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药品详细

Acenocoumarol(醋硝香豆素)

化学结构式图
中文名
醋硝香豆素
英文名
Acenocoumarol
分子式
C19H15NO6
化学名
4-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one
分子量
Average: 353.3255
Monoisotopic: 353.089937217
CAS号
152-72-7
ATC分类
B01A 抗血栓药
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

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.

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    封装厂家
    参考
    Synthesis Reference Not Available
    General Reference
    1. Cesar JM, Garcia-Avello A, Navarro JL, Herraez MV: Aging and oral anticoagulant therapy using acenocoumarol. Blood Coagul Fibrinolysis. 2004 Oct;15(8):673-6. Pubmed
    2. Lengyel M: [Warfarin or acenocoumarol is better in the anticoagulant treatment of chronic atrial fibrillation?] Orv Hetil. 2004 Dec 26;145(52):2619-21. Pubmed
    3. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. Pubmed
    4. Montes R, Ruiz de Gaona E, Martinez-Gonzalez MA, Alberca I, Hermida J: The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients. Br J Haematol. 2006 Apr;133(2):183-7. Pubmed
    5. Girard P, Nony P, Erhardtsen E, Delair S, Ffrench P, Dechavanne M, Boissel JP: Population pharmacokinetics of recombinant factor VIIa in volunteers anticoagulated with acenocoumarol. Thromb Haemost. 1998 Jul;80(1):109-13. Pubmed
    剂型
    规格
    化合物类型
    Type small molecule
    Classes Not Available
    Substructures Not Available
    适应症
    药理
    Indication 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.
    Pharmacodynamics 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.
    Mechanism of action 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.
    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.

    Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

    Substrate Enzymes Product
    Acenocoumarol
    		6-Hydroxy-R-acenocoumarol Details
    Acenocoumarol
    		7-Hydroxy-R-acenocoumarol Details
    Acenocoumarol
    		8-Hydroxy-R-acenocoumarol Details
    Route of elimination Mostly via the kidney as metabolites
    Half life 8 to 11 hours.
    Clearance Not Available
    Toxicity 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.
    Affected organisms
    • Humans and other mammals
    Pathways
    Pathway Name SMPDB ID
    Smp00269 Acenocoumarol Pathway SMP00269
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    melting point 197 °C PhysProp
    water solubility practically insoluble MSDS
    logP 1.98 SANGSTER (1994)
    Predicted Properties
    Property Value Source
    water solubility 1.06e-02 g/l ALOGPS
    logP 2.53 ALOGPS
    logP 2.68 ChemAxon
    logS -4.5 ALOGPS
    pKa (strongest acidic) 5.79 ChemAxon
    pKa (strongest basic) -6.8 ChemAxon
    physiological charge -1 ChemAxon
    hydrogen acceptor count 5 ChemAxon
    hydrogen donor count 1 ChemAxon
    polar surface area 109.42 ChemAxon
    rotatable bond count 5 ChemAxon
    refractivity 94.18 ChemAxon
    polarizability 34.35 ChemAxon
    药物相互作用
    Drug Interaction
    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.
    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 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.
    Propoxyphene Propoxyphene 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.
    Rifampin 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.
    食物相互作用
    • High doses of vitamin A, C, E and K (e.g. avocado, green vegetables)

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