Tìm theo
Acenocoumarol
Các tên gọi khác (17 ) :
  • 3-(alpha-(4'-Nitrophenyl)-beta-acetylethyl)-4-hydroxycoumarin
  • 3-(alpha-(P-Nitrophenol)-beta-acetylethyl)-4-hydroxycoumarin
  • 3-(alpha-Acetonyl-4-nitrobenzyl)-4-hydroxycoumarin
  • 3-(alpha-Acetonyl-P-nitrobenzyl)-4-hydroxycoumarin
  • 3-(alpha-P-Nitrophenyl-beta-acetylethyl)-4-hydroxycoumarin
  • 4-Hydroxy-3-(1-(4-nitrophenyl)-3-oxobutyl)-2H-1-benzopyran-2-one
  • 4-Hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one
  • Acenocoumarin
  • Acenocoumarolum
  • Acenocumarol
  • Acenocumarolo
  • Acenokumarin
  • Nicoumalone
  • Nicumalon
  • Nitrophenylacetylethyl-4-hydroxycoumarine
  • Nitrovarfarian
  • Nitrowarfarin
Thuốc tác dụng lên quá trình đông máu
Thuốc Gốc
Small Molecule
CAS: 152-72-7
ATC: B01AA07
CTHH: C19H15NO6
PTK: 353.3255
Acenocoumarol is a coumarin derivative used as an anticoagulant. Coumarin derivatives inhibit the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of vitamin K-dependent clotting factors, II, VII, XI and X, and interferes with coagulation. Hematocrit, hemoglobin, international normalized ratio and liver panel should be monitored. Patients on acenocoumarol are prohibited from giving blood.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C19H15NO6
Phân tử khối
353.3255
Monoisotopic mass
353.089937217
InChI
InChI=1S/C19H15NO6/c1-11(21)10-15(12-6-8-13(9-7-12)20(24)25)17-18(22)14-4-2-3-5-16(14)26-19(17)23/h2-9,15,22H,10H2,1H3
InChI Key
InChIKey=VABCILAOYCMVPS-UHFFFAOYSA-N
IUPAC Name
4-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one
Traditional IUPAC Name
acenocoumarol
SMILES
CC(=O)CC(C1=CC=C(C=C1)[N+]([O-])=O)C1=C(O)C2=CC=CC=C2OC1=O
Độ tan chảy
196-199
Độ hòa tan
practically insoluble
logP
1.98
logS
-4.5
pKa (strongest acidic)
5.79
pKa (Strongest Basic)
-6.8
PSA
109.42 Å2
Refractivity
94.18 m3·mol-1
Polarizability
34.35 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
5
H Bond Donor Count
1
Physiological Charge
-1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Acenocoumarol inhibits the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of certain glutamic acid residues near the N-terminals of clotting factors II, VII, IX and X, the vitamin K-dependent clotting factors. Glutamic acid carboxylation is important for the interaction between these clotting factors and calcium. Without this interaction, clotting cannot occur. Both the extrinsic (via factors VII, X and II) and intrinsic (via factors IX, X and II) are affected by acenocoumarol.
Cơ Chế Tác Dụng : Acenocoumarol is a coumarin derivative used as an anticoagulant. Coumarin derivatives inhibit the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of vitamin K-dependent clotting factors, II, VII, XI and X, and interferes with coagulation. Hematocrit, hemoglobin, international normalized ratio and liver panel should be monitored. Patients on acenocoumarol are prohibited from giving blood. Acenocoumarol inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent clotting factors, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited resulting in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
Dược Động Học :
▧ Absorption :
Rapidly absorbed orally with greater than 60% bioavailability. Peak plasma levels are attained 1 to 3 hours following oral administration.
▧ Volume of Distribution :
The volume of distribution at steady-state appeared to be significantly dose dependent: 78 ml/kg for doses < or = 20 microg/kg and 88 ml/kg for doses > 20 microg/kg respectively
▧ Protein binding :
98.7% protein bound, mainly to albumin
▧ Metabolism :
Extensively metabolized in the liver via oxidation forming two hydroxy metabolites and keto reduction producing two alcohol metabolites. Reduction of the nitro group produces an amino metabolite which is further transformed to an acetoamido metabolite. Metabolites do not appear to be pharmacologically active.
▧ Route of Elimination :
Mostly via the kidney as metabolites
▧ Half Life :
8 to 11 hours.
Độc Tính : The onset and severity of the symptoms are dependent on the individual's sensitivity to oral anticoagulants, the severity of the overdosage, and the duration of treatment. Bleeding is the major sign of toxicity with oral anticoagulant drugs. The most frequent symptoms observed are: cutaneous bleeding (80%), haematuria (with renal colic) (52%), haematomas, gastrointestinal bleeding, haematemesis, uterine bleeding, epistaxis, gingival bleeding and bleeding into the joints. Further symptoms include tachycardia, hypotension, peripheral circulatory disorders due to loss of blood, nausea, vomiting, diarrhoea and abdominal pains.
Chỉ Định : For the treatment and prevention of thromboembolic diseases. More specifically, it is indicated for the for the prevention of cerebral embolism, deep vein thrombosis, pulmonary embolism, thromboembolism in infarction and transient ischemic attacks. It is used for the treatment of deep vein thrombosis and myocardial infarction.
Tương Tác Thuốc :
  • Acetaminophen Acetaminophen may increase the anticoagulant effect of acenocoumarol. Monitor for changes in the therapeutic and adverse effects of acenocoumarol if acetaminophen is initiated, discontinued or dose changed.
  • Acetylsalicylic acid Acetylsalicylic acid increases the effect of the anticoagulant, acenocoumarol.
  • Allopurinol Allopurinol may increase the anticoagulant effect of acenocoumarol.
  • Aminoglutethimide Aminoglutethimide may decrease the anticoagulant effect of acenocoumarol.
  • Amiodarone Amiodarone may increase the anticoagulant effect of acenocoumarol.
  • Amprenavir Amprenavir may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.
  • Aprepitant Aprepitant may decrease the anticoagulant effect of acenocoumarol by decreasing its serum concentration.
  • Atazanavir The protease inhibitor, atazanavir, may increase the anticoagulant effect of acenocoumarol.
  • Azathioprine Azathioprine may decrease the anticoagulant effect of acenocoumarol.
  • Azithromycin Azithromycin may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.
  • Betamethasone The corticosteroid, betamethasone, alters the anticoagulant effect, acenocoumarol.
  • Bosentan Bosentan may decrease the anticoagulant effect of acenocoumarol by increasing its metabolism.
  • Butabarbital Barbiturates like butabarbital may increase the metabolism of Vitamin K Antagonists like acenocoumarol. onitor for decreased therapeutic effects of oral anticoagulants if a barbiturate is initiated/dose increased (anticoagulant dosage increases of 30% to 60% may be needed based on monitored PT), or increased effects if a barbiturate is discontinued/dose decreased. An increased frequency of PT monitoring should be considered for the period immediately following barbiturate initiation/dosage changes.
  • Butalbital Barbiturates such as butalbital may increase the metabolism of Vitamin K Antagonists such as acenocoumarol. Monitor for decreased therapeutic effects of oral anticoagulants if a barbiturate is initiated/dose increased (anticoagulant dosage increases of 30% to 60% may be needed based on monitored PT), or increased effects if a barbiturate is discontinued/dose decreased. An increased frequency of PT monitoring should be considered for the period immediately following barbiturate initiation/dosage changes.
  • Capecitabine Capecitabine may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.
  • Carbamazepine Carbamazepine may decrease the anticoagulant effect of acenocoumarol by decreasing its serum concentration.
  • Cefotetan The cephalosporin, cefotetan, may increase the anticoagulant effect of acenocoumarol.
  • Cefoxitin The cephalosporin, cefoxitin, may increase the anticoagulant effect of acenocoumarol.
  • Ceftriaxone The cephalosporin, ceftriaxone, may increase the anticoagulant effect of acenocoumarol.
  • Celecoxib Celecoxib may increase the anticoagulant effect of acenocoumarol.
  • Cholestyramine The bile acid sequestrant, cholestyramine, may decrease the anticoagulant effect of acenocoumarol by decreasing its absorption.
  • Cimetidine Cimetidine may increase the anticoagulant effect of acenocoumarol.
  • Ciprofloxacin The quinolone antibiotic, ciprofloxacin, may increase the anticoagulant effect of acenocoumarol.
  • Cisapride Cisapride may increase the anticoagulant effect of acenocoumarol.
  • Citalopram The SSRI, citalopram, increases the effect of anticoagulant, acenocoumarol.
  • Clarithromycin The macrolide, clarithromycin, may increase the anticoagulant effect of acenocoumarol.
  • Clofibrate The fibrate increases the anticoagulant effect
  • Colestipol The bile acid sequestrant, colestipol, may decrease the anticoagulant effect of acenocoumarol by decreasing its absorption.
  • Cyclophosphamide The antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of acenocoumarol.
  • Danazol The androgen, danazol, may increase the anticoagulant effect of acenocoumarol.
  • Demeclocycline The tetracycline, demeclocycline, may increase the anticoagulant effect of acenocoumarol.
  • Dexamethasone The corticosteroid, dexamethasone, alters the anticoagulant effect, acenocoumarol.
  • Dextropropoxyphene Propoxyphene may increase the anticoagulant effect of acenocoumarol.
  • Dextrothyroxine The thyroid hormone, dextrothyroxine, increase the anticoagulant effect of acenocoumarol.
  • Dicloxacillin Dicloxacillin may decrease the anticoagulant effect of acenocoumarol.
  • Diflunisal The NSAID, diflunisal, may increase the anticoagulant effect of acenocoumarol.
  • Disulfiram Disulfiram may increase the anticoagulant effect of acenocoumarol.
  • Doxycycline The tetracycline, doxycycline, may increase the anticoagulant effect of acenocoumarol.
  • Erythromycin The macrolide, erythromycin, may increase the anticoagulant effect of acenocoumarol.
  • Ethchlorvynol Ethchlorvynol may decrease the anticoagulant effect of acenocoumarol.
  • Ethinyl Estradiol Increased thrombotic risk due to estrogen
  • Etodolac The NSAID, etodolac, may increase the anticoagulant effect or acenocoumarol.
  • Etoricoxib Etoricoxib may increase the anticoagulant effect of acenocoumarol.
  • Fenofibrate Fenofibrate may increase the anticoagulant effect of acenocoumarol.
  • Fenoprofen The NSAID, fenoprofen, may increase the anticoagulant effect of acenocoumarol.
  • Fluconazole Fluconazole may increase the serum concentration of acenocoumarol by decreasing its metabolism.
  • Fludrocortisone The corticosteroid, fludrocortisone, alters the anticoagulant effect, acenocoumarol.
  • Fluorouracil The antineoplasic agent, fluorouracil, may increase the anticoagulant effect of acenocoumarol.
  • Fluoxetine The SSRI, fluoxetine, increases the effect of anticoagulant, acenocoumarol.
  • Fluoxymesterone The androgen, fluoxymesterone, may increase the anticoagulant effect of acenocoumarol.
  • Flurbiprofen The NSAID, flurbiprofen, may increase the anticoagulant effect of acenocoumarol.
  • Fluvastatin Fluvastatin may increase the anticoagulant effect of acenocoumarol. Monitor for changes in the therapeutic and adverse effects of acenocoumarol if fluvastatin is initiated, discontinued or dose changed.
  • Fluvoxamine Fluvoxamine may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.
  • Fosamprenavir The protease inhibitor, fosamprenavir, may increase the anticoagulant effect of acenocoumarol.
  • Fosphenytoin Increased hydantoin levels and risk of bleeding
  • Gefitinib Gefitinib may increase the anticoagulant effect of acenocoumarol.
  • Gemcitabine Gemcitabine may increase the anticoagulant effect of acenocoumarol.
  • Gemfibrozil Gemfibrozil may increase the anticoagulant effect of acenocoumarol.
  • Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
  • Glutethimide Glutethimide may decrease the anticoagulant effect of acenocoumarol.
  • Griseofulvin Griseofulvin may decrease the anticoagulant effect of acenocoumarol.
  • Hydrocortisone The corticosteroid, hydrocortisone, alters the anticoagulant effect, acenocoumarol.
  • Ibuprofen The NSAID, ibuprofen, may increase the anticoagulant effect of acenocoumarol.
  • Imatinib Imatinib may increase the anticoagulant effect of acenocoumarol.
  • Indinavir The protease inhibitor, indinavir, may increase the anticoagulant effect of acenocoumarol.
  • Indomethacin The NSAID, indomethacin, may increase the anticoagulant effect of acenocoumarol.
  • Isoniazid Isoniazid may increase the anticoagulant effect of acenocoumarol.
  • Itraconazole Itraconazole may increase the anticoagulant effect of acenocoumarol.
  • Ketoconazole Ketoconazole may increase the anticoagulant effect of acenocoumarol.
  • Ketoprofen The NSAID, ketoprofen, may increase the anticoagulant effect of acenocoumarol.
  • Ketorolac The NSAID, ketorolac, may increase the anticoagulant effect of acenocoumarol.
  • Leflunomide Leflunomide may increase the anticoagulant effect of acenocoumarol.
  • Levamisole Levamisole may increase the anticoagulant effect of acenocoumarol.
  • Levofloxacin The quinolone antibiotic, levofloxacin, may increase the anticoagulant effect of acenocoumarol.
  • Levothyroxine The thyroid hormone, levothyroxine, increase the anticoagulant effect of acenocoumarol.
  • Lovastatin Lovastatin may increase the anticoagulant effect of acenocoumarol. Monitor for changes in the therapeutic and adverse effects of acenocoumarol if lovastatin is initiated, discontinued or dose changed.
  • Lumiracoxib Lumiracoxib may increase the anticoagulant effect of acenocoumarol.
  • Medroxyprogesterone Acetate Medroxyprogesterone may increase the anticoagulant effect of acenocoumarol.
  • Mefenamic acid The NSAID, mefanamic acid, may increase the anticoagulant effect of acenocoumarol.
  • Mefloquine Mefloquine may increase the anticoagulant effect of acenocoumarol.
  • Meloxicam Meloxicam may increase the anticoagulant effect of acenocoumarol.
  • Mercaptopurine Mercaptopurine may decrease the anticoagulant effect of acenocoumarol.
  • Methimazole The antithyroid agent, methimazole, may decrease the anticoagulant effect of acenocoumarol.
  • Metronidazole Metronidazole may increase the anticoagulant effect of acenocoumarol.
  • Miconazole Miconazole may increase the serum concentration of acenocoumarol by decreasing its metabolism.
  • Minocycline The tetracycline, minocycline, may increase the anticoagulant effect of acenocoumarol.
  • Mitotane Mitotane may decrease the anticoagulant effect of acenocoumarol.
  • Moxifloxacin The quinolone antibiotic, moxifloxacin, may increase the anticoagulant effect of acenocoumarol.
  • Nabumetone The NSAID, nabumetone, may increase the anticoagulant effect of acenocoumarol.
  • Nalidixic Acid The quinolone antibiotic, nalidixic acid, may increase the anticoagulant effect of acenocoumarol.
  • Naproxen The NSAID, naproxen, may increase the anticoagulant effect of acenocoumarol.
  • Nelfinavir The protease inhibitor, nelfinavir, may increase the anticoagulant effect of acenocoumarol.
  • Nevirapine Nevirapine may decrease the anticoagulant effect of acenocoumarol.
  • Norfloxacin The quinolone antibiotic, norfloxacin, may increase the anticoagulant effect of acenocoumarol.
  • Ofloxacin The quinolone antibiotic, ofloxacin, may increase the anticoagulant effect of acenocoumarol.
  • Orlistat Orlistat may increase the anticoagulant effect of acenocoumarol.
  • Oxaprozin The NSAID, oxaprozin, may increase the anticoagulant effect of acenocoumarol.
  • Oxyphenbutazone The NSAID, oxyphenbutazone, may increase the anticoagulant effect of acenocoumarol.
  • Paroxetine The SSRI, paroxetine, increases the effect of the anticoagulant, acenocoumarol.
  • Pentoxifylline Pentoxifylline may increase the anticoagulant effect of acenocoumarol.
  • Phenobarbital The barbiturate, phenobarbital, decreases the anticoagulant effect of acenocoumarol.
  • Phenylbutazone The NSAID, phenylbutazone, may increase the anticoagulant effect of acenocoumarol.
  • Phenytoin Increased hydantoin levels and risk of bleeding
  • Piroxicam The NSAID, piroxicam, may increase the anticoagulant effect of acenocoumarol.
  • Prednisolone The corticosteroid, prednisolone, alters the anticoagulant effect, acenocoumarol.
  • Prednisone The corticosteroid, prednisone, alters the anticoagulant effect, acenocoumarol.
  • Primidone The barbiturate, primidone, decreases the anticoagulant effect of acenocoumarol.
  • Propafenone Propafenone may increase the anticoagulant effect of acenocoumarol.
  • Propylthiouracil The anti-thyroid agent, propylthiouracil, may decrease the anticoagulant effect of acenocoumarol.
  • Quinidine Quinidine may increase the anticoagulant effect of acenocoumarol.
  • Quinine Quinine, a moderate CYP2C9 inhibitor, may increase the serum concentration of acenocoumarol by decreasing its metabolism via CYP2C9.
  • Ranitidine Ranitidine may increase the anticoagulant effect of acenocoumarol. (Conflicting evidence)
  • Rifabutin Rifabutin may decrease the anticoagulant effect of acenocoumarol by increasing its metabolism.
  • Rifampicin Rifampin may decrease the anticoagulant effect of acenocoumarol by increasing its metabolism.
  • Sulindac The NSAID, sulindac, may increase the anticoagulant effect of acenocoumarol. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.
  • Tamoxifen Tamoxifen may increase the serum concentration of Acenocoumarol increasing the risk of bleeding. Concomitant therapy should be avoided.
  • Telithromycin Telithromycin may increase the anticoagulant effect of acenocoumarol.
  • Tenoxicam The NSAID, tenoxicam, may increase the anticoagulant effect of acenocoumarol.
  • Testolactone The androgen, Testolactone, may incrase the anticoagulant effect of the Vitamin K antagonist, Acenocoumarol. Monitor for changes in the therapeutic effect of Acenocoumarol if Testolactone is initiated, discontinued or dose changed.
  • Testosterone The androgen, Testosterone, may incrase the anticoagulant effect of the Vitamin K antagonist, Acenocoumarol. Monitor for changes in the therapeutic effect of Acenocoumarol if Testosterone is initiated, discontinued or dose changed.
  • Testosterone Propionate The androgen, Testosterone, may incrase the anticoagulant effect of the Vitamin K antagonist, Acenocoumarol. Monitor for changes in the therapeutic effect of Acenocoumarol if Testosterone is initiated, discontinued or dose changed.
  • Tetracycline Tetracycline may increase the anticoagulant effect of acenocoumarol.
  • Thiabendazole The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Acenocoumarol by decreasing Acenocoumarol metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Acenocoumarol if Thiabendazole is initiated, discontinued or dose changed.
  • Thiopental Thiopental may increase the metabolism of the Vitamin K antagonist, Acenocoumarol. Acenocoumarol dose adjustment may be required.
  • Tiaprofenic acid Increased risk of bleeding.
  • Tigecycline Tigecycline may increase the anticoagulant effect of acenocoumarol.
  • Tolbutamide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Acenocoumarol. Consider alternate therapy or monitor for changes in Acenocoumarol therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
  • Tolmetin Increased risk of bleeding. Monitor for signs and symptoms of bleeding.
  • transdermal testosterone gel The androgen, Testosterone, may incrase the anticoagulant effect of the Vitamin K antagonist, Acenocoumarol. Monitor for changes in the therapeutic effect of Acenocoumarol if Testosterone is initiated, discontinued or dose changed.
  • Treprostinil The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the anticoagulant, Acenocoumarol. Monitor for increased bleeding during concomitant thearpy.
  • Triamcinolone The corticosteroid, triamcinolone, alters the anticoagulant effect, acenocoumarol.
  • Trimetrexate The anticoagulant effect of Acenocoumarol, a Vitamin K antagonist, may be altered by antineoplastics such as Trimetrexate. Monitor for changes in the anticoagulant effects of warfarin and other coumarin derivatives during concomitant use.
  • Zafirlukast Zafirlukast may inhibit the metabolism of the vitamin K antagonist Acenocoumarol and increase INR and risk of bleeding.
Liều Lượng & Cách Dùng : Tablet - Oral - 1 mg
Tablet - Oral - 4 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Sintrom 4 mg Tablet
    Giá bán buôn : USD >1.6
    Đơn vị tính : tablet
  • Biệt dược thương mại : Sintrom 1 mg Tablet
    Giá bán buôn : USD >0.51
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty : Star
    Sản phẩm biệt dược : Ascumar
  • Công ty :
    Sản phẩm biệt dược : Mini-sintrom
  • Công ty :
    Sản phẩm biệt dược : Sinkumar
  • Công ty : Paladin
    Sản phẩm biệt dược : Sintrom
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01418
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D07064
PharmGKB
http://www.pharmgkb.org/drug/PA452632
Wikipedia
http://en.wikipedia.org/wiki/Acenocoumarol
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