Warfarin affecting

Pharmacokinetics. Warfarin is readily absorbed from the gastrointestinal tract and like all the oral anticoagulants, is more than 90% bound to plasma proteins. Its action is terminated by metabolism in the liver. Warfarin (t/ 36 h) is a racemic mixture of approximately equal amounts of two isomers S (t)/ 35 h) and R 50 h) warfarin, i.e. it is in effect two drugs. S warfarin is four times more potent than R warfarin. Drugs which interact with warfarin affect these isomers differently. 

Interestingly, microsomal 7-hydroxylation of racemic warfarin appears to be lower than that of S-warfarin, indicating the possibility of a metabolic interaction between warfarin enantiomers [61]. These in vitro studies showed that R-warfarin affected the catalytic activity of CYP2C9 by a noncompetitive mechanism [61]. However, in an earlier in vivo study a lack of enantiomeric interaction between R- and S-warfarin was suggested after single 1.5mg/kg doses of the individual enantiomers and racemic warfarin [62]. The enantiospecific results obtained were successfully used to predict the pharmacokinetics and pharmacodynamics of racemic warfarin. The apparently contradictory findings between the two studies may be due to a number of experimental factors. One study used a supraclinical dose of warfarin in vivo, whereas the other involved human microsomes in vitro, the relevant hepatic concentrations of which are difficult to determine. 

Warfarin has been the mainstay of oral anticoagulant therapy for many years, principally for atrial fibrillation, mechanical heart valves, or venous thromboembolism. Adverse-effects profile of patients on warfarin therapy parallel what would be seen in vitamin K deficiency. Dne to its inhibitory effect on VKOR in the liver, warfarin affects the fnnction of the MGP and has been associated with vascular calcification in various animal and human studies. 

What does this suggest about the way in which warfarin affects blood clotting ... 

Maintenance doses widely vary among patients (e.g., from 1 to 20 mg/day for warfarin), and are influenced by diet (variable vitamin K intake) and medications that affect coumarin metabolism (decreased drug clearance e.g., cotrimoxazole, amiodarone, erythromycin increased clearance e.g., barbiturates, carbamaze-pine, rifampin). Thus, regular monitoring is needed... 

The pharmacological and/or adverse effects of a drug can be reversed by co-administration of drugs which compete for the same receptor. For example, an opioid receptor antagonist naloxone is used to reverse the effects of opiates. Drugs acting at the same site with opposite effects also can affect each other, e.g. the reduction in the anticoagulant effect of warfarin by vitamin K. 

COX-2 inhibitors are susceptible to the same drug interactions as nonselective agents. However, the interaction with warfarin is less pronounced because platelet function is affected to a lesser degree. 

Lastly, Llerena etal. (2004) compared the CYP2C9 polymorphisms 1, 2, 3, 4, 5, and 6 in Mexican Americans (n = 98) and Spanish subjects (n = 102). Lower frequencies of the variant CYP2C9 2, one of two alleles reported to have altered catalytic activity, were found among the Mexican Americans. Since no phenotypic comparisons were conducted in this study, the clinical implications remain unclear. The authors suggest the need for further studies to assess whether the drug metabolism of medications such as warfarin maybe affected in this population. 

Background pesticide contamination of the natural environment affects most animal species, mainly influencing their behavior and physiology [1]. For example, white rats natural resistance to plague is weakened by even the smallest dose of warfarin (0.075 mg per individual over 24 days). There are many such examples [88]. 

The answer is b. (Hardmanr p 906.) Cimetidine reversibly inhibits cytochrome P450. This is important in phase I bio transformation reactions and inhibits the metabolism of such drugs as warfarin, phenytoin, propranolol, metoprolol, quinidine, and theophylline. None of the other enzymes are significantly affected. 

As tinzaparin may theoretically affect the prothrombin time (PT)/INR, draw blood for PT/INR determination just prior to the next scheduled dose of tinzaparin for patients receiving tinzaparin and warfarin. 

Conversion from heparin therapy - As heparin may affect the PT/INR, patients receiving both heparin and warfarin should have blood for PT/INR determination drawn at least ... 

Drugs that may interact with raloxifene include ampicillin and cholestyramine. Raloxifene may affect warfarin. 

Highly protein-bound drugs In vivo, raloxifene did not affect the binding of warfarin, phenytoin, or tamoxifen. However, use caution when raloxifene is coadministered with other highly protein-bound drugs, such as diazepam, diazoxide, and lidocaine. 

Drugs that maybe affected by danazol are carbamazepine, cyclosporine, and warfarin. 

Drugs that may be affected by HMG-CoA reductase inhibitors include oral contraceptives, diclofenac, digoxin, glyburide, phenytoin, and warfarin. Atorvastatin, lovastatin, and simvastatin are primarily metabolized by CYP3A4 they may interact with CYP3A4 inhibitors. 

Drugs that may affect zafirlukast include aspirin, erythromycin, and theophylline. Drugs that may be affected by zafirlukast include warfarin. 

Aprepitant may be affected by paroxetine, CYP2C9 substrates (eg, phenytoin, tolbutamide, warfarin), CYP3A4 substrates (eg, alprazolam, cisapride, dexamethasone, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, methylprednisolone, midazolam, paclitaxel, pimozide, triazolam, vinblastine, vincristine, vinorelbine), and oral contraceptives. 

Drugs that may affect venlafaxine include cimetidine, cyproheptadine, and MAOIs. Drugs that may be affected by venlafaxine include clozapine, desipramine, haloperidol, indinavir, St. John s wort, trazodone, sibutramine, sumatriptan, and warfarin. 

Drugs that may be affected by duloxetine include drugs extensively metabolized by CYP2D6 (eg, flecainide, phenothiazines, propafenone, tricyclic antidepressants, thioridazine), alcohol, CNS-acting drugs, MAOIs, and drugs highly bound to plasma proteins (eg, warfarin). 

Drugs that may be affected by SSRIs Drugs that may be affected by SSRIs include alcohol, benzodiazepines, beta blockers, buspirone, carbamazepine, cisapride, clozapine, cyclosporine, diltiazem, digoxin, haloperidol, hydantoins, lithium, methadone, mexiletine, nonsedating antihistamines, NSAIDs, olanzapine, phenothiazines, phenytoin, pimozide, procyclidine, ritonavir, ropivacaine, sumatriptan, sulfonylureas, sympathomimetics, tacrine, theophylline, tolbutamide, tricyclic antidepressants, and warfarin. 

Drugs that may affect valproic acid include carbamazepine, charcoal, chlorpromazine, cholestyramine, cimetidine, erythromycin, ethosuximide, felbamate, lamotrigine, phenytoin, rifampin, and salicylates. Drugs that may be affected by valproic acid include carbamazepine, clonazepam, diazepam, ethosuximide, lamotrigine, phenobarbital, phenytoin, tolbutamide, tricyclic antidepressants, warfarin, and zidovudine. 

Drugs that may be affected by proton pump inhibitors include azole antifungal agents (eg, itraconazole, ketoconazole), benzodiazepines, cilostazol, clarithromycin, digoxin, phenytoin, salicylates, sulfonylureas, and warfarin. Drugs that may affect proton pump inhibitors include sucralfate and clarithromycin. 

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