Anti Platelet Agents (STEMI/NSETMI/UA) Flashcards
ASA MOA
Irreversible *
Inhibits platelet COX and TXA2 formation can also inhibit PGI2 at tx doses
*This begins in 5-7 minutes
ASA indications
TIA/Stoke
Coronary thrombosis prevention
ACS
24 hours before PCI/Stenting
ASA Metabolism
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)
ASA DI/CI
ASA and NSAIDS compete for same receptor—so NSAIDS can block and prevent acetylation *space these 3 hrs apart!!
ASA SE
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
ASA Considerations
Daily maintenance therapy following ACS
Milk or food can help with GI discomfort
Enteric coating interferes with absorption, ulcer in distal GI
Clopidogrel MOA
Selective Irreversible
Inhibits ADP mediated platelet activation (cold, shear stress)
Binds platelet P2Y12 and P2Y1 receptors
NO effects of TXA2 or PGI2
Clopidogrel Indications
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
Clopidogrel Metabolism
Prodrug: 2 step oxidation and hydrolysis into active metabolite by CYP2C19 and CYP1A: ETENSIVE HEPATIC METABOLISM
Clopidogrel DI/CI
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
Clopidogrel SE
Increased bleeding rates
When given with ASA 30% complain of GI
Monitor for purpura and TTP in first 2 weeks
Clopidogrel Considerations
Replaces ticlopidine
-no neutropenia, leucopenia
platelet recovery begins with turnover in 7-10 days
Prasugrel MOA
Binds platelets P2Y12 and P2Y1 receptors
CYP2C19 do not affect prasugrel!
Indications for Prasugrel
UA/NSTEMI when PCI planned
After dx. Cath
Maintenance
Loading dose and maintenance
Reduces non fatal MI
Metabolism Prasugrel
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
DI/CI Prasugrel
- Stroke or TIA in past 3mo
- > /= 75 yrs
- wt
SE Prasugrel
Monitor Bleeding Increase major bleed risk Short and long term bleeding increased N/V/D TTP
Stop 5-7 days before CABG or surgery
Ticagrelor MOA
Reversible
Inhibits ADP P2Y12 receptors
Binds platelets P2Y12 and P2Y1 receptors
Ticagrelor Indications
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
Ticagrelor Metabolism
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!!!!!!**
Ticagrelor DI/CI
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%
Ticagrelor SE
Monitor: dyspnea
Bradycardia
Heart block
bleeding
Stop 5 days prior to surgery or CABG
Ticagrelor Considerations
Reduces MI and vascular death by 1.1% each at 12 months
No excess major bleeding
Ticlodipine MOA
Irreversible thienopyridine
P2Y12 inhibitor
No effects on TXA2 or PGI2
Ticlodipine Metabolism
Onset 6 hrs
Peaks 3-5 days
Levels don’t correlate with efficacy
Ticlodipine
SE
Considerations
Severe purpura
Leucopenia
Neutropenia in 1/50 pts
Replaced by clopidogrel/prasugrel
Dipyridamole MOA
Inhibits adenosine deaminase and phosphodiesterase
Allows cAMP and adenosine accumulation and vasodilatation
Dipyridamole Indications
Combine with ASA for secondary prevention of stroke (maintenance therapy)
Used prior to thallium for radionuclide imaging (vasodilate and antiplatelet activity)
Cilostazol MOA
Cilostazol and metabolites inhibit phosphodiesterase III increases cAMP allows vasodilatation inhibits vascular SMC proliferation inhibits platelets
Indications of Cilostazol
PAD for intermittent claudication
