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Epilepsy and antiepileptic drugs
Epilepsy: is a very common chronicdisorder characterized by recurrent
seizures.
Seizure: excessive discharge of cortical
neuron
Convulsion: involuntary contraction of
voluntary muscles
Patients may have epilepsy or seizure
disorders without convulsions
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Any Seizure Result From
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Types Of Ion Channels
Voltage-gated
Channels Na+ & ca ++
depolarize the
cell membrane
(E)
K+ hyperpolarize
the cell membrane
(I)
Ion Channels
Ligand -gated
channels
Glutamate (E)
GABA (I)
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Primary
Types of
s
(focal)
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International Classification Of Seizures
a. Partial focal :
In which the discharge involves one part
of the cortex.
1.Simple: consciousness is preserved
2.Complex: consciousness is impaired
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b. Generalized
In which the discharge involves the whole
cortex
1. Tonic-Clonic: Grandmal seizures
Tonic: abrupt loss of consciousness (less than
1 min)
Clonic: jerking of body muscles with lip or
tongue biting, fecal & urinary incontinence
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2. Absence or petit mal: altering of
consciousness lasting 10-30 seconds,
onset of this type occurs from ages 3-16
years
3. Myoclonic: Single or Multiple muscle jerk
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c. Status epilepticus:
Series of seizures without recovery ofconsciousness between attacks
It is life threatening emergency
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Febrile seizures
Young child (3 months to 5 years)
frequently develop seizures with illnessaccompanied by high fever
Treatment: acute case Diazepamrectally
Diagnosis of specific seizure type is importantfor prescribing the most appropriate anti-seizure drug
Treatment may involve combination of drugs
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Generalized tonic clonic seizures
(grand mal seizures)
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Generalized Seizure (Absence or Petit Mal )
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ATONIC SEIZURE
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Aim of Treatment
a: Complete suppression of fits and if not
possible.
b: Reduction of fit frequency as much as
possible, with minimum and tolerable
ADRs.
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The management of patients with epilepsy is
focused on 3 main goals:
Goals
Improve
Quality Of
Life
Avoiding
Side
Effects
Controlling
Seizures
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Etiology of epilepsy
Some seizures arise secondary to other
conditions. However, in most cases, the
cause of the seizure is unknown.
1. Primary (idiopathic) seizures have noidentifiable cause.
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2.Secondary seizures (symptomatic or acquires
seizures) occur secondary to an identifiable cause.* Intracranial neoplasms.
* Infectious diseases, such as meningitis, influenza,
* High fever (in children)* Head trauma.
* Metabolic disorders, such as hypoglycemia and
hypocalcemia.
* Alcohol or drug withdrawal.
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Clinical evaluation
Historyincludes an evaluation of the
seizure, including interviews of the
patients family
Laboratory testmay also identify an
underlying etiology
Neurological imagingstudies
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EEG studies measure the electrical activity
of the brain.
- An EEG is useful for classifying the
seizure, but the EEG by itself cannot rule
seizures in or out, as there are patients
with normal EEGs who have seizure
disorders.
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Therapy
Principles of drug therapy
Seizure control.
Approximately 50% of epileptics achievecomplete seizure control through drug
therapy. In another 25% drugs reduce the
frequency of seizures. Epileptics generally
require continuous drug therapy for at
least 4 seizure-free years before the drug
can be discontinued.
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Antiepileptics are indicated when there is
two or more seizures occurred in short
interval
An initial therapeutic aim is to use only one
drug (monotherapy)
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Before any drug treatment is instituted,
remedial causes of the seizure activity
should be excluded.
A single primary drug that is most
appropriate for the seizure type must be
selected. If there is more than one
appropriate primary drug, age, sex, and
compliance of the patient must be
considered
Treatment:
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Treatment
Additional therapy. If seizures recur after themaximal tolerated dose is reached; a second
drug is added at a low dose.
The dose of the second drug is increased until a
therapeutic level is reached.
The first drug is maintained until the optimaldose of the second drug is determined; then the
first drug is discontinued gradually to avoid
triggering seizure activity.
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The sudden withdrawal of drugs should be
avoided
withdrawal may be considered after
seizure- free period of 2-3 or more years
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MOA of antiepleptic drugs:
inhibitory tone by facilitation of GABA-mediatedhyperpolarization-barbiturates, benzodiazepines
axonal conduction by preventing Na' influx
through fast Na channels-carbamazepine,phenytoin; also, at high doses, barbiturates andvalproic acid
presynaptic ca2 + influx through type-Tchannels in thalamic neurons-ethosuximide andvalproic acid
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DRUG THAT BLOCK VOLTAGE-DEPENDENT SODIUM
CHANNELS
Pharmacology of antiepileptic drug
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Anti-epileptic drugs
Phenytoin
MOA: blocks voltage gated sodium channels in
neuronal membrane
Clinical uses: partial seizures & generalized
tonic-clonic seizures
It has narrow therapeutic index
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Phenytoin
the relation between thedose & plasma
concentration is not
linear.
Has high drug
Interactions.
Induction of dug
metabolizing enzymes
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S/Es
1. CNS: ataxia, diplopia, nystagmus
2. Gingival hyperplasia
3. Hairsutism
4. Teratogenic effect (not given during
pregnancy)5. Abnormalities of vitamin D catabolism
6. folate levels megaloblastic anemia
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Gingival hyperplasia
Carbamazepine
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Carbamazepine
MOA: blocks sodium channels
Uses: as phenytoin & for Trigeminal
Neuralgia & Rx of mania Similarities between phenytoin & carbamazepine:
Both are liver enzyme inducers
Both enhance catabolism of vitamin D
Both cause megaloblastic anemia but morewith phenytoin
Both are not used in absence seizures
S/Es
CNS: ataxia, diplopia
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Valproic acid
MOA
Interfere with sodium channels at high doses
Can potentiate the inhibitory effect of GABA Therapeutic uses
Generalized Tonic-Clonic, partial & can beused in absence seizure S/Es
Alopecia (hair loss)
Teratogenicity
Liver damage
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Ethosuximide
MOA: act by blocking T-calcium channel
The main drug used to treat absence seizures
S/Es: nausea & anorexia
Phenobarbital
clinical use: the same as phenytoin, for Tonic-
Clonic seizures
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Benzodiazepines
1. Diazepam: given I.V. to treat status
epilepticus
2. Clonazepam
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Drugs Used in Seizure Disorders
Tonic-Clonic & Partial Seizure Absence Seizure Myoclonic
CarbamazepinePhenytoin
Valproic acid
phenobarbital
EthosuximideValproic acid
Clonazepam
ClonazepamValproic acid
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Management of status epilepticus
1.Establish airway, oxygenate, recoveryposition
2. Establish IV access and give IVlorazepam 2-4mg (IV diazepam 5-10mgalternative; Buccal midazolam 10mgpreferred over rectal diazepam)
3. Check blood for: glucose, urea andelectrolytes, Calcium, anticonvulsant
levels, and arterial blood gas and pH.
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4.If seizures continue, administerintravenous phenobarbital orphenytoin assecond-line treatment
5. In sever status epilepticus especially thatnot respond to these meausres, generalanesthesia and neuromuscular blocker
and artificial respiration.
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