Cardio Exam 2: Elsaid Fibrinolytics (DRUGS + PATHWAYS)

What initiates platelet activation in coronary artery disease (CAD)?

• _____ rupture → exposure of _____ and _____ → _____ adhesion and _____

Plaque, collagen, tissue factor, platelet, activation

Which enzyme converts arachidonic acid into thromboxane A2 (TxA2)?

COX-1

What two platelet activators are released from activated platelets?

Thromboxane A2 (TxA2) and ADP

Which receptor does ADP bind?

P2Y12 receptor

Which receptor does thromboxane A2 bind?

TP receptor

What is the final receptor activated before platelet aggregation occurs?

GP IIb/IIIa receptor

What molecule bridges adjacent platelets?

Fibrinogen

What is the final common pathway of platelet aggregation?

Fibrinogen binding GP IIb/IIIa receptors

Describe the platelet activation pathway from plaque rupture to clot formation.

• _____ rupture → _____ exposure → _____ → _____ → _____ → _____ → _____ → _____ expression → _____ → _____ → Arterial _____

Plaque, collagen, platelet activation, COX-1 activation, TxA2 production, ADP release, P2Y12 activation, GP IIb/IIIa, Fibrinogen bridge, Platelet aggregation, thrombus

What enzyme does aspirin inhibit?

COX-1

What is aspirin's MOA?

Irreversibly inhibits COX-1, which decreases thromboxane A2 synthesis

What platelet activator decreases when aspirin is given?

Thromboxane A2 (TxA2)

What adverse effects are dose-dependent with aspirin?

N/V and Tinnitus

What receptor does clopidogrel inhibit?

P2Y12 (ADP) receptor

Is clopidogrel reversible or irreversible?

Irreversible

Is clopidogrel a prodrug?

yes

Which enzyme activates clopidogrel?

CYP2C19

Why does clopidogrel have a black box warning?

Poor CYP2C19 metabolizers cannot adequately convert it into its active metabolite

What happens if clopidogrel is not activated?

• ↓ _____

• ↑ _____

Platelet inhibition and efficacy, clot risk

What is the most commonly used P2Y12 inhibitor?

Clopidogrel (Plavix)

Which P2Y12 inhibitor is more potent than clopidogrel?

Prasugrel

Which P2Y12 inhibitor is preferred in STEMI and diabetic patients?

Prasugrel

What is the major adverse effect of prasugrel?

Increased bleeding

Which patients are at highest bleeding risk with prasugrel?

Age >75 years and Weight <60 kg

What is a major contraindication to prasugrel?

History of stroke or TIA

Which oral P2Y12 inhibitor is reversible?

Ticagrelor

How does ticagrelor compare with clopidogrel?

More potent antiplatelet effect without a significant increase in bleeding

What major drug interactions occur with ticagrelor?

CYP3A4 inhibitors and inducers

Which P2Y12 inhibitor is IV only?

Cangrelor (Kengreal)

Is cangrelor reversible or irreversible?

Reversible

When is cangrelor commonly used?

During PCI as IV bolus and infusion

Match each P2Y12 inhibitor with reversible vs irreversible.
Irreversible

• _____

• _____

Reversible

• _____

• _____

Clopidogrel, Prasugrel, Ticagrelor, Cangrelor

Which receptor represents the final common pathway of platelet aggregation?

GP IIb/IIIa

What is the MOA of GP IIb/IIIa inhibitors?

Block fibrinogen binding to GP IIb/IIIa receptors, preventing platelet aggregation

Which drugs are GP IIb/IIIa inhibitors?

Abciximab, Tirofiban, and Eptifibatide

What receptor does Vorapaxar block?

PAR-1 receptor

What platelet activator is blocked by Vorapaxar?

Thrombin-mediated platelet activation

What is the mechanism of HIT?

Antibody-mediated platelet activation causing thrombosis despite thrombocytopenia

Which enzyme actually breaks down fibrin?

Plasmin

What is the MOA of alteplase?

• _____ converts _____ → _____ → _____

Recombinant tPA, plasminogen, plasmin, fibrinolysis

What receptor/substrate does alteplase bind first?

Fibrin within the thrombus

What are the major indications for alteplase?

Ischemic stroke, Pulmonary embolism, and Acute MI

What blood pressure is a C/I to alteplase?

Uncontrolled HTN >185/110 mmHg

What is the major contraindication to fibrinolytics?

Active internal bleeding

What is tenecteplase?

Alternative fibrinolytic to alteplase

Why is tenecteplase becoming more popular?

Easier dosing as a single IV bolus

Drug	Target
Aspirin
Clopidogrel
Prasugrel
Ticagrelor
Cangrelor
Abciximab
Eptifibatide
Tirofiban
Vorapaxar
Alteplase
Tenecteplase

ENTER AFTER EACH BOX

COX-1

P2Y12

P2Y12

P2Y12

P2Y12

GP IIb/IIIa

GP IIb/IIIa

GP IIb/IIIa

PAR-1

Plasminogen

Plasminogen

Which GP IIb/IIIa inhibitor is a monoclonal antibody?

Abciximab

Which GP IIb/IIIa inhibitor is marketed as Integrilin?

Eptifibatide

Which GP IIb/IIIa inhibitor is marketed as Aggrastat?

Tirofiban

What is the maximum dose of alteplase for ischemic stroke?

0.9 mg/kg (maximum 90 mg)

What is the dosing advantage of tenecteplase over alteplase?

Single IV bolus administration

Which antiplatelet drugs are commonly used during PCI?

Clopidogrel, Prasugrel, Ticagrelor, Cangrelor (IV only), and GP IIb/IIIa inhibitors (high-risk PCI)

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