Oral anticoagulants, effects

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. 

Drugs That Increase Oral Anticoagulant Effects... 

Costigan DC, Freedman MH, Ehrlich RM. Potentiation of oral anticoagulant effect by L-thyroxine. Chn Pediatr (Phila) 1984 23(3) 172-4. 

Hirsh J, Dalen JE, Anderson DR et al (2001) Oral anticoagulants mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 119 (Suppl.) 8S-21S... 

Concurrent use of the fluoroquinolones with theophylline causes an increase in serum theophylline levels. When used concurrently with cimetidine, the cimetidine may interfere with the elimination of the fluoroquinolones. Use of the fluoroquinolones with an oral anticoagulant may cause an increase in the effects of the oral coagulant. Administration of the fluoroquinolones with antacids, iron salts, or zinc will decrease absorption of the fluoroquinolones. There is a risk of seizures if fluoroquinolones are given with the NSAIDs. There is a risk of severe cardiac arrhythmias when the fluoroquinolones gatifloxacin and moxifloxacin are administered with drains that increase the QT interval (eg, quini-dine, procainamide, amiodarone, and sotalol). 

The effects of oral hypoglycemic drugs, oral anticoagulants, and phenytoin may be increased when administered with chloramphenicol. Fhenobarbital or rifampin may decrease chloramphenicol blood levels. 

Sulfinpyrazone may increase die anticoagulant activity of oral anticoagulants. There is an increased risk of hypoglycemia when sulfinpyrazone is administered with tolbutamide. Concurrent administration of sulfinpyrazone widi verapamil may decrease die effectiveness of verapamil. 

The HMG-CoA reductase inhibitors have an additive effect when used with the bile acid sequestrants, which may provide an added benefit in treating hypercholesterolemia that does not respond to a single-drug regimen. There is an increased risk of myopathy (disorders of the striated muscle) when the HMG-CoA reductase inhibitors are administered with erythromycin, niacin, or cyclosporin a When the HMG-CoA reductase inhibitors are administered with oral anticoagulants, there is an increased anticoagulant effect. 

Patients receiving oral anticoagulants need to avoid eating excessive amounts ot food containing vitamin K. Otherwise, the anticoagulant will not be effective. Be sure your patient knows what foods contain vitamin K. Include the following list in your teaching plan ... 

When administered with cholestyramine or colestipol there is a decreased absorption of the oral thyroid preparations. These drugs should not be administered within 4 of 6 hours of the thyroid hormones. When administered with the oral anticoagulants there is an increased risk of bleeding. It may be advantageous to decrease the dosage of the anticoagulant when a thyroid preparation is prescribed. There is a decreased effectiveness of the digitalis preparation if taken with a thyroid preparation. 

Bicalutamide may increase the effect of oral anticoagulants. Flutamide enhances the action of leuprolide. Additive antineoplastic effects may occur when leuprolide is administered with megestrol or flutamide. Estrogens decrease the effectiveness of tamoxifen. 

A number of laboratory tests are available to measure the phases of hemostasis described above. The tests include platelet count, bleeding time, activated partial thromboplastin time (aPTT or PTT), prothrombin time (PT), thrombin time (TT), concentration of fibrinogen, fibrin clot stabifity, and measurement of fibrin degradation products. The platelet count quantitates the number of platelets, and the bleeding time is an overall test of platelet function. aPTT is a measure of the intrinsic pathway and PT of the extrinsic pathway. PT is used to measure the effectiveness of oral anticoagulants such as warfarin, and aPTT is used to monitor heparin therapy. The reader is referred to a textbook of hematology for a discussion of these tests. 

Warfarin has been the primary oral anticoagulant used in the United States for the past 60 years. Warfarin is the anticoagulant of choice when long-term or extended anticoagulation is required. Warfarin is FDA-approved for the prevention and treatment of VTE, as well as the prevention of thromboembolic complications in patients with myocardial infarction, atrial fibrillation, and heart valve replacement. While very effective, warfarin has a narrow therapeutic index, requiring frequent dose adjustments and careful patient monitoring.15,29... 

Warfarin has not been adequately studied in non-cardioembolic stroke, but it is often recommended in patients after antiplatelet agents fail. One small retrospective study suggests that warfarin is better than aspirin.30 More recent clinical trials have not found oral anticoagulation in those patients without atrial fibrillation or carotid stenosis to be better than antiplatelet therapy. In the majority of patients without atrial fibrillation, antiplatelet therapy is recommended over warfarin. In patients with atrial fibrillation, long-term anticoagulation with warfarin is recommended and is effective in both primary and secondary prevention of stroke.12 The goal International Normalized Ratio (INR) for this indication is 2 to 3. 

Onset of action is slow at around 30 minutes, which limits spontaneity. In addition, patients and partners may complain of a cold, lifeless, discolored penis that has a hinge-like feel. Painful ejaculation or inability to ejaculate are additional adverse effects. VEDs are contraindicated in persons with sickle cell disease and should be used with caution in patients on oral anticoagulants or who have bleeding disorders due to the increased possibility of priapism. 

The analgesic effects of NSAIDs are attributed to inhibition of the COX-2 enzyme, whereas the negative GI effects are due to inhibition of COX-1.28 Patients taking oral anticoagulants, those with a history of peptic ulcer disease, or others at high risk for GI complications may be considered candidates for a COX-2 inhibitor or a combination of a nonselective NSAID with a gastroprotective agent such as a proton pump inhibitor (PPI). Because most PPIs are available by prescription only, such patients should be referred to a physician. 

Application of topical salicylates can lead to systemic effects, especially if the product is applied liberally. Repeated application and occlusion with a wrap or bandage also can increase systemic concentrations.41 Salicylate-containing counterirritants should be used with caution in patients in whom systemic salicylates are contraindicated, such as patients with severe asthma or aspirin allergy.42 Topical salicylates have been reported to increase prothrombin time in patients on warfarin and should be used with caution in patients on oral anticoagulants.43... 

The most commonly used oral anticoagulant drug in the U.S. is warfarin. It acts by altering vitamin K so that it is unavailable to participate in synthesis of vitamin K-dependent coagulation factors in the liver (coagulation factors II, VII, IX, and X). Because of the presence of preformed clotting factors in the blood, the full antithrombotic effect of warfarin therapy may require 36 to 72 h. 

Fibrates may potentiate the effects of oral anticoagulants, and the international normalized ratio should be monitored very closely with this combination. 

Warfarin is an oral anticoagulant agent available as 1 mg (brown tablets), 3 mg (blue tablets) and 5 mg (pink tablets). The main side-effect of warfarin is increased bleeding. The approximate price of warfarin per tablet is 0.014 ( 0.013). 

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

Predictable effects that derive from the known pharmacological drug properties. Examples are masculin-ization of the female fetus by androgenic hormones brain hemorrhage due to oral anticoagulants bradycardia due to p-blockers. 

Decreased anticoagulant effects Endogenous factors that may reduce the response to the oral anticoagulants or decrease the PT or INR include Edema ... 

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

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