Antithrombotics Flashcards
Primary hemostasis steps
Platelet shape change and activation
Platelet adhesion
Platelet aggregation
Secondary hemostasis step
Activation of intrinsic/extrinsic coagulation cascades
ADP activates platelets through a G_ protein coupled receptor
Gi
Anti platelet drugs
Aspirin
Clopidogrel
Abciximab
Vorapaxar
Thrombolytic drug
T-PA
Vitamin K antagonist
Warfarin
ADP receptor antagonist
Clopidogrel
Clopidogrel MOA
Prodrug metabolized in liver
Blocks platelet aggregation by binding irreversibly to P2Y12 ADP receptors
Clinical uses of clopidogrel
Reduce rate of stroke, MI, atherosclerosis
Similar but slightly.,more effective than aspirin
Black box warning for clopidogrel
Therapeutic failure in patients with loss of CYP2C19*2 allele
(Need to be tested for allele before starting drug)
Adverse effects of Clopidogrel
Bleeding
GI upset
Thrombotic thrombocytic purpura
Drug interactions with Clopidogrel
NSAIDs
omeprazole
Abciximab MOA
GPIIb/IIIa antagonist
Blocks platelet aggregation/fibrinogen binding
Clinical use of abciximab
Most effective anti platelet drug (very expensive)
Short term to prevent ischemic events
Vorapaxar MOA
Blocks PAR-1 receptor
Vorapaxar clinical use
Reduce thrombosis post-MI
How long does Vorapaxar effect last?
Up to 4 weeks
Boxed warning of vorapaxar
Bleeding (intracranial hemorrhage)
Antiplatelet drugs are effective against arterial/venous thrombi
Arterial
Anticoagulants are effective against arterial/venous thrombi
Venous
PTT is used to monitor intrinsic/extrinsic pathway anticoagulants
Intrinsic
PT is used to monitor intrinsic/extrinsic pathway anticoagulants
Extrinsic
Heparin inactivates ____ and ___ equally
Thrombin, Xa
LMWh inactivates ___ well and ___ poorly
Xa, thrombin
____ inactivates factor Xa only
Fondaparinux
LMW heparin drugs
Enoxaparin
Fondaparinux
MOA of heparins
Blocks formation of fibrin
Heparin has no intrinsic/extrinsic activity
Intrinsic
Clinical uses of heparin
Initial treatment of DVT/PE
Surgeries to prevent thrombosis
Heparin antidote
Protamine sulfate (doesn’t work against fondaparinux)
Heparin black box warning
Derived from pigs (cultural and allergic cautions)
Vitamin K antagonist prototype
Warfarin
MOA of vitamin K antagonists
Decreases vitamin K-dependent clotting factors by inhibiting VKORC1 in liver
Decreases formation of fibrin
Vitamin K antagonists have slower/faster onset than heparin
Slower (takes several days for full effect vs 5 minutes for heparin; heparin used until warfarin takes effect)
Patients on warfarin should be advised to avoid excess ___ in their diet
Vitamin K (leafy greens, fish, alcohol)
Warfarin depletes endogenous anticoagulants, causing an initial _____ state
Hyper-coagulable
Route of administration for warfarin
Oral
Warfarin is ___% albumin bound
99%
Warfarin therapy requires close monitoring via ___
PT/INR
Warfarin is metabolized by which enzyme?
CYP2C9
Clinical use of warfarin
Long-term prophylaxis of venous thrombosis
Adverse effects of warfarin
Bleeding
Teratogen
Tissue necrosis
Purple toe syndrome
Warfarin antidote
Vitamin K (phytonadione)
Direct thrombin inhibitor drugs
Bivalirudin
Dabigatran etexilate
Dabigatran advantage over warfarin
Don’t need to monitor INR
Dabigatran antidote
Idarucizumab
t-PA MOA
Converts plasminogen to plasmin that digests fibrin
