Antiepileptic Drugs

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AEDs: Intro & Classes - Seizure Stoppers 101

  • Epilepsy: Disorder of recurrent, unprovoked seizures; abnormal neuronal firing in CNS.
  • AEDs: Control seizure activity, not curative. Monotherapy preferred initially.
  • Key Mechanisms & Classes:
    • Na+ channel blockade: Phenytoin, Carbamazepine, Lamotrigine
    • GABA potentiation: Benzodiazepines, Barbiturates, Valproate, Vigabatrin
    • Ca2+ channel (T-type) blockade: Ethosuximide (Absence seizures)
    • SV2A modulation: Levetiracetam (Broad-spectrum)
    • Glutamate antagonism: Perampanel, Topiramate

⭐ Valproate: Broad-spectrum AED for most seizure types; significant teratogenic risk (neural tube defects).

AED MoA - Brain's Electrical Fixers

AEDs stabilize hyperexcitable neurons by targeting:

  • These actions collectively reduce excessive neuronal firing. Valproic acid (VPA) mechanisms of action

⭐ Valproate has multiple mechanisms: enhances GABA, blocks Na+ channels, and blocks T-type Ca2+ channels.

Key AEDs: Profiles & Pitfalls - The Drug Lineup

DrugUsesKey Pitfalls / SEs
PhenytoinFocal, GTC, SEGingival hyperplasia, hirsutism, nystagmus, ataxia, fetal hydantoin, CYP inducer, zero-order kinetics.
CarbamazepineFocal, GTC, Trigeminal NeuralgiaAplastic anemia (⚠️ CBC), SIADH, diplopia, ataxia, CYP inducer, autoinduction, neural tube defects.
ValproateBroad (Focal, GTC, Absence, Myoclonic)Hepatotoxicity (⚠️ LFTs), pancreatitis, weight gain, alopecia, neural tube defects (highest risk), CYP inhibitor.
LamotrigineFocal, GTC, AbsenceSJS/TEN (⚠️ slow titration with VPA), rash. Safer in pregnancy.
LevetiracetamFocal, GTC, MyoclonicBehavioral changes, somnolence. Minimal interactions.
EthosuximideAbsence (DOC)GI distress, lethargy, hiccups. T-type $Ca^{2+}$ blocker.

AED Selection - Match Drug to Seizure

  • Broad-spectrum (multiple types): Valproate (VPA), Lamotrigine (LTG), Levetiracetam (LEV), Topiramate.
  • Narrow-spectrum (specific types):
    • Carbamazepine (CBZ), Phenytoin (PHT): Focal, GTC.
    • Ethosuximide (ESX): Pure Absence.

⭐ Ethosuximide is Drug of Choice (DOC) for uncomplicated absence seizures. Carbamazepine & Phenytoin can worsen absence/myoclonic seizures.

Status Epilepticus - Emergency Protocol

  • Stage 1 BZDs: Lorazepam (IV 0.1mg/kg), Diazepam (IV 0.2mg/kg), Midazolam (IM 10mg / IV 0.2mg/kg).
  • Stage 2 AEDs: IV Phenytoin/Fosphenytoin 20mg/kg; IV Valproate 20-40mg/kg; IV Levetiracetam 60mg/kg.
  • Stage 4 (Refractory SE): Anesthesia (Midazolam, Propofol, Pentobarbital).

⭐ IV Lorazepam: preferred BZD (longer CNS action vs Diazepam).

High‑Yield Points - ⚡ Biggest Takeaways

  • Phenytoin: Causes gingival hyperplasia, hirsutism, fetal hydantoin syndrome; follows zero-order kinetics.
  • Valproate: Broadest spectrum; major risks: hepatotoxicity, pancreatitis, neural tube defects.
  • Carbamazepine: For trigeminal neuralgia; can cause agranulocytosis, SIADH; potent P450 inducer.
  • Lamotrigine: Risk of Stevens-Johnson syndrome, especially with valproate or rapid dose increase.
  • Ethosuximide: Drug of choice for absence seizures; common side effect is GI distress.
  • Benzodiazepines (IV Diazepam/Lorazepam): First-line for status epilepticus.

Practice Questions: Antiepileptic Drugs

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The first step on priority basis required in the management of status epilepticus is

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Flashcards: Antiepileptic Drugs

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Less common but more serious side effects such as mood and behavioural changes are associated with _____

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Less common but more serious side effects such as mood and behavioural changes are associated with _____

Levetiracetam (Anti-epileptic)

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