Warfarin anticoagulant effect

Prothrombin time PT is performed by adding thromboplastin (tissue) factor and calcium to citrate-anticoagulated plasma, recalcifying the plasma, and measuring the clotting time. The major utility of PT is to measure the activity of the vitamin K-dependent factors II, VII, and X. The PT is used in evaluation of liver disease, to monitor warfarin anticoagulant effect, and to assess vitamin K deficiency. 

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. 

The administration of cloflbrate to a patient taking warfarin will potentiate the anticoagulant effect of warfarin by displacing It from Its protein binding site (7). This Interaction will cause... 

Warfarin exerts its anticoagulant effect by inhibiting the production of the vitamin K-dependent coagulation factors... 

When administered concomitantly, clarithromycin and the oral anticoagulant warfarin may interact, resulting in an enhanced anticoagulant effect and therefore increased risk of bleeding. 

Flufenamic acid is used for moderate pain and dysmenorrhea, but it should not be used for more than 1 week due to the possibility of nephrotoxicity, gastrointestinal toxicity, and anemia. It is frequently used in combination with the anticoagulant warfarin, the effect of which is strengthened when combined with flufenamic acid. Synonyms for this drug are arlef, flexocutan, romazal, and others. 

Outpatient and inpatient treatment Initiate warfarin therapy when appropriate (usually within 72 hours of enoxaparin). Continue enoxaparin for a minimum of 5 days and until a therapeutic anticoagulant effect has... 

Missed dose - The anticoagulant effect of warfarin persists beyond 24 hours. If the patient forgets to take the prescribed dose of warfarin at the scheduled time, the dose should be taken as soon as possible on the same day. The patient should not take the missed dose by doubling the daily dose to make up for missed doses. 

Conversion from heparin therapy Because the anticoagulant effect of warfarin is delayed, heparin is preferred initially for rapid anticoagulation. Conversion to warfarin therapy may begin concomitantly with heparin therapy or may be delayed 3 to 6 days. To ensure continuous anticoagulation, it is advisable to continue full dose heparin therapy and that warfarin therapy be overlapped with heparin for 4 to 5 days, until warfarin therapy has produced the desired therapeutic response as determined by PT/INR. When warfarin has produced the desired PT/INR or prothrombin activity, heparin may be discontinued. 

Drug/Food interactions Vitamin K-rich vegetables may decrease the anticoagulant effects of warfarin by interfering with absorption. Minimize consumption of vitamin K-rich foods (eg, spinach, seaweed, broccoli, turnip greens) or nutritional supplements. Mango has been shown to increase warfarin s effect. 

Acute DVT and PE treatment In patients with acute symptomatic DVT and in patients with acute symptomatic PE, the recommended dosage of fondaparinux is 5 mg (body weight less than 50 kg), 7.5 mg (body weight 50 to 100 kg), or 10 mg (body weight greater than 100 kg) by subcutaneous injection once daily. Continue fondaparinux treatment for at least 5 days until a therapeutic oral anticoagulant effect is established (international normalized ratio [INR] 2 to 3). Initiate concomitant treatment with warfarin as soon as possible, usually within 72 hours. The usual duration of administration of fondaparinux is 5 to 9 days. 

Interferes w/ DNA synth Dose Adults. Anaerobic Infxns 500 mg IV q6-8h Amebic dysentery 750 mg/d PO for 5-10 d Trichomoniasis 250 mg PO tid for 7 d or 2 g PO X 1 C. difficile 500 mg PO or IV qSh for 7-10 d (PO preferred IV only if pt NPO) Vaginosis 1 applicator-full intravag bid or 500 mg PO bid for 7 d Acne rosacea/skin Apply bid Peds. 30 mg/ kg PO/IV/d q6H, 4 g/d max-s-. Amebic dysentery 35-50 mg/kg/24 h PO in 3 -s- doses for 5-10 d Rx 7-10 d for C. difficile-, in hepatic impair Caution [B, M] Avoid EtOH Contra 1st tri of PRO Disp Tabs, caps, IV, topical lotion, intravag gel, cream SE Disulfiram-like Rxn dizziness, HA, GI upset, anorexia, urine discoloration Interactions t Effects W/ cimetidine T effects OF carbamazepine, fluorouracil, Li, warfarin -1- effects W/ barbiturates, cholestyramine, colestipol, phenytoin EMS t Effects of anticoagulants concurrent EtOH use can cause disulfiram-like Rxn (tach, N/V, sweating, flushing, headache, blurred vision, confusion) may cause a metallic taste and discolored urine OD May cause N/V/D, numbness in hands and feet, Szs, and loss of coordination symptomatic and supportive... 

Pantoprazole (Protonix) [Gastric Acid Suppressant/Proton Pump Inhibitor] Uses GERD, erosive gastritis, ZE synd, PUD Action Proton pump inhibitor Dose 40 mg/d PO do not crush/chew tabs 40 mg IV/d (not >3 mg/min, use Protonix filter) Caution [B, /-] Disp Tabs, inj SE Chest pain, anxiety, GI upset Interactions t Effects OF warfarin t effects of photosensitivity W/ St. John s wort X effects OF ketoconazole EMS t Effects of anticoagulants may affect glucose (hypoglycemia) OD Unlikely to cause life-threatening Sxs... 

Phenylbutazone was recognised to potentiate the anticoagulant effect of warfarin as long ago as 1959. As subsequent in vitro studies confirmed that phenylbutazone displaced warfarin from its protein binding site, it was assumed that any non-steroidal antiinflammatory drug (NSAID) would enhance warfarin s anticoagulant effect in this way. However it is now known that the interaction is due instead to a stereoselective inhibition of the metabolism of warfarin. Warfarin is available as a racemic mixture of two enantiomers R and S), and of these the S enantiomer is five times more potent as an anticoagulant. Phenylbutazone inhibits the metabolism of the... 

B) The anticoagulant effect of warfarin occurs only in vivo. 

C) Drugs that are metabolized by the liver can alter the anticoagulant effect of warfarin. 

L B. Warfarin does not produce an anticoagulant effect in vitro. It inhibits coagulation of blood only in vivo, because the effect depends upon warfarin s effect in the liver on the production of clotting factors. Warfarin does not require conversion into an active drug. It inhibits the post-ribosomal carboxy-lation of glutamic acid residues in the vitamin K-dependent clotting factors. Therefore, heparin rather than warfarin is used when blood is collected from donors and stored. 

A 23-year old pregnant woman who has been administered IV heparin for treatment of deep vein thrombosis has developed heparin-induced thrombocytopenia. Altering therapy by removing heparin and adding warfarin is not a viable option, because warfarin can cross the placenta and exert an anticoagulant effect in the fetus. Suggest a treatment approach. 

Anticoagulant effect of warfarin maybe reversed by administration of vitamin Kor fresh frozen plasma should only use in situations where INR is severely elevated >10, or when patient is actively bleeding... 

Warfarin Probable induction of cytochrome P450 metabolic pathway Reduced blood levels Reduced anticoagulant effect Check prothronbin time and stop SJW Monitor prothronbin time closely and readjust dose of warfarin if necessary... 

Yue QY, Jansson K. Herbal drug Curbicin and anticoagulant effect with and without warfarin possibly related to the vitamin E component. J Am Geriatr Soc 2001 49 838. 

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