Antiplatelet, anticoagulant, thrombolytic drugs

Question 1

What are the key steps in homeostasis relating to blood loss?

Answer 1

• local vasoconstriction at site of injury
• adhesion, aggregation and and activation of platelets at injury site
• Fibrin formation

1. Vascular wall damage- exposes collagen and tissue factor (TF, thromboplastin)
2. Primary homeostasis- platelet adhesion (aforementioned)
3. Blood coagulation and formation of stable clot (fibrin enmeshing platelets)

Question 2

What is the role of fibrin and thrombin?

Answer 2

Fibrinogen- brings platelets together.
Thrombin- converts fibrinogen to fibrin

Produces a mesh that holds together the platelets and blood cells in a stable way.

Question 3

What is the key event of the coagulation cascade?

Answer 3

Production of Thrombin
Converts fibrinogen to fibrin.
This allows stable blood clots to form

Question 4

What is thrombosis?

Answer 4

Local clotting of blood.

Question 5

What are the predisposing factors for for thrombosis?

Answer 5

1. Vascular wall damage
2. increased blood coagulability
3. Abnormal blood flow.

Question 6

What is an arterial thrombus? How are they primarily treated?

Answer 6

WHITE thrombus. Mainly platelets in a fibrin mesh.

Anti-platelet drugs.

Question 7

What is a venous thrombus? Hows is primarily treated?

Answer 7

RED thrombus. Mainly fibrin with little platelets.

Anti-coagulants.

Question 8

Describe the basic process of blood clot formation.

Answer 8

Tenase, and Prothrombin –> Prothrombinase–> Thrombin–> Fibrinogen–> Fibrin–> Clot.

Question 9

What are some common drugs and what part of the coagulation cascade do they inhibit?

Answer 9

Process EG: Drug–> factor inhibited–> Production of molecule stopped.

1. Warfarin–>factor X(ten)–>tenase.
   Blocks factor II–>prothrombin.
2. Rivaroxiban–>Xa–> prothrombinase.
   Heparin, LMWH’s, fondaparinux—>Xa via anti-thrombin III–>prothrombinase.
3. Dabigatran–>IIa–>thrombin
   Heparin–>IIa via Anti thrombin III–>same effect.

Question 10

What is the role of Vitamin K in coagulation factors?

Answer 10

Needed for an enzyme which converts the coagulation factors to their active states, allowing production of thrombin.

Question 11

What does Warfarin do in relation to vitamin K?

Answer 11

Blocks Vitamin K reductase, which coverts the coagulation factors to their active states.

Question 12

What are Anti-Coagulants mainly used for?

Answer 12

To prevent venous thrombosis:

• DVT
• Post op thrombosis
• AF
• patients with artificial heart valves.

Question 13

What is the main risk of using Anti- Coagulants?

Answer 13

may cause a Haemorrhage. Need to strike a balance between risk of thrombosis and haemorrhage.

Question 14

What factors does warfarin make inactive?

Answer 14

II, VII, IX, X,

Question 15

How is warfarin administered? how long does it take to work? how long is its half life?

Answer 15

Orally. Takes 2-3 days to work. Half life of 40 hours.

Could use Heparin for rapid anti-coagulant effect.

Question 16

What is the main pharmacological use of Antithrombin?

Answer 16

Target for Heparin, which cannot directly inhibit factor IIa and factor Xa.

Binding to Anti- thrombin III increases its affinity for the aforementioned factors, increasing their inactvation.

Question 17

What does LMWH’s stand for?

Answer 17

Low molecular weight heparins. Preferred to Heparins unless there is renal failure. Eg enoxaparin, dalteparin (parin). Administered IV or SC (sub-cutaneous)

Fondaparinux and idrabiotaprainux act similarly, with short and long action durations.

Question 18

What is the advantage of dabigatran over heparin and lmwh’s?

Answer 18

Can be administered orally. directly inhibits thrombin or factor Xa.

Question 19

What are anti-platelet drugs mainly used for?

Answer 19

Arterial thrombosis.

Question 20

How does Aspirin work?

Answer 20

Irreversibly blocks cycloxygenase 1, preventing production of TXA2 (thromboxane A2).
Used orally
main side effect- GI bleeding, ulceration.

Question 21

What is the action of Clopidogrel?

Answer 21

Blocks P2Y12 receptor irreversibly. Used in people intolerant to aspirin. Oral admin.

Question 22

What is the use of Tirofiban?

Answer 22

IV, short term treatment to prevent MI in high risk patients with unstable angina (with heparin and aspirin).

Question 23

What is the role of plasminogen?

Answer 23

Naturally occuring substance that breaks down fibrin into smaller parts. Fibronyltic drugs activate plasminogen causing more breakdown of fibrin.