Stroke

MARIANTI MANGGAU
Jenis-jenis stroke
• ischemic (87%) or
• hemorrhagic (13%)
Nonmodifiable risk factors or risk markers

• Age
• Low birth weight
• Race
• Genetic factors
Modifiable, well documented

• Cigarette smoking
• Hypertension
• Diabetes
• Asymptomatic carotid stenosis
• Dyslipidemia
• Atrial fibrillation
• Poor diet
• Obesity
• Physical inactivity
• Other cardiac disease
Potentially modifiable, less well documented

• Migraine
Metabolic syndrome
Drug and alcohol abuse
• Inflammation and Infection
• Elevated Lp(a)
• Homocysteinemia
• Sleep-disordered breathing
 Signs of Stroke
• Patients usually have multiple signs of neurologic dysfunction, and the specific
deficits are determined by the area of the brain involved.
• Hemiparesis or monoparesis occurs commonly, as does a hemisensory deficit.
• Patients with vertigo and double vision are likely to have posterior circulation
involvement.
• Aphasia is seen commonly in patients with anterior circulation strokes.
• Patients may also suffer from dysarthria, visual field defects, and altered levels
of consciousness.
Patofisiologi Stroke
Warfarin
 Pharmacotherapy
• Early reperfusion (less than 4.5 hours from onset) with tissue plasminogen activator
(tPA) has been shown to reduce the ultimate disability due to ischemic stroke.
• Antiplatelet therapy is the cornerstone of antithrombotic therapy for the secondary
prevention of noncardioembolic ischemic stroke.
• Oral anticoagulation is recommended for the secondary prevention of cardioembolic
stroke in patients with atrial fibrillation.
• Blood pressure lowering in the acute ischemic stroke period (first 7 days) may result
in decreased cerebral blood flow and worsened symptoms.
Management of acute ischemic stroke
• the only two pharmacologic agents with class I recommendations are IV tPA
within 4.5 hours of onset and aspirin within 48 hours of onset.
• Early reperfusion (less than 4.5 hours from onset) with IV tPA 0.9 mg/kg over 1
hour, with 10% given as initial bolus over 1 minute
• avoidance of antithrombotic (anticoagulant or antiplatelet) therapy for 24 hours,
and close patient monitoring for elevated blood pressure, response, and
hemorrhage.
Alteplase (recombinant tissue-type plasminogen
activator, rt-PA, TPA) = trombolitika
• 10 mg, 20 mg dan 50 mg dry powder vials with solvent
• Contraindicated in recent haemorrhage, trauma, or surgery (including dental
extraction); coagulation defects; bleeding diatheses; aortic dissection; aneurysm;
coma; history of cerebrovascular disease, especially recent events or with any
residual disability; recent symptoms of possible peptic ulceration; heavy vaginal
bleeding; severe "BP; active pulmonary disease with cavitation; acute
pancreatitis; pericarditis; bacterial endocarditis; severe liver disease; and
oesophageal varices.
Preparation and administration IV injection

• Alteplase is incompatible with Gluc solutions.

• Calculate the volume of solvent (WFI) to produce a solution containing 1 or 2 mg/mL.
• Using a syringe and wide-bore needle or the manufacturer’s transfer device (only for 1 mg/mL
• solutions), direct the stream of WFI directly into the lyophilised cake.
• Gently swirl the vial (do not shake) to dissolve the drug. Allow to stand if necessary to dissipate
• bubbles.
• Withdraw the required dose.
• The solution should be clear and colourless to pale yellow. Inspect visually for particulate matter
• or discoloration prior to administration and discard if present.
 Infus iv
• Calculate the volume of solvent (WFI) to produce a solution containing 1 mg/mL.
• Using a syringe and wide-bore needle or the manufacturer’s transfer device (if available), direct
• the stream of WFI directly into the lyophilised cake.
• Gently swirl the vial (do not shake) to dissolve the drug. Allow to stand if necessary to
dissipate bubbles.
• Withdraw the required dose (bearing in mind that infusion solutions are only stable for up to 8
• hours at room temperature).
• The solution may be infused at the 1 mg/mL concentration as prepared.
 Infus iv
• Alternatively dilute to 5 times the volume with NaCl 0.9% to give a solution
containing 0.2 mg/mL.
• The solution should be clear and colourless to pale yellow. Inspect visually for
particulate matter
• or discoloration prior to administration and discard if present.
• Give by IV infusion via a volumetric infusion device at a rate appropriate to the
indication.
• Prepare a fresh infusion solution every 8 hours if required.
Blood Pressure Treatment Guidelines in Acute Ischemic
Stroke Patients Treated with tPA

None Treatment TPA

Labetalol IVa or nicardipine IVb 180-230/105-120
Nitroprussidec Diastolic >120

tPA, tissue plasminogen activator.

aLabetalol IV: 10 mg, followed by an infusion of 2-8 mg/min.
bNicardipine IV: infusion starting at 5 mg/h up to 15 mg/h.
cNitroprusside IV: infusion starting at 0.5 mcg/kg/min, with continuous arterial blood

pressure monitoring.
 Labetalol HCl
• Pharmacologic class: Nonselective beta-adrenergic blocker, selective alpha1-
adrenergic blocker
• Therapeutic class: Antihypertensive
• Solution for injection: 5 mg/mL in 20-mL and 40-mL multi dose vials
• Labetalol IV: 10 mg bolus over 2 minute, followed by an infusion of 2-8 mg/min (add
200 mg labetalol to 160 mL D5W or normal saline solution to yield 1 mg/mL solution,
to be given at 2 mL (2 mg)/minute with infusion control pump).

.
 Patient teaching

• Instruct patient to immediately report adverse reactions, such as easy bruising or

bleeding and respiratory problems.
• Tell patient dizziness may occur at start of therapy, especially if patient is receiving
diuretic concurrently.
• Advise patient to move slowly when sitting up or standing, to avoid dizziness or
light-headedness from sudden blood pressure decrease.
• Emphasize the need for follow-up care and regular blood pressure monitoring.
Caution patient to closely follow oral therapy protocol after I.V. therapy (100 mg, 200
and 400 mg) and not to stop taking drug abruptly, as this may cause heart attack or
may worsen angina.
 Secondary Prevention in
noncardioembolic strokes
• Antiplatelet therapy antithrombotic therapy should be used in Acetylsalicylic acid
(ASA), extended- release dipyridamole plus aspirin (ERDP-ASA) and
clopidogrel.

Other pharmacotherapy recommended includes blood pressure lowering and statin

therapy.
Pharmacotherapy yang direkomendasikan
berdasarkan Clinical Trials
Pertimbangan Tambahan pada Pemilihan Obat
Antihipertensi
Diuretika sebagai Antihipertensi
statin
• Side Effects: headache, dyspepsia, myositis (myalgia, CPK > 10 times normal)
• Drug interactions: increase myositis risk with drugs inhibit CYP3A4: niasin,
fibrate, ketoconazole, CCB, cyclosporine, erythromycine
• Lovastatin increase pro-time with concurrent warfarin.
• Lipid Profile 4-8 wk after dose change, then Q 12 mo long term, LFT at base line
in 3 months and periodically there after
Secondary Prevention in patients with atrial
fibrillation and a presumed cardiac source of
embolism

• oral anticoagulation with either vitamin K antagonism (warfarin),

• Apixaban (inhibitor faktor Xa direct)
• Dabigatran (direct inhibitor thrombin), or
• rivaroxaban (inhibitor faktor Xa direct)
Recommendations for Pharmacotherapy of Ischemic
Stroke

Acute treatment tPA 0.9 mg/kg IV (maximum 90 mg) over 1 hour in selected
patients within 3 hours of onset
tPA 0.9 mg/kg IV (maximum 90 mg) over 1 hour in selected
patients within 3-4,5 hours of onset
ASA 160-325 mg daily started within 48 hours of onset
Secondary prevention
Noncardioembolic Antiplatelet therapy IA Aspirin 50-325 mg daily
Aspirin 25 mg + extended-release dipyridamole 200 mg twice daily
Clopidogrel 75 mg daily
Cardioembolic (especially
atrial fibrillation) VKA (INR = 2.5)
Apixaban 5 mg twice daily
Dabigatran 150 mg twice daily
Rivaroxaban 20 mg daily
Atherosklerosis + High intensity statin therapy
LDL > 100 mg/dL
BP > 140/90 BP reduction
PERSONALIZED PHARMACOTHERAPY

• Clopidogrel is a thienopyridine prodrug and needs to be biotransformed by the liver

to an active metabolite. clopidogrel can be diminished in patients with reduced-
function cytochrome P450 2C19 (CYP2C19) or in those receiving agents that inhibit
hepatic metabolism.
• In patients receiving clopidogrel after stent placement, reduced- function CYP2C19 is
associated with an increase in recurrent vascular events.
• in a retrospective analysis of 8,205 patients, concomitant proton pump inhibitor and
clopidogrel treatment was associated with increased adverse vascular outcomes after
acute coronary syndromes.
Monitoring Stroke Therapy

• Perdarahan: TPA, ASA, Clopidogrel, antikoagulan oral,warfarin

• ERDP-ASA sakit kepala dan perdarahan
• Monitoring setiap hari
• Warfarin: INR, Hb/Hct