Linked Life Data

19799531

Source:http://linkedlifedata.com/resource/pubmed/id/19799531

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-10-5
pubmed:abstractText
Oral anticoagulants, the main drugs used for the prevention and treatment of thromboembolic diseases, are a leading cause of fatal haemorrhagic complications due to the variable reactions that different patients can have when taking the drugs. The reaction to coumarins is affected by both diet such as the patient daily intake of vitamin K, and also by genetically determined levels of critical proteins. Clinically available, warfarin consists of a racemic mixture of two active optical isomers, (R)- and (S)- isoforms, and their pharmacokinetic and pharmaco-dynamic properties differ considerably, because the (S)-enantiomer is three times more potent than the (R)-enantiomer. Metabolism of warfarin occurs through the action of three different cytochrome P-450 enzymes. S-warfarin, predominantly responsible for the anticoagulation effect, is metabolized mostly by the CYP2C9 enzyme. A number of polymorphisms in CYP2C9 gene have been identified but the most important are CYP2C9*2 and CYP2C9*3. The second enzyme that is involved in coumarins metabolism is the vitamin K epoxide reductase (VKORC). This enzyme is the target of coumarins and converts oxidized vitamin K to the reduced active form that is required for the post-translational (gamma) carboxylation of the vitamin K-dependent coagulation factors. VKORC activity levels are affected by several polymorphisms that can be divided into high or low level haplotypes. There is a considerable controversy about the clinical use of genotyping before starting the anticoagulant therapy so, further randomized, prospective and large trials are required to recommend the use of pharmacogenetic testing.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1875-5453
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
632-42
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Implications of pharmacogenetics for oral anticoagulants metabolism.
pubmed:affiliation
Department of Hematology and Oncology, Hospital Morales Meseguer, Murcia, Spain.
pubmed:publicationType
Journal Article