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Epilepsy & Anti-epileptic Drugs Dr. B. K. Iyer
Epilepsy The background
Epilepsy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Epilepsy ,[object Object],[object Object]
Seizures ,[object Object],[object Object],[object Object],[object Object]
Causes for Acute Seizures ,[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]
Neuronal Substrates of Epilepsy  The Brain The Synapse The Ion Channels/Receptors ions
Cellular and Synaptic Mechanisms of Epileptic Seizures (From Brody et al., 1997)
Cellular mechanisms of seizure generation ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Neuronal (Intrinsic) factors modifying neuronal excitability ,[object Object],[object Object],[object Object],[object Object]
Extra-Neuronal (Extrinsic) factors modifying neuronal excitability ,[object Object],[object Object],[object Object]
Mechanisms of generating hyperexcitable networks ,[object Object],[object Object],[object Object]
Hippocampal Circuitry and Seizures
Basic mechanisms underlying  seizures & epilepsy ,[object Object],Babb TL, Brown WJ. Pathological Findings in Epilepsy. In: Engel J. Jr. Ed.  Surgical Treatment of the Epilepsies. New York: Raven Press 1987: 511-540.
Epilepsy types The background
Classification of Epileptic Seizures ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Adult Seizure Types ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Insights into epilepsy
I. Partial (Focal) Seizures ,[object Object],[object Object]
Scheme of Seizure Spread Simple (Focal) Partial  Seizures   Contralateral spread
I. Partial (Focal) Seizures ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Scheme of Seizure Spread Complex Partial Seizures Complex Secondarily Generalized Partial Seizures
I. Partial (focal) Seizures ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
II. Generalized Seizures ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
II. Generalized Seizures ,[object Object],[object Object],[object Object]
II. Generalized Seizures ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
II. Generalized Seizures ,[object Object]
II. Generalized Seizures ,[object Object],[object Object],[object Object],[object Object]
II. Generalized Seizures ,[object Object],[object Object],[object Object],[object Object]
Scheme of Seizure Spread Both hemispheres are involved from outset   Generalized Tonic-Clonic Seizures
Neuronal Correlates of Paroxysmal Discharges
II. Generalized Seizures ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],Generalized Absence Seizures
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Scheme of Seizure Spread Thalamocortial relays are believed to act on a hyperexcitable cortex Primary Generalized Absence Seizures
Scheme of Seizure Spread
II. Generalized Seizure ,[object Object],[object Object],[object Object]
II. Generalized Seizure ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
II. Generalized Seizure ,[object Object],[object Object],[object Object],[object Object]
II. Generalized Seizures ,[object Object],[object Object],[object Object],[object Object]
Treatment of Seizures ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Treatment of Seizures ,[object Object],[object Object],[object Object],[object Object]
Treatment of Seizures ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Antiepileptic Drug ,[object Object],[object Object],[object Object],[object Object]
Current Pharmacotherapy ,[object Object],[object Object],[object Object]
Epilepsy therapy The background
Targets for AEDs ,[object Object],[object Object],[object Object],[object Object],[object Object]
History of Antiepileptic Drug Therapy ,[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]
Anti-epileptics
Anti-epileptics
Actions of Phenytoin on Na+ Channels ,[object Object],Sustain channel in this conformation ,[object Object],[object Object]
Ca2+ Channels ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],B
GABAergic SYNAPSE ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
GLUTAMATERGIC SYNAPSE ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
GLUTAMATERGIC SYNAPSE                                                                                   
Antiepileptics The background
Choosing Antiepileptic Drugs ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
General facts about AEDs ,[object Object],[object Object],[object Object],[object Object],[object Object]
Chemical Structure of Classical  Antiseizure Agents ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Small changes can alter clinical activity and site of action. e.g. At R1, a phenyl group (phenytoin) confers activity against partial seizures, but  an alkyl group (ethosuximide) confers activity against generalized absence seizures .
Treatment of Seizures ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Pharmacokinetic Parameters
Effects of 3 antiepileptic drugs on high frequency discharge of cultured neurons ,[object Object],(From Katzung B.G., 2001) Block of sustained high frequency repetitive firing of action potentials.
PHENYTOIN (Dilantin) ,[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]
Fetal Hydantoin Syndrome ,[object Object],[object Object],[object Object],[object Object]
CARBAMAZEPINE (Tegretol) ,[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]
OXCARBAZEPINE (Trileptal) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
PRIMIDONE (Mysolin) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
VALPROATE ,[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]
ETHOSUXIMIDE ,[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]
CLONAZEPAM ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
VIGABATRIN (  -vinyl-GABA)  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
LAMOTRIGINE (Lamictal)  ,[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]
FELBAMATE ,[object Object],[object Object],[object Object],[object Object],[object Object]
TOPIRAMATE ,[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]
ZONISAMIDE ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
GABAPENTIN ,[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 ,[object Object],[object Object],[object Object],[object Object]
DIAZEPAM & LORAZEPAM ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Treatment of Status Epilepticus in Adults ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Treatment of Seizures ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Treatment of Seizures ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Infantile Spasms ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

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E P I L E P S Y U P D A T E

Notes de l'éditeur

  1. Slide 2: Brain regions and neuronal pathways Certain parts of the brain govern specific functions. Point to sensory, motor, association and visual cortex to highlight specific functions. Point to the cerebellum for coordination and to the hippocampus for memory. Indicate that nerve cells or neurons travel from one area to another via pathways to send and integrate information. Show, for example, the reward pathway. Start at the ventral tegmental area (VTA) (in magenta), follow the neuron to the nucleus accumbens, and then on to prefrontal cortex. Explain that this pathway gets activated when a person receives positive reinforcement for certain behaviors ("reward"). Indicate that you will explain how this happens when a person takes an addictive drug.