YEAH

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
5

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%
12

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
17

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
20

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