Antithrombotic Drugs Flashcards
What are the two major anticoagulant drugs?
Warfarin
Heparin
What is the mechanism of action of warfarin?
Blocks vitamin K epoxide reductase, preventing reduction of vitamin K back to its acted form which is needed as a cofactor for coagulation factor synthesis.
Why might you give heparin alongside warfarin initially?
Warfarin has a slow onset of action - heparin covers you for the first few days
List 4 uses of warfarin
- Prevention of recurrence of VTE
- Prevention of AF
- Prevention of thrombosis in mechanical heart valves
- Prevention of thrombosis in thrombophilic conditions
Why isn’t warfarin used to prevent stroke/MI
These are arterial and caused by platelet aggregation - therefore anti-platelet drugs more efficacious
What is the main ADR associated with warfarin?
Bleeding
List two circumstances in which Warfarin use is contraindicated
- Liver disease
- Pregnancy
List two major groups of DDI associated with warfarin use. Give examples.
- CYP450 inducers reduce warfarin levels - e.g. Rifampicin, St John’s Wort
- CYP450 inhibitors increase warfarin levels - e.g. Macrolides, alcohol
How would you monitor warfarin levels? Give the full name.
What would the ideal range be
International normalised ratio (INR)
In most conditions, 2 - 3, but in mechanical heart valves 3 - 6
List the steps taken to reverse warfarin in the case of bleeding
Reduce warfarin Stop warfarin Oral vitamin K IV vitamin K Fresh frozen plasma
What are the two types of heparin and how do they differ in administration/monitoring?
Unfractionated heparin - IV, non-linear PK - needs monitoring via aPTT
Low molecular weight heparin - subcutaneous injection - more predictable PK - no monitoring needed.
Give an example of a low molecular weight heparin
Dalteparin
Describe the mechanism of action of heparin (both unfractionated and LMW)
Binds to antithrombin III (ATIII) which activates it.
ATII in turn inhibits:
- Xa
If heparin is unfractionated, also binds to IIa - inhibits this too.
End result is prevention of fibrin plug formation
List 3 major uses of heparin
- VTE prophylaxis
- First-line treatment of VTE
- Safe in pregnancy
List 3 important ADRs of heparin
- Bleeding
- Injection site reactions
- Heparin-induced thrombocytopenia (autoimmune)
How is heparin reversed?
Stop heparin
Give protamine sulphate
List the 3 anti-platelet drugs on the PPE drug list
- Aspirin
- Dipyridamole
- Clopidogrel
Briefly outline the mechanism of action of aspirin
- Inhibits COX-1 by binding irreversibly
- Therefore inhibits conversion of arachadonic acid to prostaglandin H2
- In turn, this prevents production of thromboxanes which promote platelet aggregation - hence decreased aggregation
List the 2 major uses of aspirin as an antiplatelet
- Acute coronary syndrome - prevents clot progression
- Prevention of thrombosis in CVS disease
List 3 ADRs associated with aspirin
How could you overcome one of these?
- GI irritation +/- ulceration/haemorrhage - use PPI
- Bronchospasm
- Tinnitus
In whom should aspirin be used with caution? (4 examples)
- Children under 16
- Asthmatics
- Peptic ulcers
- 3rd trimester of pregnancy
What is the mechanism of action of dipyridamole?
- Phosphodiesterase inhibitor - increases cAMP, therefore decreases Ca2+.
- Therefore decreased thromboxane synthesis and hence decreased platelet aggregation
What is the major use of dipyridamole?
List 2 ADRs - why do they occur?
Secondary prevention of stroke
Can cause flushing and headaches - positive inotropic effect and vasodilatory
What is the mechanism of action of Clopidogrel? (And therefore what is its class?)
- ADP Antagonist
- Binds irreversibly to the P2Y12 ADP receptor on the platelet surface - therefore decreases platelet aggregation due to decreased downstream signalling.
