Pharmacotherapy of Stroke

Hendra Wana Nur’amin, dr., M.Sc

Department of Pharmacology
Faculty of Medicine
Lambung Mangkurat University

1 9/26/2016
 Skenario
Ny. Wafroh (65 tahun) dirawat di rumah sakit dengan
keluhan utama kaki dan tangan susah digerakkan dan
bicara pelo. Kekuatan ekstremitas atas (kanan-kiri): 222-
222 dan ekstremitas bawah: 010-110. Ada riwayat
diabetes mellitus sejak dua tahun yang lalu. Selama
perawatan, pasien susah untuk berkomunikasi, susah
untuk melakukan aktivitas. Pasien juga mendapatkan
obat-obatan dari dokter selama perawatan. Melihat
kondisi tersebut, keluarga (anak) pasien tampak cemas
dan menangis karena takut terjadi sesuatu. Keluarga
berencana mau membawa pasien pulang ke rumah dan
perawat memberikan informasi tentang peran keluarga
selama merawat pasien di rumah.
 What Is Stroke ?
A stroke occurs when blood flow
to the brain is interrupted by
a blocked or burst blood vessel.

Loss of speech, or difficulty speaking or understanding speech

Cerebrovascular Disease: Pathogenesis
Hemorrhagic Stroke (17%) Ischemic Stroke (83%)
Atherothrombotic
Cerebrovascular
Intracerebral Disease (20%)
Hemorrhage (59%) Cryptogenic (30%)

Subarachnoid Hemorrhage (41%)

Lacunar (25%) Embolism (20%)
Small vessel disease
 Ischemic Stroke

PENUMBRA :That tissue surrounding the infarct that

is salvageable, but at risk.

Rapid transfer to the stroke center will allow for protection of

penumbra through emergency interventions and medical
management.
§ No oxygen, nerve cells die in minutes

§ In first three hours, some cells

can be saved (up to 35% recovery)

§ Thrombolytics ( ‘clot -busting ’) drugs

dissolve clots; prevent more strokes:
§ Administered via IV pump
§ Heparin (mixed results)
§ t-PA, “Activase” (good results)
 Strategy for Acute Severe Stroke
Intensive Management
Strategy
Optimal Neuroprot
hemodynamic care ective
• antihypertensive therapy
Free radical
Patency of scavengers
supplying
NMDA
vessels
antagonist
Antiplatelet
Avoid
thrombolytics hyperthermia,
hypoxemia,
hyperglycemia
..
General Management of Patients With Acute Stroke

Treat hypoglycemia with dextrose

Blood glucose Treat hyperglycemia with insulin if serum glucose >200
mg/dL
Blood pressure Consider for thrombolysis candidates and noncandidates
Continuous monitoring for ischemic changes or atrial
Cardiac monitor
fibrillation
Avoid D5W and excessive fluid administration
Intravenous fluids IV isotonic sodium chloride solution at 50 mL/h unless
otherwise indicated
aspiration risk is great, avoid oral intake until swallowing
Oral intake
assessed
Oxygen Supplement if indicated (Sa02 < 94%)
Avoid hyperthermia; use oral or rectal acetaminophen and
Temperature
cooling blankets as needed
 Blood Pressure Management in Patients With Stroke

Blood Pressure Treatment

Labetalol 10-20 mg IVP repeated every 10-20 minutes
Pretreatment:
or
Candidates for SBP >185 or DBP >110 mm
Nicardipine 5 mg/h, titrate by 2.5 mg/h every 5-15 min, maximum 15
fibrinolysis Hg
mg/h; when desired blood pressure reached, lower to 3 mg/h or
Enalapril 1.25 mg IVP
Sodium nitroprusside (0.5 mcg/kg/min)
Posttreatment:
Labetalol 10-20 mg IVP and consider labetalol infusion at 1-2 mg/min or
DBP >140 mm Hg
nicardipine 5 mg/h IV infusion and titrate
SBP >230 mm Hg or
or
DBP 121-140 mm Hg
Nicardipine 5 mg/h, titrate by 2.5 mg/h every 5-15 min, maximum 15
SBP 180-230 mm Hg or DBP
mg/h; when desired blood pressure reached, lower to 3 mg/h or
105-120 mm Hg
Labetalol 10 mg IVP, may repeat and double every 10 min up to
maximum dose of 300 mg
Sodium nitroprusside 0.5 mcg/kg/min; may reduce approximately 10-
DBP >140 mm Hg 20%
SBP >220 or Labetalol 10-20 mg IVP over 1-2 min; may repeat and double every 10
DBP 121-140 mm Hg or min up to maximum dose of 150 mg or nicardipine 5 mg/h IV infusion
MAP >130 mm Hg and titrate
SBP < 220 mm Hg or or
Noncandidates
DBP 105-120 mm Hg or Nicardipine 5 mg/h, titrate by 2.5 mg/h every 5-15 min, maximum 15
for fibrinolysis
MAP < 130 mm Hg mg/h; when desired blood pressure reached, lower to 3 mg/h
Antihypertensive therapy indicated only if acute myocardial infarction,
aortic dissection, severe CHF, or hypertensive encephalopathy present
Thrombolytics
 Strategy for Acute Severe Stroke
Intensive Management
Management on patency of supplying vessels
Within 3 hours, t-PA IV
Within 6 hours, urokinase, IA
Aspirin 100mg
+/- Low molecular weight heparin (Clexane 0.5-
1mg/kg Q12h SC)
 Tissue Plasminogen Activator
• Natural body substance. Recombinant TPA
converts Plasminogen to plasmin, which in
turn breaks down fibrin and fibrinogen,
thereby dissolving the clot.
• Dose for Stroke: 0.9mg/kg up to a dose not to
exceed 90mg. 10% of dose as an IV bolus; the
rest over one hour by IV drip.
• IV window of opportunity is < 3 hours of
known symptom onset.
 rTPA Alteplase
• Do not mix t-PA with any other medications.
• Do not use IV tubing with infusion filters.
• All patients must be on a cardiac monitor
• When infusion is complete, saline flush with
Normal saline
• t-PA must be used within 8 hours of mixing
when stored at room temperature or within
24 hours if refrigerated
 Complications of Thrombolysis
• Intra -cerebral
haemorrhage-1.7% , 0.28%
fatal
• Bleeding-minor bleeding is
common (IV site)
• Anaphylaxis- 1%
Strategy for Acute Severe Stroke
Management on Neuroprotection
Fever
• Cold blanket use
• Acetaminophen prn
• Early antibiotics use
Hyperglycemia
Blood glucose < 150mg/dl
Insulin use
Avoid hypoxemia, SpO2>95%
 PIRACETAM
Scavenging Oxygen-free radicals
• the first of the so-called 'nootropic' drugs, a
unique class of drugs which affect mental
function
• did not have significant antioxidant capacity at
therapeutic concentrations
• increasing antioxidant concentrations 10 times
• Effect of Piracetam on Recovery and
Rehabilitation After Stroke: improvement in
aphasia in patients undergoing rehabilitation
after a stroke after 12 weeks' treatment
• Piracetam is completely absorbed after oral
administration
• peak plasma concentrations are reached after 30 to
40 minutes,
• oral bioavailability is close to 100%.
• Piracetam can be administered orally or
intravenously
• dosages ranging from 20 to 150 mg/kg daily in
divided doses.
• For long term treatment of senility, it is
recommended that 2.4 to 4.8g orally be given daily,
depending on the severity of the symptoms.
 CITICOLINE
• Citicoline is considered a promoter of neuronal repair.
• Cytidine-5¢-diphosphocholine (citicoline or CDP-choline), an
intermediate in the biosynthesis of phosphatidylcholine (Ptd-
Cho)
• has shown benefecial effects in a number of CNS injury
models and pathological conditions of the brain.
• The therapeutic action of citicoline is thought to be caused by
stimulation of PtdCho synthesis in the injured brain
• also provides choline for synthesis of neurotransmitter
acetylcholine, stimulation of tyrosine hydroxylase activity and
dopamine release.
 Hemorrhagic Stroke
(17%)

Intracranial Hemorrhage Subarachnoid Hemorrhage

( ICH): 59% (SAH): 41%
Intracranial Hemorrhage (Hypertensive)
(ICH)

– > twice as common as SAH

– more likely to result in death or severe disability
– 37,000 Americans/year
– 35-52% dead within 1 month (half of deaths in the
first 2 days)
– Only 10% living independently in 1 month; improves
to only 20% within 6 months
Intracranial Hemorrhage—ICH

• Risk factors:
– Hypertension
– Advancing age
– Coagulation disorders & therapy
– Alcohol abuse
– Drug use (meth, cocaine, crack, etc.)
– Ischemic stroke—hemorrhagic transformation
 ICH: Goals for Early Management
• Airway management
– Assure adequate oxygenation & reduce
hypercapnea (Remember: ↑CO2 = ↑ ICP)
– Prevent aspiration (Remember: 50% of ICH patients
vomit and have ALOC)
• Prevent seizures
– Acute mgt: phenytoin
– Prevention: Phenytoin 500-1000 mg/20-30 min
 ICH: Goals for Early Management
• Blood Pressure Management:
– Very poor outcomes if BP is allowed to stay very
high—more bleeding
– Very poor outcomes if BP is allowed to drop
precipitously—removes the brain’s attempt to
perfuse a “tight” brain
• Guidelines:
– In general, keep BP about 160/90 or MAP <130
– In the first 48 hours: BP drop 15-25% of presenting
value
 Medical Management for Hemorrhagic Stroke

• Medical Management for Hemorrhagic Stroke Prevention:

control of hypertension
• Diagnosis: CT scan, cerebral angiography, and lumbar
puncture if CT is negative and ICP is not elevated to confirm
subarachnoid hemorrhage
• Care is primarily supportive Bed rest with sedation Oxygen
Treatment of vasospasm, increased ICP, hypertension,
potential seizures, and prevention of further bleeding
• Intracranial pressure elevation, Cerebral edema  mannitol
• Seizure  anticonvulsant
• Surgery consideration
Contact: hendranuramin@gmail.com

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