Introduction to epilepsy, types of epilepsy, anti-epileptic drugs and recent advances in the field of AED's.

1. Presented By,
K . Nandhini
Department Of Pharmacology

2. • A seizure is any clinical event caused by an abnormal
electrical discharge in the brain
• It is excessive discharge of cortical neurons and is
characterized by changes in electrical activity as
measured by the electroencephalogram (EEG).
• Epilepsy implies a periodic recurrence of seizures with
or without convulsions.
• It is transient uncontrolled discharges of the neurons

3. • A single seizure is not epilepsy
• Major seizures cause loss of consciousness with the patient
falling to the ground and presenting with the history of
blackouts
• Minor seizures cause alterations of consciousness without the
patient falling to the ground.

4. • A seizure is defined by release of excessive and uncontrolled
electrical activity in the brain. Seizures themselves are not a
disease, they are an event.
• Epilepsy (seizure disorder) is a neurological condition, that in
different times produce brief disturbances in the electrical
functions of the brain. Seizures are a symptom of epilepsy.

7. • They are classified based on the location of the focus and the
pathways involved in its spread
• Based on the area of the brain in which the abnormal discharge
originates they are classified into two types
A. Generalized seizures
B. Partial seizures

8. • If the initial activation of the discharge involves both the
hemispheres of the brain simultaneously then it is generalized
seizure.
• These seizures result in the impairment of consciousness from
onset
• They are further classified into 4 types
i. Tonic-clonic
ii. Absence
iii. Myoclonic
iv. Atonic

10. • Tonic-clonic: they are called as grand mal attacks, most common, the patient
suddenly goes stiff, falls and convulses with laboured breathing and
salivation.
• Cyanosis and tongue biting may occur
• It is then followed by drowsiness, confusion, headache and sleep
• Absence: it is also called as petit mal attacks. These attacks are seen in
childhood and adolescence. The child goes blank and stares, fluttering of the
eyelids and flopping of the head may occur. The attacks last only for few
seconds
• Myoclonic: These are involuntary shock like jerks, which may involve whole
body or the arms or the head. They are usually seen in the morning after
waking
• Atonic: Sudden loss of muscle tone and are very rare

11. • If the discharge starts in the localized area of the brain the
seizure is termed as partial or focal
• They are further classified as
i. Simple partial
ii. Complex partial
iii. Secondary generalized

12. • Simple partial: There is no loss of consciousness
• What happens during the attack depends on the area of discharge and
there is high inter-individual variability
• Localized jerking of the limb or the face, numbness are some examples
of what may occur
• Complex partial: altered behavior such as plucking his or her cloths,
performing aimless activities
• These seizures originate from the frontal or temporal lobes of the brain
• Secondary generalized: they are simple or complex in which the
discharge spreads to the entire brain

13. • Sleep deprivation
• Alcohol (particularly
withdrawal)
• Physical and mental exhaustion
• Flickering lights
• Infections
• Metabolic disturbances
Status Epilepticus:
When seizure activity occurs for more than 30mins or 2 or
more seizure without recovery of consciousness. Quick
treatment can prevent from death and permanent brain damage

14. • A variety of different electrical or chemical stimuli can easily
give rise to a seizure in any normal brain
• A single neuron discharging in an abnormal manner has no
clinical significance, it is only when the whole population of
the neurons discharges abnormally epilepsy results.
• This abnormal discharge may remain localized or it may spread
to adjacent areas, recruiting more neurons as it expands

15. Neurons are
interconnected in
a complex network
and linked through
synapses
Small electrical
current is
discharged by the
neurons to release
neurotransmitters
Excitatory
Inhibitory
Activation
of the
next
neuron
The information is
conveyed,
transmitted and
processed
Normal Neuronal Activity:

16. Neurons which
are damaged,
injured, metabolic
or chemical insult
Change in the
discharge
pattern leading
to bursts of high
frequency
discharges
Excitatory
No
Inhibition
Excessive
Activation
of the next
neurons
Seizures

17. CLASSIFICATION OF
ANTIEPILEPTICSBarbiturates
Phenobarbital
Methylphenobarbital,
Metharbital, Barbexaclone
Benzodiazepines
clobazepam, clonazepam,
clorazepate, diazepam,
midazolam, lorazepam.
Bromides
potassium bromide
Carbamates
felbamate
Hydantoins
ethotoin, phenytoin,
mephenytoin, fosphenytoin
Carboxamides
carbamazepine,
oxacarbazepine,
eslicarbazepine
acetate.
Fatty acids
valproic acid,
sodium valproate,
vigabatrin,
progabide,
tiagabine.
Fructose
derivatives
topiramate
GABA analogs
gabapentine,

20. • Block sodium channels
• Use: Partial seizures; Generalized tonic-clonic
seizures
• Oral, IV
• highly bound to plasma proteins
• T ½ of 12 -36 hrs
• Metabolized & dose dependent elimination

21. • Nystagmus, diplopia, ataxia, sedation, gingival hyperplasia &
hirsutism, coarsening of facial features, mild peripheral
neuropathy, megaloblastic anemia fever, skin rash, fetal
hydantoin syndrome(areneoxide metabolite)
• Drugs used:
T.Eptoin- 5,100mg/2ml inj.
C.Fentoin-ER 100mg extended release cap.

22. 1. Sulfonamides, valproate & phenylbutazone:
displace phenytoin from binding sites
2. Cimetidine, disulfiram, doxycycline, isoniazid,
phenylbutazone, warfarin, chloramphenicol:
inhibits phenytoin metabolism
3. Barbiturates & carbamazepine, pyridoxine
theophylline: enhance phenytoin metabolism
4. PHENYTOIN decreases serum levels of:
carbamazepine, chloramphenicol, corticosteroids,
haloperidol, quinidine, theophylline, oral
contraceptives, warfarin

23. • BLOCK SODIUM CHANNELS
• for partial seizures & Generalized tonic-clonic
seizures
• Orally absorbed with slow distribution
• Completely metabolized
Adverse Effects: diplopia & ataxia idiosyncratic
blood aplastic anemia, agranulocytosis
leukopenia
• Dose: 200-400mg

24. 1. Increase carbamazepine levels via metabolism:
cimetidine, erythromycin, isoniazid
2. Decrease carbamazepine levels via increase
metabolism: phenytoin, valproic acid
3. Carbamazepine decreases drug levels :
warfarin, oral contraceptives, doxycycline,
phenytoin, haloperidol
4. Carbamazepine increases drug levels :
cimetidine, isoniazid
5. Lithium induces carbamazepine toxicity.

25. • Inhibits tonic hind limb extension in the
maximal electroshock model, clonic seizures
evoked by pentylenetetrazol, and kindled
seizures
• Enhancement of inhibitory process
• Diminution of excitatory transmission
• USE: partial & generalized tonic-clonic
seizures
Dose: T.Gardenal- 30,60mg
inj- 200mg/ml inj.,

26. • Metabolized to: PHENOBARBITAL
• PHENYLETHYLMALONAMIDE(PEMA)
• Mechanism of action similar to phenytoin
• May cause sedation, ataxia, vertigo, GIT upset,
megaloblastic anemia
• Dose: 250-500mg BD

27. • Inhibits GABA transaminase
• Partial seizures
• In patients unresponsive to conventional drugs
• Rapid absorption
• T ½ of 6 -8 hrs
• CAUSES: drowsiness, behavioral & mood changes, weight
gain, visual field defect

28. • Inhibits sodium channels
• Partial seizures & Absence seizures
• Completely absorbed
• T ½ of 24 hours
• Broad therapeutic profile
• CAUSES: hypersensitivity reactions, diplopia, ataxia,
headache, dizziness, life threatening skin disorders.
• Dose: 50mg/day & increased upto 300mg/day

29. • MOA: alters GABA metabolism, its non-
synaptic release or its reuptake by GABA
transporters
• Also binds to the α2δ subunit of voltage
sensitive calcium channels
• FOR PARTIAL & GENERALIZED
SEIZURE
CAUSE: somnolence,dizziness,ataxia,headache
& tremor
Dose: 300mg OD

30. • Complex action: GABA effect, blocks voltage dependent
sodium channels
• Blocks glutamate receptors
• Similar to phenytoin with lower side effects & simpler
pharmacokinetics
• Risk of teratogenesis
• Sedation, mental dulling, renal stones, weight loss
• Dose: 25mg OD, increase weekly upto 100-200mg BD

31. • Nicotinic acid derivative
• GABA uptake inhibitor in both neurons &
glia
• Partial seizures
• Dizziness, tremor, difficulty in
concentration, psychosis

32. A pyrolidine
For partial & secondarily generalized tonic-
clonic seizures
MOA: unknown
Add on to drugs used for partial seizures
ADR: somnolence, asthenia and dizziness
Dose: 0.5g BD

33. • For absence seizures
• ↓ calcium channels (T type) currents
• Inhibits NA/K/ ATPase, depresses the cerebral metabolic
rate & inhibits GABA aminotransferase
• Absorption is complete
• Completely metabolized
• ADVERSE EFFECTS: gastric distress, lethargy,
headache
• DI: valproic acid inhibits its metabolism
• Dose: 20-30mg/kg/day

35. 1. Third-generation AEDs introduced in the last 5 years
include lacosamide, (LCM), rufinamide (RFN),
ezogabine (EZG), eslicarbazepine (ESL), and
perampanel (PER)
2. Intranasal, diazepam auto injectables are used
3. Stiripentol, bivaracetam, carisbamate, ganalaxone,
valrocemide are other drugs in pipeline.