Warfarin Corticosteroids

Patients at increased risk of NSAID-induced gastrointestinal adverse effects (e.g., dyspepsia, peptic ulcer formation, and bleeding) include the elderly, those with peptic ulcer disease, coagulopathy, and patients receiving high doses of concurrent corticosteroids. Nephrotoxicity is more common in the elderly, patients with creatinine clearance values less than 50 mL/minute, and those with volume depletion or on diuretic therapy. NSAIDs should be used with caution in patients with reduced cardiac output due to sodium retention and in patients receiving antihypertensives, warfarin, and lithium. 

Drugs that may affect fluconazole include cimetidine, hydrochlorothiazide, and rifampin. Drugs that may be affected by fluconazole include alfentanil, benzodiazepines, buspirone, carbamazepine, cisapride, oral contraceptives, corticosteroids, cyclosporine, haloperidol, HMG-CoA reductase inhibitors, losartan, nisoldipine, phenytoin, protease inhibitors, rifabutin, sirolimus, sulfonylureas, tacrolimus, theophylline, tolterodine, tricyclic antidepressants, vinca alkaloids, warfarin, zidovudine, and zolpidem. 

Indirect response models have been successfully applied for a number of drugs that display a relatively slow onset of effect compared to their distribution to the site of action. Examples are corticosteroids, warfarin, furosemide and terbutalin. Such models are also particularly appropriate if the measured response is a change in circulating blood cells or endogenous proteins (e.g. hormones or cytokines). 

Rifampicin is a potent inducer of cytochrome P450 enzymes and thus can diminish the activity of a multitude of other agents such as warfarin, gluco-corticosteroids, cyclosporin, oral contraceptives and sulphonylurea-type oral antidiabetic agents. 

Zafirlukast and montelukast are well tolerated. Zafirlukast increases plasma concentrations of warfarin and decreases the concentrations of theophylline and erythromycin. In rare cases, treatment of patients with CysLT receptor antagonists is associated with the development of Churg-Strauss syndrome, a condition marked by acute vasculitis, eosinophilia, and a worsening of pulmonary symptoms. Because these symptoms often appear when patients are given the leukotriene receptor antagonists when they are being weaned from oral corticosteroid therapy, it is not clear whether they are related to the action of the antagonists or are due to a sudden reduction in corticosteroid therapy. 

Synergism Increased anticoagulation of warfarin with clofibrate, corticosteroids, tetracycline, vitamin K and naloxone. 

Medications known to increase the risk of bleeding in cirrhotic patients include aspirin, clopidogrel, dipyridamole, corticosteroids, NSAIDs, heparin and warfarin. Mrs MW would need to be counselled about the risks associated with these medications and advised to always check with the pharmacist before buying any medications over the counter. 

It is important to be aware that many herbal preparations may contain adulterants such as corticosteroids (e.g. eczema preparations), analgesics (even those banned in the UK, e.g. phenylbutazone, fenfluramine) and warfarin. For example, PC-SPES, a mixture of at least eight herbs taken for prostate cancer, was shown to contain baikal skullcap and warfarin. 

In addition to warfarin, Sharma and Jusko (1) have listed a large number of other drugs with delays attributable to changes in mediator turnover. These range from H2-receptor antagonists, diuretics, and bronchodilators to corticosteroids, nonsteroidal antiinflammatory drugs, and interferon. 

Pharmacokinetics. Carbamazepine is extensively metabolised one of the main products, an epoxide (a chemically reactive form), has anticonvulsant activity similar to that of the parent drug but may also cause some of its adverse effects. The t) of carbamazepine falls from 35 h to 20 h over the first few weeks of therapy due to induction of hepatic enzymes that metabolise it as well as other drugs, including corticosteroids (adrenal and contraceptive), theophylline and warfarin. Cimetidine and valproate inhibit its metabolism. There are complex interactions with other antiepilepsy drugs, which constitute a reason for monodrug therapy. 

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