Cerebrovascular Accident: Pathophysiology and Pharmacologic Management

This study material from Desklib discusses the pathophysiology and pharmacologic management of cerebrovascular accident (CVA). It explains the causes, symptoms, and treatment options for CVA, including thrombolytic agents, antiplatelet agents, and hypertensive agents.

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Name of the Student
Name of the university
Author’s note

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Table of Contents
Introduction......................................................................................................................................2
Pathophysiology..............................................................................................................................2
Pharmacologic management............................................................................................................5
Conclusion.......................................................................................................................................6
References........................................................................................................................................8

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Introduction
Stroke is a neurological disease that is the cause of death and disability all around the
world. The pathophysiology of the stroke is complicated and generally involves inflammatory
pathways, excitotoxicity, oxidative damage apoptosis, angiogenesis and ionic imbalances
(Brown et al.,2015). A stroke occurs when there is a sudden death of the cells in some of the
parts of the brain causing a lessening of the blood flow in the brain. This paper would describe
the pathophysiology of stroke linking with the symptoms manifested by Mr. Kwon. The paper
would also throw light on the pharmacological management in relation to the symptoms
displayed.
Pathophysiology
Ischeamic stroke can occur due to the sudden blockage of the cerebral artery. The region of the
brain supplied by this artery can become ischemic and can cause an infarct. And due to high
metabolic demands of brain an irreversible damage might occur within few minutes of ischemia
(Bullock & Hales, 2016).
The concerned patient might have suffered from Ischemia, which might have been
manifested in the form of thrombotic stroke, embolic stroke or systemic hypo perfusion or
venous thrombosis. Thrombosis might have occurred due to the deposition of the atherosclerotic
plaque within the walls of the arteries and a thrombi can easily develop on the surface of the
atherosclerotic lesions (Bullock & Hales, 2016). Low respiratory reserve and the complete
dependence of the aerobic metabolism make the tissues of the brain vulnerable to the effects of
ischemia. Thus a part of the brain parenchyma suffers from immediate death, while the others

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might be injured partially with the potential to recover. Ischemia causes damage to the brain by
the activation of the ischemic cascade that causes the local depletion of oxygen and thus the high
energy phosphate compound is not produced for the brain cells to survive (DeLaune et al., 2016).
The case study reveals that Mr. Sam Kwon had suffered from a stroke because the
clinical manifestation shown by Mr. Kwon complies with the probable signs and the symptoms
of stroke, which are facial drooping, impaired speech, right-sided hemiparalysis and aphasia
Individuals having stroke on the right side of the brain are likely to have problems with the
spatial-perceptual orientation (Brown et al.,2015).
The case study reveals that Mr. Kwon had previous medical history of hypertension,
congestive heart failure and type 2 diabetes. High blood pressure can weaken the blood vessels
of the brain causing them to narrow and rupture. Due to the strain on the blood vessels, the heart
has to keep functioning harder for keeping the blood circulating. Once the blood vessels are
weakened they are likely to form a block by the atheromatous deposits (Burke, Wissel &
Donnan, 2013). The atheroma and the ischemic consequences damage the cerebral arterioles and
the brain tissues. One might expect that slowing down the rate of the cerebral flow can give more
time for the clots to form. According to studies, people who have type 2 diabetes are two to four
times more likely to suffer from ischemic strokes. T2D also helps in the formation of heart
diseases or have strokes at an earlier age in comparison to those without diabetes. People with
diabetes have excess glucose in their blood while the cells are deprived of the glucose for making
the energy (Chen, Ovbiagele & Feng, 2016). Over time the glucose leads to clots or fatty
deposits on the inner walls of the blood vessels for causing blockages or clots. These blocks cut
off the blood supply to the brain. There are several possible mechanisms by which diabetes can
cause stroke in elderly people. This involves dys-functioning of the vascular endothelium, the

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systemic inflammation, age related arterial stiffness and the thickening of the basal membrane of
the capillaries. The vascular endothelium functioning is necessary for maintaining the function
and the integrity of the blood vessels and controlling of the vasomotor system. Vasodilatation is
mediated by nitric oxide. People with diabetes have impaired NO- mediated vasodilatation, due
to the decreased reactivity of the smooth muscles to NO. Furthermore individuals with T2D have
decreased elasticity of the blood vessels (Chen, Ovbiagele&Feng, 2016). Furthermore, a
heightened inflammatory response is also seen in individuals with T2D and is responsible for the
formation of the atherosclerotic plaque. Some of the serum markers such as the C-reactive
protein, cytokines and adiponectin are found in people with T2D(Chen, Ovbiagele&Feng, 2016).
T2D can also be linked to congestive heart failure and the rate of stroke is increased in
people with congestive heart failure. Studies have shown that 10-24 % of the patients who have
had stroke had previous history of congestive heart diseases (Kim & Kim, 2018). The risk factors
associated to stroke in heart failure are as follows:- The disrupted ventricular function, the
restrictive diastolic filling patters, calcified lesions in the aorta and the echo contrast between the
left and the right aorta(Kim & Kim, 2018). Moreover HF creates a stroke prone environment
within the body and is likely to facilitate cognitive impairment in patients.
Another clinical priority that can be identified in this case study is that the patient had been a
chain smoker, in spite of the multiple clinical issues. A vast number of literature have admitted
the established the risk factors for all kinds of stroke. The mechanisms by which smoking can
trigger the risks of smoke are carboxyhemoglobinemia, increased levels of fibrinogen, reduced
HDL cholesterol and increased aggregability of the platelets (Shah&Cole, 2010). Studies
involving animal models have proven the toxic effects of a compound 1, 3-butadiene, present in

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tobacco smoke. They have direct effect on the acceleration of the atherosclerosis and arterial
damage, leading to stroke.
Pharmacologic management
The initial goal of the management of stroke is the assessment with proper neuro-imaging
techniques. Secondly, the administration of the thrombolytic agents and generalized supportive
care should be provided.
The pharmacologic intervention for the stroke can be classified in to stroke specific
treatment regimen and stroke prevention treatment regimen. The pharmacotherapeutic options
for ischemic stroke are antiplatelet agents and tissue plasminogen activator (tPA). For treating
Iscehnic stroke, Alteplase is the only approved tPA (George & Steinberg, 2015). Alteplase and
other activators of plasminogen, such as the urokinase and the streptokinase help to promote
thrombolysis by the hydrolysis of the arginine-valine peptide bond in plasminogen forming the
active proteolytic enzyme plasmin. This plasmin then degrades the fibrin matrix of the thrombus,
thus preventing the formation of the clots (Emberson et al., 2014). The thrombolytic agents like
the streptokinase and urokinase activates the fibrin bound and the circulating plasminogen
(Bansal, Sangha & Khatri, 2013). The systemic activation of the plasminogen increases the
amount of plasmin in the blood circulation, thus accelerating the process of thrombolysis (Brown
et al., 2015). Alteplase is normally given by infusion and has been found to be effective within 3
hours of the onset of the symptoms.
Antiplatelet agents such as aspirin can be used in the treatment of acute stroke. Aspirin
works as an irreversible cyclooxygenase (COX) inhibitor, that acylates the hydroxyl functional
group of the COX enzyme, which in turn inhibits the conversion of the arachidonate to

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prostaglandin G2/H2 (Yip & Benavente, 2011). This helps in the inhibition of the platelet
aggregation. clopidogrel on the other hand prevents the binding of the adenosine 5-diphosphate
to glycoprotein IIb/IIIa and prevents the fibrinogen binding to the receptor. Dipyridamole
normally has different mechanisms of action than aspirin or clopidogrel (Brown et al., 2015). It
inhibits the platelet phosphodiesterase causing an increase in the intraplatelet cyclic adenosine
monophosphate level. This initiates the platelet-inhibitory activities of prostacyclin. Due to this
wide range of mechanism of actions, these anti-platelets can give vascular protection to the
stroke patients (Bullock & Hales, 2016). Additionally the use of statins has been found to be
effective for patients with ischemic stroke. This therapy helps to reduce the lipid level (Brown et
al., 2015). Patients having arterial fibrillation can be provided with oral anticoagulants such as
warfarin, rivaroxaban (Bullock & Manias, 2013).
It is evident from the case study that the patient had a medical history of elevated blood
pressure and hence hypertensive agents can be given only if diastolic blood pressure is above
120 mmHg or the systolic pressure is above 220mg (Hankey et al., 2015). Medications like
labetatol, having very less vasodilator effect is preferred. People who have been administered
with thrombolytic agents like Altepase should be properly assessed before the administration of
Alteplase. It should be remembered that, hyperglycemia can deteriorate the stroke symptoms
(George & Steinberg, 2015). In that case a prompt measurement of the serum glucose level is
important. In certain cases, oral agents like lisinopril or labetalol can be given. They act on the
rennin-angiostenin system and block the conversion of angiostenin I into vasoconstrictor
angiostenin II (Bullock & Manias, 2013). Calcium channel antagonist, like nifedipine should be
avoided due to its secondary precipitous declination in blood pressure and very fast absorption.
Nicardipine or labetalol can also be given as intravenous infusion for allowing a careful titration

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(Bullock & Manias, 2013). Subcutanous insulin should be administered to the patient to keep the
glucose level less than 80 mg/dL.
Conclusion
Stroke is a condition that is lethal and time sensitive. Several factors like high blood
pressure, congestive heart diseases, and diabetes and lifestyle factors such as smoking contribute
to the occurrence of stroke in elderly patients. Although the pharmaco-therapeutic options are
limited for stroke, but proper dosage of medicines at timely interval can prevent adverse
situations.

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References
Bansal, S., Sangha, K. S., & Khatri, P. (2013). Drug treatment of acute ischemic
stroke. American Journal of Cardiovascular Drugs, 13(1), 57-69.
Brotto, V., & Rafferty, K. (2016). Clinical Dosage Calculations for Australia and New Zealand.
Cengage Learning.
Brown, D., Edwards, H., Seaton, L., & Buckley, T. (2015). Lewis's Medical-surgical Nursing:
Assessment and Management of Clinical Problems. Elsevier Health Sciences.
Bullock, S. & Hales, M., (2016). Principles of Pathophysiology. Pearson Australia
Bullock, S., & Manias, E. (2013). Fundamentals of pharmacology. Pearson Higher Education
AU.
Burke, D., Wissel, J., & Donnan, G. A. (2013). Pathophysiology of spasticity in
stroke. Neurology, 80(3 Supplement 2), S20-S26.
Chen, R., Ovbiagele, B., & Feng, W. (2016). Diabetes and stroke: epidemiology,
pathophysiology, pharmaceuticals and outcomes. The American journal of the medical
sciences, 351(4), 380-386.
Deb, P., Sharma, S., & Hassan, K. M. (2010). Pathophysiologic mechanisms of acute ischemic
stroke: An overview with emphasis on therapeutic significance beyond
thrombolysis. Pathophysiology, 17(3), 197-218.

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DeLaune, S. C., Ladner, P. K., McTier, L., Tollefson, J., & Lawrence, J. (2016). Fundamentals
of Nursing: Australia & NZ Edition-Revised. Cengage AU.
Emberson, J., Lees, K. R., Lyden, P., Blackwell, L., Albers, G., Bluhmki, E., ... & Grotta, J.
(2014). Effect of treatment delay, age, and stroke severity on the effects of intravenous
thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual
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Hankey, G. J., Norrving, B., Hacke, W., & Steiner, T. (2014). Management of acute stroke in
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