EXAM #2: HEMATOLOGICAL AGENTS II Flashcards Preview

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Flashcards in EXAM #2: HEMATOLOGICAL AGENTS II Deck (64):
1

What is Type I HIT?

Heparin Induced Thrombocytopenia
- Decreased platelet numbers in first 2-5 days of treatment

****Not of much clinical consequence*****

2

What is Type II HIT?

Uncommon but SERIOUS Heparin Induced Thrombocytopenia

- Heparin binds platelet factor 4 (PF4)
- Antibodies formed against PF4/Heparin
- Antibodies activates platelets can cause their consumption by splenic macrophages

****Result is BOTH thrombocytopenia and thrombosis*****

3

What type of heparin causes HIT Type II?

Unfractionated/ HMW

4

What patient populations is Type II HIT seen in most often?

1) Surgical
2) Cancer
3) Women

5

What is Enoxaparain?

LMW Heparin (Lovenox)

6

What are the advantages of LMWH vs. HMWH?

1) Easier to dose
2) Less risk of HIT
3) Less risk of osteoporosis

*****LMWH is generally safer than HMWH*****

7

What is the contraindication for LMWH?

LMWH is cleared by the kidneys; thus, NOT indicated in patients with severe renal insufficiency

8

What is the disadvantage of LMWH?

Protamine only PARTIALLY reverses it

9

What is the mechanism of action of Fondaparinux?

Synthetic analog of the antithrombin binding pentasaccharide sequence of Heparin

*****Cannot bridge AT and Thrombin like Heparin*****

10

Can Protamine be used to reverse Fondaparinux?

NO

11

In what patients is Fondaparinux contraindicated?

Severe renal insufficiency

12

What assay is used to monitor LMWH and Fondaparinux?

Anti-factor Xa Assay

13

List the direct thrombin inhibitors (DTIs).

Argatroban
Bivalrudin
Dabigatron
Lepirudin

14

What is the mechanism of action of the direct thrombin inhibitors?

- Bind either fibrin binding (active site) of thrombin or,
- Bind BOTH E1 and active site, fibrin binding site of thrombin

15

What are the univalent DTIs?

These are the direct thrombin inhibitors that only bind at the active site, i.e. the fibrinogen binding site
- Aragatroban
- Dabigatran

"an"= univalent

16

What are the divalent DTIs?

These are the direct thrombin inhibitors that only bind at BOTH the active site and E1
- Bivalrudin
- Lepirudin

"din"= DIvalent/ bivalent

17

List the DTIs that can be given parenterally.

Aragatroban
Bivalrudin
Lepirudin

18

What DTI can be given orally?

Dabigatran

19

What is the major advantage of DTIs over Heparin?

- Heparin CANNOT inhibit thrombin bound to fibrin
- DTIs CAN inhibit thrombin bound to heparin

20

What DTIs are used to treat HIT?

All BUT Dabigatran
- Bivalrudin
- Lepirudin
- Aragatroban

21

What DTI is used to treat CVA?

Dabigatran

22

What DTI is used for PCI and HIT in patients undergoing PCI?

Bivalirudin

23

What is the drawback to the DTIs?

No antidote as there is with Heparin

24

What are the indications for Warfarin?

Venous thrombosis or thromboembolism

25

What is the mechanism of action of Warfarin?

Competes with Vitamin K for Vitamin K reductase

26

What is the normal role of Vitamin K in clotting?

Activation of II, VII, IX, X and Protein C and S are Vitamin K dependent

27

How long does it take for Warfarin to start working? Why?

3-5 days b/c Warfarin cannot reduce the activity of PREVIOUSLY SYNTHESIZED coagulation factors

28

How is the 3-5 day onset of action of Warfarin combated in the clinical setting?

Bridge with LMWH (Lovenox)

29

What enzyme metabolizes Warfarin? Why is this important?

CYP2C9

- High genetic polymorphisms that can alter dosing in patients

30

What assay is used to monitor Warfarin?

PT/INR

Prothrombin time*

31

What is the normal/target INR with Warfarin therapy?

2.0-3.0

32

What is the effect of broad spectrum antibiotics on Warfarin therapy?

Increases the effect of Warfarin by decreasing endogenous Vitamin K

33

What is the effect of NSAIDs on Warfarin therapy?

Interfere with primary hemostasis and increase effects

34

What is the effect of SSRIs on Warfarin therapy?

Interfere with primary hemostasis and increase effects

35

What is the effect of certain statins on Warfarin therapy?

Decrease hepatic metabolism and increase effects

36

What is the effect of Rifampin on Warfarin therapy?

Increases hepatic metabolism and decreases effects

37

What is the effect of barbiturates on Warfarin therapy?

Increases hepatic metabolism and decreases effects

38

What is the effect of Carbamazepine on Warfarin therapy?

Increases hepatic metabolism and decreases effects

39

What is the effect of drugs that potentiate warfarin's effects on PT/INR?

Increase INR

40

What is the effect of drugs that inhibit warfarin's effects on PT/INR?

Decrease INR

41

What is the effect of impaired hepatic function of warfarin?

- Decreased clearance
- Increased INR

42

What is the effect of Crohn's Disease that reduce Vitamin K on warfarin therapy?

Increase INR

43

What are the clinical considerations in patients with renal insufficiency and Warfarin?

- Renal insufficiency can cause hypoalbuminemia
- This will INCREASE the INR

44

What are the adverse effects of Warfarin?

1) Hemorrhage
2) Placental transfer
3) Birth defects
4) Warfarin necrosis (caused by a drop in Protein C)

45

How can the effects of Warfarin therapy be reversed?

1) Vitamin K
2) Plasma transfusion

46

What are the limitations and challenges associated with Warfarin?

1) Narrow TI
2) Long half-life
3) Slow onset of action

47

List the new oral anticoagulants.

1) Rivaroxaban
2) Apixaban
3) Dabigatran

48

What are the benefits of the new oral anticoagulants compared to Warfarin?

1) Faster onset
2) Larger TI
3) Low potential for food and drug interactions
4) Predicatable anticoagulant effects that limits need for blood monitoring
5) Less overall bleeding risk

49

What is the mechanism of action for Rivaroxaban?

Oral direct Xa inhibitor

50

What should be remembered about Riavorxaban in the treatment of PE?

As efficacious in the treatment of PE as warfarin/heparin bridge, but LESS major bleeding

51

What is the mechanism of action of Dabigatran?

Oral thrombin inhibitor

52

What is the contraindication of Dabigatran?

Mechanical heart valve

53

Which class of anticogulants is safe to use druing pregnancy?

Heparin

(Rivaroxaban and apixaban are "use with caution")

54

What is the main enzyme that breaks down the fibrin clot? What is its precuror?

Plasminogen-->plasmin

- Plasmin is the enzyme that breaks down the fibrin clot

55

What factors activate plasminogen to plasmin?

tPA
u-PA

56

What is unique about the selectivity of tPA?

tPA has a high affinity for fibrin, which prevents plasminogen from being activated randomly in the bloodstream

57

List the fibrinolytic drugs.

1) Streptokinase
2) u-PA
3) t-PA
- Endogenous
- Alteplase
- Reteplase
- Tenecteplase

58

What is the mechanism of action of Streptokinase?

- Forms a complex with plasminogen
- Streptokinase/plasminogen activate free plasminogen to plasmin

59

What is the drawback associated with Streptokinase?

- Tolerance
- Hypersensitivity with repeated use

60

What are the indications for tPA e.g. altepalse?

STEMI within 12 hour onset
CVA

61

What are the absolute contraindications to thrombolytic therapy?

1) Greater than 24 hours from onset
2) Prior intracranial hemorrhage
3) CVA within last year
4) Intracranial neoplasm
5) Active bleeding
6) Aortic dissection
7) Head or facial trauma within the past 3 months

62

List the inhibitors of fibrinolysis.

Aminocaproic acid
Tranexamic acid

63

What are inhibitors of fibrinolysis used to treat?

1) Hemophilia
2) Reverse bleeding from fibrinolytic therapy

64

What is the mechanism of action of the inhibitors of fibrinolysis?

Block the interaction of plasmin with fibrin i.e. plasmin cannot degrade the fibrin clot

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