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)