Neurology · USMLE Step 1 and Step 2

Phenytoin, Carbamazepine & Valproate song

Phenytoin, Carbamazepine & Valproate - Toxicity, as a song. Hear the short teaser here. The full song is on YouTube and Spotify.

Phenytoin, Carbamazepine & Valproate

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Key points in this song10

Phenytoin blocks voltage-gated sodium channels by prolonging the inactive state, reducing repetitive neuronal firing; it follows zero-order (saturable) kinetics at therapeutic doses, making small dose increases disproportionately toxic.
Phenytoin toxicity follows a "CAVE" progression: Cerebellar ataxia, nystagmus, diplopia at low toxic levels, progressing to Altered mental status at higher levels; gingival hyperplasia, hirsutism, and coarsening of facial features are chronic adverse effects.
Carbamazepine is first-line for trigeminal neuralgia and partial (focal) seizures; it also blocks voltage-gated sodium channels and is used as a mood stabilizer in bipolar disorder.
Carbamazepine induces cytochrome P450 (CYP3A4) and induces its own metabolism (auto-induction); it can cause aplastic anemia, agranulocytosis, and SIADH-mediated hyponatremia.
Carbamazepine causes a Stevens-Johnson syndrome risk dramatically increased in patients carrying the HLA-B*1502 allele, which is most prevalent in Han Chinese and Southeast Asian populations — screen before prescribing.
Valproate inhibits voltage-gated sodium channels and increases GABA levels by inhibiting GABA transaminase; it is the broadest-spectrum antiepileptic, effective against absence, myoclonic, tonic-clonic, and partial seizures.
Valproate is teratogenic — neural tube defects (spina bifida) via folate metabolism inhibition — and is strongly contraindicated in pregnancy; it is also associated with fatal hepatotoxicity, most commonly in children under 2 on polytherapy.
Valproate inhibits CYP450 enzymes and is a potent inhibitor of drug metabolism, increasing levels of phenytoin, lamotrigine, and other co-administered drugs.
All three drugs are hepatically metabolized and are strong inducers (phenytoin, carbamazepine) or inhibitors (valproate) of CYP450, making drug-drug interactions a high-yield testing target — especially with oral contraceptives, warfarin, and other antiepileptics.
Phenytoin and carbamazepine are contraindicated in absence seizures as they can worsen them; valproate and ethosuximide are the preferred agents for absence seizures.