1. Antiplatelets (aspirin, P2Y12 receptor antagonists)

Question 1

aspirin MOA

Answer 1

Irreversible inhibits COX1 and COX2 enzymes, decreasing formation of PG precursors; irreversible inhibits formation of thrombaxane

Question 2

aspirin (dosing)

Answer 2

75-325 mg daily

Avoid in eGFR

Question 3

aspirin ADR

Answer 3

bleeding, GI ulcer (most are dose-related)

Question 4

P2Y12 MOA

Answer 4

bind to ADP P2Y12 receptor on platelet surface, preventing ADP-mediated activation of the GPIIb/IIIa receptor complex, reducing platelet aggregation

Question 5

The thienopyridines are ___ & ___; they [are/aren’t] products and bind [reversibly/irreversibly].

Answer 5

clopidogrel, prasugrel; are; irreversibly

Question 6

clopidogrel (brand, dosing, indication)

Answer 6

Plavix
LD: 300-600 mg PO (600 mg for PCI, omit if >75 yo pt received fibrinolytic therapy for STEMI)
MD: 75 mg PO daily

ACS, recent MI, stroke, PAD

Question 7

clopidogrel BBW

Answer 7

Prodrug - effectiveness depends on activation by CYP2C19; poor metabolizers exhibit higher CVEs, tests to check CYP2C19 genotype can be used to guide therapeutic strategy; consider alternatives if a poor metabolizer = CYP2C19*2 and *3 alleles

Question 8

clopidogrel CI

Answer 8

active pathological bleed (PUD, ICH)

Question 9

clopidogrel warning

Answer 9

–CYP2C19 inhibitors: avoid concomitant use with omeprazole and esomeprazole
–inc. bleeding risk, d/c 5 days prior to elective surgery
–thrombotic thrombocytopenic purpura (TTP) reported
–do not start in pts likely to undergo CABG
–MedGuide required

Question 10

clopidogrel SEs

Answer 10

bleeding, bruising, pruritus

Question 11

clopidogrel monitoring

Answer 11

sx of bleeding, Hgb/Hct as necessary

Question 12

prasugrel (brand, dosing, indication)

Answer 12

Effient
LD: 60 mg PO (no later than 1 hr after PCI)
MD: 10 mg PO daily (5 mg if

Question 13

prasugrel BBW

Answer 13

significant, sometimes fatal bleeding

Question 14

prasugrel CI (2)

Answer 14

–active pathological bleed

–hx of TIA or stroke

Question 15

prasugrel warning (2)

Answer 15

–inc. bleeding risk, d/c 7 days prior to elective surgery

–TTP reported

Question 16

prasugrel SEs

Answer 16

bleeding (more than clopidogrel)

Question 17

prasugrel notes (4)

Answer 17

–keep in original container
–do not start in pts likely to undergo CABG
–not recommended in pts >75 yo except in high-risk pts (DM or prior MI)
–MedGuide required

Question 18

The non-thienopyridines are ___ & ___; they [are/aren’t] products and bind [reversibly/irreversibly].

Answer 18

ticagrelor, cangrelor; aren’t; reversibly

Question 19

ticagrelor (brand, dosing, indications)

Answer 19

Brilinta
LD: 180 mg
MD: 90 mg PO BID x1 yr, then 60 mg BID

ACS

Question 20

ticagrelor BBW (2)

Answer 20

–significant, sometimes fatal, bleeding
–MD of aspirin >100 mg reduce effectiveness of ticagrelor and should be avoided (after any initial aspirin dose, MD should not exceed 100 mg daily)

Question 21

ticagrelor CI (2)

Answer 21

–active pathological bleed

–history of ICH

Question 22

ticagrelor warnings (2)

Answer 22

–inc. bleeding risk, d/c 5 days prior to elective surgery

–hepatic impairment

Question 23

ticagrelor SEs

Answer 23

bleeding, dyspnea (>10%), inc. SCr, bradyarrhythmias, inc. uric acid

Question 24

ticagrelor DDIs, notes (2)

Answer 24

–DDIs: ticagrelor is a major CYP3A4 substrate, avoid with strong inducers/inhibitors; avoid simvastatin and lovastatin doses >40 mg/day; monitor digoxin levels with initiation or any change in ticagrelor dose
–do not start in pts likely to undergo CABG
–MedGuide required

Question 25

cangrelor (brand, dosing, indication)

Note: not incorporated in guidelines

Answer 25

Kengreal (IV)
30 mcg/kg IV bolus prior to PCI, then 4 mcg/kg/min IV infusion for 2 hrs or duration of procedure (whichever is longer)

adjuct to PCI to dec. risk of periprocedural MI, repeat revascularization and stent thrombosis in pts who are P2Y12 inhibitor naïve and are not receiving a GPIIb/IIIa inhibitor

Question 26

cangrelor CI, SEs

Answer 26

CI: significant active bleeding
SE: bleeding

Question 27

cangrelor notes (2)

Answer 27

–pregnancy category C

–no reversal agent, effects are gone 1 hr after drug d/c

Question 28

cangrelor IV to PO

Answer 28

–ticagrelor 180 mg given during or immediately after stopping cangrelor
–prasugrel 60 mg or clopidogrel 600 mg immediately after stopping cangrelor
(do not give prior to stopping cangrelor)

Question 29

P2Y12 inhibitor DDIs

Answer 29

Avoid use with other agents that inc. bleeding risk (NSAIDs, anticoagulants, SSRIs, SNRIs, thrombolytics, etc.)
If pt experiences bleeding, manage without d/c P2Y12 inhibitor if possible; stopping, especially within the first few months after ACS, inc. risk of subsequent CVEs