Tìm theo
Amiodarone
Các tên gọi khác (6 ) :
  • 2-Butyl-3-(3,5-diiodo-4-(2-diethylaminoethoxy)benzoyl)benzofuran
  • 2-Butyl-3-benzofuranyl 4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl ketone
  • 2-N-Butyl-3',5'-diiodo-4'-N-diethylaminoethoxy-3-benzoylbenzofuran
  • Amiodarona
  • Amiodarone
  • Amiodaronum
Thuốc tim mạch
Thuốc Gốc
Small Molecule
CAS: 1951-25-3
ATC: C01BD01
ĐG : Alphapharm Party Ltd. , http://www.alphapharm.com.au
CTHH: C25H29I2NO3
PTK: 645.3116
An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C25H29I2NO3
Phân tử khối
645.3116
Monoisotopic mass
645.023680639
InChI
InChI=1S/C25H29I2NO3/c1-4-7-11-22-23(18-10-8-9-12-21(18)31-22)24(29)17-15-19(26)25(20(27)16-17)30-14-13-28(5-2)6-3/h8-10,12,15-16H,4-7,11,13-14H2,1-3H3
InChI Key
InChIKey=IYIKLHRQXLHMJQ-UHFFFAOYSA-N
IUPAC Name
(2-{4-[(2-butyl-1-benzofuran-3-yl)carbonyl]-2,6-diiodophenoxy}ethyl)diethylamine
Traditional IUPAC Name
amiodarone
SMILES
CCCCC1=C(C(=O)C2=CC(I)=C(OCCN(CC)CC)C(I)=C2)C2=CC=CC=C2O1
Độ tan chảy
156
Độ hòa tan
Low
logP
7.57
logS
-5.1
pKa (Strongest Basic)
8.47
PSA
42.68 Å2
Refractivity
145.05 m3·mol-1
Polarizability
56.78 Å3
Rotatable Bond Count
11
H Bond Acceptor Count
3
H Bond Donor Count
0
Physiological Charge
1
Number of Rings
3
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Amiodarone belongs to a class of drugs called Vaughan-Williams Class III antiarrhythmic agents. It is used in the treatment of a wide range of cardiac tachyarhthmias, including both ventricular and supraventricular (atrial) arrhythmias. After intravenous administration in man, amiodarone relaxes vascular smooth muscle, reduces peripheral vascular resistance (afterload), and slightly increases cardiac index. Amiodarone prolongs phase 3 of the cardiac action potential. It has numerous other effects however, including actions that are similar to those of antiarrhythmic classes Ia, II, and IV. Amiodarone shows beta blocker-like and calcium channel blocker-like actions on the SA and AV nodes, increases the refractory period via sodium- and potassium-channel effects, and slows intra-cardiac conduction of the cardiac action potential, via sodium-channel effects.
Cơ Chế Tác Dụng : An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [PubChem] The antiarrhythmic effect of amiodarone may be due to at least two major actions. It prolongs the myocardial cell-action potential (phase 3) duration and refractory period and acts as a noncompetitive a- and b-adrenergic inhibitor.
Dược Động Học :
▧ Absorption :
Slow and variable (about 20 to 55% of an oral dose is absorbed).
▧ Protein binding :
>96%
▧ Metabolism :
Amiodarone is extensively metabolized in the liver via CYP2C8 (under 1% unchanged in urine), and can effect the metabolism of numerous other drugs. The major metabolite of amiodarone is desethylamiodarone (DEA), which also has antiarrhythmic properties. The metabolism of amiodarone is inhibited by grapefruit juice, leading to elevated serum levels of amiodarone.
▧ Route of Elimination :
Amiodarone is eliminated primarily by hepatic metabolism and biliary excretion and there is negligible excretion of amiodarone or DEA in urine.
▧ Half Life :
58 days (range 15-142 days)
▧ Clearance :
* 90-158 mL/h/kg [Healthy with a single dose IV (5 mg/kg over 15 min)] * 100 mL/h/kg [Normal subjects > 65 yrs] * 150 mL/h/kg [younger subjects] * 220 and 440 mL/h/kg [patients with VT and VF]
Độc Tính : Intravenous, mouse: LD50 = 178 mg/kg. Some side effects have a significant mortality rate: specifically, hepatitis, exacerbation of asthma and congestive failure, and pneumonitis.
Chỉ Định : Intravenously, for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation and hemodynamically unstable ventricular tachycardia in patients refractory to other therapy. Orally, for the treatment of life-threatening recurrent ventricular arrhythmias such as recurrent ventricular fibrillation and recurrent hemodynamically unstable ventricular tachycardia.
Tương Tác Thuốc :
  • Acenocoumarol Amiodarone may increase the anticoagulant effect of acenocoumarol.
  • Alvimopan Decreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
  • Amprenavir The protease inhibitor, amprenavir, may increase the effect and toxicity of amiodarone.
  • Anisindione Amiodarone may increase the anticoagulant effect of anisindione.
  • Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Atazanavir Increased risk of cardiotoxicity and arrhythmias.
  • Atomoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
  • Cisapride Increased risk of cardiotoxicity and arrhythmias
  • Clarithromycin Increased risk of cardiotoxicity and arrhythmias
  • Colesevelam Bile Acid Sequestrants may decrease the bioavailability of Amiodarone. Consider alternative antilipemic agent. The risk of subtherapeutic amiodarone serum concentrations when such is being used for the treatment of malignant arrhythmias can be very large. The effect (ie, reduced risk) of separating doses of these agents is unknown. Amiodarone should be administered at least 1 hour before or 4 hours after colesevelam.1 Similar dosing with other agents seems warranted.
  • Cyclosporine Amiodarone may increase the therapeutic and adverse effects of cyclosporine.
  • Dabigatran etexilate Amiodarone may increase the serum concentration of dabigatran etexilate, resulting in increased risk of bleeding. Consider modifying therapy.
  • Dicoumarol Amiodarone may increase the anticoagulant effect of dicumarol.
  • Digoxin Amiodarone may increase the effect of digoxin.
  • Dihydroquinidine barbiturate Increases the effect of quinidine
  • Diltiazem Increased risk of cardiotoxicity and arrhythmias
  • Eltrombopag Affects hepatic enzyme CYP2C9/10 metabolism, increases effect/level of eltrombopag.
  • Erythromycin Increased risk of cardiotoxicity and arrhythmias
  • Ethotoin Increases the effect of hydantoin
  • Etravirine Amiodarone, when used concomitantly with etravirine, may decrease in serum concentration. If possible, monitoring for decreased amiodarone levels is recommended.
  • Etravirine Amiodarone, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. If possible, monitoring of amiodarone levels is recommended.
  • Fentanyl Possible bradycardia, hypotension
  • Fingolimod Pharmacodynamic synergist. Contraindicated. Increased risk of bradycardia, AV block, and torsade de pointes.
  • Flecainide Amiodarone may increase the effect and toxicity of flecainide
  • Fosamprenavir The protease inhibitor, fosamprenavir, may increase the effect and toxicity of amiodarone.
  • Fosphenytoin Amiodarone may increase the effect of fosphenytoin.
  • Gatifloxacin Increased risk of cardiotoxicity and arrhythmias
  • Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
  • Indacaterol Concomitant therapy with monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs that prolong the QTc interval should be monitored closely. These drugs may potentiate the effect of adrenergic agonist on the cardiovascular system.
  • Indinavir Indinavir increases the effect and toxicity of amiodarone
  • Iohexol Increased risk of cardiotoxicity and arrhythmias
  • Levofloxacin Increased risk of cardiotoxicity and arrhythmias
  • Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Mephenytoin Increases the effect of hydantoin
  • Mesoridazine Increased risk of cardiotoxicity and arrhythmias
  • Moxifloxacin Increased risk of cardiotoxicity and arrhythmias
  • Nelfinavir Nelfinavir may increase the effect and toxicity of amiodarone.
  • Phenytoin Amiodarone may increase the therapeutic and adverse effects of phenytoin.
  • Procainamide Amiodarone may increase serum levels and toxicity of procainamide.
  • Quinidine Amiodarone may increase the effect of quinidine.
  • Quinidine barbiturate Increases the effect of qiunidine
  • Ranolazine Possible additive effect on QT prolongation
  • Rifampicin Rifampin decreases the effect of amiodarone
  • Ritonavir Ritonavir increases the effect and toxicity of amiodarone
  • Roflumilast Increases roflumilast levels.
  • Saquinavir The protease inhibitor, saquinavir, may increase the effect and toxicity of amiodarone.
  • Simvastatin Increased risk of rhabdomyolysis
  • Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
  • Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Tamoxifen Amiodarone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
  • Tamsulosin Amiodarone, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Amiodarone is initiated, discontinued, or dose changed.
  • Telavancin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Telithromycin Telithromycin may reduce clearance of Amiodarone. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Amiodarone if Telithromycin is initiated, discontinued or dose changed.
  • Terfenadine Increased risk of cardiotoxicity and arrhythmias
  • Thioridazine Increased risk of cardiotoxicity and arrhythmias
  • Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
  • Tipranavir Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Amiodarone. Concomitant therapy is contraindicated.
  • Tizanidine Amiodarone may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
  • Tolterodine Amiodarone may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
  • Topotecan The p-glycoprotein inhibitor, Amiodarone, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
  • Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
  • Tramadol Amiodarone may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Amiodarone may decrease the effect of Tramadol by decreasing active metabolite production.
  • Trazodone The CYP3A4 inhibitor, Amiodarone, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Amiodarone is initiated, discontinued or dose changed.
  • Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Vardenafil Increased risk of cardiotoxicity and arrhythmias
  • Verapamil Additive bradycardic effects may occur. One case report of sinus arrest has been reported. Monitor for changes in the therapeutic effect and signs of Verapamil toxicity if Amiodarone is initiated, discontinued or dose changed.
  • Voriconazole Additive QTc prolongation may occur. Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of amiodarone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of amiodarone if voriconazole is initiated, discontinued or dose changed.
  • Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
  • Warfarin Amiodarone may increase the anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if amiodarone is initiated, discontinued or dose changed.
  • Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
  • Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Liều Lượng & Cách Dùng : Liquid - Intravenous
Solution - Intravenous
Tablet - Oral
Dữ Kiện Thương Mại
Giá thị trường
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Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01118
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2157
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507387
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C06823
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D02910
ChemSpider
http://www.chemspider.com/Chemical-Structure.2072.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=18957
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0703-1332-03
PharmGKB
http://www.pharmgkb.org/drug/PA448383
Wikipedia
http://en.wikipedia.org/wiki/Amiodarone
RxList
http://www.rxlist.com/cgi/generic/amiodarone.htm
Drugs.com
http://www.drugs.com/amiodarone.html
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