What is the drug interaction commonly seen when a patient on warfarin is given Bactrim (trimethoprim/sulfamethoxazole)?
Correct Answer A:
Taking warfarin and bactrim may cause more of a chance for bleeding. It has been reported that bactrim can prolong the prothrombin time in patients who are receiving the anticoagulant warfarin.
Using warfarin together with sulfamethoxazole is usually not recommended, but may be required in some cases. Potential interaction can cause the patient to feel dizzy or lightheaded, have blood in the urine, have bloody, black or sticky bowel movements, have unusual bleeding in the vagina, have unusual bruising.
A 35-year-old man is seen in the Emergency Department after attempting suicide by taking an overdose of warfarin.
Which one of the following is used as a treatment for this circumstance?
Correct Answer E:
Warfarin overdose is evident mainly as excessive bleeding, which may first be noticed as bleeding gums with brushing or easy bruising. Vitamin K is used to reduce INR in cases of warfarin overdose.
A 48-year-old alcoholic man has had a deep venous thrombosis (DVT) and the INR is well-controlled on warfarin. He is noted to have an INR of 6.0 following a weekend binge.
Which one of the following is the most likely pharmacological explanation of this finding?
Correct Answer C:
Intermediate use (2-3 drinks per day) probably does not alter the INR at all.
Intermittent large amount of alcohol drinking leads to an increase in INR, because the alcohol interferes with warfarin metabolism, i.e. warfarin is metabolized less rapidly. This excessive warfarin activity results from alcohol-related inhibition of warfarin metabolism by cytochrome P450 (CYP) in the liver. In the absence of alcohol, CYP activity is relatively low. CYP breaks down the medication, and the resulting products (i.e., metabolites) are excreted. After moderate alcohol consumption, CYP metabolizes alcohol in addition to the medication. As a result of competition for CYP between alcohol and the medication, the medication’s metabolism is reduced, and the production of metabolites as well as their excretion declines, resulting in higher medi- cation levels in the body.
Which one of the following is the best choice for rapidly restoring normal coagulation in a patient on warfarin (Coumadin) with serious gastrointestinal bleeding?
Treatment with coumarin oral anticoagulants, such as warfarin, is effective antithrombotic therapy, but patients treated with these drugs are at significant risk of bleeding.
With serious bleeding, immediate reversal of the anticoagulant effect of warfarin is necessary. The only effective strategy is to give fresh frozen plasma intravenously (choice C), restoring the vitamin K-dependent factors VII, IX, and X which are depleted in patients taking warfarin.
→ Tissue plasminogen activator (choice A) is a thrombolytic agent, and would make any serious bleeding condition worse.
→ Methylprednisolone (choice B) is a corticosteroid that has no effect on the synthesis of vitamin K-dependent factors.
→ Oral vitamin K (choice D) is an effective method of reversing the effects of warfarin, but takes 24 hours to reach full effect.
→ Packed red blood cells(choice E) is incorrect. The transfusion of red cell concentrates is indicated in order to achieve a fast increase in the supply of oxygen to the tissues, when the concentration of haemoglobin is low and/or the oxygen carrying capacity is reduced, in the presence of inadequate physiological mechanisms of compensation. This is not the most appropriate treatment in a patient who needs warfarin reversal.
A 66-year-old male is hospitalized for new-onset atrial fibrillation. His heart rate is controlled, and he is anticoagulated first with low molecular weight heparin and then with warfarin (Coumadin). His INR at discharge is 2.3. He presents 3 days later for follow-up and states that he feels well. His INR is now 10.0.
The most appropriate management at this time would be to withhold warfarin until his INR is therapeutic and to:
The most cost-effective management for excessive anti-coagulation is to administer oral vitamin K and retest the prothrombin time. This patient is not hemorrhaging, and a recent analysis has shown oral vitamin K to be as effective as intravenous or subcutaneous vitamin K. An INR greater than 8.0 does carry a risk of bleeding, so simply withholding warfarin would not be appropriate, and neither would readmission, given the high likelihood of correcting the patient’s excessive anti-coagulation with oral vitamin K alone.
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