Stroke can be either ischemic (caused by blockage of a blood vessel) or hemorrhagic (caused by bleeding). The goals of treatment are to reduce ongoing brain injury, prevent complications, and prevent future strokes. For ischemic strokes, intravenous tPA within 4.5 hours can reperfuse brain tissue. Aspirin is also given to reduce risk of future strokes. Hemorrhagic strokes require controlling blood pressure and intracranial pressure to prevent further brain damage.

1. Pharmacotherapy of stroke

2. Stroke
 Injury or death of brain tissue due to oxygen deprivation;
usually due to an interruption of blood flow
 Characterized by abrupt onset of focal neurologic deficit
that is attributable to a focal vascular cause
 Also referred to as “Brain Attack” or “Cerebrovascular
Accident” (CVA)

3. Introduction
 Clinically stroke is
 A sudden onset non convulsive neurologic deficit
characterized by the rapid appearance (usually over
minutes) of a focal deficit of brain function
 Including a hemiplegia with or without signs of focal
higher cerebral dysfunction (such as aphasia),
hemisensory loss, visual field defect or brain-stem deficit
 In stroke the evidence of brain dysfunction ( neurologic
deficit) lasts for at least 24h or more

4. Introduction
Transient Ischemic Attack (TIA)
 “Mini-stroke”
 a temporary focal neurologic deficit lasting < 24 hours
(typically < 30 minutes)
 Caused by brief interruption of blood supply to part of
the brain
 35% of untreated patients will develop a stroke within
5 years of TIA

5. Introduction
 Stroke can be either
 Ischemic (88% )
 Hemorrhagic (12%)
 Ischemic stroke:
 Caused either by
 In situ thrombosis of an intracranial vessel,
typically affecting the small penetrating arteries or
 Occlusion of an intracranial vessel by an embolus
that arises from a distant site (e.g., cardiogenic
embolus)
 Hypoperfusion caused by flow-limiting stenosis of a
major extracranial artery
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6. Causes of Ischemic Stroke

7. Ischemic Stroke
 Normal cerebral blood flow: 50 mL/100 g per minute
 Arterial occlusion-----severe reductions in cerebral blood
flow-----infarction
 Tissue that is ischemic but maintains membrane integrity
is referred to as the ischemic penumbra ----- surrounds the
infarct core------salvageable through therapeutic
intervention

8. Hemorrhagic stroke
Hemorrhagic stroke
 less common but lethal
 Pathogenesis: mechanical effect (mass effect) of blood and
neurotoxicity of the blood components and their degradation
products
 Includes
 Subarachnoid hemorrhage
 Intracerebral hemorrhage
 Subdural hematomas

9. Hemorrhagic stroke
 Subarachnoid hemorrhage
 Occurs when blood enters the subarachnoid space
(where cerebrospinal fluid is housed)
 Caused by trauma, rupture of an intracranial
aneurysm, or rupture of an arteriovenous
malformation

10. Hemorrhagic stroke
 Intracerebral hemorrhage
 Occurs when a blood vessel ruptures within the
brain parenchyma itself, resulting in the formation of
a hematoma
 Associated with uncontrolled high blood pressure,
antithrombotic or thrombolytic therapy

11. Hemorrhagic stroke
 Subdural hematomas
 Collections of blood below the dura (covering of the
brain)
 Caused by trauma

12. Stroke Classification
Transient
Ischemic Attack
(TIA)
Stroke
Ischemic Stroke
Hemorrhagic stroke
• Intracrebral (ICH)
• Subarachnoid
•Subdural hematoma
Cryptogenic
Stroke
Atherosclerotic
cerebrovascular
disease
Penetrating
artery disease
(Lacunes)
Other causes
• Prothrombotic states
• Dissections
• Arteritis
• Migraine/Vasospasm
• Drug abuse
• Many more
Cardiogenic emboli
• Atrial fibrillation
• Valve disease
• Ventricular thrombi
• Many others
87%
13%
20% 25% 20% 30% 5%
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13. Risk factors
 Classified into
 Non-modifiable risk factors
 Modifiable risk factors

14.  Nonmodifiable risk
factors
 Age
 Risk doubles for each
decade after 55 years of
age
 Sex
 Men >>>> women
 Women more likely to
die from stroke
 Low birth weight
 Race/ethnicity
 family history
 Modifiable risk factors
 Arterial hypertension:3-4x
 DM-2-4x
 Smoking -2-3x
 Atrial fibrillation: 5% to
20% per year
 Dyslipidemia
 TIA
 Prior stroke
 Carotid disease
 Excessive alcohol
 High fibrinogen
 High homocystein
 Low folate
 Anticardiolipin Ab
 Obesity

15. Clinical Presentation
General
 The patient may have cognitive or language deficits
Symptoms
 Weakness on one side of the body
 Inability to speak
 Loss of vision
 Vertigo or falling
 Headache severe with hemorrhagic stroke

16. Clinical Presentation
Signs
 Neurologic dysfunction
 Hemiparesis or monoparesis
 Hemisensory deficit
 Vertigo and double vision
 Aphasia: anterior circulation strokes
 Dysarthria
 Visual field defects
 altered levels of consciousness

17. Facial Droop
Normal Abnormal
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18. Clinical Presentation
Laboratory Tests
 Hypercoagulable states: protein C deficiency, protein
S, antithrombin III, and antiphospholipid antibody
Diagnostic Tests
 CT scan of the head
 Area of hyperintensity (white): hemorrhage and
 Normal or hypointense (dark): infarction
 MRI of the head: ischemia detected with higher
resolution and earlier than the CT scan
 Carotid Doppler (CD): Stenosis in the carotid arteries
supplying blood to the brain (extracranial disease)
 ECG: AF
 Echocardiography: Valve or wall motion
abnormalities

19. Treatment
Desired Outcomes
 To reduce the ongoing neurologic injury
 To decrease mortality and long-term disability
 To prevent complications secondary to immobility and
neurologic dysfunction and
 To prevent stroke recurrence

20. Organization of Stroke Management
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21. Treatment
General Approach to Treatment
 Respiratory and cardiac support
 Determine whether the lesion is ischemic or
hemorrhagic
 Ischemic stroke
 Evaluate for reperfusion therapy

22. Treatment
General Approach to Treatment
 Do not treat elevated blood pressure unless it exceeds
220/120 mm Hg, or there is evidence of
 Aortic dissection
 Acute myocardial infarction (AMI)
 Pulmonary edema, or
 Hypertensive encephalopathy
 SAH: if an aneurysm is found by angiography,
endovascular coiling or clipping
 ICH: EVD if
 There is intraventricular blood and evolving
hydrocephalus

23. Acute Ischemic Stroke
Blood Pressure Treatment
 Short acting agents should be used
 Labetalol IV: 10-20 mg doubled every 10-20
minutes(max: 300 mg) or infusion of 2-8 mg/min
 Nicardipine IV: infusion 5 mg/hr – 15 mg.hr
 Nitroprusside IV: infusion 0.5 mcg/kg/min
 Selection of agents depends on the elevation in BP

24. Pharmacologic Therapy
Ischemic Stroke
 Acute treatment
 Two agents with class I recommendations
 IV tissue plasminogen activator (tPA) within 4.5 hours
of onset
 0.9 mg/kg over 1 hour, with 10% given as initial bolus
over 1 minute
 avoid antithrombotic (anticoagulant or antiplatelet)
therapy for 24 hours
 Monitor: blood pressure, response, and hemorrhage
 Monitor BP every 15 minutes for 2 hours after start of
infusion, then every 30 minutes for 6 hours, and every
60 minutes for 16 hours
 Aspirin within 48 hours of onset
 160-325 mg QD

25. Pharmacologic Therapy
 Inclusion criteria for tPA therapy
 Age > 18 yrs
 Ischemic stroke
 Persistent neurologic deficit
 CT negative for hemorrhage
 Symptom onset < 4.5 hours

26. Pharmacologic Therapy
 Exclusion criteria for tPA therapy

27. Pharmacologic Therapy
 Early aspirin therapy
 Reduce long-term death and disability
 Should never be given within 24 hours of the
administration of tPA
 Increase the risk of bleeding

28. Pharmacologic Therapy
 Antiplatelet therapy
 Cornerstone of antithrombotic therapy for the
secondary prevention of ischemic stroke
 should be used in noncardioembolic strokes
 First-line antiplatelet agents
 Aspirin: 62-325 mg QD
 Clopidogrel: 75 mg QD
 Extended-release dipyridamole plus aspirin (ERDP-
ASA): 200 mg/25 mg BID

29. Pharmacologic Therapy
Secondary prevention of ischemic stroke
 In patients with atrial fibrillation and a presumed cardiac
source of embolism
 Oral anticoagulation
 Warfarin, dabigatran (direct thrombin inhibitor),
rivaroxaban, and apixaban (direct factor Xa
inhibitors)
 INR: 2.5

30. Pharmacologic Therapy
Statins
 reduce the risk of stroke by 30% in patients with CAD
and elevated plasma lipids
 Ischemic stroke patients, regardless of baseline
cholesterol, be treated with high-intensity statin therapy
 Atorvastatin: 80 mg/day
 Simvastatin: 80 mg/day

31. Pharmacologic Therapy
Prophylaxis of Deep Vein Thrombosis (DVT)
 Decreased mobility owing to stroke: risk of DVT
increases
 LMWH or UFH
 Enoxaparin: 1 mg/kg/day
 UFH: 5,000 units three times daily

32. Hemorrhagic Stroke
 SAH: can cause delayed cerebral ischemia (DCI) between
4 and 21 days after the bleed
 Cause: vasospasm of the cerebral vasculature
 Treatment: nimodipine 60 mg every 4 hours for 21 days

33. Hemorrhagic Stroke
ICH

34. Treatment
 Management of ICH involves a combination of medical
and surgical interventions
 Use of antipyretic medications to lower body
temperature to normothermia in febrile patients with
stroke
 Hyperglycemia in the first 24 hours after stroke is
associated with adverse outcomes
 Insulin treatment for elevated serum glucose >140 to
185 mg/dL

35. Treatment
 All anticoagulant and antiplatelet drugs should be
discontinued acutely for at least one to two weeks after the
onset of hemorrhage
 Anticoagulant effect should be reversed immediately with
appropriate agents
 Vitamin K, unactivated prothrombin complex concentrate
(also called factor IX complex)
 High doses (ie, 10 to 20 mg) of intravenous vitamin K can
fully reverse warfarin-induced anticoagulation

36. Intracranial pressure control
 Increased ICP
 Contribute to brain injury and neurologic
deterioration
 Management of elevated ICP
 Elevate the head of the bed to 30 degrees, once
hypovolemia is excluded
 Analgesia and sedation, particularly in unstable,
intubated patients: reduce cerebral metabolism

37. Intracranial pressure control
 IV mannitol
 Dose: initial bolus of 1 g/kg, followed by infusions of
0.25 to 0.5 g/kg every six hours
 The goal of therapy is to achieve plasma
hyperosmolality (300 to 310 mosmol/kg) while
maintaining an adequate plasma volume
 Side effects: pulmonary edema, hyponatremia and
metabolic acidosis, and hyperkalemia

38. Evaluation Of Therapeutic Outcomes
Monitoring of the Pharmaceutical Care Plan
 Monitor for the development of
 Neurologic worsening (recurrence or extension)
 complications (thromboembolism or infection), or
 Adverse effects from pharmacologic or non-
pharmacologic interventions

39. Evaluation Of Therapeutic Outcomes