Epilepsy is a disorder due to disturbed electrical

activity in the brain, which may have many

etiologies.
Seizures that are prolonged or repetitive can be
life-threatening.
Epilepsy is defined by occurrence of at least 2
unprovoked seizures separated by 24 hours.

SEIZURES
Causes: meningitis, trauma, tumors, exposure to
toxins - may become recurrent & require chronic
treatment with antiepileptic drugs (AEDs).
Clinical manifestations: sudden & transitory
abnormal phenomena that may include
alterations of consciousness, motor, sensory,
autonomic, or psychic events perceived by the
patient or observer.

Seizures can be described as epileptic

syndromes that may include cause (if
known), precipitating factors, age of onset,
characteristic EEG patterns, severity,
chronicity, family history, & prognosis.

PATHOPHYSIOLOGY
Seizures result from excessive
excitation, or in the case of
absence seizures, from disordered
inhibition of a large population of
cortical neurons.
This is reflected on EEG as a
sharp wave or spike.
Initially, a number of neurons fire
abnormally.

LABORATORY TESTS

NON PHARMACOLOGICAL
TREATMENT
Surgery: the treatment of choice in selected patients with
refractory focal epilepsy, especially those patients with
seizures originating from the temporal lobe.
Ketogenic diet (low-carbohydrate, high- fat): for patients
who cannot tolerate AEDs or for seizures that are not
completely responsive to AEDs: persistent ketosis, which
is believed to play a major role in therapeutic effect. Most
commonly used & seems to be most beneficial in
children. Long-term effects include kidney stones,
increased bone fractures, and adverse effects on growth

NON PHARMACOLOGICAL
TREATMENT
Vagus nerve stimulator: as adjunctive therapy in
reducing the frequency of seizures in adults and
adolescents older than 12 years of age with
partial-onset seizures that are refractory to
AEDs. It is also used off-label in the treatment of
refractory primary generalized epilepsy
Avoiding of precipitating factors (stress, sleep
deprivation, ingestion of excessive amounts of
caffeine or alcohol)

ANTIEPILEPTIC DRUG
THERAPY (AED)
If a decision is made to start AED therapy, monotherapy is preferred, & ~ 5070% of all patients can be maintained on 1 drug.

However, many of these patients are not seizure free.

After 12 months of treatment, 48-55% of patients with only GTC seizures are
seizure-free, but only 2326% of those with CP seizures are seizure-free.
Of 35% of patients with unsatisfactory control, 10% will be well controlled with
2-drug treatment.
Of the remaining 25%, 20% will continue to have unsatisfactory control despite
multiple drug treatment.
Some of these patients may become candidates for surgery or vagal nerve
stimulator

TONIC CLONIC SEIZURES

Tonic-clonic seizures (formerly known as grand mal seizures) are a type
of generalized seizures that affects the entire brain. Tonicclonic seizures
are the seizure type most commonly associated with epilepsy and seizures
in general.
Tonic phase
The patient will quickly lose consciousness, and the skeletal muscles will
suddenly tense, often causing the extremities to be pulled towards the body or
rigidly pushed away from it, which will cause the patient to fall if standing or
sitting. The tonic phase is usually the shortest part of the seizure, usually lasting
only a few seconds. The patient may also express brief vocalizations like a loud
moan or scream during the tonic stage, due to air forcefully expelled from the
lungs.

Clonic phase
The patient's muscles will start to contract and relax rapidly, causing convulsions.
These may range from exaggerated twitches of the limbs to violent shaking or
vibrating of the stiffened extremities. The patient may roll and stretch as the
seizure spreads. The eyes typically roll back or close and the tongue often
suffers bruising or lacerations sustained by strong jaw contractions. The lips or
extremities may turn slightly bluish (cyanosis) and inconsistence is seen in some
cases.

When to stop AEDs?

AED withdrawal should be done gradually,

especially in patients with profound
developmental disabilities.
Some patients will have a recurrence of
seizures as AEDs are withdrawn.
Sudden withdrawal is associated with
precipitation of status epilepticus, particularly
with Barbs & BDZs
Seizure relapse has been reported to be more
common if these AEDs are withdrawn over 1 to 3
months compared to over 6 months.

Patient Presentation

Chief Complaint
I had a seizure a few weeks ago and banged up my head.
HPI
Carter McNeely is a 68-year-old man whose seizures are well controlled with
carbamazepine monotherapy. The seizure 2.5 weeks ago was the first seizure
in 20 months. During the seizure, he fell to the floor and sustained a laceration
to his occipital region that required staples for closure. The description of his
seizures is vague because there have been only six seizures documented
since he developed epilepsy 3 years ago. Because Mr McNeely lives alone in
an assisted living facility, only half of the documented seizures have been
witnessed by another individual who could provide a description. Two seizures
were witnessed by other residents who described him as falling to the ground
and starting to shake. One seizure occurred in the day room when a facility
nurse was in the room, and he documented that Mr McNeely fell to the ground,
developed rhythmic extensions to both his legs, became incontinent of urine,
and was sleepy and disoriented for 2 hours after the episode.
He has only been treated with carbamazepine. This was started by his family
practice physician after his second seizure. An EEG was obtained at that time
and was unremarkable. Because the seizures are so infrequent, the dose of
carbamazepine has never been adjusted.

PMH
Tonicclonic seizures diagnosed 3 years ago
HTN adequately controlled with lisinopril monotherapy
Dyslipidemia controlled with atorvastatin and low-cholesterol diet
BPH, currently symptom-free on dutasteride
FH
Mother died at age 74 of natural causes; had HTN for many years. Father died at age 70
of natural causes; did not have any known medical illnesses. All of his children and
grandchildren are alive and well. One son and one daughter have HTN.
SH
Retired factory worker; resides in an assisted living facility. He is widowed and has six
children and nine grandchildren, whom he sees frequently. He denies past or present
tobacco and illicit drug use. He reports a history of regular alcohol use but now only
drinks one beer that his grandson brings to him every Saturday evening.
Meds
Aspirin 81 mg orally once daily
Atorvastatin 40 mg orally once daily
Carbamazepine XR 200 mg orally twice daily
Dutasteride 0.5 mg orally once daily
Lisinopril 20 mg orally once daily
Multivitamin with minerals one tablet orally once daily

All
NKDA
Adverse drug effect historynone
Physical Examination
Gen
Exam reveals an elderly Caucasian man who appears his stated age in NAD.
VS
BP 126/78 mm Hg, HR 72, RR 16, temperature not measured; Ht 510, Wt 72.5 kg
HEENT
Normocephalic; scalp: healing 3-cm lesion in the occipital region with corresponding mild
tenderness and bruising; PERRL
Neck/LN
No thyromegaly, lymphadenopathy, or carotid bruits
Chest/Lungs
Lungs CTA
CV
RRR, no m/r/g
Abd
Soft, nontender; no HSM; (+) BS
MS/Ext
Normal tone; 5/5 strength in all extremities
Neuro
Awake; A & O 3; CN IIXII intact, reflexes 2+ and symmetric throughout

LABS

42-52% normal Hct range

95-105 mEq/L normal Cl range
135-145 mEq/L normal sodium range

EEG: Sleep-deprived EEG unremarkable. Photic stimulation

failed to produce any other changes.
Assessment
Sixty-eight-year-old man with fairly well-controlled seizures on
carbamazepine monotherapy

CLINICAL PEARL
Many important historical figures had
epileptic seizures, including Buddha,
Socrates, Alexander the Great, Julius
Caesar, St. Paul the Apostle, Mohammed,
Peter the Great, Handel, Napoleon,
Paganini, Kierkegaard, Alfred Nobel, and
Dostoyevsky. It may be useful to share
some of these names with patients to
break the stigma of mental illness
associated with epilepsy.

Questions :

1.A list the drug therapy problems for this

patient
1.generalized tonic clonic :not seizure free
2. Hyponatremia and hypochloremia most
likely secondary to the chronic use of
carbamazepine, Common complaints include
confusion, dizziness, fatigue, and disorientation
3. asymptomatic anemia that could be due to
nutritional
deficiency, anemia of chronic disease, or
chronic use of AEDs

4. hypertension (well-controlled)
5.BPH (well-controlled)
6.dyslipidemia(controlled)
7.Injury (laceration) caused by fall
secondary to a seizure.

1.b. What additional information is needed to

fully assess the patients problems related
to epilepsy or his drug therapy?
A good seizure record should be kept that includes
the frequency and duration of episodes, any
precipitating factors, times the episodes occurred
Serum carbamazepine concentrations should be
obtained at least annually
Carbamazepine levels should be obtained
whenever medications with known drug
interactions are started or stopped
Assessment of compromised bone health. :
hypocalcemia, hypophosphatemia, elevated serum
alkaline phosphatase, elevated parathyroid
hormone, and reduced levels of vitamin D and its
active metabolites.

1.c. What are the age-specific

management issues for this patient?
Pharmacokinetic parameters including protein
binding, distribution, decreased enzyme
inducibility, and elimination change with age, The
changes seen in the elderly can alter dosing and
monitoring of the AEDs. Drug accumulation due to
reduced clearance and increased sensitivity to
drug effects also puts elderly epileptic patients at
risk for adverse effects. In the elderly epileptic
patient, the presence of concomitant illnesses
requiring multiple medications increases the
potential for drug interactions.
the elderly are at greater risk of bone fractures
resulting from falls.

Bone health: AEDs may decrease bone

mineral density and alter bone mineral
metabolism. The severity of bone
abnormalities can be correlated to duration of
AED use and the type and number of AED
used. All patients with epilepsy should
receive adequate calcium and vitamin D and
routinely engage in gravity-resisting exercise

2. What are the goals of

pharmacotherapy in this case?
Ideally, one would like to see the patient
become seizure-free on monotherapy.
Keep the patient free of adverse effects
of therapy and drug interactions.
Ensure adherence to the prescribed
regimen.
Provide the best quality of life possible

3.a. What nonpharmacologic interventions

may be helpful for this patient?
Counseling or talk therapy with a
psychologist or social worker could be
beneficial in this individual because the
elderly with epilepsy are more prone to
anxiety and depression. Even in the absence
of symptoms of anxiety or depression,
counseling can provide an opportunity for the
patient to address other non-epilepsy quality
of life issues such as loss of independence,
loss of productivity, loss of drivers license,
and financial issues associated with health
care expenses on a fixed income.

3.b. What pharmacotherapeutic options are

available to treat his
epilepsy?
Add an additional agent to his regimen.
Replace the carbamazepine with another agent
1.Phenytoin (Dilantin, generics) is indicated for the treatment of generalized
seizures. Its mechanism of action includes sodium channel blockade.
2. Valproic acid and derivatives (Depakene, Depakote) are indicated for the
treatment of multiple seizure types including generalized seizures. Their
mechanism of action includes blockade of sodium channels and increasing
circulating gamma-aminobutyric acid (GABA) levels.
3. Phenobarbital is indicated for the treatment of partial and generalized
seizures. The mechanism of action includes blockade of sodium channels
and increasing circulating GABA levels.
4. Lamotrigine, Lacosamide , Gabapentin, Levetiracetam, Topiramate are
indicated as add-on therapy for the treatment of partial-onset and
generalized seizures
5. Felbamate (Felbatol) is indicated for the treatment of both
partial and generalized seizures. It is an agent of last resort
due to the risk of aplastic anemia and liver failure.

4. What is the best pharmacotherapeutic

plan for this patient?
Carbamazepine should be continued until another agent is initiated
and titrated upward to a therapeutic dose. Monotherapy,if possible,
is preferred in all patients with epilepsy. However,in the elderly,
monotherapy is especially important to minimize potential adverse
reactions, drug interactions, and financial burden. Because the
blood level is therapeutic in this patientand he is still experiencing
breakthrough seizures, monotherapy with carbamazepine is not
likely to be effective.
Gabapentin is a good choice of therapy to replace the
carbamazepine. Gabapentin does not have FDA approval as a sole
AED in generalized tonicclonic seizures but is a good choice due to
its efficacy in several seizure types, good absorption, lack of protein
binding, lack of drug interactions, and limited adverse effects. dose
is 300 mg orally three times daily.
Levetiracetam is also a good choice to replace carbamazepine.
Levetiracetam possesses clinical advantages of good oral
absorption, little protein binding (<10%), lack of hepatic metabolism,
and lack of drug interactions. The initial dose is 500 mg orally twice
daily or 1,000 mg orally once daily

5. Which clinical and laboratory parameters are

needed to evaluate
the therapy to ensure the best possible outcome?
A record of all seizures should be kept and
reviewed at each follow-up visit
Serum sodium levels should be monitored more
closely in this patient because of the existing
hyponatremia. Electrolytes should be obtained
semiannually or as clinically indicated to ensure
that the hyponatremia is stable.
Gabapentin and levetiracetam is monitored with
baseline and annual renal function tests (SCr,
BUN, and electrolytes) because of its route of
elimination.

6. What information should the patient

receive to ensure successful
therapy and to minimize adverse effects?
Your doctor may have to adjust the dosage of new
medicines. It
may take 12 months before your dose is stable.
Take your medicines by mouth exactly as
prescribed. For best effects, take them at the
same time each day. If you are taking more than
one daily dose of a medicine, take the doses at
evenly spaced times throughout the day. This will
ensure a constant level of drug in your body.
Do not take your medicines more often and do not
increase the Doses without consulting your doctor

Gabapentin:
You may take this medicine with or without food.
You may experience drowsiness or dizziness, especially when
first taking this medication. To reduce dizziness, do not sit up
or stand up quickly.
Do not take this medication with antacids.
Report episodes of sadness that do not go away or thoughts of
suicide to your physician.
Be sure to drink plenty of fluids. Do not restrict your fluid
intake unless specifically instructed by your physician.

Levetiracetam:
You may take this medicine with or without food.
You may experience drowsiness or dizziness, especially when
first taking this medication. To reduce dizziness, do not sit up
or stand up quickly.
This medication may also cause agitation and difficulties with
coordination.
Notify your physician as soon as possible if you experience
agitation, difficulty walking or controlling muscle movements,
or unusual weakness or tiredness.
Be sure to drink plenty of fluids. Do not restrict your fluid
intake unless specifically instructed by your physician.
Report episodes of sadness that do not go away or thoughts of
suicide to your physician.