Antiepileptics by Dr. Pramod P Bhalerao

1. ANTIEPILEPTICS
Dr. Pramod P Bhalerao

2. Epilepsy
 Brief episodes (seizures) of loss or
disturbance of consciousness, with or without
characteristic body movements (convulsions).

3. Classification
 I. Generalised seizures
 1. Generalised tonic-clonic seizures
 2. Absence seizures
 3. Atonic seizures
 4. Myoclonic seizures
 5. Infantile spasms (Hypsarrhythmia)
 II. Partial seizures
 1. Simple partial seizures
 2. Complex partial seizures
 3. Simple partial or complex partial seizures secondarily
generalized

4. Generalised tonic-clonic seizures
(Grand mal)
 Commonest,
 lasts 1–2 min.
 The usual sequence is aura—cry—
unconsciousness—tonic spasm of all body
muscles—clonic jerking followed by prolonged
sleep and depression of all CNS functions.

5. Absence seizures(Petit Mal)
 prevalent in children,
 lasts about 1/2 min.
 Momentary loss of consciousness, patient
apparently freezes and stares in one direction,
no muscular component.

6.  Atonic seizures (Akinetic epilepsy):
Unconsciousness with relaxation of all
muscles due to excessive inhibitory
discharges. Patient may fall.
 Myoclonic seizures Shock-like momentary
contraction of muscles of a limb or the whole
body.

7. Partial seizures
 Simple partial seizures
 lasts 1/2–1 min.
 Often secondary.
 Convulsions are confined to a group of
muscles or localized sensory disturbance
depending on the area of cortex involved in
the seizure, without loss of consciousness.

8.  Complex partial seizures
 attacks of bizarre and confused behaviour and
purposeless movements, emotional changes
lasting 1–2 min along with impairment of
consciousness. An aura often precedes.
 The seizure focus is located in the temporal
lobe.

9.  Simple partial or complex partial seizures
secondarily generalized
 The partial seizure occurs first and evolves
into generalized tonic-clonic seizures with loss
of consciousness.

10.  Most of the cases of epilepsy are primary
(idiopathic),
 Some may be secondary to
 trauma/ surgery on the head,
 intracranial tumour,
 tuberculoma,
 cysticercosis,
 cerebral ischaemia, etc.

11. Phenobarbitone
 The first efficacious antiepileptic introduced in
1912.
 Enhancement of GABAA receptor mediated
synaptic inhibition.
 Adverse effect- 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.

12. Phenobarbitone : Mechanism of
action

13.  Phenobarbitone is one of the cheapest drug.
 It has broad spectrum efficacy in 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.
 It has become less popular than
carbamazepine, phenytoin or valproate
because of its dulling and behavioural side
effects.

14. Phenytoin
 Prolonging the inactivated state of voltage
sensitive neuronal Na+ channel.

15. Adverse effects of Phenytoin
 At therapeutic levels
 Gum hypertrophy
 Hirsutism
 Hypersensitivity reactions
 Megaloblastic anaemia
 Osteomalacia
 foetal hydantoin syndrome(hypoplastic phalanges, cleft
palate, hare lip, microcephaly)
 At high plasma levels (dose related toxicity)
 (a) Cerebellar and vestibular manifestations:ataxia,
vertigo, diplopia, nystagmus.

16. Uses of Phenytoin
 Phenytoin is a first line antiepileptic drug, but less
commonly used now because side effects are
frequent.
 Indications are:
 1. Generalized tonic-clonic, simple and complex
partial seizures. It is ineffective in absence
seizures.
 2. Status epilepticus: occasionally used by slow
i.v. injection (fosphenytoin has replaced it).
 3. Trigeminal neuralgia: second choice drug to
carbamazepine.

17. 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.

18. 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.

19. Carbamazepine
 Uses
 CPS
 GTCS
 SPS
 Trigeminal and related neuralgias.

20. 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;

21. 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.

22. Adverse effects of valproate
 Alopecia, curling of hair, weight gain
 Asymptomatic rise in serum transaminase
 Used during pregnancy, it has produced spina
bifida and other neural tube defects in the
offspring; should be avoided.

23. Uses of Valproate
 Drug of choice for absence seizures.
 Alternative/adjuvant drug for GTCS, SPS and
CPS.
 Myoclonic and atonic seizures—control is
often incomplete, but valproate is the drug of
choice.

24. Diazepam(Benzodiazepines)

25. 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
 Limitation: Development of tolerance.

26. Gabapentin
 Enhances GABA release

27. Gabapentin
 Gabapentin is considered to be a first line drug
for neuralgic pain due to diabetic neuropathy
and postherpetic neuralgia.

28. Vigabatrin
 Inhibitor of GABA-transaminase, the enzyme
which degrades GABA.
 Anticonvulsant action may be due to increase
in synaptic GABA concentration.

29. 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.

32. 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.