Biochem Ch 45 Part 2

Front 1

What is plasminogen?

Back 1

is a circulating protein with a high affinity for fibrin of a developing clot

Front 2

What is APC and where is it located?

Back 2

1. Activated Protein C

2. It is on platelets

Front 3

What does APC do? (3)

Back 3

Turns off the following:

1. Pro-coagulation factors V and VIII

2. Stimulate release of tPA and scu-PA, which binds to the clot

3. Inhibits plasminogen activator inhibitor (PAL-1)

Front 4

What is the function plasminogen activators (tPA)

Back 4

convert plasminogen to active plasmin

Front 5

T/F tPA is an endogenous single-chain urokinase

Back 5

False it is an endogenous tissue plasminogen activator

Front 6

T/F scu-PA is an endogenous single-chain urokinase

Back 6

True

Front 7

Streptokinase: _______ beta-hemolytic streptococci

Back 7

Exogenous

Front 8

Plasmin degrades ______

Back 8

Fibrin

Front 9

What 2 components activate plasmin?

Back 9

1. tPA

2. scu-PA

Front 10

PAI-1 does what?

Back 10

Inhbits clot bound plasmin

Front 11

What is α2-antiplasmin and what does it do?

Back 11

1. α2-antiplasmin is a circulating protease inhibitor

2. It inhibits plasmin that has been released from clots

Front 12

What are 3 inhibitors of eicosanoids synthesis?

Back 12

1. Aspirin

2. NSAIDS

3. Glucocorticoids

Front 13

What specifically does aspirin and NSAIDs inhibit?

Back 13

Inhibit thromboxane and prostaglandin synthesis

Front 14

What do glucocorticoids specifically inhibit?

Back 14

cortisol, hyrodocortisol inhibit all eicosanoid synthesis

Front 15

What are the 2 nonspecific Thrombin inhibitors?

Back 15

1. Antithrombin III (ATIII) activators

2. Vitamin K antagonists

Front 16

What are 2 examples of ATIII activators

Back 16

•Heparin (soluble & used as an injectable drug) & Heparin sulfate (membrane bound)

Front 17

What is a specific vitamin K antagonist?

Back 17

Warfarin

Front 18

How does warfarin work?

Back 18

decrease activity of coagulation proteins (II,VII,IX,X) by inhibiting their activation in the liver by g-carboxylation

Front 19

What are 2 specific thrombin (II) inhibitor

Back 19

1. Fondaparinus

2. Bivalirudin

Front 20

How does Fondaparinus work?

Back 20

inactivates Factor Xa, thus Factor II activation

Front 21

How does Bivalirudin work?

Back 21

–reversibly binds to Factor II (thrombin)

Front 22

Describe the specific MOA of Aspirin and NSAIDs

Back 22

•inhibit the cyclo-oxygenase that converts arachidonic acid to prostaglandin H2, a precursor to thromboxanes and other signal molecules involved in fibroblast recruitment

Front 23

Describe the specific MOA of glucocorticoids (hydrocortisol)

Back 23

•Inhibit the release of arachidonic acid from its storage site on plasma membrane phospholipids

Front 24

What is this structure?

Back 24

Thromboxane

Front 25

What are heparins?

Back 25

–Glycosaminoglycans (repeating disaccharides, GAGs) of varying molecular wt

Front 26

Heparin can induce ______ and _______

Back 26

1. Clotting

2. Thrombocytopenia

Front 27

Heparins bind to and activate what?

Back 27

Antithrombin III (ATIII)

Front 28

What is the function of ATIII (2)

Back 28

1. Inactivates thrombin

2. ATIII inactivates Factors VIIIa, IXa, Xa and Xla

Front 29

T/F Heparin treatment can induce excessive clotting and thrombocytopenia in patients that develop antibodies to the platelets

Back 29

True

Front 30

Heparin binds to ______ changing its conformation

Back 30

platelet factor 4 (PF4)

Front 31

_____ recognize the heparin-PF4 complex as foreign material and binds to the ______

Back 31

1. IGgs

2. Platelet

Front 32

_____ activates the platelet increasing _____

Back 32

1. IGg

2. thrombosis

Front 33

IGg tagged platelets are removed by the _______ producing _______

Back 33

1. spleen

2. thrombocytopenia

Front 34

Warfarin is structurally similar to _____

Back 34

Vitamin K

Front 35

Which is vitamin k and which is warfarin?

Back 35

Left is vitamin K

Right is warfarin (3 rings)

Front 36

What is the specific MOA of warfarin?

Back 36

•Acts as a competitive inhibitor to Vit K epoxide reductase blocking the reduction of Vit K epoxide (KO) to active reduced Vit K (KH2)

Front 37

Reduced vitamin K is required for what?

Back 37

•is required for the formation of g-carboxylated glutamate residues in all of the Vit K dependent coagulation factors II (thrombin), VII, IX and X

Front 38

What is needed to bind to calcium and what does this binding do?

Back 38

•gamma-carboxylated glutamate residues are needed to bind calcium (Ca) which links the coagulation factors to the negatively charged phospholipids (PL) in the platelet membrane

Front 39

Warfarin also blocks activity of _______ activity of proteins ____ and _____

Back 39

1. antithrombogenic

2. S

3. C

Front 40

what is an indirect inhibitor of thrombin?

Back 40

Fondaparinus

Front 41

Heparin and warfarin lack what?

Back 41

specificity

Front 42

T/F Fundaparinus is a disaccharide

Back 42

False it is a pentasaccharide

Front 43

Fundaparinus is a specific inhibitor of ______

Back 43

Factor Xa

Front 44

T/F Fondaparinus enhances the binding of ATIII to Factor Xa by 300 fold, thus preventing Factor Xa activation of thrombin

Back 44

True

Front 45

What is this drug?

Back 45

Fondaparinus (pentasaccharide, 5 rings)

Front 46

Bivalirudin was developed based on what?

Back 46

•Bivalirudin, 20 aa peptide, was developed based on hirudin which is secreted by leeches.

Front 47

What is the advantage of bivalirudin over hirudin?

Back 47

High binding affinity and specificity for thrombin yet the binding is reversible, whereas, hirudinbinds irreversibly

Front 48

T/F Hirudin is safer to use than bivalirubin in that the anticlotting activity of hirudin is more easily controlled

Back 48

False

Bivalirubin is safer to use than hirudin in that the anticlotting activity of bivalirubin is more easily controlled