Antiepileptics

• Antiepileptic drugs


  Drugs used to prevent or control epilepsy (seizures)
• Seizure


  • A sudden burst of uncontrolled electrical activity in the brain that occurs when neurons become excessively active
  • Can be classified into focal seizures (affect only a portion of the brain) or generalized seizures (affect both sides of the brain)
• Inhibitory and excitatory processes in the brain


  Seizures result from an imbalance between inhibition and excitation, either too little inhibition or too much excitation
• Action potential in neurons

  1. Voltage-gated sodium channels open

  2. Sodium ions rush in, reversing polarization

  3. Voltage-gated calcium channels open

  4. Calcium ions enter, triggering release of glutamate

  5. Glutamate binds to AMPA and NMDA receptors on postsynaptic neuron
• Inhibitory neurons


  Release GABA, which binds to GABA-A receptors on excitatory neurons, allowing chloride ions to enter and limiting the neuron's ability to respond to further stimulation
• GABA reuptake and degradation


  GABA is removed from the synaptic cleft by reuptake through GABA transporter-1 (GAT-1) and then degraded by GABA aminotransferase (GABA-T)
• Goal of antiepileptic drugs


  • To lower neuronal excitability and/or enhance neuronal inhibition
• Antiepileptic drugs that block sodium channels


  • Carbamazepine
  • Oxcarbazepine
  • Lamotrigine
  • Phenytoin
  • Topiramate
  • Valproic acid
  • Zonisamide
• Antiepileptic drugs that block calcium channels


  • Lamotrigine
  • Topiramate
  • Valproic acid
  • Zonisamide
• Gabapentin and Pregabalin


  Bind to the alpha-2-delta-1 subunit of high-voltage-activated calcium channels, inhibiting the release of excitatory neurotransmitters
• Levetiracetam


  Binds to the SV2A protein in synaptic vesicles, impairing the release of glutamate
• Felbamate


  Inhibits excitatory neurotransmission by blocking NMDA receptors
• Antiepileptic drugs that target the GABA system


  • Benzodiazepines
  • Barbiturates
• Tiagabine


  Selective inhibitor of the GABA transporter, blocking GABA reuptake
• Vigabatrin


  Irreversibly inhibits GABA aminotransferase, increasing GABA concentrations in the brain
• Potential side effects of antiepileptic drugs


  • Sedation
  • Dizziness
  • Hyponatremia (with Carbamazepine and Oxcarbazepine)
  • Visual field loss (with Vigabatrin)
  • Double vision (with Lamotrigine and Phenytoin)
  • Gingival hyperplasia and hirsutism (with Phenytoin)
  • Cognitive problems (with Topiramate and Zonisamide)
  • Weight loss (with Topiramate)
  • Weight gain (with Valproic acid, Gabapentin, Pregabalin)
  • Peripheral edema (with Gabapentin and Pregabalin)
  • Liver toxicity (with Valproic acid and Felbamate)
  • Aplastic anemia (with Felbamate)