Antithrombotics

Question 1

Antiplatelet drug classes (4)

Answer 1

COX-1 inhiitors
PDE inhibitors
ADP receptor antagonists
GP IIb/IIIa antagonists

Question 2

ADP-recpetor antagonist

Answer 2

clopidogrel

Question 3

GP IIb/IIIa antagonist

Answer 3

abciximab

Question 4

MOA of clopidogrel

Answer 4

Irriversibly antagonizes ADP receptor reducing inactivation of AC, increasing cAMP and increasing PKA, leading to reduced platelet aggregation

Question 5

MOA of abciximab

Answer 5

binds to GP to prevent them from crosslinking through fibrinogen bridge

Question 6

Pharmaco genetics of clopidogrel

Answer 6

prodrug metabolized by CYP2C19. Black boxed warning

Question 7

Pharmacokinetics of clopidogrel

Answer 7

orally effective, maximal efficacy 8-11 days

Question 8

Therapeutic use of colpidogrel

Answer 8

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

Question 9

Adverse effects of colpidogrel

Answer 9

bleeding

thrombotic thrombocytopenic purpura

Question 10

Drug interactions with colpidogrel

Answer 10

avoid NSAIDS

CYP2C19 inhibitors, omeprazole

Question 11

Pharmacokinetics of abciximab

Answer 11

half life 10 min duration of action 48 hours due to irreversible binding

Question 12

Therapeutic use of abciximab

Answer 12

most effective, most expensive

short term in combo with asprin to prevent ischemic events in hospital setting

Question 13

Adverse effects of abciximab

Answer 13

bleeding, anaphylaxis

Question 14

Heparin MOA

Answer 14

indirect inhibitors of thrombin and/or Xa through antithrombin

Question 15

Enoxaparin MOA

Answer 15

~17 saccharide heparin

Question 16

Fondaparinux MOA

Answer 16

pentasaccharide heparin

Question 17

Pharmacokinetics of heparin

Answer 17

immediate onset
parenteral
“sticky,” must monitor aPTT
LMWH/fondaparinux- don’t need to monitor aPTT

Question 18

Selectivity of heparins

Answer 18

Heparin inactivates thrombin and Xa
LMWH inactivates Xa well, thrombin poorly
Fondaparinux inactivates Xa only

Question 19

Therapeutic use of heparin

Answer 19

initial treatment of DVT/PE
transition to warfarin
safe in pregnancy

Question 20

Adverse effects of heparin

Answer 20

bleeding, protamine sulfate antidote

HIT/HITT - CBC needed

Question 21

Alternative anticoagulants in HIT

Answer 21

bivalirudin, fondaparinux

Question 22

Vitamin K antagonist

Answer 22

warfarin

Question 23

MOA of warfarin

Answer 23

inhibits synthesis of K-dependent clotting factors by inhibiting VKOR1C in the liver

Question 24

Pharmacokinetics of warfarin

Answer 24

oral
delayed onset, dependent on clotting factor turnover
metabolized by CYP2C9

Question 25

Dosing of warfarin

Answer 25

must be monitored by PT/INR

Question 26

Therapeutic use of warfarin

Answer 26

prevent progression of recurrence of DVT or PE Prevention of thromboembolism in patient with prosthetic heart valves not useful in an emergency

Question 27

Adverse effects of warfarin

Answer 27

boxed warning for bleeding antidote is vitamin K, takes hours, for immediate need- prothrombin complex concentrate (PPC) or plasma. Teratogen

Question 28

Drug interactions with warfarin

Answer 28

CYP inhibitors displacement of plasma albumin broad spectrum antibiotics anything that promotes bleeding Reduce warfarin effect CYP inducers excessive vitamin K

Question 29

Direct inhibitors of thrombin

Answer 29

bivalirudin- parenteral | dabigatran etexilate- oral

Question 30

bivalirudin MOA

Answer 30

binds to and inhibits thrombin

Question 31

Pharmacokinetics of bivalirudin

Answer 31

given IV and monitored by aPTT, short half life, excreted by the kidney

Question 32

Therapeutic use of bivalirudin

Answer 32

used for HITT and during PCI

Question 33

Adverse effect of bivalirudin

Answer 33

bleeding

Question 34

Pharmacokinetics of dabigatran etexilate

Answer 34

orally active onset 2-3 hrs dosed 2x per day without monitoring

Question 35

Therapeutic use of dabigatran

Answer 35

"warfarin replacement" | no monitoring required

Question 36

Adverse effect of dabigatran

Answer 36

bleeding with no antidote

Question 37

Thrombolytic agents

Answer 37

t-PA

Question 38

MOA of t-PA

Answer 38

activates plasminogen and breaks up fibrinogen clot.

Question 39

Therapeutic use of t-PA

Answer 39

within the first three hours after MI