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Flashcards in Clotting Pharm Deck (71):
1

Function: Thromboxane A2

Platelet aggregation, Release response, Arterial constriction

2

Activates platelet aggregation

Thromboxane A2

3

Functions: Prostacyclin

Inhibit platelet aggregation, Relaxation of blood vessels

4

Inhibits platelet aggregation

Prostacyclin

5

Binds to the enzyme inhibitor antithrombin III (AT) causing a conformational change that results in its activation through an increase in the flexibility of its reactive site loop. The activated AT then inactivates thrombin and other proteases involved in blood clotting, most notably factor Xa. It can increase (by up to 1000-fold )the rate of inactivation of these proteases by AT

Unfractionated Heparin

6

MOA: Unfractionated Heparin

Inhibition of factor Xa and thrombin activity

7

Kinetics: Unfractionated Heparin

Short T1/2 of approx 2 hours. The drug can be given SC or IV bolus and infusion.

8

The drug requires frequent monitoring with activated partial thromboplastin time (aPTT). The levels of aPTT need to be evaluated ever 6 hours to ensure the drug falls into the range of 1.5 to 2.5 times the control (per lab)

Unfractionated Heparin

9

Unfractionated Heparin can be reversed by

Protamine

10

MOA: Enoxaparin (IV only)

Inhibition of factor Xa (and thrombin)

11

IV only drugs with a longer T1/2. Less bound to plasma proteins and endothelial cells giving them more predictable dosing and activity. Eliminated via the kidneys, therefore will require adjustment in renal disease and contraindicated in hemodialysis (HD) patients

Enoxaparin, Dalteparin, and Tinzaparin

12

MOA: Dalteparin (IV only)

Inhibition of factor Xa (and thrombin)

13

No required monitoring involved, however can be monitored by evaluating anti-Xa levels to assess activity

Enoxaparin, Dalteparin, and Tinzaparin

14

MOA: Tinzaparin (IV only)

Inhibition of factor Xa (and thrombin)

15

Uses: DVT prophylaxis, DVT or PE treatment, AMI, and used during PCI in the coronary cath-lab

Enoxaparin, Dalteparin, and Tinzaparin

16

Uses: AMI, DVT prophylaxis, DVT or PE, and stroke. Also may be used to transition patients as they await the INR to raise from warfarin therapy. Useful for anticoagulation during open-heart surgery

Unfractionated Heparin

17

Adverse events: Enoxaparin, Dalteparin, and Tinzaparin

Bleeding, lower incidence of causing thrombocytopenia than heparin

18

Adverse events: Unfractionated Heparin

Bleeding, thrombocytopenia, hypersensistivity reaction, and long-term use is associated with osteoporosis (secondary to activity on osteoclasts/osteoblasts)

19

Synthetically manufactured, intravenous infusion given to patients requiring anticoagulation therapy. Infusion therapy is titrated to aPPT, similar to heparin.

Argatroban

20

Dosing adjustment: Argatroban (IV only)

Required for hepatic dysfunction

21

Leech-saliva derived, intravenous infusion given to patients requiring anticoagulation. Infusion is titrated to aPPT, similar to UFH.

Lepirudin

22

Dosing adjustment: Lepirudin (IV only)

Required for patients with renal dysfunction

23

Synthetically manufactured, intravenous infusion. Can be utilized for patients requiring acute coronary syndrome treatment via Percutaneous coronary intervention. The infusion is given as a bolus and infusion dosing.

Bivalrudin

24

IV only Direct Thrombin Inhibitors

Argatroban, Lepirudin, and Bivalrudin

25

MOA: Warfarin

Inhibition of hepatic-vitamin K dependent clotting factors (II, VII, IX, and X). The reduced form of vitamin K is required for gamma-carboxylation of these clotting factors. Warfarin inhibits vitamin K reductase, inhibiting the conversion of vitamin K to the reduced form, and thus inhibiting the production of II, VII, IX, and X

26

Warfarin has 2 isomers. What are they and which one is more potent

(R-) and (S-) isomers. The (S-) isomer is more potent.

27

Kinetics: Warfarin

Long-acting therapy. Drug is primarily protein bound (greater than 90%).

28

Metabolism: Warfarin

Warfarin has 2 isomers (R-) and (S-) formations. The (S-) isomer is more potent. Metabolism of the (S-) is via CYP 2C9 and (R-) is CYP 3A4

29

Drug can also cross the placenta, therefore contraindicated in pregnancy

Warfarin

30

Indications: Long-term outpatient anticoagulation with oral therapy for treatment of DVT, PE, stroke, anticoagulation required for patients with atrial fibrillation, and for inherited clotting disorders (Protein C and S deficiencies)

Warfarin

31

Prothrombin time (PT) is not standardized lab value. What is a lab standard that patients can have measured in any laboratory

International normalized ratio (INR). Monitoring range is dependent on the disease state (ie DVT or PE range of 2-3, but for mechanical heart valve range goal (2.5 to 3.5)

32

Oral direct thrombin inhibitor pro-drug with lower potential to need extensive monitoring and drug interactions.

Dabigatran

33

Dabigatran is reversed by

There is no specific way exists to reverse the anticoagulant effect of dabigatran in the event of a major bleeding event

34

MOA: Apixaban

Oral direct Xa inhibitors (act directly for the inhibition of factor Xa)

35

MOA: Rivaroxaban

Oral direct Xa inhibitors (act directly for the inhibition of factor Xa)

36

Can cause an antigenic activity as it is derived from B-hemolytic streptococci

Streptokinase

37

MOA: Streptokinase

It binds to Plasminogen to form a complex that converts substrate plasminogen to plasmin

38

This is a recombinant tissue plasminogen activator. FDA-approved for treatment of myocardial infarction with ST-elevation, but also many other indications where thrombolytic therapy is needed

Alteplase

39

MOA: Alteplase

Tissue plasminogen activator is a protein involved in the breakdown of blood clots. It is a serine protease found on endothelial cells. It catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown.

40

This is a recombinant tissue plasminogen activator. FDA-approved for acute myocardial infarction, where it shows fewer bleeding complications but otherwise similar mortality rates after one year compared to alteplase

Tenecteplase

41

MOA: Tenecteplase

Tissue plasminogen activator is a protein involved in the breakdown of blood clots. It is a serine protease found on endothelial cells. It catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown.

42

This is a recombinant tissue plasminogen activator. FDA-approved for acute myocardial infarction, where it has more convenient administration and faster thrombolysis than Alteplase

Reteplase

43

MOA: Reteplase

Tissue plasminogen activator is a protein involved in the breakdown of blood clots. It is a serine protease found on endothelial cells. It catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown.

44

Irreversible inhibition of COX in platelets which will lead to decreased activation

ASA

45

Used for prophylaxis for AMI and/or the first dose for the event.

ASA

46

MOA: Ticlopidine

ADP inhibitors- blockade of the P2Y12 receptors on platelets to decrease their activation by ADP. This prevents ADP-induced activation of GP IIb/IIIa receptors required for platelets to bind to fibrinogen and to each other

47

What order is consistent with their onset of action from slowest to fastest on inhibition of platelet activation when the loading doses are used

Ticlopidine (Slowest), clopidogrel, and prasugrel (Fastest)

48

The notable adverse reaction of ticlopidine is

Thrombocytopenic purpura (TTP)

49

MOA: Clopidogrel

ADP inhibitors- blockade of the P2Y12 receptors on platelets to decrease their activation by ADP. This prevents ADP-induced activation of GP IIb/IIIa receptors required for platelets to bind to fibrinogen and to each other
 

50

Why do ADP inhibitors have drug interaction with proton pump inhibitors

Since the PPI's are metabolized and serve as substrates via 2C19; therefore there is science that there is competitive inhibition which could potentially result in lower concentrations of ADP antagonists, particularly ticlopidine and clopidogrel.

51

MOA: Prasugrel

ADP inhibitors- blockade of the P2Y12 receptors on platelets to decrease their activation by ADP. This prevents ADP-induced activation of GP IIb/IIIa receptors required for platelets to bind to fibrinogen and to each other

52

MOA: Abciximab

Glycoprotein (GP) IIb/IIIa receptor inhibitor (> 80% blockade results in activity). They work by preventing platelet aggregation and thrombus formation by inhibition of the GpIIb/IIIa receptor on the surface of the platelets. The GP IIb/IIIa receptors are the final step in platelet-platelet aggregation.

53

Uses: Abciximab, Eptifibatide, and Tirofiban

These drugs are used for medical management of acute coronary syndrome (ACS) and are indicated for cases during the PCI-Cath lab procedures

54

Indicated for cases during the PCI-Cath lab procedures. Drug involves hepatic metabolism and given as intravenous bolus and infusion. In addition, the drug's metabolism occurs via the reticular endothelial system (RES) and dosing adjustment not needed for renal dysfunction.

Abciximab

55

MOA: Eptifibatide

Glycoprotein (GP) IIb/IIIa receptor inhibitor (> 80% blockade results in activity). They work by preventing platelet aggregation and thrombus formation by inhibition of the GpIIb/IIIa receptor on the surface of the platelets. The GP IIb/IIIa receptors are the final step in platelet-platelet aggregation.
 

56

MOA: Tirofiban

Glycoprotein (GP) IIb/IIIa receptor inhibitor (> 80% blockade results in activity). They work by preventing platelet aggregation and thrombus formation by inhibition of the GpIIb/IIIa receptor on the surface of the platelets. The GP IIb/IIIa receptors are the final step in platelet-platelet aggregation.
 

57

Indicated for cases during the PCI-Cath lab and for medical management. Given as an intravenous bolus and infusion and does require dosing adjustment for renal dysfunction

Tirofiban and Eptifibatide

58

When does warfarin begin to have an effect

3-5 days after administration

59

What reverses the effects of warfarin

Vitamin K

60

What are the half lives of factors VII, IX, X, and II

VII: 6-7 hours, IX: 24 hours, X: 40 hours, II: 60 hours

61

What natural anticoagulant factor is also vitamin K dependent and inhibited by warfarin.

Protein C. It has a short half life like factor VII so early in warfarin therapy, patients may experience a paradoxical hypercoagulable state.

62

Name the oral Xa inhibitor(s)

Rivaroxaban and Apixaban

63

Name the intravenous Xa inhibitor(s)

Enoxaparin, Dalteparin, and Tinzaparin

64

Name the oral thrombin inhibitor(s)

Dabigatran

65

Name the intravenous thrombin inhibitor(s)

Argatroban, Lepirudin, and Bivalrudin
 

66

What reverses the action of alteplase, tenecteplase, and reteplase

Cryoprecipitate (lots of fibrinogen), Aminocaproic acid, or Tranexamic acid

67

What is given in place of aspirin to a patient with an aspirin allergy

Clopidogrel or Prasugrel. Ticlopidine is used far less frequently

68

MOA: Dipyridamole

Coronary vasodilation by inhibiting the cellular uptake of adenosine. It also has some weak antiplatelet activity by increasing intracellular cAMP through the inhibition of the phosphodiesterase enzyme, resulting in decreased Thromboxane A2 synthesis

69

What is usually given in combination with Aspirin because it is ineffective alone

Dipyridamole

70

Which GP IIb/IIIa inhibitors are long vs short acting

long acting (18-24 hrs): Abciximab.  Short acting (6-12 hrs): Tirofiban and Eptifibatide

71

What is Abciximab usually administered with

Heparin or aspirin