Oral anticoagulants, drug reaction

The oral anticoagulant drugs act indirectly on the process of Glu carboxylation of the vitamin K-dependent proteins. The vitamin K antagonists prevent the reduction of the reaction intermediate, vitamin K epoxide. Blockage of the epoxide reductase reaction results in the accumulation of vitamin K epoxide and other nonfunctional forms of vitamin K. Without regeneration of the vitamin K-related reaction intermediates through the cycle shown in Figure 36-22, a depletion of functional vitamin K occurs. 

Interactions. Drugs that lower gastric acidity, e.g. antacids, histamine H2 receptor antagonists, impair the absorption of ketoconazole from the gastrointestinal tract. Like all imidazoles, ketoconazole binds strongly to several cytochrome P450 isoenzymes and thus inhibits the metabolism (and increases effects of) oral anticoagulants, phenytoin and cyclosporin, and increases the risk of cardiac arrhythmias with terfenadine. A disulfiram-like reaction occurs with alcohol. Concurrent use of rifampicin, by enzyme induction of CYP 3A, markedly reduces the plasma concentration of ketoconazole. 

Warfarin is the most commonly prescribed oral anticoagulant, with four million U.S. patients taking the drug for treatment and prevention of atrial fibrillation, stroke, deep vein thrombosis, or pulmonary embolism, and for those who have had heart valve replacement surgery. Adverse reactions to warfarin... 

This drug is indicated for infections of skin and nails due to dermatophytes or Candida species and vulvovaginal infections due to Candida species. Miconazole is used orally for prophylactic purposes in patients who have been treated with cytostatics or immunosuppressants, in particular, to prevent candidosis of the mouth and digestive tract. Side effects include possible nausea during oral treatment. Miconazole tablets may increase the anticoagulant effect of coumarin derivatives. Topical treatment with cream or powder is well tolerated. Local irritation and alleigic reactions of the skin and mucosa occur only rarely. 

Doses of griseofulvin are 15-20 mg/kg/d for 6 to 8 weeks in children with the microsized form. More frequent side effects are minor headaches, gastrointestinal reactions and cutaneous eruptions. The major drug interactions have been noted with phenobarbital, anticoagulants and oral contraceptives. 

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