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Epilepsy
• It is a Chronic medical condition produced by
sudden changes in the electrical function of
the brain.
(focal) Primary
A) Focal or partial
1) Simple partial( Jacksonian )- The electrical discharge is cofined to the
motor area.
2)Complex partial( psychomotor )- The electrical discharge is confined in
certain parts of the temporal lobe concerned with mood as well as
muscle.
B) Primary generalized
1) Tonic- clonic. Pt fall in convulsion & may bite his tongue & may lose control
of his bladder or bowel.
2) Tonic. Some pts, after dropping unconscious experience only the tonic phase
of seizure.
3) Atonic ( akinetic). Unconsciousness and relaxation of pt’s muscles & he
drops down.
4) Myoclonic . Sudden, brief shock like contraction which may involve the
entire body or be confined to the face, trunk or extremities.
5) Absence (petit mall) .momentary loss of consciousness without involving
motor area. Most common in children ( 4-12 yrs ).
EEG- symmetric 3 Hz spikes and wave pattern.
6) Status epilepticus ( re-occuring seizure ). Continuous seizure (>30 min)
without intervening return of consciousness.
• Lennox-Gastaut syndrome- occurs in children
and is defined by the following triad:
• (1) multiple seizure
• (2) EEG showing slow (<3 Hz) spike-and-wave
discharges
• (3) impaired cognitive function,associated
with CNS disease or dysfunction
Mesial temporal lobe epilepsy (MTLE)-
• characteristic hippocampal sclerosis
• refractory to treatment with anticonvulsants
but responds extremely well to surgical
intervention.
PROLONGATION OF FACILITATION OF
N a+ CHANNEL GABA MEDIATED
INACTIVATION Cl CHANNEL OPENING
• Phenytoin • Barbiturate (Barb.)
• Carbamazepine • Benzodiazepine (Bzd.)
• Valproate
• Vigabatrin (Viga.)
• Lamotrigine
• Topiramate
• Valproate (Valpr.)
• Zonisamide • Gabapentin (Gabp.)
• Tiagabine (Tiag.)
INHIBITION OF 'T' TYPE Ca2+
CURRENT
• Ethosuximide
• Trimethadione
• Valproate
TREATMENT OF SEIZURES
Seizure disorder Drugs
Tonic-clonic(Grand mal) Valproate
Drug of Choice Topiramte
Lamotrigine
Alternatives: Carbamazepine
Phenobarbital
Phenytoin
• Metabolism shows saturation kinetics and hence t ½ increases as the dose increased
• Pharmacokinetic Interactions
• Clinical Use:
– Very effective against absence, myoclonic
seizures.
– Also, effective in gen. tonic-clonic siezures
(primarly Gen)
– Less effective as compared to carbamazepine for
partial seizures
– Like Carbamazepine also can be used for Rx of
mania
• Side Effects of Sod. valproate:
• Nausea, vomiting and GIT disturbances (Start
with low doses)
• Increased appetite & weight gain
• Transient hair loss.
• Hepatotoxicity
• Thrombocytopenia
• Neural Tube defect (e.g. Spina bifida) in the
offspring of women. (contraindicated in
pregnancy)
Newer Antiepileptic Drugs
( Second- Generation )
1. Vigabatrin 1989
2. Gabapentin 1993**
3. Lamotrigine 1994**
4. Topiramate 1996**
5. Tiagabine 1997
6. levetiracetam 1999
7. Oxcarbazepine 2000 (safety profile similar to CBZ).
Hyponatremia is also problem, however it is less likely
to cause rash than CBZ.
8. Zonisamide 2000
• NEWER AGENTS DIFFER FROM OLDER
DRUGS BY
Relatively lack of drug-drug interaction
(simple pharmacokinetic profile) Improved
tolerability
HOWEVER THEY ARE
Costly with limited clinical experience
Lamotrigine
Pharmacological effects
Resembles phenytoin in its pharmacological effects
Well absorbed from GIT
Metabolised primarily by glucuronidation
Does not induce or inhibit C. P-450 isozymes ( its metabolism is
inhibitted by valproate )
Plasma t 1/2 approx. 24 hrs.
• Mechanism of Action:
Inhibits excitatory amino acid release (glutamate & aspartate )
by blockade of Na channels.
• Side effects:
• Skin rash, somnolence, blurred vision, diplopia, ataxia,
headache, aggression, influenza – like syndrome
Gabapentin
• Structural analogue of GABA .May increase the
activity of GABA or inhibits its re-uptake.
Pharmacokinetics:
Not bound to proteins
Not metabolized and excreted unchanged in urine
• Does not induce or inhibit hepatic enzymes (similar
to lamotrigine)
• Plasma t ½ 5-7 hours
Gabapentin ( Cont. )
• Side effects:
• Somnolence, dizziness, ataxia, fatigue and
nystagmus.
• Uses:
• As an adjunct with other antiepileptics
• Pain due to diabetic neuropathy, postherpetic
neuralgia
Topiramate
• Pharmacological Effects:
• Well absorbed orally ( 80 % )
• Food has no effect on absorption
• Has no effect on microsomal enzymes
• 9-17 % protein bound ( minimal )
• Mostly excreted unchanged in urine
• Plasma t1l2 18-24 hrs
• Mechanism of Action:
• Blocks sodium channels (membrane stabilization)
and also potentiates the inhibitory effect of GABA.
Topiramate (cont’d)
Side effects:
• Psychological or cognitive dysfunction
• Weight loss
• Sedation
• Dizziness
• Fatigue
• Urolithiasis
• Paresthesias (abnormal sensation )
• Teratogenecity (in animal but not in human)
Vigabatrin (restricted)
Pharmacological effects:Drug of choice for infantile
spasms
• Not bound to proteins ,Not metabolized and
excreted unchanged in urine
• Plasma t1/2 4-7 hrs
Mechanism of action :
Inhibits GABA metabolising enzyme & increase GABA
content in the brain( similar to valproate).
Side effects:
Visual field defects, psychosis and depression (limits
its use).
Zonisamide
Pharmacokinetics:
• Well absorbed from GIT (100 %)
• Protein binding 40%
• Extensively metabolized in the liver
• No effect on liver enzymes
• Plasma t ½ 50 -68 hrs
• Pharmacological effects
• Bioavailability > 90 %
• Plasma t ½ 4 -7 hrs
• Mode of action:
• inhibits GABA uptake and increases its level
Tiagabine cont’d
• Side effects:
• Asthenia
• Sedation
• Dizziness
• Mild memory impairment
• Abdominal pain
Clinical Advices for the Use of Drugs in the
Treatment of Epilepsy.
• General features:
• It is essential to have an accurate and
comprehensive diagnosis.
• EEG( supportive)
Clinical Advices ( Cont. )
• Ans D
Q2. Which one of the following antiepileptic
drugs can cause permanent vision loss?
A. Lacosamide
B. Vigabatrin
C. Topiramate
D. Levetiracetam
• Ans - B
Q3. Mechanism of action of vigabatrin is
A. Increase in GABA concentration
B. Sodium channel blockade
C. NMDA receptor blockade
D. Calcium channel blockade
• Ans- A
Q4. Mechanism of action of ethosuximide is
A. Reduction of low threshold Ca2+ current (T-
type current)
B. Sodium channel blockade
C. Increase in GABA
D. NMDA receptor blockade
• Ans- A
Q5. Ethosuximide is the drug of choice in:
A. Absence seizures
B. Febrile convulsions
C. Generalized tonic clonic seizures
D. Myoclonic seizures
Ans- A
Q6. Which one of the following is broad-
spectrum anti-seizure drug?
A. Ethosuximide
B. Valproate
C. Phenytoin
D. Phenobarbital
• Ans-B
Thank you
Bibliography
Bibliography
• Essentials of Medical Pharmacology -7th edition by KD Tripathi
• Goodman & Gilman's the Pharmacological Basis of Therapeutics 12th
edition by Laurence Brunton (Editor)
• Lippincott's Illustrated Reviews: Pharmacology - 6th edition by Richard A.
Harvey
• Basic and Clinical pharmacology 11th edition by Bertram G Katzung
• Rang & Dale's Pharmacology -7th edition
by Humphrey P. Rang
• Clinical Pharmacology 11th edition By Bennett and Brown, Churchill
Livingstone
• Principles of Pharmacology 2nd edition by HL Sharma and KK Sharma
• Review of Pharmacology by Gobind Sparsh