Pharmaceutical Care of Stroke

Dr. WIDYATI, MClin Pharm, Apt

 Definition of Stroke
• Sudden brain damage
• Lack of blood flow to the brain caused by a
clot or rupture of a blood vessel

Ischemic = Clot
(makes up approximately
87% of all strokes)
Embolic Thrombotic

Hemorrhagic = Bleed
- Bleeding around brain
- Bleeding into brain
 THREE STROKE TYPES
Focal Brain Dysfunction

Ischemic Intracerebral Subarachnoid

Stroke Hemorrhage Hemorrhage

85% 10% 5%

Clot occluding Bleeding Bleeding

artery into brain around brain

Diffuse Brain Dysfunction

 Pokok Bahasan

Secondary
Pharm Common
DRP
Prevention
Care in
Stroke
Monitoring
Konsellng
 PROBLEM MEDIK UMUM
1. Munculnya komplikasi neurologis menyulitkan
penatalaksanaan

2. Munculnya komplikasi medik seperti ISK, pneumonia, luka

baring, thromboemboli.

3. Pasien memiliki gagal organ eliminasi seperti GGK,

maupun Cirrhosis hepatik (CH) yang mempersulit
penatalaksanaan.

4. Pasien memiliki penyakit penyerta DM yang memerlukan

perhatian khusus.
 Stroke Thrombotik
• Peningkatan TIK bila Stroke luas
• Hiperglikemia
 SAH
• Hyperdinamik
• Vasospasme
• Nyeri kepala hebat
 Stroke ICH
• Peningkatan TIK
• Nyeri kepala
• Seringkali disertai kejang
 1. Neurological Complications
a. Reduced Level of Consciousness (↓LOC)
b. Worsening of neurological/physical deficits
c. New deficits indicating dysfunction in
another part of the brain
d. Epileptic seizures
 1a. Reduce LOC
• Occurring in approximately 15% of stroke patients
• Most likely to occur within the first few days after
stroke
• Important indicator of the severity of the stroke
• Potential causes:
– Direct damage
• Hemorrhage or infarction of the brainstem
– Indirect damage
• Supratentorial lesions associated with brain swelling and midline
shift
– Combination
• Global hemispheric ischemia and
• Increased intra-cranial pressure (ICP)
 1b. Worsening Neurological/Physical
Deficits
• Common with initial stroke
• Can worsen hours, days or, rarely weeks after the
initial assessment
• The earlier the stroke is diagnosed, there is an
increase in the likelihood the worsening deficits
will be recognized
• Within the first couple of days the worsening
effects most likely have a neurological
cause/origin
• Beyond the first couple days, non-neurological
causes must be considered
Common Reasons for Deteriorating
• Extension of original lesion (ischemic or bleeding)
• Development of cerebral oedema & ICP↑
• Hypertensive emergency
• Nosocomial Infection
• DVT
• Electrolyte abnormalities and cardiac
disturbances
• Recurrent stroke
 Non-Neurological Causes
• Infection: • Hypoxia:
– Respiratory – Pneumonia/chest
– Urinary infection
– Septicemia – Pulmonary embolism
• Metabolic – Chronic pulmonary
disease
– Dehydration
– Pulmonary edema
– Electrolyte imbalances
• Hypercapnea
– Hypoglycemia
– Chronic pulmonary
• Drugs: disease
– Major and minor • Limb or bowel ischemia in
tranquilizers patients with a cardiac or
– Baclofen aortic arch source of
– Lithium toxicity embolism
– Anti-epileptic drug toxicity
– Anti-emetics
 1d. Epileptic Seizures
• Occurring in approximately 5% of stroke
patients, most occurring within 24 hours
• The highest overall risk population includes
those who have hemorrhagic strokes and
infarcts involving the cerebral cortex
• Most seizures begin as partial (focal) although
with secondary generalization
 Neurological Causes (Epilepsy)
• Primary stroke lesion location
• Hemorrhagic transformation of infarction
• Arteriovenous malformation
• Intracranial venous thrombosis
• Mitochondiral cytopathy
• Hypertensive encephalopathy
• Wrong diagnosis:
– Herpes simplex encephalitis
– Cerebral abscess
– Intracranial tumor
– Subdural empyema
 General Causes of Epilepsy
• Alcohol withdrawal • Drugs:
• Anti-epileptic drug – Baclofen (for
spasticity)
withdrawal
– Antibiotics
• Hypoglycemia
– Antidepressants
• Hyperglycemia, non- – Phenothiazines (for
ketotic agitation hiccups)
• Hyper/hyponatremia – Anti-arrhythmics (for
atrial fibrillation)
• Hypocalcemia
• Hypomagnesemia
 2. Medical Complication
• UTI
• Pneumonia
• Falls
• Pressure Ulcer
• Thromboembolism
• Cardiac abnormality
• Hiperglikemia
 2a. Urinary Tract Infection
• Occurs in approximately 25% of hospitalized stroke
patients within the first two months after stroke
• Prevention:
– Maintaining adequate hydration and thus urine output
– Avoid unnecessary bladder catheterization
– Avoid constipation (will assist with complete bladder
emptying)
– Avoid drugs with anticholinergic effects
– Assess for fever, investigate cause if present in
combination with broad spectrum antibiotics
 2b. Pneumonia
• Occurring in approximately 20% of stroke patients
during the acute stage
• Increased incidence in tube fed patients or with
alterations in the mouth’s bacterial flora
• Probable causes:
– Aspiration
– Failure to clear secretions
– Patient immobility
– Reduced chest wall or diaphragmatic movement on the
hemiparetic side
– Comorbidities:
• Chronic airway disease
 Pneumonia (cont.)
• Prevention:
– Careful positioning (HOB at 30˚)
– Oral care, using peridex every 12 hours for those
on ventilators
– Physiotherapy and suction to avoid accumulation
of secretions
– Aspiration precautions
 2c. Falls
• Very common after stroke
• Patient’s with lessened deficits after stroke are more likely
to fall, because the patient’s with more severe deficits are
mobilized less decreasing their likelihood of fall
• Often associated with an increased risk of intracranial
hemorrhage associated with anticoagulation (atrial
fibrillation population)
• Risk reduction:
– Mobilize patients with adequate supervision and support
– Utilization of bed alarms
– Safety alert/Fall risk
– Withdrawal of unnecessary diuretics and psychotropic drugs
– Convenient room set up
 2d. Pressure Ulcers
• Most common in patients that are immobile and unable to
redistribute their own weight when lying or sitting
• Increased risk factors:
– Malnourishment
– Infection
– Incontinence
– Serious underlying illnesses
• Prevention:
– Accurate skin assessment daily and as needed (with removal of
the graded compression stockings)
– Frequent repositioning
– Pressure relieving mattresses
– Nutrition support
– Local treatments (creams, lotions etc.)
 2e.Hyperglycemia and Stroke
• Blood glucose elevated in 40-50% of patients
in the first 24 hours. Over half are not D.M.
• Insulin Tx reduces infarct size and improves
prognosis (benefits focal & global brain
ischemia)
• Aim to maintain normal glucose and avoid
poor outcome.
 Blood glucose management
• Hyperglycaemia has been associated with aggravation of
cerebral oedema as well as increased stroke severity and
mortality.

• Hypoglycaemia cam mimic the symptoms of stroke.

 2f.Cardiac Abnormalities in Stroke
• One-third of patients – ST Segment
Depression or Ventricular Arrhythmias – first 5
days
• Previously undiagnosed Arrhythmias including
A-Fib – seen in 50%
• Insular Cortex Lesions predispose to EKG
changes Arrhythmias and sudden death. Rec-
24-48 hour monitor and treatment.
 Fluid balance and hydration
Why do a fluid balance?

 Cardiac function

 Renal function

 Endocrine function

 Electrolytes
 Signs of dehydration
• Tachycardia
• Hypotension
• Low urine output (less than 0.5ml/Kg/hr)
• Dark concentrated urine
• Dry mucosa

Think what the problem is!

 DRP UMUM
• Pemilihan antiplatelet kurang tepat
• Pemilihan antihipertensi kurang tepat
• Pemilihan antibiotika pada pasien dengan infeksi
nosokomial menjadi penting karena terkait pula
dengan progress neurologinya.
• Pemilihan antikejang perlu hati-hati baik karena insiden
peningkatan SGOT/SGPT menjadi lebih mudah juga
pada pasien dengan CH.
• Waspada ADR khususnya terhadap fungsi ginjal
maupun liver.
• Di RSAL : interaksi obat 39,4% (Jane, 2007)
 Anti Platelet
• Digunakan pada stroke iskemik
• Agen: aspirin, ticlopidin, clopidogrel,
dipiridamol, aspirin+dipiridamol,
aspirin+clopidogrel, cilostazol
• Awasi gastric bleeding khususnya pada masa
akut, pasien dengan CH, pasien dg riwayat
gastric ulcer.
 Blood Pressure – ASA Guidelines
• High or Low may affect stroke outcome
• Early stage – systolic BP 150-170 is optimal
• More aggressive Tx with malignant HTN
Myocardial Ischemia, Aortic Dissection, post
TPA
• LBP – often Hypovolemia & Tx with Fluids,
pressors PRN
 Blood Pressure Control

• In poor flow states―which occur with thrombotic and

embolic ischemic stroke, as well as with increased ICP
due to cerebral edema―the cerebral vasculature loses
vasoregulatory capability and thus relies directly on
mean arterial pressure (MAP) and cardiac output for
maintenance of cerebral blood flow. Therefore,
aggressive efforts to lower blood pressure may
decrease perfusion pressure and may prolong or
worsen ischemia. Rapid reduction of blood pressure,
no matter the degree of hypertension, may in fact be
harmful. Both elevated and low blood pressures are
associated with poor outcomes in patients with acute
Management of Hypertension in Patients With Acute ICH

Acute (<6 h from symptom onset)

spontaneous ICH

SBP 150–220 mm Hg SBP >220 mm Hg

SBP lowering with

SBP lowering to
continuous IV infusion and
<140 mm Hg
close BP monitoring
(Class III:Harm)
(Class IIa)

Colors correspond to Class of Recommendation in Table 1.

BP indicates blood pressure; ICH, intracerebral hemorrhage; IV, intravenous;
and SBP, systolic blood pressure.
 Acute Ischemic Stroke
Recommendations for Management of Hypertension in
COR LOE
Patients With Acute Ischemic Stroke
Adults with acute ischemic stroke and elevated BP who are eligible
for treatment with intravenous tissue plasminogen activator should
I B-NR have their BP slowly lowered to less than 185/110 mm Hg before
thrombolytic therapy is initiated.

In adults with an acute ischemic stroke, BP should be less than

185/110 mm Hg before administration of intravenous tissue
I B-NR plasminogen activator and should be maintained below
180/105 mm Hg for at least the first 24 hours after initiating
drug therapy.
Starting or restarting antihypertensive therapy during
hospitalization in patients with BP greater than 140/90 mm Hg
IIa B-NR who are neurologically stable is safe and reasonable to
improve long-term BP control, unless contraindicated.
 Acute Ischemic Stroke (cont.)

Recommendations for Management of Hypertension

COR LOE
in Patients With Acute Ischemic Stroke
In patients with BP of 220/120 mm Hg or higher who did not
receive intravenous alteplase or endovascular treatment and
have no comorbid conditions requiring acute antihypertensive
IIb C-EO treatment, the benefit of initiating or reinitiating treatment of
hypertension within the first 48 to 72 hours is uncertain. It
might be reasonable to lower BP by 15% during the first 24
hours after onset of stroke.
In patients with BP less than 220/120 mm Hg who did not
receive intravenous thrombolysis or endovascular treatment
III: and do not have a comorbid condition requiring acute
No A antihypertensive treatment, initiating or reinitiating treatment of
Benefit hypertension within the first 48 to 72 hours after an acute
ischemic stroke is not effective to prevent death or
dependency.
 INFEKSI NOSOKOMIAL
• Bakteri Patogen: Acinetobacter sp,
Staphylococcus sp, Klebsiella, Pseudomonas
• Pilih antibiotika yang tersensitif di RS untuk atasi
INOS.
• Untuk klebsiella, pseudomonas: AB+
aminoglikosida
• AB: Cefalosporin Gen III, IV, Carbapenem, Fluoro
Quinolon generasi terbaru
• Aminoglikosida: amikasin, tobramycin, kanamicin,
dibekacin
PEMILIHAN ANTIBIOTIKA PADA INFEKSI
NOSOKOMIAL
Pemilihan antibiotika secara empirik yang tepat
pada awal terapi dapat mengurangi risiko SEPSIS,
KEMATIAN, LAMA TERAPI, menggunakan
ventilator serta BIAYA HOSPITALISASI.
Sulit digeneralisasi, mengingat pola
sensitivitasnya berbeda di setiap rumah sakit.
Peran Mikrobiologis untuk menghasilkan
antibiogram sebagai panduan awal
Perlunya setiap rumah sakit memiliki Komite
Penggunaan Antibiotika di samping Komite
Pengendalian Infeksi Nosokomial (WHO, 2002)
 PRINSIP PEMILIHAN ANTIBIOTIKA
INFEKSI NOSOKOMIAL
STRATEGI DE-ESKALASI
KOMBINASI dg AMINOGLIKOSIDA PADA:
Sepsis, bakteremia, demam neutropeni, atau
infeksi oleh Pseudomonas aeruginosa, MDR
Berikan loading dose bila menggunakan
aminoglikosida, dosis pemeliharaan disesuaikan
fungsi ginjal
Sesuaikan antibiotika dengan hasil kultur segera
Alihkan antibiotika parenteral ke oral segera
setelah kondisi klinik membaik
 Anti Kejang
• Agen: Benzodiazepin, Carbamazepin,
Phenytoin,Luminal
• ADR: semua antikejang memberikan ADR ke liver hanya
berbeda frekuensi kejadian dan jenis gangguan livernya
kecuali Luminal
• Jaundice: Diazepam, CBZ
• Peningkatan SGOT/SGPT: CBZ, Phenytoin
• Hepatitis: CBZ
• Strategi:Pilih yg less hepatotoxic pada CH, awasi
SGOT/SGPT/Bil, bila terjadi peningkatan stop terapi.
 Monitoring
 Efektivitas terapi:
• Fungsi neurologi; dengan mengamati fungsi motorik,
verbal untuk menilai kecukupan terapi neuroprotektant.
• Tanda vital seperti tekanan darah untuk menilai
kecukupan terapi hipertensi. Tanda vital pengamatan
penyakit infeksi khususnya pada pasien dengan infeksi
nosokomial.
• Kadar elektrolit untuk menilai kecukupan terapi cairan
• Ada-tidaknya kejang untuk menilai kecukupan terapi
anti-kejang.
 ADR: fungsi ginjal : kadar kreatinin dan BUN (Mannitol),
liver: SGOT, SGPT, Bilirubin (AED).
 Konseling
 Akut: Efek dan kegunaan obat, cara pakai obat yang self
administered
 KRS:
• Efek dan kegunaan obat
• Penggunaan NSAID secara kronik khususnya yang bisa diperoleh
secara bebas perlu dihindari karena risiko peningkatan tekanan
darah, gastric ulcer. Termasuk pula penggunaan obat tradisional
yang berpotensi mengandung NSAID.
• Kontinuitas terapi
• Pentingnya Non-pharmacologic Therapy
• Pentingnya mengatur terapi penyakit penyerta yang khususnya
menjadi faktor risiko terjadinya stroke seperti hipertensi, Atrial
Fibrilasi, DM.
 SECONDARY STROKE PREVENTION:
ANTIPLATELET AGENTS FOR ARTERIAL DISEASE
• Aspirin
– Prevents MI & stroke
– Stroke rec 50-365 mg/d, but MI rec 75-162 mg/d
– Low dose with less side effects, > 1200 mg/d ineffective
– Enteric coating, NSAIDs may lessen efficacy
• Clopidogrel 75 mg per day
– Prevents MI and stroke
– Routine combination with aspirin not indicated in stroke pts, though
not resolved for subset of pts with large-artery athero
– PPIs lessen efficacy
• Aspirin / dipyridamole XR 25/200 twice daily
– Data regarding MI prophylaxis lacking
– Headache common side effect of dipyridamole
– Not superior to clopidogrel…with more bleeding side effects
 SECONDARY STROKE PREVENTION:
ANTITHROMBOTIC RX BASED ON CAUSE

High-flow states: Low-flow & hypercoagulable states:

platelets cause clots clotting factors cause clots

Platelets are like Velcro Clotting factors are like dissolved powdered gelatin
sticking to bumpy walls that forms clumps of Jello when liquid is static

large-artery small-artery hypercoagulable

cardioembolism
atherosclerosis disease state

ANTIPLATELET AGENT ANTICOAGULANT

aspirin 81-325/d warfarin
clopidogrel 75/d INR 2.0-3.0
aspirin + dipyridamole XR 25/200 twice/d or
INR 2.5-3.5
 ISCHEMIC STROKE / TIA
2 PREVENTION SUMMARY 1 OF 2
– Antithrombotic agent based on cause
– ARB or ACE-I regardless of BP
– Statin regardless of cholesterol
• Maintain:
– Hgb A1C < 7.0
– BP < 120/80, including ARB or ACE-I
– LDL < 70, including statin
– Nutrition w/ fruits, Mediterranean diet
– Alcohol intake < 2 oz/d (men) or < 1 oz/d (women)
– BMI 18.5-24.9 kg/m2
– Aerobic exercise > 20 min/d, > 3 d/wk
 Kasus1
• Tn S, 62th MRS dengan keluhan lemah tangan dan kaki kiri, tak bisa
bicara sejak 7 jam yang lalu. Istri mengaku bahwa Tn S memiliki
riwayat sakit jantung dan obat yang terakhir diminum adalah
Digoxin 1x250 ug, Noperten 1x10mg, Amlodipin 1 x 5mg, Q-ten 1x1
tab. Didukung hasil CT-scan Tn S didiagnosa dengan Ischemic Stroke
embolik. Selanjutnya pasien diterapi dengan Enoxaparin 2x0,4 U
s.c.; Brain Act 3 x 500mg; Plavix 1 x 75mg; Neurobion injeksi 1x1
i.m. Pada hari ketiga muncul komplikasi berupa kejang dan sesak
napas yang disertai panas tinggi hingga 38,2 C. TD yang semula
170/90mmHg pada saat masuk kini turun menjadi 100/70 mmHg.
Pasien didiagnosa sebagai suspect pneumonia. Hasil lab adalah sbb:
leukosit: 17.000/mm3, Cr 2,3 mg/dl ; BUN 29mg/dl. Bagaimana
Pharm Care pada kasus ini?
 References
Warlow et al. (Eds.). (2007). Stroke practical
management. Malden: Blackwell Publishing.
Johnson, K.C., Li, J.Y. et al. (1998). Medical and
neurological complication of ischemic stroke:
Experience from the RANTTAS trial. Stroke, 29, 447-
453.
Dromerick, A. & Reding, M. (1994). Medical and
neurological complications during inpatient stroke
rehabilitation. Stroke, 25, 358-361.
Langhorne, P., Stott, D.J., et al. (2000). Medical
complications after stroke: A multicenter study. Stroke,
31, 1223-1229.