Epilepsy

Introduction
 65 Million People Have Epilepsy Worldwide
 Incidence of epilepsy is 20 - 50 cases per year per 100,000 persons
in a general population.
 Prevalence rate is 500-1000 cases per 100,000 persons in the
population.
 Going by these statistics, there will be about 200,000 to 500,000 new
cases in the whole of India (estimated population about 100 crores).
 Similarly at the present time there may be approximately about 50-100
lakhs in whole of India.

Differences between terminologies

 Seizures
 Epilepsy
 Fits
 Convulsions
Classification of epilepsy
 Partial seizures
 Simple partial seizures
 Complex partial seizures
 Partial seizures evolving to secondarily generalized seizures

 Generalized seizures
 Tonic-clonic seizures (Grand mal)
 Absence seizures (Petit mal)
 Tonic seizures
 Atonic seizures
 Myoclonic & Clonic seizures

 Unclassified seizures
 Infantile spasms
 Febrile seizues
 Catamenial epilepsy
Partial seizures with secondary generalization
Absence seizures
Tonic seizures
Atonic seizures
Myoclonic seizures
Infantile spasm
Febrile seizures
Antiepileptic drugs
 Hydantoins: Phenytoin, Fosphenytoin
 Barbiturates: Phenobarbital
 Deoxy barbiturates: Primidone
 Iminostilbene: Carbamazepine, Oxcarbamazepine
 Succinimides: Ethosuximide
 Aliphatic carboxylic acid: Valproic acid, Divalproex
 Benzodiazepines: Clonazepam, Diazepam,
Lorazepam, Clobazam
 Phenyltriazenes: Lamotrigine
 Cyclic GABA Analogue: Gabapentin
 Newer drugs: Vigabatrin, Topiramate, Tiagabine,
Zonisamide, Levetiracetam
Phenytoin / Fosphenytoin
 MOA: prolongation of inactivated state of Na channel

 PK:
 Oral/im/iv, PPB (80-90%), liver, mixed order kinetics, inducer
 t1/2 -12-24 hrs, TDM (10-20mcg/ml)
 Steady state plasma conc – 5 days

 Uses:
 GTCS, SPS, CPS, Status (100mg bd, max 400mg)
 Trigeminal neuralgia
ADR:
 At therapeutic doses

 At high plasma levels

Phenobarbital / Primidone
 1912,
 MOA: GABAA (facilitator & mimetic)

 PK:
 Oral, t1/2-80-120 hrs, steady state – 2-3 weeks,
 Enzyme inducer,

 Uses: cheapest and least toxic

 GTC, SP, CP (60mg-1-3 times a day)
 ADR:
 hyper excitability in children, mental confusion in old age,
 Impairment of learning and memory
Carbamazepine / Oxcarbamazepine
 1960, 1st line antiepileptic
 MOA:
 PK:
 Oral, PPB (75%), liver, enzyme inducer, t1/2-20-40hrs,
 Autoinduction,
 Uses:
 Antiepileptic use: DOC for CPS, Also in GTCS, SPS (200-400mg TDS)
 Nonepileptic use: MDP, Neuralgias
 ADR:
 Acute intoxication: coma, death
 Water retention, hyponatremia (ADH like action)
Ethosuximide
 MOA: Thalamocortex (Absence seizures), inhibit T type Ca channel

 PK:
 Oral, t1/2-40 hrs,,
 Enzyme inducer,

 Uses:
 Pure petit mal drug (20-30mg/kg/day)
 ADR:
 GI, dizziness, lethargy, euphoria,
 Hypersensitivity,
 Bone marrow depression
 Valproic acid / Divalproex
 Broad spectrum antiepileptic
 MOA: All mechanism
 PK:
 Oral, PPB (90% ), t1/2-10-15 hrs, liver
 Enzyme inhibitor,
 Uses:
 DOC-Absence seizures, (200mg TDS, Max-800mg)
 GTCS, SPS, CPS
 Myoclonic, Atonic
 Mania, BPD, Migraine
 ADR:
 GI, drowsiness, ataxia, tremors,
 Alopecia, curling of hairs, bleeding tendencies
 LFT, pancreatitis
 Spina bifida
 Benzodiazepines
 MOA: GABAA
Diazepam: DOC for emergency control of many convulsions
 20-30mg slow iv, rectally in children (febrile seizures)

Clonazepam
 Absence, myoclonic, Atonic, Infantile spasm (0.5-5mg TDS)

Lorazepam : Alternative to Diazepam & action is more sustained

 0.1 mg/kg slow iv

Clobazam
 PS, Secondarily generalized, Absence, Myoclonic, Atonic
 10-20mg HS orally

Chlorazepate
 CPS, Myoclonic
 Benzodiazepines
 ADR
 Drugs affecting GABA transmission
Adverse effects
Generic Principal Uses Typical Dose; Half-
Name Dose Interval Life Neurological Systemic

Gabapentin Focal-onset 900–2400 mg/d; 5–9 h Sedation Gastrointestinal

tid-qid Dizziness irritation
Ataxia Weight gain
Fatigue Edema
Pregabalin

Vigabatrin Partial seizures 2-4 gm daily Behavioral changes, Visual field

with or without sedation, amnesia, disturbances
generalization Wt gain
Tiagabine Focal-onset 32–56 mg/d; bid- 7–9 h Confusion Gastrointestinal
qid Sedation irritation
Depression
Dizziness
Speech or language
problems
Paresthesias
Psychosis
 Dosage and Adverse Effects of Newer Antiepileptic Drugs
Adverse Effects
Generic Principal Uses Typical Dose; Half- Neurologic Systemic
Name Dose Interval Life
Lamotrigine Focal-onset 150–500 mg/d; bid 25 h Dizziness Skin rash
Tonic-clonic Diplopia Stevens-Johnson
Atypical absence Sedation syndrome
Myoclonic Ataxia
Lennox-Gastaut Headache
syndrome
Topiramate Focal-onset 200–400 mg/d; bid 20–30 h Psychomotor slowing Renal stones
Tonic-clonic Sedation Glaucoma
Lennox-Gastaut Speech or language Weight loss
syndrome problems Hypohidrosis
Fatigue
Paresthesias
 Adverse Effects
Generic Name Principal Uses Typical Dose; Half- Neurologic Systemic
Dose Interval Life
Felbamate Focal-onset 2400–3600 mg/d, 16–22 h Insomnia Aplastic anemia
Lennox-Gastaut tid-qid Dizziness Hepatic failure
syndrome Sedation Weight loss
Tonic-clonic Headache Gastrointestinal
irritation

Levetiracetam Focal-onset 1000–3000 mg/d; 6–8 h Sedation Anemia

qd-bid Fatigue Leukopenia
Incoordination
Mood changes

Zonisamide Focal-onset 200–400 mg/d; 50–68 h Sedation Anorexia

Tonic-clonic qd-bid Dizziness Renal stones
Confusion Hypohidrosis
Headache
Psychosis
 Adverse Effects
Generic Principal Uses Typical Dose; Half- Neurologic Systemic
Name Dose Interval Life

Lacosamide Focal-onset 200-400 mg/d; 13 h Dizziness GI irritation

bid Ataxia Cardiac conduction (PR
Diplopia interval prolongation)
Vertigo

Rufinamide Lennox-Gastaut 3200 mg/d 6-10 h Sedation GI irritation

syndrome (45 mg/kg, Fatigue Leukopenia
child); bid Dizziness Cardiac conduction (QT
Ataxia interval prolongation)
Headache
Diplopia

Ganaxolone Absence seizures Usual adverse effects of

(Neurosteroid) Catamenial epilepsy steroids
Drug therapy of epilepsy: General consideration

 AEDs suppress seizures but do not cure.

 Choice of drug: Dose?

 Initiation of treatment?
 Early, monotherapy, combination, substitution,
 Seizure diary
 Dose regulation?
 Termination of treatment?
 Prolonged therapy, Gradual,
 Newer drugs are merely ‘add on’ drugs
Selection of Antiepileptic Drugs
Generalized-onset Focal Typical Absence Atypical Absence,
Tonic-Clonic Myoclonic, Atonic
First-Line
Valproic acid Lamotrigine Valproic acid Valproic acid
Lamotrigine Carbamazepine Ethosuximide Lamotrigine
Topiramate Oxcarbazepine Topiramate
Phenytoin
Levetiracetam
Alternatives
Zonisamide Topiramate Lamotrigine Clonazepam
Phenytoin Zonisamide Clonazepam Felbamate
Carbamazepine Valproic acid
Oxcarbazepine Tiagabine
Phenobarbital Gabapentin
Primidone Lacosamide
Felbamate Phenobarbital
Primidone
Felbamate
Pregnancy and AEDs

 Should not be stopped during pregnancy

 Use lowest dose of least teratogenic drug

 Folic acid supplements

Thank You
Dr. Rohit Dixit
Asst Professor
Dept of Pharmacology
Famous persons with epilepsy
 Sir Isaac Newton  Aristotle

 Napoleon Bonaparte  Theodore Roosevelt

 Alexander the Great  Pythagoras

 Alfred Nobel  Martin Luther

 Leonardo Da Vinci  Charles Dickens