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Sophomore - Pharm test 3 > Hematologic > Flashcards

Hematologic Flashcards

1
Q

What does an endothelial cell normally secrete to repel circulating thrombocytes? (Two things)

A
  1. Prostocyclin (PG12)

2. Nitrous oxide (NO)

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2
Q

This proteolytic enzyme converts fibrinogen to fibrin:

A

Thrombin

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3
Q

What are the three phases of clotting?

A
  1. Platelet Adhesion
  2. Platelet Activation
  3. Platelet Aggregation
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4
Q

How do NO and PGI2 affect platelets?

A

They induce cAMP synthesis, which decreases intracellular Ca++ and INHIBITS GPIIb/IIIa activation

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5
Q

Damaged endothelial cells expose what?

A

Von Willebrand factor (vWF) and collagen

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6
Q

Name the top three chemical mediators secreted by adhered/activated platelets:

A
  1. ADP (Adenosine diphosphate)
  2. TXA2 (thromboxane A2)
  3. 5HT (Serotonin)
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7
Q

What action does local 5HT released by activated platelets have in the area of the endothelial damage?

A

Vessel spasm, reducing blood loss

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8
Q

Primary actions of TXA2?

A
  1. Stimulate activation and aggregation of platelets

2. Potent vasoconstrictor

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9
Q

What is thrombin’s job?

A

To convert fibrinogen to fibrin

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10
Q

What is the function of the GPIIb/IIIa receptors on thrombocytes?

A

Facilitate platelet-platelet interaction; fibrin bridge connects the GPIIb/IIIA receptors of one platelet to another

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11
Q

This pathway is shorter, and measured by PT/INR:

A

Extrinsic pathway

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12
Q

This pathway in longer, and measured by aPTT:

A

Intrinsic pathway

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13
Q

Which pathway is vitamin K dependent? Extrinsic or intrinsic?

A

Extrinsic, because it starts with Factor VII (which is Vitamin K dependent)

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14
Q

Name three natural anticoagulants:

A
  1. Protein C
  2. Protein S
  3. Anti-thrombin III
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15
Q

Which pathway is prothrombin time (PT) used to monitor?

Which factor is involved?

What does that factor need in order to be synthesized?

A

Extrinsic pathway
Factor VII
Vitamin-K dependent

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16
Q

Which factors are Vitamin K-dependent?

Which has the shortest life-span?

Which has the longest?

A

Factors II, VII, IX, X

Shortest: VII

Longest: II (thrombin)

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17
Q

Which pathway does the aPTT test assess?

A

The intrinsic pathway

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18
Q

What are the elements of Virchow’s Triad?

A
  1. Vascular wall injury
  2. Stasis
  3. Hypercoagulable state
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19
Q

MOA for ASA?

A

IRREVERSIBLY inhibits COX-1 and 2

Stops conversion of AA to prostaglandin, leading to less TXA2

Leads to inhibition of platelet aggregation, decreased inflammation

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20
Q

ASA dose range for prevention of cardiovascular events:

A

50mg to 160mg

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21
Q

Top risk of ASA use:

A

GI bleeding

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22
Q

Rare SE of ASA?

A

Reye’s Syndrome - swelling of the liver and brain (peds)

Avoid use of salicylates in children

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23
Q

ASA pregnancy category?

A

C/D —> avoid in 3rd trimester

*APAP —> preferred for pregnancy

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24
Q

Dipyrimadole MOA?

A
  1. Stimulates PGI2 synthesis
  2. Stimulates cAMP
  3. Inhibits platelet aggregation
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25
Q

Dipyrimadole use?

A
  1. Combined with ASA to prevent CVA (ischemic)

2. Post-heart valve replacement thrombus prevention

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26
Q

Dipyrimadole SE’s?

A

Coronary steal phenomenon: unstable angina patients

Caution when used with anticoagulants

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27
Q

Aggrenox (ASA and Dipyridamole) - use?

A

Reduce risk of stroke in pt’s who have already experienced TIA or CVA

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28
Q

Aggrenox - CI’s?

A

Reye’s Syndrome

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29
Q

Cilostazol - MOA?

A

PDE3 inhibitor

Inhibits cAMP breakdown

Inhibits platelet aggregation

Vasodilatory in vascular smooth muscle

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30
Q

Cilostazol - use?

A

Intermittent claudication (muscle pain) symptom relief

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31
Q

Cilostazol - SE’s?

A

Cardiac (palpitation, tachyarryhthmias)

HA

Diarrhea

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32
Q

Cilostazol - CI’s?

A

BLACK BOX: HF

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33
Q

Vorapaxar - MOA?

A

PAR-1 antagonist

Inhibits thrombin-induced platelet aggregation

Does NOT inhibit platelet aggregation via ADP, vWF, etc

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34
Q

Vorapaxar - use?

A

Prevention of thrombotic events in pt’s with hx of MI or PAD

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35
Q

Vorapaxar - CI’s?

A

Not for use in ACS

Avoid use with strong CYP3A inhibitors or inducers

Avoid use with anticoagulants

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36
Q

Clopidogrel (Plavix) and Prasugrel (Effient) - MOA?

A

IRREVERSIBLY inhibits ADP from binding to P2Y12 receptor - leads to inhibition of GPIIb/IIIa expression (required for platelet aggregation)

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37
Q

Ticagrelor - MOA?

A

REVERSIBLY inhibits ADP from binding to P2Y12 receptor - leads to inhibition of GPIIb/IIIa expression (required for platelet aggregation)

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38
Q

Clopidogrel/Prasugrel - use?

A

Prevention of atherosclerotic events for pt’s with:
Recent stroke or MI, or PAD
Post-PCI patients

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39
Q

Ticagrelor - use?

A

ACS patients

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40
Q

Clopidogrel - active or prodrug?

A

Prodrug

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41
Q

Prasugrel- active or prodrug?

A

Prodrug

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42
Q

Ticagrelor - active or prodrug?

A

Active

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43
Q

Cangrelor - MOA?

A

Inhibits binding of ADP to P2Y12 receptor

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44
Q

Cangrelor - use?

A

Adjunct to PCI

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45
Q

Abciximab - MOA?

A

Monoclonal antibody GPIIb/IIIa receptor inhibitor

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46
Q

Abciximab - use?

A

Adjunct to PCI

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47
Q

Ebtifibatide - MOA?

A

GPIIb/IIIa receptor inhibitor - prevents binding of fibrin to GPIIb/IIIa, preventing platelet aggregation

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48
Q

Eptifibatide - use?

A

ACS, PCI

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49
Q

Tirofiban - MOA?

A

GPIIb/IIIa receptor inhibitor - prevents binding of fibrin to GPIIb/IIIa, preventing platelet aggregation

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50
Q

Tirofiban - use?

A

ACS, PCI

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51
Q

Eptifibatide and Tirofiban - considerations?

A

Renal insufficiency

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52
Q

Pharmacological management of unstable angina?

A
  1. Antiplatelet (P2Y12, GP)

2. Anticoag (UFH, LMWH, etc)

53
Q

Clinical use for anticoagulants?

A

Reduce existing thrombi expansion (STEMI, CVA, PE) and prevent formation of new thrombi (a-fib)

54
Q

What does UFH complex with to accelerate anticoagulation in the body?

A

Antithrombin III

55
Q

Which factor(s) does UFH bind to and inhibit?

A

IIa (thrombin)

Xa

56
Q

Onset of UFH?

A

Minutes

57
Q

Adverse reactions UFH?

A

Heparin-Induced Thrombocytopenia with paradoxical embolization

58
Q

Antidote for UFH?

A

Protamine sulfate

59
Q

UFH - CI’s?

A
  1. Hx of HIT
  2. Hypersensitivity
  3. Recent surgery (increased bleeding risk)
  4. Intracranial hemorrhage
60
Q

What laboratory test do we use to evaluate UFH response and adjust dosage (titrate to effect)?

A

Activated partial thromboplastin time(aPTT)

61
Q

An aPTT of longer than ___ may indicate bleeding:

A

70 seconds

62
Q

UFH - pregnancy category?

A

C (recommended for certain situations)

63
Q

LMWH - MOA?

A

Similar to heparin - binds anti-thrombin III, but only inactivates Xa rather than IIa AND Xa

64
Q

Which is more preferable in pregnancy - UFH or LMWH?

A

LMWH

65
Q

Enoxaparin - uses?

A
  1. DVT prophylaxis
  2. Unstable angina
  3. STEMI
66
Q

Dalteparin - uses?

A
  1. DVT prophylaxis

2. Preferred Rx for tx of recurrent VTE in cancer patients

67
Q

Monitoring considerations for LMWH?

A

Not necessary to monitor aPTT, but LMWH does have a longer half-life than UFH

68
Q

LMWH advantages over UFH?

A
  1. No need to monitor aPTT
  2. Less incidence of HIT
  3. Longer T1/2
  4. Pregnancy-safe
69
Q

Protamine sulfate - CI’s?

A

Fish allergy

70
Q

Fondaparinux - MOA?

A

Binds with anti-thrombin III, SELECTIVELY inhibiting Xa

71
Q

Fondaparinux - use?

A
  1. DVT prophylaxis
  2. Acute DVT (w/ warfarin)
  3. Acute PE (w/ warfarin)
72
Q

Fondaparinux - black box warning?

A

Spinal/Epidural hematoma

73
Q

Fondaparinux - AE?

A

Less likely to cause HIT, but still CI in pt’s with thrombocytopenia (<100K)

74
Q

Warfarin - MOA?

A

Inhibits Vitamin K epoxide reductase (in the liver), reducing the available Vitamin K for cofactors II, VII, IX, and X, as well as Proteins C and S

75
Q

Warfarin - uses?

A
  1. DVT, PE, a-fib - treatment and prophylaxis
  2. Post-MI / CVA
  3. Protein C and S deficiency
76
Q

What factor is “half-life” of warfarin actually based on?

A

The lifespan of the Vitamin K-dependent clotting factors and Protein C and S

First to die - VII (6 hours)
Last to die - II (3 days)

77
Q

Warfarin monitoring?

A

PT (prothrombin time)

INR (international normalized ratio)

78
Q

Target INR for DVT prophylaxis?

A

2 to 3

79
Q

Target INR for artificial valve thrombosis prevention?

A

2.5 to 3.5

80
Q

Warfarin in pregnancy?

A

Category X

81
Q

Warfarin AE?

A

Purple Toe syndrome (from cholesterol microembolization)

82
Q

Foods that can disrupt target warfarin therapy?

A

Vitamin-K heavy foods (mostly dark, leafy-green veggies)

83
Q

Actions to take if INR is above target but less than 4.5?

A

Skip a dose

84
Q

Actions to take if INR is 4.5 to 10?

A

Skip 1 to 2 doses, monitor, lower dose

85
Q

Actions to take if INR is >10?

A

Hold warfarin and give Vit-K

86
Q

If major bleeding associated with Warfarin use is present?

A

PCC (prothrombin complex concentrate)

Or

FFP (fresh frozen plasma)

87
Q

Phytonadione - MOA?

A

Fat soluble Vitamin K

88
Q

Phytonadione - use?

A

Warfarin reversal agent

89
Q

Bivalirudin - action and indication?

A

Direct thrombin inhibitor (factor IIa) // patients at risk for HIT

90
Q

Bivalirudin - clearance?

A

Renal

91
Q

Argatriban - MOA and use?

A

Direct thrombin inhibitor, used for treatment or prevention of HIT

92
Q

Argatroban - clearance?

A

Liver

93
Q

Dabigatran (Pradaxa) - MOA and use?

A

Direct thrombin inhibitor, DVT/PE/afib

94
Q

Dabigatran (Pradaxa) - metabolized by?

A

P-glycoprotein

95
Q

Dabigatran - pregnancy?

A

C

96
Q

Dabigatran advantages over warfarin?

A
  1. Monitoring not required
  2. Lower risk of brain bleed
  3. More effective at preventing CVA
97
Q

Dabigatran disadvantages over warfarin?

A
  1. Renal elimination
  2. Risk for dyspepsia
  3. Twice daily dosing
98
Q

Idarucizumab (Praxbind) - MOA and use?

A

Monoclonal Ab fragment - binds dabigatran, neutralized anticoagulant effect

Reverses dabigatran effects

99
Q

Suffix for direct oral factor Xa inhibitors?

A

-Ban (banning the factor Xa fox)

100
Q

Oral direct Xa inhibitors - MOA?

A

Selectively blocks Xa, preventing conversion of prothrombin to thrombin

101
Q

Major disadvantage for oral direct Xa inhibitors?

A

No antidote

102
Q

Rivaroxaban and Apixaban - caution in which population?

A

Liver disease

103
Q

Edoxaban - caution in which population?

A

Liver disease AND renal insufficiency

104
Q

Which oral Xa direct inhibitor is best for pregnancy?

A

Apixaban

105
Q

Fibrinolytics - MOA?

A

Activates conversion of plasminogen to plasmin that hydrolyzes (cleaves) fibrin

106
Q

What classes are co-administered along with fibrinolytics?

A

Antiplatelet

Antithrombotic

107
Q

Examples of two thrombolytic enzymes?

A

Streptokinase

Urokinase

108
Q

Examples of tissue plasminogen activators?

A

Alteplase
Reteplase
Tenecteplase

109
Q

Which TPA’s are only for STEMI?

A

Reteplase

Tenecteplase

110
Q

Absolute contraindications for fibrinolytics? (Pneumonic - BD-HINT)

A
  1. Bleeding (any active bleeding)
  2. Dissection (aortic)
  3. Hemorrhagic CVA (ever)
  4. Ischemic CVA (< 3 months ago)
  5. Neoplasm (cranial)
  6. Trauma (head/face < 3 months ago)
111
Q

Criteria for “massive” PE?

A
  1. SBP < 90 x15 minutes
  2. Loss of palpable pulse
  3. Requiring inotropic support
112
Q

Alteplase - use?

A

CVA, STEMI, PE

113
Q

Cryoprecipitate - what is it, what is it used for?

A

Plasma protein from whole blood, containing clotting factors, used to treat acute bleeding problems

114
Q

Prothrombin Complex Concentrate (PCC) - what is it, what is it used for?

A

Blood coagulation factors, used to reverse effects of the “-bans” (Xa inhibitors) (bc there’s no actual antidote for the -ban’s)

115
Q

Tranexamic Acid - MOA?

A

Displaces plasminogen from fibrin, resulting in inhibition of fibronolysis (promotes clotting)

116
Q

Tranexamic Acid - AE?

A

Severe thrombotic events

117
Q

Trsanexamic acid - elimination?

A

Renal

118
Q

Tranexamic acid - caution with pt’s with…?

A
  1. Hx thrombotic events

2. Renal dysfunction

119
Q

What are three essential nutrients for bone marrow hematopoiesis?

A
  1. Iron
  2. Vitamin B12
  3. Folic Acid
120
Q

What percentage of orally administered iron actually gets absorbed?

A

25%

121
Q

Antidote for iron overdose?

A

Deferoxamine - iron-chelating agent

122
Q

What is required in the stomach for B12 absorption?

A

Intrinsic factor

123
Q

Hepatic stores of Vit-B12 can last how long?

A

Up to 5 years

124
Q

Folate, Folic Acid, Vitamin B9 - required for…?

A

DNA synthesis

125
Q

Pt’s that may need folic acid:

A
  1. Pregnancy
  2. Alcoholics
  3. Hemolytic Anemia
  4. Dialysis
126
Q

Leucovorin?

A

Folic acid antagonist (OD)

127
Q

Where is eryhtropoietin produced?

A

Renal peritubular cells

128
Q

Epoetin Alfa and Darbapoetin Alfa - MOA and use?

A

Increase the rate of proliferation and differentiation of erythroid precursor cells in the bone marrow

Used for anemia of chronic renal failure, chemotherapy-induced anemia

129
Q

Filgrastim and Sargramostim - MOA and use?

A

Colony stimulating factors that cause the production, maturation, and activation of neutrophils

Chemotherapy, leukemia, stem cell transplant

Sophomore - Pharm test 3 (7 decks)

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