Anti-Coagulants Physical Process of Clotting Chemical Process of Clotting Fibrin formation, extrinsic and intrinsic pathways Anti-coagulants Definition Heparin, Low molecular weight heparins, pentasaccharide Structure, properties, biochemical mechanism Coumarins and 1,3-indanediones 12/5/2018 MEDC 604 Anti-coagulants

A) Physical Process B) Chemical Process The Clotting Process A) Physical Process B) Chemical Process Wound antithrombins factor Xa thrombin prothrombin fibrinogen fibrin (monomers) (polymer) vitamin K-dependent g-carboxylation of Glu residues coumarins platelet activation release thrombin release of of ADP generation thromboxane A2 Further activation of platelets Platelet aggregation aspirin ADP receptor antagonists GP IIb-IIIa CLOT Taken from Desai UR (2004) Med. Res. Rev. 24, 151-181. 12/5/2018 MEDC 604 Anti-coagulants

Physical Process of Clotting 12/5/2018 MEDC 604 Anti-coagulants

Chemical Process of Clotting 12/5/2018 MEDC 604 Anti-coagulants

Heparin and Low molecular weight heparins Structure and sequence 12/5/2018 MEDC 604 Anti-coagulants

Pentasaccharide 12/5/2018 MEDC 604 Anti-coagulants

Biochemical Mechanism of Heparin Action AT + H AT:H AT-E + H E 12/5/2018 MEDC 604 Anti-coagulants

Direct Thrombin Inhibitors HIRUDIN – Isolated from leech, hirudino medicinalis. A polypeptide consisting of 65 amino acid residues that binds thrombin in the active site as well as another site called exosite I 12/5/2018 MEDC 604 Anti-coagulants

Coumarins and 1,3-indanediones 12/5/2018 MEDC 604 Anti-coagulants

Clinically useful coumarins and 1,3-indanediones 12/5/2018 MEDC 604 Anti-coagulants

Biochemical Mechanism of Action 12/5/2018 MEDC 604 Anti-coagulants