The direct thrombin inhibitors (DTIs) exert their anticoagulant effect by directly binding to the active site of thrombin, thereby inhibiting thrombin’s downstream effects. This is in contrast to indirect thrombin inhibitors such as heparin and LMWH (see above), which act through antithrombin.
These DTIs include parenteral DTIs like argatroban, melagatran, Hirudin and lepirudin.
Oral DTIs includes Dabigatran. Ximelagatran was an oral direct thrombin inhibitor, however, it was subsequently withdrawn from the market because concerns of hepatic toxicity. Rivaroxiban is in the pipeline.
Advantages of ORAL DTIs (Direct Thrombin Inhibitors) over warfarin:

1. Predictable pharmacokinetics & bioavailability
2. Fixed Dosing
3. Predictable anti-coagulant response
4. Thus Monitoring unnecessary
5. No interference with P-450 so no drug interactions in this aspect
6. Not bound to plasma proteins, so again no drug interactions in this aspect
7. Rapid onset of action and thus immediate coagulation
8. Rapid cessation of activity thus avoid overlap between different anti-coagulants and also need of other anti-coagulants
9. Wider therapeutic index (Warfarin has low Therapeutic Index)
10. Less adverse effects (no local necrosis)

1. Both given orally
2. Both contraindicated in pregnancy
3. Equal Efficacy

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