ANTI EPILEPTIC DRUGS / ANTI CONVULSION AGENTS / ANTI SEIZURE AGENTS, Drugs used in the treatment of epilepsy. B.Pharm & Pharm.D

1. ANTI EPILEPTIC DRUGS
- By Dr.S.Kameshwaran

5. EPILEPSY
 It is known as “Disease of lightening”.
 They are group of disorders of the CNS.
Characterized by:
 Paroxysmal cerebral dysrhythmia (a diffusely
abnormal electroencephalogram often seen with
epilepsy).
 Loss / disturbance of consciousness,
 With or without characteristic body movements.
 Autonomic hyperactivity.

7. Most of the epilepsies are primary (Idiopathic)
Idiopathic - cause is not known
Some may be secondary
occurs due to:
Trauma/surgery on head
Intracranial tumor
Tuberculoma
(non-neoplastic mass (a tumor-like mass that is not a cancer)
caused by ifection with mycobacterium tuberculosis)
Cysticercosis
It is a tissue infection by the pork tapeworm

9. GENERALISED SEIZURES
GENERALISED TONIC – CLONIC SEIZURES (GTCS):
Also known as major epilepsy, grand mal
Commonest,
Lasts 1-2min
The usual sequence is
AURA – CRY – UNCONSCIOUSNESS
– TONIC Spasm of all body muscles
– CLONIC Jerking
prolonged sleep and depression of all CNS
functions

11. ABSENCE SEIZURES
 Also known as Minor Epilepsy, Petit Mal
 Prevalent in children,
 Lasts about ½ minute.
 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
(Electroencephalography - EEG measures voltage
fluctuations resulting from ionic current flows
within the neurons of the brain

13. ATONIC SEIZURES:
Also known as Akinetic Epilepsy
Unconsciousness with relaxation of all muscles
Patient may fall
MYOCLONIC SEIZURES:
Shock-like momentary contraction of muscles
of a limb or the whole body

14. ATONIC SEIZURES MYOCLONIC

15. INFANTILE SPASMS:
Also known as Hypsarrhythmia
Seen in infants.
Probably not a form of epilepsy.
Intermittent muscle spasm and progressive
mental deterioration.

16. PARTIAL SEIZURES
SIMPLE PARTIAL SEIZURES (SPS)
It is also known as cortical focal epilepsy
Lasts ½ -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.

17. COMPLEX PARTIAL SEIZURES (CPS)
Also known as Temporal lobe epilepsy,
Psychomotor
Seizure attack , Confused behavior, Purposeless
movements, Emotional changes
Lasting 1-2 min along with impairment of
consciousness,
An Aura often proceeds. (a warning sensation
experienced before an attack of epilepsy)
The seizure focus is located in the temporal lobe.
The partial seizure occurs first and evolves into
generalized tonic-clonic seizures with loss of
consciousness.

18. CLASSIFICATION OF ANTI EPILEPTIC DRUGS (AED’S)
 BARBITURATES
Phenobarbitone
 DEOXYBARBITURATE
Primidone
 HYDANTOIN
Phenytoin
Fosphenytoin
 IMINOSTILBENE
Carbamazepine (CBZ)
Oxcarbazepine
 SUCCINIMIDE
Ethosuximide
 ALIPHATIC CARBOXYLIC ACID
Valproic acid (sodium valproate)
Divalproex

19.  BENZODIAZEPINES
Clonazepam
Diazepam
Lorazepam
Clobazam
 PHENYLTRIAZINE
Lamotrigine
 CYCLIC GABA ANALOGUE
Gabapentin
Pregabalin
 NEWER DRUGS
Vigabatrin
Topiramate
Tiagabine
Zonisamide
Levetiracetam

20. MECHANISM OF ACTION
There are THREE major mechanisms
1st TYPE:
DRUGS:
PHENYTOIN,
CBZ,
SOD.VALPORATE,
LAMOTRIGINE

21. MECHANISM ;1
PROLONGATION OF INACTIVATED Na+
CHANNELS

DECREASE THE ENTRY OF Na+ IONS IN TO THE
NEURON

PROLONGS THE DEPOLARIZATION

DECREASE THE EPILEPTIC EPISODES

ANTI EPILEPTIC ACTIVITY

24. 2nd Type:
DRUGS:
BARBITURATE
BZD
VIGABARTIN
VALPORATE
GABAPENTIN

25. MECHANISM ;2
FALICITATE THE BINDING OF GABA TO GABA-A
RECEPTOR

INCREASE THE ENTRY OF Cl- IN TO THE NEURON

HYPERPOLARIZATION

PROLONGED DEPOLARIZATION

CALMNESS & ANTI EPILEPTIC ACTIVITY

27. 3rd TYPE:
DRUGS
ETHOSUXIMIDE
VALPORATE
TRIMETHADIONE
MECHANISM ;3
BLOCKS THE L TYPE VOLTAGE SENSITIVE CALCIUM
CHANNELS

DECREASE THE ENTRY OF CALCIUM IONS IN TO THE
NEURON

ANTI CONVULSANT ACTIVITY

29. BARBITURATES:
Eg: PHENOBARBITONE
Most older anticonvulsant
Phenyl substitution present in the structure
responsible for its Activity against Tonic-Clonic
seizure [Grand mal epilepsy]
It is the first efficacious anti epileptic drug
[1912]
It act by depressing the CNS
It is the cheapest and least toxic anti epileptics.
MECHANISM OF ACTION: 2nd TYPE

30. Pharmacokinetics:
Slowly absorbed orally
t ½ is long 80 -120 hrs in plasma
Metabolized in liver
Excreted unchanged by kidney
Single daily dose used for maintenance
ADR:
Sedation
Behavioral abnormalities
Diminution of intelligence
Impairment of learning and memory
Rashes
Anemia

31. Use:
Grand mal epilepsy
Complex partial epilepsy
Simple partial epilepsy

32. HYDANTOIN:
Eg : Phenytoin
• It is a diphenyl hydantoin
• It was Synthesized as barbiturate analogue
• Its anti convulsant activity was tested in
1938, since then this is the major anti
epileptic drug.
• It is not a CNS depressant
• Little sedation produced at therapeutic dose
• It abolishes the tonic phase of maximal
electro shock seizures
• It limits the spread of seizure activity

33. Mechanism of action:
At therapeutic dose: 1st type
Higher toxic doses: 2nd &3rd types
Pharmacokinetics:
Oral route –slowly absorbed due to poor
solubility
Widely distributed in body
80-90% drug bound to plasma proteins
Metabolized in liver by hydroxylation and GA
conjugation
Excreted in urine

34. ADR:
Gum hypertrophy,
Hirsutism, (excessive hairiness on women)
Rashes,
Magloblastic anaemia
Osteomalacia
USE:
GTCS-Grand mal epilepsy
Simple and complex partial seizure
Trigemial neuralgia
Ineffective in absence seizure

35. Gum hypertrophy

36. IMINOSTILBENE
Eg:
CARBAMAZEPINE
OXCARBAZEPINE
CARBAMAZEPINE
Chemically related To Imipramine
First introduced in 1960s for trigeminal neuralgia (A
chronic pain condition affecting the trigeminal nerve in
the face)
Due to good anticonvulsant activity currently used as
first line anti-epileptic drug
Its pharmacological activity resembles Phenytoin
It modifies maximal electro shock seizures as well as
raise threshold to PTZ and electro shock convulsion
Also has anti-diuretic activity

37. MECHANISM OF ACTION:
1st type
PHARMACOKINETICS:
Oral absorption is slow because of poor water
soluability
75% bound to plasma proteins
Metabolized in lever by oxidation and
hydroxylation
t1/2 20-40 hours

38. ADR:
Dose related neurotoxicity
Sedation
Vertigo
Ataxia (is a neurological sign consisting of lack of
voluntary coordination of muscle movements)
Vomiting
Diarrhea
Rashes
Uses
Most effective drug for CPS
First choice drug with Phenytoin for GTCS and
Simple partial seizure

39. SUCCINAMIDES
Eg: Ethosoximide
 Most predominantly antagonizes the PTZ induced
clonic seizure
 It raise the seizure threshold ( the balance between
excitatory and inhibitory forces in the brain which
affect how susceptible a person is to seizures)
 Clinically effective only in absence seizures
MECHANISM OF ACTION: 3rd type
PHARMACOKINETICS:
 Rather slowly but completely absorbed on oral
administration
 Not protein bound
 Metabolized in liver by hydroxylation &GA
conjugation
 Excreted in urine

40. ADR
GI-intolerance (avoidance or minimal intake
of food)
Tiredness
Mood change
Head ache
Drowsiness
USE
Absence seizure

41. ALIPHATIC CARBOXYLIC ACID
VALPORIC ACID
Also known as sodium valporate
It is a branched chain aliphatic carboxylic acid
Has broad spectrum anti-convulsant activity
Effective in partial seizures &GTCS
At therapeutic doses it produce little sedation
MECHANISM OF ACTION:
It acts through all the three types

42. Pharmacokinetics:
Oral absorption is good
90% bound to plasma protein
Completely metabolized in liver by oxidation
&GA conjugation
Excreted in urine
ADR
Anorexia
Vomiting
Drowsiness
Alopecia
USES
Drug of choice for Absence seizure
Alternative/Adjuvant drug for GTC, SPS, CPS.

43. THANK
U