1. EPILEPSY
PRESENTED BY :- KINJAL S. GAMIT
DEPARTMENT OF PHARMACOLOGY
EN.NO :- 172280825005
M.PHARM
SEM -1
L.M.C.P.
1

2. WHAT IS EPILEPSY?
2

3. WHAT IS EPILEPSY?
3
• EPILEPSY -These are a group of disorders of the CNS
characterized by paroxysmal cerebral dysrhythmia,
manifesting as brief episodes (seizures) of loss or
disturbance of consciousness, with or without
characteristic body movements (convulsions), sensory
or psychiatric phenomena.
• Epilepsy has a focal origin in the brain, manifestations
depend on the site of the focus, regions into which the
discharges spread and postictal depression of these
regions.
• It is a Chronic medical condition produced by sudden
changes in the electrical function of the brain;
characterized by excessive excitability of neurons
within the CNS producing a variety of symptoms ranging
from brief periods of unconsciousness to violent convulsions,
sensory or psychiatric phenomenon.

4. CONT…
4
• A CONVULSION is a medical condition where body muscles
contract and relax rapidly and repeatedly, resulting in an
uncontrolled shaking of the body.
• A SEIZURES refers to a transient alteration of behavior due to
the disordered, synchronous, and rhythmic firing of population
of brain neurons.
• A seizure is a symptom of epilepsy.

5. C0NT…
SEIZURES can be :
• NON-EPILEPTIC - when evoked in normal brain by
treatments such as electroshock or chemical
convulsants.
• EPILEPTIC - when occurring without evident
provocation.
• seizures are thought to arise from the cerebral cortex, and not
from other CNS structures such as the thalamus, brainstem, or
cerebellum.
5

6. CONT…
• An international seizure classification scheme based on the
clinical features of seizures combined with EEG data is
widely used to describe seizures.
• It divides seizures into two main groups according to the
area of the brain in which the abnormal discharge
originates.
• EPILEPTIC classified into generalized and localized.
• If it involves initial activation of both hemispheres of
the brain simultaneously, the seizures are termed
‘generalized’.
• If a discharge starts in a ‘localized’ area of the brain,
the seizure is termed ‘partial’ or ‘focal’.
6

7. 7
SEIZURES
Complex
partial
Simple
partial
myoclonic
Absence
Infantile
spasms
(Hypsarrhyth
mia)
Simple
partial or
complex
partial
seizures
secondarily
generalized
Tonic- clonic
Atonic
GENERALIZEDPARTIAL
Epileptic seizures types :

8. I. PARTIAL SEIZURES :
1. Simple partial seizures (SPS, cortical focal epilepsy):
• lasts 1/2–1 min.
• Often secondary.
• Convulsions are confined to a group of muscles or localized
sensory disturbance depending on the area of cortex involved in
the seizure,
• without loss of consciousness.
2. Complex partial seizures (CPS, temporal lobe
epilepsy, psychomotor):
• attacks of bizarre and confused behavior and purposeless
movements,
• emotional changes lasting 1–2 min along with impairment of
consciousness.
• An aura often precedes.
• The seizure focus is located in the temporal lobe.
8

9. 9

10. CONT…
3. Simple partial or complex partial seizures
secondarily generalized :
• The partial seizure occurs first and evolves into generalized
tonic-clonic seizures with loss of consciousness.
10

11. 11

12. II. GENERALISED SEIZURES :
• focal symptoms may be prognostic in generalized
epilepsies
12

13. CONT…
1. Generalised tonic-clonic seizures (GTCS,
major epilepsy, GRAND MAL):
• commonest,
• lasts 1–2 min.
• The usual sequence is aura—cry—unconsciousness—tonic
spasm of all body muscles—clonic jerking followed by
prolonged sleep and depression of all CNS functions.
13

14. 2. Absence seizures (minor epilepsy, PETIT
MAL):
• prevalent in children,
• lasts about 1/2 min.
• Momentary loss of consciousness, patient apparently freezes
and stares in one direction, no muscular component or little
bilateral jerking.
• EEG shows characteristic 3 cycles per second spike and wave
pattern.
14

15. 3. Atonic seizures (Akinetic epilepsy or drop
attacks):
• Unconsciousness with relaxation of all muscles due to excessive
inhibitory discharges.
• Patient may fall.
• The seizures are brief – usually less than fifteen seconds.
15

16. 4. Myoclonic seizures :
• Shock-like momentary contraction of muscles of a limb or the
whole body.
16

17. 5. Infantile spasms (Hypsarrhythmia) :
• Seen in infants.
• Probably not a form of epilepsy.
• Intermittent muscle spasm and progressive mental
deterioration.
• Diffuse changes in the interseizure EEG are noted.
Status epilepticus :
• seizure activity occurs for >30 min, or two or more seizures
occur without recovery of consciousness.
• Recurrent tonic-clonic convulsions without recovery of
consciousness in between is an emergency; fits have to be
controlled as quickly as possible to prevent death and
permanent brain damage.
17

18. 18

19. EPIDEMEIOLOGY :
• As per a recent study, 70 million people
have epilepsy worldwide and nearly 90% of them are found in
developing regions.
• The study also estimated a median prevalence of 1.54% (0.48-
4.96%) for rural and 1.03% (0.28-3.8%) for urban studies in
developing countries.
19

20. ETIOLOGY :
• Seizures may result from primary or acquired disturbances of
CNS function, metabolic derangements, or a variety of systemic
disorders.
• Common cause of seizures vary according to patient age. For
example, fever is only a precipitant of seizures during late
infancy and early childhood.
• Similarly, inherited forms of epilepsy usually begin in
childhood or adolescence.
• In adulthood, acquired causes of seizures and epilepsy e.g.,
stroke, CNS tumor, CNS infection, and drug and alcohol toxicity
are more common, and are referred to as “symptomatic”
epilepsy.
• When no cause of seizures can be identified by history, physical
examination, laboratory investigation, or neuroimaging studies,
the seizure disorder is termed “cryptogenic”.
20

21. CONT…
• VITAMINS D
 V - VASCULAR
stroke, bleeding, A-V malformation
 I - INFECTIONS
meningitis, brain abscesses
 T - TRAUMA
road accidents, penetrating injuries
 A - AUTOIMMUNE DISEASES
CNS vasculitis, SLE (systemic lupus erythematosus)
 M - METABOLIC DISORDERS
hypoglycemia, hyponatremia
 I - IDIOPATHIC
cause unknown
 N - NEOPLASMS
space occupying tumors
 S - PSYCHIATRIC DISORDERS
 D - DRUGS
alcohol, cocaine, phencyclidine
21

22. 22
• Seizures are caused by a perturbation in the normal
balance of excitatory & inhibitory influences within
the brain.
• Synchronized, high- frequency bursts of action potentials are
the initiating event of a seizure.
• These bursts are caused by an influx of extracellular calcium
followed by opening of voltage-dependent sodium channels.
• This depolarization phase is followed by hyper polarization
phase that is mediated by the inhibitory neurotransmitter
GABA or by potassium channels.
• Most AEDs suppress seizures by altering ion flux through
membrane channels or by altering neurotransmitter
activity within the CNS.
PATHOPHYSIOLOGY :

23. SIGNS AND SYMPTOMS :
• Characteristics of seizures vary and depend on where in the
brain the disturbance first starts, and how far it
spreads.
• Temporary symptoms occur, such as
loss of awareness or consciousness,
disturbances of movement,
sensation (including vision, hearing and taste),
mood, or other cognitive functions.
• People with seizures tend to have more physical problems
(such as fractures and bruising from injuries related to
seizures), as well as higher rates of psychological
conditions, including anxiety and depression.
23

24. DIAGNOSIS :
PATIENT HISTORY
perinatal & development history
History of febrile seizures (feverish)
History of CNS infection, trauma
Family history of epilepsy
PHYSICAL EXAMINTION
• SEIZURE DESCRIPTION
Preictal phenomena (aura)
Ictal manifestation (including level of consciousness)
Postictal state
Provocative factors
24

25. CONT…
• LABORATORY ASSESSMENT
Blood urea nitrogen
Cerebrospinal fluid profile (only if meningitis is suspected)
Complete blood count
Electrolytes and glucose
Osmolality
Toxicology screen (if indicated)
• NEUROLOGICAL EXAINATION
Electroencephalogram (EEG)
Computed tomography (only for trauma)(CT scan)
Magnetic resonance imaging (MRI)
25

26. 26

27. Key points on the diagnosis and management
of epilepsy(National Institute for Health and
Clinical Excellence, 2004a)
• Diagnosis to be made urgently by a specialist with an interest in
epilepsy
• EEG to be used to support diagnosis
• MRI to be used in people who develop epilepsy as adults, in
whom focal onset is suspected, or in whom seizures persist
• Seizure type(s) and epilepsy syndrome, aetiology and co-
morbidity to be determined
• Initiation of appropriate treatment to be recommended by a
specialist
• Treatment individualised according to seizure type, epilepsy
syndrome, co-medication and co-morbidity, the individual's
lifestyle and personal preferences
27

28. CONT…
• The individual with epilepsy, and their family and/or carers, to
participate in all decisions about care, taking into account any
specific need
• Comprehensive care plans to be agreed
• Comprehensive provision of information about all aspects of
condition
• Regular structured review at least once a year
• Patient to be referred back to secondary or tertiary care if:
– Epilepsy inadequately controlled
– Pregnancy considered or pregnant
– Antiepileptic drug withdrawal considered
• MRI (magnetic resonance imaging)
• EEG (electroencephalogram)
28

29. CLASSIFICATION OF ANTIEPILEPTIC DRUGS :
1. Drugs that block voltage- dependant sodium channels.
2. Drugs that affect GABA metabolism.
3. Drugs that Affect Calcium Currents.
4. Drugs with multiple mechanisms of action.
5. Drugs with unknown mechanism of action.
29

30. CLASSIFICATION :
• 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,
Clobazam
• 8. Phenyltriazine : Lamotrigine
• 9. Cyclic GABA analogue : Gabapentin
• 10. Newer drugs : Vigabatrin, Topiramate, Tiagabine,
Zonisamide, Levetiracetam
30

31. THE MAJOR ANTIEPILEPTIC DRUGS ARE THOUGHT
TO ACT BY THREE MAIN MECHANISMS:
1– reducing electrical excitability of cell membranes,
mainly through use-dependent block of sodium
channels
31

32. 1. drugs that block voltage- dependant sodium
channels
Carbamazepine
Phenytoin
Lamotrigine
Oxcarbazepine
Zonisamide

33. Carbamazepine
Clinical uses :
- Primary generalized tonic clonic seizures.
- Partial seizures with or without secondarily
generalization.
- Bipolar disorders.
- Chronic pain syndromes: trigeminal neuralgia.
Neurotoxic side effects :
- Drowsiness, dizziness
- Blurred or double vision
- Lethargy, headache.
- Worsening of myoclonic, Atonic & absence seizures.

34. Carbamazepine
Systemic side effects :
- Nausea, vomiting, diarrhea
- Hyponatremia & fluid retention.
- Rash, pruritus
Rare side effects :
- Blood dyscrasias: Agranulocytosis, aplastic anemia.
- Dermatitis/rash,
- Stevens-Johnson syndrome.
- Serum sickness, pancreatitis,
- hepatic failure

35. Phenytoin
Clinical uses :
- Partial & generalized tonic clonic seizures.
- 2nd line agent for patients with mixed seizures
(myoclonic/tonic-clonic).
- Status epilepticus.
Neurotoxic Side effects:
- Dose related : Diplopia & Ataxia.
- Peripheral neuropathy.
- Behavior changes.

36. Phenytoin
Systemic side effects :
- Skin rash.
- Lymphadenopathy. ( abnormally enlarged lymph nodes)
- Gingival hyperplasia.
- Pulmonary fibrosis.
- Hirsutism,
-Teratogenic ( Fetal Hydantoin syndrome includes cleft lip and
palate, congenital heart disease, slow growth
- Megaloplastic anemia ( folate deficiency ).
NOTE – phenytoin is also an anti-arrthymetic drug treatment with
phenytoin should not be stopped abruptly.

37. Lamotrigine
Decreases the release of excitatory neurotransmitters
(glutamate/aspartate).
Clinical uses :
- Monotherapy in partial seizures.
- Adjunctive therapy in generalized tonic clonic seizure
- Mixed seizures.
Side effects :
- Dizziness, headache, Diplopia.
- Nausea.
- Hypersensitivity skin rash…(SJS, Angioedema)
life – threatening in 1-2% of pediatric patients.
not to be used in those < 16 years.

38. Oxcarbazepine
It is a 10- keto analogue to carbamazepine.
Clinical uses:
- Partial seizures.
- Generalized tonic clonic seizures.
- Affective disorders.
- Trigeminal neuralgia.
Side effects :
- CNS : sedation, dizziness, ataxia, diplopia…
- Hyponatremia… less than carbamazepine.
- Allergic skin reaction.

39. Zonisamide
• Sulfonamide derivatives.
• Blocking of voltage dependent Na & T- type Ca channels.
• Partial & Generalized tonic clonic seizures.
• Useful against infantile spasm and certain types of myoclonias.
Side effects :
- CNS: confusion, ataxia, sedation, poor concentration…
- Anorexia & weight loss.
- Skin rash.
- decreased sweating …hyperthermia
- Renal stones…rare…
C/I : Allergy to sulfonamides.

40. 2– enhancing GABA-
mediated synaptic
inhibition; this may be
achieved by an enhanced
postsynaptic action of
GABA, by inhibiting
GABA transaminase or by
inhibiting GABA uptake
into neurons and glial
cells
40

41. 2.Drugs That Affect GABA Metabolism
● Phenobarbital.
● Gabapentin.
● Tiagabine.
● Vigabatrin.
● Benzodiazepines.

42. Phenobarbital
M.O.A :
Binds to GABA receptor improving its effect by
extending GABA mediated chloride channel opening.
Clinical uses:
- Partial seizures.
- Generalized tonic clonic seizures.
- Neonatal seizures.
- Status epilepticus.
Side effects:
- Sedation, ataxia, nystagmus ( rapid, rhythmic and involuntary
eye movements), vertigo…
- Agitation & confusion… at high doses.
- Alteration of sleep cycles

43. Gabapentin
It is an amino acid, an analogue to GABA.
Clinical uses:
- Partial seizures.
- Generalized tonic clonic seizures.
- Neuropathic pain: post herpetic neuralgia.
Side effects:
- CNS: sedation, ataxia, headache, tremor…
- GI upset.
- Weight gain.

44. Tiagabine
Inhibition of GABA reuptake into presynaptic neurons.
Clinical uses:
Adjunctive treatment for partial and generalized seizures.
Side effects:
- CNS: sedation, tremor, depression, confusion…
- Nausea, abdominal pain.
Not recommended in children under age of 12 years.

45. Vigabatrin
Irreversible inhibitor of GABA transaminase.
Clinical uses:
- 2nd line treatment in patients with refractory partial
seizures.
- 1st line treatment in infantile spasm (west’s syndrome).
May worsen myoclonic jerks and generalized absence and precipitate
status epilepticus.
Side effects :
CNS: sedation, dizziness, headache…
Change in mood, agitation … 10%.
Retinal toxicity… irreversible
Weight gain.
Teratogenic…

46. Clonazepam
Clinical uses:
- Myoclonic seizures .
- Generalized seizures (mainly absence)
- Status epilepticus .
- Infantile spasm .
- Lennox Gastaut ( severe from of epilepsy, early childhood)
- Partial seizures .
Side effects:
- Sedation, ataxia, irritability.
- Cardiovascular & Respiratory depression .
- Hyper salivation in pediatric .
- Idiosyncratic reaction like blood dyscrasia is rare.

47. 3– inhibiting T-type calcium channels (important in
controlling absence seizures).
• Newer drugs act by other mechanisms, some yet to be
elucidated.
47

48. 3.Drugs That Affect Calcium Channels
Ethosuximide:
- Reduces T- type calcium currents in thalamic
neurons.
- Effective against absence seizures.
- May increase tonic- clonic seizures
Side effects :
- Nausea & Vomiting.
- Sleep disturbances.
- Drowsiness & Hyperactivity.

49. 49

50. 4. Drugs With Multiple Mechanisms Of Actions
● Valproate
● Felbamate
● Topiramate

51. Valproate
M.O.A:
- Blocking voltage- dependent sodium channels.
- Enhances GABA synthesis.
- Inhibits GABA transaminase.
- Acts against T- type calcium current.
Clinical uses:
- Absence seizures.
- Generalized tonic clonic seizures.
- Bipolar disorders.
- Migraine prophylaxis.

52. Valproate
Side effects:
- CNS: Tremor
- Dose related GI symptoms.
- Increase appetite & weight gain.
- Hair loss.
- Hepatotoxicity esp. < 2 years.
- Thrombocytopenia.
- Teratogenic… spina bifida ( major birth defect, type of neural
tube defect )(abnormal development of neural tube)

53. Felbamate
M.O.A:
- Inhibition of voltage – dependent sodium channels.
- Potentiate GABA response at GABA receptors.
- Inhibition of the excitatory N-methyl-D-aspartate
(NMDA) receptors.
Clinical uses:
- Broad spectrum of action.
- Effective in some patients with partial seizures.
- 3rd line drug in refractory seizures esp. Lennox
Gastaut syndrome due to its serious side effects.
Side effects:
- CNS: Insomnia, Diplopia, Ataxia
- GI: Anorexia, N & V.
- Weight loss.
- Aplastic anemia…rare
- Hepatotoxicity… rare

54. Topiramate
M.O.A:
- Blockage voltage – dependent sodium channels.
- Enhances activity of GABA at non benzodiazepine
site on GABA (A) receptors.
- Antagonizes NMDA receptors.
- Weakly inhibits carbonic anhydrase enzyme.
Clinical uses:
- Adjunctive therapy for partial & generalized seizures
- Adjunctive therapy for Lennox-Gastaut syndrome &
infantile spasm.

55. Topiramate
Side effects:
- CNS: confusion, ataxia, poor concentration.
- Cognitive impairment.
- Visual disorders: myopia, glaucoma (rare).
- Weight loss.
- Parasthesia & renal stones due to its
inhibition of carbonic anhydrase enzyme.
- Teratogenic in animals.

56. 5. Drugs With Unknown Mechanism Of Actions
Levetiracetam:
- Broad spectrum AED.
- Add- on therapy for refractory partial seizures.
Side effects:
- CNS: Fatigue, dizziness, agitation, anxiety…
- Increases susceptibility to infection, rhinitis or flu
like symptoms.
- Anemia, leukopenia.

57. Pregabalin
Clinical uses:
- Adjunctive therapy for partial seizures
- Peripheral neuropathic pain.
Renally excreted and is not hepatically metabolized
Side effects :
- Dizziness, somnolence and ataxia
- Blurred or double vision
- Weight gain
- Peripheral edema
- May cause euphoria
- New onset myoclonus has been reported.

58. 58

59. 59

60. CONT…
60

61. 61

62. CONT…
62

63. 63

64. ECT
64
• Electroconvulsive therapy (ECT), formerly known
as electroshock therapy, and often referred to as shock
treatment, is a psychiatric treatment in which seizures are
electrically induced in patients to provide relief from mental
disorders.

65. TYPES OF TREATMENT
65
• Medication
• Surgery
• Non-pharmacologic treatment
Ketogenic diet
Vagus nerve stimulation (VNS)
Lifestyle modifications

66. KETOGENIC DIET :
66
• Based on finding that starvation -- which burns
fat for energy -- has an antiepileptic effect
• Used primarily to treat severe childhood epilepsy,
has been effective in some adults & adolescents
• High fat, low carbohydrate
and protein intake
• Usually started in hospital
• Requires strong family commitment

67. VAGUS NERVE STIMULATION :
67
• Device is implanted to control seizures by delivering
electrical stimulation to the vagus nerve in the neck,
which relays impulses to widespread areas of the brain
• Used to treat partial seizures when medication does
not work

68. SURGERY :
68
• Factors influencing decision
• Likelihood seizures are due to epilepsy
• Likelihood surgery will help
• Ability to identify focus of seizures
• Other treatments attempted

69. COMMON CAUSES OF FAILURE OF
ANTIEPILEPTICS :
1. Improper diagnosis of the type of seizures
2. Incorrect choice of drug
3. Inadequate or excessive dosage
4. Poor compliance
69

70. TREATMENT IN SPECIAL SITUATIONS
ANTIEPILEPTIC AND PREGNANCY :
• Seizure very harmful for pregnant women.
• Monotherapy usually better than drugs combination.
• Folic acid is recommended to be given for every
pregnant women with epilepsy.
• Phenytoin, sodium valproate are absolutely
contraindicated and oxcarbamazepine is better than
carbamazepine.
• Experience with new anticonvulsants still not reliable to
say that are better than old ones.
70

71. EPILEPSY IN ADOLESCENTS AND YOUNG ADULTS
• Important points to remember are:
Avoiding sleep deprivation,
alcohol and substance abuse, driving, potentially risky leisure
activities like rock climbing, horse riding, etc.
prolonged television (TV) viewing, playing video games and
dancing in dark rooms with flickering/flashing lights
(discotheques).
71

72. EPILEPSY IN ELDERLY
• Generalized tonic-clonic seizures dominate for metabolic or
toxic etiologies, whereas partial seizures with or without
secondary generalization are most frequent for vascular or
other circumscribed brain lesions.
• A convulsive SE (tonic-clonic) is more frequent at an advanced
age as compared to younger age group.
• Patients with nonconvulsive status epilepticus (NCSE) may not
have clinical seizures and usually present with history of
sudden change in mental status.
• Every elderly patient with epilepsy should undergo, at least a
CT scan, though MRI is preferable as symptomatic epilepsy is
common in elderly.
72

73. CONT…
• The choice of AEDs in elderly depends on many factors:
changes in liver, kidney, gastrointestinal (GI) system and brain
itself.
• Bioavailability of the drug in elderly is altered.
• Existence of comorbid conditions in elderly may cause
interaction with AEDs and other drugs leading to AED toxicity
or other complications.
• Phenytoin, CBZ and VPA as well as most of the newer AEDs
can safely be used in the elderly.
73

74. SURGERY IN EPILEPSY
• All patients with medically intractable epilepsy (MIE) should be
evaluated at a center performing epilepsy surgery.
• A patient having MIE with an identifiable lesion on imaging,
correlated with electrophysiology [Electroencephalogram
(EEG), Vidio EEG] is a potential candidate for epilepsy surgery.
Even if imaging is negative, patients still can be surgical
candidates on further investigation.
• Epilepsy surgery should be done only in specialized centers.
• Surgery has a high chance of achieving seizure freedom (in 60–
70% of cases) and a reduction in seizure frequency in the
remaining 30–40% cases.
• When indicated it should be considered as early as feasible
rather than an option of last resort.
74

75. CONT…
• Epilepsy surgery may be resective or nonresective.
• Resective surgery includes lesionectomy (resection of the lesion
and the surrounding epileptogenic area),
amygdalohippocampectomy with or without temporal lobe
resection, multilobar resection and hemispherectomy.
• Nonresective surgery includes multiple subpial transections
corpus colostomy and vagus nerve stimulation (VNS).
75

76. REFERENCE :
• http://www.who.int/mediacentre/factsheets/f
s999/en/
• Essentials of pharmacology by K.D.Tripathi
• Clinical Pharmacy and Therapeutics Edited by Roger
Walker
• Goodman & Gilman's the pharmacological basis of
therapeutics (12th edition)
• RANG AND DALE’S Pharmacology
• Indian Guidelines on Epilepsy (Mrinal Kanti
Roy, Dhiman Das )
76

77. THANK YOU
77