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DR.UMA KADAM   M.B.B.S. MD ASSOCIATE PROFESSOR PHARMACOLOGY SKNMC
Definition ,[object Object]
SELECTED EPILEPSY TERMS Epilepsy:   A clinical paroxysmal disorder of recurring  seizures  Seizure:   A  transient dysfunction of brain    due to an abnormal firing of cerebral neurons, which may or may  not have  a clinical  manifestation.
Myoclonus:  A single abrupt shock like extensor movement of a limb.  myoclonic seizures. Petit Mal : Used  to describe absence seizures as well as atypical absence. Tonic :  Sustained contraction of one or more muscle groups, independent of position  (i.e. can be flexed, extended, or opisthotonic). Aura:  A generic term for a warning. A colloquial term for simple partial seizure. Convulsion:  Tonic , clonic or tonic-clonic seizure
[object Object],[object Object],[object Object],[object Object]
Differential diagnosis of seizures ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Epidemiology ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object]
Revised ILAE (International League Against Epilepsy) Seizure Classification I.  PARTIAL (FOCAL, LOCAL) SEIZURES A.   Simple partial seizures B.  Complex partial seizure C.  Partial seizures evolving to generalized  tonic-clonic convulsions (GTC)
II.  GENERALIZED SEIZURES A. 1.   Absence seizures 2.  Atypical absence B.  Myoclonic seizures,  Myoclonic jerks  (simple or multiple) C.  Clonic seizures D.  Tonic seizures E.  Tonic-clonic seizures F.  Atonic seizures (astatic)
III.  UNCLASSIFIED EPILEPTIC SEIZURES Includes all seizures that cannot be classified because of inadequate or incomplete data and some that defy classification in hitherto described categories.  This includes some neonatal seizures, e.g.,  rhythmic eye movements, chewing, and swimming movements .
 
Antiepileptic drug (AED) ,[object Object],[object Object],[object Object]
CLASSIFICATION OF ANTIEPILEPTICS: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],i i e i a
CLASSIFICATION ON THE BASIS OF CLINICAL USE
History of Antiepileptic  Drug Therapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
History of AED therapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Principles of AED Selection ,[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],Principles of AED Selection…cont.
Principles of AED Selection…cont. ,[object Object],[object Object],[object Object]
  Therapeutic Drug Monitoring Use AED levels to assess: i.  Poor clinical control (compliance,  metabolism) ii.  Dose-related side effect iii. Drug or disease interaction iv.  "Routine" levels on controlled, nontoxic patients are not indicated.
Applied Pharmacokinetics of  Antiepileptic Drugs (AEDs)
Absorption ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Absorption ,[object Object],[object Object],[object Object],[object Object],[object Object]
Mechanism of action of Antiepileptic Drugs
Cellular Mechanisms of  Seizure Generation ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Inhibition  Stimulation
AEDs: Molecular and Cellular Mechanisms ,[object Object],[object Object],[object Object]
Open Na + Na + Na + Inactivation gate Activation gate Carbamazepine Phenytoin Felbamate Lamotrigine Inactivated channel Blocked channel firing at high frequencies Barbiturates Topiramate Na + Na+ Na+ Na+
AEDs: Molecular and Cellular Mechanisms ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
AEDs: Molecular and Cellular Mechanisms ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Ca ++ Ca ++ Voltage regulated  Ca ++  current, low  threshold “T” current  in thalamus Involved in 3 per second spike and wave rhythm Ca ++ Ethosuximide Valproate Reduction in the flow of Ca ++  through T – type Ca ++  channels in thalamus Ca ++ Ethosuximide:
Newer AEDs: Molecular and cellular Mechanisms ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Newer AEDs: Molecular and cellular Mechanisms ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
GABA metabolites Succinic  Semialdehyde Gabapentin GT: GABA transaminase SSD:Succinic semialdehyde dehydrogenase GT SSD Vigabatrin Valproate Benzodiazepines Barbiturates Cl - Gabapentin Tiagabine Topiramate
Status Epilepticus-Definition ,[object Object],[object Object],[object Object]
Status epilepticus ,[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Status Epilepticus - Definite Treatment
Status Epilepticus-Definitive Treatment  ,[object Object],[object Object],[object Object],[object Object]
OR Lorazepam -  4 mg IV push (2mg/min) may be repeated. i.  Fast acting, medium lasting.  ii.  Respiratory depression only in the extubated patient.
Status Epilepticus-Definite Treatment  ,[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object]
Adverse effects of antiepileptics: ,[object Object],[object Object],[object Object]
Drug interactions- points to consider ,[object Object],[object Object],[object Object]
Drug interactions- points to consider ,[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Thank you

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Antiepileptics I & Ii

  • 1. DR.UMA KADAM M.B.B.S. MD ASSOCIATE PROFESSOR PHARMACOLOGY SKNMC
  • 2.
  • 3. SELECTED EPILEPSY TERMS Epilepsy: A clinical paroxysmal disorder of recurring seizures Seizure: A transient dysfunction of brain due to an abnormal firing of cerebral neurons, which may or may not have a clinical manifestation.
  • 4. Myoclonus: A single abrupt shock like extensor movement of a limb. myoclonic seizures. Petit Mal : Used to describe absence seizures as well as atypical absence. Tonic : Sustained contraction of one or more muscle groups, independent of position (i.e. can be flexed, extended, or opisthotonic). Aura: A generic term for a warning. A colloquial term for simple partial seizure. Convulsion: Tonic , clonic or tonic-clonic seizure
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  • 9. Revised ILAE (International League Against Epilepsy) Seizure Classification I. PARTIAL (FOCAL, LOCAL) SEIZURES A. Simple partial seizures B. Complex partial seizure C. Partial seizures evolving to generalized tonic-clonic convulsions (GTC)
  • 10. II. GENERALIZED SEIZURES A. 1. Absence seizures 2. Atypical absence B. Myoclonic seizures, Myoclonic jerks (simple or multiple) C. Clonic seizures D. Tonic seizures E. Tonic-clonic seizures F. Atonic seizures (astatic)
  • 11. III. UNCLASSIFIED EPILEPTIC SEIZURES Includes all seizures that cannot be classified because of inadequate or incomplete data and some that defy classification in hitherto described categories. This includes some neonatal seizures, e.g., rhythmic eye movements, chewing, and swimming movements .
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  • 15. CLASSIFICATION ON THE BASIS OF CLINICAL USE
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  • 21. Therapeutic Drug Monitoring Use AED levels to assess: i. Poor clinical control (compliance, metabolism) ii. Dose-related side effect iii. Drug or disease interaction iv. "Routine" levels on controlled, nontoxic patients are not indicated.
  • 22. Applied Pharmacokinetics of Antiepileptic Drugs (AEDs)
  • 23.
  • 24.
  • 25. Mechanism of action of Antiepileptic Drugs
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  • 28. Open Na + Na + Na + Inactivation gate Activation gate Carbamazepine Phenytoin Felbamate Lamotrigine Inactivated channel Blocked channel firing at high frequencies Barbiturates Topiramate Na + Na+ Na+ Na+
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  • 30.  
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  • 32. Ca ++ Ca ++ Voltage regulated Ca ++ current, low threshold “T” current in thalamus Involved in 3 per second spike and wave rhythm Ca ++ Ethosuximide Valproate Reduction in the flow of Ca ++ through T – type Ca ++ channels in thalamus Ca ++ Ethosuximide:
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  • 35.  
  • 36. GABA metabolites Succinic Semialdehyde Gabapentin GT: GABA transaminase SSD:Succinic semialdehyde dehydrogenase GT SSD Vigabatrin Valproate Benzodiazepines Barbiturates Cl - Gabapentin Tiagabine Topiramate
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  • 42. OR Lorazepam - 4 mg IV push (2mg/min) may be repeated. i. Fast acting, medium lasting. ii. Respiratory depression only in the extubated patient.
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