Stroke

Question 1

tPa

Answer 1

Tissue-type plasminogen activator
Helps facilitate conversion of PLASMinogen to PLASMIN which breaks up the fibrin clot

Question 2

Stroke “Time Window”

Answer 2

Reversal at:
<2 hours: reversible deficits
2-6 hours: some but incomplete recovery
>6 hours: little recovery

Question 3

TPA

Answer 3

Alteplase

Question 4

TNK

Answer 4

Tenecteplase

Question 5

Most Important Side Effect of Thrombolitics

Answer 5

Intracranial Hemorrhage (ICH)

Question 6

TPA Dosage

Answer 6

0.9 mg/kg actual body weight
Maximum dose 90mg
10% of dose given as initial bolus over 1 minute

Question 7

BP must be kept at what level and for how long during thrombolytic therapy
Agents of choice to do this?

Answer 7

<180 mmHg systolic BP and <110 DBP for 24 hours

Labetalol 10 to 20 mg IV

Nicardipine 5 mg/hr IV titrated to effect

Question 8

Acute Ischemic Stroke (AIS) Inclusion Criteria for TPA/TNK Use

Answer 8

Ischemic Stroke causing measurable deficit
Onset of symptoms <4.5 hours prior to treatment (3 hours if pt 80 yo or older)
Age 18 years or older
Deficit measurable on NIHSS
CT with no evidence of ICH

Question 9

Most Important Exclusion Criteria for Acute Ischemic Stroke (AIS) TPA/TNK Use

Answer 9

1. Seizure at the onset of stroke
2. Anticoagulants within 48 hours of stroke onset (antiplatelets okay)

Question 10

Exclusion Criteria for Acute Ischemic Stroke (AIS) TPA/TNK Use

Answer 10

*Seizure at the onset of stroke
*Anticoagulant use within 48 hours of stroke onset
Stroke or serious head trauma within 3 months
Major surgery within 14 days
History or signs of hemorrhage
SBP >185 mmHg or DBP >110 mmHg
Rapidly improving or minor symptoms (relative exclusion)
Blood Glucose <50 mg/dL or >400 mg/dL

Question 11

Relative Exclusion Criteria for Thrombolytic Therapy

Answer 11

Minor symptoms or rapidly improving
Seizure at onset – postictal neurologic deficit?
Major surgery or trauma in previous 14 days
Recent GI bleed (~21 days)
Recent acute MI (~3 months)

Question 12

Additional Exclusion Criteria for 3 - 4.5 hour Time Window

Answer 12

Age >80 years old
Severe stroke (NIH >25)
History of stroke and diabetes

Question 13

If pt is not a TPA/TNK candidate, but BP is 200/110 mmHg, what do you do?

Answer 13

Nothing! Permissive HTN
– Maintain perfusion to ischemic penumbra
– Allow blood pressures up to 220 mmHg systolic
(More damage would be done from hypo perfusion in this case)

Question 14

Initial cerebrovascular events: What class of agents is used for a small vessel lacunar, large vessel embolic, large vessel thrombotic, and cardioembolic stroke?

Answer 14

Cardioembolic = originated outside cerebral vasculature. —> Anticoagulants
All others = Antiplatelets

Question 15

Aspirin dosing guidelines for secondary stroke prevention

Answer 15

50-325 mg/day ACCP, FDA

Question 16

Aspirin use: required amount of cyclooxygenase blockage for anti platelet effect?

Answer 16

Inhibition of platelet aggregation requires that greater than 97% of COX1 be inhibited

Question 17

PK Profile of Aspirin

Answer 17

Inhibition of thromboxane generation was complete for both suggesting that acetylation of COX occurs pre-systemically in portal circulation.

Since inhibition of platelet aggregation depends only on pre hepatic exposure to ASA, based on pharmacokinetics there should not be a greater effect with higher doses

Enteric-coated products are erratically absorbed from the GI tract
(Just reading this card 5 times is good enough)

Question 18

Effect of Enteric Coating on Bleed Risk from Aspirin

Answer 18

GI bleeds are the result of the systemic inhibition of Prostaglandin E
Not a local GI irritation

Question 19

Patient reports aspirin resistance to 81mg dose. What does data show?

Answer 19

A significant number of patients taking ASA 81 mg with continued ability for platelet aggregation are under dosed rather than truly resistant

Question 20

Aspirin vs. Clopidogrel (Plavix) for Stroke, MI, and PAD Prophylaxis

Answer 20

Both essentially equivalent except Plavix> aspirin for PAD prophylaxis

Question 21

Study outcome is stroke. Which is better, Brilinta, Plavix, or Aspirin?

Answer 21

No difference between agents
All better than placebo

Question 22

Migraine Hx, Antiplatelet option?

Answer 22

Not Aggrenox

Question 23

Spastic Colon, Irritable Bowel Hx, bad acid reflux, Barrett’s Esophagitis antiplatelet agent?

Answer 23

No aspirin

Question 24

Need for rapid antiplatelet effect, which agent?

Answer 24

Load aspirin 325mg x1 dose, effect seen in 4-6 hours
Plavix can be loaded but isn’t done with neurology, only cardiology, because hemorrhagic stroke potential
Maintenance doses takes ~5-7 days for aspirin and Plavix effect and ~3-5 days for Brilinta

Question 25

Which antiplatelet agent is most forgiving with poor compliance?

Answer 25

Aspirin

Question 26

Does you patient warrant dual anti platelet therapy?

Answer 26

– Coronary Artery Stents and new cerebral ischemia – Cerebral ischemia within 90 days ( Moving Target) – Atrial Fibrillation not a candidate for anticoagulants – Cerebral Vessel Dissection Duration based on neurologist discretion

Question 27

Approach to ASA resistance

Answer 27

Assure Compliance – Urinary Salicylates Remove Drugs that compromise ASA effects – NSAIDS other than Celebrex (which is COX-2 selective) – Some herbal supplements Change from EC to Chewable ASA or *Alka Seltzer* (the one with only aspirin. This is best delivery system, but difficult to use due to GI tolerability) – Particularly in older woman Change ASA dose where appropriate

Question 28

Approach to Plavix resistance:

Answer 28

Recall, it’s a prodrug converted to active thiolmetabolite via CYP 2C19 and 3A4 - Minimize use of other drugs that inhibit CYP3A4 and CYP2C19 (nineTEEN) - Substitute drugs that have lessor effect on these P450 is iso enzymes - Add medications that can induce CYP enzyme activity

Question 29

Common Medications that influence CYP 3A4 or CYP 2C19

Answer 29

Statins other than Crestor Calcium channel blockers, not beta blockers, ace inhibitors or angio receptor blockers Ambien , Lunesta, (Sonata least likely) Gliburide, not glypizide or metformin Enablex, Ditropan, Not Detrol or Sanctura Proton Pump Inhibitors

Question 30

What do you do if the patient is truly resistant to both aspirin and clopidogrel?

Answer 30

BRILINTA ticagrelor, a cyclopentyltriazolopyrimidine, inhibitor of platelet activation and aggregation mediated by the P2Y12 ADP-receptor. **Not a prodrug** Dose : – Loading Dose ? (People don’t do this yet) – 90 mg BID **Maximum ASA dose 100 mg daily**