Mariano Marcos State University

College of Health Sciences

Pharmacy Department
City of Batac 2906 Ilocos Norte

PCARE 105: Clinical Pharmacy and Pharmacotherapeutics 1

1st Semester of A.Y. 2024-2025

Title

Pharmacotherapy of Brain Injury – Acute Management

(Nervous System Disorders)

Introduction

This chapter introduces the clinical concepts of brain injury which is a condition of the
nervous system. It deals with the clinical presentation and factors that could induce or
potentiate the disorder as well as the relevant laboratory tests. This prepares the clinical
pharmacy students and consequently construct PWDT that is meant to serve as a
systematic guideline for the documentation of patient management. Hence, the students
are projected to design and present a plan based on scientific evidences of
pharmacotherapeutics on the given medical condition.

Learning Outcomes

At the end of the chapter, student must have:

1. explained the pathophysiology of nervous system disorders specifically the brain
injury;
2. described the clinical presentations of the disorders and correlate with the patient’s
symptomatology;
3. analyzed and interpret diagnostic and laboratory tests of the disorders with the given
patient case; and
4. designed the patient’s pharmacotherapy plan based on the principles of
pharmacotherapeutics.

Warm-Up Activity

• Do you give respect to traffic signs?

1
Learning Inputs

Pharmacotherapy of Brain Injury

Traumatic Brain Injury

• Is currently the leading cause of death and disability among children and young adults
in the industrialized world. A focus on TBI prevention, improved acute care, and
rehabilitation must remain national priorities.

Pathophysiology of Brain Injury

• The neurologic sequelae of brain trauma can occur instantaneously as a consequence

of the primary injury or can result from secondary injuries that follow within minutes,
hours, or days. Primary injury involves the external transfer of kinetic energy to various
structural components of the brain (eg, neurons, nerve synapses, glial cells, axons, and
cerebral blood vessels).

• The biomechanical forces responsible for primary brain injury can be classified broadly
as contact (eg, blunt-object blow, penetrating-missile injuries) and
acceleration/deceleration (eg, instantaneous brain movements following motor vehicle
accidents). Contact forces commonly result in skull fractures, brain contusions, and/or
hemorrhages. Primary injuries are categorized further as focal (eg, contusions,
hematomas) or diffuse. The latter usually are associated with shearing or stretch forces,
which primarily affect axons within the brain (ie, diffuse axonal injury). The type of
primary injury (ie, focal vs diffuse) is a major factor as to which of the secondary injury
mechanisms will predominate following a TBI; however, many patients, especially
those involved in high-speed accidents, sustain both types of injury.

• A complex sequence of pathophysiologic events precipitated by primary brain injury

may seriously disrupt the normal central nervous system (CNS) balance between
oxygen supply and demand resulting in a metabolic crisis. Hypotension in particular
during the early posttraumatic period is a major contributor to this imbalance and a
primary determinant of outcome. The end result of this imbalance may be cerebral
ischemia, the key pathophysiologic event triggering secondary injury.

• The brain is particularly susceptible to ischemia because of its normally high resting
energy requirement and its limited capacity to store oxygen, glucose, and adenosine
triphosphate (ATP). These phenomena can result in imbalances in cerebral oxygen
delivery (CDO2) and consumption (CMRO2), processes that are closely autoregulated

2
 under normal circumstances. Factors that can diminish cerebral oxygen supply
following brain injury include cerebral edema, expanding mass lesions (eg, epidural,
subdural, andintracerebral hematomas), cerebral vasospasm, and loss of
vasoregulatory control.

• Vasogenic cerebral edema can develop as a consequence of cerebral capillary

endothelial damage and disruption of the blood – brain barrier. Cytotoxic cerebral
edema is a consequence of loss of cell wall integrity that accompanies ischemia or
hypoxia with accumulation of lactic acid secondary to anaerobic metabolism. With
cytotoxic and vasogenic edema comes expansion of the intracellular and extracellular
fluid spaces, respectively.

• Elevated intracranial pressure (ICP) is the most detrimental consequence of cerebral

edema formation and occurs as the brain tissue volume increases within the
nondistensible skull. A significant increase in ICP may further compromise cerebral
blood flow (CBF) and extend cytotoxic edema. Hence, an increase in ICP can be self-
perpetuating unless this cycle is reversed. Hypoxemia can further exacerbate local
decreases in cerebral oxygen supply following acute respiratory failure and systemic
hypotension. Metabolic demand also can increase following neurotrauma secondary to
seizures, agitation, and temperature elevation.

Clinical Presentation

• The GCS was designed over 40 years ago and is still the most widely used system to
grade the arousal and functional capacity of the cerebral cortex. The GCS defines the
level of consciousness according to eye opening, motor response, and verbal response.

• A GCS score of 15 corresponds to a normal neurologic examination based on eye,

motor, and verbal responses. A GCS score of 3 to 8, 9 to 12, and 13 to 15 is consistent
with severe, moderate, and mild or minor brain injury, respectively.

3
 (Dipiro et al., 2017)
General

• Level of consciousness on admission ranges from awake and alert to completely

unresponsive (ie, Glasgow Coma Scale [GCS] 15-3, respectively).

Symptoms

• Posttraumatic amnesia (eg, greater than 1 hour), increasing dizziness, a moderate-to-

severe headache, nausea/vomiting, limb weakness, or paresthesia may indicate more
severe injury.

Signs

• Cerebrospinal fluid (CSF) otorrhea or rhinorrhea, seizures, or unequal or unreactive

pupils may indicate more severe injury.
• A rapid deterioration in mental status strongly suggests the presence of an expanding
lesion within the skull.
• Severe TBI may be accompanied by significant alterations or instability in vital signs,
including abnormal breathing patterns (eg, apnea, Cheyne–Stokes respiration,
tachypnea), hypertension, or bradycardia.

Laboratory Tests

• Arterial blood gases (ABGs) indicating hypoxia (ie, decreased PaO2) or hypercapnia (ie,
increased PaCO2) may indicate compromised ventilation.
• A positive blood ethanol concentration and/ or positive urine drug screen indicates that
drug intoxication may be affecting the patient’s mental status in addition to the TBI.
• Electrolyte disturbances can cause alterations in mental status, and their effects may
interfere with assessment of neurological status relative to brain lesion.

Other Diagnostic Tests

• Computed tomography (CT) of the head is an important diagnostic tool for detecting
the presence of mass lesions and structural signs of edema.

4
 General Treatment for Traumatic Brain Injury

Initial Resuscitation

• The first priority in the unconscious patient is the establishment of an airway, which
ensures adequate oxygenation and prevents aspiration. Thereafter, restoration and
maintenance of systolic blood pressure (SBP) between 120 and 140 mm Hg is desired
since admission SBP outside this range is associated with increased mortality.

Postresuscitative Care

• Following successful resuscitation, priorities shift toward diagnostic evaluation of

intracranial and extracranial injuries and emergent surgical intervention as needed. In
many patients, evaluation of intracranial hematomas (ie, epidural, subdural, and
intracerebral hematomas) is essential to control ICP and improve outcome.

Treatment to Intracranial Hypertension

• The use of analgesics and sedatives has an important primary role in the management
of intracranial hypertension. Morphine sulfate is the most commonly used analgesic
and sedative in this setting. Therapeutic hypothermia has been an attractive strategy
for attempting to minimize secondary brain injury after TBI for decades. The
mechanism underlying a protective effect of hypothermia is likely multifactorial,
although a reduction in CMRO2 is offered most frequently as the basis of any
therapeutic benefits.

Pharmacologic Management

• Various pharmacologic agents are used to manage patients with brain injury. Each
agent plays an important role in both the resuscitation and postresuscitative care or in
supportive treatment. The drugs employed include osmotic agents, barbiturates,
corticosetoids and opiods.

Treatment and Prophylaxis of Complications

• In addition to specific management of TBI problems such as intracranial hypertension,

the potential for secondary complications must also considered in addition to rendering
general supportive care. Development and implementation of clinical pathways for
consistency of care, and clinical investigation of neuroprotective agents are important
in advancing TBI treatment in the future.

5
 • Posttraumatic seizures - adult patients who have experienced one or more seizures
following a moderate-to-severe TBI should receive anticonvulsant therapy to avoid
increases in CMRO2 that occur with the onset of subsequent seizures and to prevent
the development of (sometimes subclinical) status epilepticus with associated increase
in mortality.

Supportive Care

• While normalizing ICP and maintaining an adequate CPP are the highest priorities in
preventing secondary injury following severe TBI, attention also must be given to
preventing and/or treating systemic and extracranial complications. One such
complication is systemic hypertension. Antihypertensives that can be used include IV
labetalol, nicardipine, and enaliprilat. Fluid and electrolyte management is another
important area of focus in the critically ill TBI patient.

Central Activities

Activity 1: Lecture, case presentation and analysis.

• Couse learning material available for viewing/downloading via mVLE.

Wrap-Up Activity

Discussion Forum (Open-Ended Questions)

• You are expected to participate in the discussion forum as scheduled. Please refer to the
course guide for your scheduled time.
• Open-ended questions will be asked randomly among students during the discussion
proper.
• Moreover, you are also given the opportunity to ask/raise any clarifications or questions
during the discussion.

Assessment (Post-assessment)

Quiz

Case Presentation and Analysis

• Reporters are requested to present assigned topics.
• Reporters are expected to present assessment of clinical cases.

6
Course Facilitator

Franklin Viernes Ibana, MSc, CPh, RPh, CIP

Assistant Professor III
Pharmacy Department
09673375038
fvibana@mmsu.edu.ph

Reference:

DiPiro, J. T. Talbert, R. L., Yee, G. C., Matzke, G. R., Wells, B. G. & Posey, L, M. (2017).
Pharmacotherapy A Pathophysiologic Approach, 10th Edition. McGraw Hill Education.