2. Epilepsy
An assortment of different seizure types & syndromes
originating from several mechanisms that have
common sudden, excessive & synchronous discharge of
cerebral neurons resulting in loss of
consiousness,abnormal movements, odd behaviour
/distorted perceptions.

3. Introduction
Seizures occurs when there’s a sudden change in communication of
braincells through electrical signal.
During seizures,some brain cells send abnormal signals which stop
other cells from working perfectly leading to temporary changes n
Behaviour,Sensation,Movement/Consciousness.
Onset---- During childhood & after 65 years of age.
Most seizures are Benign which lasts for longtime called Status
Epilepticus ,a life threatening disease characterised by Continuous
seizures, sustained loss of consiousness, Respiratory distress.

4. Epidemiology
• Epilepsy does impact on an individual's human rights, for
example, access to health and life insurance is affected.
• A person who suffers from epilepsy may not be able to
obtain a driving licence and it has an impact on the choice
of career.
• Epilepsy is a chronic neurological disorder that affects
people of all ages.
Around 50 million people worldwide have epilepsy.
Nearly 90% of the people with epilepsy are found in
developing regions.
Epilepsy responds to treatment 70% of the time. Despite
this, approximately 75% of affected people in developing
countries do not get the treatment they need.
People with epilepsy and their families suffer from stigma
and discrimination in many parts of the world.

5. Etiology

6. Pathogenesis of Epilepsy

7. There are multiple mechanisms that might contribute to
synchronous hyperexcitability, including:
1) alterations in the distribution, number, type, and biophysical
properties of ion channels in the neuronal membranes;
(2) biochemical modifications of receptors;
(3) modulation of second messaging systems and gene
expression;
(4) changes in extracellular ion concentrations;
(5) alterations in neurotransmitter uptake and metabolism in
glial cells; and
(6) modifications in the ratio and function of inhibitory circuits.

8. Transitory imbalances between the main neurotransmitters, glutamate
(excitatory) and γ -aminobutyric-acid (GABA) (inhibitory),&
neuromodulators (e.g., acetylcholine, norepinephrine,and
serotonin) might play a role in precipitating seizures in susceptible
patients.

10. • Diagnosing epilepsy can be difficult as it is first
necessary to demonstrate a tendency to recurrent
episodes of epilepsy.
There are other conditions that may cause impairment or loss of consciousness
and which can be misdiagnosed as epilepsy; these include
syncope,
breath-holding attacks,
transient ischaemic attacks,
psychogenic attacks, etc.
Other problems such as metabolic dysfunction,
infection,
head trauma
or flashing lights (photosensitive seizures).
These conditions have to be clearly ruled out before a diagnosis of epilepsy is
made.

11. • The EEG is often the only examination required,
particularly in generalised epilepsies, and it aims
to record abnormal neuronal discharges.
• Neuroimaging with magnetic resonance imaging
(MRI) is the most valuable investigation when
structural abnormalities such as stroke, tumour,
congenital abnormalities or hydrochephalus are
suspected. MRI should be carried out in anyone
presenting with partial seizures or where a
structural lesion on the brain may be responsible
for seizures.

12. Neuro-imaging techniques such as:
MRI,PET,SPECT.
Abnormal electrcal activity during a seizure can be detected
by EEG.
Seizures have been categorized by site of origin, etiology,
electrophysiologc correlation ,clinical presentation.
Seizures have been classified in to2 broad groups:
• Partial (Simple & Complex)
• Generalized(Tonic-Clonic & Absence).
• Others (Myoclonic, Febrile, Status epilepticus).

18. • Absence seizures:
These involve brief, abrupt, self-limiting loss of
consiousness.
In 3-5 years of age patients(onset occurs) & lasts
till puberty.
Patient stops speaking in mid-sentence, & stares vacantly for
few seconds(3-5sec).

20. Febrile seizures
Young children may develop with illness accompanied by
high fever.
Intermittent muscle spasm & progressive metal
deterioration.

23. ANTI -EPILEPTICS
These are the drugs used in the treatment of EPILEPSY.
Barbiturates : Phenobarbitone.
Deoxybarbiturate : Primidone.
Hydantoin : Phenytoin,Fosphenytoin.
Immunostilbines : Carbamazepine,Carbazepine.
Succimide : Ethosuximide.
Aliphatic carboxylic acids: Sodium valproate, Divalproate.
Phenylriazine : Lamotrigine.
Cyclic GABA analogue : Gabapentin.
Newer drugs :Vigabatrine, Tiagabine,Topiramate,
Levetiractem.
BZD’s : Diazepam,Lorazepam,Oxazepam,
Clonazepam.

24. Mechanism of Action

25. The 3 mechanisms appear to be
important action of Epilepsy.
I. Enhancement of GABA action.
II. Inhibition of Na+2 channel function.
III. Inhibition of Ca+2 channel function.
IV. Inhibition of Glutamate release & Blockade of
receptors.

27. Enhancement of GABA action:( BZD’s, Barbiturates)
Vigabatrin -- Inhibits enzyme“GABATransaminase”.
Tiagabine --Inhibits GABAuptake & enhance action of
GABA.
Gabapetin – designed as an agonist @ GABAA Receptors.
Inhibition of Na+2 channel function:
(Phenyltriazine,Hydantoins,Immunostibines,
Aliphatic –COOH’s).
These drugs affect membrane excitabilty by an action on voltage-
gated Na+2 channels, which carry the inward membrane current
necessary for generation of Action potential.
Inhibition of Ca+2 channels: (Suucimides,Gabapetin).
Succimides blocks T-type Ca+2 channels .
Gabapentin blocks L-type Ca+2 channels .

28. Pharmacokinetics:
Absorption ----Slow on oral administration.
Bioavailability differs in market preparations.
Distribution is wide & 80-90% bound to plasma proteins.
Metabolism– Liver by Hydroyxlation & Glucoronide
conjugation.
T1/2– 12-24hrs & increases up to 60 hrs.
Only 5%Unchanged Phenytoin is excreted in urine.

29. Adverse Effects:
@ Therapeutic levels— Due to over growth of
Collagen fibres causes Gum Hypertrophy.(Can b minimized by
Oral hygiene).
Girls- Hirsutism,Acne,Coarsening of facial features.
Hypersensitivity Reactions-Rashes,Lymphadenopathy,Neutropenia.
Megaloblastic AnaemiaIt decreases Folate absorption &
increases folate excretion.
Osteomalacia, Hypergycemia, In pregnancy—causes
FOETAL HYDANTOIN SYNDROME.

30. @ Higher levels– Cerebellar & Vestibular
manifestations: Ataxia, Vertigo, Diplopia,
Nystagmus. Drowsiness,Mental confuion,
Hallucinations, Disorientation, Muscle rigidity.
Epigastric pain, Nausea & vomiting
(Can b minimized when taken with meals).
I.V injection causes Local injury, oedema, vein
thrombosis, Discolouration of injected
limb,Hypotension & Cardiac arrhythmias.

31. Carbamazepine + Phenytoin creases each others Metabolism.
Isoniazid, Cimetidine, Dicumerol,Warfarin  Inhibits Phenytoin
metabolsim.
Phenytoin induces Steroid degradation.
Sodium Valproate Decreases metabolism & Increases Phenyton
plasma levels.

32. USES
1st line Anti-Epileptic for Generalized Tonic-Clonic
,Simple &Complex partial seizures.
In Status Epilepticus.
In Trigeminal Neuralgia.