brief account on antiepileptics

1. ANTIEPILEPSY
Dr.Padma Prashanthini.V
Dept. Of Pharmacology

2. TYPES OF SEIZURE
PARTIAL
Simple
Complex
Partial with
Secondarily
Generalised
GENERALISED
Absence
Myoclonic
Atonic
Tonic- Clonic

3. SEIZURES ,CONVULSIONS, EPILEPSY
• Episode of brain dysfunction due
to abnormal discharge of cerebral
neurons.
SEIZURE
• Involuntary , violent and
spasmodic /Prolonged contraction
of the skeletal muscle.
CONVULSIONS
• Disorder of Brain function
characterized by episodes of
seizures.
EPILEPSY

5. CLASSIFICATION
1. Hydantoin: Phenytoin, Mephenytoin.
2. Barbiturates: Phenobarbitone,
Mephenobarbitone.
3.Deoxybarbiturate: Primidone.
4. Iminostillbene: Carbamazepine
5. Succinimide: Ethosuximide
6. GABA Transaminase : Valproic acid, Vigabatrin
Inhibitors
7. Bezodiazepines: Diazepam, clonazepam.
8. Miscellaneous: MgSo4 & Acetazolamide.

6. PHENYTOIN
• ACTION: Anti-seizure activity without CNS
depression.
• MOA: Blocks voltage dependent Na+ channels
and stabilises neuronal membrane.
• PK : Poor H2o solubility, Should not be given
IM, except Fosphenytoin . 90% PP bound.
t1/2 :12-36 Hrs. 1st pass metabolism

7. PHENYTOIN
• A/e: Nausea,Nystagmus, Peripheral neuropathy,
Vestibulae effects, GI Disturbances, Gum
hyperplasia and megaloblastic Anaemia,
Teratogenicity, Hirustism, acne, Osteomalacia,
Hypersensitivity, Hyperglycaemia,
 USES: Generalised tonic-clonic seizures
Partial seizures.
Status Epilepticus: I.V
Trigeminal Neuralgia, Digitalis induced arrhythmias

8. FOSPHENYTOIN
• Water soluble prodrug of phenytoin.
• On i.v. injection it is less damaging to the intima.
• it can be injected at a faster rate.

9. PHENOBARBITONE
• ACTION: Anti-epileptic and raises seizure
threshold.
• MOA: Enhances inhibitory neurotransmission
in CNS by activating GABA A receptors
facilitating GABA- mediated opening of
chloride channels.
• PK: 50% PP Bound., Enzyme inducer

10. PHENOBARBITONE
• A/e: Sedative action. Long term administration (as
needed in epilepsy) may produce additional side
effects like—behavioral abnormalities, diminution of
intelligence, impairment of learning and memory,
hyperactivity in children, mental confusion in older
people.
• USES: Generalized tonic-clonic (GTC), simple partial
(SP) and complex partial (CP) seizures in a dose of 60
mg 1–3 times a day in adults.

11. CARBAMAZEPINE
• It is a first line antiepileptic drug.
• Its pharmacological actions resemble
phenytoin.
• Adverse effects: Carbamazepine produces
dose-related neurotoxicity—sedation,
dizziness, vertigo, diplopia and ataxia.
• USES: CPS, GTCS, SPS , Trigeminal and related
neuralgias.

12. ETHOSUXIMIDE
• Ethosuximide selectively suppresses
T current.
• Thalamic neurones exhibit
prominent ‘T’ (transient) current
which is low threshold Ca2+ current
(due to inward flow of Ca2+ through
T type Ca2+ channels).
• Use: Absence seizures;

13. VALPROIC ACID (SODIUM VALPROATE)
• Valproate appears to act by multiple mechanisms:
• (i) A phenytoin-like frequency-dependent
prolongation of Na+ channel inactivation.
• ii)Weak attenuation of Ca2+ mediated ‘T’ current
(ethosuximide like).
• (iii) Augmentation of release of inhibitory
transmitter GABA by inhibiting its degradation (by
GABA-transaminase) as well as probably by
increasing its synthesis from glutamic acid.

14. ADVERSE EFFECTS OF VALPROATE
• Alopecia, curling of hair, weight gain
• Asymptomatic rise in serum transaminase
• Teratogenic:
Spina bifida and other neural tube defects in the
offspring; should be avoided in pregnancy..

15. DIAZEPAM(BENZODIAZEPINES)
• A first line drug for emergency
control of convulsions, e.g.
status epilepticus.
• Rectal instillation of diazepam is
now the preferred therapy for
febrile convulsions in children.
• Adverse effects: sedation,
Thrombophlebitis of injected
vein, development of tolerance.

16. GABAPENTIN
• Enhances GABA release.
• Gabapentin is considered to be a
first line drug for neuralgic pain
due to diabetic neuropathy and
post herpetic neuralgia.

17. VIGABATRIN
• Inhibitor of GABA-
transaminase, the enzyme
which degrades GABA.
• Anticonvulsant action may
be due to increase in
synaptic GABA
concentration.

18. TIAGABINE
• This newer anticonvulsant potentiates GABA
mediated neuronal inhibition by depressing GABA
transporter GAT-1 which removes synaptically
released GABA into neurones and glial cells.

20. STATUS EPILEPTICUS
• When seizure activity occurs for >5 min, or
• Two or more seizures occur without recovery of
consciousness,
• Lorazepam 4 mg (0.1 mg/kg in children) injected
i.v. at the rate of 2 mg/min, repeated once after
10 min if required, is the first choice drug now.