Antithrombotic drugs

Question 1

What is thrombosis?

Answer 1

• Unwanted clot formation
• Heart attack~myocardial infarction
• Stroke~ischaemic/thromboembolic stroke

Question 2

Explain the coagulation mechanism.

Answer 2

Question 3

What are platelets?

Answer 3

• Non-nuclear cellular fragments
• Form mechanical plugs during blood vessel injury
• Adhesion and aggregation reactions:
  1. Adhesion: to subendothelial surface on damage/disease-due to binding to von willebrand’s factor
  2. Adhesion casues release reaction: ADP and thromboxane which promote platelet aggregation

Question 4

Explain disorders of clotting and bleeding.

Answer 4

• Thrombosis-Unwanted blood clots
• Venous: clots (thrombi) form in veins (DVT) due to stasis of blood, may travel to lungs, PULMONARY EMBOLISM (economy class syndrome)
• Atrial fibrillation: Risk of TIA (transient ischaemic attack) or stroke

Question 5

What is Arterial Thrombosis?

Answer 5

• Arterial: Form at atherosclerotic sites, lead to arterial blockage:
• Heart (heart attack, MI)
• Cerebral vessels (stroke)

Question 6

What is the difference between arterial and venous thrombosis?

Answer 6

• Venous is ‘more’ of a coagulattion factor event (DVTs)
• Arterial is ‘more’ of a platelet event (MIs and ischaemic stroke)

Question 7

What do anti-platelet drugs do?

Answer 7

• PGI2-prev platelet aggregation-acts on platelets to inc cAMP
• Thromboxane (TXA2)-Promotes aggregation and dec cAMP
• Nitric oxide(NO)- prev both platelet adhesion and aggregation by inc platelet cGMP

Question 8

How does low dose Aspirin work on MI?

Answer 8

• Used to prevent MI in patients who’ve previously had an MI-recommended for secondary use but not primary prevention
• Reduces incidence of stroke
• Inhibits cyclo-oxygenase (irreversible)

(see PP for diag)

Question 9

What is GP IIb/IIIa?

Answer 9

• ADP from aggregating platelets, leads to expression of glycoprotein IIb/IIIa
• GP IIb/IIIa-binds to fibrinogen

Question 10

How do ADP receptor antagonists at the P2Y12 receptor work?

Answer 10

• Clopidogrel-Inhibits ADP-induced expression of GP
• Prasugrel-irreversible antagonist~ more effective, faster onset, and predictable
• Ticagrelor-Reversible via allosteric modulation
• Abciximab-monoclonal antibody against GP IIb/IIIa- given to patients undergoing angioplasty-only use once.

Question 11

What is Fibrinolysis?

Answer 11

• e.g. Alteplase
• Thrombolytics/Fibrinolytics/Clot busters
• Endogenous system to dissolve clots
• Activated in parallel with clotting system
• Plasmin- digests the fibrin of the clot (and also some of the clotting factors)

Question 12

What are the primary uses of Fibrinolysis?

Answer 12

1. Used in thromboembolic stroke-dissolves the thrombus that has caused blockage of the cerebral arteries-Alteplase for ischaemic stroke
2. Sometime is MI-Emergency angioplasty now in treatment

Question 13

What are anticoagulants?

Answer 13

• Drugs used to prevent coagulation
  1. Heparins
  2. Oral anticoagulants: Warfarin
  3. Direct Oral Anticoagulants (e.g. Rivaroxban)

Question 14

What are injectable Anticoagulants?

Answer 14

• Unfractioned heparin
• Or LMWHs (e.g. enoxaparin)
• Activate Antithrombin III (natural protein)
• Antithrombin- inactivates some clotting factors and thrombin by complexing with serine protease of the factors

Question 15

What is Heparin?

Answer 15

• Immediate action
• Used to prevent thrombosis (e.g. DVT) and used to prevent blood clotting on collection
• Used whilst warfarin takes effect

Question 16

What is Deep Vein Thrombosis(DVT)?

Answer 16

• Form in veins-immobility in hospital
• A major risk for pulmonary embolism

Question 17

What are DOACs (direct oral anticoagulants)?

Answer 17

• Dabigatran: an oral thrombin inhibitor
• Prevents Thromboembolism
  1. Less bleeding then warfarin
  2. Fewer drug interactions
  3. Does not require monitoring
• RE-LY trial: equally effective as warfarin in AF

Question 18

What are Apixiban and Rivaroxaban?

Answer 18

• Oral inhibitors of activated factor X
• Reversal for Dabigatran: Idrucizumab reverses within mins

Question 19

What is Warfarin?

Answer 19

• Oral anticoagulant-Vitamin K antagonist
• Essential for the production of Prothrombin and factors VII, IX, X
  1. Narrow therapeutic window
  2. Many interactions

Question 20

What is International Normalised Ratio(INR)?

Answer 20

Time taken for coagulation following the addition of thromboplastin.