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Antiepileptics (Epilepsy (classification by seizure origin (Partial…

- - - - Simple partial
        
        consciousness preserved
        
        only small part of the brain is affected
        
        may involve motor cortex - twitching of one
        contralateral limb or part of the limb
        
        may involve sensory cortex - an unusual smell, taste or feeling
        
        patients remain conscious and have full memories of the seizures
      - Complex partial
        
        consciousness altered
        
        can involve automatic movements
        
        subject may have little or no memory of the seizure
        
        often occurs in the temporal lobes (Temporal lobe epilepsy)
      - begins with a local electrical discharge
        in one area of the brain on 1 hemisphere
      - may progress to affect a whole hemisphere or
        progress to a secondary generalised seizure
    - - Secondary generalised seizures
        
        come as a result of partial seizures spreading
        across both hemispheres of the brain
        
        subjects become unconscious and may not be
        aware that their seizure began as a partial seizure
      - Primary generalised
        
        may have little warning
        
        involve loss of consciousness
        
        Status epilepticus
        
        worst case of Epilepsy
        
        prolonged or clustered seizures may develop into non-stop seizures -Satatus Epilepticus
        
        seizures follow one another with no intervening periods of normal neurologic function
        
        requires hospital treatment to bring seizures under control
        
        generalised convulsive status epilepticus may be fatal
        
        most seizures are limited in their duration
        
        both hemispheres affected from the onset
        
        Tonic seizure - sustained increase in muscle contraction
        
        Atonic seizure - sudden loss of muscle tone
        
        Myoclonic seizure - sudden involuntary muscle contraction
        
        Tonic-clonic seizure - sequence of tonic and clonic pahses
        
        Absence seizure - brief interruption of consciousness (involves thalamo-cortical circuits)
      - begins with a widespread electrical discharge
        that involves both sides of the brain at once
  - - - no obvious cause
      - genetic basis - faults in ion channels, receptors
    - - present underlying cause
      - ceregrovascular lesions
      - perinatal or postnatal trauma
      - CNS infections
      - tumors
      - congenital malformations of the CNS
- - - - Na+ - gain of function (impaired inactivation)
      - K+ - loss of function
      - Cl- - loss of function
    - - GABAa - reduction of function
      - NAChR - gain of function
- - - - increase K+ channel activity
      - Increase efficacy of inhibtory synapses
      - block GABA metabolism
        
        Valproate
        
        inhibitor of GABA transaminase (GABA-T),
        responisible for the breakdown of GABA
        
        also blocks Na+ channels
      - potentiation of GABA action
        
        Benzodiazepines
        
        allosteric modulators of GABAa receptors
        
        Diazepam
        
        Clonzepam
        
        Barbiturates
        
        Phenbarbitone
        
        increasing postsynaptic efficacy of GABA
        by allosteric modulation of GABAa receptors
    - - decrease efficacy of excitatory synapses
      - Na channels
        
        Phenytoin
        
        Carbemazepine
        
        Valproate
        
        target na channels in cells that fire frequently
      - Ca channels
        
        Ethosuximide
        
        prime effects on Ca channels, but also on NA channels
        
        used in absense epilepsy
        
        work on t-type Ca2+ channels in thalamic neurons
      - decrease activity of voltage-gated Na+ and/or Ca2+ channels
  - - - Lamotrigine
      - Topiramate
      - target hyperactive cells, without affecting normal activity
    - - Tiagabine
        
        selective GAT-I inhibitor
      - increasing the spread and duration of action of GABA can be achieved by inhibition of membrane transporters normally responsible for GABA uptake
    - - Felbamate
        
        acts at glycine site on NMDARs
    - - Parampanel
        
        non-competitive antagonist
    - - Levetiracetam
  - - - decrease activity of vg Na+/Ca2+ channels
      - decrease efficacy of excitatory synapses
    - - increase K+ channel activity
      - increase efficacy of inhibitory synapses