1. ANTI EPILEPTIC DRUGS
AFSAR FATHIMA
M.Pharm

2. CONTENTS DEFINITION EPIDEMIOLOGY AETIOLOGY PATHOPHYSIOLOGY
TYPES OF SEIZURES
GENERAL MECHANISM OF ACTION
DRUGS

3. EPILEPSY: A chronic disorder characterized by
recurrent seizure
SEIZURE: Is a violent involuntary spasmodic
contraction of skeletal muscle
EPIDEMIOLOGY: 1% worlds population & 57/1000

4. AETIOLOGY in children-idiopathic
in young- hypoxia, birth asphyxia, intracranial trauma during birth, metabolic disturbances, infection
In adult- head injury, alcohol abuse, cerebrovascular disease
DIAGNOSIS: EEG( electroencephalo gram)
MRI(magnetic resonance imaging)
CT scan
brain mapping

5. ACTIVATION OF EXCITATORY NEURO TRANSMITTOR INHIBITION OF INHIBITORY
PATHOPHYSIOLOGY
ACTIVATION OF EXCITATORY
NEURO TRANSMITTOR
INHIBITION OF INHIBITORY
IDIOPATHIC &
HERIDITORY
TISSUE DAMAGE

6. PARTIAL GENERALISED SEIZURE CLASSIFICATION SIMPLE COMPLEX FEBRILE
ONE PART OF BRAIN
GENERALISED
ENTIRE BRAIN
SIMPLE
COMPLEX
STATUS
EPILEPTIC-US
MYOCLONIC
ABSENCE
TONIC CLONIC
FEBRILE
SEIZURE

7. MECHANISM OF ANCTIONS
a) enhancement of GABAnergic transmission
b) diminution of excitatory transmission
c) modification of ionic conductance

10. SEIZURE TYPE
1ST LINE TREATMENT
2ND LINE TREATMENT
PARTIAL SEIZURE
SIMPLE PARTIAL SEIZURE
CARBAMAZEPINE
VIGABATRIN ,ZONISAMIDE
COMPLEX PARTIAL SEIZURE
PHENYTOIN
CLOBAZAM
GENERALISEDSEIZURES
TONIC CLONIC
VALPROATE
VIGABATRIN
TONIC
CLONIC
PHENYTOIN, LAMOTRIGINE
PHENOBARBITAL
ABSENCE
ETHOSUXIMIDE ,VALPROATE
CLONAZEPAM, LAMOTRIGINE
ACETAZOLAMIDE
ATONIC
CLONAZEPAM ,CLOBAZEPAM
LAMOTRIGINE ,CARBAMAZEPINE
PHENYTOIN ,ACETAZOLAMIDE
MYOCLONIC
VALPROATE, CLONAZEPAM
PHENOBARBITAL, ACETAZOLAMIDE
TOPIRAMATE

11. Cyclic ureides: Phenytoin, fosphenytoin
MECHANISM OF ACTION
Blocks high-frequency firing of neurons through action on voltage-gated (VG) Na+channels, decreases synaptic release of glutamate
PHARMACO KINETICS
Absorption is formulation dependent,highly bound to plasma proteins
no active metabolites ,Dose dependent elimination, ,t1/ h
fosphenytoin is for IV, IM routes
Toxicity: Diplopia, ataxia,, hirsutism, neuropathy
Interactions: isoniazid, felbamate, oxcarbazepine, topiramate, fluoxetine, fluconazole, digoxin, quinidine, cyclosporine, steroids, oral contraceptives,.

12. Phenobarbital Mechanism of action:
Enhances phasic GABAa receptor responses ,Reduces excitatory synaptic responses
Pharmaco kinetics:
Nearly complete absorption, not significantly bound to plasma Proteins,peak concentrations in 4 h, no active metabolites,t1/2 varies from 75 to 125h
Toxicity: Sedation, cognitive issues, ataxia, hyperactivity
Interactions:Valproate,carbamazepine,felbamate,phenytoin,cyclosporine, felodipine,,nifedipine, nimodipine, steroids,theophylline, verapamil,

13. Ethosuximide
Mechanism of action: Reduces low threshold Ca2+ currents (Ttype)
Pharmacokinetics: Well absorbed orally, with peak levels in 3-7 h, not protein-bound completely metabolized to inactive compounds ,t1/2 typically 40 h
Toxicity: Nausea, headache, dizziness,hyperactivity
Interactions: Valproate,phenobarbital, phenytoin, carbamazepine,rifampicin

14. Tricyclics: Carbamazepine
Mechanism of action: Blocks high- frequencyfiring of neurons through action on VG Na+ channels decreases synaptic release of glutamate
pharmacokinetics: Well absorbed orally, with peak levels in 6 to 8 h
no significant protein binding
metabolized in part to active epoxide
t1/2 of parent ranges from 8to 12 h in treated patients to 36 h in normal subjects
Toxicity: Nausea,, headache
Interactions: valproate, fluoxetine, verapamil, macrolide antibiotics, isoniazid.

15. Benzodiazepines : Diazepam &LORAZEPAM
MECHANISM OF ACTION: Potentiates GABAA responses
PHARMACO KINETICS:
Well absorbed orally
rectal administration gives peakconcentration in ~1 h with 90% bioavailability
IV for status epilepticus,highly protein-bound
extensively metabolized to several active metabolites, t1/2 ~2 d
Toxicity: Sedation

16. Clonazepam MECHANISM OF ACTION: As for diazepam PHARMACO KINETICS:
>80% bioavailability
Extensively metabolized but no active metabolites
t1/ h
Toxicity: Similar to diazepam

17. GABA derivatives :Gabapentin
MECHANISM OF ACTION: Decreases excitatory transmission by acting on VG Ca2+ channels presynaptically
PHARMACO KINETICS:
Bioavailability 50%, decreasing with increasing doses ,not bound to plasma proteins
not metabolized,t1/2 6-8 h
Toxicity: Somnolence, dizziness, ataxia

18. Pregabalin MECHANISM OF ACTION: As for gabapentin PHARMACO KINETICS:
Well absorbed orally ,not bound to plasma proteins
not metabolized,t1/2 6-7 h
Toxicity: Somnolence, dizziness, ataxia

19. Vigabatrin MECHANISM OF ACTION:
Irreversibly inhibits GABA-trans aminase
PHARMACO KINETICS:
70% bioavailable ,not bound to plasma proteins
not metabolized,t1/2 5-7 h
Toxicity: Drowsiness, dizziness, psychosis visual field loss

20. Miscellaneous: Valproate
MECHANISM OF ACTION: Blocks high-frequency firing of neurons, modifies amino acid metabolism
PHARMACO KINETICS:
Well absorbed from several formulations
highly bound to plasma proteins
Extensively metabolized, t1/ h
Toxicity: Nausea, tremor, weight gain, hair loss, teratogenic, hepatotoxic
Interactions: felbamate, rifampin, ethosuximide, primidone

21. Lamotrigine
MECHANISM OF ACTION: Prolongs inactivation of VG-Na+ channels,acts presynaptically on VG-Ca2+ channels,decreasing glutamate release
PHARMACO KINETICS:
Well absorbed orally
no significant protein binding
extensively metabolized, but no active metabolites
t1/ h
Toxicity: Dizziness, headache, diplopia, rash
Interactions: Valproate, oxcarbazepine, primidone, succinimides, topiramate

22. Levetiracetam MECHANISM OF ACTION: Action on synaptic protein SV2A
PHARMACO KINETICS:
Well absorbed orally
not bound to plasma proteins
metabolized to 3 inactive metabolites
t1/ h
Toxicity: Nervousness, dizziness, depression,
Interactions:,primidone

23. Tiagabine
MECHANISM OF ACTION: Blocks GABA reuptake in forebrain by selective blockade of GAT-1
PHARMACO KINETICS:
Well absorbed
highly bound to plasma proteins
extensively metabolized, but no active metabolites
t1/2 4-8 h
Toxicity: Nervousness, dizziness, depression, seizures
Interactions: Phenobarbital, phenytoin, carbamazepine, primidone

24. Topiramate
MECHANISM OF ACTION: Multiple actions onsynaptic function, probably via actions on phosphorylation
PHARMACO KINETICS:
Well absorbed, not bound to plasma proteins
extensively metabolized, but 40% excreted unchanged in the urine
no active metabolites
t1/2 20 h, but decreases with concomitant drugs
Toxicity: confusion
Interactions: Phenytoin, carbamazepine, oral contraceptives,, lithium

25. Zonisamide
MECHANISM OF ACTION: Blocks high-frequency firing via action on VG Na+ channels
PHARMACO KINETICS:
Approximately 70% bioavailable orally
minimally bound to plasma proteins
>50% metabolized, t1/ h
Toxicity: Drowsiness,, confusion.

26. Lacosamide MECHANISM OF ACTION: PHARMACO KINETICS:
Enhances slow inactivation of Na+ channels
Blocks effect of neurotrophins (via CRMP-2)
PHARMACO KINETICS:
Well absorbed ,minimal protein binding
one major nonactive metabolite ,t1/ h
Toxicity: Dizziness, headache, nausea small increase in PR interval

27. RETIGABINE MECHANISM OF ACTION: Enhances k+ channel opening
PHARMACOKINETICS: Readily absorbed,Requires 3-times daily dosing
TOXICITY : dizziness, confusion, blurred vision

28. RUFINAMIDE
MECHANISM OF ACTION: Prolongs inactivation of VG Na+ channels
PHARMACOKINETICS:
Well absorbed orally,Peak concentration in 4-6h
t1/2 6-10h,Minimal plasma protein binding
No active metabolites ,Excreted in urine
TOXICITY: vomiting ,diarrhea
INTERACTIONS: not metabolized by CYP 450 Enzymes

29. REFERENCES
Basic and clinical pharmacology- katzung, RogerJ.Porter,MD ,& Brain S. Meldrum,MB, PhD 11th edition
RANG & DALE’S Pharmacology 7th edition
CLINICAL PHARMACOLOGY BY Rooger & Walker
Conceptual pharmacology by D. jagadeesh Prasad
Goodman & Gilman