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.
⭐ Valproate has multiple mechanisms: enhances GABA, blocks Na+ channels, and blocks T-type Ca2+ channels.
Key AEDs: Profiles & Pitfalls - The Drug Lineup
| Drug | Uses | Key Pitfalls / SEs |
|---|---|---|
| Phenytoin | Focal, GTC, SE | Gingival hyperplasia, hirsutism, nystagmus, ataxia, fetal hydantoin, CYP inducer, zero-order kinetics. |
| Carbamazepine | Focal, GTC, Trigeminal Neuralgia | Aplastic anemia (⚠️ CBC), SIADH, diplopia, ataxia, CYP inducer, autoinduction, neural tube defects. |
| Valproate | Broad (Focal, GTC, Absence, Myoclonic) | Hepatotoxicity (⚠️ LFTs), pancreatitis, weight gain, alopecia, neural tube defects (highest risk), CYP inhibitor. |
| Lamotrigine | Focal, GTC, Absence | SJS/TEN (⚠️ slow titration with VPA), rash. Safer in pregnancy. |
| Levetiracetam | Focal, GTC, Myoclonic | Behavioral changes, somnolence. Minimal interactions. |
| Ethosuximide | Absence (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.
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