PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
acenocoumarol

2D structure

Overview

Generic Names: Acenocoumarin; Acenocoumarolum [inn-latin]; Nicoumalone; Nicumalon; Nitrophenylacetylethyl-4-hydroxycoumarine; Nitrovarfarian; Nitrowarfarin
Trade Names: Ascumar; Neositron; Sincoumar; Sinkumar; Sinthrom; Sinthrome; Sintrom; Syncoumar; Syncumar; Syntrom; Zotil
PharmGKB Accession Id: PA452632

Description

A coumarin that is used as an anticoagulant. Its actions and uses are similar to those of warfarin. (From Martindale, The Extra Pharmacopoeia, 30th ed, p233) (source: Drug Bank)

Indication

For the treatment and prevention of thromboembolic diseases. (source: Drug Bank)

ATC Therapeutic Category

  • B01AA:Vitamin K antagonists

Pharmacology, Interactions, and Contraindications

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 proteins, 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. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots. (source: Drug Bank)

Pharmacology

Acenocoumarol is a coumarin that is used as an anticoagulant. Its actions and uses are similar to those of warfarin. (From Martindale, The Extra Pharmacopoeia, 30th ed, p233) (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. (source: Drug Bank)

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 poisoning 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. (source: Drug Bank)

Isomeric SMILES Code:

CC(=O)CC(c1ccc(cc1)N(=O)=O)c2c(c3ccccc3oc2=O)O (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs1057910 at chr10:96731043 in CYP2C9
    The CYP2C9*3 allele influenced the Factor VII coagulant activity, measured before and 24 hours after acenocoumarol intake, in 263 healthy volunteers. The study conludes that CYP2C9-related genetic variability accounts for 14% of the interindividual variability in acenocoumarol pharmacodynamic response.
    Variant Name:
    CYP2C9*3; CYP2C9:359Ile>Leu
    Related Drugs:
    acenocoumarol
    Evidence:
    PMID:15116053
  2. rs9934438 at chr16:31012379 in VKORC1
    Double homozygous VKORC1 1173T/T, CYP4F2 433Val/Val (n = 5) showed the highest INR (3.1; 2.0-4.7) and required the lowest acenocoumarol dose (11 ± 3 mg/week) The addition of the V433M genotype to the VKORC1 genotype raised the R2 from 8% to 14% for INR, and from 12% to 19% for acenocoumarol dose requirements.
    Variant Name:
    VKORC1:C1173T
    Related Drugs:
    acenocoumarol
    Related Diseases:
    Arteriosclerosis, Heart Diseases, Hemorrhage, Intracranial Hemorrhages, Myocardial Infarction, Peripheral Vascular Diseases, Pulmonary Embolism, Stroke, Thromboembolism, venous thromboembolism, Venous Thrombosis
    Evidence:
    PMID:19270263
  3. rs2108622 at chr19:15851431 in CYP4F2
    In a study of 100 white men with nonvalvular atrial fibrillation, the CYP4F2 rs2108622 (V433M) genotype significantly contributes to both early anticoagulant effect (international normalized ratio [INR]) (R2 = 0.14) and acenocoumarol dose requirements (R2 = 0.19). The V433M genotype had a gene dosage-dependent effect in decreasing plasma clotting factors in early drug response, with 433V homozygotes being the most sensitive. After initiation of therapy, the INR showed a gene significant dosage-dependent effect (P = .015), and 433V subjects needing 4 mg/week less than 433M carriers to achieve a steady anticoagulation (P = .043). The dose required to achieve a steady INR was also influenced by CYP4F2 genotype, similar to data reported for warfarin therapy. The CYP4F2 433M allele is reported to have decreased activity.
    Variant Name:
    CYP4F2:V433M
    Related Drugs:
    acenocoumarol
    Related Diseases:
    Arteriosclerosis, Heart Diseases, Hemorrhage, Intracranial Hemorrhages, Myocardial Infarction, Peripheral Vascular Diseases, Pulmonary Embolism, Stroke, Thromboembolism, venous thromboembolism, Venous Thrombosis
    Evidence:
    PMID:19270263
  4. rs2108622 at chr19:15851431 in CYP4F2
    Double homozygous VKORC1 1173T/T, CYP4F2 433Val/Val (n = 5) showed the highest INR (3.1; 2.0-4.7) and required the lowest acenocoumarol dose (11 ± 3 mg/week) The addition of the V433M genotype to the VKORC1 genotype raised the R2 from 8% to 14% for INR, and from 12% to 19% for acenocoumarol dose requirements.
    Variant Name:
    CYP4F2:V433M
    Related Drugs:
    acenocoumarol
    Related Diseases:
    Arteriosclerosis, Heart Diseases, Hemorrhage, Intracranial Hemorrhages, Myocardial Infarction, Peripheral Vascular Diseases, Pulmonary Embolism, Stroke, Thromboembolism, venous thromboembolism, Venous Thrombosis
    Evidence:
    PMID:19270263
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
APOE
  •   
  •   
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP4F2
  •   
  •   
  •   
  •   
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
VKORC1
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
ALB Uncurated Annotation (source: Drug Bank)
ORM1 Uncurated Annotation (source: Drug Bank)
VKORC1 Uncurated Annotation (source: Drug Bank)

A list of non-curated publications that mention this drug along with other drugs is available.

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Arteriosclerosis
  • CO
  •   
  •   
  •   
  •   
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Death
  • CO
  •   
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Heart Diseases
  •   
  • PD
  • PK
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Hemorrhage
  • CO
  •   
  •   
  •   
  •   
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Intracranial Hemorrhages
  • CO
  •   
  •   
  •   
  •   
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Myocardial Infarction
  • CO
  •   
  •   
  •   
  •   
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Peripheral Vascular Diseases
  • CO
  •   
  •   
  •   
  •   
Publications, Variants
Phenotype data available No genotype data Literature annotations available Not annotated
Pulmonary Embolism
  • CO
  •   
  •   
  •   
  •   
Publications, Variants
Phenotype data available No genotype data Literature annotations available Not annotated
Stroke
  • CO
  •   
  •   
  •   
  •   
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
venous thromboembolism
  • CO
  •   
  •   
  •   
  •   
Publications, Variants
Phenotype data available No genotype data Literature annotations available Not annotated
Venous Thrombosis
  • CO
  •   
  •   
  •   
  •   
Publications, Variants

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01418
PubChem Compound ID:
9052
PubChem Substance ID:
10321722

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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