Antiepileptic Drugs (Anticonvulsants, antiseizure drugs)

1. Anticonvulsants are also called anti epileptic drugs.

2. Anticonvulsants are drugs used to treat epilepsy.
3. Epilepsy is a disorder of brain characterized by periodic and unpredictable occurrence of
seizures.
4. Seizures refer to temporary alternation of behavior due to disoriented firing of neurons in brain.

Epilepsy
Partial seizures Generalized seizures
1. Simple partial 1. Generalised tonic-clonic seizures
A simple partial seizure will affect only one area (GTCS/Grandmal seizures)
of your brain. It doesn't cause you to lose  A scream. Some people may cry out at the
consciousness. It's also very quick, typically beginning of a seizure.
lasting only a minute or two.  Loss of bowel and bladder control. This may
happen during or following a seizure.
2. Complex partial
 Stare blankly or look like they're daydreaming.  Unresponsiveness after convulsions.
Unconsciousness may persist for several minutes
 Be unable to respond.
after the convulsion has ended.
 Wake from sleep suddenly.
 Confusion. Fatigue. Severe headache.
 Swallow, smack their lips, or otherwise move their

mouth repetitively.
 Pick at things like the air, clothing, or furniture. 2. Absence seizure
 Sudden stop in motion without falling.
 Say words repetitively.
 Lip smacking.
 Scream, laugh, or cry.
 Eyelid flutters.
 Chewing motions.
 Finger rubbing.
 Small movements of both hands.

3. Atonic seizures
 Going limp and falling.
 Sudden loss of muscle tone.
 Briefly losing consciousness.
 Drooping eyelids.
 Nodding head.
 Jerking.

4. Myoclonic seizures
 Quick jerking, often after waking up.
 Rhythmic movements.
 Sensation of an electric shock.
 Unusual clumsiness.
Classification of antiepileptic drugs

1. Barbiturate: Phenobarbitone

2. Deoxybarbiturate: Primidone

3. Hydantoin: Phenytoin Fosphenytoin

4. Iminostilbene: Carbamazepine Oxcarbazepine

5. Succinimide: Ethosuximide

6. Aliphatic carboxylic acid: Valproic acid (sodium valproate) Divalproex

7. Benzodiazepines: Clonazepam Diazepam Lorazepam Clobaz

8. Phenyltriazine: Lamotrigine

9. Cyclic GABA analogues Pregabalin, Gabapentin

10. Newer drugs Topiramate Zonisamide Levetiracetam Vigabatrin Tiagabine

Lacosamide

Mechanism of action of antiepileptic drug

 1. Phenytoin (Diphenylhydantoin)
Phenytoin is one of the most commonly used antiepileptic drugs.

Mechanism of action:

1. Phenytoin acts by stabilizing neuronal membrane and prevents spread of seizure

discharge.

2. The sodium channel exists in three forms: resting, activated and inactivated states.

3. Phenytoin delays recovery of Na+ channels from inactivatedstate thereby reduces

neuronal excitability and inhibits the high frequency firing.

4. At high concentrations, phenytoin inhibits Ca2+ influx into neuron, reduces

glutamate levels and increases responses to GABA.
Pharmacokinetics

Phenytoin is absorbed slowly through the GI tract, widely distributed and highlybound to
plasma proteins.

Uses: it is used in the treatment of

 Generalized tonic-clonic seizures (grand mal epilepsy)

 Partial seizures
 Status epilepticus: phenytoin is administered i.v in normal saline.

Adverse effects

At therapeutic dose

 Hypersensitivity reactions like skin rashes, neutropaenia and rarely

hepatic necrosis.
 Hirsutism- due to increased androgen secretion.
 Hyperglycaemia- due to decreased insulin release.
 Megalobalstic anaemia- due to folate deficiency.
 Administered during pregnancy, phenytoin can produce 'foetal hydantoin
syndrome' (hypoplastic phalanges, cleft palate, harelip, microcephaly), which is
probably caused by its arene-oxide metabolite.

At high dose

 Fall in BP and cardiac arrhythmias occur only on i.v. injection.

 Drowsiness, behavioural alterations, mental confusion, hallucinations,
disorientation and rigidity.
 Intravenous injection can cause local vascular injury → intimal damage
and thrombosis of the vein → edema and discolouration of the injectedlimb.
 2. Fosphenytoin:
1. It is a prodrug of phenytoin, introduced to overcome the difficulties in i.v.
administration of phenytoin.

2. While phenytoin cannot be injected in a drip ofglucose solution (because it gets

precipitated), fosphenytoin can be injectedwith both saline and glucose.

3. Carbamazepine
1. Chemically related to imipramine.

2. Mechanism of action

Like phenytoin, it slows the rate of recovery of Na+ channels from inactivating,thereby
reduces neuronal excitability.

3. Adverse effects: sedation, drowsiness, vertigo, ataxia, blurred vision, nausea,vomiting,

allergic reactions like skin rashes etc.

4. Uses: Carbamazepine is the drug of choice in GTCS and partial seizures and of
trigeminal neuralgias.
5. Phenobarbitone
1. It is a barbiturate.
2. It acts by enhancement of GABAA receptormediated synaptic inhibition.
3. It is used in GTCS and partial seizures.

6. Ethosuximide:
1. It is effective for the treatment of absence seizures.
2. It acts by inhibiting T- type Ca2+ channels in the thalamic neurons.
3. Side effects are nausea, vomiting,headache etc.
7. Valporic acid (sodium valporate): carboxylic acid derivative

Sodium valproate is a broad spectrum antiepileptic drug.

Valproate appears act by multiple mechanisms:

1. A phenytoin-like frequency-dependent prolongation of Na+ channel

inactivation.
2. Like ethosuximide, it blocks T-type Ca2+ current in thalamic neurons.
3. Enhanced release of inhibitory neuro transmitter GABA due to inhibition of
itsdegradation (by GABA-transaminase)
4. Blockade of excitatory NMDA glutamate receptors.

Uses

Sodium valproate is highly effective in absence, myoclonic, partial and generalized

tonic-clonic seizures. Other uses of valproate are mania, migraineetc.

Adverse effects:

 Teratogenicity: orofacial and digital abnormalities; neural tube defectswith

increased incidence of spina bifida, so it should not be given during
pregnancy.
 Nausea, vomiting, anorexia, and abdominal discomfort.

5. Benzodiazepine (Diazepam, Larazepam, Clonazepam)

Diazepam and lorazepam are effective in controlling status epilepticus.

Clonazepam, a long acting benzodiazepam, is used in absence and myoclonic seizures.

i.v diazepam is used in the emergency treatment of status epilepticus, convulsion,

febrile convulsions etc.

Mechanism of action

Benzodiazepines potentiate GABA induced Cl– influx.

Adverse effects: i.v diazepam and lorazepam may cause hypotension and respiratory
depression. Other side effects are lack of concentration, lethargy.
Newer antiepileptics

Drugs Mechanism of Uses Adverse effects and

action other important
points
Lamotigrine Prolongation of As monotherapy or sleepiness, dizziness,
Na+ channel add on therapy in diplopia (double vision
inactivation. GTCS, or seeing double),
absence, Ataxia (poor co-
myoclonic and ordination, balance and
partial seizures. speech) and vomiting.

Gabapentin Enhances GABA Used in treatment mild sedation,

release of partial seizures, tiredness, dizziness,
Diabetic tremor and
neuropathy unsteadiness

Levetiracetam Binds selectively Used in partial sleepiness, dizziness,

to a synaptic seizures, and weakness
vesicular protein myoclonic epilepsy.
'SV2A' , and alter
release of
glutamate across
the synapse.
It also inhibits
N-type calcium
channels which
may affect
intracellular
Ca2+ release.
Topiramate prolongation of Used as a impairment of
Na+ channel monotherapy in attention, sedation,
inactivation, GTCS, ataxia,
myoclonic and poor memory, weight
GA BA partial seizures, loss,
release increase, migraine, chronic paresthesias (a burning or
alcoholism prickling sensation that is
usually felt in the hands,
antagonism of
arms, legs, or feet).
glutamate
receptors

neuronal
hyperpolarization
through K+
channels

Vigabatrin Inhibitor of therapyof partial Sedation, confusion,

(yvinyl GABA- seizures psychosis and visual
GABA) transaminase, the disturbances.
enzyme which
degrades GABA.

Lacosamide enhancing Na+ therapyof Ataxia, vertigo,

channel inactivation partial seizures diplopia.
and tremor, depression
suppressing repetitive and cardiac
firing of arrhythmia.
neurones.

Tiagabine Blocks GABA therapyof mild sedation,

transponer GAT-1 partial seizures nervousness,asthenia,
which removes Amnesia, dermatitis
synaptically and abdominal pain.
released GABA
into neurone and
glial cells.
Choices of antiseizure drugs:

Febrile convulsions: Some children, especially under 5 years age, developconvulsions

during fever.

Status epilepticus: When seizure act1v1ty occurs for >30 min, or two or moreseizures
occur without recovery of consciousness, the condition is called status epilepticus.