Anti Platelet Agents (STEMI/NSETMI/UA)

Question 1

ASA MOA

Answer 1

Irreversible *
Inhibits platelet COX and TXA2 formation can also inhibit PGI2 at tx doses

*This begins in 5-7 minutes

Question 2

ASA indications

Answer 2

TIA/Stoke

Coronary thrombosis prevention

ACS

24 hours before PCI/Stenting

Question 3

ASA Metabolism

Answer 3

Weak acid absorbed from stomach/upper GI with peak serum concentration 1-2 hrs

CHEW tablets to inhibit platelets 50% faster

Chewing 162 mg daily inhibits platelet COX-1 completeley
325 is max dose for TXA2 inhibition (higher dose increases bleeding risk and can block prostacyclin-endogenous vasodilator-which reduces efficacy)

Question 4

ASA DI/CI

Answer 4

ASA and NSAIDS compete for same receptor—so NSAIDS can block and prevent acetylation *space these 3 hrs apart!!

Question 5

ASA SE

Answer 5

Prolongs wound healing after CABG so hold it for 6 hrs after CABG and 24 hrs after thrombolytics

ASA resistance 10-15% -can measure with platelet aggregometry.. platelet turnover rates of 10%/day

GI bleeding
SX GI ulcers
2-4x higher with daily long term dose, or bigger dose of ASA and chronic NSAID, GI bleed risk can be reduced with H2 blockers and PPIs

Question 6

ASA Considerations

Answer 6

Daily maintenance therapy following ACS

Milk or food can help with GI discomfort

Enteric coating interferes with absorption, ulcer in distal GI

Question 7

Clopidogrel MOA

Answer 7

Selective Irreversible
Inhibits ADP mediated platelet activation (cold, shear stress)

Binds platelet P2Y12 and P2Y1 receptors

NO effects of TXA2 or PGI2

Question 8

Clopidogrel Indications

Answer 8

Use with ASA for 1 year following coronary stent placement

Alt for ASA for: TIA/Stroke
Coronary thrombosis—UA/NSTEMI/STEMI ACS

Loading dose and maintenance

Question 9

Clopidogrel Metabolism

Answer 9

Prodrug: 2 step oxidation and hydrolysis into active metabolite by CYP2C19 and CYP1A: ETENSIVE HEPATIC METABOLISM

Question 10

Clopidogrel DI/CI

Answer 10

PPIs and other potent CYP219 inhibitors (omeprazole/esomeprazole, cimetidine, azole antifungals, fluoxetine, fluvoxamine) see slide 17 more info
Also:
Reduced bioactivation in Chinese, or pts with cyp219*2 or *3 alleles (it will fail in these ppl with ppi)

Hold before CABG or surgery

Question 11

Clopidogrel SE

Answer 11

Increased bleeding rates
When given with ASA 30% complain of GI

Monitor for purpura and TTP in first 2 weeks

Question 12

Clopidogrel Considerations

Answer 12

Replaces ticlopidine
-no neutropenia, leucopenia

platelet recovery begins with turnover in 7-10 days

Question 13

Prasugrel MOA

Answer 13

Binds platelets P2Y12 and P2Y1 receptors

CYP2C19 do not affect prasugrel!

Question 14

Indications for Prasugrel

Answer 14

UA/NSTEMI when PCI planned

After dx. Cath

Maintenance

Loading dose and maintenance

Reduces non fatal MI

Question 15

Metabolism Prasugrel

Answer 15

Prodrug:rapidly converted by esterases then one step CYP450 oxidation to active metabolite

Half life 6-8 hrs
Nml platelet function after 10 day washout

Question 16

DI/CI Prasugrel

Answer 16

• Stroke or TIA in past 3mo
• > /= 75 yrs
• wt

Question 17

SE Prasugrel

Answer 17

Monitor Bleeding
Increase major bleed risk
Short and long term bleeding increased 
N/V/D
TTP

Stop 5-7 days before CABG or surgery

Question 18

Ticagrelor MOA

Answer 18

Reversible
Inhibits ADP P2Y12 receptors

Binds platelets P2Y12 and P2Y1 receptors

Question 19

Ticagrelor Indications

Answer 19

ACS undergoing PCI given at presentation and continued for 1 yr after PCI

Clopidogrel non responders

CYP2C19 genotype or reocclusion in clopiidogrel

Loading dose and maintenance dose

Question 20

Ticagrelor Metabolism

Answer 20

Orally active then Met into inactive metabolite by CYP3A4

Half life 6-8 hrs
Nml platelet function in 10 days

do not give > 81 mg ASA when on ticagrelor!!!!!!**

Question 21

Ticagrelor DI/CI

Answer 21

Intracranial hemorrhage
Severe hepatic impairment
Active bleeding
Bradycardia
Strong CYP3A4 inhibitors
Inducers or fibrinolytics within 48 hrs 

DI: lovastatin or simvastatin—so use non 3A4 statins: tx discontinuations 1.4%

Question 22

Ticagrelor SE

Answer 22

Monitor: dyspnea
Bradycardia
Heart block
bleeding

Stop 5 days prior to surgery or CABG

Question 23

Ticagrelor Considerations

Answer 23

Reduces MI and vascular death by 1.1% each at 12 months

No excess major bleeding

Question 24

Ticlodipine MOA

Answer 24

Irreversible thienopyridine
P2Y12 inhibitor

No effects on TXA2 or PGI2

Question 25

Ticlodipine Metabolism

Answer 25

Onset 6 hrs
Peaks 3-5 days
Levels don’t correlate with efficacy

Question 26

Ticlodipine
SE
Considerations

Answer 26

Severe purpura
Leucopenia
Neutropenia in 1/50 pts

Replaced by clopidogrel/prasugrel

Question 27

Dipyridamole MOA

Answer 27

Inhibits adenosine deaminase and phosphodiesterase

Allows cAMP and adenosine accumulation and vasodilatation

Question 28

Dipyridamole Indications

Answer 28

Combine with ASA for secondary prevention of stroke (maintenance therapy)

Used prior to thallium for radionuclide imaging (vasodilate and antiplatelet activity)

Question 29

Cilostazol MOA

Answer 29

Cilostazol and metabolites inhibit phosphodiesterase III
increases cAMP 
allows vasodilatation
inhibits vascular SMC proliferation
inhibits platelets

Question 30

Indications of Cilostazol

Answer 30

PAD for intermittent claudication