Top Gene Interactions
- 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.
- Uses/Sources: Acenocoumarol is an anticoagulant drug derived from coumarin. (L1261) 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.
- Health Effects: Acenocoumarol is an anticoagulant and may cause internal bleeding, leading to shock, loss of consciousness, and eventually death. (L1257)
- Symptoms: 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.
- Treatment: The primary antidote to acenocoumarol poisoning is immediate administration of vitamin K1 (initially slow intravenous injections of 10-25 mg repeated all 3-6 hours until normalisation of the prothrombin time; then 10 mg orally four times daily as a "maintenance dose"). It is an extremely effective antidote, provided the poisoning is caught before too much damage has been done to the victim's circulatory system. At high doses acenocoumarol can affect the body for many months, and the antidote must be administered regularly for a long period of time. (L1257)
- Route of Exposure: Ingestion (L1817) ; dermal (L1817). Rapidly absorbed orally with greater than 60% bioavailability. Peak plasma levels are attained 1 to 3 hours following oral administration.
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 1470 mg/kg (Oral, Mouse) (T14) LD50: 115 mg/kg (Intraperitoneal, Mouse) (T14)
Mechanism of Action
|Target Name||Mechanism of Action||References|
Vitamin K epoxide reductase complex subunit 1
Alpha-1-acid glycoprotein 1
|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.||
Acenocoumarol Interacts with Diseases
|Disease||Inference Score||References/Inference Genes|
|Drug-Related Side Effects and Adverse Reactions||7.83|
|Coronary heart disease||7.11||
|Chronic obstructive pulmonary disease||6.81||
|VITAMIN K-DEPENDENT CLOTTING FACTORS, COMBINED DEFICIENCY OF, 2||6.66||
|Acute lymphoblastic leukemia||6.15||
|Drug Metabolism, Poor, CYP2C19-Related||6.1|
|Sea-Blue Histiocyte Syndrome||6.09||
|Alzheimer disease type 2||5.74||
|Cerebral amyloid angiopathy||5.74||
|Inflammatory Bowel Disease 13||5.72||