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Pharmacology > Week 1: Anticoagulation > Flashcards

Week 1: Anticoagulation Flashcards

1
Q

Coag factors are _____

A

enzymes

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2
Q

Where are coagulation factors made?

A

the liver

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3
Q

What does the final pathway result in? (2)

A

conversion of prothrombin (II) to thrombin

catalyzes the conversion of fibrinogen to fibrin

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4
Q

What does fibrin activate in the fibrinolytic system?

A

plasmin

tissue plasminogen activator (t-PA)

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5
Q

Balance is maintained by homeostasis of what? (2)

A

procoagulants (coag factors)

endogenous anticoagulants

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6
Q

What is the endogenous anticoagulant that is important for warfarin dosing?

A

Proteins C &S

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7
Q

What is the endogenous anticoagulant important for heparin dosing?

A

Antithrombin III

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8
Q

The fibrinolytic system degrades _____.

A

fibrin

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9
Q

What is the result of the fibrinolytic system? (3)

A

Fibrin split products (FSP)
AKA: Fibrin degregation products (FDPs)
Fibrin Dimers (D-Dimers)

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10
Q

Increased levels of the fibrinolytic system, suggest what?

A

presence of thrombi (think DVT)

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11
Q

What are consequences of venous thrombi? (5)

A 
DVT 
"Red Thrombus"
AKA: "Venous Stasis" thrombi
VTE (Venous thromboembolism)
Complication= Pulmonary embolus
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12
Q

What are the consequences of arterial thrombi? (3)

A

platelet driven
“white thrombus”
complication= stroke, MI

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13
Q

What are the risk factors of a partial thrombosis?

A 
surgery
cancer
immobility
varicose veins
pregnancy
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14
Q

What is a potential complication of anticoagulation agents?

A

Bleeding

NOT allergy! extension of their MOA

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15
Q

What is heparin’s mechanism of action?

A

heparin binds to antithrombin III (ATIII)

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16
Q

Heparin requires the binding of what for its MOA?

A

binding requires specific pentasaccharide sequence

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17
Q

What is heparins limitation?

A

The heparin AT complex inhibits only soluble thrombin not fibrin-bound thrombin

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18
Q

What is a heterogenous mix of sulfated glycosaminoglycans?

A

unfractionated heparin (UFH)-1

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19
Q

What percent of UFH molecules have the pentasaccharide?

A

1/3

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20
Q

UFH is only effective on _____ _____.

A

soluble fibrin not clot-bound fibrin

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21
Q

UFH prevents the growth/propagation of what?

A

the thrombus

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22
Q

UFH allows the _____ ___ to degrade the clot.

A

fibrinolytic system

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23
Q

How is UFH measured?

A

measured by the activated partial thromboplastin time (aPTT)

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24
Q

What is used for DVT prophylaxis- SubQ Heparin?

A

UFH

5,000 units SubQ every 12 hours or every 8 hours

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25
Q

What is a risk of IV UFH?

A

risk of HIT

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26
Q

What are the advantages of UFH? (6)

A 
immediate anticoagulation
measured by aPTT
effects reversed by protamine
prevents propagation of clot
may be given subQ for prophylaxis
Usually done by pharmacy dosing service
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27
Q

What are the disadvantages of UFH? (5)

A 
Non-linear kinetics
frequent lab tests required 
Increased risk of bleeding
Potential for life threatening immune mediated thrombocytopenia (HIT)
minimal effect on interior of clot
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28
Q

When is protamine sulfate used? What is its MOA?

A

used to reverse UFH

combines with strongly acidic heparin

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29
Q

What are the 2 types of HIT?

A

HIT (I) non immune

HIT (II) Immune

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30
Q

What is significant about HIT I (non-immune)?

A

OK
10% of patients
transient due to clumping of platelets (artifact)
happens immediately

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31
Q

What is significant about HIT-II (immune)?

A 
very bad
< 3% of patients
seen after 5-10 days of heparin
Platelet count falls by >50%
immune mediated by anti-platelet factor 4 (test for PF4)
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32
Q

What is significant about low molecular weight heparin?

A

more favorable benefit/risk ratio
more predictable dose response ratio
weight based dosing
less risk of HIT (if started initially)

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33
Q

How is fractionated (low MW) heparin administered?

A

Sub Q

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34
Q

What is a example of a LMWH?

A

enoxaparin (Lovenox)

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35
Q

What are the indications for LMWH? (4)

A

ACS treatment
DVT
PE
VTE prophylaxis in high risk populations

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36
Q

What is the dose of enoxaparin (lovenox) for acute DVT with or without PE INPATIENT?

A

1mg/kg/dose subQ every 12 hours or 1.5 mg/kg subQ daily

37
Q

What is the dose of enoxaparin (lovenox) for acute DVT with our without PE OUTPATIENT?

A

1mg/kg/dose subQ every 12 hours

38
Q

What is an example of a vitamin K antagonist?

A

warfarin

39
Q

What is the MOA of warfarin?

A

inhibits post-translational carboxylation of coagulation factors II (prothrombin), VII, IX & X
inhibits two vitamin K sensitive synthetic enzymes

40
Q

How is warfarin reversed?

A

pharmacological doses of vit K (phytonadione;Mephyton)

41
Q

What are the doses of vit K (phytonadione;Mephyton) to reverse warfarin?

A

2.5-10mg po (5mg tablet)

1-10mg IVPB (rare risk of anaphylaxis with rapid infusion)

42
Q

Warfarin is often started with ______, which is Dcd when warfarin is therapeutic?

A

Heparin

43
Q

How long does it take for full anticoagulation with warfarin?

A

5-7 days

44
Q

How can you measure the effects of warfarin?

A

PT & INR

45
Q

What is the therapeutic ranges of INR for AFIB, DVT and PE when on warfarin?

A

2-3

46
Q

What is the therapeutic range with mechanical heart valve when on warfarin?

A

2.5-3.5

47
Q

How long does it take for each dose of warfarin to take effect?

A

48 hours

48
Q

What is a complication of starting 10mg daily of warfarin?

A

warfarin-induced skin necrosis

49
Q

Drugs that inhibit ____ increase INR and increase ______.

A

CYP2C9;risk of bleeding

50
Q

Drugs that induce CYP2C9, ______ INR and ____ risk of thrombosis

A

decrease INR

INCREASE the risk of thrombosis

51
Q

What is an example of a medication that inhibits CYP2C9?

A

bactrim and flagyl

52
Q

What is an example of a mediation that induces CYP2C9?

A

contraceptives (estrogens/progestins)

53
Q

What are sources of high dietary folate?

A

beef, pork liver
green tea
leafy green vegetables
spinach

54
Q

What is a synthetic pentasaccharide that is mainly renally eliminated?

A

anti-factor Xa inhibitors

55
Q

When are anti-factor Xa inhibitors contraindicated?

A

CrCl <30

56
Q

What is the unlabeled use of anti-factor Xa inhibitors ?

A

DVT patients with h/o HIT

57
Q

What is an example of anti-factor Xa inhibitors?

A

fondaparinux (Atristra) profiled syringes

58
Q

What is an oral direct Xa inhibitor?

A

Xarelto (rivaoxaban)

59
Q

What is a benefit of xarelto (rivaroxaban)?

A

no lab monitoring

60
Q

What is the recent reversal agent of xarelto (rivaroxaban)??

A

Aadexant alfa

61
Q

What is the most common adverse effect of xarelto (rivaroxaban)?

A

bleeding

“>5%”

62
Q

What are the types of direct thrombin inhibitors (DTIs)?

A

bivalent and univalent

63
Q

What are examples of bivalent DTIs? (3)

A

lepirudin (refludan)
bivalrudin (angiomax)
desirudin (iprivask)

64
Q

What are examples of univalent DTIs?

A

Argatroban

Dabigatran (pradaxa)

65
Q

What is significant about DTIs?

A

may be used in patients with h/o HIT II

66
Q

What DTI is given in patients with HIT and poor renal function (not really eliminated), can be given IV and monitored with PTT?

A

Argatroban

67
Q

What DTI was withdrawn in AC in 2006, many patients developed hepatotoxicity after stopping the drug?

A

Ximelagatran (Exanta)

68
Q

What was the second oral DTI that requires no lab testing and has a new reversal agent (2015)?

A

Dabigatran etexilate (pradaxa)

69
Q

What is the Dabigatran etexilate (pradaxa) reversal agent?

A

Idarucizumab (Praxbind)

70
Q

What medication is a humanized monoclonal antibody that binds to Pradaxa and its acylglucuronide metabolites?

A

Idarucizumab (Praxbind)

71
Q

What is the dosage of Idarucizumab (Praxbind)?

A

two consecutive 2.5 gram doses IV

$3,500 for 5 gram dose

72
Q

What medication is a factor Xa inhibitor reversal agent?

A

Aadexant alfa

73
Q

What medication is a decoy protein that corrects apixaban, rivaroxaban, edoxaban, enoxaparin or fondaparinux?

A

Aadexant alfa

74
Q

What are types of anti platelet drugs?

A

glycoprotein IIb/IIIa Inhibitors

ADP receptor antagonists

75
Q

What medication is a glycoprotein IIb/IIIa Inhibitors that can be administered IV :ACS or PCI and or stent?

A

eptifibatide (integrilin)

76
Q

What medication is a monoclonal antibody (human/murine) that has numerous sin effects and therefore minimally used?

A

abciximab (RepPro)

77
Q

What is the blackbox warning of Ticlopidine?

A

neutropenia
agranulocytosis
thrombotic thrombocytopenia purpura
aplastic anemia

78
Q

When is Ticlopidine (Ticlic) used?

A

reserved for patients intolerant to aspirin or those who failed aspirin therapy

79
Q

What is a prodrug converted to unidentified active metabolite that ultimately prevents platelet aggregation?

A

clopidogrel (plavix)

80
Q

What is the drug interaction with clopidogrel (plavix)?

A

decreased activity with PPIs via CYP2C19 inhibition

increased risk of restenosis while on PPIs

81
Q

What antiplatlet medication is more effective than clopidogrel or ticlopidine and has less inhibition by PPIs ?

A

Prasugrel (Efient)

82
Q

What is a platelet antagonist that inhibits platelet aggregation by acetylation of ADP receptor that lasts the life of the platelet?

A

Aspirin

83
Q

What are the adverse effects of asa that are weighted against the benefits?

A

GI bleed and tinitis

minimal at low doses

84
Q

What is the MOA of dipyridamole (persantine)?

A

platelet aggregation inhibit and vasodilator

85
Q

When is dipyridamole (persantine) used?

A

with warfarin in patients with mechanical heart valved (rare)
Diagnostic agent in CAD (persantine stress test)

86
Q

What is an example of a tissue plasminogen activators (TPA)?

A

Alteplase (activase, cathflo)

87
Q

When is Alteplase (activase, cathflo) used?

A

lysis of coronary artery thrombi in AMI (less common)
management of ischemic stoke (more common)
lysis of occluded ports and catheters

88
Q

What is the stroke dose of Alteplase (activase, cathflo)?

A

load: 0.09 mg/kg over 1 minute (10% of total)

Followed by: 0.81 mg/kg CIV over 1 hour (90%)

Pharmacology (17 decks)

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