Antithrombotics Flashcards
What are the 3 classes of anticoagulant drugs?
Warfarin
Heparins (unfractionated or low molecular weight)
NOAC’s (Novel oral anticoagulants): Dabigatran
Describe the mechanism of action of warfarin?
Acts as a Vitamin K antagonist by competitively inhibiting the Vitamin K reductase enzyme essential (carboxylation of the carbonic acid residues) in the production of prothrombin factors VII, IX and X.
Describe the indications for using warfarin?
DVTs/PE’s
AF
Mechanical heart valves
Note takes several days to start working.
Describe how warfarin is monitored and the reasoning for monitoring?
In patients on warfarin their INR (international normalised ratio) is monitored this is a number derived form the prothrombin time.
1 indicates a patients prothrombin time is normal.
2 indicates a patients prothrombin time is twice as long aka they will bleed more easily.
The INR is measured as warfarin has a narrow TI, and many food and drug interactions.
The Therapeutic aim is to keep patient’s INR’s between 2-3
Describe the important drug interactions associated with warfarin?
Warfarin is metabolised by the Cytochrome P450 enzymes.
Therefore CytP450 inhibitors can potentiate the effects of warfarin and increase a patients INR:
Erythromycin, cimetidine (H2 receptor antagonist), Amiodarone
CytP450 inducers can reduce the effects causing the patients INR to drop and for the treatment to fail:
Barbituates, Carbamazepine, Rifampicin, St John’s Wort
Describe the contraindications and risks of taking warfarin?
Contraindications: Always way up bleeding vs clot risk (HAS BLED vs WELLS)
Haemophilia’s
Pregnancy: teratogenic paticularly in 1st trimester
Risks:
Bleeding:
Gastric, cerebral.
Haempotysis, haematuria, easy bruising.
Describe the mechanism of action of heparins?
Activates antithrombin III which inhibits the serine proteases involved in the production of thrombin, factors IX, X and XI.
Describe the practical difference between LMWH and unfractionated heparins and the indications for each?
LMWH are more predicatable and therefore do not require monitoring whilst unfractionated heparins need monitoring via the activated partial thromboplastin time (APTT).
They are used to prevent venous thrombosis, and whilst the the effects of warfarin are waiting to kick in (they work immediately) .
Used in patients who may have difficulty taking warfarin (unreliable patients) and in patients that need anticoagulation during pregnancy.
Longer term use (>5 days) is associated with thrombocytopenia and platelets should be monitored.
LMWH: subcutaneous inj
Unfractionated: IV
Describe the how NOACs work and the pros and cons they have when compared to warfarin?
Dabigatran.
They are oral thrombin inhibitors.
They have less side effects and drug interactions than warfarin. BUT there is no known antidote and they cannot be monitored.
Describe how low dose aspirin acts as an anti-platelet drug?
Irreversibly inhibits cyclo-oxygenase.
COX is found in endothelial cells and in platelets.
In endothelial cells it is involved in the production of PGI2 (prostacyclin) which inhibits platelet aggregation.
In platelets it is involved in the production of TXA2 (thromboxane) which facilitates platelet aggregation.
Aspirin inhibits the COX in both cells but in endothelial cells the COX regenerates, whereas in platelets where there is no nucleus it doesn’t.
The net result is that it favours the production of PGI2 (prostacyclin) inhibiting platelet aggregation and is therefore protective against thrombus formation.
Describe the method of action of Dipyridamole?
cAMP and gAMP both inhibit platelet aggregation.
cAMP and gAMP are broken down by phosphodiesterases.
Dipyrimadole acts by inhibiting phosphodiesterases.
Describe the mechanism of action of clopidogrel?
ADP from aggregating platelets, leads to expression of glycoprotein IIb/IIIa (GP IIb/IIIa).
GP IIb/IIIa binds fibrinogen which leads to the cross linking of platelets.
Clopidogrel inhibits ADP induced expression of GP IIb/IIIa. (equally as efficacious as asprin, good for those who cannot take aspirin)
Describe the basis of how thrombolytic drugs work?
Stimulates the conversion of plasminogen into plasmin which digests the fibrin in a clot.
