Antithrombotic drugs Flashcards
1
Q
What is thrombosis?
A
- Unwanted clot formation
- Heart attack~myocardial infarction
- Stroke~ischaemic/thromboembolic stroke
2
Q
Explain the coagulation mechanism.
A
3
Q
What are platelets?
A
- 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
4
Q
Explain disorders of clotting and bleeding.
A
- 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
5
Q
What is Arterial Thrombosis?
A
- Arterial: Form at atherosclerotic sites, lead to arterial blockage:
- Heart (heart attack, MI)
- Cerebral vessels (stroke)
6
Q
What is the difference between arterial and venous thrombosis?
A
- Venous is ‘more’ of a coagulattion factor event (DVTs)
- Arterial is ‘more’ of a platelet event (MIs and ischaemic stroke)
7
Q
What do anti-platelet drugs do?
A
- 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
8
Q
How does low dose Aspirin work on MI?
A
- 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)
9
Q
What is GP IIb/IIIa?
A
- ADP from aggregating platelets, leads to expression of glycoprotein IIb/IIIa
- GP IIb/IIIa-binds to fibrinogen
10
Q
How do ADP receptor antagonists at the P2Y12 receptor work?
A
- 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.
11
Q
What is Fibrinolysis?
A
- 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)
12
Q
What are the primary uses of Fibrinolysis?
A
- Used in thromboembolic stroke-dissolves the thrombus that has caused blockage of the cerebral arteries-Alteplase for ischaemic stroke
- Sometime is MI-Emergency angioplasty now in treatment
13
Q
What are anticoagulants?
A
- Drugs used to prevent coagulation
1. Heparins
2. Oral anticoagulants: Warfarin
3. Direct Oral Anticoagulants (e.g. Rivaroxban)
14
Q
What are injectable Anticoagulants?
A
- 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
15
Q
What is Heparin?
A
- Immediate action
- Used to prevent thrombosis (e.g. DVT) and used to prevent blood clotting on collection
- Used whilst warfarin takes effect
16
Q
What is Deep Vein Thrombosis(DVT)?
A
- Form in veins-immobility in hospital
- A major risk for pulmonary embolism
17
Q
What are DOACs (direct oral anticoagulants)?
A
- 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
18
Q
What are Apixiban and Rivaroxaban?
A
- Oral inhibitors of activated factor X
- Reversal for Dabigatran: Idrucizumab reverses within mins
19
Q
What is Warfarin?
A
- Oral anticoagulant-Vitamin K antagonist
- Essential for the production of Prothrombin and factors VII, IX, X
1. Narrow therapeutic window
2. Many interactions
20
Q
What is International Normalised Ratio(INR)?
A
Time taken for coagulation following the addition of thromboplastin.
