Antithrombotics

Question 1

what are the 3 categories of antithrombotic drugs?

Answer 1

• antiplatelets
• anticoagulants
• fibrinolytics

Question 2

what do antiplatelets do?

Answer 2

prevent thrombus

Question 3

what do anticoagulants do?

Answer 3

Prevent initial thrombus and prevent extension of current thrombus

Question 4

what do fibrinolytics do?

Answer 4

Lyse active thrombus

Question 5

all antithrombotics have a risk of ____

Answer 5

bleeding

Question 6

antiplatelet drug names to be familiar with

Answer 6

• Aspirin

- clopidogrel (Plavix)

Question 7

Aspirin MOA

Answer 7

• inhibits COX-1 and COX-2
• reduces production of thromboxane A2
• inhibits platelet aggregation

Question 8

At low doses (81 mg), Aspirin primarily inhibits COX-1 for _____

Answer 8

cardiovascular protection

Question 9

clopidogrel (Plavix) is an ADP receptor inhibitor, also known as ____ or ____

Answer 9

thienopyridines; P2Y12 inhibitors

Question 10

clopidogrel (Plavix) MOA

Answer 10

• prevents ADP from binding to platelet by irreversibly blocking PY12 receptor
• prevents platelet aggregation for lifespan of platelet (7-10 days)

Question 11

clopidogrel (Plavix) AEs

Answer 11

• generally well tolerated

- biggest concern is bleeding (monitor symptoms and lab values for Hgb/Hct)

Question 12

T/F: clopidogrel (Plavix) is a prodrug

Answer 12

• true

- CYP2C19 to active metabolite

Question 13

boxed warnings for clopidogrel (Plavix)

Answer 13

↓ efficacy in some genetic variants that make them CYP2C19 poor metabolizers (present in 50% of Asians, 30% African-Americans, 25% Caucasians)

Question 14

heparin MOA

Answer 14

prevents conversion of fibrinogen to fibrin

Question 15

heparin tx doses require monitoring of ____ levels

Answer 15

• aPTT

- these levels indicate how long it takes your blood to form a clot

Question 16

what is the reversal agent for heparin?

Answer 16

• protamine sulfate

- binds heparin so it is inactivated

Question 17

Heparin induced thrombocytopenia (HIT)

Answer 17

• Body creates antibodies which bind to heparin when it is in a complex platelet factor IX
• this activates platelets
• clotting and ↓ platelet levels
• Treat with direct thrombin inhibitors or Factor Xa inhibitors

Question 18

Low-molecular weight heparin (LMWH) MOA

Answer 18

prevents conversion of fibrinogen to fibrin

Question 19

why is LMWH preferred over regular heparin?

Answer 19

more simple dosing, no monitoring required, ↓ risk HIT

Question 20

LMWH drug to be familiar with

“we love not being hit”

Answer 20

enoxaparin (Lovenox)

Question 21

warfarin (Coumadin) MOA

Answer 21

• vitamin K antagonist (VKA)

- depletes vitamin K stores and inhibits synthesis of factors VII, IX, X and II, and protein C and S

Question 22

warfarin reversal agent

Answer 22

vitamin K

Question 23

warfarin usually takes ____ days for full effect

Answer 23

• 3-5

- takes even longer to stabilize dose

Question 24

warfarin is an NTI drug and requires frequent monitoring of ____

Answer 24

INR (international normalized ratio)

Question 25

low INR = risk of ____

Answer 25

clot

Question 26

high INR = risk of ____

Answer 26

bleeding

Question 27

PO Direct Thrombin Inhibitor MOA

Answer 27

- binds directly and reversibly to thrombin with high selectivity - inhibits conversion of fibrinogen to fibrin

Question 28

PO Direct Thrombin Inhibitor risks

Answer 28

- Less intracranial bleeding than warfarin but more GI bleeding - Beers List: ↑ risk of GI bleeding in >75 years

Question 29

other AE for PO Direct Thrombin Inhibitor

Answer 29

- dyspepsia (aka indigestion) | - 10%, take with food, improves with time

Question 30

Factor XA Inhibitors MOA

Answer 30

- selectively and reversibly binds FXa | - stops further coagulation cascade

Question 31

Factor XA Inhibitor drug names to know (end in "xaban")

Answer 31

- apixaban (Eliquis) | - rivaroxaban (Xarelto)

Question 32

rivaroxaban is on the Beers List because it has more risk of ____

Answer 32

GI bleed

Question 33

which factor XA inhibitor has lowest bleed risk?

Answer 33

apixaban (Eliquis)

Question 34

All factor XA inhibitors have less ____ than warfarin

Answer 34

- risk of intracranial bleed | - drug interactions

Question 35

andexanet alfa (Andexxa) is a reversal agent for which drugs?

Answer 35

- LMWH | - Factor XA Inhibitors

Question 36

T/F: rivaroxaban must be taken with food

Answer 36

true

Question 37

fibrinolytics MOA

Answer 37

- mimic endogenous tissue plasminogen activator (TPA) which converts plasminogen to plasmin - plasmin breaks fibrin links in the thrombus

Question 38

when are fibrinolytics used?

Answer 38

immediately after stroke, MI, PE