Dr. RAGHU PRASADA M S
DEPT. OF PHARMACOLOGY
SSIMS & RC.
Epilepsies are the group of disorders of CNS
characterized by paroxysmal cerebral dysrhythmia,
manifesting as brief episodes of loss of
consciousness with or without characteristic body
movements(convulsions), sensory or psychiatric
phenomena.(periodic and unpredictable)
Seizure is transient alteration of behavior due to
disordered synchronous rhythmic firing of
population in brain neurons
1. GTCS-generalized tonic clonic seizures-
Time -1-2 min
Sequence –Aura Cry unconsciousness tonic
spasms Clonic jerking prolonged sleep
prolonged sleep depression of CNS function
Common in children
Time -30 sec
Momentary loss of consciousness
Patient apparently freezes and stares in one
3hz-spikes discharge- voltage regulated Ca+ channels
Unconsciousness with relaxation of all muscles due
to excessive inhibitory discharges
Infantile spasms- intermittent muscle spasm and
progressive mental deterioration
Occasional, sudden, excessive, rapid and local
discharges of gray matter
Simple partial seizures-consciousness is preserved
Localized sensory disturbances
Complex partial seizures-temporal lobe epilepsy
bizarre confused behavior
Todds paralysis, jacksonian seizures- simple partial or
1. Inhibition of voltage-gated Na+ channels to slow
2. Enhancement of the inhibitory effects of the
3. Inhibition of calcium channels-absence seizures
Mechanism of drugs used in grandmal seizures
Inhibition of use-dependent Na channels
Enhancement of GABA ergic action
Phenobarbital and Benzodiazepines
Blockade of NMDA or AMPA receptors
Blockade of voltage gated N-type Ca+ channels
Lamotrigine and Gabapentin
Selective binding to synaptic vesicular protein (SV2A)
By blocking the effect of neurotropic factors
Inhibition of T type Ca channels
blocks voltage-gated sodium channels by selectively binding to
the channel in the inactive state and slowing its rate of recovery
Finally glutamate release is inhibited
Limited water solubility – not given i.m.
Slow, incomplete and variable absorption.
Extensive binding to plasma protein.
Metabolized by hepatic ER by hydroxylation. Chance
for drug interactions.
Therapeutic plasma concentration: 10-20 µg/ml
Shift from first to zero order elimination within
therapeutic concentration range.
High i.v. rate: cardiac arrhythmias ± hypotension;
Acute oral overdose: cerebellar and vestibular
symptoms and signs:
nystagmus, ataxia, diplopia vertigo.
Folate Deficiency - megaloblastic anemia
Hypoprothrombinemia and hemorrhage in newborns
Hypersensitivity Reactions – could be severe. SLE, fatal
hepatic necrosis, Stevens-Johnson syndrome.
Pseudo lymphoma syndrome
Drug Interactions: decrease (cimetidine, isoniazid) or
increase (phenobarbital, other AED’s) rate of
metabolism; competition for protein binding sites.
A Prodrug. Given i.v. or i.m. and rapidly converted to
phenytoin in the body.
Avoids local complications associated with
phenytoin: vein irritation, tissue damage, pain and
burning at site, muscle necrosis with i.m. injection,
need for large fluid volumes.
Otherwise similar toxicities to phenytoin.
CARBAMAZEPINE: derivative of iminostilbene with a
carbamyl group, structurally related to TCAs
-GTCS, trigeminal neuralgia
Manic depressive psychosis
may have adrenergic mechanism as well
Also for trigeminal neuralgia
Serious hematological toxicity: aplastic anemia, aplastic
anemia Antidiuretic effect increase ADH
Mild enzyme inducer
is a sulfonamide derivative that has a broad
spectrum of actionPartial, generalized tonic clonic
and myoclonic seizures, lennox-gastaut syndrome
Other Mechanism of Action:
▪ Inhibits T-type Ca2+ currents.
▪ Binds to GABA receptors.
▪ Facilitates dopaminergic and serotonergic
S/E-drowsiness, amnesia, kidney stones
Other Mechanism of Action: May inhibit synaptic
release of glutamate.
Adjunct therapy-Simple & complex partial seizures
Generalized seizures of Lennox-Gastaut Syndrome
Monotherapy: Simple & complex partial seizures
S/E-dizziness, diplopia, enzyme inducers
Wide spectrum antiepileptic
Blocks voltage gated Na channels
Blockade of NMDA receptors
Drug refractory epilepsies- lennox-gastaut syndrome
Atonic seizures, atypical seizures, partial seizures
S/E- Aplastic anemia, hepatotoxicity
Binds selectively to SV2A protein of synaptic vesicles
in glutamatergic and GABAergic neurons.
Acts by inhibiting voltage gated Na channels
CRMP-2(Collapsin Response Mediator Protein) Brain
Derived Neurotropic Factor epileptogenesis
The only barbiturate with selective anticonvulsant
MOA-Bind at allosteric site on GABA receptor and
↑ dura on of opening of Cl channel.
↓ Ca-dependent release of neurotransmitters at
Use dependent Na+ channels blockade
AMPA receptors-inhibit glutamate
Febrile seizures, simple partial
P/K-Plasma t1/2- 100hrs
Dose 60-180mg orally HS
Inducer of microsomal enzymes – drug interactions.
sedation (early; tolerance develops)
Gingival hyperplasia, hirsutism
Nystagmus & ataxia at higher dose;
Osteomalacia, folate deficiency and vit. K deficiency.
In children: paradoxical irritability, hyperactivity and
Deoxybarbiturates: primidone: active but also
converted to phenobarbital. Some serious additional
ADR’s: leukopenia, SLE-like.
C/I-Petitmal And Porphyria's
Sedative - hypnotic- anxiolytic drugs.
Bind to another site on GABA receptor. Other
mechanisms may contribute. ↑ frequency of
opening of Cl channel.
Clonazepam and clorazepate for long term
treatment of complex partial seizures.
Diazepam and lorazepam: for control of status
epilepticus. Disadvantage: short acting.
Toxicities: chronic: lethargy drowsiness.
in status epilepticus: iv administration
respiratory and cardiovascular depression.
Phenytoin and PB also used.
Vigabatrin: Irreversible inhibitor of GABA
Simple and complex partial seizures
Drug refractory epilepsy and infantile spasm
Potential to cause psychiatric disorders (depression
and psychosis). Weight gain
Vigabatrin can cause irreversible visual field defects
Tiagabine: decreases GABA uptake by neuronal,
extraneuronal tissues and increases the GABA
content of brain
Developed as GABA analogues readily cross BBB
Mechanism: Increases release of GABA
Inhibit N type Ca channelsinhibit synaptic release of
Absorption of gabapentin from intestine depends on the
Resistant partial seizures, GTCS
Chronic nerve injury α2δ subunits of L-type Ca channels, in
peripheral nerves, get upregulated resulting in various
types of neuropathiesgabapentin binds to α2δ subunits
Post-herpetic neuralgia, trigeminal neuralgia, multiple
Effective in multiple seizure types.
Blocks Na and Ca channels.
Inhibits GABA transaminase. Increases GABA synthesis.
Decrease in the glutamate
Antiepileptic use- absence seizures
GTCS, myoclonic seizures
DOC- Lennox gastaut syndrome
Non-epileptic use-manic depressive psychosis,
Migraine, cluster headache, cushings syndrome,
Tardive dyskinesia, trigeminal neuralgia
Toxicity: most serious: fulminant hepatitis.
More common if antiepileptic polytherapy in
children < 2 years old.
Tremors, thrombocytopenia, hair loss
Drug interactions: inhibits Phenobarbital and
multiple mechanisms of action (Na channel, GABA
enhancement like BZD, antagonist at AMPA subtype
of glutamate receptors (not NMDA).
GTCS, partial and absence seizures
S/E- urolithiasiscarbonic anhydrase inhibition
Broad spectrum anticonvulsant
Blockade of use dependant Na channels
Inhibition of t-type of Ca channels
Negligible protein binding and renal excretion
GTCS, myoclonic seizures
Lennox- gastaut syndrome
S/E-drowsiness, amnesia, kidney stones
Drug of choice for Absence.
Blocks Ca++ currents (T-currents) in the thalamus.
Pure petitmal drug
Preferred in pregnancy
GI complaints most common
CNS effects: drowsiness lethargy
Has dopamine antagonist activity ( In seizure control)
but causes Parkinsonian like symptoms.
Potentially fatal bone marrow toxicity and skin
Premonitory stage-diazepam-10-15mg repeated once
after 15 min
Early status-lorazepam-0.1mg/kg repeated once
after 15 min
Give usual AED medications if already on treatment
Established status-fosphenytoin infusion15-20mg/kg
Refractory status-general anaesthesia-propofol 2-
-Thiopental sodium 3-5mg/kg
Anaesthesia continued for12-24 hrs after last clinical or