Coag Cascade, Antiplatelet, Anticoagulatns & Thrombolytics

Question 1

What is naturally released by the endothelial cells of blood vessels to prevent clotting?

Answer 1

Nitric oxide & prostaglandins

Question 2

What is nitric oxides job?

Answer 2

Dilate blood vessels

Question 3

What is prostacylin’s job?

Answer 3

Bind to receptors on platelets, binding triggers reactions to prevent platelet activation and aggregation

Question 4

What happens when there is a damaged blood vessel?

Answer 4

Less nitric oxide and less prostacyclin

1. Blood vessels become more constricted and platelets become activated
2. Platelets adhere to expose collagen with help of VWF = change shape
3. Activated, different shaped platelets released ADP thrombin, thrombosis A2, 5HT, TA2
4. Fibrinogen causes agglutination

Question 5

Example of a popular antiplatelet?

Answer 5

Aspirin

Question 6

How do platelets work?

Answer 6

1. Platelet activated
2. AA released from membrane phospholipid —> prostaglandin H2 (via COX-1)
3. Prostaglandin H2 —> thromboxane A2
4. TXA2 stimulates new platelets and aggregation

Question 7

What stimulates aggregation of platelets and forms new platelets

Answer 7

TXA2 (thromboxane A2)

Question 8

Aspirin MOA?

Answer 8

Irreversibly Inhibits COX-1 = no clot formation

Question 9

Other examples of anti platelet drugs? (4)

Answer 9

1. Clopidogrel
2. Ticagrelor
3. Ticlopidine
4. Prasurgel

Question 10

What (that is important) in platelet formation/aggregation does platelet release? (2)

Answer 10

Arachidonic Acid + ADP

Question 11

What does ADP bind to in platelets?

Answer 11

P2Y12

Question 12

What drugs are P2Y12 inhibitors?

Answer 12

Clopidogrel, tricagrelor

Question 13

Why is ADP important in platelet aggregation? (MOA)

Answer 13

ADP binds to P2Y12, this activates GPIIb/IIIa receptors needed for fibrin-platelet linking and aggregation.

Question 14

What drugs inhibit the GPIIb/IIIa receptors also causing anti platelet aggregation? (3)

Answer 14

Abciximab, eptifibatide and tirofiban

Question 15

what pathways are in the clotting cascade?

Answer 15

Intrinsic and extrinsic

Question 16

What is the intrinsic pathway?

Answer 16

Damage to the blood vessel wall directly

Question 17

What is the extrinsic pathway?

Answer 17

Damage to the blood vessel wall plus surrounding tissues

Question 18

Explain the intrinsic pathway?

Answer 18

XII activated when blood comes into contact with collagen = XIIa

XIIa activates XI = XIa

XIa activates IX = IXa

IXa activates X = Xa

Xa converts prothrombin = thrombin

Thrombin converts fibrinogen = fibrin

Fibrin = mesh that forms the clot

Question 19

Explain the extrinisc pathway?

Answer 19

VII is activated by tissue factor released by damaged cells —> VIIa

VIIa activates X = INTRINSIC/COMMON PATHWAY

Question 20

What is the common pathway?

Answer 20

Xa = prothrombin = thrombin = fibrinogen = fibrin = clot

Question 21

3 Examples of anticoagulants?

Answer 21

Heparin, LMWH (enoxapasin & daltepasin)

Question 22

Anticoagulants bind to natural anticoagulants floating in blood called?

Answer 22

Antithrombin III

Question 23

What part of the coagulation cascade does antithrombin III attach to?

Answer 23

Xa and Thrombin

Question 24

How does anticoagulants affect antithrombin III

Answer 24

Rapidly increases its activity

Question 25

What does antithrombin III do to coag cascade Xa and thrombin?

Answer 25

Inactivates

Question 26

MOA of heparin

Answer 26

Bind to antithrombin III increasing its activity, increasing inactivation of Xa and Thrombin and CLOTS

Question 27

MOA of LMWH

Answer 27

Don’t bind to antithrombin they bind to Xa selectively, no affect on thrombin!!!

Question 28

Thrombin is not affected by what drug?

Answer 28

LMWH

Question 29

Major Side effect of heparin?

Answer 29

HIT (heparin induced thrombocytopenia)

Question 30

What happens in HIT

Answer 30

Antibody complexes formed when heparin bound to platelet factor 4

Question 31

MOA of apixaban and Rivaroxaban

Answer 31

Inhibits Xa preventing prothrombin —> thrombin

Question 32

Risk of apixaban?

Answer 32

BLEEDING

Question 33

When is protamine sulfate used?

Answer 33

When bleeding is excessive but cant be used for fondaparinux

Question 34

With which anticoagulants cant bleeding be controlled

Answer 34

Fondaparinux

Question 35

What is one of the oldest anticoagulants?

Answer 35

Warfarin

Question 36

What coag factor is prothrombin?

Answer 36

2

Question 37

What coag factors does vitamin K carboxylate/activate

Answer 37

2, 7 , 9, 10

Question 38

when does carboxylation of coag factors occur?

Answer 38

When reduced Vit K is present

Question 39

How does warfarin work?

Answer 39

Inhibits vit K epoxied reductase
- this stops vitamin K epoxide being recycled back into reduced vit K and being re-used to make more clotting factors

Question 40

Vit k is reduced into what?

Answer 40

Vit k epoxide

Question 41

What recycles vit k epoxide?

Answer 41

Vit k epoxide reductase

Question 42

3 disadvantages of warfarin?

Answer 42

1. Many drug drug interactions
2. Many drug food interactions
3. Small therapeutic range

Question 43

How is patients on wafarin measured?

Answer 43

INR

Question 44

How is bleeding from warfarin managed?

Answer 44

Vitamin K - but takes up to 24 hours to reverse

Fresh frozen plasma preferred in emergencies

Question 45

What do thrombolytics act on?

Answer 45

Acts on current clot!

Question 46

Examples of thrombolytics? (3/2)

Answer 46

Alteplase
Rete please
Tenetecteplase
Urokinase/streptokinase (less selective)

Question 47

How to reverse thrombolytics?

Answer 47

Aminocaproic acid
Tranexamic acid

Stop fibrinolytic but Inhibit binding of plasminogen to fibrin + conversion of plasminogen to plasmin