Stroke Flashcards
What is a stroke?
a cerebrovascular accident that occurs when blood flow to an area of the brain is interrupted; can be ischemic or hemorhagic
What is an acute ischemic stroke caused by?
- non-cardioembolic: a thrombus (localized clot) that forms during a cerebral atherosclerotic infarction (obstruction of blood supply)
- cardioembolic: an embolus that forms in the heart and travels to the brain ( commonly caused by A.fib)
What is a hemorrhagic stroke caused by?
- intracranial hemorrhage
- subarachnoid hemorrhage
What is a transient ischemic attack>
cause by a temporary clot ( and blockage of blood flow to the brain) symptoms resemble acute ischemic stroke but resolve within minutes to hours without permanent damage; should be medically managed with the same risk reduction strategies
What are modifiable stroke risk factors?
- HYPERTENSION
- Atrial fibrillation
- dyslipidemia
- diabetes
- physical inactivity
- smoking
What are non-modifiable stroke risk factors?
- Prior stoke or TIA
- advanced age (>80y/o)
- race (higher risk in AA)
- genetic disorders (sickle cell disease)
What are signs and symptoms of stroke?
FAST:
Face drooping (one-sided)
Arm weakness (one sided)
Speech difficulty (slurred)
Time to call 911 (time is brain)
What is used to diagnose stroke?
brain imaging using computed tomography (CT) is ideally performed within 20 minutes of arrival to the ER to quickly identify if the stroke is hemorrhagic or ischemic
What is the immediate goal of treating acute ischemic stroke?
restore blood flow to the ischemic area
What is monitored during the management of acute ischemic stroke?
- intracranial pressure (ICP)
- cerebral perfusion pressure (CPP)
- blood pressure
What agents are fibrinolytic used to treat acute ischemic stoke?
- Alteplase (FDA approved)
- Tenecteplase (off-label)
How does alteplase work to treat acute ischemic stroke?
recombinant tissue plasminogen activator binds to fibrin in a thrombus (clot) and converts plasminogen to plasmin, resulting in fibrinolysis
What patients are candidates for alteplase?
- no bleeding seen on brain imaging
- stroke symptom onset ≤4.5 hours (FDA-approved timeline is ≤ 3 hours)
- alteplase can be administered within 60 minutes of hospital arrival (door-to-needle time)
- no contraindications
What puts patients at increased risk for bleeding when using alteplase?
- active internal bleed (intracranial hemorhage)
- severe hypertension (>185/110 mmHg)
- other conditions/head trauma
- Labs (elevated INR, low platelets)
- drug interactions (anticoagulant use)
What are CIs with alteplase?
- active internal bleeding or known bleeding diathesis
- history of recent stroke (past 3 months)
- severe uncontrolled HTN (>185/110)
- any prior ICH
- treatment dose of LMWH (w/in 24 hours)
- use of direct thrombin inhibitor or Xa inhibitor (w/in 48 hours)
- taking warfarin with INR >1.7
- blood glucose <50
- labs (INR >1.7, Plt <100,000, aPTT>40)
- other conditions that increase risk of bleeding
What are SEs with alteplase?
major bleeding (ICH)
What should be monitored when taking alteplase?
- Hgb/Hct
- s/sx bleeding
- neurological assessment
- BP ( must be <180/105 before alteplase is administered and maintained for at least 24 hours during the infusion, usually IV nicardipine or labetalol used)
- head CT 24 hours after treatment, before starting antiplatelets/anticoagulants
What is dosing of alteplase?
0.9 mg/kg (MAX 90mg dose)
administer 10% of the calculated dose as a plus over 1 min then infuse the remainder over 60 min
Alteplase
Activase
Cathflo Activase
What should be done if severe headache, acute HTN, N/V, or worsening of neurological function occurs during alteplase injection?
D/C infusion and obtain emergent head CT
Which dosage form of alteplase is used to clear clotted central IV lines and devices?
Cathflo Activase (2mg vial)
What drugs interact with alteplase?
additive effects with other drugs that increase bleeding
What other treatments are used for acute ischemic stroke?
- aspirin
- DVT prophylaxis
- HTN management
- Hyperglycemia management
When should aspirin be started for acute ischemic stroke?
- initiate aspirin 81-325mg PO QD within 48 hours after stroke onset
- do not administer within 24 hours of fibrinolytic use
How should HTN be managed if alteplase is NOT used?
- IV antihypertensives may not be needed unless BP ≥220/120; 15% reduction reduction in BP in the first 24 hours after stroke onset is safe
- once neurologically stable PO antihypertensive can be used
How is hyperglycemia managed with acute ischemic stroke?
maintain glucose 140-180 to prevent hypoglycemia
What MUST be done before initiating alteplase?
rule out hemorrhagic stroke (ICH, SAH)
What agents are recommended for HTN treatment in patients with previous stroke TIA?
- thiazide diuretics
- ACE/ARB
What agents are recommended for dyslipidemia treatment in patients with previous stroke TIA?
high-intensity statin (guidelines recommend atorvastatin 80mg/day); if not able to achieve LDL goal, add ezetimibe or PCSK9 monoclonal antibody
What lifestyle modifications should be made as secondary prevention of stroke/TIA?
- smoking cessation
- heart-healthy diet (Mediterranean)
- sodium restriction (<1.5g/day)
- physical activity (10 min 4x/wk or 20 min 2x/wk)
- maintain BMI 18.5-24.9
- maintain waist circumference <35 inches (women) and <40 (men)
- limit alcohol intake ≤1 drink/day (women) and ≤2 drinks/day (men)
What is recommended for patients who had non-cardioembolic stroke to reduce risk of recurrence?
aspirin, aspirin + ER dipyridamole, or clopidogrel
What drug is CI in patients with a history of TIA or stroke due to increased intracranial bleeding risk?
Prasugrel
What can be initiated for minor ischemic stroke if alteplase was not used?
aspirin + clopidogrel initiated within 24 hours and continued for 21-90 days
Why should dual antiplatelet therapy only be used short-term for secondary prevention of stroke?
increases risk of hemorrhage
What can be initiated for minor to moderate ischemic stroke if alteplase was not used?
aspirin + ticagrelor for 30 days
What is the MOA of aspirin?
irreversibly inhibits COX-1 and COX-2 enzymes, resulting in decreased prostaglandin and thromboxane A2 production; thromboxane A2 is a potent vasoconstrictor and inducer of platelet aggregation
What is the MOA of dipyridamole (given with aspirin)?
inhibits the uptake of adenosine into platelets and increases cAMP levels, which inhibits platelet aggregation
What is the MOA of clopidogrel?
prodrug that irreversibly inhibits P2Y12 ADP-mediated platelet activation and aggregation
What are CIs to using aspirin?
- NSAID/salicylate allergy
- children/teenagers with vial infections due to risk of Reye’s syndrome ( symptoms include somnolence, N/V, confusion)
- rhinitis
- nasal polyps
- asthma (risk of urticaria, angioedema, bronchospasm)
What are warnings with aspirin?
- bleeding (GI bleeding/ulceration, increased risk with heavy alcohol use or other drugs that increase bleeding risk)
- tinnitus (salicylate overdose)
What are SEs with aspirin?
- dyspepsia
- heartburn
- bleeding
- nausea (use EC or buffered product or take with food)
What is the recommended dosing of aspirin for stroke?
50mg-325mg (usually 81mg) daily
Aspirin
Bayer
Bufferin
Ecotrin
Aspirin + omeprazole delayed-release tablet
Yosprala
Aspirin ER capsule
Durlaza
Extended-release dipyridamole + aspirin capsule
Aggrenox
What may be used with to protect the gut with NSAID and aspirin use; and also to reduce the risk of aspirin-associated gastric ulcers?
PPIs
What are warnings for the dipyridamole component of ER dipyridamole + aspirin?
- hypotension
- chest pain (in patients with CAD) can occur due to vasodilatory effects
What are SEs for the dipyridamole component of ER dipyridamole + aspirin?
headache (due to vasodilatory effect)
What is important to note about the dose of ER dipyridamole + aspirin?
dose of aspirin is not adequate to prevent cardiac events (MI)
What is the dosing for ER dipyridamole + aspirin?
200mg/25mg BID; if intolerant to headache low dose aspirin Qam and 200mg/25mg Qhs
What is dosing of clopidogrel?
75mg QD
What are boxed warnings with clopidogrel?
- clopidogrel is a prodrug
- effectiveness depends on the conversion to active metabolites maily by CYP2C19
- poor metabolizers of CYP2C19 exhibit higher cardiovascular events than normal metabolizers
- tests to check CYP2C19 genotype can be used to aid therapeutic strategy
- consider alternative therapy in CYP2C19 poor metabolizers
What are SEs with clopidogrel?
generally well tolerated unless bleeding occurs
What are warnings with clopidogrel?
- bleed risk: stop 5 days prior to elective surgery
- DO NOT use with omeprazole or esomeprazole
- premature discontinuation increases risk of thrombotic events
- thrombotic thrombocytopenic purpura
What are CIs to clopidogrel use?
active serious bleeding (GI bleed, ICH)
When is clopidogrel preferred over aspirin?
patients with CI or allergy to aspirin; not used in combination with aspirin for long term stroke prevention
What drugs interact with antiplatelets?
drugs that increase bleeding risk:
anticoagulants
NSAIDs
SSRI/SNRI
some herbals
What drugs interact with clopidogrel?
- avoid combination with omeprazole and esomeprazole
- other drugs that inhibit CYP2C19
What should be used to prevent DVT in those with hemorrhagic stroke?
IPC devices
What can be done to treat increased ICP during ICH?
IV osmotic therapy draws water out of the brain into vascular space where it can be renally excreted:
1. mannitol
2. hypertonic saline (3%, 23.4%)
3. elevate head of the bed by at least 30 degrees
What should be done to manage ICH?
- replace deficiencies (factor replacement, platelet infusions)
- D/C anticoagulation and administer reverasal agent
- if clinical evidence of a seizure, give antiseizure medications
What are CIs to mannitol?
- severe renal disease (anuria)
- severe hypovolemiaa
- pulmonary edema or congestion
- active intracranial bleed (except during craniotomy)
What are warnings with mannitol?
- CNS toxicity (can accumulate in the brain, causing rebound increases in ICP, if used for long periods of time as a continuous infusion; intermittent boluses preferred)
- extravasation (vesicant)
- nephrotoxicity
- fluid and electrolyte imbalances (dehydration, hyper-osmolar induced hyperkalemia, acidosis, increased osmolar gap)
What are SEs with mannitol?
- dehydration
- headache
- lethargy
- hypo/hypertension
What should be monitored with mannitol?
- renal function
- intake/output
- serum electrolytes
- serum and urine osmolality
- ICP
- CPP
What are important administration points with mannitol?
- maintain serum osmolality<300-320 mOsm/kg
- inspect for crystals before administration; if present warm the solute
- use a filter for administration with mannitol concentrations >20%
Clopidogrel
Plavix
Mannitol
Osmitrol
What is SAH?
bleeding in the space between the brain and surrounding membrane (subarachnoid space)
What is SAH usually caused by?
cerebral aneurysm rupture
What is the most common symptom of SAH?
severe headache, “worst headache ever”
What agent is used to reduce cerebral artery vasospasm-induced ischemia?
Nimodipine
What is associated with increased morbidity and mortality related to SAH?
cerebral artery vasospasm 3-21 days after the bleed
What is the MOA of Nimodipine?
dihydropyridine CCB; more selective for cerebral arteries due to increased lipophilicity; only indicated fornSAH
NImodipine
Nymalize
What are boxed warnings with Nimodipine?
do not administer IV or by parenteral routes (PO only) death and serious life-threatening events have occurred ( cardiac arrest, cardiovascular collapse, hypotension, and bradycardia) when content of Nimodipine capsules have been injected
What are CIs to using Nimodipine?
increased risk of significant hypotension whenused in combination with strong inhibitors of CYP3A4
What are SEs with nimodipine?
hypotension
What should be monitored with nimodipine?
- CCP
- ICP
- BP
- HR
- neurological checks
What is important about the administration of nimodipine?
- swallow capule whole on an empty stomach (1 hour before a meal or 2 hours after meals)
- if capsules cannot be swallowed, and the oral solution is unavailable the capsule contents may be withdrawn with a parenteral syringe and transferred to an oral syringe that cannot accept a needle and that can only administer medication orally NOT via NG tube; draw up in pharmacy to reduce errors and label “for oral use only” or “not for IV use” (including oral syringe supplies with commercially available solution
What are drug interactions with nimodipine, major substrate of CYP3A4?
Contraindicated with strong CYP3A4 inhibitors:
Clarithromycin
Protease inhibitors
Azole antifungals
grapefruit juice
Strong CYP3A4 inducers can decrease nimodipine, avoid:
rifampin
carbamazepine
phenytoin
john’s wort
What is dosing for nimodipine?
60mg PO Q4H x 21 days
cirrhosis: 30mg PO Q4H x 21 days
