Anticoag Pharm Flashcards
Aspirin
irreversibly inhibits COX enzyme –> COX can’t make TXA –> prevents plt aggregation
NSAIDs
reversibly inhibits COX enzyme
clopidigrel/plasugrel
thienopyridines
targets ADP PDY12 receptor –> prevents platelet aggregation
IRREVERSIBLE (but partial) alterations of ADP
ticagrelor
ADP P2Y12 receptor antagonist –> prevents plt aggregation
REVERSIBLE antagonist of ADP
active parent drug and metabolite
indications for anti-platelet aggregation
prevention of arterial thrombosis
pre-ecclampsia
prevention of venous thromboembolism in limited situations
pharmacokinetics of clopidogrel
CYP3A4 processing
inhibits by concurrent use of atorvastatin
peak effect 4-6 hrs after oral dosing
plasugrel
PRODRUG (req activation by enzymatic metabolism)
SE of ticagrelor
bleeding
dyspnea, bradycardia (similar to adenosine)
gynecomastia in men
GPIIb/IIIa receptor antagonists
all admin IV
- abciximab: mAb Fab fragment
- eptifibatide: cyclic heptapeptide
- tirofiban: small molecule
MOA: block fibrinogen binding to GPIIb/IIIa –> prevent final pathway of platelet aggregation
indication: prevent vessel closure after PCI
anticoag of choice in pregnancy
heparin
heparin MOA
inhibits factor Xa and IIa by accelerating inhibition by antithrombin
- inhibits activity of preformed coag factors
side effects of heparin
bleeding
osteoporosis
skin lesions
hypoaldosteronism
heparin-induced thrombocytopenia
immune-mediated IgG directed against heparin/PF4 on platelet surface
occurs w/in 5-15 days of heparin therapy initiation
mild thrombocytopenia
highly thromboic state
low molecular weight heparins
dalteparin
enoxaparin
tinziparin
fondaparinux
advantages of LMWH over UH
fixed dose (weight-based) SC admin- can be done at home no routine lab monitoring more predictable response less HIT
disadvantages of LMWH
longer half- life might be a problem if pt bleeds b/c no antidote
renal excretion - bad to use in renal insufficiency
how to reverse heparin effect
short-half life –> discontinue b/f invasive procedures
severe bleeding –> protamine sulfate (this doesn’t work well for LMWH)
warfarin MOA
vit K antagonist (blocks epoxide reductase in the liver)
vit K req for coag factors II, VII, IX, X, protein C, protein S
inhibits synthesis of active coag factors
warfarin pharmacokinetics
metabolized by CYP450, excreted in urine
clearance not affected by renal dysfunction, but increased by dialysis
LONG HALF LIFE (33hrs), takes 7-10 days to reach steady state
warfarin SEs
bleeding
skin necrosis
teratogenic in early fetal development
how to reverse warfarin
vit K - effect w/in hrs
fresh frozen plasma (contains coag factors) - immediate effect
prothrombin concentrates - immediate effect
parenteral direct thrombin inhibitors
argatroban, bivalirudin
for rx and prevention of thrombosis in HIT, anticoagulation during PCI in pts w/ HIT
dabigatran
inhibits thrombin
prodrug - does not involve CYP450
renal excretion
rivaroxaban
inhibits X directly
active drug metabolized by CYP3A4
renal excretion
