Pharmacotherapy of Epilepsy

PST 06106

Basic Pharmacotherapy

Session 27: Pharmacotherapy of Epilepsy

Learning Tasks

By

the end of this session students are expected to be able to:

Define epilepsy

Explain pathophysiology of epilepsy

Explain the clinical presentation of epilepsy

Outline diagnosis of epilepsy

Describe pharmacological treatment of epilepsy

Describe the monitoring of epilepsy therapy

Activity: Buzzing

What is

Epilepsy ?

Definition of Epilepsy

The term 'epilepsy' is used to define a group of neurological disorders all of which exhibit periodic seizures.

Seizures are associated with episodic high-frequency discharge of impulses by a group

of neurons (sometimes referred to as the

focus

) in the brain.

Epilepsy implies a periodic recurrence of seizures with or without convulsions.

A seizure results from an excessive discharge of cortical neurons and is characterized by changes in electrical activity as measured by the electroencephalogram (EEG).

Definition of Epilepsy

Cont.….

A convulsion implies violent, involuntary contraction(s) of the voluntary muscles

The site of the primary discharge and the extent of its spread determine the symptoms that are produced, which range from a brief lapse of attention to a full convulsive fit lasting for several minutes, as well as odd sensations or behaviours

Table

27.1 Classification of Epilepsy

Pathophysiology of Epilepsy

Seizures result from excessive excitation, or in the case of absence seizures, from disordered inhibition of a large population of cortical neurons.

Initially, a small number of neurons fire abnormally.

Normal membrane

conductance

and inhibitory synaptic currents break down, and excess excitability spreads, either locally to produce a focal seizure or more widely to produce a generalized seizure.

This onset propagates by physiologic pathways to involve adjacent or remote areas.

The clinical manifestations depend on the site of the focus, the degree of irritability of the surrounding area of the brain, and the intensity of the impulse.

Pathophysiology of

Epilepsy Cont…

There

are multiple mechanisms that might contribute to synchronous

hyper excitability,

including:

A

lterations

in the distribution, number, type, and biophysical properties of ion channels in the neuronal membranes;

B

iochemical

modifications of receptors;

M

odulation

of second messaging systems and gene expression;

C

hanges in extracellular ion concentrations;

A

lterations in neurotransmitter uptake and metabolism in glial cells

Pathophysiology of Epilepsy Cont…

Modifications in the ratio and function of inhibitory circuits.

Local neurotransmitter imbalances between the main neurotransmitters, glutamate (excitatory) and γ -aminobutyric-acid (GABA) (inhibitory), and neuromodulators (e.g., acetylcholine, norepinephrine, and serotonin) might play a role in precipitating seizures in susceptible patients.

Clinical Presentation and Diagnosis of Epilepsy

General

In most cases, the healthcare provider will not be in a position to witness a seizure.

Many patients (particularly those with complex partial (CP) or generalized tonic

clonic

(GTC) seizures are amnestic to the actual seizure event.

Obtaining an adequate history and description of the actual event (including time course) from a witness is critically important.

Clinical Presentation and Diagnosis of Epilepsy

Cont….

Symptoms

Symptoms

of a specific seizure will depend on seizure type.

Although seizures can vary between patients, they tend to be stereotyped within an individual.

Cerebral palsy (CP) seizures

can include somatosensory or focal motor

features(jerking, loss of muscle tone or repeated movement).

CP seizures are associated with altered consciousness

.

Clinical Presentation and Diagnosis of Epilepsy Cont….

Symptoms…

Absence

seizures can be almost non-detectable with only very brief (seconds) periods of altered consciousness.

GTC (Grand mal seizures )are major convulsive episodes and are always associated with a loss of consciousness.

Cerebral palsy is a congenital disorder of movement, muscle tone or posture, it is due to abnormal brain development often before birth

Clinical Presentation and Diagnosis of Epilepsy Cont….

Signs

Interictally

(between seizure episodes), there are typically no objective or pathognomonic signs

.

Laboratory Tests

There are currently no diagnostic laboratory tests for epilepsy.

Laboratory tests can be done to rule out treatable causes of seizures (e.g., hypoglycemia, altered electrolyte concentrations, infections, etc.) that do not represent epilepsy

.

Clinical Presentation and Diagnosis of Epilepsy Cont….

Other

Diagnostic Tests

EEG(electroencephalogram) is very useful in the diagnosis of various seizure disorders.

A prolactin serum level obtained within 10 to 20 minutes of a tonic-

clonic

seizure can be useful in differentiating seizure activity from pseudo-seizure ( are seizures that occurs as a result of psychological cause such as severe mental stress) activity but not from syncope(loss of consciousness)

Magnetic resonance imaging (MRI) is very useful especially imaging of the temporal lobes

Activity

: Small Group Discussion

What

is the treatment of Epilepsy?

Pharmacological Treatment Of Epilepsy

The general approach to treatment involves assessment of seizure type and frequency, identification of treatment goals, development of a care plan, and a plan for follow-up evaluation.

During the assessment phase, it is critical to establish an accurate diagnosis of the seizure type and classification in order to select the appropriate initial AEDs

.

Pharmacological Treatment Of

Epilepsy Cont….

Pharmacological Treatment Of Epilepsy Cont….

Pharmacological Treatment Of Epilepsy Cont….

Monitoring of epilepsy Therapy

Patients should be monitored long term for seizure control, comorbid conditions, social adjustment, drug interactions, compliance, and adverse effects.

Periodic screening for comorbid neuropsychiatric disorders such as depression and anxiety is also important.

Clinical monitoring involves identifying the number and type of seizures.

Patients should record the severity and the frequency of seizures in a seizure diary. ‘

There should be a decrease in the number and/or severity of seizures.

Patients and family should be questioned regularly to determine whether they are truly seizure free

.

Key Points

The

term 'epilepsy' is used to define a group of neurological disorders all of which exhibit periodic seizures.

Seizures are associated with episodic high-frequency discharge of impulses by a group

of neurons (sometimes referred to as the

focus

) in the brain.

Seizures result from excessive excitation, or in the case of absence seizures, from disordered inhibition of a large population of cortical neurons

The general approach to treatment involves assessment of seizure type and frequency, identification of treatment goals, development of a care plan, and a plan for follow-up evaluation

Evaluation

What

is Epilepsy?

What is the pathophysiology of

Epilepsy?

What are the signs and symptoms of Epilepsy?

How is the treatment of Epilepsy

References

Wells

BG,

DiPiro

J,

Schwinghammer

T (2013),

Pharmacotherapy Handbook

(6

th

Ed). New York, NY: McGraw-Hill.

DiPiro

JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):

Pharmacotherapy: A Pathophysiologic Approach

(7

th

ed

): New York, NY: McGraw-Hill.

Katz M D.,

Matthias KR.,

Chisholm-Burns M A.,

Pharmacotherapy(2011)

Principles & Practice Study Guide: A Case-Based Care Plan Approach

:

New York, NY: McGraw-Hill.

Schwinghammer

TL, Koehler JM (2009)

Pharmacotherapy Casebook: A Patient-Focused Approach

(7

th

ed

): New York, NY: McGraw-Hill.

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