Anti-clotting drugs

Question 1

What are the parenteral directing acting factor II inhibitors?

Answer 1

• Argatroban (IV)
• Bivalirudin (IV)
• Desirduin (SubQ)

Question 2

What are the parenteral direct acting factor Xa inhibitors?

Answer 2

None

Question 3

What are the parenteral indirect acting (heparin derived inhibitors)? Those that inhibit both factor II and Xa

Answer 3

• UFH (IV, SubQ)
• Bemiparin (LMWH SubQ)
• Enoxaparin (LMWH SubQ)
• Tinzaparin (LMWH SubQ)

Question 4

What is an example of a parenteral indirect specific factor Xa inhibitor?

Answer 4

Fondaparinux (SubQ)

Question 5

UFH, LMWH, and fondaparinux all bind to what protein? What does this protein do?

Answer 5

Anti-thrombin, which inactivates thrombin (and factor Xa)

Question 6

Heparins are administered ___ due to __ size and lack of oral absorption

Answer 6

parenterally (IV/SC, not MI); large

Question 7

What is a toxicity of UFH?

Answer 7

HIT; leading to activation of platelets and platelet removal by splenic macrophages

Question 8

What is an alternative to heparins in patients with HIT?

Answer 8

Argatroban

Question 9

What are the oral direct acting thrombin inhibitors?

Answer 9

Dabigatran

Question 10

What are the oral direct acting factor Xa inhibitors?

Answer 10

Apixaban, rivaroxaban, edoxaban

Question 11

What are the indirect acting vitamin K inhibors?

Answer 11

Warfarmin/coumadin

Question 12

What enzyme in particular is affected via warfarin? What factors are reduced?

Answer 12

Warfarin Inhibits Vitamin K reductase; 2, 7, 9, 10 C and S are affected

Question 13

What are the half lives for factor IIa, VIIa, IXa, and Xa respectively?

Answer 13

60h, 6h, 24h, 40h. These factors must degrade before effects begin

Question 14

How long may it take for warfarin to reach therapeutic levels?

Answer 14

1 week. Thus heparin bridging is used

Question 15

What are some indirect thrombin inhibitor drug interactions? (warfarin)

Answer 15

Warfarin travels in blood stream via albumin. NSAIDs and some other drugs also bind to albumin and can therefore kick off warfarin. This would lead to free warfarin thus increasing risk of bleeding and amplified effects of warfarin

Question 16

What polymorphisms may ensure with warfarin?

Answer 16

VKORC1 and CYP2C9 polymorphisms affect dosing. Those with these polymorphisms should be given lower doses.

• VKORC1 is part of vitamin K reductase
• CYP2C9 is part of the conversion from S-warfarin to 7-OH warfarin. Increases conversion 4x?

Question 17

What are some foods that can affect warfarin dosing?

Answer 17

Parsley, swiss chard, Kale, Dandelion greens (All these contain vitamin K in high levels)

Question 18

What are some birth defects that can arise from warfarin?

Answer 18

Fetal warfairn syndrome (bone defects, intellectual disability etc.). Category X rating

Question 19

What are some drugs that can increase risk of bleeding?

Answer 19

CYPs 1A1, 1A2, 3A4: Amiodarone, cimetidine
CYP2C9: Amiodarone, cimetidine, SMZ/TMP, fluconazole, metronidazole

These cytochromes promote degradation of warfarin, but are degraded by the drugs listed above. So if you adminster one of these other drugs, you’ll increase risk of bleeding since more warfarin will be in circulation.

Question 20

Cox 1/2 inhibs (Aspirin, ibuprofen) should be used for what conditions?

Answer 20

Unstable angina, MI, stroke

Question 21

P2Y12 inhibitors should be used for which conditions (Clopidogrel, prasugrel, ticagrelor, ticlopidine)

Answer 21

MI and stroke

Question 22

GPIIB/IIIA inhibs hsould be used for which conditions? (Abciximab, eptifibitide, tirofiban)

Answer 22

angioplasty/stent placement

Question 23

Cox-1/2 inhibitors work by what function?

Answer 23

Inhibit TXA2 synthesis in platelets. TXA2 usually activates other platelets and promotes aggregation

Question 24

P2Y12 inhibitors work by what function? (Clopidogrel, pasugrel, ticagrelor, ticlopidine)

Answer 24

Inhibits ADP receptor, which is used for platelet activation. Clopidogrel and pasugrel are irreversible non-competitive antagonists ADP

Question 25

What are some pharmacokinetic issues that are relevant with clopidogrel?

Answer 25

Clopidogrel is ingested as an inactive form but is activated by the CYP2C19. And then esterified into its anticoagulant form. Those with reduced CYP2C19 activity will not received benefit of clopidogrel while those with increased CYP2C19 activity will have increased risk of bleeding

Question 26

Abciximab inhibits clotting by what mechanism?

Answer 26

It is an antibody that binds to GPIIb/IIIa receptors that prevent aggregation

Question 27

What are some examples of plasminogen activators?

Answer 27

streptokinase, urokinase, alteplase (t-PA)

Question 28

Thrombin __ fibrin

Answer 28

produces

Question 29

Plasminogen __ fibrin

Answer 29

degrades

Question 30

Alteplase and streptokinase work by what mechanism?

Answer 30

They convert inactive plasminogen into active plasmin

Question 31

What are some drugs that can be given immediatley to treat PE

Answer 31

Streptokinase or alteplase

Question 32

What drug can be given immediately to treat stroke?

Answer 32

Alteplase. Only effective in select patients. Significant increase in excellent outcome and reduced disability at 3 months

Question 33

Fibrinolytics should not be given to whom?

Answer 33

Those for whom clotting is “good”. I.e. those with prior intracranial hemorrhage, ischemic stroke within 3 months, suspected aortic dissection, active bleeding, etc.