Lecture 3 Medchem

What is Hemostasis 

Cessation of bleeding at a site of injury 

What are the 3 steps of Hemostasis

Vasoconstriction at the site of injury 

Formation of platelet plug -primary hemostasis

Coagulation- secondary hemostasis

What are the classes of Anticoagulants

Vitamin K antagonist

Indiriect Thrombin Inhibitors

Direct Thrombin Inhibitors

Direct Factor Xa Inhibitors

Antiplatelet drugs

What are examples of Vitamin K antagonists

Coumarins and Warfarin

What is the pharmacophore of Coumarins

3-arylalkyl 4-hydroxycoumarin

Which OH group on coumarin is slightly more acidic 

C4

Which isomer of isomer is more active

S

What is the MOA of Warfarin

Inhibits Vitamin K dependent y carboxylation of inactive proenzymes and reduced levels of coagulation factors.

True or false Warfarin is extensively plasma protein bound

True

What are the types of Heparin

Unfractioned High MW

Low Molecular weight heparins

What is the MOA of Heparin

Indirect Thrombin Inhibitor

Accelerates binding of anti thrombin 3 to thrombin and other serine proteases needed for normal coagulation

What is the difference between Glucoronic Acid and Isoronic acid 

Orientation of Carboxyl group

What is the role of antithrombin 3

Inactivates thrombin and factors

What does Heparin bind to

ATIII

What is the binding of Heparin and ATIII mediated by

Sulfate and carboxylate anions with Lys/Arg

What is Fondaparinux

Ultra low MW Heparin

What activity does Fondaparinux have

Inhibits factor Xa by binding to ATIII and increasing catalytic activity of ATIII to inactivate factor Xa

What is an example od a Low Molecular Weigh Heparin

Enoxaparin

What are the 3 functional domains of Thrombin 

Active sit and 2 positively charged exosites I and 2 

Is Bivalrudin bivalent or univalent

Bivalent

Is Argobatran Univalent or bivalent

Univalent

What is Argatroban 

Highly polar synthetic thrombin inhibitor derived from L-arginine binds selectively to tohrombin 

Is argatroban reversible or irreversible

Reversible inhibitor

What is Argotroban indicated for

Heparin Induced thrombocytopenia

What is Dabigatran

Non peptidic prodrug biotransformed to highly polar dabigatran and is a reversible inhibitor of both thrombin and clot bound thrombin

What is Rivaroxaban 

Inhibits free and clot bound Factor Xa 

Oxazolidinone derivative 

Binds directly and reversibly to Factor Xa via S1 and S4 pockers 

What is the indication for Rivaraxoban

VTE

DVT

PE

What is Apixaban

Highly selective direct factor Xa inhibitor

Exerts effect on free and clot bound factor Xa