The major oral anticoagulant used in the United States is the coumarin compound warfarin.
Pharmacokinetics
Warfarin is absorbed rapidly and almost completely when it’s taken orally. It binds extensively to plasma albumin and is metabolized in the liver and excreted in urine. Although warfarin is absorbed quickly, its effects don’t occur for about 48 hours, with the full effect taking 3 to 4 days.
Because warfarin is highly plasma-protein-bound and is metabolized by the liver, administration of warfarin with other medications may alter the amount of warfarin in the body. This may increase the risk of bleeding or clotting, depending upon the medications administered.
Pharmacodynamics
Oral anticoagulants alter the ability of the liver to synthesize vitamin K’dependent clotting factors, including prothrombin and factors VII, IX, and X. However, clotting factors already in the bloodstream continue to coagulate blood until they become depleted, so anticoagulation doesn’t begin immediately.
Pharmacotherapeutics
Oral anticoagulants are prescribed to treat or prevent thromboembolism. Patients with this disorder begin taking the medication while still receiving heparin. However, outpatients at high risk for thromboembolism may begin oral anticoagulants without first receiving heparin.
Deep in the veins
Oral anticoagulants are also the drugs of choice to prevent DVT and for patients with prosthetic heart valves or diseased mitral valves. To decrease the risk of arterial clotting, oral anticoagulants are sometimes combined with an antiplatelet drug, such as aspirin, clopidogrel, or dipyridamole.
Monitoring warfarin levels
Patients taking warfarin need close monitoring of prothrombin time and International Normalized Ratios to make sure they are maintaining therapeutic levels of the drug. If laboratory results fall outside the accepted range, warfarin dosage should be adjusted.
Drug interactions
Many patients who take oral anticoagulants also receive other drugs, placing them at risk for serious
drug interactions.
- Many drugs, such as highly protein-bound medications, increase the effects of warfarin, resulting in an increased risk of bleeding. Examples include acetaminophen, allopurinol, amiodarone, cephalosporins, cimetidine, ciprofloxacin, clofibrate, danazol, diazoxide, disulfiram, erythromycin, fluoroquinolones, glucagon, heparin, ibuprofen, isoniazid, ketoprofen, methylthiouracil, metronidazole, miconazole, neomycin, propafenone, propylthiouracil,quinidine, streptokinase, sulfonamides, tamoxifen, tetracyclines, thiazides, thyroid drugs, tricyclic antidepressants, urokinase, and vitamin E.
- Drugs metabolized by the liver may increase or decrease the effectiveness of warfarin. Examples include barbiturates, carbamazepine, corticosteroids, corticotropin, mercaptopurine, nafcillin, hormonal contraceptives containing estrogen, rifampin, spironolactone, sucralfate, and trazodone.
- The risk of phenytoin toxicity increases when phenytoin is taken with warfarin, and phenytoin may increase or decrease the effects of warfarin.
Other interactions include the following:
- A diet high in vitamin K reduces the effectiveness of warfarin.
- Chronic alcohol abuse increases the patient’s risk of clotting while taking warfarin. Acute alcohol intoxication increases the risk of bleeding.
- Vitamin K and fresh frozen plasma reduce the effects of warfarin.
Warning!
Adverse reactions to oral anticoagulants
The primary adverse reaction to oral anticoagulant therapy is minor bleeding. Severe bleeding can occur, however, with the most common site being the GI tract. Bleeding into the brain may be fatal. Bruises and hematomas may form at arterial puncture sites (for example, after a blood gas sample is drawn). Necrosis or gangrene of the skin and other tissues can occur.
Quick fix
The effects of oral anticoagulants can be reversed with phytonadione (vitamin K1).
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