Antithrombotics Flashcards
Antiplatelet drug classes (4)
COX-1 inhiitors
PDE inhibitors
ADP receptor antagonists
GP IIb/IIIa antagonists
ADP-recpetor antagonist
clopidogrel
GP IIb/IIIa antagonist
abciximab
MOA of clopidogrel
Irriversibly antagonizes ADP receptor reducing inactivation of AC, increasing cAMP and increasing PKA, leading to reduced platelet aggregation
MOA of abciximab
binds to GP to prevent them from crosslinking through fibrinogen bridge
Pharmaco genetics of clopidogrel
prodrug metabolized by CYP2C19. Black boxed warning
Pharmacokinetics of clopidogrel
orally effective, maximal efficacy 8-11 days
Therapeutic use of colpidogrel
alternative to low dose asprin
reduces rate of stroke, MI and death in those with recent stroke, MI, ACS, PAD
In combination with asprin for prevention of coronary stent thrombosis and ACS
Adverse effects of colpidogrel
bleeding
thrombotic thrombocytopenic purpura
Drug interactions with colpidogrel
avoid NSAIDS
CYP2C19 inhibitors, omeprazole
Pharmacokinetics of abciximab
half life 10 min duration of action 48 hours due to irreversible binding
Therapeutic use of abciximab
most effective, most expensive
short term in combo with asprin to prevent ischemic events in hospital setting
Adverse effects of abciximab
bleeding, anaphylaxis
Heparin MOA
indirect inhibitors of thrombin and/or Xa through antithrombin
Enoxaparin MOA
~17 saccharide heparin
Fondaparinux MOA
pentasaccharide heparin
Pharmacokinetics of heparin
immediate onset
parenteral
“sticky,” must monitor aPTT
LMWH/fondaparinux- don’t need to monitor aPTT
Selectivity of heparins
Heparin inactivates thrombin and Xa
LMWH inactivates Xa well, thrombin poorly
Fondaparinux inactivates Xa only
Therapeutic use of heparin
initial treatment of DVT/PE
transition to warfarin
safe in pregnancy
Adverse effects of heparin
bleeding, protamine sulfate antidote
HIT/HITT - CBC needed
Alternative anticoagulants in HIT
bivalirudin, fondaparinux
Vitamin K antagonist
warfarin
MOA of warfarin
inhibits synthesis of K-dependent clotting factors by inhibiting VKOR1C in the liver
Pharmacokinetics of warfarin
oral
delayed onset, dependent on clotting factor turnover
metabolized by CYP2C9
Dosing of warfarin
must be monitored by PT/INR
Therapeutic use of warfarin
prevent progression of recurrence of DVT or PE
Prevention of thromboembolism in patient with prosthetic heart valves
not useful in an emergency
Adverse effects of warfarin
boxed warning for bleeding
antidote is vitamin K, takes hours, for immediate need- prothrombin complex concentrate (PPC) or plasma.
Teratogen
Drug interactions with warfarin
CYP inhibitors
displacement of plasma albumin
broad spectrum antibiotics
anything that promotes bleeding
Reduce warfarin effect
CYP inducers
excessive vitamin K
Direct inhibitors of thrombin
bivalirudin- parenteral
dabigatran etexilate- oral
bivalirudin MOA
binds to and inhibits thrombin
Pharmacokinetics of bivalirudin
given IV and monitored by aPTT, short half life, excreted by the kidney
Therapeutic use of bivalirudin
used for HITT and during PCI
Adverse effect of bivalirudin
bleeding
Pharmacokinetics of dabigatran etexilate
orally active
onset 2-3 hrs
dosed 2x per day without monitoring
Therapeutic use of dabigatran
“warfarin replacement”
no monitoring required
Adverse effect of dabigatran
bleeding with no antidote
Thrombolytic agents
t-PA
MOA of t-PA
activates plasminogen and breaks up fibrinogen clot.
Therapeutic use of t-PA
within the first three hours after MI
