SM 124 Pharmacology of Anticoagulants

Question 1

What does Heparin bind, and how does this compare to LMWH and Fondapurinex?

Answer 1

Heparin binds Antithrombin and increases it’s affinity for Factor Xa and Thrombin

LMWH and Fondapurinex bind Antithrombin as well, but only increase affinity for Factor Xa and cannot increase affinity for Thrombin

Question 2

Describe the Mechanism of Action of Heparin?

Answer 2

Heparin uses a critical pentasaccharide region to bind Antithrombin

Binding of Heparin to Antithrombin increases Antithrombin’s affinity for Thrombin

Heparin has a long tail that allows it to bind Thrombin

Question 3

What advantages do Low Molecular Weight Heparins have over Heparin?

Answer 3

Low Molecular Weight Heparins have a higher bioavailability and a longer half life

Question 4

What advantages does Fondapurinex have over Heparin?

Answer 4

Fondapurinex has a much longer half life but is not safe in patients with Renal failure

Question 5

What advantages does Heparin have over LWMH and Fondapurinex?

Answer 5

Heparin is approved for surgical prophylaxis, while LMWH and Fondapurinex are not

Heparin can inhibit Factor Xa and Thrombin

LMWH and Fondapurinex only inhibit Factor Xa

Question 6

What is the reversal agent for Heparin?

Answer 6

Protamine Sulfate

Question 7

What is Protamine Sulfate?

Answer 7

Protamine Sulfate is the reversal agent for Heparin

Most effective on Heparin, somewhat effective on LMWH, and no effect on Fondapurinex

Question 8

How does Heparin-induced Thrombocytopenia arise?

Answer 8

Heparin-induced Thrombocytopenia is an adverse reaction to Heparin and LMWH (less often)

Heparin and LMWH are negatively charged while Platelet Factor 4 is positively charged

Heparin/LMWH binds Platelet Factor 4 and causes Platelets to agglutinate

Widespread agglutination of Platelets leads to Thrombocytopenia

Question 9

What risk does Warfarin pose to pregnant women?

Answer 9

Warfarin is a teratogen

Question 10

How does Warfarin cause Disseminated Intravascular Coagulation?

Answer 10

DIC arises because Warfarin can block both pro and anti coagulative factors, including Protein C

Warfarin can decrease Gamma carboxylation of Protein C before other coagulation factors, causing a risk for forming clots

Risk is higher in people who have lower levels of Protein C

Question 11

How does Warfarin work?

Answer 11

Block Vitamin K reductase which results in inhibition of gamma carboxylation of both pro and anti coagulation factors

Question 12

List the direct Factor Xa inhibitors?

Answer 12

Direct Factor Xa inhibitors include: RABE (-xaban)

Rivarobaxan
Apibaxaban
Betriaxaban
Edoxaban

Use with Asprin

Question 13

What are Direct Factor Xa inhibitors approved for?

Answer 13

Direct Factor Xa inhibitors are approved for Thromoboprophylaxis and Treatment of Acute Venus Thrombus

Question 14

What is the reversal agent for Dagibatran?

Answer 14

Idanucizab is the reversal agent for Dagibatran

Question 15

What is the reversal agent for Direct Factor Xa inhibitors?

Answer 15

Direct Factor Xa inhibitors are reversed by Andaxanet

Question 16

List the Direct Thrombin Inhibitors?

Answer 16

The direct Thrombin inhibitors include: (DAB)

Dagibatran
Argatorban = binds Thrombin catalytic site only
Bivalrudin = binds Thrombin catalytic and exosite

Question 17

How is Bivalrudin differentiated from Argatorban?

Answer 17

Bivalrudin binds both the Thrombin catalytic and exosite while Argatorban binds the catalytic site only

Question 18

What is Bivalirudin indicated for?

Answer 18

Bivalirudin is indicated for Coronary Artery Angioplasty

Question 19

What is Aragorbin indicated for?

Answer 19

Argatorbin is indicated for Heparin Induced Thrombocytopenia