Pharmaceutical Care II

Cerebrovascular Disease
FALL 24-25
Luma Ameer
Learning Objectives
By the end of this lecture you will be able to:

● Describe the different types of cerebrovascular accidents (including

ischaemic strokes, and hemorrhagic strokes)
● Revise the pathophysiology of strokes
● Describe the clinical presentation of patients with a stroke, and interpret
diagnostic data
● Optimize patient therapy in line with current evidence based guidelines.
Definition
“Stroke involves the abrupt onset of of neurologic dysfunction that lasts at
least 24 hours and is caused by cerebral, spinal or retinal infarction. Stroke can
be either ischemic or hemorrhagic”

Transient Ischemic attacks (TIAs are focal ischemic neurological deficits lasting
less than 24 hours and usually less than 30 minutes)

Schwinghammer T.L., & DiPiro J.T., & Ellingrod V.L., & DiPiro C.V.(Eds.), (2021). Pharmacotherapy
Handbook, 11e. McGraw Hill. pp149
https://www.neofect.com/us/blog/what-are-the-different-types-of-stroke
Hemorrhagic stroke
● This includes subarachnoid hemorrhage (SAH) and intracerebral
hemorrhage
● Arises from a trauma, or rupture of an intracerebral aneurysm

https://www.rch.org.au/kidsinfo/fact_sheets/Cerebral_Aneurysm/
Ischemic stroke
● 87% of all strokes
● Due to occlusion of cerebral artery, which reduces cerebral blood flow
● Due to local thrombus formation or emboli from a distant site (consider
cardioembolic causes)
● Modifiable risk factors:
○ Hypertension
○ Cigarette smoking
○ Diabetes
○ Atrial fibrillation
○ Dyslipidemia
National Institute of
Health Stroke Scale

Determines the the severity

of a stroke, and guide
treatment
PDFfiller - nihss stroke scale pdf.pdf
Clinical presentation
Depends on the area of the brain involved

● Cognitive or language deficits (cannot respond or speak)

● Unilateral weakness
● Inability to speak
● Loss of vision
● Vertigo
● Falling
● Headache (more common in hemorrhagic stroke)
https://www.health.com/stroke-overview-7254292
 Diagnosis
● Brain imaging (CT) within 20
minutes of arrival to ER
● Blood glucose, platelet count,
and coagulation parameters are
needed to determine treatment
eligibility.

https://radiopaedia.org/articles/ischaemic-stroke
Non Pharmacological Management (not
examinable)
Ischemic stroke

● Removal of clot (thrombectomy with stents)

● Decompressive hemicraniectomy

Hemorrhagic stroke

Surgical clipping of embolism

Pharmacological Treatment - Acute
Alteplase in a plasminogen activator used for ischemic stroke within 4.5 hours of
symptom onset improves functional ability (FDA Approval up to 3 hours) in patients
over 18 years
Contraindications:
● Use of treatment dose (1mg/kg or 1.5mg/kg) enoxaparin in last 24 hours
● Active internal bleeding (such as intercranial hemorrhage)
● Gastrointestinal malignancy, or bleeding in last 21 days
● Persistent blood pressure elevation (systolic ≥185 mmHg or diastolic ≥110
mmHg)
● Lab results which increase bleeding risk (INR more than 1.7, aPTT more
than 40 sec, platelet count less than 100,000/mm3
Monitoring: monitor for bleeding (HgB, Hct, signs and symptoms of bleeding)
with neurological exam and BP every 15 minutes for 1 hour, then every half
hour for 6 hours, then every hour for 17 hours. Head CT after 24 hours, before
starting antiplatelets
Pharmacological Treatment- Alteplase
● STOP IF SEVERE HEADACHE, NAUSEA OR VOMITING OCCUR, AND REPEAT
CT
● Thrombolytic therapy can only be given if the BP is ⋜185/110mmHg (see
next slide)- if high BP is the only contraindication, then lower BP first (see
later). Maintain BP below 180/110mmHg for at least first 24 hours after
treatment
● Other treatment Aspirin 160mg-325mg within 48 hours of therapy.
● (Avoid antiplatelet for 1st 24 hours after alteplase)
Sample calculation (EXAMINABLE)
Alteplase 0.9milligram/kg (MAXIMUM 90mg)
10% perfused as an initial bolus over 1 minute, remainder given over 1 hour
Mr H presents to the ER with slurred speech, and left sided weakness, which
started 1 hour ago. Following a CT scan which shows areas of ischemia, the
doctor decides to prescribe alteplase.
The patient weighs 76kg.
1) What is the total dose of alteplase?
2) How many milligrams would be given over the first minute?
Acute management of BP
● If the patient is to have thrombolytic therapy, the goal is

⋜185/110mmHg

● If the patient is not going to have thrombolytic therapy, the BP can remain as high
as 220/120mmHG for 48-72 hours (because early BP reduction is not proven to
prevent death, or reduce morbidity)
● Use of short acting, titratable IV meds is preferred:
● Labetalol 10-20mg over 1-2 minutes
● Nicardipine 5mg/hour
Other management issues
● Maintain glucose levels between 140-180mg/dl, and closely monitor to
prevent hypoglycemia
● DVT prevention- avoid using anticoagulants (including enoxaparin and
heparin)within 24 hours of using alteplase.
● Intermittent pneumatic compression is recommended
Secondary prevention of ischemic stroke
● For non cardioembolic ischemic stroke or TIA the patient should use one
of the following long terms therapies
○ Aspirin
○ Clopidogrel
○ Aspirin + dipyridamole (extended release)
○ Combination aspirin and clopidogrel can be used, for 21 then continue with
monotherapy
● For Stroke or TIA due to AF or cardioembolism use one of the following
○ Warfarin
○ Apixaban/ Rivaroxaban/dabigatran/edoxaban
Secondary prevention
● Blood pressure more than 130/80mmHG should be treated (preferred
agents)
○ Thiazide (examples______________)
○ ACEI/ ARB (examples_____________)

Target BP 130/80mmHG

● Statin therapy is recommended irrespective of baseline cholesterol levels.

● ⋜ 75 years high intensity statin therapy (see next slide)
● More than 75 years moderate or high dose statin therapy (atorvastatin 80mg preferred)
● If patients do not achieve LDL ⋝ 70mmHg such as Ezetimibe may be added
Intensity of statin therapy- ACC Guidelines

Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blu-
menthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-
Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling L, Virani SS, Yeboah J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/
ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart
Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;73:e285–350.
Hemorrhagic stroke
● Hemorrhagic stroke has significant morbidity, and mortality.
● Management is supportive, including
○ Airway management
○ Establishing homeostasis
○ Prevention and management of seizures
○ Assessing dysphagia
○ DVT prophylaxis
 Intracerebral or subarachnoid hemorrhage
Subarachnoid hemorrhage between the
brain, and surrounding membrane

Usually caused by a cerebral aneurysm

rupture presents as a severe headache .

Intracerebral is the rupture of a fine

blood vessel INSIDE the brain

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Hemorrhagic stroke
Unlike ischemic stroke, patients with a very HIGH BP should have the BP
aggressively managed in the acute setting, to less than 160mmHg systolic BP

Mannitol is used for intracerebral hemorrhage is used because it leads to

osmotic diuresis which reduced intracranial pressure (WARNING: CNS toxicity
can occur due to accumulation in the brain)

A frequent cause of hemorrhagic stroke is use of anticoagulants. The following

are the antidotes/ reversal agents
https://www.grepmed.com/images/7778/anticoagulation-reversal-criticalcare-pharmacology-hematology
Evaluation of Therapeutic Outcomes
● Monitor patient for neurological worsening, adverse drug reactions, and
complications
● Monitor the following (common causes of complications)
○ Cerebral edema, raised intracranial pressure
○ Hypertensive emergency
○ Infection
○ Venous thromboembolism
○ Electrolyte abnormalities
○ Recurrent stroke
References.

Schwinghammer T.L., & DiPiro J.T., & Ellingrod V.L., & DiPiro C.V.(Eds.), (2021). Pharmacotherapy
Handbook, 11e. McGraw Hill.

Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, Kamel H, Kernan WN,
Kittner SJ, Leira EC, Lennon O, Meschia JF, Nguyen TN, Pollak PM, Santangeli P, Sharrief AZ, Smith SC Jr,
Turan TN, Williams LS. 2021 Guideline for the prevention of stroke in patients with stroke and transient
ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke.
2021;52:e364–e467. doi: 10.1161/STR.0000000000000375

Matthew Schrag, Howard Kirshner,Management of Intracerebral Hemorrhage: JACC Focus Seminar,Journal

of the American College of Cardiology,Volume 75, Issue 15,2020,Pages 1819-1831,