Antiepileptic drugs and second generation

Antiepileptic drugs

1. Ethosuximide
MOA : ↑ seizure threshold
(−) Propagation of abnormal elec.
Activity
Selectively (−) ‘T’ current of Ca Channels
in thalamocortical neurons
( ↑ ‘T’ current absence seizures )

2. •USE : ONLY ABSENCE SEIZURES
•Kinetics :
Slow, complete oral Abs.
No Pr. Binding
No enzyme induction
Hepatic Metabolites -inactive

3. ADR
•Dose Related :
•GIT : N, V, D
•CNS : Sedation, headache, dizziness
Agitation, inability to concentrate
•HSR : St-J Syn., urticaria, SLE,
Blood dyscrasias.
•Rare but fatal BM-depression

4. Benzodiazepines
•MOA : GABA facilitator, ↑ Cl
−
cond.
•Oral : DOC in myoclonic S
ALTERNATIVE in Absence S.
ADD on drug for PS
Clobazepam & Clorazepate
For chronic use
Clobazepam for refractory cases
•IV Agents : DOC in Status Epilepticus
Diazepam , Lorazepam (long acting)

5. ADR
•Dose related :
•Sedation Fatigue, Ataxia,& Dizziness
•On IV Use :
•Respiratory & Cardiac depression
•* SAFEST among the antiepileptics
•* FREE from SEVERE side effects

6. Newer Agents
GABAPENTIN (GABA analogue )
↑ GABA synthesis & Release
•No Drug Interaction ? NO
•Metabolism / Plasma Pr. Binding /
Enz. Ind.
•USE : ADD on drug in PS, PC, GTC
•ADR : Mild & Related to CNS
(Cerebellar / Vestibular )

7. LAMOTRIGINE
•MOA :
(−) Glutamate & Aspartate Release
(−) Na Channels
Prevents repetitive firing
•USE : SP, CP, GTC
•T
1/2↓ by Enz Inducers (Carb, Phyn)
↑ by valproate & Enz inhibitors
•ADR : Mild CNS –E * Rash * DIC

8. VIGABATRIN
•Irreversible GABA-T ase Inhibitor
•Kinetics : same as gabapentin
•USE : Refractory Complex Seizures
as adjuvant
•ADR : Psychiatric problems
Memory loss
Diplopia
Agitation in children

9. Topiramate
•MOA : Acts by multiple mechanisms
•Prolongation of Na Channel inactivation
•GABA potentiation by post synaptic E.
•Antagoniism at Glutamate R
•USE : ADD on drug
in SP, CP, GTC & MC Seizures
•ADR : Attention impairment, Psychiatry
problems, renal stones

10. TIAGABIN
•GABA potentiation by (−) reuptake
•USE : Add on Drug to PS
•ADR : Sedation & Amnesia
LEVETIRACETAM
•MOA : not known
•(−) kindled seizures
•USE : Adjuvant in refractory PS

11. ZONISAMIDE
•MOA : (−) Na & Ca Channels
•USE : Add on Drug in
PS, GTC,MC Seizues
PROGABIDE
•Pro drug of GABA
•ADR : Hepatotoxic
•USE : controversial

12. FELBAMATE
USE : in poorly controlled PS
ADR : aplstic anemia, CNS (C & V)
OXACARBAZEPINE
•Carbamazepine derivative
•USE & ADR : same as CARB.
•Advantage : ADR & DI < CARB.
FOSPHENYTOIN
•Prodrug of phenytoin , IM / IV
route

13. Status Epilepticus
•Repeated Grandmal S. without
recovery of consciousness between
attacks
•Medical emergency
•Treatment needed to prevent
permanent brain damage & death
HOSPITALIZE

14. •1. IV drip of saline
•2. Keep CPR support ready
•3. Drugs
•Diazepam 10 mg IV bolus
(2mg / min) repeated at 10 mins
intervals or slow infusion titrated
dose, to control fits is the DOC
Rectal Diazepam if IV not possible
(Clonazepam 1-2 mg IV , alternative)

15. 2.Phenytoin 25 mg / min , upto 1G, IV
Phenobarbitone 100-200 mg IM / IV
Slow acting, used as an alternative to
diazepam or as substitution after
convulsions stop.
3. A GA & curarization with respiratory
Support may be needed if not
controlled with above drugs

16. General measures Needed
Maintenance Of
1.Air Way
2.Oxygenation
3.Fluid & Electrolyte Balance
4.Normal Cardiac Rhythm
5.Euglycemia
6.BP