Pharmacotherapy of Stroke

*PHARMACOTHERAPY
OF STROKE
*Ike Dhiah R.
*ikedhiah@gmail.co
*Definition
*Classification
*Pathophysiology
*Drug Used in Ischemic Stroke
*Drug Used in Hemorrhagic Stroke
*OUTLINE
Forum Apoteker Indonesia 2
2013
IC
genic
ryptogenic
cerebrovascular
embolism disease
hrombus, emboli)
STROKE
HEMORRHAGE
Sub Arachnoid Intraparenchymal

2013
Gender Stroke 2006;37:1583–1633.
Modifiable Non Modifiable
Hypertension Family History

Dislipidemia Age
Diabetes Atrial FIbrillation

*Risk Factors
2013
*Pathophysiological
Approach
2013
Click icon to add picture
* DRUG THERAPY IN ISCHEMIC STROKE

2013
Antiplatelet Statin Trombolytic
NeuroprotectiveAntihypertensive
Agent
*DRUG USED IN
ISCHEMIC STROKE
2013
* TROMBOLYTIC
2013
Ischemic Stroke Age ≥ 18 yearsOnset of symptoms < 3 hours
*Criteria for
Trombolytic
Forum Apoteker Indonesia Jauch,et
9 al. Guidelines for the Early Management of Patients
2013 With Acute Ischemic Stroke Stroke,2013;44:870-947
*Significant head trauma or prior stroke in
previous 3 months
*SAH
*Intracranial neoplasm, arteriovenous
malformation, aneurysm
*Blood pressure > 185/110 mmHg
*Active internal bleeding
*Blood glucose concentration <50 mg/dl
*Exclusion Criteria for

Trombolytic
*Intravenous rtPA (0.9 mg/kg, maximum dose 90
mg) is recommended for selected patients who
may be treated within 3 hours of onset of ischemic
stroke
(Class I; Level of Evidence A)
*Physicians should review the criteria outlined to

determine the eligibility of the patient.
*Recommendations
*Infuse 0,9 mg/kg (max.dose 90 mg) over 60
minutes, with 10% of the dose given as a bolus
over 1 minute
*If the patient develop severe headache, acute

hypertension, nausea, or vomiting or has a
worsening neurological examination,
discontinue the infusion
*Measure blood pressure every 15 minutes

* Intravenous administration
during and after rTPA infusion for 2 hours, then
every 30 minutes for 6 hours, then hourly until
24 hours of Trombolytic

*Antiplatelet
2013
*Oral administration of aspirin (initial dose is
325 mg) within 24 to 48 hours after stroke
onset is recommended for treatment of most
patients (Class I; Level of Evidence A).
*The usefulness of clopidogrel for the treatment

of acute ischemic stroke is not well established
(Class IIb; Level of Evidence C)
*Antiplatelet
*In two large randomized trials, the use of
aspirin , initiated within 48 hours after the
onset of stroke and continued for 2 weeks or
until discharge, led to reduced rates of death
or dependency at discharge or at 6 months,
probably by means of reducing the risk of
recurrent ischemic stroke.
*In both trials, the routine use of aspirin was

recommended as secondary prevention after
the first few weeks. Although the benefit was
small *Aspirin trials
2013 N Engl J Med 2007;357:572-9
*The blood pressure is often higher in acute
stroke patients with a history of hypertension
than in those without premorbid hypertension.
*Blood pressure typically decreases

spontaneously during the acute phase of
ischemic stroke, starting within 90 minutes
after onset of stroke symptoms.
*Blood Pressure in Stroke

2013
Extreme arterial hypotension →
→ encephalopathy, cardiac
↓ perfusion complications,
to multiple and
organs, especially the renal
ischemic insufficie
brain, exacerbati

2013
*long-term antihypertensive therapy after the
initial 24 hours from stroke onset in most patients.
*An optimal long-term antihypertensive therapy for

patients after stroke has not been definitively
established, and it might be best to individualize
such therapy based on relevant comorbidities,
ability to swallow, and likelihood to continue with
the prescribed therapy.
*Blood Pressure control

*Patients who have elevated blood pressure and
are otherwise eligible for treatment with
intravenous rtPA should have their blood
pressure carefully lowered so that their systolic
blood pressure is <185 mm Hg and their
diastolic blood pressure is <110 mm Hg before
fibrinolytic therapy is initiated.
(Class I; Level of Evidence B)
* Blood Pressure Control

*In patients with markedly elevated blood
pressure who do not receive fibrinolysis, a
reasonable goal is to lower blood pressure by
15% during the first 24 hours after onset of
stroke. The level of blood pressure that would
mandate such treatment is not known, but
consensus exists that medications should be
withheld unless the systolic blood pressure is
>220 mm Hg or the diastolic blood pressure is
>120 mm Hg
* Blood Pressure Control
(Class I; Level of Evidence C).
*Individualized
*ACE inhibitor + diuretic
*Ca channel blocker
*Antihypertensive agents

2013
*Evidence indicates that persistent in-hospital
hyperglycemia during the first 24 hours after
stroke is associated with worse outcomes than
normoglycemia
*Blood glucose levels in a range of 140 to 180
mg/dL
*monitor to prevent hypoglycemia in patients
(Class IIa; Level of Evidence C)
*Blood glucose
2013
*Among patients already taking statins at the
time of onset of ischemic stroke, continuation
of statin therapy during the acute period is
reasonable (Class IIa; Level of Evidence B).
*Statin
*At present, no pharmacological agents with
putative neuroprotective actions have
demonstrated efficacy in improving outcomes
after ischemic stroke, and therefore, other
neuroprotective agents are not recommended
(Class III; Level of Evidence A)
*Neuroprotective
Agent
*Citicoline may improve the chance of a good
recovery after three months (OR 1,38, 95% CI
1,10-1,72). A further large phase III trial is
ongoing
(Davalos, et al. Oral citicoline in acute ischemic stroke: an

individual patient data pooling analysis of clinical trials. Stroke
2002;33(12):2850-7
*Citicholine
2013
*Multiple, randomized clinical stroke trials have
investigated citicoline and reported that
administration of citicoline was effective early in the
post-ischemia recovery process, as demonstrated by
improved level of consciousness , and improvements
in the modified Rankin score.
* Oral treatment with citicoline within the first 24
hours after onset of moderate to severe stroke was
reported to increase the probability of complete
recovery at 3 months in a meta-analysis of 4
randomized clinical trials, with the highest favorable
response observed in the 2000-mg dose group .
*Citicholine trials
2013 Neurotherapeutics (2011)8 :434-451
*This was followed by a comprehensive
metaanalysis of 8 randomized clinical trials of
citicoline, which enrolled 2063 patients
reporting that treatment with citicoline was
associated with absolute reductions of 10 to
12% in rates of long-term death and disability,
although no individual trial demonstrated
treatment benefit unequivocally. Pooled
analysis of 2 citicoline trials collecting serial
magnetic resonance imaging data similarly
suggested a dose-dependent reduction in
infarct growth.
*Citicholine trials
*An international, multicenter, phase III
randomized trial (International Citicoline Trial
on Acute Stroke [ICTUS]) comparing the
efficacy of a 2-gram daily dose of citicoline
started within 24 hours of ischemic stroke
onset and continued for 6 weeks against a
placebo is currently ongoing to date
*Citicholine trials
*Limited data showed no difference between
treatment and control group for functional
outcome, dependence or proportion of patients
dead or dependent. Adverse effects were not
reported
(Cochrane Database Syst Rev, 2012 Sep 12)
*Piracetam trials
2013
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* DRUG THERAPY IN HEMORRHAGIC

STROKE
2013
*Between the time of aSAH symptom onset
and aneurysm obliteration, blood pressure
should be controlled with a titratable
agent to balance the risk of stroke,
hypertension-related rebleeding, and
maintenance of cerebral perfusion pressure
(Class I; Level of Evidence B)
*Blood Pressure
Forum Apoteker Indonesia Connoly,et
31 al. Guidelines for the Management of Aneurysmal
2013 Subarachnoid Hemorrhage. Stroke,2012;43:1711-1737
*The magnitude of blood pressure control to
reduce the risk of rebleeding has not been
established, but a decrease in systolic blood
pressure to 160 mm Hg is reasonable
(Class IIa; Level of Evidence C).
*Blood Pressure
*Oral nimodipine should be administered to all
patients with aSAH
(Class I; Level of Evidence A).

* The use of prophylactic anticonvulsants may be
*Anticonvulsants
considered in the immediate posthemorrhagic
period
(Class IIb; Level of Evidence B).
* The routine long-term use of anticonvulsants is not

recommended
(Class III; Level of Evidence B)
* but may be considered for patients with known risk

factors for delayed seizure disorder, such as prior
seizure, intracerebral hematoma, intractable
hypertension, infarction, or aneurysm at the middle
cerebral artery
(Class IIb; Level of Evidence B).
lowering
Fibrillation
Risk Factor Antiplatelet Special Case
Statin Aspirin
*Secondary Prevention
2013
*Oral antithrombotic
2013 Stroke,2012;43: 3442-3452
2013

Pharmacotherapy of Stroke

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*PHARMACOTHERAPY

Sub Arachnoid Intraparenchymal

Forum Apoteker Indonesia 3

Modifiable Non Modifiable

Hypertension Family History

Forum Apoteker Indonesia 4

* DRUG THERAPY IN ISCHEMIC STROKE

Forum Apoteker Indonesia 6

*Exclusion Criteria for

*Physicians should review the criteria outlined to

*If the patient develop severe headache, acute

*Measure blood pressure every 15 minutes

Forum Apoteker Indonesia Jauch,et

*The usefulness of clopidogrel for the treatment

*In both trials, the routine use of aspirin was

*Blood pressure typically decreases

*Blood Pressure in Stroke

Forum Apoteker Indonesia 17

*An optimal long-term antihypertensive therapy for

*Blood Pressure control

(Class I; Level of Evidence B)

* Blood Pressure Control

Forum Apoteker Indonesia 21

time of onset of ischemic stroke, continuation

of statin therapy during the acute period is

reasonable (Class IIa; Level of Evidence B).

(Class III; Level of Evidence A)

(Davalos, et al. Oral citicoline in acute ischemic stroke: an

(Cochrane Database Syst Rev, 2012 Sep 12)

* DRUG THERAPY IN HEMORRHAGIC

(Class I; Level of Evidence B)

(Class IIa; Level of Evidence C).

(Class I; Level of Evidence A).

Forum Apoteker Indonesia Connoly,et

* The routine long-term use of anticonvulsants is not

* but may be considered for patients with known risk

Risk Factor Antiplatelet Special Case

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