Lecture 6.6: Drugs affecting coagulation

Question 1

What are the three outcomes following blood vessel damage? Aka Physiological haemostasis?

Answer 1

Vasoconstriction (5-HT is a powerful vasoconstrictor, released by platelets). Platelet adhesion, activation. They release ADP which activates other platelets to release granules synthesise mediators, aggregate and adhere via fibrinogen. Fibrin formation formed from fibrin, cleaved by thrombin.

Question 2

What is the difference between extrinsic and intrinsic cascade reactions?

Answer 2

We never get intrinsic as it is due to factors in the blood causing clot. Occurs in vitro. Extrinsic is when damaged tissues release thromboplastin, then factors 7, 10 come in play. Both pathways lead to factor 10, prothrombin to thrombin, fibrinogen to fibrin, stable clot.

Question 3

How does antithrombin work?

Answer 3

Antithrombin (still known as thrombin),

Question 4

How does antithrombin work? In other words, how does fibrinolysis work?

Answer 4

Antithrombin (still known as thrombin), now bound to thrombomodulin (effectively modulates the thrombin) to activate protein C. APC then inactivates the inhibitor of plasminogen (effectively activating plasminogen), making plasmin, resulting in fibrinolysis.

Question 5

Describe the actions of heparin.

Answer 5

Heparin helps anticoagulation. It enhances the activity of antithrombin.

LMW heparin has a lesser effect on thrombin, but longer half life.

APTT is used to monitor effect (remembering that it is only a measure of intrinsic pathway).

Question 6

What does warfarin do?

Answer 6

Used for prolonged therapy, warfarin competes with vitamin K reductase. It is also an anticoagulant.

Monitored by PT and INR (extrinsic pathway)

Because it strongly binds to plasma proteins, any change in plasma protein levels can severely affect warfarin activity.

Question 7

True or false? Warfarin is only active in vivo.

Answer 7

True. This is because it is affecting formation.

Question 8

How is warfarin metabolised?

Answer 8

Via cytochrome p450 pathway. Same as alcohol, so those on warfarin cannot take alcohol.

Question 9

Give an example of an ADP receptor antagonist and its effects.

Answer 9

Clopidogrel. Remember that ADP is released by platelets to encourage an orgy of platelets. It inhibits glycoprotin complex which inhibits the platelet aggregation.

Question 10

What is the mechanism of action of aspirin?

Answer 10

Inhibits TXA2 production. Action is irreversible. Decreases vasoconstriction.

Question 11

True or false? Abciximab is a glycoprotein receptor antagonist.

Answer 11

True.

Question 12

What are the effects of streptokinase and alteplase?

Answer 12

Streptokinase activates plasminogen, one time use only.

Alteplase is a human plasminogen.