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Antithrombotics Flashcards

1
Q

If someone is septic or has another immunocompromising condition what lab value is a more accurate indicator of heparin efficacy?

A

antifactor Xa levels

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2
Q

When it is a drug-eluting stent when is the risk of thrombosis higher?

A

6-12 months post surgery

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3
Q

If Rivaroxaban (Xarelto) and Apixaban (Eliquis) have the same characteristics why is Xarelto 2x a day and Eliquis 1x a day?

A
  • d/t the way Eliquis was studied in order to be more attractive than Xarelto
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4
Q

What substance activates plasminogen and turns it into plasmin?

A

TPA

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5
Q

What is the mechanism of action of heparin?

A
  • binds to and produces conformational change in AT III = enhances inactivation of factors IIa and Xa
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6
Q

Which of the oral anti-platelet drugs has the fastest onset of action and has a long lasting effect?

a. Clopidogrel (Plavix)
b. Vorapaxar (Zontivity)
c. Dipyridamole (Persantine)
d. Tirofiban (Aggrastat)
e. Aspirin

A

e. Aspirin

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7
Q

Which of the following anti-platelet drugs has the lowest bleeding risk?

a. Clopidogrel (Plavix)
b. Vorapaxar (Zontivity)
c. Dipyridamole (Persantine)
d. Tirofiban (Aggrastat)

A

c. Dipyridamole (Persantine)

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8
Q

What are the 4 precautions of DOACs highlighted in class?

A
  • kidney function
  • quick onset/short duration = cant skip dose
  • reversal agents are very expensive
  • CYP450 & P-gp interaction
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9
Q

If someone has a history of HIT can we give LMWH?

enoxaparin (Lovenox)

A

NO

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10
Q

Which of the DOACs has the least % of renal clearance and is BEST for patients with kidney disease?

a. Dabigatran
b. Rivaroxaban (Xarelto)
c. Apixaban (Eliquis)
d. Edoxaban (Savaysa)
e. Betrixaban (Bevyxxa)

A

c. Apixaban (Eliquis)

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11
Q

How does Rifampin effect the efficacy of Warfarin?

A
  • Rifampin induces CYP2C9 which decreases efficacy of Warfarin
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12
Q

How can you measure the breakdown of Fibrin?

A

D-Dimer

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13
Q

Which of the anti-platelet agents block thromboxane A2 by irreversibly inhibiting COX I?

A

aspirin

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14
Q

Why do we use anti-platelet drugs to prevent clot formation in the arterial system?

A
  • most clots in the arterial system are composed of primarily platelets
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15
Q

What are the 3 major adverse effects of thrombolytics?

Alteplase (Activase)

A
  • antigenic (if derived from bacteria = streptokinase)
  • hemorrhage = main worry!
  • arrhythmias
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16
Q

What do we need to monitor when administering LMWH?

enoxaparin (Lovenox)

A

kidney function

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17
Q

Which of the anti-platelet agents are a thrombin receptor antagonists?

a. Clopidogrel (Plavix)
b. Vorapaxar (Zontivity)
c. Dipyridamole (Persantine)
d. Tirofiban (Aggrastat)

A

b. Vorapaxar (Zontivity)

* protease activated receptor*

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18
Q

What is the most common indications of anti-platelet drugs? (2)

A
  • secondary prevention of MI/stroke

- post-surgery after stent placement

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19
Q

What lab test is used to monitor the efficacy of heparin?

A

aPTT

measures what is happening in the intrinsic pathway

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20
Q

What test is used to measure the efficacy of Warfarin?

A
  • PT = test used for monitoring

- INR = use to standardize test result

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21
Q

What are the 3 adverse effects of heparin?

A
  • bleeding
  • thrombocytopenia
  • osteopenia/osteoporosis (pregnancy)
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22
Q

What is the preferred anticoagulant for VTE if the patient has cancer?

a. Clopidogrel (Plavix)
b. enoxaparin (Lovenox)
c. Dipyridamole (Persantine)
d. Apixaban (Eliquis)
e. Warfarin

A

b. enoxaparin (Lovenox)

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23
Q

What are the 2 most important adverse effects of Warfarin?

A
  • bleeding

- teratogen = transition to Lovenox (LMWH) if patient gets pregnant

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24
Q

What facilitates the breakdown of Fibrin?

A

Plasmin

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25
Q

Which of the following is a direct Factor Xa inhibitor?

a. Clopidogrel (Plavix)
b. Vorapaxar (Zontivity)
c. Dipyridamole (Persantine)
d. Apixaban (Eliquis)
e. alteplase (Activase)

A

d. Apixaban (Eliquis)

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26
Q

What is the mechanism of action of Warfarin?

A
  • inhibition of vitamin K dependent clotting factors
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27
Q

What factors are inhibited with use of Warfarin?

What 2 endogenous anticoagulant proteins are also inhibited?

A
  • Factors II, VII, IX, X

* also inhibits Protein C+S = endogenous anticoagulant proteins*

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28
Q

What is unique about Fondaparinux (Arixtra)?

A
  • it is safe to use for patients with history of HIT even though it is a LMWH-like drug
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29
Q

Which of the following anticoagulants can be used as an alternative to the GP IIb/IIIa receptor blockers?

a. enoxaparin (Lovenox)
b. Fondaparinux (Arixtra)
c. heparin
d. Bivalirudin (Angiomax)

A

Bivalirudin (Angiomax)

direct thrombin inhibitors

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30
Q

What is the main indication for anticoagulants (heparins)?

A

prevention of pulmonary embolism

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31
Q

delete

A
  • Bleeding
  • Thrombocytopenia
  • Hypersensitivity
  • Miscellaneous others
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32
Q

Which of the following anticoagulants has the highest selectivity for factor Xa?

a. Enoxaparin (Lovenox)
b. Fondaparinux (Arixtra)
c. heparin

A

b. Fondaparinux (Arixtra)

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33
Q

What is the key factor for success with thrombolytics?

A

time since onset of symptoms

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34
Q

What diet recommendation should you give to a patient on Warfarin?

A
  • be consistent
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35
Q

Which of the thrombolytics were the first to be used in practice?

A

Streptokinase

  • problem was it could only be used once*
  • TPA is now made from humans*
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36
Q

What was the reason that Bivalirudin (Angiomax) were created?

A

anticoagulant therapy in patients with a history of HIT

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37
Q

Protamine is derived from what?

A

salmon sperm

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38
Q

How would you describe the onset, half-life and duration of DOACs?

A
  • fast onset
  • short half-life
  • short duration
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39
Q

Before the direct thrombin inhibitors were made, what was used for anticoagulation in a patient with a hx of HIT?

A
  • Hirudin

* came from saliva of leeches*

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40
Q

What about Warfarin can cause alopecia, urticaria or dermatitis?

A
  • allergies from food dye used to color Warfarin
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41
Q

Why does Warfarin reach peak level at 2-8 hours but the peak effect takes 4-5 days?

A
  • because clotting factors already activated need to eliminated on it’s own
42
Q

The mechanism of this drug is to directly inhibit thrombin.

a. enoxaparin (Lovenox)
b. Fondaparinux (Arixtra)
c. heparin
d. Bivalirudin (Angiomax)

A

d. Bivalirudin (Angiomax)

43
Q

With Warfarin we typically aim for an INR level of what? What if the patient has a mechanical valve?

A
  • INR = 2-3

- mechanical valve = 2.5-3.5

44
Q

The mechanism of action of this drug is to inhibit the enzyme phosphodiesterase inside the platelet to prevent the platelet-forming mediators from leaving the platelet.

a. Clopidogrel (Plavix)
b. Vorapaxar (Zontivity)
c. Dipyridamole (Persantine)
d. Tirofiban (Aggrastat)

A

c. Dipyridamole (Persantine)

45
Q

Why can’t DOACs be used in patients with mechanical valves?

A
  • initial study done on Dabigatran did not show positive results so no more research was pursued
46
Q

How long before surgery should aspirin be withheld?

A
  • needs to be held for 1 week
47
Q

What reversal agent is specific for overdose of a DOAC?

Because this is so expensive, what reversal agent is commonly used?

A
  • Recombinant Factor Xa (Andexxa)

- PCC (Kcentra)

48
Q

How often is Warfarin monitored?

A
  • initially every few days>every week>every 4-6 weeks

* seldom go past 6 weeks without monitoring*

49
Q

This drug is used to lyse pre-existing thrombus.

a. Clopidogrel (Plavix)
b. Vorapaxar (Zontivity)
c. Dipyridamole (Persantine)
d. Tirofiban (Aggrastat)
e. alteplase (Activase)

A

e. alteplase (Activase)

50
Q

T/F: If you forget a dose of Warfarin there is some forgiveness for that.

51
Q

Why has the incidence of HIT increased?

A
  • we now have drugs to treat it so it is more often diagnosed
52
Q

If someone overdosed on Lovenox (LMWH) what is the antidote?

A
  • fresh frozen plasma OR Prothrombin complex concentrate (Kcentra)
  • Kcentra = Factors 2, 7, 9, 10*
53
Q

Which of the following DOACs is a direct thrombin (Factor IIa) inhibitor?

a. apixaban (Eliquis)
b. Rivaroxaban (Xarelto)
c. Edoxaban (Savaysa)
d. Dabigatran (Pradaxa)

A

d. Dabigatran (Pradaxa)

* analog of Bivalirudin (Angiomax)*

54
Q

How do we pharmacologically enhance fibrin degradation?

55
Q

T/F: In most cases, “bridging” Warfarin with a shorter-acting anticoagulation is not necessary pre-surgery.

56
Q

Why is LMWH much easier to use than heparin?

A

it is administered SQ and requires less monitoring

57
Q

Which of the anti-platelet agents work by blocking adenosine diphosphate by binding to the P2Y12 receptors?

a. Clopidogrel (Plavix)
b. Vorapaxar (Zontivity)
c. Dipyridamole (Persantine)
d. Tirofiban (Aggrastat)

A

a. Clopidogrel (Plavix)

58
Q

What is the purpose of anti-platelet drugs? (2)

A
  • prevent clot formation

- prevent pre-existing clots from further propagating

59
Q

If you are using heparin for prophylaxis of DVT what dosage and route of administration is used?

A

SQ with a lower amount compared to treating an acute problem

60
Q

What was Warfarin initially used for?

A
  • was used for rat poison
61
Q

If someone is on a drug that induces the CYP2C19 enzyme and is on Clopidogrel (Plavix) they are at an increased risk of what?

A

increased risk of bleeding

62
Q

What are the 3 most common indications for thrombolytics?

A
  • Acute MI
  • Ischemic stroke
  • Pulmonary embolism
63
Q

What is the main clotting factor that facilitates Fibrin to Fibrinogen?

A
  • Thrombin (Factor IIa)

* comes from prothrombin*

64
Q

If someone lacks the CYP2C19 enzyme what would you expect the efficacy of Clopidogrel (Plavix) to be?

A

efficacy would be diminished

Clopidogrel is a pro-drug

65
Q

How does heparin administration cause thrombocytopenia?

A

heparin can combine with platelet factor 4 which can be identified and destroyed by IgG

immune system turns on heparin

66
Q

How does antibiotics effect Warfarin?

A
  • antibiotics increase efficacy of Warfarin
67
Q

What does Ciprofloxacin do that increases the efficacy of Warfarin?

A
  • Ciprofloxacin inhibits the enzyme CYP2CP9
68
Q

Where is the site of action and clearance of Warfarin?

69
Q

If a patient overdosed on Heparin and is bleeding what medication do you give to reverse the effects?

A
  • Protamine

* if only too much heparin = lower the dose but don’t discontinue*

70
Q

Why do we use anticoagulant drugs to prevent clot formation in the venous system?

A
  • most clots in the venous system are composed of primarily coagulation factors
71
Q

How do we manage heparin induced thrombocytopenia (HIT)?

A
  • take away heparin

- administer protamine

72
Q

Because DOACs interact with the P-gp transporter what does that mean for any dose of the drug?

A
  • some % of that drug never gets absorbed

* some drugs can interact with P-gp as well*

73
Q

What is the typical presentation of HIT?

A
  • patient has been on heparin for a week and now presents with thrombocytopenia
74
Q

Warfarin targets what enzyme?

A

VKOR1

under expression will increase effect of Warfarin

75
Q

What is the main indication for oral anticoagulants (coumarins)?

A

prophylaxis for thrombus from A-fib

76
Q

What is the best anticoagulant therapy for pregnant females who have a mechanical valve?

A

IV heparin

because we can monitor every 6 hours

77
Q

What aPTT do we generally aim for with heparin?

When should these values be checked?

A
  1. 5-2.5 x control

- 6 hours after bolus or dose changes d/t half-life = 90 minutes

78
Q

What are the 2 consequences of heparin binding to platelet factor 4?

A
  • increased risk of bleeding (thrombocytopenia)

- increased risk of clotting

79
Q

What is the risk of LMWH administration in patients undergoing spinal anesthesia?

A
  • bleeding in the spinal cord that can lead to paralysis

* need to wait 12-24 hours before procedure or switch to heparin*

80
Q

How long before a surgical procedure would Warfarin need to be stopped?

81
Q

Which of the following has a better efficacy heparin or LMWH?

A

they have the same efficacy

82
Q

Which of the following is a contraindication to thrombolytics?

a. recent major surgery or non-head trauma
b. current anticoagulant therapy
c. pregnancy
d. severe, uncontrolled hypertension

A

d. severe, uncontrolled hypertension

* others are precautions*

83
Q

When administering Clopidogrel why do we need to give a loading dose?

A

Clopidogrel (Plavix) is a pro-drug = onset of action is hours = give a loading dose to speed up onset

84
Q

Out of all these drugs which of the following has the HIGHEST risk of bleeding?

a. Clopidogrel (Plavix)
b. Vorapaxar (Zontivity)
c. Dipyridamole (Persantine)
d. Tirofiban (Aggrastat)
e. alteplase (Activase)

A

e. alteplase (Activase) = TPA

85
Q

What are 5 positive features of DOACs highlighted in class?

A
  • fixed doses
  • less monitoring
  • quick onset/ short duration
  • less impact of food
  • fewer drug-drug interactions
86
Q

If a patient is on an anti-platelet drug and begins this type of antidepressant therapy they are at an increased risk of bleeding.

A

SSRI/SNRI antidepressants

87
Q

We do not need to, but IF we wanted to monitor the efficacy of LMWH what lab value might be of use?

In which 2 specific populations would this monitoring be recommended?

A

anti-factor Xa

  • looking at peak effect 4 hours after administration*
  • obese or patients with kidney insufficiency
88
Q

This anti-platelet drug is used most often test the heart for blocked arteries during a chemical stress test by causing vasodilation of the arteries.

a. Clopidogrel (Plavix)
b. Vorapaxar (Zontivity)
c. Dipyridamole (Persantine)
d. Tirofiban (Aggrastat)

A

c. Dipyridamole (Persantine)

89
Q

What enzyme metabolizes warfarin?

A

CYP2C9

over expression will decrease effect of Warfarin

90
Q

This drug is less used today, but in the past it was commonly used by continuous IV during cardiac catheterization procedures.

a. Clopidogrel (Plavix)
b. Vorapaxar (Zontivity)
c. Dipyridamole (Persantine)
d. Tirofiban (Aggrastat)
e. Aspirin

A

d. Tirofiban (Aggrastat)

91
Q

If a patient is on Warfarin and presents with a very high INR + bleeding what drug therapy can you give to reverse the effects?

A
  • Phytonadione (Vitamin K)

- “most commonly administered per protocol “

92
Q

What receptors allow the platelets to bind to another? What substance binds the two receptors together?

A
  • Gp IIa/IIIb receptors

- Fibrin binds the receptors together

93
Q

Which of the anti-platelet agents are the strongest inhibitor of platelet aggregation and, therefore, have the greatest bleeding risk?

a. Clopidogrel (Plavix)
b. Vorapaxar (Zontivity)
c. Dipyridamole (Persantine)
d. Tirofiban (Aggrastat)

A

d. Tirofiban (Aggrastat)

* IIb/IIIa antagonist*

94
Q

What is the mechanism of action of LMWH?

enoxaparin (Lovenox)

A
  • binds to and produces conformational change in AT III = enhances inactivation of factors Xa > IIa
95
Q

Which of the vitamin K clotting factors has the longest half life vs the shortest half life?

A
  • longest half-life = Factor II

- shortest half-life = Factor VII

96
Q

What are the 2 drugs most commonly used for prophylaxis of thrombi formation post stent placement surgery? How long are they usually on this dual therapy for?

A
  • aspirin
  • clopidogrel (Plavix)

-6 to 12 months

97
Q

When it is a bare metal stent when is the risk of thrombosis higher?

A

3-6 months post surgery

98
Q

Why do we need to give large amounts of heparin by bolus + continuous infusion when treating an acute problem?

A
  • heparin has a very short half life d/t clearance via the reticulo-endothelial system
99
Q

If you are taking this type of drug the efficacy of Clopidogrel (Plavix) might be reduced.

A

protein pump inhibitors

they are a CYP2C19 inhibitor

100
Q

Why is adherence higher in DOACs than in Warfarin?

A
  • does not require monitoring

Pharmacology (6 decks)

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