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Colchicine, a drug for gout, interferes with the function of the structural protein tubulin, while digitalis, a drug still used in heart failure, inhibits the activity of the carrier molecule, Na-K-ATPase pump. The widest class of drugs act as ligands that bind to receptors that determine cellular effects.
Colchicine interacts with the P-glycoprotein transporter, and the CYP3A4 enzyme involved in drug and toxin metabolism. [ 26 ] [ 42 ] Fatal drug interactions have occurred when colchicine was taken with other drugs that inhibit P-glycoprotein and CYP3A4, such as erythromycin or clarithromycin .
Warfarin (actually the S-warfarin enantiomer) is a specific probe for CYP2C9. The '+ 1' refers to the vitamin K that is given together with the warfarin to prevent any anticoagulant effect. The Cooperstown cocktail and the Cooperstown 5 + 1 cocktail are powerful tools for investigating the activity of important drug metabolising enzymes.
Warfarin interacts with many commonly used drugs, and the metabolism of warfarin varies greatly between patients. [27] Some foods have also been reported to interact with warfarin. [27] Apart from the metabolic interactions, highly protein bound drugs can displace warfarin from serum albumin and cause an increase in the INR. [63]
Warfarin resistance In incomplete warfarin resistance, people only respond to high doses of warfarin; in complete warfarin resistance, the drug has no effect. This can be because the drug is metabolized quickly or because the clotting cascade does not interact with warfarin as it should.
Germline mutations in drug targets can also influence response to medications, though this is an emerging subfield within pharmacogenomics. One well-established gene-drug interaction involving a germline mutation to a drug target is warfarin (Coumadin) and VKORC1, which codes for vitamin K epoxide reductase (VKOR).
An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. [1] Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which help keep the bite area unclotted long enough for the animal to obtain blood.
Ximelagatran showed good efficacy compared with warfarin in several trials in prevention and treatment of deep vein thrombosis and as thromboprophylaxis in atrial fibrillation. [1] Development was stopped by manufacturer AstraZeneca , however, because of reports of liver enzyme derangements and liver failure .