Transcript File

Epilepsy and antiepileptic drugs
Epilepsy: is a very common chronic
disorder 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
3
Types Of Ion Channels
Ion Channels
Voltage-gated
Channels
•
•
Ligand -gated
channels
Na+ & ca ++
depolarize the
cell membrane
(E)
•
•
K+ hyperpolarize
the cell membrane
(I)
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Glutamate (E)
GABA (I)
Classification of Seizures
Seizures
Loss of Consciousness?
Yes
No
Generalized
Seizures
Partial Seizures
Alteration of Consciousness?
Yes
No
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Complex Partial
Simple Partial
I. Partial “focal” :
 In which the discharge involves one part
of the cortex.
A. Simple Partial Seizures
B. Complex Partial Seizures
II. 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
Generalized tonic clonic seizures
(grand mal seizures)
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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
Generalized Seizure (Absence or Petit Mal )
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3. Myoclonic: Single or Multiple muscle
jerking
c. Status epilepticus:
Series of seizures without recovery of
consciousness between attacks
It is life threatening emergency
ATONIC SEIZURE
• Are characterized by a sudden loss of
postural tone so that the individual falls to
the ground.
Febrile seizures
Young child (3 months to 5 years)
frequently develop seizures with illness
accompanied by high fever
Treatment: acute case  Diazepam
rectally
Diagnosis of specific seizure type is important
for prescribing the most appropriate antiseizure drug
Treatment may involve combination of drugs

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.
The use of single or combination drug
therapy using careful grading of drug
dosage.
Regular monitoring of drug toxicity.
Regular monitoring of patient status
regarding drug interactions.
The management of patients with epilepsy is
focused on 3 main goals:
Improve
Quality Of
Life
Goals
Avoiding
Side
Effects
Controlling
Seizures
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NURSING ASSESSMENT
 NURSING ASSESSMENT OF SEIZURE
ACTIVITY SHOULD OCCUR AND BE
DOCUMENTED IN THE NURSING NOTES.
1. Appropriate information about what occurred
during the ictal (active seizure) phase should be
documented. If the nurse does not actually
witness the seizure, persons present should be
consulted to obtain the information.
2.The individual should be monitored during
the postictal phase of the seizure. The
individual’s postictal condition and activity
should be documented.
3. Any action taken, including a request for
medical consultation, should be
documented in the nursing notes.
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 no
identifiable cause.
2.Secondary seizures (symptomatic or
acquires seizures) occur secondary to an
identifiable cause.
Clinical evaluation
History includes an evaluation of the
seizure, including interviews of the
patient’s family
Laboratory test may also identify an
underlying etiology
Neurological imaging studies
Special Cases: Pregnancy
 Seizures in pregnancy constitute major risk to mother
and fetus
 Must maintain therapy
Monotherapy usually better than drugs
combination.
Folic acid is recommended to be given for every
pregnant women with epilepsy
Teratogenicity
Antiepileptic drugs associated with
increased (2-3 fold) incidence of birth
defects (cleft lip/palate and cardiac
defects)
Significant risk of neural tube defects
 Phenytoin, sodium valproate are absolutely
contraindicated
MOA of antiepleptic drugs:
 inhibitory tone by facilitation of GABA-mediated
hyperpolarization-barbiturates, benzodiazepines
 axonal conduction by preventing Na' influx
through fast Na channels-carbamazepine,
phenytoin; also, at high doses, barbiturates and
valproic acid
 presynaptic ca2 + influx through type-T
channels in thalamic neurons-ethosuximide and
valproic acid
Classification of AEDs
Newer
Classical
•
•
•
•
•
Phenytoin
Phenobarbital
Carbamazepine
Ethosuximide
Valproate
(valproic acid)
Lamotrigine
Felbamate
Topiramate
Gabapentin
Vigabatrin
Pharmacology of antiepileptic drug
DRUG THAT BLOCK VOLTAGEDEPENDENT SODIUM
CHANNELS
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Block channels
firing at high
frequencies
Inactivated
channel
Na+
Barbiturates
Valproate
Topiramate
Carbamazepine
Phenytoin
Anti-epileptic drugs
1. Phenytoin
MOA: blocks voltage gated sodium channels in
neuronal membrane
Clinical uses: partial seizures & generalized
tonic-clonic seizures
 It has narrow therapeutic index
 Metabolized by MES
 Has high drug Interactions.
 S/Es
1.
2.
3.
4.
CNS: diplopia, nystagmus
Gingival hyperplasia
Hairsutism
Teratogenic effect (not given during
pregnancy)
Gingival hyperplasia
2. Carbamazepine
 MOA: blocks sodium channels
 Uses: as phenytoin & for Trigeminal
Neuralgia & Rx of mania
 Similarities between phenytoin & carbamazepine:
 Both are liver enzyme inducers
 Both are not used in absence seizures
 S/Es
 Rashes, dizziness, blurred vision
3. Valproic acid
 MOA:
 Interfere with sodium channels at high doses
 Can potentiate the inhibitory effect of GABA
 Therapeutic uses:
 Generalized Tonic-Clonic, partial & can be
used in absence seizure
 S/Es:
 Teratogenicity
 Weight gain..
 Very rarely it causes liver damage
T type Ca++ current inhibition:
 Ethosuximide
 MOA: act by blocking T-calcium channel
 The main drug used to treat absence seizures
 S/Es: gastric upset.
Ca++
Reduction in the flow of Ca++ through
T - type Ca++ channels in thalamus
Gitanjali-15:
Facilitation of GABA-mediated hyperpolarization
 Barbiturates:
Phenobarbital
 clinical use: the same as phenytoin, for TonicClonic seizures.
 Alternative to phenytoin in treatment of status
epilepticus.
 Benzodiazepines
1. Diazepam
2. Clonazepam
3. Lorazepam
Other AEDs:
New drugs (second generation)
Have potential advantages in terms of
pharmacokinetics, tolerability, and lesser risk for
drug-drug interactions
 Vigabatrin : In all types, specially in pts
resistant to other AEDs.
Irreversible GABA transaminase inhibitor.
 Gabapentin In spite of its close structural
relationship to GABA, gabapentin
appears not to act on GABA receptors .
Drugs Used in Seizure Disorders
Tonic-Clonic & Partial Seizure
Carbamazepine
Phenytoin
Valproic acid
phenobarbital
Absence Seizure
Ethosuximide
Valproic acid
Clonazepam
Myoclonic
Clonazepam
Valproic acid
Management of status epilepticus
1.Establish airway, oxygenate, recovery
position
2. Establish IV access and give IV
lorazepam 2-4mg (IV diazepam 5-10mg
alternative;
3. Check blood for: glucose, urea and
electrolytes, Calcium, anticonvulsant
levels, and arterial blood gas and pH.
4.If seizures continue, administer
intravenous phenobarbital or phenytoin as
second-line treatment
5. In sever status epilepticus especially that
not respond to these meausres, general
anesthesia and neuromuscular blocker
and artificial respiration.
It is important that anticonvuslants are not
discontinued too suddenly as they may
precipitate seizures.
Patients with seizures should be warned
against driving vehicles,swimming and
working under conditions where a seizure
could produce disaster.
Attentions
Selection of an appropriate antiseizure
agent
Use of single drug
Withdrawal
Toxicity
Fetal malformations