Secondary Stroke- Drug Therapy, Selection Criteria, Therapy Optimization Flashcards
P2Y12 inhibitors
ticlodipine, clopidogrel, prasugrel
P2Y12i MoA
Irreversibly blocks ADP receptors
ASA MoA
Irreversibly inhibits COX by acetylating it and thromboxane
What turns ASA off?
Platelet turnover
Dipyramidole MoA
Increases plasma adenosine and inhibits platelet phosphodiesterase
Only anti platelet agent that acts reversibly
Dipyramidole
Treatment for small vessel lacunar, large vessel embolic, large vessel thrombotic strokes
Antiplatelet therapy
Treatment for cardioembolic stroke
WARFARIN (AFib)
Best antiplatelet agent
NONE, they’re all equally efficacious
ASA dosing guidelines
5-325mg/day, most patients are on 81mg
ASA concentrations after a 325mg dose
ASA concentrations in systemic circulation are undetectable; salicylic acid has no antiplatelet activity
ASA and salicylate concentrations after 800mg dose
Concentrations were higher
When does COX acetylation occur?
Pre-systemically in the portal circulation
ASA effect with higher doses
There shouldn’t be a greater effect with super high doses because platelet aggregation depends on pre hepatic exposure
GI bleeds are a result of what?
Systemic inhibition of prostaglandin E
What do EC products do?
Decrease GI effects, not GI bleeds
Who may benefit from chewable ASA?
Older female patients, patients with diabetic gastroparesis
Who will need higher doses of ASA?
Younger patients, heavier patients
Ticlodipine isn’t used anymore because…
…of its side effect profile
Ticlodipine ADEs
Diarrhea, rash, nausea, gastritis, ulcers, GI bleeding, severe neutropenia, cerebral hemorrhage
The only thing clopidogrel was better than ASA at
PAD risk reduction
Clopidogrel MoA
Prodrug metabolized by 3A4 and 2C19, so drugs metabolized by these enzymes may inhibit Plavix activation to the active metabolite
Dipyramidole
Not available in the US as a standalone product
Problem with dipyramidole
It reversibly inhibits platelet function, so the IR formulation needs to be dosed QID ATC
Aggrenox is a combo product of what drugs?
ASA/ER dipyramidole
Survival rate when taking Aggrenox compared to placebo, ASA, ER-DP alone
higher survival probability than those
Factors to consider when choosing an antiplatelet med
Side effect profile
Agent that produces an inhibition of aggregation that can be used in the lowest effective dose to reduce bleed risk
Dual antiplatelet therapy
Agents that may be less than optimal
If patients may be resistant
Don’t use Aggrenox in what patients?
Migraine Hx, Crohn’s, UC, IBS
(ADEs are HA and GI upset, abdominal cramping, diarrhea)
Avoid ASA in what patients?
Severe ASA allergy, for epigastric reasons, bleeding risk the patient may have
Don’t use dipyridamole in what patients?
Spastic colon or irritable bowel history
81mg ASA vs. 325mg ASA
Use 325mg ASA for rapid effect x1 week, then 81mg after
How long does it take for 81mg ASA to have full anti platelet effect
7-10 days
Avoid what antiplatelet agent in someone taking a CCB
Plavix/clopidogrel
Patients who qualify for dual anti platelet therapy
Patients with CAD that had a stent placed and has a stroke while taking clopidogrel
New cerebral ischemia within 90 days
Afib patients who don’t qualify for PO coagulation (warfarin); they can take a DOAC and have dual anti platelet treatment for the first 30-90 days
ASA and Plavix together
no long-term benefit but improves stroke outcome and decreases the risk of a second stroke in the first 30-90 days, but bleeding risk increases after that
Approach to ASA resistance
Assure compliance
Remove drugs that compromise ASA effects (NSAIDs other than celecoxib, herbal supplements)
Change from EC to chewable ASA or Alka-Seltzer (sodium bicarb and 325 mg ASA), particularly in older women
Change ASA dose where appropriate
Approach to Plavix resistance
Minimize use of other drugs that inhibit 3A4 and 2C19
Substitute drugs that have lesser effects on the enzymes (ACEis, H2RAs)
Add medications that can induce CYP enzyme activity (500mg of vitamin C BID will induce 3A4)
Common meds that influence 3A4 or 2C19
Statins (not rosuvastatin)
CCBs (not ACEis/ARBs. beta blockers)
Ambient, Lunesta (not Sonata)
Glyburide (not glipizide or metformin)
Enablex and ditropan (not detrol or Sanctura)
PPIs
What to use if patients are truly resistant
Ticagrelor, prasugrel
NOT FDA-APPROVED FOR SECONDARY STROKE TREATMENT THOUGH
Individualized pharmacotherapy considerations
Urgency of needing full antiplatelet effect
Agent least likely to produce ADEs
Agent least likely for DDIs
Dual antiplatelet therapy
