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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.
Important drug interactions are rare. [38] [39] However, the most significant major drug interaction concern is the decreased activation of clopidogrel when taken together with omeprazole. [40] Although still controversial, [41] this may increase the risk of stroke or heart attack in people taking clopidogrel to prevent these events.
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]
Direct factor Xa inhibitors can be considered as an alternative to warfarin, particularly if a person is on several other medications that interact with warfarin, or if attending medical appointments and laboratory monitoring becomes difficult. [8]
When two drugs affect each other, it is a drug–drug interaction (DDI). The risk of a DDI increases with the number of drugs used. [1] A large share of elderly people regularly use five or more medications or supplements, with a significant risk of side-effects from drug–drug interactions. [2] Drug interactions can be of three kinds ...
In fact, adverse drug reactions (ADRs) often result from unanticipated changes in CYP2C9 enzyme activity secondary to genetic polymorphisms. Especially for CYP2C9 substrates such as warfarin and phenytoin, diminished metabolic capacity because of genetic polymorphisms or drug-drug interactions can lead to toxicity at normal therapeutic doses.
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.
Interactions with other drugs, food and drink, and other factors may increase or decrease the effect of certain analgesics and alter their half-life. Because some listed analgesics are prodrugs or have active metabolites , individual variation in liver enzymes (e.g., CYP2D6 enzyme) may result in significantly altered effects.