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

Antiplatelet, anticoagulant, & fibrinolytics Flashcards

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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
What are contraindications of ticagrelor?
hx of intracranial hemorrhage
26
What are indications for GPIIB/IIIA receptor antagonists?
percutaneous coronary intervention and acute coronary syndromes (not for long term use, all are IV!)
27
When should you be cautious with GPIIB/IIIA receptor antagonists?
renal dysfunction
28
What are contraindications for GPIIB/IIIA receptor antagonists??
- 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
29
What are ADRs of GPIIB/IIIA receptor antagonists?
abciximab (reopro): anaphylaxis, thrombocytopenia eptifibatide (integrillin) & tirofiban (aggrasat) anaphylaxis, thrombocytopenia, renal dysfunction
30
What's the MOA of dipyridamole?
inhibits platelet function by inhibiting adenosine uptake + cGMP phosphodiesterase activity (PDE3 inhibitor)
31
What are the indications of dipyridamole?
used w/ another agent -- - aspirin combo to prevent cerebrovascular ischemia - + warfarin for primary prophylaxis against thromboembolism w/ prosthetic heart valves - chemical stress tests
32
ADRs of dipyridamole?
headaches, GI distress, dizziness
33
What is the MOA of cilostazol (pletal)?
inhibition of phosphodiesterase II -- inhibits platelet function but also improves endothelial function
34
What is the indication for cilostazol (pletal)?
intermittent claudication during/after exercise usually
35
What are ADRs of cilostazol (pletal)?
headache, GI
36
What are interactions of cilostazol (pletal)?
high fat diet raises level, grapefruit
37
what's a CI of cilostazol (pletal)?
HF
38
Is the coagulation phase before or after the platelet phase ?
after
39
What are main uses of anticoagulants?
prevention of venous thromboembolism, stroke prevention in afib
40
What is Virchow's triad?
3 factors that contribute to blood clot formation: 1) endothelial injury 2) hypercoagulability 3) stasis
41
What are types of anticoagulants?
vitamin K antagonists, direct oral anticoagulants, heparin
42
What's the MOA of warfarin?
inhibits activation of vitamin K dependent clotting factors (VII, IX, X, II) as well as protein C+S
43
What are indications for warfarin?
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
What are ADRs for warfarin?
bleeding, teratogenic, skin necrosis
45
What are CIs of warfarin?
hemorrhagic tendencies, unsupervised/noncompliant patients, pregnancy/BF, alcoholism
46
What's the goal for warfarin INR range?
2-3
47
What are reversal agents of warfarin?
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
What drug interactions should you be aware of with warfarin and increasing INR?
**amiodarone**, fluoroquinolone abx, metronidazole, azole antifungals, bactrim, macrolide (azithro), tamoxifen
49
What interactions should you be aware of with warfarin and decreasing INR?
barbiturates, rifampin, cholesytramine
50
What is the MOA of direct factor Xa inhibitors (direct oral anticoagulants)?
selectively and reversibily to clotting factor Xa
51
What are examples of meds in direct factor xa inhibitors?
rivaroxaban (xarelto) and apixaban (eliquis)
52
What are indications of direct oral anticoagulants/direct factor Xa inhibitors?
treatment and 2ndary prevention of DVT and PE 1 prevention of DVT and PE in nonvalvular afib, postop thromboprophylaxis (knee and hip surgery)
53
What advice should you give for rivaroxaban (xarelto), a direct oral anticoagulant/direct factor Xa inhibitor?
take w/ food for doses >10, metabolized by 3A4 and p-glycoprotein avoid in severe renal and hepatic impairment
54
What should you consider with apixaban (eliquis), a direct oral anticoagulant/direct factor Xa inhibitor?
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
What to consider with direct factor Xa inhibitors?
renal impairment, abrupt discontinuation = risk of thrombotic events, epidural + spinal hematoma can occur in patients receiving neuraxial anesthesia or undergoing spinal puncture
56
What are parenteral direct thrombin inhibitors (DOACs)?
bivalirudin (angiomax) - percutaneous coronary intervention argatroban (acova) - HIT (**heparin-induced thrombocytopenia**)
57
What are oral direct thrombin inhibitors (DOACs)?
dabigatran (pradaxa) - reduction of stroke + systemic embolism risk in patients w/ nonvalvular afib DVT and PE treatment + prevention Postop thromboprophylaxis
58
What are advantages to dabigatran (pradaxa)?
direct thrombin inhibitor! no routine monitoring, doesn't interact with CYP450, rapid onset and offset
59
What are disadvantages to dabigatran (pradaxa)?
renal adjustments, black box warnings (spinal/epidural hematomas, abrupt discontinuation)
60
What are the reversal agents for warfarin?
oral/parenteral v K (phytonadione), FFP, clotting factors
61
What are the reversal agents for DOAC?
andexxa (coag factor Xa)
62
What are the reversal agents for dabigatran?
idarucizumab
63
What are the pros and cons of warfarin?
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
What are the pros and cons of newer oral anticoagulants (DOACs)?
pros; rapid onset/offset, no monitoring, fewer drug interactions cons: noncompliance, hard to monitor, antidotes pending
65
What are indirect thrombin inhibitors?
heparin low molecular weight heparins (LMWH) = enoxaparin (lovenox), dalteparin (fragmin), tinzaprin sythetic heparin = fondaparinux (arixtra)
66
What's the MOA of unfractionated heparin?
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
What's the MOA of low molecular weight + synthetic heparin?
binds to antithrombin but not fibrin, makes dosing more predictable
68
What are indications for indirect thrombin inhibs?
prophylaxis + tx of deep vein thrombosis, PE, thromboembolic comps ass w/ afib
69
What are indications for unfractionated heparin?
prevention of clotting in arterial and cardiac surgery, anticoagulant for extracorporeal circulation and dialysis procedures, maintain patency of IV devices
70
What are indications for low molecular weight heparin like enoxaparin, dalteparin, tinzaparin?
acute coronary syndromes (unstable angina, NSTEMI, STEMI, arrhythmia) preferred in trauma, oncology, pregnancy
71
How do you monitor unfractionated heparin?
aPTT or PTT aPTT for DOACs bc they can falsely elevate PTT NO RENAL DOSING
72
When should you monitor LMW heparin?
w/ renal insufficiency, obese, pregnant, underweight monitoring anti Xa units otherwise, monitor platelet count + signs of bleeding
73
How do you monitor fondaparinux heparin?
renal insufficiency, obese, pregnant, underweight -- anti Xa units otherwise, clinical signs of bleeding and platelet count
74
What are ADRs of indirect thrombin inhibitors?
bleeding, thrombocytopenia (immune response, 5-14d post therapy -- STOP agent! no platelet transplant! change to fondiparinux!
75
What are contraindications of indirect thrombin inhibitors?
HIT development, active bleeds, hemophilia
76
How do you reverse indirect thrombin inhibitors?
protamine sulfate
77
What are the MOAs of fibrinolytics?
fibrinolysis by binding to fibrin in a clot --> plasminogen to active plasmin clot busting!
78
What type of drug: alteplase, reteplase, tenecteplase
fibrinolytics
79
What are indications for fibrinolytics?
acute ischemic stroke, acute massive PE, ST-elevation MI
80
What are the indications for alteplase?
tissue plasminogen activator TPA TIA - w/n 3 hours of symptom onset, sometimes 4.5 for MI
81
What are contraindications for altepase?
-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
What about tenecteplase?
same indication/contraindications as altepase but with better adverse drug reaction panel, less bleeding, better outcomes, cheaper!

Clinical Pharmacology 2 (13 decks)

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