Anticoagulants and Antiplatelets/Thrombolytics

Question 1

Heparin MOA.

Answer 1

FAST: Complexes with antithrobmin and irreversibly inactivates thrombin and factor Xa

Question 2

Warfarin MOA.

Answer 2

SLOW: inhibits vitamin K poxide reductase and interferes with addition of gamma-carboxy glutamic acid to 2, 7, 9, 10 and Protein C and S (so they are not produced correctly)

Question 3

Danaproid (LMWH) MOA.

Answer 3

heparinoid that has selective anti-factor X activity

Question 4

Hirudin MOA.

Answer 4

direct thrombin inhibitor

Question 5

Lepirudin MOA.

Answer 5

(IV) binds to thrombin’s active site/ thrombin substrate and inhibits enzymatic action

Question 6

Argatroban MOA.

Answer 6

direct thrombin inhibitor that binds directly to thrombin-active site with short half life

Question 7

Dabigatran MOA.

Answer 7

(Oral) binds to thrombin’s active site and inhibits enzymation action

Question 8

Aspirin MOA.

Answer 8

Non-selective, irreversible COX innhibitor–
COX1: reduces platelet producaiton of TXA2, so no stimulation of platelet aggregation
COX2: prevents synthesis of PGI2, so no increase in cAMP to decrease platelet activity)

Question 9

Dypyridamole MOA.

Answer 9

inhibits adenosine uptake and inhibits phosphodiesterase enzymes that degrade cAMP and cGMP (so no platelet activation)

Question 10

Prostacyclin MOA.

Answer 10

.

Question 11

Clopidogrel MOA.

Answer 11

prodrug CYP2C19: active metabolite irreversibly inhibits platelet ADP receptor (so no expression of GPIIb/IIIa for aggregation)

Question 12

Prasugrel MOA.

Answer 12

prodrug CYP3A4/2B6: better than clopidogrel (inhibits ADP receptor) with higher bleeding risk

Question 13

Eptifibidate MOA.

Answer 13

reversible GP IIb/IIIa inhibitors that are smaller than abciximab (prevent binding of fibrinogen and vWF)

Question 14

Abciximab MOA.

Answer 14

Inhibits platelet aggregation by interfering with GPIIb/IIIa binding to fibrinogen and other ligands

Question 15

Streptokinase MOA.

Answer 15

bacterial protein that forms complex with plasminogen that converts it rapidly to plasmin

Question 16

Urokinase MOA.

Answer 16

human enzyme synthesized by the kidney that directly converts plasminogen to active plasmin.

Question 17

TPA MOA.

Answer 17

Converts plasminogen to plasmin which degrades fibrin in thrombi

Question 18

Reteplase MOA.

Answer 18

longer half-life recombinant TPA and is less fibrin-specific

Question 19

Heparin Indications.

Answer 19

Used when anticoagulation is needed immediately (DVT, pulmonary embolism, and acute MI). Cannot cross placenta, so good for pregnant women.

Question 20

Heparin toxicities.

Answer 20

Bleeding (reversed with protamine)
HIT
Osteoporosis

Question 21

How do you monitor Heparin?

Answer 21

PTT

Question 22

Direct Thrombin Inhibitor indications.

Answer 22

Alternatives to heparin therapy in patients with HIT.

Question 23

Direct Thrombin Inhibitor toxicities.

Answer 23

bleeding (no reversal agents);

prolonged lepirudin use can induce antibodies to form complex with it and prolong its action→ possibly inducing anaphylactic reaction

Question 24

How do you monitor Direct Thrombin Inhibitors?

Answer 24

PTT

Question 25

Factor Xa Inhibitor indications.

Answer 25

prevention of venous thrombosis after surgery and prevention of stroke for patients with atrial fibrillation

Question 26

Factor Xa Inhibitor toxicities.

Answer 26

bleeding (no reversal agents)

Question 27

Warfarin indications.

Answer 27

Used when anticoagulation is needed immediately (DVT, pulmonary embolism, and acute MI). Can cross placenta, so teratogen!!

Question 28

Warfarin toxicities.

Answer 28

bleeding (reversed with Vitamin K or fresh frozen plasma)
early hypercoagulability (due to deficient protein C) leading to dermal vascular necrosis
bone defects/hemorrhage in developing fetus

Question 29

How do you monitor Warfarin?

Answer 29

PT

Question 30

Warfarin interaction with Cytochrome P-450 inducers (rifampin, barbituates,etc)?

Answer 30

rapid metabolism, reduce anticoagulant effect (thrombus)

Question 31

Warfarin interaction with Cytochrome P-450 inhibitors (ex. SSRIs)?

Answer 31

slowed clearance, could lead to bleeding

Question 32

What should people who are going to be treated with warfarin get checked for (genetic variability)?

Answer 32

CYP450 2C9

Question 33

Which of the following does NOT prevent BOTH venous and arterial thrombi:
Anticoagulants
Antiplatelets
Thrombolytics

Answer 33

Antiplatelets are way, way better at preventing arterial thrombi than venous thrombi

Question 34

Why is the COX2 activity of aspirin bad for patients?

Answer 34

COX2 generates prostaglandins that inhibit acid secretion, so if you inhibit COX2, you get more acid in stomach and increased chance of peptic ulcers

Question 35

Who should take prophylactic aspirin (325 mg/day)?

Answer 35

MEN 45-79 w/risk
WOMEN 55-79 w/risk
(not for men under 45 or women under 55 OR for the elderly (because increased risk of GI bleed))

Question 36

Why should people taking warfarin NOT take aspirin?

Answer 36

increased risk of hemorrhagic stroke

Question 37

Clopidogrel CANNOT be taken with what drug? Why?

Answer 37

Ometrozol (interferes with formation of clopidogrel from prodrug (CYP2C19 inhibitor) and reduces its efficiency)

Question 38

What ADP antagonist CAN you take with ometrozol?

Answer 38

Prasugrel

Question 39

Prasugrel use is contraindicated in what situations? Why?

Answer 39

prior history of stroke/TIA because of its increased bleeding risk

Question 40

What is the current standard therapy for patients with coronary angioplastic stent/unstable angina?

Answer 40

clopidogrel (more effective/higher risk) + aspirin

not longer than 1 year