EPILEPSY

EPILEPSY
•Achronic neurologic disorder manifesting by repeated
epileptic seizures (attacks or fits) which result from
paroxysmal uncontrolled discharges of neurons within the
central nervous system (grey matter disease).

•Chronic brain disorder of various etiologies characterized

by recurrent seizures.
 Epilepsy: a chronic disorder
 Epileptic seizure: a event
 Epilepsy syndrome: grouping of epileptic patterns
IDIOPATHIC AND SYMPTOMATIC SEIZURES
Idiopathic epilepsy
When no specific anatomic cause
for the seizure, such as trauma or
neoplasm, is evident, a patient
may be diagnosed with idiopathic or
cryptogenic (primary) epilepsy.
These seizures may result from an
inherited abnormality in the
central nervous system (CNS).
Patients are treated chronically
with antiseizure drugs or vagal
nerve stimulation.
Most cases of epilepsy are idiopathic.
Symptomati
c epilepsy
A number of causes, such as illicit drug
use, tumor, head injury,
hypoglycemia,meningeal infection can
precipitate seizures. When two or more
seizures occur,the patient may be
diagnosed with symptomatic
(secondary) epilepsy.
Chronic treatment with antiseizure
medications, vagal nerve stimulation,
and surgery are all appropriate
treatments and may be used alone
or in combination
 Causes of epilepsy

70%no cause ---idiopathic— genetic

30%---symptomatic
CLASSIFICATION OF SEIZURES
 Partial
Partial seizures involve only a portion of the brain, typically part of
one lobe of one hemisphere.
 A. Partial

. 1. Simple partial:

These seizures are caused by a group of hyperactive

neurons exhibiting abnormal electrical activity, which are
confined to a single locus in the brain.

The electrical discharge does not spread, and the patient does not lose
consciousness.
The patient often exhibits abnormal activity of a single limb or muscle group
that is controlled by the region of the brain experiencing the disturbance.

2. Complex partial

These seizures exhibit complex sensory hallucinations

and mental distortion. Motor dysfunction may involve chewing
movements, diarrhea, and/or urination. Consciousness is altered.
 Generalized
Generalized seizures may begin locally and then progress to include
abnormal electrical discharges throughout both hemispheres of the
brain.
Primary generalized seizures may be convulsive or nonconvulsive,and
the patient usually has an immediate loss of consciousness.
 1. Tonic-clonic:
(previously known as grand mal)

These seizures result in loss of consciousness, followed

by tonic (continuous contraction) and clonic (rapid contraction
and relaxation) phases.

The seizure may be followed by a period of confusion and exhaustion due to the depletion of glucose and
energy stores.

2. Absence
(previously known as petit mal)

These seizures involve a brief, abrupt, and self-limiting

loss of consciousness.

The onset generally occurs in patients at 3 to

5 years of age and lasts until puberty or beyond.

The patient stares and exhibits rapid eye-blinking,

which lasts for 3 to 5 seconds.
 3. Myoclonic:

These seizures consist of short episodes of muscle contractions

that may recur for several minutes.
They generally occur after wakening and exhibit as brief jerks of the limbs.
4. Febrile seizures:
Young children may develop seizures with illness
accompanied by high fever.
This tendency may run in siblings. Febrile seizures consist of generalized tonic-clonic
convulsions of short duration and do not necessarily lead to a diagnosis of epilepsy.

5. Status epilepticus:

In status epilepticus, two or more seizures occur without recovery of full consciousness
between them.
These may be partial or primary generalized, convulsive or nonconvulsive.
Status epilepticus is life-threatening and
requires emergency treatment.
 Treatment
PRIMARY ANTIEPILEPTIC DRUGS
The list of drugs approved since 1990 includes
 Felbamate

 Gabapentin

 Lacosamide

 Lamotrigine

 Oxcarbazepine

 Rufinamide

These are labeled“second generation” when compared with older antiepileptics, such as
 Carbamazepine

 Divalproex

 Ethosuximide

 Phenobarbital

 Phenytoin

 Valproic acid
ANTISEIZURES CLASSIFICATION
I. TONIC-CLONIC & PARTIAL SEIZURES
 Carbamazepine. Phenytoin, valproic acid

II.ABSENCE SEIZURES
 Ethosuximide, valproic acid, clonazepam

III MYOCLONIC SEIZURES

 Valproic acid, clonazepam

IV. ADJUNCT/NEWER ANTICONVULSANTS

MECHANISM OF ACTION
◦ INHIBITION OF SODIUM CHANNELS
FUNCTION:
 phenytoin,
 carbamazepine,
 lamotrigine
◦ INHIBITION OF CALCIUM CHANNEL
FUNCTION:
 ethosuximde
◦ ENHANCEMENT OF GABA ACTION:
 benzodiazepines,
 phenobarbital
 gabapentin,
 vigabatrin, tiagabine
◦ Multiple & Complex Mechanism:
 Valproic Acid
 PHENYTOIN
Mechanism of Action:
It acts by stabilizing membranes
(1)Blocking voltage-dependence Na+ channel
(2) Blocking voltage-dependence Ca2+ channel
(3) Inhibiting calcium-induced secretory
processes, including release of hormones
and neurotransmitters.
PHARMACOKINETICS
 Because phentoin is a weak acid, its intestinal
absorption is variable and plasma
concentration can vary widely. Monitoring is
therefore needed
 It is metabolized by the microsomal system

and is excreted first in the bile and then in

the urine.
Therapeutic uses
 Antiseizure: used in the treatment of grand
mal epilepsy and tonic-clonic seizure
disorders, not in absence seizures.
 Treatment on peripheral neuralgia .
 Antiarrhythmias
Adverse effects
 Gastrointestinal irritation
 Ataxia and diplopia.
 Blood dyscrasias.
 Gingival hyperplasia, hirsutism, increased

collagen proliferation.
PHENYTOIN DRUG INTERACTIONS
1. Sulfonamides, valproate &
phenylbutazone: displace phenytoin
from binding sites(PPB)
2. Cimetidine, disulfiram, doxycycline,
isoniazid, phenylbutazone, sulfas,
warfarin, chloramphenicol: inhibits
phenytoin metabolism(hepatic
microsomal enzyme inhibitor)
PHENYTOIN DRUG INTERACTIONS
3.Barbiturates & carbamazepine,
pyridoxine, theophylline: enhance
phenytoin metabolism
4.PHENYTOIN decreases serum levels
of: carbamazepine,
chloramphenicol, corticosteroids,
haloperidol, quinidine, theophylline,
oral contraceptives, warfarin
(hepatic microsomal inducer)
Valproate
 Valproate is very effective against absence
seizure.
 Mechanism: facilitate glutamic acid

decarboxylase((GAD) is an enzyme that
catalyzes the decarboxylation
of glutamate to GABA)
 inhibit GABA-transaminase(formation of

glutamate)
 some effect on sodium channels
 Relatively few unwanted effects: anorexia,

nausea, teratogenicity, liver damage (rare, but

serious)
Ethosuximide
 The main drug used to treat absence
seizures, may exacerbate other forms
 Acts by blocking T-type Ca2+-channels
 Inhibits NA/K/ ATPase, depresses the cerebral
metabolic rate & inhibits GABA aminotransferase

 Relatively few unwanted effects, mainly

nausea and anorexia.
Benzodiazepine
 Diazepam: preferred drugs for Status
epilepticus.
 Nitrazepam: petit mal ,especially myoclonic

seizures and infantile spasms.

 Clonazepam: is one of the most effective in

some cases of myoclonic seizures. Used in

petit mal and status epilepticus
Barbiturates
 Phenobarbital, Luminal: is useful in the
treatment of generalized tonic-clonic
seizures and statue epilepticus.
 Mechanism:
 (1) block Ca2+ currents presynaptic
membrane and decrease neurotransmitter
release.
 (2) prolong the openings of the Cl- channel
in postsynaptic membrane and decrease it’s
response.
 Adverse effects: sedation, depression