Cardio Exam 2: Anti-Platelets + Fibrinolytics

Platelet Activation Pathway (ENTER AFTER EACH BULLET POINT):

• Disrupted _____ in the artery → exposure of collagen + tissue factor

• _____ adhere + become activated → activated platelets stimulate _____ → _____ converts arachidonic acid to TxA2 (_____)

• Activated _____ release _____ from their granules

• _____ binds to the _____ receptor on platelets and _____ binds to _____ receptors → Amplification of _____ → activation + increased expression of _____ receptors

• _____ bridges _____ receptors between adjacent platelets → _____ → formation of the _____ (arterial thrombus)

plaque

Platelets, COX-1, COX-1, thromboxane A2

platelets, TxA2 and ADP

ADP, P2Y12, TxA2, TP, platelet activation, GP IIb/IIIa

Fibrinogen, GP IIb/IIIa, platelet aggregation, platelet plug

Drug Targets Along Pathway:

• _____: inhibits COX-1 → ↓ _____ production.

• _____ (clopidogrel, prasugrel, ticagrelor, ticlopidine, cangrelor): block the _____ receptor → prevent _____-mediated platelet _____

• _____ (abciximab, eptifibatide, tirofiban): block _____ receptors → prevent _____-mediated platelet _____

• Vorapaxar: blocks the PAR-1 receptor → inhibits _____-induced platelet _____

Aspirin, TxA2, P2Y12 Inhibitors, P2Y12, ADP, activation, GP IIb/IIIa Inhibitors, GP IIb/IIIa, fibrinogen, aggregation, thrombin, activation

• Thromboxane A2 + ADP = _____

• GPIIb/IIIa → _____ (at the _____)

• Disrupted plaque in artery (CAD) → _____

within platelet, Receptor, surface of platelet, collagen anchored

KNOW IMAGE

Prevent _____

• _____

  • MOA: irreversibly inhibits COX-1 → inhibits TxA2 synthesis

  • _____ Dose-Dependent Effects: N/V, Tinnitus

Thromboxane A2, Aspirin (Salicylate), Aspirin

Prevent Thromboxane A2

• Aspirin (Salicylate)

  • MOA: _____ → inhibits _____

  • Aspirin Dose-Dependent Effects: _____, _____

irreversibly inhibits COX-1, TxA2 synthesis, N/V, Tinnitus

Prevent _____:

• _____ (Plavix)

  • Prodrug 

  • Came out 1st

  • Most extensively used P2Y12 inhibitor

  • Primary PCI → loading + daily maintenance dose

  • Affected by 2C19 inhibition (DDIs)

  • Black Box Warning regarding poor 2C19 metabolized

    • Decreased efficacy → lack of conversion to active metabolite → decreased platelet inhibition + efficacy

    • Inactive (GP IIb/IIIa) = no platelet aggregation

  • MOA: Irreversible inhibitor of the platelet P2Y12 (ADP) receptor → prevents ADP-mediated activation of GP IIb/IIIa

Activation, Clopidogrel

Prevent Activation:

• Clopidrogrel (Plavix)

  • _____ 

  • Came out _____

  • Most extensively used _____

  • Primary PCI → loading + daily maintenance dose

  • Affected by _____ inhibition (DDIs)

  • Black Box Warning regarding poor _____ metabolized

    • Decreased efficacy → lack of conversion to active metabolite → decreased platelet inhibition + efficacy

    • Inactive (_____) = no platelet aggregation

  • MOA: _____ of the platelet _____ (_____) receptor → prevents _____-mediated _____ of _____

Prodrug, 1st, P2Y12 inhibitor, 2C19, 2C19, GP IIb/IIIa, irreversible inhibitor, P2Y12, ADP, ADP, activation, GP IIb/IIIa

Prevent _____:

• _____ (Effient)

  • 2nd drug that came after Clopidogrel

  • No Reversal

  • More potent effects compared to Clopidogrel

    • Better efficacy → increased Adverse Effects

    • Higher rates of bleeding

      • >75 y/o or weight <60 kg = higher risk of bleeding

    • Best in STEMI + diabetic pts

  • Primary PCI → for MI pts and has loading + maintenance dose

  • C/I in pts with h/o stroke or TIA

Activation, Prasugrel

Prevent Activation:

• Prasugrel (Effient)

  • 2nd drug that came after Clopidogrel

  • _____

  • _____ potent effects compared to Clopidogrel

    • _____ efficacy → increased Adverse Effects

    • Higher rates of _____

      • >__ y/o or weight <__ kg = higher risk of bleeding

    • Best in _____ pts

  • Primary PCI → for _____ pts and has loading + maintenance dose

  • C/I in pts with h/o _____ or _____

No reversal, more, better, bleeding, 75, 60, STEMI and diabetic, MI, stroke, TIA

Prevent _____:

• _____ (Brilinta)

  • _____ anti-platelet effects compared to Clopidogrel w/o significant increase in _____

  • Loading + maintenance dose

Activation, Ticagrelor, more potent, bleeding

Prevent _____:

• _____ (Kengrel)

  • _____ agent

  • Similar _____ to Clopidogrel but with _____ incidence

  • IV bolus then IV infusion during PCI

Activation, Cangrelor, Only IV, effectiveness, more bleeding

Meds that Prevent Platelet Activation + are ADP Receptor (P2Y12) Inhibitors (5):

Clopidogrel, Prasugrel, Ticagrelor, Cangrelor, and Ticlopidine

Meds that Specifically Prevent Platelet Aggregation + are GP IIb/IIIa Inhibitors (3):

Abciximab, Eptifibatide, and Tirafiban

Clopidogrel

• MOA: _____ P2Y12 inhibitors

• Administration: _____

• DDIs: _____

Irreversible, oral (prodrug), 2C19 inhibitors

Prasugrel

• MOA: _____ P2Y12 inhibitors

• Administration: _____

• DDIs: _____

Irreversible, Oral, none

Ticagrelor

• MOA: _____ P2Y12 inhibitors

• Administration: _____

• DDIs: _____

Reversible, Oral, 3A4 inhibitors and inducers

Cangrelor

• MOA: _____ P2Y12 inhibitors

• Administration: _____

• DDIs: _____

Reversible, IV, n/a

Prevention Aggregation → _____

• Blocks the final common pathway of platelet aggregation

• MOA:

  • _____ Platelet → _____ rupture + _____ adhesion → _____ + _____ Agonists released → _____ (GP IIb/IIIa expression)

  • _____ (where GP IIb/IIIa _____) → Prevents _____

• _____

GP IIb/IIIa Inhibitors, resting, plaque, platelet, TxA2, ADP, Platelet activation, Fibrinogen, inhibits, platelet aggregation, IV treatments only

Drug-Induced Thrombocytopenia

• Platelet Clearance (removal) by _____

• Heparin Induced thrombocytopenia Abs also _____ cells + _____

• _____ platelet-derived microparticles → _____ Formation

• Heparin-Induced Thrombocytopenia (HIT) = _____

phagocytic cells, activate endothelial, monocytes, Procoagulant, thrombus, platelet activation

Fibrinolytics

• MOA: _____ (_____) binds to _____ in _____ → converts entrapped _____ to _____ → initiates local _____ (breaks down _____ + dissolves _____)

• Ex. _____(_____, _____) and _____ (_____)

Recombinant t-PA, Alteplase, fibrin, thrombus, plasminogen, plasmin, fibrinolysis, clots, fibrin, t-PA, Alteplase, Activase, Tenectaplase, TNKase

t-PA (Alteplase, Activase)

• MOA: _____ (from recombinant _____)

• Used for _____, _____, and _____

• 0.9 mg/kg (Max = 90 mg)

• C/I: _____ + _____ (>_____)

tissue plasminogen activator, DNA, stroke, pulmonary embolism, acute MI, active internal bleeding, uncontrolled HTN, 185/110

Tenectaplase (TNKase)

• Alternative to Alteplase

• Increasing in _____

• _____ of dosing

• _____ (0.25 mg/kg with Max = 25 mg)

Use, Ease, IV bolus