Drugs for Thromboembolic Disorders

Question 1

Briefly describe the process of clot formation.

Answer 1

1. Damaged endothelium reveals collagen and other proteins.
2. Platelets aggregate and adhere to form a seal
3. CLotting factors work to form a strong thrombin-fibrin clot.

Question 2

Describe the intrinsic clotting factor cascade.

Answer 2

1. Abnormal vessel wall activates XII to XIIa.
2. XIIa activates XI to XIa
3. XIa activates IX to IXa
4. IXa activates X to Xa
5. Xa promotes prothrombin conversion to thrombin.

Question 3

Briefly describe the process of clot lysis.

Answer 3

Antithrombin III (ATIII) inhibits thrombin through inhibition of Factor X. 
Plasmin and other proteins degrade clot.

Question 4

Describe how warfarin works.

Answer 4

Vitamin K is the cofactor for Factors II, VII, IX and X.

Warfarin inhibits vitamin K recyclying from KO (inactive) to KH2 (active), preventing these factors from participating in clotting cascade.

Question 5

Describe the extrinsic clotting cascade.

Answer 5

1. Damaged tissue activates factor VII into VIIa.
2. VIIa acts on factor X, converting to Xa.
3. Xa acts on prothrombin to convert to thrombin.

Question 6

Describe 4 adverse effects of warfarin.

Answer 6

1. Teratogenic in pregnancy
2. Decreases protein S and protein C, which leads to HYPERCOAGULABLE state in people genetically deficient in protein S/C
3. Increases bleeding risk
4. Drug-Drug interactions (metabolised by CYP450

Question 7

How do you monitor warfarin therapy?

Answer 7

Monitor blood - prothrombin time (extrinsic pathway)

Question 8

What is the international normalised ratio (INR)

Answer 8

Patient prothrombin time: normal prothrombin time ratio

Question 9

Describe how heparin works.

Answer 9

Heparin inactivates factor Xa and thrombin by binding antithrombin III.

Heparin increases ATIII affinity for Xa and thrombin, accelerating their inactivation, preventing conversion of fibrinogen to fibrin.

Question 10

What are Dabigatran and Rivaroxaban?

Answer 10

Direct enzyme inhibitors.

Dabigatran inhibits thrombin.
RIvaroxaban inhibits Xa formation.

Question 11

How does aspirin work?

Answer 11

Activated platelets release thromboxane A2 (TxA2) and ADP. These enhance platelet activation and aggregation.

Aspirin blocks TxA2 formation by inhibiting cyclooxygenase.

Question 12

How does clopidogrel work?

Answer 12

Activated platelets release thromboxane A2 (TxA2) and ADP. These enhance platelet activation and aggregation.

Clopidogrel blocks ADP receptors on platelets.

Question 13

What is tissue plasminogen activator?

Answer 13

Tissue plasminogen activator (t-PA) converts plasminogen to plasmin.

Plasmin breaks down fibrin clots. Administering t-PA has rapid onset of action (IV) and works to break down clots.