Stroke Therapeutics
Transcript of Stroke Therapeutics
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ro e erapeu cs
Stroke
Clinical syndrome
Characteristics
y Rapidly developing clinical symptoms
y Signs of focal (or global) loss of cerebral function
y Symptoms lasting > 24h (or leading to death)
y No apparent cause other than vascular origin
Clinical Features
Anterior (carotid) artery circulationPosterior (vertebrobasilar) artery
circulation
Middle cerebral artery
y Aphasia (dominant hemisphere)y Hemiparesis/ plegia
y Hemisensory loss/ disturbance
y Homonymous hemianopia
y Parietal lobe dysfunction
(eg. astereognosis,
agraphaesthesia, impaired 2-
point)
y Discrimination, sensory & visual
inattention, left-right
dissociation, acalculia
Anterior cerebral artery
y Weakness of lower limb more
than upper limb
Homonymous hemianopia
Cortical blindnessAtaxia
Dizziness, vertigo
Dysarthria
Diplopia
Dysphagia
Horners syndrome
Hemiparesis/ hemisensory loss
(contralateral to cranial nerve palsy)
Cerebellar signs
Types of Stroke
Ischaemic Haemorrhagic
Majority (85%) ischemic origin
Main phenomena
y Platelet activation cascade
(adhesion, activation,
aggregation)
y Blood coagulation cascade
(fibrin formation)
Smaller percentage (15%)
Types
Intracranial
haemorrhage
(ICH)
Subarachnoid
haemorrhage
(SAH)
Hypertension Aneurysm
AVM
Early changes
Ischaemic coreIschaemic
penumbra
Region of brain
without
significant
blood supply
Regions of
decreased or
marginal
perfusion
Dies within
minutes
May remain
viable for a few
hours
Neuronal
tissue
preservation
possible
Risk FactorsUnmodifiable Modifiable
Age
Sex
Ethnicity
Family history
Hypertension
Diabetes
Coronary heart disease
Atrial fibrillation
Hyperlipidaemia
Smoking
Obesity
Previous stroke
Sedentary life style
Dietary salt, alcohol
Prognosis
Depends on
y Type
y Size
y Location
Higher mortality in haemorrhagic stroke
Poor prognosis
y Brainstem infarct
y Large hemispheric infarct
y Cardio embolic stroke
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Ischaemic Stroke Therapeutics
Fibrinolytics Antiplatelets Anticoagulants
rt-PA
Recombinant tissue-type plasminogen activator
Treatment of ischaemic stroke
(streptokinase not recommended)
Indication - Acute treatment of ischaemic stroke
Reperfuse ischaemic brain & salvage penumbra area
IV rt-PA within 3h of onset
(can likelihood of return to normal by 30%)
t-PA promote formation of plasmin from plasminogen
(enzyme that digests fibrin)
Aspirin (COX Inhibitor)
Indication Acute treatment of ischaemic stroke
y Recommended to start within 48h of stroke
onset
y Not recommended within 24h of fibrinolytic
administration
Prevention
Primary (1°) Secondary (2°)
Only useful in
females > 65 y/o
Given to all patients of
stroke to prevent
further stroke
Aspirin inhibit platelet aggregation
(by inhibiting synthesis of TxA2)
(irreversibly inhibiting COX enzyme)
Heparin, Warfarin
Indications
y Not indicated in acute treatment of ischaemic
stroke
y Followingcardio embolic stroke
Need to monitor closely for haemorrhage
Anticoagulants
Heparin (UHF) Warfarin
Given in high risk
patient
Given after patient has
stabilised
Clopidogrel/ Ticlopidine (ADP Inhibitors)
Indications - Secondary (2°) prevention
y Alternative to aspirin (eg. intolerant)
y Double therapy
(aspirin + clopidogrel/ ticlopidine)
indicated only in selected high risk patients
if benefit outweighs risk
Treatment Guidelines Prevention
Primary (1°) Secondary (2°)
Hypertension
DiabetesMellitus
Hyperlipidaemia
Smoking
Aspirin therapy
Post menopausal HRT
Alcohol
Strategies used after a stroke
(prevent recurrence)
Risk for recurrent vascular event
(after stroke or TIA)
y 5% per year for stroke
y 3% per year for myocardial
infarction
Antiplatelets
Aspirin
Clopidogrel
Ticlopidine
Anti-hypertensive treatment
Lipid lowering
Diabetic controlCigarette smoking
Cardioembolism
Account for up to 20% of ischaemic stroke
Associated with poor prognosis
Common source
y Intra-atrial emboli
y Intra-ventricular emboli
Causes
y Atrial fibrillation (50%)
y Prosthetic heart valves
y Rheumatic valvular heart disease
y Recent MI
y Non thrombotic endocarditis, myxoma
Treatment
y Aspiriny Warfarin
y Heparin (unfractionated)
y Anticoagulation
Revascularization
Carotid endarterectomy (CEA) Angioplasty/ stenting (CAS)
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Management of Haemorrhagic Stroke
Depend on
y Underlying cause of haemorrhage
y Extent of damage
Repair of cause of bleeding surgical removal (large clots)
Symptomatic treatment
y Intracranial pressure (ICP)
Haemorrhagic stroke is often associated with symptoms of ICP
y Blood pressure
y Seizures
Location
Subarachnoid Intracerebral Cerebellar Lobar
Neurosurgical
intervention
Management of
ICP
Surgical
evacuation(good outcome)
Neurosurgical
evacuationNimodipine
(CCB)
Neurosurgical
decompression
Management
Mannitol Antihypertensives Factor VIIa
Osmotic diuretic If BP not controlled Limit bleeding &
hematoma formation
if given early (< 4h)Effective in acutely
reducing raised ICP
Risk of
thromboemoblism
Removal of anticoagulants/
antithromboticsOthers
Haemorrhagic stroke results from
administration of anticoagulants/
antithrombotics
Pain relievers
Antianxiety medications
Anticonvulsants for seizures