3. Parenteral Anticoagulants

Question 1

What is the major plasma protease inhibitor of thrombin?

Answer 1

antithrombin

Question 2

Antithrombin inhibits what clotting factors?

Answer 2

Xa > IXa > XIIa

Question 3

The rate of formation of inactivating complexes is increased several thousand fold in the presence of what?

Answer 3

heparin

Question 4

Heparin is present as an endogenous component of vessel walls. (T/F)

Answer 4

True

Question 5

Heparin is present in the fluid phase of plasma. (T/F)

Answer 5

False

Question 6

Unfractionated heparin MW ranges from ______ - ______ .

Answer 6

3,000 - 30,000

Question 7

What causes the anticoagulant effect produced by heparin?

Answer 7

interaction with antithrombin

Question 8

What pharmacological compound neutralizes thrombin and other activated clotting factors?

Answer 8

heparin-bound antithrombin

Question 9

Antithrombin is a ______ substrate.

Answer 9

suicide

Question 10

Describe antithrombin’s “suicidal” mechanism

Answer 10

protease attacks a specific Arg-Ser peptide bond in antithrombin and becomes trapped as a 1:1 complex

Question 11

______ serves as a catalytic template for inhibitor and protease to bind.

Answer 11

Heparin

Question 12

Only heparin molecules that contain less than 18 monosaccharide units can catalyze inhibition of thrombin by antithrombin.

Answer 12

False: Heparin molecules of this size do not catalyze inhibition of thrombin by antithrombin

Question 13

Heparin molecules of 18 monosaccharide units or more are required to bind thrombin and antithrombin _______.

Answer 13

simultaneously

Question 14

Shorter heparin polysaccharides catalyze primarily inhibition of factor __ by antithrombin.

Answer 14

Xa

Question 15

Heparin is ______ absorbed from the GI tract.

Answer 15

poorly

Question 16

Heparin must be administered ________.

Answer 16

parenterally

Question 17

IV infusion of heparin has a ________ effect.

Answer 17

immediate

Question 18

Subcutaneous injection of heparin has a ________ effect.

Answer 18

delayed

Question 19

SQ administration of heparin takes how long to take effect?

Answer 19

1-2 hours

Question 20

What method of administration of heparin causes more bleeding complications?

Answer 20

intermittent IV injections

Question 21

In addition to ACS, what other conditions are treated with heparin?

Answer 21

• venous thrombosis

- pulmonary embolism

Question 22

Why is heparin used in ACS, DVT, and PE instead of warfarin, for example?

Answer 22

rapid onset of action

Question 23

Unfractionated heparin has ________ PK and _______ therapeutic range.

Answer 23

• unpredictable

- narrow

Question 24

What labs should be monitored when using unfractionated heparin?

Answer 24

activated partial thromboplastin time (aPTT)

Question 25

What is the usual dose for unfractionated heparin in a UA/NSTEMI?

Answer 25

- IV bolus of 60u/kg (4000 u max) - 12 u/kg/hr (1000 u/hr max) - adjust to maintain aPTT at 1.5 - 2 times the control

Question 26

What should aPTT value be after administration of heparin?

Answer 26

1.5 - 2 times the control value

Question 27

When might very high doses of unfractionated heparin be given?

Answer 27

- PCI | - cardiac bypass surgery

Question 28

In patients who require very high doses of unfractionated heparin, what lab values should be monitored?

Answer 28

- aPTT | - ACT

Question 29

What are the 3 main limitations of heparin therapy?

Answer 29

- PK: binds to plasma proteins - does not inactivate thrombin already bound to fibrin - binds to platelets and inhibits function: could lead to uncontrolled bleeding

Question 30

Why is the plasma protein binding of heparin an issue?

Answer 30

- Poor BA at low doses - variability in dose response - dose-dependent clearance

Question 31

Why is it a problem that heparin does not bind thrombin that is already bound to fibrin?

Answer 31

It limits the effectiveness in preventing arterial thrombosis.

Question 32

Why is it a problem that heparin binds to platelets and inhibits function?

Answer 32

heparin-induced bleeding

Question 33

The half-life of heparin in plasma depends on ______.

Answer 33

dose

Question 34

What is the half-life of 100 u/kg IV heparin?

Answer 34

1 hr

Question 35

What is the half-life of 400 u/kg IV heparin?

Answer 35

2.5 hours

Question 36

What is the half-life of 800 u/kg IV heparin?

Answer 36

5 hours

Question 37

What are contraindications of heparin?

Answer 37

- surgery within 10 days - serious GI bleed - HTN - active bleeding - previous stroke

Question 38

What are the ADRs of heparin?

Answer 38

- hemorrhage - thrombocytopenia - osteoporosis

Question 39

What is the antidote to heparin?

Answer 39

protamine

Question 40

How does protamine stop heparin action?

Answer 40

protamine binds mostly long heparin molecules, thereby preventing complex with antithrombin III

Question 41

How is protamine administered?

Answer 41

IV infusion

Question 42

What is the onset of action of protamine?

Answer 42

5 minutes

Question 43

What is the low molecular weight heparin agent?

Answer 43

enoxaparin (Lovenox)

Question 44

What is the average weight of LMWH?

Answer 44

4,500 daltons

Question 45

How is the MOA of LMWH different than unfractionated heparin?

Answer 45

- ↑ inhibition of factor Xa - ↓ inhibition of thrombin - shorter molecules can't bind antithrombin III and thrombin together - anti-factor Xa/antithrombin activity is 4:1 vs 1:1 for unfractionated heparin

Question 46

________ has easier administration. (UH/LMWH)

Answer 46

LMWH

Question 47

________ has a shorter half life. (UH/LMWH)

Answer 47

UH

Question 48

________ has a more predictable response. (UH/LMWH)

Answer 48

LMWH

Question 49

_______ is administered by once or twice daily SQ injections. (UH/LMWH)

Answer 49

LMWH

Question 50

_______ has a higher incidence of thrombocytopenia. (UH/LMWH)

Answer 50

UH

Question 51

________ has a lower incidence of major bleeding complications. (UH/LMWH)

Answer 51

LMWH

Question 52

Osteoporosis occurs more often with _______ long-term administration. (UH/LMWH)

Answer 52

UH

Question 53

What is the factor Xa selective inhibitor agent?

Answer 53

fondaparinux (Arixtra)

Question 54

What is the MOA of fondaparinux?

Answer 54

- binds antithrombin to selectively inhibit factor Xa | - does not inhibit thrombin

Question 55

What are the approved indications of fondaparinux?

Answer 55

- DVT | - PE

Question 56

In what condition is fondaparinux used off label in the US?

Answer 56

ACS

Question 57

What are the advantages of using fondaparinux over heparin?

Answer 57

- easier administration - more predictable response - long half-life - increased efficacy - less variation between preparations

Question 58

What is the disadvantage of using fondaparinux over heparin?

Answer 58

no antidote

Question 59

Which parenteral anticoagulant is synthetic?

Answer 59

fondaparinux

Question 60

Which parenteral anticoagulant has the highest bioavailability?

Answer 60

fondaparinux

Question 61

Which parenteral anticoagulant has the longest half-life?

Answer 61

fondaparinux

Question 62

Which parenteral anticoagulant is NOT eliminated renally?

Answer 62

unfractionated heparin

Question 63

What are the hirudin analog agents?

Answer 63

- argatroban (Acova) - lepirudin (Refludan) - bivalirudin (Angiomax) - desirudin ( Ipravask)

Question 64

Where is hirudin naturally found?

Answer 64

produced by leeches

Question 65

What is the route of administration of hirudin analogs?

Answer 65

injection

Question 66

Which hirudin analogs are approved for heparin-induced thrombocytopenia?

Answer 66

- argatroban | - lepirudin

Question 67

What is the MOA of hirudin analogs?

Answer 67

- direct inhibitor of thrombin (independent of antithrombin III) - effectively inhibits thrombin bound to fibrin