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Epilepsy
An assortment of different seizure types & syndromes
originating from several mechanisms that have
common sudden, excessive & synchronous discharge of
cerebral neurons resulting in loss of
consiousness,abnormal movements, odd behaviour
/distorted perceptions.
Neuro-imaging techniques such as:
MRI,PET,SPECT.
Abnormal electrcal activity during a seizure can be
detected by EEG.
Seizures have been categorized by site of origin,
etiology, electrophysiologc correlation ,clinical
presentation.
Seizures have been classified in to2 broad groups:
• Partial (Simple & Complex)
• Generalized(Tonic-Clonic & Absence).
• Others (Myoclonic, Febrile, Status epilepticus).
• Absence seizures:
These involve brief, abrupt,self-limiting loss of
consiousness.
In 3-5 years of age patients(onset occurs) & lasts
till puberty.
Patient stops speaking in mid-sentence, & stares vacantly for
few seconds(3-5sec).
Febrile seizures
Young children may develop with illness accompanied by
high fever.
Intermittent muscle spasm & progressive metal
deterioration.
ANTI -EPILEPTICS
These are the drugs used in the treatment of EPILEPSY.
Barbiturates : Phenobarbitone.
Deoxybarbiturate : Primidone.
Hydantoin : Phenytoin,Fosphenytoin.
Immunostilbines : Carbamazepine,Carbazepine.
Succimide : Ethosuximide.
Aliphatic carboxylic acids: Sodium valproate, Divalproate.
Phenylriazine : Lamotrigine.
Cyclic GABA analogue : Gabapentin.
Newer drugs :Vigabatrine, Tiagabine,Topiramate,
Levetiractem.
BZD’s : Diazepam,Lorazepam,Oxazepam,
Clonazepam.
Mechanism of Action
The 3 mechanisms appear to be
important action of Epilepsy.
I. Enhancement of GABA action.
II. Inhibition of Na+2 channel function.
III. Inhibition of Ca+2 channel function.
IV. Inhibition of Glutamate release & Blockade of
receptors.
Enhancement of GABA action:( BZD’s, Barbiturates)
Vigabatrin -- Inhibits enzyme“GABATransaminase”.
Tiagabine --Inhibits GABAuptake & enhance action of
GABA.
Gabapetin – designed as an agonist @ GABAA Receptors.
Inhibition of Na+2 channel function:
(Phenyltriazine,Hydantoins,Immunostibines,
Aliphatic –COOH’s).
These drugs affect membrane excitabilty by an action on voltage-
gated Na+2 channels, which carry the inward membrane current
necessary for generation of Action potential.
Inhibition of Ca+2 channels: (Suucimides,Gabapetin).
Succimides blocks T-type Ca+2 channels .
Gabapentin blocks L-type Ca+2 channels .
Pharmacokinetics:
Absorption ----Slow on oral administration.
Bioavailability differs in market preparations.
Distribution is wide & 80-90% bound to plasma proteins.
Metabolism– Liver by Hydroyxlation & Glucoronide
conjugation.
T1/2– 12-24hrs & increases up to 60 hrs.
Only 5%Unchanged Phenytoin is excreted in urine.
Adverse Effects:
@ Therapeutic levels— Due to over growth of
Collagen fibres causes Gum Hypertrophy.(Can b minimized by
Oral hygiene).
Girls- Hirsutism,Acne,Coarsening of facial features.
Hypersensitivity Reactions-Rashes,Lymphadenopathy,Neutropenia.
Megaloblastic AnaemiaIt decreases Folate absorption &
increases folate excretion.
Osteomalacia, Hypergycemia, In pregnancy—causes
FOETAL HYDANTOIN SYNDROME.
@ Higher levels– Cerebellar & Vestibular
manifestations: Ataxia, Vertigo, Diplopia,
Nystagmus. Drowsiness,Mental confuion,
Hallucinations, Disorientation, Muscle rigidity.
Epigastric pain, Nausea & vomiting
(Can b minimized when taken with meals).
I.V injection causes Local injury, oedema, vein
thrombosis, Discolouration of injected
limb,Hypotension & Cardiac arrhythmias.
Carbamazepine + Phenytoin creases each others Metabolism.
Isoniazid, Cimetidine, Dicumerol,Warfarin  Inhibits Phenytoin
metabolsim.
Phenytoin induces Steroid degradation.
Sodium Valproate Decreases metabolism & Increases Phenyton
plasma levels.
USES
1st line Anti-Epileptic for Generalized Tonic-Clonic
,Simple &Complex partial seizures.
In Status Epilepticus.
In Trigeminal Neuralgia.
Pharmacology of Anti-Epileptics

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Pharmacology of Anti-Epileptics

  • 1.
  • 2. Epilepsy An assortment of different seizure types & syndromes originating from several mechanisms that have common sudden, excessive & synchronous discharge of cerebral neurons resulting in loss of consiousness,abnormal movements, odd behaviour /distorted perceptions. Neuro-imaging techniques such as: MRI,PET,SPECT.
  • 3. Abnormal electrcal activity during a seizure can be detected by EEG. Seizures have been categorized by site of origin, etiology, electrophysiologc correlation ,clinical presentation. Seizures have been classified in to2 broad groups: • Partial (Simple & Complex) • Generalized(Tonic-Clonic & Absence). • Others (Myoclonic, Febrile, Status epilepticus).
  • 4.
  • 5.
  • 6.
  • 7.
  • 8. • Absence seizures: These involve brief, abrupt,self-limiting loss of consiousness. In 3-5 years of age patients(onset occurs) & lasts till puberty. Patient stops speaking in mid-sentence, & stares vacantly for few seconds(3-5sec).
  • 9.
  • 10. Febrile seizures Young children may develop with illness accompanied by high fever. Intermittent muscle spasm & progressive metal deterioration.
  • 11.
  • 12. ANTI -EPILEPTICS These are the drugs used in the treatment of EPILEPSY. Barbiturates : Phenobarbitone. Deoxybarbiturate : Primidone. Hydantoin : Phenytoin,Fosphenytoin. Immunostilbines : Carbamazepine,Carbazepine. Succimide : Ethosuximide. Aliphatic carboxylic acids: Sodium valproate, Divalproate. Phenylriazine : Lamotrigine. Cyclic GABA analogue : Gabapentin. Newer drugs :Vigabatrine, Tiagabine,Topiramate, Levetiractem. BZD’s : Diazepam,Lorazepam,Oxazepam, Clonazepam.
  • 14. The 3 mechanisms appear to be important action of Epilepsy. I. Enhancement of GABA action. II. Inhibition of Na+2 channel function. III. Inhibition of Ca+2 channel function. IV. Inhibition of Glutamate release & Blockade of receptors.
  • 15.
  • 16. Enhancement of GABA action:( BZD’s, Barbiturates) Vigabatrin -- Inhibits enzyme“GABATransaminase”. Tiagabine --Inhibits GABAuptake & enhance action of GABA. Gabapetin – designed as an agonist @ GABAA Receptors. Inhibition of Na+2 channel function: (Phenyltriazine,Hydantoins,Immunostibines, Aliphatic –COOH’s). These drugs affect membrane excitabilty by an action on voltage- gated Na+2 channels, which carry the inward membrane current necessary for generation of Action potential. Inhibition of Ca+2 channels: (Suucimides,Gabapetin). Succimides blocks T-type Ca+2 channels . Gabapentin blocks L-type Ca+2 channels .
  • 17. Pharmacokinetics: Absorption ----Slow on oral administration. Bioavailability differs in market preparations. Distribution is wide & 80-90% bound to plasma proteins. Metabolism– Liver by Hydroyxlation & Glucoronide conjugation. T1/2– 12-24hrs & increases up to 60 hrs. Only 5%Unchanged Phenytoin is excreted in urine.
  • 18. Adverse Effects: @ Therapeutic levels— Due to over growth of Collagen fibres causes Gum Hypertrophy.(Can b minimized by Oral hygiene). Girls- Hirsutism,Acne,Coarsening of facial features. Hypersensitivity Reactions-Rashes,Lymphadenopathy,Neutropenia. Megaloblastic AnaemiaIt decreases Folate absorption & increases folate excretion. Osteomalacia, Hypergycemia, In pregnancy—causes FOETAL HYDANTOIN SYNDROME.
  • 19. @ Higher levels– Cerebellar & Vestibular manifestations: Ataxia, Vertigo, Diplopia, Nystagmus. Drowsiness,Mental confuion, Hallucinations, Disorientation, Muscle rigidity. Epigastric pain, Nausea & vomiting (Can b minimized when taken with meals). I.V injection causes Local injury, oedema, vein thrombosis, Discolouration of injected limb,Hypotension & Cardiac arrhythmias.
  • 20. Carbamazepine + Phenytoin creases each others Metabolism. Isoniazid, Cimetidine, Dicumerol,Warfarin  Inhibits Phenytoin metabolsim. Phenytoin induces Steroid degradation. Sodium Valproate Decreases metabolism & Increases Phenyton plasma levels.
  • 21. USES 1st line Anti-Epileptic for Generalized Tonic-Clonic ,Simple &Complex partial seizures. In Status Epilepticus. In Trigeminal Neuralgia.