Chapter 19  ·  Module 5
Absence Seizures and Newer Agents
Ethosuximide, levetiracetam, topiramate, gabapentin, and pregabalin
Figure 1 — Drugs That Treat vs. Worsen Absence (Gemini)
Ethosuximide T-Type Calcium Channel Blocker
  • First-line for pure childhood absence epilepsy
  • Blocks T-type calcium channels in thalamic relay neurons
  • No efficacy against tonic-clonic or myoclonic seizures
  • Use valproate instead when absence coexists with other seizure types
Levetiracetam
  • Synaptic vesicle protein 2A modulator
  • NOT sodium, calcium, or gamma-aminobutyric acid
  • No cytochrome P450 interactions
  • Key adverse effect: irritability, aggression (behavioral, not sedation)
  • Preferred in pregnancy
Topiramate
  • Multiple mechanisms including carbonic anhydrase inhibition
  • Cognitive impairment ("Dopamax") — dose-limiting
  • Weight loss (used therapeutically)
  • Kidney stones from carbonic anhydrase inhibition
  • Teratogenicity — cleft palate and lip
Gabapentin / Pregabalin
  • Alpha-2-delta subunit of voltage-gated calcium channels
  • NOT gamma-aminobutyric acid receptor agonists — name is misleading
  • Gabapentin: focal seizures, neuropathic pain; worsens absence
  • Pregabalin: same + fibromyalgia, generalized anxiety disorder; Schedule V
Figure 2 — Gabapentin vs. Pregabalin Comparison (Gemini)
High-Yield Trap — Gabapentin and Pregabalin
Despite their names, gabapentin and pregabalin are NOT gamma-aminobutyric acid receptor agonists. They bind the alpha-2-delta subunit of voltage-gated calcium channels. A question asking which drug acts at gamma-aminobutyric acid receptors should never have gabapentin or pregabalin as the answer.