Difference between seizures and convulsion, types of epilepsy,drugs used in epilepsy as per different mechanism of action,treatment of status epilepticus,guidlines for treatment of epilepsy

1. Antiepileptic drugs
Dr.Rahul Bhalsinge
Professor
Department of Pharmacology

4. Classification of Seizures
based on seizure types & their characteristic
feature a this is more useful in selecting the appropriate drug for
treating a particular type of seizure
“Syndrome Classification” is based on
epilepsy syndrome which includes etiological factors, frequency of
attacks, age at the onset & clinical manifestations a more useful in
assessing the long-term prognosis after deciding the therapeutic
strategy

5. Generalised Seizures
These arise from both cerebral hemispheres & diencephalon
simultaneously, involving the entire body a have bilateral
pattern in EEG recording.
Grand Mal Seizures (GTCS)
Petit Mal Seizures
Myoclonic Seizures
Atonic Seizures
Clonic & Tonic Seizures

6. Generalized tonic-clonic seizures
(GTCS, grand mal epilepsy)
Aura prior to seizures :
An aura is a perceptual disturbance experienced by
patients before the headache or seizure begins.
- Manifests as the perception of a strange light
- an unpleasant smell
- Confusing thoughts or experiences.
Stiff tonic phase(legs extended ) :With an epileptic cry
caused by tonic contraction of laryngeal muscles. This is
followed by clonic convulsions (repetitive bilateral muscle
jerking) & then loss of consciousness.
Recovery is associated with stupor,amnesia,mental
confusion, postectal depression, exhaustion.

9. Status epilepticus
In some cases, grand mal seizures occur repeatedly with no
recovery of consciousness in between the attacks. These type
of seizures are called as status epilepticus.

10. Absence seizures
1) Sudden onset of staring, unresponsiveness with
momentary loss of consciousness.
Myoclonic seizures Single or multiple sudden,brief,
shock like contractions

11. Atonic seizure – are characterized by
sudden loss of muscle strength or
postural tone and the person may fall
down to ground for no oblivious reason

12. Partial seizures
1. Simple partial seizures: no loss of consciousness and the symptoms may
be comparatively simple,e.g. recurrent(involuntary) contraction of one
side of face or of a finger.
2) Complex partial seizures or psychomotor : Aura/amnesia/abnormal
behaviour and automatism with impaired consciousness.

14. Hydantoin : Phenytoin, fosphenytoin
Barbiturates : Phenobarbitone
Deoxybarbiturates : Primidone
Iminostilbenes: Carbamazepine, oxcarbamazepine
Succinamide : Ethosuximide
Benzodiazepines:Diazepam,lorazepam,clonazepam,Clobazam
Carboxylic acid derivative: Valproic acid
Newer drugs : vigabatrin ,lamotrigine, gabapentin,
topiramate, zonisamide,tiagabine,levetiracetam.

17. Drugs act on GABA channels

18. Drugs act on NMDA receptors

19. Drugs act by blocking the effect of Neurotropic factors
Play an important role in epileptogenesis and provoking neuronal excitability

20. • Enzyme induction
• IV or orally
Uses: Therpeutic plasma conn - 10-20ug/ml
Antiepileptic use: Grand mal epilepsy,Partial
seizures, status epilepticus (IV)
Non-antiepileptic use: (a)Trigeminal neuralgias,
(b)To treat ventricular arrhythmias due to
digitalis toxicity (c) To enhance wound healing

21. Phenytoin
• Hypertrophy, or hyperplasia of gums
• Hyperglycemia
• Hypocalcaemia
• Hypersensitivity
• Hirusutism
• Hydantoin syndrome
Cleft palate,cleft lip
Congenital heart disease
Slowed growth
Mental retardation

22. • Enzyme induction
• IV, orally
Uses:
• GTCS, partial seizures, Prophylaxis for febrile
convulsion, status epilepticus(IV)
A/E: Hyperexicitibility in children
• Free of teratogenic effect,
• Megaloblastic anaemia
Sedation

23. • Enzyme induction
Uses:
• GTCS, partial seizures, Trigeminal neuralgias
and other neuralgias, neuropathic disorder,
acute mania, bipolar disorder
A/E:
vertigo
Skin rashes
Ataxia sedation

24. Teratogenicity
- Finger nail hypoplasia
- Craniofacial defects
- Delayed development of fetus

26. Teratogenecity: orofacial, digital
abormalities, neural tube defect, spina bifida

27. • Effective in treatment of status epilepticus e.g. diazepam,
lorazepam
• Used in absence and myoclonic seizures.
• IV route diazepam–status epilepticus, eclamptic
convulsions, tetanus, febrile convulsions
• Rectal route- Febrile convulsion
• Diazepam & lorazepam : hypotension & respiratory
depression
• Clonazepam: sedation,lethargy
• Hypotonia, behavioural disturbances like hyperactivity
,irritability, lack of concentration etc.
Recently, FDA approved diazepam nasal spary for short
term management of epilepsy
D/I : Alcohol/hypnotics – more sedation if combined with
diazepam

28. Teratogenicity of BZDs

29. - Analogue of GABA
- By releasing GABA
- No enzyme inducing property
: It is mainly used in simple and complex partial seizures
Migraine prophylaxis, Diabetic neuropathy, Bipolar
disorder, Sedation, ataxia, fatigue, tremor
: Sedation, ataxia, fatigue, tremor
- Mechanism similar to gabapentin
- useful in partial seizures and neuralgias
- Sedation

30. - Broad spectrum antiepileptic activity
- Na+ channels
carbamazepine, phenytoin,phenobarbitone
- useful as monotherapy or add-on therapy in GTGS,
absence, myclonic, partial(SPS/CPS) seizures
Sedation,ataxia,skin rashes,nausea
- Broad spectrum antiepileptic activity
• Na+ channels
• GABA activity
• glutamate
it reduces effectiveness of OCPs.
- use in GTGS, myoclonic seizures, partial seizures
Weight loss,nervousness,sedation confusion.

31. -
Levetiracetam Tiagabine Zonisamide Lacosamide
Binds to vesicular
protein ‘SV2 A in
synaptic vesicle –
modifies release
of glutamate
• also inhibit N
type of Ca++
channels
Inhibit GABA
transpoter (GAT-
1)- removal of
released GABA in
synapse –
stimulates GABA
receptors
- Blocks Na+
channels
-Blocks ‘T’ type
Ca++ channels
-
Blocks Na+
channels
Blocks CRMP
(Collapsing
Response
Mediator Protein)
Refractory partial
seizures, GTCS &
myoclonic seizures
Adv- No drug
interactions
As add on therapy
in refractory
partial seizures.
It has been also
been tried as
monotherapy
Monotherapy &
add on therapy
for refractory
partial seizures
Used in
refractory partial
seizures &
diabetic
neuropathic pain
Sleepiness,
behavioural
changes, ataxia &
dizzininess,
hypersensitivity
reaction
Contrainn -< 4yrs
Tremor,confusion,
dizziness &
fatigue
Amnesia,
nervousness,
dermatitis
Amnesia,
somnolence,irritab
ility, rash,
metabolic acidosis
due to inhibition
of carbonic
anhydrase
Diplopia,
fatigue,tremor,
loss of balance&
suicidal ideations,

32. 1. Hospitalized the patient
2. Maintain and establish a proper
i.v.line.
3. Administer oxygen
(maintain BP)
4. Collect blood for estimation of glucose,
calcium,electrolytes and urea
5. Maintain and balance

33. If seizures continues
General anaesthesia with i.v. midazolam or propofol
If seizures continues
Phenobarbitone 10-15mg/kg i.v. infusion 100mg/min
Diazepam 10mg i.v. slowly, repeat after 10min if
necessary or lorazepam 0.1mg/kg i.v. slowly
Phenytoin 25mg/kg i.v. or fosphenytoin 20mg/kg i.v.

34. • Children < 18 months,
those with neurological abnormaties
• Those with seizures lasting > 15min
Prevention
- Diazepam (0.5mg/kg) given orally or rectally at the
onset of convulsions
- Timely use of paracetamol & tepid sponging prevent
high fever
- If convulsions occur, diazepam (rectally or iv) can
be used
All
have
greater
risk
of
recurrence

35. • In pregnancy, antiepileptics should be continued because sudden
discontinuation increases the risk of status epilepticus which is
hazardous to fetus.
•
• Treatment should be restricted to a single drug as far as
possible.
supplementation (500ug daily) should be given during
2nd and 3rd trimester to avoid neural tube defects
10mg/day given for last 2-4 wks to avoid vitamin K
deficiency & bleeding disorders.