Pharmacotherapy Stroke

Setyo Purwono
Dept. Pharmacology & Therapy
Faculty of Medicine
Universitas Gadjah Mada

The Major Circulation to the Brain

Circulation is supplied via 2
pairs of arteries:
Internal carotids
Vertebrals
One quarter of cardiac
output goes to the 5 - 6
pound organthe brain.
The brain needs a constant
supply of:
Oxygen
Glucose
Other nutrients

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%)

Intracerebral
Hemorrhage (59%)

Atherothrombotic
Cerebrovascular
Disease (20%)

Cryptogenic (30%)

Subarachnoid Hemorrhage (41%)

Lacunar (25%)
Small vessel disease

Albers GW, et al. Chest. 1998;114:683S-698S.

Rosamond WD, et al. Stroke. 1999;30:736-743.

Embolism (20%)

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.

Ischemic
Stroke
What is Stroke?
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
Activase (good results)

Copyright 2004 MEDRAD, Inc. All rights reserved.

Strategy for Acute Severe Stroke

Intensive Management
Strategy

Optimal
hemodynamic care
normotensive or
hypertensive (by
Dopamine,
phenylephedrine)
hypervolemic but isoosmolar (by colloid)
hypoviscosity (by
mannitol 0.25-0.5g/kg
q6h, phlebotomy)

Neuroprot
ective
therapy
Patency of
supplying
vessels
antiplatlet
antithrombotics
thrombolytics

Free radical
scavengers
NMDA
antagonist
Avoid
hyperthermia,
hypoxemia,
hyperglycemia
..

Strategy for Acute Severe Stroke Intensive

Management
Management on optimal
hemodynamic care
BP
Acquire baseline mean BP
before stroke
Do not adjust high BP unless
MAP>130 or SBP>230 or
DBP>120 or do nothing but
observing.
Do elevate low BP to his/her
baseline mean BP by adequate
fluid supplement, Dopamine,
phenylephedrine
if stroke-in-evolution:
Do elevate mean BP to his/her
baseline mean BP + 30%

Volume
CVP, electrolyte guided
Colloid (Geloplasma or
Gelofusine 1-2 bottle qd)
if stroke-in-evolution
R/O dehydration

Viscosity
Serum osmolarity, Hematocrit
guided
Low dose mannitol
Trental (400mg in 500ccIVF q12h)
Nootropil 1200mg qd
Phlebotomy (Hct 30-35%)

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 st & qd
+/- Low molecular weight heparin (Clexane 0.51mg/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.

Aspirin is a cyclooxygenase inhibitor

thienopyridines, ticlopidine, and clopidogrel
inhibit the binding of adenosine diphosphate to
its platelet receptor
Dipyridamole is thought to enhance
antithrombotic activity of the vessel

the

(e.g., via potentiation of nitric oxide, anti-oxidant properties, and

inhibition of smooth muscle cell proliferation).

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. I

CITICOLINE
Cytidine-5-diphosphocholine (citicoline or CDP-choline),
an
intermediate
in
the
biosynthesis
of
phosphatidylcholine (Ptd-Cho),
has shown benecial 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.

CITICOLINE
Citicoline is considered a promoter of neuronal repair.

Included in the trial, which lasted 10 to 14 days,

were 123 patients who had an acute stroke
within a maximum of 48 hours of the study.
During the first 5 days, citicoline was
administered intravenously (2 g per 24 hours).
From day 6, it was administered intrumnscularly
(1 g per 24 hours).
It has been shown in humans to be effective in the
treatment of several cerebral pathologic conditions,
including acute stroke.

Ginko Biloba
Ginkgo Extraction: Acetone: Water and Spray Drying.
Standardized to Contain:
24% Flavonoid glycosides
6% Lactonic di- and sesqui-Terpenes
1Kg Extract = 70 Kg dried Leaves
Pharmaceutical Forms: Capsules & Tablets, 40; 60;
and 120 mg.
Trade Names: Ginexin F; EGB 761; Ginkgold;
Status Classification:
In USA: Dietry Supplement
In Canada: Food Additive
In France and Germany:As overthe Counter Drugs
Availability : In more than 50 Countries

Ginexin F use in stroke

Ginexin F can be used as a prophylactic agent
following recovery from stroke to prevent recurrencies:
The patient will benefit from its:
a) Vasodilating action resulting from the direct effect
and the indirect action of release of [NO].
b) Anti-oxidant effect that prevents availability of free
oxygen radicals via scavengation due to its flavonoidal
glycosides.
c) Anti-aggregatory effect on platelets.
d) Anti-inflammatory action.

Physiologic Subtypes of ThrombosisRelated Ischemic Stroke

What are the risks factors for

Ischemic Stroke?
Modifiable Risks

HTN
CAD/Carotid Disease/PVD
Atrial Fibrillation
Diabetes
Weight
High Cholesterol/Diet
Lack of exercise
ETOH/Drug abuse
Coagulopathy- Cancer,
Sickle Cell Anemia
PFO- Patent Foramen Ovale

Non-Modifiable Risks
Age->55
Race- African Americans
have 2x the risk of death
and disability. Asians have
1.4x the risk of death and
disability.
Sex- 9% greater chance in
men. (61% of stroke deaths
occur in women)
Previous Stroke or TIA
Family History of Stroke

Hemorrhagic Stroke
(17%)

Intracranial Hemorrhage
( ICH) : 59%

Subarachnoid Hemorrhage
(SAH) : 41%

Albers GW, et al. Chest. 1998;114:683S-698S.

Rosamond WD, et al. Stroke. 1999;30:736-743.

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 HemorrhageICH

Risk factors:
Hypertension
Advancing age
Coagulation disorders & therapy
ETOH abuse
Drug use (meth, cocaine, crack, etc.)
Ischemic strokehemorrhagic 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: Fosphenytoin 500-1000 PE
(phenytoin equivalents over 3-6 minutes)
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
highmore bleeding
Very poor outcomes if BP is allowed to drop
precipitouslyremoves the brains attempt to
perfuse a tight brain

Guidelines:
In general, keep BP about 160/90 or MAP <130
In the first 48 hours: no 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

Post Test
1.

Which of the following are types of ischemic strokes?

a.
b.
c.
d.

Middle cerebral artery occlusion

Vertebral-basilar occlusion
Lacunar stroke
All of the above

2.

A vertebral-basilar stroke might have bilateral

weakness as a symptom. (True or False)

3.

This quick stroke assessment scale accurately

identifies stroke 80% of the time. ________________

Clinician's quick guide for

management after TIA or Stroke - I

Clinician's quick guide for

management after TIA or Stroke - II

Clinician's quick guide for

management after TIA or Stroke - III