Pharmacology of Anticoagulation Therapy

Question 1

What are the three classes of antithrombotic drugs?

Answer 1

1. heparin and oral anticoagulants (interfere with coag. cascade).
2. fibrinolytic agents (promote lysis of clots by increasing formation of plasmin)
3. Anti-platelet drugs (inhibit formation of platelet products or block platelet adhesion)

Question 2

What are the three forms of heparin?

Answer 2

1. unfractionated- sulfated polysaccharide of varying lengths
2. Low-Molecular Weight- one third size of heparin
3. Fondaparinux (Atrixtra)- a pentasaccharide; the minimal sequence in heparin for binding antithrombin

Question 3

Heparin accelerates the decay of which cofactors by antithrombin?

Answer 3

IXa, Xa, XIIa

Question 4

How do you reverse the effects of heparin; how does it work?

Answer 4

give protamine sulfate. It is positiviely charged and heparin is negatively charged.

Question 5

Which forms of heparin can inactivate factor II?

Answer 5

only unfractionated (does X also). LMWheparin and fondaparinux can only bind Factor X.

Question 6

Why are LMWH and Fondaparinux more predictable than unfractionated heparin?

Answer 6

1. they are given subQ vs IV (unfractionated can also be given SubQ for delayed effect)
2. longer half life
3. outpatient treatment vs. hospital admission required
4. better bioavailability

Question 7

What are the typical cases you would want to use heparin?

Answer 7

treatment and prevention of: venous thrombosis, Pulmonary embolism, unstable angina, acute MI (use fibrinolytics also). Also, ab surgery, hip and knee replacement.

Question 8

What is HIT (heparin-induced thrombocytopenia syndrome)

Answer 8

antibodies made to platelet factor 4 and heparin complexes. result in prothrombotic state

Question 9

How does Warfarin (coumadin) work?

Answer 9

inhibits enzymes that use vitamin K as a cofactor. As a result some coag proteins will lack gamma carboxylation which is required for binding Ca2+. Binding to ca2+ is required for activation. Thus they are non-functional

Question 10

Would you give hep or warfarin to a patient with clotting problems first?

Answer 10

hep. Heparin is immediate whereas warfarin has more lon term effects and requires that the existing cofactors in circulation be removed in order to take effect (2-3 days).

Question 11

Adverse effects of warfarin?

Answer 11

1. drug-drug interactions
2. delayed onset of action
3. requires constant monitoring (drug-drug and drug-food interactions)
4. crosses placenta (can’t be used in pregos)

Question 12

How to reverse effects of warfarin?

Answer 12

administer vitamin K (takes 2-3 days to resynthesize clotting factors however so also give plasma with clotting factors).

Question 13

Advantages of new oral anticoagulants (Direct thrombin and and Factor Xa inhibitors)?

Answer 13

• Rapid onset of action
• absence of food and drug interactions
• do not require monitoring

Question 14

Disadvantages of new oral anticoagulants (Direct thrombin and and Factor Xa inhibitors)?

Answer 14

• kidney disease
• Short half life (requires 2 pills a day)
• Cost is much greater
• no antidote to reverse side effects

Question 15

Dagibatran is a______

Answer 15

direct inhibitor of thrombin

Question 16

How does streptokinase work?

Answer 16

a fibrinolytic agent. complexes with plasminogen and converts to plasmin

Question 17

When would you use antiplatelet drugs?

Answer 17

acute coronary syndrome (angina, MI)

Question 18

What are the three types of antiplatelet drugs and what do they do?

Answer 18

1. aspirin- inhibit formation of platelet products (inhibits TXA2 production)
2. ADP receptor antagonists- prevent activation/aggregation
3. glycoprotein IIb/IIIa inhibitors- block adhesion proteins

Question 19

Say whether each is reversible or irreversible:

• Aspirin
• Thienopyridines (clopidogrel)
• Ticagrelor

Answer 19

irreversible
irreversible
reversible

Question 20

What is GPIIb/IIIa and how do GPIIb/IIIa inhibitors work?

Answer 20

it is an adhesion protein on the surface of platelets that is a receptor for fibrinogen. The inhibitor simply blocks the receptor and prevents aggregation.

Question 21

Aspirin is almost always used following ________

Answer 21

an MI or thromb stroke

Question 22

Abciximab is used following______

Answer 22

coronary angioplasty and for unstable angina