title: Warfarin toxicity and individual variability-clinical case.
abstract: Warfarin is a widely used anticoagulant in the treatment and prevention of thrombosis, in the treatment for chronic atrial fibrillation, mechanical valves, pulmonary embolism, and dilated cardiomyopathy. It is tasteless and colorless, was used as a poison, and is still marketed as a pesticide against rats and mice. Several long-acting warfarin derivatives-superwarfarin anticoagulants-such as brodifacoum, diphenadione, chlorophacinone, bromadiolone, are used as pesticides and can produce profound and prolonged anticoagulation. Several factors increase the risk of warfarin toxicity. However, polymorphisms in cytochrome P450 genes and drug interactions account for most of the risk for toxicity complications. Each person is unique in their degree of susceptibility to toxic agents. The toxicity interpretation and the health risk of most toxic substances are a subject of uncertainty. Genetically determined low metabolic capacity in an individual can dramatically alter the toxin and metabolite levels from those normally expected, which is crucial for drugs with a narrow therapeutic index, like warfarin. Personalized approaches in interpretation have the potential to remove some of the scientific uncertainties in toxicity cases.
authors: Diversity Health Institute, DHI Laboratory, ICPMR level 2, Sydney-West Area Health Service, Westmead Hospital, Westmead, NSW 2145, Australia. irina.piatkov@swahs.health.nsw.gov.au
authors: Irina
authors: I
authors: Piatkov
authors: Colin
authors: C
authors: Rochester
authors: Trudi
authors: T
authors: Jones
authors: Steven
authors: S
authors: Boyages
mesh_terms: D000925:Anticoagulants / Q000493:pharmacokinetics / Q000633:toxicity*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D020246:Venous Thrombosis / Q000188:drug therapy / Q000235:genetics; D014859:Warfarin / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases