Definition
Description
Top Gene Interactions
General Information
- Metabolism: Phenprocoumon is stereoselectively metabolized by hepatic microsomal enzymes (cytochrome P-450) to inactive hydroxylated metabolites (predominant route) and by reductases to reduced metabolites. Cytochrome P450 2C9 is the principal form of human liver P-450 responsible for metabolism. Half Life: 5-6 days
- Uses/Sources: Phenprocoumon is an anticoagulant drug. (L1260) Used for the prevention and treatment of thromboembolic disease including venous thrombosis, thromboembolism, and pulmonary embolism as well as for the prevention of ischemic stroke in patients with atrial fibrillation (AF).
- Health Effects: Phenprocoumon is an anticoagulant and may cause internal bleeding, leading to shock, loss of consciousness, and eventually death. (L1257)
- Symptoms: Symptoms of overdose includes suspected or overt abnormal bleeding (e.g., appearance of blood in stools or urine, hematuria, excessive menstrual bleeding, melena, petechiae, excessive bruising or persistent oozing from superficial injuries).
- Treatment: The primary antidote to phenprocoumon 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 phenprocoumon 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). Bioavailability is close to 100%.
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Serum albumin Vitamin K epoxide reductase complex subunit 1 Alpha-1-acid glycoprotein 1 |
Phenprocoumon 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 decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots. |
18048412 |
Phenprocoumon Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Coumarin Resistance | 13.09 |
|
VITAMIN K-DEPENDENT CLOTTING FACTORS, COMBINED DEFICIENCY OF, 2 | 6.83 |
|
Hemorrhage | 6.07 |
|
Aortic Rupture | 5.73 |
|
Peptic Ulcer Hemorrhage | 5.18 |
|
Drug-Related Side Effects and Adverse Reactions | 4.85 | |
Blood Coagulation Disorders | 4.84 |
|
Coronary heart disease | 4.53 |
|
Vascular Diseases | 4.4 |
|
Stroke | 4.25 |
|
Brain Neoplasms | 4.02 |
|
Nephritis, Interstitial | 3.54 |
|
Drug Hypersensitivity | 3.37 |
|
Cardiomyopathies | 3.34 |
|
Nervous System Diseases | 3.28 |
|
Acute kidney injury | 3.09 |
|
Drug-induced liver injury | 2.85 |
|