STEPTRACKERPHARMACOLOGY + NEUROLOGY | NEUROLOGY | HIGH-YIELD REVIEW

Anticonvulsants

Seizure drugs quiet neurons by blocking Na⁺ or Ca²⁺ channels, boosting GABA or damping glutamate — the seizure type picks the drug, and each drug has a signature toxicity.

FOCUS ON
Status epilepticus: IV lorazepam (or IM midazolam) → fosphenytoin, levetiracetam or valproate → anesthesia. Absence: ethosuximide (T-type Ca²⁺) or valproate. Focal: lamotrigine, levetiracetam, carbamazepine, oxcarbazepine. Generalized tonic-clonic: valproate, lamotrigine, levetiracetam. Eclampsia: MgSO₄. Trigeminal neuralgia: carbamazepine. Signature toxicities: phenytoin — gingival hyperplasia, hirsutism, nystagmus, ataxia, fetal hydantoin, SJS, megaloblastic anemia, osteomalacia, zero-order kinetics, purple glove (IV); carbamazepine — agranulocytosis/aplastic anemia, SIADH, SJS (HLA-B*15:02), autoinduction, teratogen; valproate — hepatotoxicity, pancreatitis, neural tube defects, tremor, weight gain, hyperammonemia; lamotrigine — SJS (slow titration; valproate ↑ levels); ethosuximide — GI, rash; topiramate — kidney stones, weight loss, word-finding, angle-closure glaucoma; levetiracetam — irritability, depression; felbamate — aplastic anemia, liver; vigabatrin — visual field loss.
DRUG
MECHANISM
MAIN USE
SIGNATURE TOXICITY
Phenytoin · fosphenytoin
Blocks inactivated Na⁺ channels
Focal, GTC, status (2nd line)
Gingival hyperplasia, hirsutism, nystagmus, ataxia, teratogen, SJS, CYP inducer
Carbamazepine · oxcarbazepine
Na⁺ channel block
Focal seizures, trigeminal neuralgia, bipolar
Agranulocytosis, aplastic anemia, SIADH/hyponatremia, SJS, CYP inducer
Lamotrigine
Na⁺ channel block, ↓ glutamate release
Focal, GTC, absence, bipolar depression; pregnancy-preferred
SJS/TEN — titrate slowly
Valproate
Na⁺ block, ↑ GABA, T-type Ca²⁺ block
Broad: GTC, absence, myoclonic; bipolar; migraine
Hepatotoxicity, pancreatitis, NTD, tremor, weight gain, hyperammonemia, CYP inhibitor
Ethosuximide
Blocks thalamic T-type Ca²⁺ channels
Absence seizures only
GI upset, fatigue, rash, SJS
Levetiracetam
Binds SV2A synaptic vesicle protein
Focal, GTC, status; few interactions
Irritability, depression, behavior change
Gabapentin · pregabalin
α2δ subunit of voltage-gated Ca²⁺ channels
Focal seizures, neuropathic pain, postherpetic neuralgia, fibromyalgia
Sedation, ataxia, edema; renal dosing
Topiramate
Na⁺ block, ↑ GABA, AMPA block, carbonic anhydrase inhibition
Focal, GTC, migraine prophylaxis, weight loss
Kidney stones, cognitive slowing, weight loss, angle-closure glaucoma, metabolic acidosis
Benzodiazepines
lorazepam, diazepam, midazolam
↑ Frequency of GABA-A Cl⁻ channel opening
Status epilepticus, eclampsia (2nd line), alcohol withdrawal seizures
Respiratory depression, sedation
Phenobarbital
↑ Duration of GABA-A opening
Neonatal seizures, refractory status
Sedation, CYP induction, respiratory depression
Tiagabine · vigabatrin
Block GABA reuptake · irreversibly inhibit GABA transaminase
Focal seizures · infantile spasms (vigabatrin)
Vigabatrin permanent visual field loss
Felbamate · lacosamide · cannabidiol
NMDA block · slow Na⁺ inactivation · multiple
Refractory epilepsy (Lennox-Gastaut, Dravet)
Felbamate aplastic anemia; lacosamide PR prolongation
Magnesium sulfate
NMDA block, Ca²⁺ antagonism
Eclampsia, preeclampsia with severe features
Loss of reflexes → respiratory arrest; antidote calcium gluconate

Mechanism — status epilepticus sequence

0–5 minABCs, glucose
→
5–20 minBenzodiazepine (lorazepam IV)
→
20–40 minFosphenytoin, levetiracetam or valproate
→
RefractoryMidazolam, propofol, pentobarbital infusion

Seizure type → drug

TYPE
FIRST CHOICE
AVOID
Absence
Ethosuximide, valproate
Carbamazepine, phenytoin
Myoclonic
Valproate, levetiracetam
Carbamazepine
Focal
Lamotrigine, levetiracetam
—
Pregnancy
Lamotrigine, levetiracetam
Valproate

How it's tested

COMMON CONFUSIONCarbamazepine and phenytoin can worsen absence and myoclonic seizures — use broad-spectrum drugs for generalized epilepsy.
THE TRAPEnzyme-inducing anticonvulsants (carbamazepine, phenytoin, phenobarbital, topiramate at high dose) make OCPs fail — counsel on contraception.
YOUR APPROACHSeizure type + patient (pregnancy, liver, interactions) → drug → monitor signature toxicity.

If you see… think…

Child staring spells with 3-Hz spike-wave → ethosuximide
Gum overgrowth, coarse facies, hirsutism → phenytoin
Hyponatremia and agranulocytosis on seizure drug → carbamazepine
Epigastric pain radiating to back, ↑ lipase → valproate pancreatitis
Rash and mucosal sloughing after fast titration → lamotrigine SJS
Kidney stones and weight loss on migraine/seizure drug → topiramate
Infantile spasms, visual field loss → vigabatrin
Eclamptic seizure → magnesium sulfate
Lamotrigine level doubles → valproate inhibits glucuronidation
Trigeminal neuralgia first-line → carbamazepine