Anticoagulant and antiplatelet drugs Flashcards
Anticoagulant drugs
Warfarin
Heparin
- unfractionated heparin
- LMW heparin
Newer agents
- dabigatran (oral direct thrombin (factor IIa) inhibitor)
- rivaroxaban (oral factor Xa inhibitor)
Anti-platelet drugs
Anti-fibrinolytics
Warfarin
Vitamin K antagonist
Prevents gamma-carboxylation of factors II, VII, IX, X
Prolongs the extrinsic pathway (prothrombin time)
Monitored by the INR
Target INR usually 2.5 for DVT/PE and AF
Target 3.5 for recurrent VTE or metal heart valves
Clotting factor half life
VII- 6 hours
IX- 24 hours
X- 40 hours
II- 60 hours
Pharmacodynamics of warfarin
Can take >3 days to achieve therapeutic levels
Warfarin also inhibits the natural anti-coagulants
- protein C
- protein S
Prescribing warfarin
Patient usually loaded with LMW heparin
- typical regime, 10mg, 10mg, 5mg
Fall in protein C and S occurs within hours and can result in a temporary pro-coagulant state
LMW usually continued until the INR >2.0 for 2 consecutive days
Warfarin interactions
Beware interactions with other drugs due to cytochrome P450
Enzyme inhibition potentiate warfarin
- carbamazepine, azathioprine, allopurinol
- erythromycin, ciprofloxacin, metronidazole, fluconazole
Enzyme inducers inhibit warfarin
- rifampicin, amiodarone, citalopram, phenytoin
Warfarin side effects
Teratogenic- therefore use LMW heparin in pregnancy
Significant haemorrhage risk- intra-cranial bleeds up to 1% per year, increased risk in elderly and with higher INR target
Minor bleeding up to 20% per year
Skin necrosis
Alopecia
Reversing warfarin
If life threatening bleed, give activated prothrombin complex (octaplex) containing factors II, VII, IX, X
Give vitamin K 2-10mg iv/po depending on INR level
Fresh frozen plasma can also be used
Heparin
Mucopolysaccharide that potentiates anti-thrombin
Irreversibly inactivates factors IIa (thrombin) and Xa
Administered parenterally
Two formulations of heparin
- unfractionated heparin given i.v. infusion
- LMW heparin given as s.c. injection
Safe in pregnancy
Unfractionated heparin
Not often used due to inconvenience
Given i.v. with 5000U bolus and 1000U/ hour infusion
Monitored by APTT with target range of 1.5-2.5 x normal
Safe in renal failure
Can be partially reversed wit protamine sulphate
Thrombocytopenia and VTE rare complication resulting in heparin induced thrombocytopenia
LMW heparin
Very convenient due to once daily s.c. injections
Prescribed according to patient’s weight
Not usually monitored
Patient must have creatinine clearance over 30ml/minute
LMW heparin formulations
Tinzaparin
Enoxaparin
Dalteparin
Other parenteral anticoagulants
Hirudin
- snake venom derived
- argatroban- direct thrombin inhibitor
- used in place of heparin in patients with HIT
Heparinoids
- danaparoid- heparin like compound
Fondaparinux
- arixtra- potentiates anti-thrombin, inhibits factor Xa
Direct oral anti-coagulants
Developed as an alternative to warfarin
Orally available, no monitoring, good safety profile
Two classes of DOACs
Direct thrombin (IIa) inhibitor - dabigatran
Direct factor Xa inhibitor
- rivaroxaban
Rivaroxaban
Direct factor Xa inhibitor
- causes irreversible anti-coagulation
Indications
- VTE prophylaxis
- used for treatment of DVTs and PEs
- stroke prevention in af
Dosing is 15mg bd for 3 weeks, then 20mg od
Apixaban is alternative drug
- less affected by renal function
Dabigatran
Direct thrombin inhibitor
Indications
- VTE prophylaxis
- used for treatment of DVTs and PEs
- stroke prevnetion in af
Dosing
- treatment dose 150mg bd
- prophylactic dose 110mg bd
Can be reversed by praxbind (idarucizumab)
Aspirin
Anti-platelet
Cyclo-oygenase inhibitor
Clopidogrel
Anti-platelet
ADP receptor blocker
Dipyridamole
Anti-platelet
Inhibits phosphodiesterase
Proastcyclin
Anti-platelet
Stimulates adenylate cyclase
Glycoprotein IIb/IIIa inhibitors
Anti-platelets
Abciximab- monoclonal antibody
Eptifibatide- snake venom derivativee
Tirofiban- blocks platelet aggregation
Fibrinolytic agents
Thrombolytic agents used to lyse fresh thrombi (arterial) by converting plasminogen to plasmin
Tissue plasminogen activator (alteplase) and streptokinase
Administered systemically in acute MI, recent thrombotic stroke, major PE or iliofemoral thrombosis
Standardised dosage regimens aim to use within 6 hours
Beware of contra-indications to thrombolysis
