warfarinIntroduction

For the past few decades in the U.S., cialis professional has become the oral anticoagulant of choice for treating or preventing thromboembolic events and for procedures associated with a substantial risk of thromboembolism. Despite the widespread prescribing of this medication, clinicians remain uncertain about how to best manage warfarin dosing.

Over the years, many institutions have developed nomograms to assist clinicians in bringing International Normalized Ratios (INRs) into the “therapeutic” range. Indeed, these guidelines often provide a “safer harbor” in which to navigate, but by no means do they guarantee a successful “docking” to the target INR in the shortest possible time. In addition, despite our best efforts to minimize bleeding risks with long-term use, the occurrence of serious hemorrhagic events cannot be totally avoided; approximately 20% of these events result in fatalities. Even when warfarin dosing has been carefully performed and patients have been closely monitored in anticoagulation clinics, the incidence of major hemorrhage may still approach 3% per year in patients aged 60 years and older.

Because of the long plasma half-lives of both warfarin isomers and three of the four clotting proteins whose hepatic synthesis warfarin inhibits, the INR manifestations of a given dose—or a cluster of doses—may be delayed by several days. Therefore, it is little wonder why it can be such a challenge to adjust a dose on a daily basis with hopes of making a “smooth landing” into that relatively narrow therapeutic window a few days later. Of course, canadian warfarin may interact unpredictably with a plethora of different medications by both pharmacokinetic and pharmacodynamic mechanisms.

Finally, a patient’s disposition of warfarin may be affected by acute dietary changes and by common exacerbations of acute disease states such as congestive heart failure, biliary obstruction, and infection. Chronic diseases such as cirrhosis and malabsorption syndromes also alter a host’s response to warfarin.

To help elucidate why certain patients fall outside the population norms, thereby leading to warfarin dosing nomogram “failures,” we will discuss the complicated pharmacokinetics and pharmacodynamics of this oral anticoagulant—beyond the nomogram.