Secondary Stroke- Drug Therapy, Selection Criteria, Therapy Optimization

Question 1

P2Y12 inhibitors

Answer 1

ticlodipine, clopidogrel, prasugrel

Question 2

P2Y12i MoA

Answer 2

Irreversibly blocks ADP receptors

Question 3

ASA MoA

Answer 3

Irreversibly inhibits COX by acetylating it and thromboxane

Question 4

What turns ASA off?

Answer 4

Platelet turnover

Question 5

Dipyramidole MoA

Answer 5

Increases plasma adenosine and inhibits platelet phosphodiesterase

Question 6

Only anti platelet agent that acts reversibly

Answer 6

Dipyramidole

Question 7

Treatment for small vessel lacunar, large vessel embolic, large vessel thrombotic strokes

Answer 7

Antiplatelet therapy

Question 8

Treatment for cardioembolic stroke

Answer 8

WARFARIN (AFib)

Question 9

Best antiplatelet agent

Answer 9

NONE, they’re all equally efficacious

Question 10

ASA dosing guidelines

Answer 10

5-325mg/day, most patients are on 81mg

Question 11

ASA concentrations after a 325mg dose

Answer 11

ASA concentrations in systemic circulation are undetectable; salicylic acid has no antiplatelet activity

Question 12

ASA and salicylate concentrations after 800mg dose

Answer 12

Concentrations were higher

Question 13

When does COX acetylation occur?

Answer 13

Pre-systemically in the portal circulation

Question 14

ASA effect with higher doses

Answer 14

There shouldn’t be a greater effect with super high doses because platelet aggregation depends on pre hepatic exposure

Question 15

GI bleeds are a result of what?

Answer 15

Systemic inhibition of prostaglandin E

Question 16

What do EC products do?

Answer 16

Decrease GI effects, not GI bleeds

Question 17

Who may benefit from chewable ASA?

Answer 17

Older female patients, patients with diabetic gastroparesis

Question 18

Who will need higher doses of ASA?

Answer 18

Younger patients, heavier patients

Question 19

Ticlodipine isn’t used anymore because…

Answer 19

…of its side effect profile

Question 20

Ticlodipine ADEs

Answer 20

Diarrhea, rash, nausea, gastritis, ulcers, GI bleeding, severe neutropenia, cerebral hemorrhage

Question 21

The only thing clopidogrel was better than ASA at

Answer 21

PAD risk reduction

Question 22

Clopidogrel MoA

Answer 22

Prodrug metabolized by 3A4 and 2C19, so drugs metabolized by these enzymes may inhibit Plavix activation to the active metabolite

Question 23

Dipyramidole

Answer 23

Not available in the US as a standalone product

Question 24

Problem with dipyramidole

Answer 24

It reversibly inhibits platelet function, so the IR formulation needs to be dosed QID ATC

Question 25

Aggrenox is a combo product of what drugs?

Answer 25

ASA/ER dipyramidole

Question 26

Survival rate when taking Aggrenox compared to placebo, ASA, ER-DP alone

Answer 26

higher survival probability than those

Question 27

Factors to consider when choosing an antiplatelet med

Answer 27

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

Question 28

Don’t use Aggrenox in what patients?

Answer 28

Migraine Hx, Crohn’s, UC, IBS

(ADEs are HA and GI upset, abdominal cramping, diarrhea)

Question 29

Avoid ASA in what patients?

Answer 29

Severe ASA allergy, for epigastric reasons, bleeding risk the patient may have

Question 30

Don’t use dipyridamole in what patients?

Answer 30

Spastic colon or irritable bowel history

Question 31

81mg ASA vs. 325mg ASA

Answer 31

Use 325mg ASA for rapid effect x1 week, then 81mg after

Question 32

How long does it take for 81mg ASA to have full anti platelet effect

Answer 32

7-10 days

Question 33

Avoid what antiplatelet agent in someone taking a CCB

Answer 33

Plavix/clopidogrel

Question 34

Patients who qualify for dual anti platelet therapy

Answer 34

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

Question 35

ASA and Plavix together

Answer 35

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

Question 36

Approach to ASA resistance

Answer 36

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

Question 37

Approach to Plavix resistance

Answer 37

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)

Question 38

Common meds that influence 3A4 or 2C19

Answer 38

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

Question 39

What to use if patients are truly resistant

Answer 39

Ticagrelor, prasugrel

NOT FDA-APPROVED FOR SECONDARY STROKE TREATMENT THOUGH

Question 40

Individualized pharmacotherapy considerations

Answer 40

Urgency of needing full antiplatelet effect
Agent least likely to produce ADEs
Agent least likely for DDIs
Dual antiplatelet therapy