This document discusses epilepsy and seizure disorders. It defines a seizure as abnormal electrical discharges of cerebral neurons resulting in changes to motor, sensory or psychomotor activity. Epilepsy is characterized by recurrent seizures. Seizures can involve convulsions (shaking) or not. Antiepileptic drugs are used to prevent seizures, with different classes targeting sodium channels, GABA, or calcium channels. Common antiepileptics discussed include valproate, carbamazepine, phenytoin, ethosuximide, and phenobarbital. Adverse effects and mechanisms of several drugs are outlined. Classification of seizures and epilepsy syndromes is also covered.

1. Epilepsy

2. Seizure: An sudden and temporary alteration in
brain function due to abnormal electrical discharges
of cerebral neurons resulting changes in motor,
sensory, psychomotor activity
A group of chronic syndromes : Recurrence of
seizures – (periods of abnormal discharge of cerebral
neurons)

4. Convulsions
• A convulsion : body muscles contract and relax rapidly
and repeatedly results an uncontrolled shaking of the
body.
• Because a convulsion is often a symptom of an epileptic
seizure, the term convulsion is sometimes used as a
synonym for seizure.
• However, not all epileptic seizures lead to convulsions,
and not all convulsions are caused by epileptic seizures.
• Seizure may be associated WITH or WITHOUT CONVULSIONS.

5. • Site of origin of focus epileptic focus
• Epileptogenesis: previously normal brain is
functionally altered biased towards the generation
of the abnormal electrical activity chronic seizures.
• In simple words, it is the process by which normal
brains develops epilepsy.
• “Fit” term used alternatively an epileptic seizure

6. • The process of epileptogenesis is classically thought to
occur in three phases:
Precipitating injury or event changes occurs in the
structure and physiology of the brain (latent' period) 
results in the development of epilepsy  Chronic,
established epilepsy.
• During this latent period hyper-excitable neuronal
network forms  can lead to spontaneous seizures
• Experience abnormal behavior, symptoms and
sensations, including loss of consciousness.

7. Antiseizure drugs
Antiepileptic: used on chronic basis for prevention
of epileptic attacks.
Anticonvulsant: Used to stop the episode of
convulsions.
An antiepileptic may be anticonvulsant (eg.
Phenytoin sodium), but -Every anticonvulsant may
not be antiepileptic (eg. Diazepam)

8. Classification
• 2 type of classification
1. Based on seizure types & characteristic features
2. Epilepsy syndrome
• Etiological factors
• Frequency of attacks
• Age, onset
• Clinical manifestations

9. Focal or partial (1 hemisphere)
Simple partial
(Jacksonian )
Complex partial
(psychomotor )
Secondary
Generalized
Unilateral (min.spread)
localized focus
coffined to motorarea
abnormal
movements
No loss of consciousness
First localized spreads
Temporal lobe 
behavioral changes
altered consciousness
Dreamy state (Dien
focal spreads and
generalizes,
lost consciousness

10. Generalized seizures:
• Arise from both cerebral hemispheres and
diencephalon simultaneously, involving entire body.
• Types of generalized seizures:
Tonic seizure
Clonic seizures
Grand mal epilepsy or tonic clonic epilepsy
Akinetic (atonic) seizures
Petit mal epilepsy or absence seizure
Myoclonic seizures

11. Grand mal epilepsy
• Usually associated with aura prior to seizure.
• The pt. falls to the ground in stiff tonic phase (legs
extended) with an epileptic cry due to tonic
contraction of laryngeal muscles.
• followed by clonic convulsions (repetitive bilateral
muscle jerking) and then to coma which may last for
15-30 min.
• Recovery is associated with stupor, amnesia, mental
confusion, postictal (post seizure) depression,
incontinence and exhaustion.
• Status epilepticus: emergency condition

13. Petit mal epilepsy or absence seizures
• Prevalent in children.
• Last for 20-30 second
• No aura present
• Pt apparently freezes and stares in one direction. T
• here is a trance-like state. Unresponsive and unaware to
surroundings.
– If the patient is speaking, speech is slowed or interrupted;
– If walking, he or she stands transfixed;
– If eating, the food will stop on its way to the mouth.
• No muscular component or little bilateral jerking.
• Absence seizures generally are not followed by a period of
disorientation or lethargy (post-ictal state), this is in contrast
to the majority of seizure disorders.

14. Myoclonic seizures
• Bilateral epileptic myoclonus
• Characterised by sudden and brief skeletal
muscle contraction that may involve entire
body or one part of the body.
• Shock like momentary contraction of muscle
of limb or the whole body

15. Akinetic or atonic seizures
• Unconsciousness with relaxation of all muscle
due to excessive inhibitory discharge.

16. Sensory
 Visual changes. Examples:
Bright lights.
Zigzag lines.
Slowly spreading spots.
Distortions in the size or shape of objects.
Blind or dark spots in the field of vision.
 Hearing voices or sounds (auditory hallucinations).
 Strange smells (olfactory hallucinations).
 Feelings of numbness or tingling on one side of your face or
body.
 Feeling separated from your body.
 Anxiety or fear.
 Nausea.

17. Unclassified seizures
• Febrile : young children's with hyperpyrexia
• Infantile spasm: progressive mental
retardation

18. PARTIAL(focal)
SEIZURES
(1 hemisphere)
Simple partial
Complex partial
Secondary generalized
GENERALIZED seizures
(both hemispheres,
-Generalized tonic-clonic
(Grand mal)
-Absence seizures (petit
mal)
-myoclonic jerking
-Atonic seizures
-Infantile spasm

19. To find real seizure
Sometimes twitching may miss diagnosed as epilepsy
Non-epileptic seizures are paroxysmal events that mimic an
epilepetic seizure but do not involve abnormal, rhythmic
discharges of cortical neurons. They are caused by
eitherphysiological or psychological conditions.
• 1. Tongue bite
• 2. Urinary incontinence
• 3. Arching back
• 4.limbis moving flailing (vigorously)
• 5. Eye opening resisted or eye ball roll up

20. • Recent studies suggest :
• Inc excitatory neurotransmitter: Ach,
Glutamate, Asparate (Over activity) or
• inhibitory gamma amino butyric acid (GABA)
(decreased activity )
• Or both

21. Mechanisms of actions
• Imbalance or defects in
– Na+ or Ca2+ ion conductance
in neuronal membranes
– K efflux
– GABA transmission
– Excitatory mechanism involved in NMDA receptor
to produce depolarization (not yet available for
clinical use)

22. Mechanism of action
• 1 Sodium channel blockers
• Phenytoin, Carbamazepine, Lamotrigine
• Also phenobarbitone,valproate, topiramate
• 2 drugs affecting GABA transmission
• Receptor: BZD, Barbiturates, topiramate
•  GABA transaminase: Valproate, vigabatrin
•  GABA uptake: Tiagabine, Gabapentin

23. Mechanism of action..continued
3. T-type Calcium channel blockade:
Ethosuximide, Valproate (low threshold current in thalamic cortical rhytham)
4. Glutamate antagonism
• Phenobarbital, Felbamate,
• Topiramate (Kainate, AMPA receptors)
• Also Valproate
• 5. K channel: Valproate

24. Classification
• Aliphatic carboxylic acid: Valproic acid (sodium valproate)
• Barbiturate : Phenobarbitone
• Benzodiazepines: Clonazepam, diazepam, lorazepam, clobazam
• Deoxybarbiturate : Primidone
• Hydantoin : Phenytoin, fosphenytoin
• Iminostilbene: Carbamazepine, Oxcarbamazepine
• Phenyltriazine: Lamotrigine
• Succinimide: Ethosuximide
• Cyclic GABA analogues: Gabapentin, Pregabalin
• Newer drugs: Topiramate, zonisamide, levtiracetam,
vigabatrin, tiagabin lacosamide

25. Parital seziures
-Carbamazepine
-Valproic acid
Gen Tonic-clonic
-valproic acid
- Lamotrigine
-carbamazepine
-phenytoin
-phenobarbitone
Absence seizures
-Ethosuximide *
-Valproic acid
-lamotrigine, topiramate
Myoclonic seizures
-Clonazepam
-Valproic acid
-Benzodiazepines
-topiramate
Adjuncts
Felbamate, gabapentin*
Lamotrigine*, phenobarbital
Tiagabine, topiramate
Vigabatrin, leveteracetam,
zonisamide

26. PARTIAL SEIZURES
(1 hemisphere)
Valproate, phenytoin,
carbamazepine
-Simple partial
-Complex partial
-Secondary generalized
GENERALIZED seizures
(both hemispheres,
altered consciousness)
-Generalized tonic-clonic
(Grand mal)
-Absence seizures (petit
mal)
-myoclonic jerking
-Atonic seizures
-Infantile spasm

27. Anticonvulsant drug therapy general
considerations
• Anti epileptic drugs can control but nor cure
• Obj of therapy : provide neuro protection by
minimizing from seizure attack.
• Many pt have to take medication throughout
life to ensure control of seizure
• Newer drugs are add on drug

28. Barbiturates: Phenobarbitone
• Long acting barbiturate
• Phenobarbital was the main anticonvulsant
from 1912 till the development of phenytoin
in 1938.
• Current status: Today, Phenobarbital is rarely
used to treat epilepsy in new patients since
there are other effective drugs that are less
sedating.

29. MOA
• GABAA receptors are the primary target for barbiturates in the
central nervous system.
• By binding to GABAA receptor, barbiturates potentiate the effect
of GABA at this receptor (GABA facilitatory action).
• Barbiturate potentiate GABAergic inhibition by increase in
lifetime of Cl- channel opening induced by GABA.
• At high concentrations barbiturates directly increase Cl-
conductance (GABA mimetic action) and inhibit Ca+ dependent
release of neurotransmitter.
• In addition, barbiturates depress glutamate induced neuronal
depolarization through AMPA receptors (i.e. block AMPA
receptors)

30. Adverse effects
• Major drawback of phenobarbitone as an antiepileptic is its
sedative action.
• Long term administration may produce additional side effects
– such as behavioural abnormalities,
– diminution of intelligence,
– impairment of learning and memory,
– hyperactivity in children mental confusion in older patient.
• Rashes, megaloblastic anemia and osteomalacia

31. Uses
• Phenobarbitone can be effective in all types of seizures
except absence seizure. Hence effective in GTC, SP, CP
seizures.
• Dose : 60 mg 1-3 times daily.
• Less popular than carbamazepine, phenytoin or
valproate because of its dulling and behavioural side
effects.
• Drug interaction should also be taken into consideration
while starting phenobarbitone (phenobarbitone is an
enzyme inducer.)

32. Primidone
• Deoxybarbiturate
• Convertated by liver to phenobarbitone and
phenylethyl malonamide.
• Active drug --- active metabolite
• Dose 250-500 mg BD

33. Phenytoin
• Introduced in 1938.
• It is not a CNS depressant; some sedation occurs at
therapeutic dose.

34. MOA
• Phenytoin has stabilizing influence on neuronal membrane –by
an action on voltage-dependent sodium channels
• which carry the inward membrane current necessary for the
generation of an action potential.
• They block preferentially the excitation of cells that are firing
repetitively, and the higher the frequency of firing, the greater
the block produced.
• At higher dose/ toxic concentration:

35. Pharmacokinetics
• Absorption
– oral route is slow, mainly because its poor aqueous solubility.
– Bioavailability of different market preparations may be differ.
• Metabolised
– hydroxylation involving CYP 2C9 and 2C19 as well as
glucuronidation.
• The kinetics of metabolism is capacity limited : changes
from 1st order to zero order over the therapeutic range. –
hence plasma conc. rises suddenly even after small
increase in the dose. Monitoring of plasma conc. Is very
important

36. Adverse effect
• At therapeutic level:
• Gum hypertrophy: commonest (incidence 20%), more in younger patients. It is
due to overgrowth of gingival collage fibers. Can be minimised by maintaining oral
hygiene.
• Hirsuitism, acne.
• Hypersensitivity reaction: rashes, lymphadenopathy.
Neutropenia is rare requires discontinuation of the therapy
• Megaloblastic anaemia: decreases folate absorption, Inc.excretion.
• Osteomalacia: Interferes with metabolic activation of vit D with calcium
absorption/ metabolism.
• Foetal hydantoin syndrome: hypoplastic phalanges, cleft palate, hare lip,
microcephaly) – which is probably caused by its areneoxide metabolite.
• Facial expression: less

38. • At high plasma level (dose related toxicity):
 Cerebellar and vestibular manifestations: ataxia, vertigo, diplopia,
nystagmus are the most characterised features.
 Drowsiness, behavioural alternation, mental confusion, disorientation and
rigidity
 Epigastric pain, nausea, vomiting. These can be minimised by taking the
drug with meals.
 IV injection can cause local vascular injuary  intimal damage and
thrombosis of the vein oedema and discolouration of the injected limb.
Rate of injection should not exceed 50 mg/min. tissue necrosis occurs if
the solution extravasates.
 Fall in BP and cardiac arrhythmia on IV injection
• Drug interactions:

39. Uses of phenytoin
Draw backs :
• GTC, SP, CP seizures but not effective in
absence seizures
• Dose 100 mg BD …. Max. 400 mg/ day
• Status epileptics: fosphenytoin used now.
• Trigeminal neuralgia: 2nd choice

40. Fosphenytoin
• Water soluble prodrug of phenytoin
• Introduce to overcome the difficulties in iv
administration of phenytoin.
• Advantages:
• less damage to intima
• can be injected at faster rate (150 mg/ min)
but ECG monitoring is needed.

41. Carbamazepine
• Was introduced in 1960 for trigeminal neuralgia.
Now it is 1st line antiepileptic drug
• MOA : similar to Phenytoin.
• Antidiuretic action, probably by enhancing ADH
action on renal tubules.
• Pharmacokinetics:
• Interactions

42. Adverse effects
• Dose related neurotoxicity: sedation, dizziness, vertigo,
diplopia and ataxia.
• Acute intoxication:
• GIT adverse effect
• Hypersensitivity reaction: rashes, photosensitivity,
hepatitis, lupus like syndrome, rarely agranulocytosis
and aplastic anaemia.
• Water retention and hyponatremia.
• Foetal malformation

43. Uses
• CPS, GTC, SP but not for absence seizure
• Trigeminal and related neuralgias: Carbamazepine is
the DOC.
• Second line drugs for trigeminal neuralgia: phenytoin,
lamotrigine, baclofen, gabapentin.
• Manic depressive illness and acute mania:
• Dose 200-400 mg TDS children 15-30 mg/kg/day

44. Oxcarbazepine
• Toxic effects due to epoxide metabolite are avoided.
• Less drug interactions and auto-induction
• Risk of hepato-toxicity is less but that of
hyponatremia is more.

45. Ethosuximide
• Clinically only effective in absence seizure.
• The primary action appears to be exerted on
thalmocortical system.
• Selectively suppresses/ inhibits T type Ca channel
without affecting other types and Na currents.
• Use: only indication- Absence seizure but now
superseded by valproate.

46. Valproic acid (Na valproate)
• Broad spectrum anticonvulsant action.
• MOA
• A phenytoin like frequency dependent prolongation of Na+
channel inactivation.
• Ethosuximide like T type Ca2+ channel blocking action.
• Augmentation of release of inhibitory transmitter GABA by
inhibiting its degradation (by GABA transaminase) as well as
probably by increasing its synthesis from glutamic acid.
• Pharmacokinetics

47. Adverse effects
• Toxicity is relatively low.
• GIT: Anorexia, vomiting, loose motion, heart burn are common
but mild.
• CNS: Drowsiness, ataxia, tremors.
• Hypersensitivity reactions like rashes and thrombocytopenia.
• Alopecia, curling of hair, weight gain, increased bleeding
tendency.
• Asymptomatic rise in serum transaminase is often noted;
monitoring of liver function is noted.
• Teratogenic effect:
• Rare adverse effects: Acute live failure, pancreatitis, In young girls
– PCOD menstrual abnormalitis.
• Dose: 200-800 mg tds for adults. 15-30 mg/kg/day for children

48. USES
• Doc for absence, GTCS, Myoclonic, Atonic, tonic, clonic
seizures
• Mania and bipolar disorders: alternative to lithium.
• DOC for bipolar disorder in pt. having rapid cycles (4 or more
cycles per year).
• Have some prophylactic role in migraine.
• Recently it has been used in tardive dyskinesia.
• Alternative drug to carbamazepine in trigeminal neuralgia.

49. Benzodiazepines
• Diazepam, lorazepam, clonazepam, clobazam are
benzodiazepines that act by GABA facilitatory action.
These drug increase the frequency of Cl- channel
opening.
• Diazepam, lorazepam, clonazepam are effective for the
management of acute seizures.
• For status epilepticus lorazepam is DOC.
• Diazepam (per rectally) DOC for febrile seizures.
• Drawback prominent sedative effect
• Tolerance develops to the antiepileptic effect so these
are not indicated for long term use.

50. Other antiepileptic drugs
• Lamotrigine: broad spectrum antiepileptic have inhibitory
action on Na and Ca channel. Initially found effective as add
on therapy in refractory cases. Recently found effective as
monotherapy as well.
• Gapapentin: act by increasing synthesis and release of GABA.
Gabapentin and its newer congener pregabalin exert a
specific analgesic effect in neuropathic pain. Mainly used as
add on drug in the treatment of epilepsy.
• Pregabalin : it is particularly used for neuropathic pain, such
as diabetic neuropathy, postherpetic neuralgia, CRPS.

51. • Viagabatrin: irreversible inhibitor of GABA transaminase, thus
increases GABAergic activity. Irreversible visual field defect is
the characteristic adverse effect due to retinal atrophy.
• Tiagabine : act by inhibiting GABA transporter GAT -1.
• Topiramate : weak carbonic anhydrase inhibitory activity.
Broad spectrum anticonvulsant action. MOA: prolongation of
NA channel inactivation, GABA potentiation, antagonism of
certain glutamate receptors and neuronal hyper polarization
through certain K channels.
• Zonisamide: weak carbonic anhydrase inhibitory activity. MOA
porolonation of NA channel inactivation and suppression of T
type Ca currents in certain neurons.

52. Status epilepticus-
• Prolonged seizure
• Recurrent
• No consciousness bew seizures
• Permanent damage
• Semi prone position

53. Status epilepticus-
• Lorazepam – IV 0.1 – 0.2 mg/kg bolus (5-10 mg)
or
• Diazepam- IV 0.1 – 0.2 mg/kg bolus (5-10 mg) or
• slow IV infusion (2 mg/minute) – slow
redistribution, effect lasts longer
• Fosphenytoin 100-150 mg/min in saline or
glucose Or Phenytoin 25-50 mg/min in a saline IV
line
• Phenobarbitone – 100-200 mg IM/IV
• propofol/Valproate,midazolam/thiopentone/cura
rization

54. DCO
• Partial seizure: Carba, Valproic
• Partial to Gen: Lamotri, VA
• General tonic clonic: VA, Lam
• Absence: Etho, VA
• Myoclonic : VA, Clonazepam

55. • Thank U

56. Phenytoin – diphenylhydantoin- dilantin
• Na channel blocker
• Prolongs the inactivated state of voltage
sensitive Na channel
• Prevents repetitive detonation of
neuronal cells
• Inhibits high frequency discharge
• Ca, glutamate, GABA – other mechanisms at higher
concentrations

57. Phenytoin – diphenylhydantoin- dilantin
• Partial, generalized tonic-clonic – 100 mg
q 12 hrs – children 5-8 mg/kg/day
• Status epilepticus
• Trigeminal neuralgia
• worsens absence seizures

58. Phenytoin – diphenylhydantoin- dilantin
• Oral slow but 80-90% absorp.
• low TI (10-20µg/ml)
• Mixed order kinetics (10-20µg) first order (10-20µg)
than zero order– saturation kinetics
• PPB90-92%- displacement
• Induction – HMES
• I/M: Tissue damage(Precipitated), necrosis
• IV: Thrombophlebitis
• Fosphenytoin – IV, IM, water soluble
• IV slow ( Cardio collapse)

59. INTERACTIONS
– Binds to TBG – interference with T3, T4
Induction HES – anticoagulants, OCPs, quinidine,
doxycycline, cyclosporine, mexiletine, INH,
chloramphenicol, cimetidine inhibit phenytoin
metabolism

60. Phenytoin –adverse effects
• Gingival hyperplasia/hypertrophy
• Coarsening of facial features
• Hirsutism, acne
• Megaloblastic anemia (folate defi),
Peripheral neuropathy, depletes vit
D (osteomalacia), osteoporosis

61. Phenytoin –adverse effects
• Hypersensitivity, rash, neutropenia, Aplastic
anemia, agranulocytosis, neutropenia, fever
• Pregnancy:
• Neural tube defects
• craniofacial abnormalities
• cleft lip, cleft palate
• fetal hydantoin syndrome
• heart disease,
• reduced growth,
• mental retardation
• CNS depression, behavioral changes

62. Phenytoin –adverse effects
–Vestibulocerebellar syndrome ataxia,
–vertigo,
– nystagmus,
–diplopia
• GI discomfort, N, V
• Behavioral changes, hallucinations,
confusion, disorientation
• Cardiovascular toxicity only on iv admn

65. 3 per second spike and wave pattern – absence seizure

66. Phenytoin –adverse effects
• Gingival hyperplasia/hypertrophy
• Coarsening of facial features
• Hirsutism, acne
• Megaloblastic anemia (folate defi),
Peripheral neuropathy, depletes vit
D (osteomalacia), osteoporosis

67. B) Generalized
• Both cerebral hemispheres
• Involve entire body
Tonic-clonic (Grand mal)
• Tonic: Continuous contraction
• Clonic: Rapid contraction and relaxation
• Associated with Aura
• Epileptic cry (Contraction of laryngeal muscle)
• Followed by clonic convulsions- coma
• Last 15-30min
• Recovery associated with stupor, amnesia, mental confusion
• Status epilepticus: Recurrence of 2 or more seizures without
recovery of unconsciousness between the seizures
• Clinical emergency

68. 2) Petit Mal or Absence Seizures
• No aura
• No loss of consciousness (if loss for 5sec)
• Short duration (lasts for few seconds)
• Rapid blinking of eyelids
• Chewing movements
• Small amplitude clonic jerks of hands for sec
• Main seizure type 15-20% of children's

69. 3) Tonic
Rigid violent muscular contraction
Stiff & fixed extended limbs Some pts, after dropping
4) Clonic: Repetitive muscle jerks
5) Atonic ( akinetic):
Starts between the ages 2-5 yrs.
sudden loss of postural or sudden fall
6) Myoclonic .
Sudden, brief shock like contraction
which may involve the entire body or be confined
to the face, trunk or extremities.

70. • Care should be supportive so as to minimize
the damage from the floor and near by
objectives
• Turn on one side
• Place soft item below the head
• Minimize tongue bite
• Oxygen therapy

72. Infantile spasm
• Consists of a sudden jerk followed by stiffening.
• Each seizure lasts only a second or two but usually in a
series.
• Most common just after waking up and rarely occur
during sleep.
• They typically begin between 3 and 12 months of age
and usually stop by 4 years old.
• Steroid therapy and the antiseizure medicine Sabril
are the primary treatments.
• Most children are developmentally delayed later in life.

73. Classification according MOA
• Drugs acting Na:
– Phenotoin
– Car
– VC
– Lamotrizine
– fosphenytoin
– Oxcarbazepine
– Felbamate
– Topiramate
• GABA
– BZD : Clonazepam, diazepam,
lorazepam, clobazam
– Barb: Phenobarbitone
– VC
• Ca
– Etho
– VC
• K+
– VC
– retigabine,

75. T- type Ca2+
• Ca2+ Absence seizure
• low threshold current in thalamic cortical
rhytham