DTI mechanism

Direct thrombin inhibitors : ARGATROBAN, BIVALIRUDIN, DABIGATRAN, HIRUDIN, LEPIRUDIN

work by interacting with the thrombin active site
→ inhibit thrombin activity even in the presence of bound fibrin
actions are independent of antithrombin III
(which means they can reach and inactivate fibrin-bound thrombin in thrombi)
two types:
1. derivatives of HIRUDIN (isolated from leech saliva) which are irreversible inhibitors
  - LEPIRUDIN is the recombinant form
  - BIVALIRUDIN and LEPIRUDIN are synthetic analogues
2. small molecules which bind reversibly to the thrombin active site
  - ARGATROBAN is a synthetic derivative of L-arginine
  - other drugs in this class are under development, in an attempt to generate orally active DTIs that could replace both HEPARIN and WARFARIN (DABIGATRAN ETEXILATE is the first to be approved)