Anti-thrombotic Drugs

Question 1

What are the 3 classes of anticlotting drugs?

Answer 1

Antiplatelet
Anticoagulant
Thrombolytics

Question 2

Name the 4 types of antiplatelet drugs, with examples.

Answer 2

NSAIDs
- Aspirin

Platelet GpIIb/IIIa receptor antagonists

• Abciximab
• Eptifibatide
• Tirofiban

ADP receptor blockers
- Ticlopidine

Phosphodiesterase inhibitor
- Dipyridamole

Question 3

MOA of aspirin?

Answer 3

Aspirin is an antiplatelet drug.

Inhibition of COX reduces the production of thromboxane A2 from arachidonic acid. Prevents platelet aggregation.

Question 4

Pharmacokinetics (how long is the inhibitory effect) of aspirin?

Answer 4

The inhibitory effect is rapid, and will last for the lifespan of the platelet (7-10 days).

Question 5

Clinical uses of aspirin?

Answer 5

1. Prophylactic treatment of transient cerebral ischemia
2. Reduce the incidence of recurrent MI
3. To decrease mortality in post MI patients

Question 6

Adverse effects of aspirin?

Answer 6

Gastric upset and ulcers

Question 7

What is the Gp IIb/IIIa receptor?

Answer 7

It is a platelet membrane surface protein. It functions as a receptor mainly for fibrinogen and vitronectin but also for fibronectin and VWF. Activation of this receptor complex is the final common pathway for platelet aggregation.

Question 8

Clinical uses of Gp IIb/IIIa receptor blockers?

Answer 8

Prevent restenosis after coronary angioplasty, used in acute coronary syndromes.

Question 9

Name 2 other platelet aggregation inhibitors which do not work on Gp IIb/IIIa receptors?

Answer 9

Clopidogrel and ticlopidine:
Inhibit ADP receptors

Dipyridamole:
Inhibit PDE

Question 10

Name 2 anticoagulant drugs.

Answer 10

Heparin

Warfarin

Question 11

Clinical uses of heparin?

Answer 11

1. Treatment of DVT, PE and acute MI
2. Used in combination with thrombolytics for revascularisation and in combination with Gp IIb/IIIa inhibitors during angioplasty and placement of coronary stents
3. Used in pregnancy if necessary

Question 12

Administration of heparin?

Answer 12

IV
Subcutaneous

IM will cause haematomas. DON’T give IM.

Question 13

Adverse effects of heparin?

Answer 13

1. Haemorrhage

2. Thrombosis and thrombocytopenia

Question 14

Clinical uses of vitamin K?

Answer 14

1. Treatment or prevention of bleeding resulting from the use of oral anticoagulant drugs (because warfarin inhibits Vit K reductase)
2. Prevent haemorrhagic disease of the newborn
3. Vit K deficiencies

Question 15

Actions of vitamin K?

Answer 15

Reduced vitamin K is an essential cofactor in the carboxylation of glutamate residues.

Question 16

Action of warfarin?

Answer 16

Same as heparin, but DO NOT USE for pregnant women.

Question 17

Pharmacokinetics of warfarin?

Answer 17

1. Warfarin is a small and lipid-soluble molecule which is given orally and absorbed quickly and totally
2. Small Vd, strongly bound to plasma albumin (>99%)
3. Elimination depends on metabolism by hepatic cytochrome P450

Question 18

Adverse effects of warfarin?

Answer 18

1. Bleeding
2. NOT for pregnant women: will cross placenta and cause haemorrhagic disorder in the fetus. Fetal proteins with gamma-carboxyglutamate residues found in bone and blood

Question 19

What are the 4 thrombolytic agents?

Answer 19

t-PA (alteplase)
Urokinase
Streptokinase
Anistreplase

Question 20

What is the action of the thrombolytic agents?

Answer 20

Increases the conversion of plasminogen to plasmin, which degrades fibrinogen and fibrin to fibrin degradation product.

Question 21

Clinical uses of thrombolytic agents?

Answer 21

1. Emergency treatment of coronary artery thrombosis

2. Peripheral arterial thrombosis and emboli

Question 22

Administration of thrombolytic agents?

Answer 22

Intracoronary injection

IV injection

Question 23

Adverse effects of thrombolytic agents?

Answer 23

Bleeding

Contraindication: Healing wound, pregnancy