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2020 CPR II Pulm Exam 2 > PHARM Thromboembolic Disorders (Wolff) > Flashcards

PHARM Thromboembolic Disorders (Wolff) Flashcards

1
Q

White (platelet-rich) thrombi form in arteries under what type of pressure?

A

High-pressure arteries

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2
Q

What are 2 pathologic conditions of coronoary arteries associated w/ white thrombi?

A
  • MI
  • Unstable angina
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3
Q

Red (fibrin-rich) thrombi form in vessels under what type of pressure and in which location?

A

Low-pressure veins and in the heart

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4
Q

Anticoagulants are primarily used to prevent clots form forming where?

Which specific type of thrombi?

A
  • Venous system and heart
  • Red (fibrin) thrombi
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5
Q

Antiplatelet drugs are primarily used to preven clots from forming in which vessels?

What specific type of thrombi?

A
  • Arteries
  • White thrombi
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6
Q

What are the 3 classes and drugs in each of parenteral anticoagulants which act as indirect thrombin and factor Xa (FXa) inhibitors?

A
  • Unfractionated (HMW) heparin = Heparin sodium
  • LMW heparins = Enoxaparin, Tinzaparin, and Dalteparin
  • Synthetic pentasaccharide = Fondaparinux
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7
Q

Which 3 drugs belong to the direct thrombin inhibitor class and are used as parenteral anticoagulants?

A
  • Lepirudin
  • Argatroban
  • Bivalirudin
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8
Q

The indirect thrombin and factor Xa (FXa) inhibitors bind to what in the plasma?

A

Serine protease inhibitor antithrombin III

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9
Q

Unfractionated (HMW) heparin inhibits the activity of?

A

Thrombin and factor Xa

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10
Q

LMW heparins inhibit what?

A

Factor Xa w/ little effect on thrombin

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11
Q

Which 2 drugs in the parenteral direct thrombin inhibitor class are bivalent and bind at both the active site and substrate recognition site of thrombin?

A
  • Lepirudin
  • Bivalirudin
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12
Q

Which parenteral class of heparin has increased bioavailability from the SC injection site and allows for less frequent injections and more predictable dosing?

A

LMW Heparin (-aparin’s)

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13
Q

Heparins are used during surgery or in hospitalized patients to reduce the risk of what?

A

Reduces risk of emboli

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14
Q

Heparin is administered to patients with what disorders?

A
  • DVT
  • Atrial arrhythmias
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15
Q

Why must heparins be given via IV or SC routes?

A

Very hydrophilic

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16
Q

What are 2 AE’s associated with Heparin?

A
  • Bleeding
  • Heparin-induced thrombocytopenia (HIT)
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17
Q

What are heparin locks used for?

A

Prevents clots from forming in catheters

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18
Q

What 2 lab studies are used to monitor patients on Heparin?

A
  • Activated partial thromboplastin time (aPTT)
  • Anti-Xa assay
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19
Q

Heprain-induced thrombocytopenia (HIT) is due to what underlying mechanism?

A

Immunogenicitiy of the complex of heparin with platelet factor 4 (PF4)

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20
Q

What 2 things should you be looking for in a patient on Heparin?

A
  • Thrombocytopenia
  • Thrombosis
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21
Q

Treatment for hepain-induced thrombocytopenia?

A

Discontinue heparin and administer DTI

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22
Q

What are 4 contraindications for using Heparin?

A
  • Severe HTN
  • Active TB
  • Ulcers of GI tract
  • Patients w/ recent surgeries
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23
Q

What is used clinically for reversal (antidote) of heparin action?

A

Protamine sulfate

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24
Q

The synthetic pentasaccharide, Fondaparinux, used as an anticoagulant binds to and inhibits what?

A

Acts as antithrombin III catalyst –> indirectly inhibit factor Xa (NO effect on thrombin)

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25
Q

In what 3 ways does the anticoagulant, Fondaparinux, differ from heparins?

A
  • Does not inhibit thrombin acitivity
  • Rarely induces HIT (thrombocytopenia)
  • Action is not reversed by Protamine sulfate
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26
Q

What are 3 clinical indications for the use of Fondaparinux?

A
  • Prevention of DVT’s
  • Tx of acute DVT (in conjunction w/ Warfarin)
  • Tx of pulmonary embolism
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27
Q

Which parenteral direct thrombin inhibitor binds only at the thrombin active site?

A

Argatroban

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28
Q

Which parenteral direct thrombin inhibitor is an irreversible inhibitor of thrombin?

A

Lepirudin

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29
Q

Which parenteral direct thrombin inhibitor is a reversible inhibitor of thombin and also inhibits platelet aggregation?

A

Bivalirudin

*Think Bi = 2 mechanisms!

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30
Q

Which parenteral direct thrombin inhibitor is short acting and used IV?

A

Argatroban

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31
Q

What are the clinical indications for the parenteral direct thrombin inhibitors?

What are bivalirudin and argatroban used for specifically?

A
  • HIT
  • Coronary angioplasty (bivalirudin and argatroban)
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32
Q

Repeated lepirduin use may cause what?

A

Anaphylactic rxn

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33
Q

Bleeding is an adverse effect of parenteral direct thrombin inhibitors and why may this potentially be a big deal?

A

No antidote exists

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34
Q

What is the MOA of Warfarin?

A
  • Inhibits reactivation of vitamin K, by inhibiting vit K epoxide reductase
  • Inhibits carboxylation of glutamate residues by GGCX in prothrombin and factors VII, IX, and X
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35
Q

List 4 causes of high variability in therapeutic warfarin concentrations between individuals?

A
  • Genetic make-up
  • Disease states
  • Drug-Drug interactions
  • Diet
36
Q

Warfarin has a narrow therapeutic window therefore the dose is titrated based on what lab testing?

At what range should patients be at?

A
  • Prothrombin time (PT/INR)
  • 2.0-3.0 range for pt’s on Warfarin
  • INR is monitored a patients visit the clinic regularly
37
Q

Which stereoisomer of Warfari in 3-5x more potent?

A

S-isomer

38
Q

Which steroisomer of Warfarin is metabolized primarily by CYP2C9?

A

S-isomer

39
Q

What is the bioavailability of Warfarin when administered orally?

Onset and half-life?

A
  • 100% bioavailability
  • Delayed onset of action (12 hours)
  • Long half-life (36 hrs)
40
Q

99% of Warfarin is bound to what in the plasma?

A

Plasma albumin

41
Q

What are 3 clincial uses for Warfarin?

A
  • Prevent thrombosis or prevent/treat thromboembolism
  • Atrial fibrillation
  • Prosthetic heart valves
42
Q

What are the major AE’s associated with Warfarin?

A
  • Teratogenic effect (bleeding disorder in fetus, abnormal bone formation)
  • Skin necrosis, infarction of breasts, intestines, extremities
  • Osteoporosis
  • Bleeding
43
Q

Individual variability in the action of Warfarin may be to genetic factors including a high dose and low dose haplotype of what?

A

VKORC1

44
Q

The high dose haplotype of VKORC1 for warfarin is more common in which ethnic group?

A

African Americans = more resistant to warfarin

45
Q

The low dose haplotype of VKORC1 for warfarin is more common in which ethnic group?

A

Asian Americans = less resistant to warfarin

46
Q

Which CYP is responsible for the individual variations in warfarin dose seen in some Caucasian pt’s?

A

CYP2C9

47
Q

What are 3 pharmacokinetic interactions of Warfarin?

A
  • CYP enzyme induction
  • CYP enzyme inhibition
  • Reduced plasma protein binding
48
Q

What are 3 pharmacodynamic interactions associated with Warfarin?

A
  • Synergism with other antithrombotic drugs
  • Competitive antagonism (Vit K)
  • Clotting factor concentration (diurectics)
49
Q

Which 2 disease states must be accounted for when treating with Warfarin due to possibility of increased prothrombin time?

A
  • Liver diseases (reduced clotting factor synthesis)
  • Thyroid status –> Hyperthyroidism
50
Q

What are 3 pharmacodynamic drug interactions of warfarin associated with increased prothrombin time?

A
  • Aspirin (high doses)
  • Cephalosporins, 3rd Gen.
  • Heparin
51
Q

What are 3 pharmacokinetic drug interactions of warfarin associated with decreased prothrombin time?

A
  • Barbituates
  • Cholestyramine
  • Rifampin
52
Q

What are 2 pharmacodynamic drug interactions of warfarin associated with decreased prothrombin time?

A
  • Diuretics
  • Vitamin K
53
Q

List 4 advantages of using Warfarin.

A
  • Oral administration
  • Long duration of action
  • Drug clearance is independent of renal function
  • Reversal of action strategy has been developed
54
Q

How can reversal of Warfarin action be accomplished?

What if rapid reversal needed?

A
  • Vit K administration will reverse action in 12-24 hours
  • More rapid reversal give fresh frozen plasma or prothrombin complex concentrate
55
Q

What are 3 drawbacks of using Warfarin?

A
  • Very high dosing variability, hard to maintain optimal concentration
  • May lead to bleeding complications, such as intracranial hemorrhages
  • Requires INR monitoring
56
Q

Direct ORAL anticoagulants consist of three factor Xa inhibitors and a direct thrombin inhibitor, what are the drugs in these classes?

A
  • Factor Xa inhibitors: Rivaroxaban, Apixaban, and Edoxaban
  • Direct thrombin inhibitor: Dabigatran
57
Q

What are the 3 clinical uses of the direct oral anticoagulants, which are Factor Xa inhibitors (Rivaroxaban, Apixaban, Edoxaban)?

A
  • Prevention of thromboembolism
  • Treatment of thromboembolism
  • Prevention of stroke in patients w/ atrial fibrillation
58
Q

What are 4 clinical advantages of using direct oral anticoagulants, which are Factor Xa inhibitors (Rivaroxaban, Apixaban, Edoxaban)?

A
  • Given orally
  • Administered at fixed doses and do NOT require monitoring
  • Show non-inferiority compared with Warfarin
  • Rapid onset of action as compared to warfarin
59
Q

What is one drawback of direct oral anticoagulants, which are Factor Xa inhibitors (Rivaroxaban, Apixaban, Edoxaban)?

A

Excreted by kidneys; dose adjustment is needed in renal pts

60
Q

What are the 2 clinical uses of the oral direct thrombin inhibitor, Dabigatran?

A
  • Reduce the risk of stroke and systemic embolism in patients w/ non-valvular atrial fibrillation
  • Tx of venous thromboembolism
61
Q

What is the approved antidote for the oral direct thrombin inhibitor, Dabigatran?

A

Idarucizumab

62
Q

What is a disadvantage associated w/ the oral direct thrombin inhibitor, Dabigatran?

A

80% renal excretion - may not be suitable in renal pt’s

63
Q

What are some of the advantages of the oral direct thrombin inhibitor, Dabigatran?

A
  • Predictable pharmacokinetics and bioavailability
  • Fixed dosing and predictable anticoagulant action (no INR monitoring required)
  • Rapid onset and offset of actions
  • No interaction w/ P-450 metabolized drugs
64
Q

What is the antidote for the DOAC - FXa inhibitors (rivaroxaban, apixaban, and edoxaban)?

A

Andexanet alfa

65
Q

Which blood coagulation test is used for the direct oral anticoagulants, which are FXa inhibitors (rivaroxaban, apixaban, edoxaban)?

A

Anti-Xa

66
Q

Which blood coagulation test is used for the oral direct thrombin inhibitor, Dabigatran?

A

Diluted thrombin time (TT)

67
Q

Which antiplatelet drug is an inhibitor of thromboxane A2 synthesis?

A

Aspirin

68
Q

What are the 4 ADP receptors blockers used as antiplatelet drugs?

A
  • Clopidogrel
  • Prasugrel
  • Ticlopidine
  • Ticagrelor
69
Q

What are the 3 platelet glycoprotein receptor (GP IIb/IIIa) antagonists used as antiplatelet drugs?

A
  • Abciximab
  • Eptifibatide
  • Tirofiban
70
Q

What are the 2 inhibitors of phosphodiesterases used as antiplatelet drugs?

A
  • Dipyridamole
  • Cilostazol
71
Q

What are the clinical uses of Aspirin as an antiplatelet?

A
  • Primary and seconday prevention of a heart attack
  • And other vascular events –> ischemic stroke, arterial thrombosis of the limbs resulting in intermittent claudication
72
Q

What are 2 AE’s associated with Aspirin?

A
  • Peptic Ulcer
  • GI bleeding
73
Q

What is the MOA of the antiplatelets which are blockers of ADP receptors?

A
  • Inhibition of AC by αi is relieved
  • Increased production of cAMP
74
Q

What is the MOA of the antiplatelet drugs which are inhibitors of phosphodiesterase?

A
  • Inhibition of cAMP degradation
  • Levels of cAMP in platelets are increased
75
Q

The high variability of action of the antiplatelet drug, Clopidogrel is related to metabolism by what?

A

CYP2C19

76
Q

Nonfunctional CYP2C19 allele is present in which ethnicities and has an effect on the action of the antiplatelet drug, Clopidogrel?

A
  • Chinese (50%)
  • African Americans (25%)
  • Caucasians and Mexican-Americans (19%)
77
Q

Cilostazol (inhibitor of phosphodiesterase) is primarily used for what?

A

Treat intermittent claudication

78
Q

Dipyridamole (PDE inhibitor) is used with aspirin to prevent what?

A

Cerebrovascular ischemia

79
Q

Dipyridamole (PDE inhibitor) is used with warfarin in which patients?

A

Those w/ prosthetic heart valves

80
Q

What is the MOA of the fibrinolytic (thrombolytic) drugs?

A

Activate endogenous fibrinolytic system by converting plasminogen —> plasmin

81
Q

What are the 3 tissue-type plasminogen activator drugs which are fibrinolytic?

A
  • Alteplase
  • Reteplase
  • Tenecteplase
82
Q

What is the Urokinase-type plasminogen activator drug used as a fibrinolytic?

A

Urokinase

83
Q

Which 3 classes of drugs are used as thrombolytic (fibrinolytic) drugs?

A
  • Tissue-type plasminogen activator
  • Urokinase-type plasmingoen activator
  • Streptokinase preparations
84
Q

What are 5 clinical uses for the thrombolytic (fibrinolytic) drugs?

A
  • Acute embolic/thrombotic stroke (within 3 hrs)
  • Acute MI (withing 3-6 hrs)
  • Pulmonary embolism
  • DVT
  • Ascending thrombophlebitis
85
Q

What is an AE associated with the fibrinolytic drugs, streptokinase and urokinase?

A

Bleeding from the systemic fibrinogenolysis

86
Q

Allergic reactions are an AE associated with what fibrinolytic drug?

A

Streptokinase

87
Q

Which fibrinolytic drugs need fibrin as coactivator?

A

tPA

2020 CPR II Pulm Exam 2 (28 decks)

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