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Clinical Pharmacology 2 > Antiplatelet, anticoagulant, & fibrinolytics > Flashcards

Antiplatelet, anticoagulant, & fibrinolytics Flashcards

1
Q

What are antiplatelet drug used for?

A

prevention of arterial thrombosis and for treatment of an existing clot like mechanical heart valves, afib, pad, essential thrombocytopenia

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2
Q

What does aspirin do?

A

irreversibly inhibits COX-1, reducing thromboxane A2 production

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3
Q

What do ADP or P2Y12 inhibitors like clopidogrel or ticagrelor do?

A

inhibit P2y12 receptor, blocking aDP induced platelet aggregation

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4
Q

What do GPIIb/IIIa inhibitors llike abciximab, eptifibatide do?

A

block GPIIb/IIIa receptors, preventing platelet fibrinogen binding and blocking platelet aggregation

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5
Q

What do dipyridamole and cilostazol do?

A

inhibit phosphodiesterase + adenosine uptake, increasing cAMP, preventing platelet activation

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6
Q

What’s the primary prevention of MI and 2nd prevention of vascular events in patients with Hx?

A

aspirin

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7
Q

what are ADRs of aspirin?

A

bleeding, gastric or duodenal ulcers, hypersensitivity reactions, prolonging bleeding time

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8
Q

What are contraindications of aspirin?

A

hypersensitivity, Reye’s syndrome – liver swelling, brain swelling, diarrhea, vomiting, lethargy, 4-14

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9
Q

What are s/s of an aspirin overdose?

A

fever, tinnitus, vertigo, N/V/D, AMS, hyperventilation, arrhythmia

labs: respiratory alkalosis, anion-gap metabolic acidosis (lactic and ketoacids), hypokalemia, hypoglycemia

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10
Q

How do you dx an aspirin overdose?

A

salicylate level >40mg/dl

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11
Q

How do you treat an aspirin overdose?

A

stabilize with ABCs, GI decon w/ activated charcoal, K+ if hypokalemic, sodium bicarb to aklanilize plasma and urine, monitor renal level and dialyze if renal+AMS, acidemia, cerebral or pulmonary edema

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12
Q

Clopidogrel and prasgurel are ____ ADP/P2Y12 inhibitors, while tiagrelor is ____

A

irreversible, reversible

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13
Q

What are indications of clopidogrel (plavix)?

A

unstable angina, NSTEMI, STEMI, stroke, PAD
- loading dose before PcL, reaches full action at 2 hours

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14
Q

What are ADRs of clopidogrel?

A

thrombotic thrombocytopenia purpura (allergy sign), use caution w/ thrombocytopenia

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15
Q

What interactions does clopidogrel have (review!)?

A

2C19 inhibitors!
DI = omeprazole

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16
Q

If a patient has an allergy to aspirin, they can use ____

A

plavix

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17
Q

What’s a contraindication of clopidogrel?

A

active bleeding

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18
Q

What’s the preferred ADP or PY212 inhibitor in ACS and when strong antiplatelet action more potent and efficient?

A

prasgugrel (effient)

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19
Q

If bruising on aspirin, what do you do?

A

every other day

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20
Q

Prasugrel is a 2C19 ___

A

substrate

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21
Q

What are indications for prasugrel?

A

STEMI (superior), prevent stent thrombosis

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22
Q

What are contraindications of prasugrel?

A

history of TIA or stroke, Caution in elderly, approval for high risk only if DM or MI, low weight = reduced dose

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23
Q

What ADP or P2Y12 inhibitor is indicated in acute coronary syndrome in combo with aspirin and has a max dose of 100mg and is the only reversible?

A

ticagrelor (brilinta)

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24
Q

What interactions does ticagrelor (brilinta) have?

A

Is a CYP3A substrate – up to 5x increase of active metabolites w/ strong inhibitors (anti-fungal), can be given w/ moderate inhibitors (CCB)

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25
Q

What are contraindications of ticagrelor?

A

hx of intracranial hemorrhage

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26
Q

What are indications for GPIIB/IIIA receptor antagonists?

A

percutaneous coronary intervention and acute coronary syndromes (not for long term use, all are IV!)

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27
Q

When should you be cautious with GPIIB/IIIA receptor antagonists?

A

renal dysfunction

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28
Q

What are contraindications for GPIIB/IIIA receptor antagonists??

A
  • hypersensitivity to agent component
  • active internal bleeding or recent significant GI or GU w/n 6 months
  • hx of major bleeding w/n 30 days
  • severe uncontrolled HTN
  • major surgery or trauma in last 6 months
  • stroke in past 2 years, intracranial neoplasm, arteriovenous malformation, aneurysm, tumor
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29
Q

What are ADRs of GPIIB/IIIA receptor antagonists?

A

abciximab (reopro): anaphylaxis, thrombocytopenia

eptifibatide (integrillin) & tirofiban (aggrasat)
anaphylaxis, thrombocytopenia, renal dysfunction

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30
Q

What’s the MOA of dipyridamole?

A

inhibits platelet function by inhibiting adenosine uptake + cGMP phosphodiesterase activity (PDE3 inhibitor)

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31
Q

What are the indications of dipyridamole?

A

used w/ another agent –
- aspirin combo to prevent cerebrovascular ischemia
- + warfarin for primary prophylaxis against thromboembolism w/ prosthetic heart valves
- chemical stress tests

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32
Q

ADRs of dipyridamole?

A

headaches, GI distress, dizziness

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33
Q

What is the MOA of cilostazol (pletal)?

A

inhibition of phosphodiesterase II – inhibits platelet function but also improves endothelial function

34
Q

What is the indication for cilostazol (pletal)?

A

intermittent claudication during/after exercise usually

35
Q

What are ADRs of cilostazol (pletal)?

A

headache, GI

36
Q

What are interactions of cilostazol (pletal)?

A

high fat diet raises level, grapefruit

37
Q

what’s a CI of cilostazol (pletal)?

A

HF

38
Q

Is the coagulation phase before or after the platelet phase ?

A

after

39
Q

What are main uses of anticoagulants?

A

prevention of venous thromboembolism, stroke prevention in afib

40
Q

What is Virchow’s triad?

A

3 factors that contribute to blood clot formation:
1) endothelial injury
2) hypercoagulability
3) stasis

41
Q

What are types of anticoagulants?

A

vitamin K antagonists, direct oral anticoagulants, heparin

42
Q

What’s the MOA of warfarin?

A

inhibits activation of vitamin K dependent clotting factors (VII, IX, X, II) as well as protein C+S

43
Q

What are indications for warfarin?

A

prophylaxis and treatment of DVT and PE complications from valvular and nonvalvular afib
stroke prophylaxis in valvular and nonvalvular afib -
during cardioversion, rate control therapy, adjunct to reduce risk of systemic embolism after MI
need bridge w/ indirect thrombin inhibitor until appropriate INR range

44
Q

What are ADRs for warfarin?

A

bleeding, teratogenic, skin necrosis

45
Q

What are CIs of warfarin?

A

hemorrhagic tendencies, unsupervised/noncompliant patients, pregnancy/BF, alcoholism

46
Q

What’s the goal for warfarin INR range?

A

2-3

47
Q

What are reversal agents of warfarin?

A

vitamin K given when INR 4.5-10 or pre-surg

FFP = fresh frozen plasma or clotting factors, given if active bleeding on warfarin

48
Q

What drug interactions should you be aware of with warfarin and increasing INR?

A

amiodarone, fluoroquinolone abx, metronidazole, azole antifungals, bactrim, macrolide (azithro), tamoxifen

49
Q

What interactions should you be aware of with warfarin and decreasing INR?

A

barbiturates, rifampin, cholesytramine

50
Q

What is the MOA of direct factor Xa inhibitors (direct oral anticoagulants)?

A

selectively and reversibily to clotting factor Xa

51
Q

What are examples of meds in direct factor xa inhibitors?

A

rivaroxaban (xarelto) and apixaban (eliquis)

52
Q

What are indications of direct oral anticoagulants/direct factor Xa inhibitors?

A

treatment and 2ndary prevention of DVT and PE
1 prevention of DVT and PE in nonvalvular afib, postop thromboprophylaxis (knee and hip surgery)

53
Q

What advice should you give for rivaroxaban (xarelto), a direct oral anticoagulant/direct factor Xa inhibitor?

A

take w/ food for doses >10, metabolized by 3A4 and p-glycoprotein

avoid in severe renal and hepatic impairment

54
Q

What should you consider with apixaban (eliquis), a direct oral anticoagulant/direct factor Xa inhibitor?

A

metabolized by 3A4 and p-glycoprotein, avoid use in severe renal/hepatic impariment

ABCD
Age >80
Body mass <60kg
Creatinine >1.5
Do not give

55
Q

What to consider with direct factor Xa inhibitors?

A

renal impairment, abrupt discontinuation = risk of thrombotic events, epidural + spinal hematoma can occur in patients receiving neuraxial anesthesia or undergoing spinal puncture

56
Q

What are parenteral direct thrombin inhibitors (DOACs)?

A

bivalirudin (angiomax) - percutaneous coronary intervention
argatroban (acova) - HIT (heparin-induced thrombocytopenia)

57
Q

What are oral direct thrombin inhibitors (DOACs)?

A

dabigatran (pradaxa) - reduction of stroke + systemic embolism risk in patients w/ nonvalvular afib
DVT and PE treatment + prevention
Postop thromboprophylaxis

58
Q

What are advantages to dabigatran (pradaxa)?

A

direct thrombin inhibitor!
no routine monitoring, doesn’t interact with CYP450, rapid onset and offset

59
Q

What are disadvantages to dabigatran (pradaxa)?

A

renal adjustments, black box warnings (spinal/epidural hematomas, abrupt discontinuation)

60
Q

What are the reversal agents for warfarin?

A

oral/parenteral v K (phytonadione), FFP, clotting factors

61
Q

What are the reversal agents for DOAC?

A

andexxa (coag factor Xa)

62
Q

What are the reversal agents for dabigatran?

A

idarucizumab

63
Q

What are the pros and cons of warfarin?

A

pro - antidote, familiar, can use in renal/hepatic impairment
con - narrow theraputic indicators, affected by diet/other drugs, intensive monitoring
often required for mechanical heart valves due to risk of clot formation

64
Q

What are the pros and cons of newer oral anticoagulants (DOACs)?

A

pros; rapid onset/offset, no monitoring, fewer drug interactions
cons: noncompliance, hard to monitor, antidotes pending

65
Q

What are indirect thrombin inhibitors?

A

heparin
low molecular weight heparins (LMWH) = enoxaparin (lovenox), dalteparin (fragmin), tinzaprin
sythetic heparin = fondaparinux (arixtra)

66
Q

What’s the MOA of unfractionated heparin?

A

binds to enzyme inhib antithrombin III (AT) and inactivates factors IIa and Xa
also inhibits enzyme that acts on fibrin that causes clotting
binds to thrombin

67
Q

What’s the MOA of low molecular weight + synthetic heparin?

A

binds to antithrombin but not fibrin, makes dosing more predictable

68
Q

What are indications for indirect thrombin inhibs?

A

prophylaxis + tx of deep vein thrombosis, PE, thromboembolic comps ass w/ afib

69
Q

What are indications for unfractionated heparin?

A

prevention of clotting in arterial and cardiac surgery, anticoagulant for extracorporeal circulation and dialysis procedures, maintain patency of IV devices

70
Q

What are indications for low molecular weight heparin like enoxaparin, dalteparin, tinzaparin?

A

acute coronary syndromes (unstable angina, NSTEMI, STEMI, arrhythmia)
preferred in trauma, oncology, pregnancy

71
Q

How do you monitor unfractionated heparin?

A

aPTT or PTT
aPTT for DOACs bc they can falsely elevate PTT
NO RENAL DOSING

72
Q

When should you monitor LMW heparin?

A

w/ renal insufficiency, obese, pregnant, underweight monitoring anti Xa units

otherwise, monitor platelet count + signs of bleeding

73
Q

How do you monitor fondaparinux heparin?

A

renal insufficiency, obese, pregnant, underweight – anti Xa units

otherwise,
clinical signs of bleeding and platelet count

74
Q

What are ADRs of indirect thrombin inhibitors?

A

bleeding, thrombocytopenia (immune response, 5-14d post therapy – STOP agent! no platelet transplant! change to fondiparinux!

75
Q

What are contraindications of indirect thrombin inhibitors?

A

HIT development, active bleeds, hemophilia

76
Q

How do you reverse indirect thrombin inhibitors?

A

protamine sulfate

77
Q

What are the MOAs of fibrinolytics?

A

fibrinolysis by binding to fibrin in a clot –> plasminogen to active plasmin

clot busting!

78
Q

What type of drug: alteplase, reteplase, tenecteplase

A

fibrinolytics

79
Q

What are indications for fibrinolytics?

A

acute ischemic stroke, acute massive PE, ST-elevation MI

80
Q

What are the indications for alteplase?

A

tissue plasminogen activator TPA

TIA - w/n 3 hours of symptom onset, sometimes 4.5 for MI

81
Q

What are contraindications for altepase?

A

-Intracranial hemorrhage
* Subarachnoid hemorrhage
* Internal bleeding
* Stroke within the last three months
* Intracranial or intraspinal surgery within the last three months
* Serious head trauma within the last three months
* Intracranial neoplasms, arteriovenous malformations, or aneurysms
* Conditions that increase the risk of bleeding
* Currently severe uncontrolled hypertension

82
Q

What about tenecteplase?

A

same indication/contraindications as altepase but with better adverse drug reaction panel, less bleeding, better outcomes, cheaper!

Clinical Pharmacology 2 (4 decks)

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