Medications for Thromboembolic Disorders, Angina and ACS

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Pharmacologic Approaches for thromboembolic Disorders

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Pharmacologic Approaches for thromboembolic Disorders

antiplatelet, anticlotting, thombolytics

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Drugs that interfere with platelet aggregation =

antiplatelet medications

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3

Drugs that interfering with the clotting cascade =

anticlotting medications, aka anticoagulants

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4

Drugs that lyse thrombi =

thombolytics

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5

Antiplatelet Agents / Anticoagulants:

Suppress thrombosis (thrombus formation). Do NOT "dissolve" clots

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6

Antiplatelet Agents Are used to prevent or manage conditions such as:

DVT, Atrial fibrillation sequelae, Hypercoagulable states, Supplement post-thrombolytic therapy or stent plcement

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Thrombolytics:

Lyse an existing thrombus

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8

Thrombolytics Are used to treat conditions such as:

STEMI, ischemic stroke, PE

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9

The P2Y12 receptor is the predominant __ receptor involved in the ADP-stimulated activation of the __ IIb/IIIa receptor

ADP, glycoprotein

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10

ASPIRIN blocks

COX-1

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11

CLOPIDOGREL blocks

P2Y12 receptor

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12

Aspirin Mechanism

Irreversible inhibitor of COX-1 function for the life of the platelet

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Platelets do not have a __ so they cannot make new COX -1

nucleus

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14

For the __ of the platelet (7-10 days) COX-1 cannot function

life

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15

No COX-1 --> no TxA2 produced via __ Cascade

AA

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16

Aspirin blocks production of __

TxA2

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17

Platelets have __ for pro-clotting signals

receptors

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18

Platelets secrete __-clotting substances - many of which they also have __ for

pro, receptors

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19

Aspirin class

Antiplatelet, NSAID

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Aspirin indication

Secondary prevention of MI and ischemic stroke. Acute MI

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21

Aspirin mechanism

antiplatelet; irreversibly inhibits COX (COX-1 > COX-2)

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22

Inhibition of prostacyclin (PGI2) occurs when __ is blocked

COX-2

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23

PGI2 inhibits platelets and __

vasodilates

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Inhibiting PGI2 would partially __ the benefits of aspirin therapy

offset

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25

if we keep the aspirin __-dose, we minimize the inhibition of __ , while still inhibiting TxA2

low, PGI2

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26

Aspirin adverse effects

bleeding

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Aspirin interactions

any combination of antiplatelet, anticoagulant and thrombolytic medications

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28

Aspirin In Acute MI: 325 mg of non-enteric coated aspirin should be

chewed if an MI is strongly suspected

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29

Avoid aspirin if __ is suspected, as it could be a __ stroke, and not ischemic

stroke, hemorrhagic

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30

Why 325 mg?

loading dose, minimize the size of the clot

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31

Clopidogrel Mechanism

blocks ADP receptor on platelets

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32

Clopidogrel (Plavix®) class

Antiplatelet; ADP receptor antagonist

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33

Clopidogrel (Plavix®) indication

ACS, prevent stroke, MI and death in patients with recent MI/stroke/PAD

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34

Clopidogrel (Plavix®) mechanism

antiplatelet; irreversible ADP receptor antagonist

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35

Clopidogrel (Plavix®) is what kind of drug

prodrug

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36

What converts the prodrug to its active form?

CYP2C19

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37

Clopidogrel (Plavix®) adverse effects

bleeding, dyspepsia, abdominal pain, diarrhea, rash

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38

Clopidogrel (Plavix®) interactions

PPIs that inhibit CYP2C19, Cannabis also inhibits CYP2C19

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39

Poor metabolizers will get __ or __ benefit from clopidogrel

little, no

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40

Ultra-rapid metabolizers may experience more __ effects, including bleeding, from Clopidogrel

adverse

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41

Anticoagulants are __ Alert Medications

High

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42

In high-alert meds, the consequences of an error are clearly more __ to patients

devastating

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43

warfarin prevents regeneration of active Vitamin __

K

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44

active Vitamin K, necessary to make these 4 factors __ and __

activated, functional

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45

Warfarin (Coumadin®) class

Anticoagulant; Vitamin K Antagonist

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46

Warfarin (Coumadin®) indication

prevention of thrombosis associated with DVT/PE, prosthetic valves, atrial fibrillation. Tx of DVT/PE

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47

Warfarin (Coumadin®) mechanism

anticoagulant; prevents active Vitamin K regeneration which reduces levels and functionality of activated vitamin-K-dependent clotting factors

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48

Warfarin (Coumadin®) is how protein bound?

99%

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49

How long does Warfarin (Coumadin®) take to become effective?

several days

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50

What is the specific enzyme that Warfarin (Coumadin®) inhibits?

VKORC1

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51

The Warfarin (Coumadin®) process occurs in what organ?

liver, in hepatocytes

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52

Warfarin (Coumadin®) 2 genes that may affect metabolism

VKORC1 or CYP2C9

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53

Warfarin (Coumadin ®) adverse effects

bleeding

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54

Warfarin (Coumadin ®) contraindicated in

pregnancy

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55

Warfarin (Coumadin ®) interactions

antiplatelet, anticoagulants, vitamin K, ANTIBIOTICS

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56

Warfarin (Coumadin ®) antidote

Vitamin K, 4F-PCC

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57

Warfarin Patient & Family Teaching: INR

get checked at frequency recommended by provider

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58

Warfarin Patient & Family Teaching: avoid other drugs that

increase bleeding risk

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Warfarin Patient & Family Teaching: tell other providers (including dentist)

that you are taking warfarin

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60

Warfarin Patient & Family Teaching: safety precautions to avoid

falls, cuts, bruises

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Warfarin Patient & Family Teaching: Food that contain vitamin K

maintain a consistent intake

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62

Warfarin Patient & Family Teaching: wear a

medical alert bracelet

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63

Heparin and enoxaparin increase activity of

antithrombin, which inhibits thrombin (Factor IIa) and Factor Xa

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Enoxaparin preferentially inactivates

Factor Xa

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65

Heparin (aka Unfractionated Heparin) class

Anticoagulant; unfractionated heparin (UFH)

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66

Heparin (aka Unfractionated Heparin) indication

treatment/prevention of thrombosis, prevention of postop venous thrombosis, extracorporeal circulation, dialysis

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67

Heparin (aka Unfractionated Heparin) mechanism

anticoagulant; increases antithrombin activity 1000x

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68

Heparin binds antithrombin which then binds and inactivates

Factor Xa

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69

Does Factor Xa come into direct physical contact with heparin molecule?

no

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70

Antithrombin also binds and inactivates __/thrombin but IIa must also come into direct __ contact with heparin to be inactivated

IIa, physical

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71

Heparin adverse effects

bleeding, heparin‐induced thrombocytopenia (HIT)

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72

Heparin interactions

antiplatelet, anticoagulant medications

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73

Heparin monitor

aPTT

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74

Heparin antidote

Protamine sulfate

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75

Heparin-induced thrombocytopenia (HIT)

Prothrombotic disorder caused by formation of antibodies to complexes of platelet factor 4 and heparin

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76

In HIT: The antibodies bind to the PF4-heparin complexes on quiescent platelet surface and induce

platelet activation

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77

In HIT: The activated platelets increase the __ and surface expression of __

release, PF4

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78

In HIT: this creates

a positive feedback loop in which further release of PF4 promotes further platelet activation

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79

In HIT: Platelet activation causes

release of procoagulant platelet microparticles, thrombosis, platelet consumption, and eventual thrombocytopenia

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80

In HIT: Greatly increased generation of __, activation of inflammatory cells, and endothelial __ and activation follow

thrombin, injury

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81

HIT: can cause both

venous and arterial thromboses, with devastating results

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82

Enoxaparin (Lovenox®) (Low Molecular Weight Heparin) class

Anticoagulant; low molecular weight heparin (LMWH)

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83

Enoxaparin (Lovenox®) indication

treatment and prevention of DVT, ischemic complications of acute MI, post-thrombolysis

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84

Enoxaparin (Lovenox®) mechanism

anticoagulant; low-molecular weight heparin - increases anti-thrombin activity. Preferentially inactivates Factor Xa

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85

LMWH is much shorter in __ than UFH

length

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86

Enoxaparin (Lovenox®) adverse effects

bleeding

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Enoxaparin (Lovenox®) interactions

antiplatelet agents, other anti-coagulants

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88

Enoxaparin (Lovenox®) antidote

Protamine sulfate

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89

Dabigatran Mechanism of Action

directly inhibits thrombin, preventing conversion of fibrinogen to fibrin

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90

By inhibiting thrombin, this prevents activation of Factor __ which normally causes fibrin __

VIII, crosslinking

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91

Dabigatran Etexilate (Pradaxa®) class

Anticoagulant; direct thrombin inhibitor

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92

Dabigatran Etexilate (Pradaxa®) indication

prevention of systemic embolism and stroke in patients with atrial fibrillation, DVT/PE treatment and prophylaxis

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93

Dabigatran Etexilate (Pradaxa®) mechanism

anticoagulant; direct thrombin inhibitor. Binds to free thrombin and thrombin bound to clots

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94

Dabigatran Etexilate (Pradaxa®) is what kind of drug

prodrug; active in plasma and liver

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95

Dabigatran Etexilate (Pradaxa®) contraindicated in eGFR

less than 30

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96

Dabigatran Etexilate (Pradaxa®) adverse effects

bleeding, gastritis‐like complaints

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97

Dabigatran Etexilate (Pradaxa®) interactions

P-glycoprotein inhibitors or inducers, anti-coagulants

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98

Dabigatran Etexilate (Pradaxa®) contraindicated if active __ or __ prosthetic heart valve

bleeding, mechanical

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99

P-glycoproteins pump drugs __ of cells; __ drug absorption

out, decreases

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100

P-glycoprotein pumps Dabigatran Etexilate back into the __

intestine

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