EPILEPSY AND ANTIEPILEPTIC DRUGS.ppt presentation

Medical

2. EPILEPSY refers to a disorder of brain function characterized
by the periodic and unpredictable occurrence of seizures.
Seizure is defined as the clinical manifestation of excessive (or)
hypersynchronous activity of neurons within the cerebral
cortex.
1% of population

3. What Is the Difference Between Epilepsy & Seizures?

A seizure is a brief, temporary disturbance in the electrical
activity of the brain

Epilepsy is a disorder characterized by recurring seizures (also
known as “seizure disorder”)
A seizure is a symptom of epilepsy

4. J. H. Jackson (1830 – 1911)
“Occasional, sudden ,
excessive, rapid and local
discharge of gray matter
leading to the
involvement of other
parts of the brain”
‘Disease of Lightening’

5. •Seizures are symptom of an underlying CNS
dysfunction
•It is an abnormal, uncontrolled electrical discharge from
neurons
Cell membrane disruptions (permeability)
Altered ion distributions (chemical balance)
Decreased neurotransmitters (Ach and GABA)

6. Classification of epileptic seizures
Partial seizures
simple
complex
Generalized seizures
tonic-clonic(grand mal)
absence(petit mal)
myoclonic
Status epilepticus,Catamenial epilepsy:
Classification of epileptic seizures

7. Primary
Types of s
(focal)

8. INTERNATIONL CLASSIFICATION

I. GENERALIZED SEIZURES
A. Tonic, clonic, Tonic-clonic (grandmal).
B. Absence (petitmal).
1. With loss of consciousness only
2. Complex with brief tonic, clonic movement
C. Juvenile myoclonic epilepsy.
Shock- like momentary contraction of muscles of a limb or whole body
D. Infantile spasms (west syndrome). Intermittent muscle spasm
and a progressive mental deterioration
E. Atonic ( atatic, akinetic) seizures. Unconsciousness with
relaxation of all muscles.
F. Lennox – gastaut syndrome.

9. II. PARTIAL (OR) FOCAL SEIZURES
A. simple (with out Loc / alteration in psychic Function)
1.Motor – frontal lobe origin (tonic, clonic, jacksonian)
2.Somatosensory (visual, auditary, olfactory, gustatory)
3.Autonomic Vertiginous
4.Pure psychic- dysphasia, hallucinations
B. complex (with Loc) - TEMPORAL LOBE EPILEPSY
III. SPECIAL EPILEPTIC SYNDROMES
A.Myoclonus & Myoclonic seizures
B.Reflex epilepsy
C.Acquired Aphasia with convulsive disorder.
D.Febrile & others – infancy & childhood.
E.Hysterical seizures.

10. Types of seizures
Grand mal epilepsy Petit mal epilepsy

11. Myoclonic seizure Atonic seizure

12. Status epilepticus Febrile convulsions

13. Neuronal Substrates of Epilepsy
The Brain
The Synapse
The Ion Channels/Receptors
ions

14. •Depolarising Na+ and Ca++ ionic current shifts are activated
by glutamate receptors
•Repolarising K
+
currents are mediated by GABA receptors
•Hyperpolarisation is mediated by GABAA receptors creating
an influx of Cl
-
=> inhibition of impulse generation.
Nature of Epilepsy

15. Nature of Epilepsy
•The neurochemical basis of the abnormal
discharge is not well understood.

It may be associated with
•Enhanced excitatory amino acid
transmission, impaired inhibitory
transmission, or
•Abnormal electrical properties of the
affected cells.
•The glutamate content in areas surrounding
an epileptic focus is often raised.
Depolarization shift

16. A = activation gate
I = inactivation gate
Na
+
Na
+
Carbamazepine
Phenytoin
Lamotrigine
ValproateNa
+
Na
+
I
I
Voltage gated sodium channel
Open Inactivated
X

17. Na
+
+
Ca
++
Ca
++
T - type Ca
++
channel
Open closed
X

18. GABA-A Receptor
•Oligomeric
(glycoprotein.
•It is a Cl
-
Channel.
•Binding of GABA causes
the channel to open and
Cl
-
to flow into the cell
membrane
hyperpolarization.
GABA AGONISTS
Barb

BZDs

Cl





19. Other possible causes
•Inherited mutations of proteins involved in the ion channels
•Reduction in the activity of homeostatic ATPase pumps within
neuron cell membranes

20. Targets for AEDs
•Increase inhibitory neurotransmitter system—GABA
•Decrease excitatory neurotransmitter system—glutamate
•Block voltage-gated inward positive currents—Na
+ or Ca
++
•Increase outward positive current—K
+

21. Antiepileptic Drugs
 1857 - Bromides
 1912 - Phenobarbital
 1937 - Phenytoin
 1954 - Primidone
1960 – Ethosuximide
 1974 - Carbamazepine
 1975 - Clonazepam
 1978 - Valproate
 1993 - Felbamate, Gabapentin
 1995 - Lamotrigine
 1997 - Topiramate, Tiagabine
 1999 - Levetiracetam
 2000 - Oxcarbazepine, Zonisamide

22. Antiepileptic Drugs
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, Pregabalin
Vigabatrin, Topiramate,
Zonisamide, Levetiracetam, Lacosamide
Tiagabine10. Newer drugs

23. A = activation gate
I = inactivation gate
Na
+
Na
+
Carbamazepine
Phenytoin
Topiramate
Lamotrigine
Valproate
Zonisamide
Na
+
Na
+
I
I
Voltage gated sodium channel
Open Inactivated
X
Anticonvulsants Anticonvulsants
Mechanisms of ActionMechanisms of Action

24. Na
+
+
Ca
++
Ca
++
T - type Ca
++
channel
Open closed
X
Ethosuximide
Valproic acid

25. GABA-A Receptor
• Vigabatrin
•Gabapentin
• Benzodiazepines
• Barbiturate
•Binding of GABA causes
the channel to open and
Cl
-
to flow into the cell
Membrane hyperpolarization.
GABA AGONISTS
Barb

BZDs

Cl




Tiagabine

26. 1) Maximal electroshock seizures
Tonic flexion- tonic extension- clonic convulsions.
The tonic phase is selectively abolished by drugs
effective in GTCS
2) Pentylenetetrazol (PTZ ) clonic seizures

injection of PTZ in rats
prevented by drugs effective in absence seizures.
3) Chronic focal seizures

produced by application of alumina cream
---- the motor cortex of monkey.
4) Kindled seizures
Brief bursts of weak electrical impulses are applied to the brain

(amygdale) intermittently over days.

Kindling is probably involved in the genesis of clinical epilepsy.
METHODS OF DRUG EVALUATION

27. Structure of Commonly Used AEDs
Chemical formulas of commonly used old and new
antiepileptic drugs

28. Structures of Commonly Used AEDs

29. PHENOBARBITONE
First antiepileptic - 1912
MECHANISM OF ACTION
1) GABAA receptor mediated synaptic inhibition.
(GABA- facilitatory, GABA – mimetic,)
2) Antiglutamate,
3) Ca
2+
entry reduction
Higher anticonvulsant: Hypnotic ratio –
effect on Ca
2+
channels and glutamate release
On continued usage -- sedation wanes off
not anticonvulsant action.
Raises seizure threshold
Limits spread and suppresses kindled seizures.

30. α
α αβ
β
γ
GABA
BZD
Phenobarbitone
Site and mechanism of action
GABA A
+
+
Cl
-

31. Uses
1) Generalized tonic- clonic ( GTCS)
2) Simple partial (SP)
3) Complex partial (CP) seizures
DOSE - 60mg 1- 3 times / day.
children - 3 - 5 mg / kg /day.
less commonly used - Carbamazepine, Phenytoin or
Valproate.
PRIMIDONE
Deoxybarbiturate
converted to phenobarbitone and phenylethyl malonamide

Anti epileptic efficacy is similar to phenobarbitone
Dose – 250 – 500mg BD

32. PHENYTOIN
(DIPHENYL HYDANTOIN)
Synthesized as a barbiturate analogue
poor sedative property
Major antiepileptic drug
ACTION
1) Abolition of tonic phase of maximal electroshock seizures,
no effect -- clonic phase.
2) limits spread of seizure activity
3) Threshold for PTZ convulsions is not raised.

33. Actions of Phenytoin on Na
+
Channels
A.Resting State
B.Arrival of Action
Potential causes
depolarization and
channel opens
allowing sodium to
flow in
C.Refractory State,
Inactivation
Na
+
Na
+
Na
+
Sustain channel
in this
conformation

34. MECHANISM OF ACTION
Stabilizes neuronal membrane -----
prevents repetitive detonation of normal brain cells
during ‘ depolarization shift’
Prolongs the inactivated state of
voltage sensitive neuronal Na+ channel.
High frequency discharges -- inhibited.
low frequency discharges -- little effect
which allow Na+ channels to recover.
Resting membrane potential – No effect
Normal synaptic transmission – Not impaired
Therapeutic concentration
Higher / toxic concentration
Reduction in Ca
2+
influx
Inhibition of glutamate
Facilitation of GABA responses

35. A = activation gate
I = inactivation gate
Anticonvulsants Anticonvulsants
Mechanisms of ActionMechanisms of Action
Na
+
Na
+
Carbamazepine
Phenytoin
Lamotrigine
ValproateNa
+
Na
+
I
I
Voltage gated sodium channel
Open Inactivated
X
No effect on resting membrane potential.
Normal synaptic transmission -- not impaired.

36. PHARMACOKINETICS
Poor aqueous solubility. Absorption - poor
Wide distribution
Bound to plasma proteins ---- 80 - 90%
Metabolism --- liver (CYP 2C9 & 19)
Saturation Kinetics (capacity limited)
changes from first order to zero order
Small increments in dose produce
disproportionate high plasma concentration

The t ½ - 12-24 hrs increases upto 60 hr.
Dose 100mg BD, upto 400mg/day.
Monitor plasma concentration
(10μg/ml)

37. ADVERSE EFFECTS
At therapeutic levels
1) Gum hypertrophy - commonest – 20%

2) Hirsutism, acne.

3) Hypersensitivity reactions -- rashes, DLE,
lymphadenopathy, neutropenia
4) Megaloblastic anaemia:
decreases folate absorption
increases excretion.

38. 5) Osteomalacia: desensitizes target tissues to vit D
Interferes with calcium metabolism.

6) Inhibit insulin release - hyperglycemia
7) In pregnancy - foetal hydantoin syndrome
caused by areneoxide metabolite
•Mental disorder/microcephaly
•Cleft lip /palate
•Low set ears
•Hernias
•Nail hypoplasia

39. Phenytoin-induced gingival hyperplasia
Gingival inflammation

40. At high plasma levels (dose related toxicity)
1) Cerebellar and vestibular manifestations - ataxia, vertigo, diplopia,
nystagmus
2) Drowsiness, behavioral alterations, mental confusion
3) Hallucinations, disorientation and rigidity
4) Epigastric pain, nausea and vomiting.
5) Intravenous injection - local vascular injury → intimal damage
and thrombosis of the vein → edema and discolouration of the
injected limb.
Rate of injection > 50mg/min
6) Fall in BP and cardiac arrhythmias on i.v. injection.

41. INTERACTIONS
Potent enzyme inducer - CYP 2C9/19
1)Phenobarbitone -- inhibits phenytoin metabolism,
enzyme induction enhance each other’s degradation.

2)Carbamazepine and Phenytoin increase each other’s metabolism.
3)Valproate displaces protein bound phenytoin decreases its
metabolism: Plasma unbound phenytoin levels

43. Uses
1) Generalized tonic- clonic seizures,

simple and
complex partial seizures.
2) Status epilepticus : slow i.v. injection.
3)Trigeminal neuralgia: second choice to carbamazepine
4)Drug induced (digitalis) arrhythmias .

44. Fosphenytoin
• A Prodrug - water soluble ( Liver, RBC – phosphatases)
• Given i.v. or i.m. --- rapidly converted to phenytoin in the
body.
•local complications avoided --- vein irritation,
tissue damage,
pain and burning at site,
muscle necrosis.
•Given with glucose and saline solutions (IV).

45. CARBAMAZEPINE
Chemically related to imipramine
ACTION
1) first line antiepileptic drug
a) Acting on Na
+
channels is similar to phenytoin
b) Modifies maximal electroshock seizures
c) Raises threshold to PTZ and electroshock
convulsions.
d) It also inhibits kindling.
2)Lithium like action - In mania and bipolar mood disorders
3) Anti diuretic action -- Enhances ADH action on renal tubules.
Introduced for trigeminal neuralgia

46. PHARMACOKINETICS
Poor water solubility.
Oral absorption, slow and variable
75% bound to plasma proteins
Metabolism --- liver
oxidation -- active metabolite (10-11 epoxy carbamazepine)
Hydroxylation, Conjugation
Dose - 200 – 400mg TDS
t½ 20 - 40 hours

47. Dose - related neurotoxicity
1) sedation, 2) dizziness, 3) vertigo, 4) diplopia 5) ataxia
A. D. R.
Vomiting , Diarrhoea
Hypersensitivity
In the elderly -- Enhances ADH a) Water retention b) Hyponatremia
G. I. T.
C. N. S.
Rare - - a) agranulocytosis b) Aplastic anaemia
1)Rashes, 2) Photosensitivity, 3) Hepatitis
4) Leucopenia 5) lupus like syndrome

48. 1)worsening of seizures .
2) Acute intoxication
a) cardiovascular collaps b) convulsions
c) coma
Higher doses
Teratogenic
Combination with valproate doubles teratogenic potential
Foetal malformations
A. D. R.

49. INTERACTIONS
A) As Enzyme inducer; Enhances metabolism of
1) Haloperidol, 2) Contraceptives, 3) lamotrigine 4) Topiramate
B) Enzyme inducer which enhance metabolism of carbamazepine
1) Phenobarbitone, 2) Phenytoin, 3) Valproate ( vice
versa )
C) Drugs which inhibit metabolism of carbamazepine.
1) Erythromycin, 2) Fluoxetine, 3) Isoniazid

50. Uses
1) First choice with phenytoin in
a) Generalised tonic- clonic seizures (GTCS)
b) Simple partial seizures (SPS)
2) Complex partial seizures (CPS) -- Most effective

3) Trigeminal and related neuralgia
Selective inhibitory action on high frequency nerve impulses
Not an analgesic action
4) Manic depressive illness and Acute mania --
alternative to LITHIUM

51. Oxcarbazepine
congener of carbamazepine
10 monohydroxy derivative
Better tolerated
Indications same as for carbamazepine
Weak enzyme inducer

Less risk of hepatotoxicity
Hyponatraemia is more

52. ETHOSUXIMIDE

Antagonism of PTZ induced clonic seizures
ACTION
Does not modify maximal electroshock seizures or inhibit kindling
Effective only in absence seizures
Generation of absence seizures
Thalamic neurons exhibit prominent ‘T’ (transient) current
low threshold Ca
2+
current (T type Ca
2+
channels)

amplifies repetitive spikes.

53. M. O. A. of Ethosuximide
Selectively suppresses T current
No action on other types of Ca
2+
or Na
+
currents.
Does not potentiate GABA at therapeutic concentrations

54. ca
ca
ca
ca
ca ca
Ethosuximide selectively suppresses T current
Selective action in absence seizure
‘T’ ( transient) currentsuppression of T current
ca

55. PHARMACOKINETICS
1)Slowly but completely absorbed.
2)No protein binding.
3)Metabolized in liver by hydroxylation and
glucuronidation.
4)Excreted in urine - about ¼
th
- unchanged form.
5)Plasma t ½ --- 48 hours.
6)Dose - 200 – 500mg/day

56. A. D. R.
Dose – related side effects
C. N. S.
1)Tiredness, 2) Mood changes, 3) Agitation,
4) Headache, 5) Drowsiness, 6) Poor concentration
G. I. T. Gastrointestinal intolerance
Hypersensitiviy Rare 1) Rashes, 2) DLE 3) Blood dyscrasias
No liver or kidney damage
Uses Absence seizures -- only indication
superseded by valproate

57. VALPROIC ACID
Branched chain aliphatic carboxylic acid

Broad spectrum anticonvulsant action
1) More potent in blocking PTZ seizures
2) Less action on maximal electroshock seizures

3) Kindling are also prevented.

ACTION

58. 1)Like phenytoin – prolongs inactivation of voltage
dependant Na+ channel
2)Llike ethosuximide -- Weak attenuation of Ca
2+

mediated ‘T’ current.
3) Augementation of GABA action
a) Augmentation of release of inhibitory transmitter GABA
b) Inhibition of its degradation ( by GABA – transaminase)
c) increasing synthesis from glutamic acid.
(glutamic acid decarboxylase)

59. PHARMACOKINETICS
Oral absorption ---- good

90% bound to plasma proteins
Completely metabolized in liver

Excreted in urine. T ½ --- 10- 15 hours

60. Anorexia, vomiting, heart burn
A. D. R.
G. I. T
C. N. S. Dose- related -- Drowsiness , ataxia and tremor
Fulminant hepatitis
( rare but serious )
Rare -. Fulminant hepatitis, Pancreatitis

Risk patients
Children below 3 years
Pt. with hepatic disease
With other anticonvulsant hepatotoxic drug

61. HYPERSENSITIVITY
Alopecia, curling of hair, bleeding tendency
Rashes and thrombocytopenia
Polycystic ovarian disease and menstrual
irregularities.
Pregnancy -- Spina bifida and other Neural tube defects
Long- term use --
young girls
STOP

62. 1)Drug of choice ---- For absence seizures.
2)Alternative/ adjuvant drug --- For GTCS, SPS and CPS.
3)Myoclonic and atonic seizures -- drug of choice.
4)Alternative to lithium --- In Mania and bipolar illness
5) Prophylactic --- In migraine
Uses

63. Interactions
1)Phenobarbitone + Valproate -- Inhibits metabolism of Phenobarbitone

2)Phenytoin + Valproate -- Displaces phenytoin from binding site
decreases its metabolism

3)Carbamazepine + Valproate --- Induce each other’s metabolism.
4)Valproate + carbamazepine Foetal abnormalities are more
5) Clonazepam + valproate --- Contraindicated - absence
seizures status may be
precipitated.

64. DIAZEPAM
benzodiazepine

1) Status epilepticus
2) Tetanus, eclampsia, drug poisoning.
3) Febrile convulsions in children.
Uses
Acts by potentiate GABA induced Cl channel opening.
SEDATION IS PROMINENT
LONG TERM THERAPY – NO
RAPID TOLERANCE
Dose – 0.2 – 0.5 mg / kg. IV, rectal route
Fall in BP, Respiratory depression
ACTION

65. CLONAZEPAM
2) Like phenytoin, high frequency discharges are inhibited -- large doses
1) Potentiate GABA Cl
-
influx, inhibits PTZ induced seizures
Oral absorption is good. 85% bound to plasma proteins,
Completely metabolized in liver
Excreted in urine t ½ 24 hours.
dose -- 0.5 – 5 mg TDS
PHARMACOKINETICS
M. O. A.

66. Uses
A. D. R.
1) sedation and dullness.
2) In children – Irritability and other behavioral abnormalities
3) Motor disturbances and ataxia -- dose related.
4) Salivation and increased respiratory secretion.
1) Absence seizures
2) Adjuvant myoclonic and atonic epilepsy
3) in infantile spasms
Tolerance within six months

67. CLOBAZAM
1,5 benzodiazepine

1) In partial seizures,
2) Secondarily generalized tonic- clonic seizures,
3) Absence, myoclonic, atonic & refractory seizures.
Uses
Act by facilitating GABA action
side effect similar to other BZDs
Oral bioavailability 90 % elimination t ½ 18 hrs,
active metabolite has longer t ½ ( >35hrs)
Dose – 10 – 60 mg/d
PHARMACOKINETICS
A. D. R.
ACTION

68. LAMOTRIGINE
Anticonvulsant with carbamazepine like action
1)Modifies maximal electroshock seizures
2)Dose not antagonize PTZ seizures
3)Does not block NMDA type of glutamate receptors.
ACTION

69. M. O. A.
1)Prolongation of Na+ channel inactivation
---- Suppression of high frequency firing
3) directly blocks voltage sensitive Na + channels
a) stabilizes the presynaptic membrane and
b) prevents release of excitatory neurotransmitters,
(glutamate and aspartate)
broader - spectrum antiseizure activity.
Well absorbed orally
Metabolized completely -- liver. t ½ is 24 hrs
Dose 50mg OD upto 300mg/d.
PHARMACOKINETICS

70. 1)Sleepiness, 2) dizziness, 3) diplopia,
4) ataxia 5) vomiting 6) Rash.
A. D. R.
Better tolerated than carbamazepine or phenytoin.
Uses 1) Add- on or monotherapy in refractory cases of
partial seizures and GTCS,
2) Absence and myoclonic or akinetic epilepsy
2) Phenytoin, carbamazepine or phenobarbitone + Lamotrigine = T1/2
INTERACTIONS
Valproate + lamotrigine =
1) Inhibits glucuronidation of lamotrigine, lamotrigine levels
valproate levels

71. GABAPENTIN
Lipophilic GABA derivative
Crosses BBB and enhances GABA release ,
Modulate neuronal Ca+ channels – α2ᵟ -1 subunits.
1) Refractory partial seizures with or without generalization

2) As monotherapy & add- on drug - SPS and CPS

3) Diabetic neuropathy, Post herpetic neuralgia
4) Migraine prophylaxis
Well absorbed orally
excreted unchanged in urine t½ - 6hrs
Dose 300mg OD upto 300 – 600mg TDS.
Mild sedation, tiredness, dizziness and unsteadiness.
A. D. R.
PHARMACOKINETICS
Uses

72. VIGABATRIN
Inhihitor of GABA- transaminase -- degrades GABA
Increased synaptic GABA Concentration
approved only for adjuvant medication
Refractory partial seizures
DOSE - 2 – 4g/day.
1)Visual field contraction
2) behavioral changes,
3) Depression and
4) Psychosis
ACTION
Uses
A. D. R.

73. TOPIRAMATE
ACTION
Uses
weak carbonic anhydrase inhibitor
M. O. A.
Act by multiple mechanisms
1)Phenytoin like prolongation of Na+ channel inactivation

2)GABA potentiation by a postsynaptic effect
3)antagonism of glutamate receptors
4)K+ channels – neuronal hyper polarization.
1)Refractory SPS,CPS and GTCS.
2)In myoclonic epilepsy.
3) Prophylaxis of migraine.
Dose – 25mg od, 100 – 200 mg BD.

74. A. D. R.
PHARMACOKINETICS
Readily absorbed orally

excreated unchanged in urine

t½ 24 hours
1)Impairment of attention 2) sedation
3)ataxia 4) word finding difficulties
5) psychiatric symptoms 6) weight loss

7) paresthesias 8) renal stones

75. Tiagabine
MOA: binds to GABA uptake carrier system (GAT-1)
potentiating the activity of GABA by preventing reuptake
•Indication: adjunct therapy for partial seizures
Zonisamide
Refractory epilepsy with other drugs

Levetiracetam
binds with ‘SV
2A’ synaptic protein
Refractory epilepsy

76. Status epilepticus
•Status epilepticus is a clinical or electrical seizure
lasting at least 30 minutes, or a series of seizures
without complete recovery over the same period of
time.
•Cerebral hypoglycaemia,
•Lactic acidosis
•Hypoxia
•mortality 5%
•Active resuscitation needed
Medical Emergency
CV / respiratory / metabolic management

77. 1. Lorazepam o.1 mg/kg IV rate of 2mg/minute
↓
2. Phenytoin 20 mg/kg/IV - 50mg/min
(Fosphenytoin)
↓
increase the dose of phenytoin – 25-30 mg/kg
↓
3. phenobarbitone – 20mg/kg IV, 50-75 mg/mt.
↓
Increase the dose of phenobarbitone additional 5-10mg/kg
↓

4. Anaesthesia with midazolam/ propofol/ Thiopentone.


STATUS EPILEPTICUS

78. FEBRILE CONVULSIONS
Control fever

Diazepam – rectal / IV 0.5 -1mg / kg.

79. Second Generation AED’S
•Generally lower side effect rates
•Little or no need for serum monitoring
•Once or twice daily dosing
•Fewer drug interactions
•There is no significant difference in efficacy with the
second generation agents
•Higher cost associated with the new agents

80. INTERACTIONS BETWEEN ANTISEIZURE DRUGS
With other antiepileptic Drugs
•Carbamazepine with
phenytoin Increased metabolism of carbamazepine
phenobarbitalIncreased metabolism of epoxide.
•Phenytoin with
primidone Increased conversion to phenobarbital.
•Valproic acid with
clonazepam May precipitate nonconvulsive status
epilepticus
•phenobarbitalDecrease metabolism, increase toxicity.
•phenytoin Displacement from binding, increase toxicity.

81. AED: teratogenicity
Valproate: neural tube defects (spina bifida)
Carbamazepine: craniofacial anomalies, spina bifida
Phenytoin: neural tube defects, craniofacial anomalies
Most pregnant patients exposed to AED deliver normal
infants.

82. Choice of antiseizure drugs
Type of Seizure First choice drugs Second choice drugs Alternative /Add – on
Drugs
Generalised tonic –
clonic/simple partial
with or without
generalization
Carbanazepine
Phenytoin
Valproate
Phenobarbitone
Lamatrigine,
Gabapentin,
Topiramate,
Primidone,
Levetiracetam
Complex partial with
or without
generalization
Carbamazepine,
Valproate,
Phenytoin
Gabapentin,
Lamotrigine,
Levetiracetam
Clobazam,
Zonisamide,
Topiramate
Absence Valproate Ethosuximide,
Lamotrigine
Clobazam,
Clonazepam
Myoclonic Valproate Lamatrigine, TopiramateLevetiracetam,
Clonazepam
Atonic Valproate Clonazepam, ClobazamLamatrigine
Febrile seizures Diazepam (rectal)- -
Status epilepticusLorazepam (i.v.)
Diazepam (i.v.)
Fosphenytoin (i.v.)
Phenobarbitone (i.v.,i.m)
Gen. anaesthetics

83. Therapeutic principle of Antiepilepsy drugs (AEDs)
Early treatment
Treatment as the types of epileptic seizure
Treatment with one drug
Individual therapy
Long course of treatment
Slow drug withdrawal
Periodic re-examination

84. Famous Persons with Epilepsy
AristotleAristotle
SocratesSocrates
Julius CaesarJulius Caesar
Alfred NobelAlfred Nobel
Naepoleon BonaparteNaepoleon Bonaparte
Tony GreigTony Greig