STROKE

Cerebro
Vascular
Accident” (CVA)
STRO
KE
Batasan:
Stroke adalah syndrome yang disebabkan oleh gangguan aliran
darah ke otak yang menyebabkan defisit neurologis tiba-tiba yang
bertahan selama paling tidak 24 jam.

Dipiro, 2008
 Epidemiology of Stroke

Prevalensi Stroke (Permil) berdasarkan diagnosis dokter

pada usia >15 tahun, data tahun 2013-2018, Presentasi
Indonesia berada pada 10.9 %.
Penyebab Ketigaterbanyak Disabilitas pada Lansiadi
Indonesia
Penyebab kematian kedua didunia
Data WHO menunjukkan setiap tahunnyaada 13,7
juta kasus Stroke baru, dan 5,5 juta kematian karena Stroke

Riskesdas ,Stoke, 2018.; Infodatin, Stroke, 2019

Stroke Symptoms

Sudden numbness or weakness of face, arm or leg, especially

on one side of the body
Sudden trouble walking, dizziness, loss of balance or
coordination

Sudden confusion, trouble speaking or

understanding

Sudden severe headache with no known cause

Sudden trouble seeing in one or both eyes

Faktor Resiko

Harrison Manual of Medicene ed 17, Fauci et al, 2009

Types of Stroke

ISCHEMIC STROKE HEMORRAGHIC STROKE

 Trombotic *  Intracerebral Hemorrhage

 Embolic  Intravascular Hemorrhage
 Hypoperfusion  Sub-Arachnoidal Hemorrhage
 Lacunar stroke

National Institute for Health and Clinical Exxelence, 2008

1. Ischemic Stroke
(lack of blood supply)

Permanent damage

Ischemic Stroke
The most common type of stroke -- accounting for almost 83% of all strokes -- is
caused by a clot or other blockage within an artery leading to the brain.

www.strokecenter.0rg
2. Hemorrhagic Stroke
(bleeding into the brain)

a.Intracerebral Hemorrhage
An intracerebral hemorrhage is caused by the sudden
rupture of an artery within the brain. Blood is then released
into the brain, compressing brain structures.
(HT, trauma, amyloid angiopathy)

b. Subarachnoid Hemorrhage
A subarachnoid hemorrhage caused by the sudden
rupture of an artery. A subarachnoid hemorrhage differs
from a intracerebral hemorrhage in that the location of
the rupture leads to blood filling the space surrounding
the brain rather than inside of it.
(aneurysm, AVM, trauma)

www.strokecenter.0rg
Phatogenesis of stroke

Thrombotic
damaged of endotel (aterosclerosis)deposit
lipitplaguevasospasme BV rupture of plagueactivate
trombositrelease TXA2,ADP,5HT and activate Gp IIa/IIIb
receptor agregasi plateletthrombus

Embolic: a traveling blood clot that can arise from various

areas of the body
bockage of CBF  local vasospasme
Sources of emboli: cardiac (arrhythmias, atrial fibrillation,
myocardial infarction, heart disease), and vascular

↓ sistemic perfusion

Caplan, L.R., 1993. Stroke A Clinical Approach. 2nd Edition. USA: Butterworth-Heinemann
Hemorrhagic stroke
a.Intracerebral Hemorrhage
caused by the sudden rupture
of an artery within the brain
Blood is then released into the
brain
compressing brain structures
udema
b. Subarachnoid Hemorrhage
caused by the sudden rupture
aneurysm, AVM, trauma.
rupture leads to blood filling the
space surrounding the brain
(subarachinoid space)
 Pathophisiology

Failure of energy supply to cerebral cells

Exitotoxicity and calcium homeostasis in
neuron Reactive oxygen species
Apoptosis and
necrosis
Inflammation
Yazdi, at al, 1999. Pathophysiology of Ischemic Brain Damage. ., Management of Acute Stroke.
Penatalaksanaan Stroke
 Stroke Treatment

Primary prevention

Acute treatment

Secondary prevention

Rehabilitation

Rohkamm, Color Atlas of Neurology © 2004

 Treatments of Ischemic stroke

Drug Treatments of First Choice:

Early reperfusion (<3 hours from onset) with intravenous tPA has been shown to reduce the
ultimate disability due to schemic stroke

The essentials of the treatment protocol can be summarized as ;

1. stroke team activation
2. onset of symptoms within 3 hours,
3. CT scan to rule out hemorrhage,
4. meet inclusion and exclusion criteria
5. administer tPA 0.9 mg/kg over 1 hour, with 10% given as initial bolus over 1 minute
6. avoid antithrombotic (anticoagulant or antiplatelet) therapy for 24 hours, and
7. monitor the patient closely for response and hemorrhage
 Inclusion and Exclusion Criteria for Alteplase Use
in Acute Ischemic Stroke

Inclusion Criteria:
Age 18 years or older
Clinical diagnosis of ischemic stroke causing
a measurable neurologic deficit
Time of symptom onset well established to be
less than
180 minutes before treatment would begin
Exclusion Criteria ;
Evidence of intracranial hemorrhage on noncontrast
head CT
Only minor or rapidly improving stroke symptoms
High clinical suspicion of subarachnoid hemorrhage even
with normal CT
Active internal bleeding (e.g., GI/GU bleeding within
21 days)
Known bleeding diathesis, including but not limited to platelet
count <100,000/mm3
Patient has received heparin within 48 hours and had an elevated
APTT
Recent use of anticoagulant (e.g., warfarin) and elevated PT (>15
sec)/INR
Intracranial surgery, serious head trauma, or previous stroke
within 3 months
Major surgery or serious trauma within 14 days
Recent arterial puncture at noncompressible site
Lumbar puncture within 7 days
History of intracranial hemorrhage, arteriovenous malformation,
or aneurysm
Witnessed seizure at stroke onset
Recent acute myocardial infarction
SBP >185 mm Hg or DBP >110
mm Hg at time of treatment
Recommendations for Pharmacotherapy of Ischemic Stroke

Pharmacotherapy A Pathophysiologic Approach, 6th Edition. McGraw-Hill Companies,

 Prevention of Stroke Recurrence

Strategies to prevent recurrence of ischemic stroke can be divided into two

areas:

1. Risk factor modification

Diet alterations to manage diabetes and
obesity Increase activity level
Smoking cessation
2. Treated underlying disease of
stroke Antiplatelet medications
Manage hypertension
Anticoagulation medications
Neal., Medical Pharmacology at a Glance, fifth edition, 2005
 1. Fibrinolitik

Proactivator plasminogen

Kinase (kinase jaringan,

streptokinase,stafilokinase,trombin)
r-tPA
Plasminogen activator

Urokinas
Plasminogen e Plasmin

Fibrinogen and fibrin Degradasi finrin/fibrinogen

Streptokinas
e Urokinase
Anisteplase
 r-tPA (recombinant tissue-type plasminogen activator)

no r-tPA
1 Alteplase •1-chain tissue plasminogen activator (fibrinolytic) produced by recombinant
DNA technology It has a high affinity for fibrin-bound plasminogen
•Dogase ; 0.9 mg/kgBB, to a maximum of 90 kg; give 10% as a bolus, with
the remainder given over the next 60 min

2 Tenecteplace •modified from human tissue plasminogen activator (t-PA).

•Genetic mutations of human t-PA resulted in greater thrombolytic potency,
enhanced fibrin-specificity,decreased systemic activation of plasminogen,
resistance to plasminogen activator inhibitor 1, and a longer half-life
compared with t-PA.

3 Reteplace • recombinant plasminogen activator is a nonglycosylated mutant of wild-type

IV bolus 10U+10U iv after tissue plasminogen activator. This modification results in less high-affinity
10 mnt and 30 mnt fibrin binding, longer half-life, and greater thrombolytic potency than alteplase
(rt-PA
Streptokinase •A bacterial protein derived from group C β-hemolytic streptococci.
•It acts indirectly by forming a streptokinase–plasminogen activator complex that
activates another plasminogen and converts it to the proteolytic enzyme plasmin
•Plasmin then hydrolyzes fibrin, fibrinogen, factors II, V, and VIII, complement
•Adverse Reactions: Surface bleeding complications occur frequently and
usually

Urokinase • Urokinase is a proteolytic enzyme produced by renal parenchymal cells that act
to directly convert plasminogen to plasmin, with effects similar to those of
streptokinase
•The drug’s half-life is about 10–20 min
Adverse Reactions. Side effects, contraindications, and precautions are similar
to those of streptokinase

Anisteplase (anisoylated plasminogen-streptokinase activator complex) is an acylated form of

the streptokinase–plasminogen complex that is temporarily inactive. After
deacylation, the streptokinase–plasminogen complex promotes thrombolysis by
converting plasminogen to the proteolytic enzyme plasmin.
Thrombolysis occurs through the action of plasmin on fibrin
2. Antiplatelet agent
endotel PGI2 Activated cAMP
adenilatsiklase
fosfodiesteras
Blood Vessel Injury
e
AS
Activate Platelet A Dipiridamol 5AM
Silostasol P

Release of TXA2,
ADP Eptifibati
Activate Fosfolipase C
5HT d
Tirofiban
Inositol P3 Abcixima
Inhibit Adenilatsiklase b
& Increse AMP
Naftidrofuril
cAMP Inactive GP IIb/IIIa
↑Ca intra cel receptor → active

Clopidogrel fibrinoge
Ticlopidin Platelet agregation crosslink n
No Antiplatelet agent Mecanism and dosage

1 Aspirin • Aspirin (50–325 mg/d) inhibits thromboxane A2, a platelet

aggregating and vasoconstricting

2 Ticlopidin • blocks the platelet ADP receptor

• Half-life is 4–5 days with repeated dosages
• The onset of clinical effect is delayed, with maximum efficacy
• being achieved in 3–8 days
• AR: neutropenia

3 Clopidogrel • blocks the platelet ADP receptor

• Dodage; 75 mg/ day
• the second chois if aspirin not recomended

4 Dipiridamol • Fosfodiesterase inhibitor

•Dosage; 200 mg extended release, combination with aspirin 25
mg.
No Antiplatelet agent Mecanism and dosage

5 Abciximab • a chimeric human-murine monoclonal antibody Fab fragment that

binds to and irreversibly inhibits the platelet glycoprotein IIb/IIIa
receptor
• Dosage 0.25 mg/kg as a bolus 10–60 min before starting
percutaneous coronary intervention and then 10 μg/min by
continuous infusion for 12 hr.

6 Tirofiban • Inhibition of the glycoprotein IIb/IIIa receptor prevents fibrinogen

from binding, thereby preventing platelet aggregation
•Dosage 0.15μg/kg/min for 4 hr

7 Eptifibatide • synthetic, Inhibition of the glycoprotein IIb/IIIa receptor prevents

fibrinogen from binding, thereby preventing platelet aggregation.
Eptifibatide inhibits platelet aggregation and prolongs bleeding
time in a dose-dependent
•Dosage 75-325 mg
•AR: Bleeding
Coagulation
Cascade

Color Atlas of Pharmacology, 2005

3. Anticoagulation

Protrombin
LMWH-antitrombin comp

Heparin
Xa

Antitrombin Trombin Lepirudin

III Argatroban

Antitrombin -
trombin Fibrin
Fibrinogen
complex (clot)
Heparin inhibit thrombosis by inactivating factor Xa and inhibiting the
conversion of prothrombin to thrombin
also prevents the formation of a stable fibrin clot by inhibiting
the activation of factor XIII (the fibrin stabilizing factor). Other
effects include the inhibition of thrombin-induced activation of
factors V
and VIII
Complication : bleeding
Monitoring APTT, (Protamine sulphate injection)

LMWH Enoxaparin, tinzaparin, and dalteparin are LMWHs. These

Enoxaparin, agents enhance the inhibition of Factor Xa and thrombin
Tinzaparin by binding to and accelerating antithrombin activity. They
preferentially potentiate the inhibition of Factor Xa
Dalteparin
Walfarin Anticoagulants interfere with the hepatic synthesis of vitamin
K- dependent clotting factors, which results in an in vivo
depletion of clotting factors VII, IX, X, and II (prothrombin).

Lepirudin Lepirudin (rDNA), a recombinant hirudin derived from

yeast cells, is a highly specific direct inhibitor of thrombin.
One molecule of lepirudin binds to one molecule of
thrombin
and thereby blocks the thrombogenic activity of thrombin.

Argatroban a synthetic, direct thrombin inhibitor that reversibly binds to the

thrombin active site
NEUROPROTEK
TAN
 Citicoline Mechanisms of Action

Adibhatla, RM, Hatcher, JF & Dempsey, RJ 2002, 'Citicoline: neuroprotective mechanisms in cerebral ischemia', Journal of
Neurochemistry, vol. 80, pp. 12-23

30
 4. Neuroprotektan
1 Citicolin •an essential precursor for the synthesis of phosphatidylcholine
Cytidine-5-diphosphocholine (CDP- •phosphatidylcholine is broken down into free fatty acids which
choline) in turn are used to generate free radicals, which potentiate
ischemic injury
•Increase synthesis asetilkolin (cognitif fungtion)
•At level vascular citicolin can increase cerebral blood
flow,increase Oxygen consumption, reduce vascular
resistance.

2 Nimodipin •Calcium channel blocker.

•Inhibits movement of calcium ions across cell membrane
•Has greater effect on cerebral arteries than on other arteries
•Indications Improvement of neurologic deficits caused by
vasospasm after subarachnoid hemorrhage from ruptured
congenital intracranial aneurysms
•Dosage; 60 mg q 4 hr for 21 consecutive days. Initiate therapy
within 96 hr of subarachnoid hemorrhage

Complementary Therapies in Neurology, AN EVIDENCE-BASED APPROACH Barry S.Oken, MD DEPARTMENT OF NEUROLOGY,

OREGON HEALTH & SCIENCE UNIVERSITY, PORTLAND, OR, USA 2004
3 Piracetam •Mechanism of action :unknown
•At level neuronal, banded at cell membrane ( polar head of the
phospholipid), improve/repair cell integrity, improve/repair membrane fluidity,
and also improve;repair neurotransmisi.
•At level vascular pirasetam can increase erythrocyte deformabilitity 
blood flow increased, also reduced hiperaregasi platelet and improv/repair
microsirkulation.

4 Statin • produce beneficial reductions in the risk stroke include the stabilization
and/or regression of atheromatous lesions, thereby reducing the tendency
of plaque to undergo thrombotic disruption
• increase collagen formation and reduce the size of the plaque lipid core,
and to have anti-inflammatory properties, by decreasing macrophage
numbers and metalloproteinase production

5 Pentoxifylline Hemorrheologic
Action Improves blood flow by decreasing blood viscosity
Dosage: PO 400 mg tid with meals for 8 wk. If GI and CNS side effects
occur, decrease to 400 mg bid.
If side effects persist, discontinue
 Treatments of Hemorrhagic
Stroke

Intracerebral hemorrhage
1. Treated etiology of stroke; ↓blood pressure
2. Neuroprotective agents ↓intracranial pressure
3.Surgery (carotid endarterectomy,extracranial-intracranial
bypass) depend on conscius scale
4. vitK / FFP for prevent bleeding

Smith at al, 2005.., Harrison’s Principles of Internal Medicine. 16th Edition. Rohkamm, Color Atlas of Neurology © 2004
 assessment of nerve function with Glasgow Coma Scale
(GCS) Response grades

Open eye
Spontaneus 4

to command 3
pain 2
not response 1
Response Verbal
Good orientation 5
Annoyed orientation 4
Words is less clear 3
aphasia 2
Not response 1
Response Motorik
According to comand 6
Localize pain 5
Draw out 4
Fleksi abnormal 3
Abnormal extension 2
Not response 1
• Subarachinoid Hemorrhage

1. Aneurysmsurgery
2. Management blood presure. Prevention of recurrence of
subarachnoid hemorrhage
3. Antifibrinolitik (EACA, As.tranexamat)
4. Calcium channel blocker: nimodipine is recommended to
reduce the incidence and severity of neurologic
deficits. ↓vasospasm
5. Analgetik opioid (morfin / petidin)

Smith at al, 2005.., Harrison’s Principles of Internal Medicine. 16th Edition. USA: McGraw-Hill
Stroke Prevention
Guidelines
1. Know your blood pressure. Have it checked at least annually. If it is
elevated, work with your doctor to control it.
2. Find out if you have atrial fibrillation (AF). AF is a type of irregular heart
beat.
3. If you smoke, stop.
4. If you drink alcohol, do so in moderation.
5. If you have high cholesterol, work with your doctor to control it.
6. If you are diabetic, follow your doctor’s recommendations carefully to
control your diabetes.
7. Include exercise in the activities you enjoy in your daily routine
8. Enjoy a lower sodium (salt), lower fat diet
9. Work with your doctor if you have circulation problems
10. If you experience any stroke symptoms, seek immediate medical
attention.

National Stroke Association’s

 References

1.Smith, W.S., 2005. Cerebrovascular Disease. In: Kasper, D.L, Fauci, A.S., Longo, D.L., Braunwald, E., Hauser, S.L., Jameson, J.L., Harrison’s Principles of Internal Medicine. 16th
Edition. USA: McGraw-Hill

2.Goldstein, at al. Primary Prevention of Ischemic Stroke ,Stoke, 2006

3.www.medikastone.com mei 2007, yayasan stroke indonesia

4.Yazdi, at al, 1999. Pathophysiology of Ischemic Brain Damage. In: Shuaib, A. and Goldstein, L.B.,
5.Management of Acute Stroke. United States of America: Marcell Dekker, Inc.,
6. Treatment of Acute Ischemic Stroke, Thomas B Rott,MD, The New England Journal of Medicine

7.Pharmacotherapy A Pathophysiologic Approach, 6th Edition. McGraw-Hill Companies,

8.Neal., Medical Pharmacology at a Glance, fifth edition, 2005
9. Drug Facts and Comparison, 2007
10.Complementary Therapies in Neurology, an evidence-based approach barry s.oken, md department of neurology, oregon health & science university, portland, or, usa 2004
11.Wells, B.J., Dipiro J.T., , 2002. Pharmacotherapy Handbook, 5th Edition. New York: McGraw-Hill Companies, Inc., p.

12.Rohkamm, Color Atlas of Neurology, 2004

13.www.strokecenter.org
14.Caplan, L.R., 1993. Stroke A Clinical
Approach. 2nd Edition. USA: Butterworth-
Heinemann