedipine 
nisoldipine 
nitrendipine 
verapamil 
HMG CoA Reductase Inhibitors: 
atorvastatin 
cerivastatin 
lovastatin 
NOT pravastatin 
simvastatin 
aripiprazole 
buspirone 
gleevec 
haloperidol (in part) 
methadone 
pimozide 
quinine 
NOT rosuvastatin 
sildenafil 
tamoxifen 
trazodone 
vincristine 
 INHIBITORS 
CYP 3A4/3A5/3A7 
HIV Protease Inhibitors: 
indinavir 
nelfinavir 
ritonavir 
amiodarone 
NOT azithromycin 
cimetidine 
clarithromycin 
**diltiazem** 
erythromycin 
fluvoxamine 
grapefruit juice 
itraconazole 
ketoconazole 
mibefradil 
nefazodone 
troleandomycin 
verapamil 
 INDUCERS 
CYP 3A4/3A5/3A7 
carbamazepine 
phenobarbital 
phenytoin 
rifabutin 
rifampin 
St. John's wort 
troglitazone 
  SUBSTRATES 
CYP 3A4/3A5/3A7 
Macrolide antibiotics: 
clarithromycin 
erythromycin 
NOT azithromycin 
telithromycin 
Anti-arrhythmics: 
quinidine 
Benzodiazepines: 
alprazolam 
diazepam 
midazolam 
triazolam 
Immune Modulators: 
cyclosporine 
tacrolimus (FK506) 
HIV Protease Inhibitors: 
indinavir 
ritonavir 
saquinavir 
Prokinetic: 
cisapride 
Antihistamines: 
astemizole 
chlorpheniramine 
Calcium Channel Blockers: 
amlodipine 
**diltiazem** 
felodipine 
nifedipine 
nisoldipine 
nitrendipine 
verapamil 
HMG CoA Reductase Inhibitors: 
atorvastatin 
cerivastatin 
lovastatin 
NOT pravastatin 
simvastatin 
aripiprazole 
buspirone 
gleevec 
haloperidol (in part) 
methadone 
pimozide 
quinine 
NOT rosuvastatin 
sildenafil 
tamoxifen 
trazodone 
vincristine 
 INHIBITORS 
CYP 3A4/3A5/3A7 
HIV Protease Inhibitors: 
indinavir 
nelfinavir 
ritonavir 
amiodarone 
NOT azithromycin 
cimetidine 
clarithromycin 
**diltiazem** 
erythromycin 
fluvoxamine 
grapefruit juice 
itraconazole 
ketoconazole 
mibefradil 
nefazodone 
troleandomycin 
verapamil 
 INDUCERS 
CYP 3A4/3A5/3A7 
carbamazepine 
phenobarbital 
phenytoin 
rifabutin 
rifampin 
St. John's wort 
troglitazone 
     | 
   
  
   
    | Food Interaction | 
    
       Diltiazem¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take this medication 30 minutes before meals.Avoid natural licorice. 
     | 
   
  
   
    | Drug Target | 
    
      
      [Drug Target]
     | 
   
  
   
    | Description | 
    
       Diltiazem¿¡ ´ëÇÑ Description Á¤º¸ A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [PubChem] 
     | 
   
  
   
    | Drug Category | 
    
       Diltiazem¿¡ ´ëÇÑ Drug_Category Á¤º¸ Antihypertensive AgentsCalcium Channel BlockersCalcium-channel blocking agentsCardiovascular AgentsVasodilator Agents 
     | 
   
  
   
    | Smiles String Canonical | 
    
       Diltiazem¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ COC1=CC=C(C=C1)C1SC2=CC=CC=C2N(CCN(C)C)C(=O)C1OC(C)=O 
     | 
   
  
   
    | Smiles String Isomeric | 
    
       Diltiazem¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ COC1=CC=C(C=C1)[C@@H]1SC2=CC=CC=C2N(CCN(C)C)C(=O)[C@@H]1OC(C)=O 
     | 
   
  
   
    | InChI Identifier | 
    
       Diltiazem¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C22H26N2O4S/c1-15(25)28-20-21(16-9-11-17(27-4)12-10-16)29-19-8-6-5-7-18(19)24(22(20)26)14-13-23(2)3/h5-12,20-21H,13-14H2,1-4H3/t20-,21+/m1/s1 
     | 
   
  
   
    | Chemical IUPAC Name | 
    
       Diltiazem¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ [(2S,3S)-5-(2-dimethylaminoethyl)-2-(4-methoxyphenyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl] acetate 
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