Antiplatelet, anticoagulant and thrombolytic drugs

Question 1

What is haemostasis?

Answer 1

The human body’s response to blood vessel injury and bleeding.
It involves local vasoconstriction, adhesion and activation of platelets at the site of injury and formation of fibrin.

Question 2

What is thrombosis?

Answer 2

Pathological haemostasis

It is a haematological plug in the absence of bleeding (haemostasis in the wrong place)

Question 3

What are the predisposing factors to thrombosis?

Answer 3

Virchow’s triad:
Injury to vessel wall
Abnormal blood flow
Increased coagulability of the blood

Question 4

Describe arterial thrombus

Answer 4

White thrombus
Mainly platelets in a fribrin mesh
Embolus often lodges in an artery in the brain (stoke) or other organ

Question 5

Describe venous thrombus

Answer 5

Red thrombus
White head, jelly-like red tail, firbin rich
Embolus usually lodges int the lung (PE)

Question 6

What are the two pathways that take place after endothelial damage to form a fibrin clot?

Answer 6

Platelet reactions

Blood coagulation

Question 7

What are the two blood coagulation pathways?

Answer 7

In vivo pathway and contact pathway

Question 8

What is the role of vitamin K in clot formation?

Answer 8

Vitamin K is needed to carboxylate the clotting factors to convert them into their active form

Question 9

What is the link between warfarin and vitamin K?

Answer 9

Warfarin prevents the formation of the reduced form of vitamin K that we need to drive gama carboxylation (and activate the clotting factors)

Question 10

When would you prescribe an anticoagulant?

Answer 10

VENOUS THROMBOSIS
Deep vein thrombosis (DVT)
Prevention of post-operative thrombosis
Patients with artificial heart valves
Atrial fibrillation

Question 11

Give an example of an anticoagulant

Answer 11

Warfarin

Question 12

Describe the mechanisms of Warfarin action

Answer 12

Renders factors II, VII, IX and X inactive.

Blocks coagulation in vivo.

Question 13

Is warfarin fast or slow acting?

Answer 13

Slow onset of action (2-3 days)

Has a long and variable half-life (usually about 40hours)

Question 14

What other anticoagulant could be administered if rapid anticoagulation was needed?

Answer 14

Heparin

Question 15

Why are patients on warfarin monitored?

Answer 15

Warfarin has a low therapeutic ratio and it can be difficult to stroke the balance between the desired anticoagulant effect and haemorrhage

Question 16

What factors potentiate warfarin action and increase the risk of haemorrhage?

Answer 16

Liver disease (decrease in clotting factors as they are produced by the liver)
High metabolic rate (increased clearance of clotting factors)
Drug interactions (effect enzyme action)

Question 17

What factors lessen warfarin action and result in the risk of thrombus being increased?

Answer 17

Physiological state (pregnancy increases clotting factor synthesis)
Hypothyrodism (decreased degradation of clotting factors)
Vitamin K consumption
Drug interactions

Question 18

How do you treat an overdose of warfarin?

Answer 18

Administration of vitamin K or concentrate of plasma clotting factors

Question 19

What is the role of antithrombin III?

Answer 19

Endogenous inhibitor of coagulation

Question 20

Explain the mechanisms of heparin action

Answer 20

Heparin binds to antithrombin III increasing its affinity for clotting factors. This greatly increases their rate of inactivation.

Question 21

Give two examples of low molecular weight heparins (LMWHs)

Answer 21

Enoxaparin and dalteparin

Question 22

LMWHs are now preferred except in what condition?

Answer 22

Renal failure

LMWH is eliminated via renal excretion

Question 23

Why are LMWHs preferred to heprain?

Answer 23

Heparin is less predictable due to zero order elimination

Question 24

How does endothelium damage promote thrombus formation?

Answer 24

Vascular damage reveals subendothelial molecules which the platelets adhere to

Question 25

What happens to platelets when they are activated?

Answer 25

They change shape from a simple disk to a more complex shape.
They then aggregate.

Question 26

What drives aggregation?

Answer 26

Platelet-derived substances
Coagulation factors are released from storage granules
Exposure of acidic phospholipid on platelet surface promoting thrombin (IIa) formation

Question 27

How is the clot stabilised?

Answer 27

The formation of fibrin from fibrionogen, activated by the production of thrombin (IIa).

Question 28

Name three antiplatelet drugs

Answer 28

Clopidogrel, tirofiban and aspirin

Question 29

What are anti-platelet drugs used in the treatment of?

Answer 29

Arterial thrombosis

Question 30

When would clopifogrel be prescribed?

Answer 30

In patients intolerant of aspirin

Synergistic affect with aspirin

Question 31

When would tirofiban be prescribed?

Answer 31

IV for short term treatment to prevent MI in high risk patients with unstable angina

Question 32

What is the role of plasminogen?

Answer 32

It produces plasmin which breaks down fibrin into fragments, dissolving the clot

Question 33

What do fibrinolytic drugs do?

Answer 33

Oppose the coagulation cascade

Open up occluded arteries in MI or stroke

Question 34

How are fibrinolytic drugs administered?

Answer 34

Intravenously, as close to the event as possible

Question 35

What modern technique is superior to the use of fibrinolytic drugs after MI?

Answer 35

Percutaneous coronary intervention (PCI)

Question 36

Name three fibrinolytic drugs

Answer 36

Streptokinase, alterplase and duteplase