Anticoag Pharm

Question 1

Aspirin

Answer 1

irreversibly inhibits COX enzyme –> COX can’t make TXA –> prevents plt aggregation

Question 2

NSAIDs

Answer 2

reversibly inhibits COX enzyme

Question 3

clopidigrel/plasugrel

Answer 3

thienopyridines
targets ADP PDY12 receptor –> prevents platelet aggregation
IRREVERSIBLE (but partial) alterations of ADP

Question 4

ticagrelor

Answer 4

ADP P2Y12 receptor antagonist –> prevents plt aggregation
REVERSIBLE antagonist of ADP
active parent drug and metabolite

Question 5

indications for anti-platelet aggregation

Answer 5

prevention of arterial thrombosis
pre-ecclampsia
prevention of venous thromboembolism in limited situations

Question 6

pharmacokinetics of clopidogrel

Answer 6

CYP3A4 processing
inhibits by concurrent use of atorvastatin
peak effect 4-6 hrs after oral dosing

Question 7

plasugrel

Answer 7

PRODRUG (req activation by enzymatic metabolism)

Question 8

SE of ticagrelor

Answer 8

bleeding
dyspnea, bradycardia (similar to adenosine)
gynecomastia in men

Question 9

GPIIb/IIIa receptor antagonists

Answer 9

all admin IV

1. abciximab: mAb Fab fragment
2. eptifibatide: cyclic heptapeptide
3. tirofiban: small molecule

MOA: block fibrinogen binding to GPIIb/IIIa –> prevent final pathway of platelet aggregation
indication: prevent vessel closure after PCI

Question 10

anticoag of choice in pregnancy

Answer 10

heparin

Question 11

heparin MOA

Answer 11

inhibits factor Xa and IIa by accelerating inhibition by antithrombin
- inhibits activity of preformed coag factors

Question 12

side effects of heparin

Answer 12

bleeding
osteoporosis
skin lesions
hypoaldosteronism

Question 13

heparin-induced thrombocytopenia

Answer 13

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

Question 14

low molecular weight heparins

Answer 14

dalteparin
enoxaparin
tinziparin
fondaparinux

Question 15

advantages of LMWH over UH

Answer 15

fixed dose (weight-based)
SC admin- can be done at home
no routine lab monitoring
more predictable response
less HIT

Question 16

disadvantages of LMWH

Answer 16

longer half- life might be a problem if pt bleeds b/c no antidote
renal excretion - bad to use in renal insufficiency

Question 17

how to reverse heparin effect

Answer 17

short-half life –> discontinue b/f invasive procedures

severe bleeding –> protamine sulfate (this doesn’t work well for LMWH)

Question 18

warfarin MOA

Answer 18

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

Question 19

warfarin pharmacokinetics

Answer 19

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

Question 20

warfarin SEs

Answer 20

bleeding
skin necrosis
teratogenic in early fetal development

Question 21

how to reverse warfarin

Answer 21

vit K - effect w/in hrs
fresh frozen plasma (contains coag factors) - immediate effect
prothrombin concentrates - immediate effect

Question 22

parenteral direct thrombin inhibitors

Answer 22

argatroban, bivalirudin

for rx and prevention of thrombosis in HIT, anticoagulation during PCI in pts w/ HIT

Question 23

dabigatran

Answer 23

inhibits thrombin
prodrug - does not involve CYP450
renal excretion

Question 24

rivaroxaban

Answer 24

inhibits X directly
active drug metabolized by CYP3A4
renal excretion

Question 25

fibrinolytic agents MOAs

Answer 25

1. plasminogen –> plasmin (degrades fibrin) - tPA, urokinase plasminogen activator
2. binds plasminogen and the complex degrades fibrin - streptokinase