Epilepsy drugs Flashcards
RX idiopathic generalized epilepsy: 6
VPA, lamotrigine, Ethosuximide, Topiramate, Zonisamide, Levetiracetam
Valproate
MOA
PK
RX
SE
MOA: GABA enhancer, Na and Ca channel blocker (inhibits T-type Ca2+)
PK: hepatic, inhibitor
RX: partial and general
SE: Weight gain, tremor, GI uspet, sedation, alopecia, hepatotoxicity, pancreatitis, teratogenicity, thrombocytopenia, hyper-ammonia, PCOS exacerbation
Drug interactions: inhibits CYP enzymes (↑ lamotrigine, phenobarbital, carbamazepine), highly protein bound and can displace phenytoin leading to toxicity
Black box: Hepatotoxicity, pancreatitis, teratogenicity
Lamotrigine
MOA
PK
RX
SE
Contraindications
MOA: Na and Ca channel blocker, ↓ glutamate release
PK: hepatic
SE: Rash, dizziness, diplopia, Stevens-Johnson syndrome, TEN, aseptic meningitis (rare), potentially fatal liver injury
Drug interactions: Valproate ↑ levels (risk of rash); OCPs, carbamazepine and phenytoin all ↓ lamotrigine levels
Black box: Stevens-Johnson syndrome, TEN
Contraindications: Dravet syndrome (SCN1A mutation) (Can worsen seizures)
Levetiracetam
MOA
PK
RX
SE
MOA: Binds SV2A, reduces glutamate release, modulates calcium channels stabilizing neuronal firing
PK: renal exertion, no drug-drug interactions
RX: partial and general
SE: Sedation, mood changes, depression, suicidality, psychosis, SJS (rare)
Ethosuximide
MOA
PK
RX
SE
MOA: T-type Ca2+ channel blocker
PK: hepatic, not an enzyme inducer, but increases phenytoin levels and decreases lamotrigine levels
RX: absence seizures (general)
SE: ataxia, Nausea, headache, sleep disturbances (insomnia or drowsiness), hyperactivity, confusion
SSE: Agranulocytosis (and other blood dysrasias), Stevens-Johnson syndrome, lupus like syndrome
Topiramate
MOA
PK
RX
SE
MOA: Na ch blocker, ↑ GABA, ↓ glutamate (inhibits AMPA/kainate receptors), carbonic anhydrase inhibition
PK: hepatic, inducer, renal exretion
RX: partial and general
SE: Cognitive impairment, weight loss, paresthesias (tingling), Acidosis, kidney stones, cleft palate in pregnancy, angle closure glaucoma, weight loss
Drug interactions: ↓ Oral contraceptive efficacy, ↓ valproic acid levels, excessive sedation w alcohol
Clobazam
MOA, SE, SSE, Drug interactions, Black Box
MOA: GABA-A agonist
SE: Drowsiness, dizziness
SSE: Respiratory depression, dependence, suicidal ideation
Drug interactions: CYP3A4 metabolism (interacts w inducers like rifampin and phenytoin), additive sedation w alcohol, optiods, CNS depressants
Black box: Respiratory depression, dependence
Zonisamide
MOA
PK
RX
SE
Contraindications:
MOA: Na and Ca ch blocker (inhibits T-type Ca2+ channels), carbonic anhydrase inhibition
PK: hepatic, renal excretion (not an inducer like Topiramate)
SE: Sedation, dizziness, weight loss, kidney stones, Stevens-Johnson syndrome, metabolic acidosis, oligohydrosis (reduced sweating), weight loss
Drug interactions: CYP3A4 metabolism, additive CNS depression with other AEDs
Contraindications: Kidney stones (like Topiramate), sulfa allergy, Dravet syndrome (not first-line)
Phenytoin
MOA
PK
RX
SE
Contraindications
MOA: Na ch blocker
PK: hepatic, inducer
RX: partial
SE: ataxia, rash, gingival hyperplasia, neuropathy, cardiac supresion (dysrhythmias and nodal block), drowsiness, nausea
Contraindications: Dravet syndrome, absence epilepsy, myoclonic epilepsy (Worsens seizures)
Carbamazepine
MOA
PK
RX
SE
Contraindications
MOA: Na ch blocker
PK: hepatic, inducer
RX: partial
SE: ataxia, double vision, thrombocytopenia, leukopenia, hyponatremia
Contraindications: Draven syndrome, myoclonic epilepsy, absence epilepsy, LGS
Phenobarbital
MOA
PK
RX
SE
MOA: GABA receptor enhancer
PK: hepatic, inducer
RX: partial
SE: sedation, mental slowing
Oxcarbazepine
MOA
PK
RX
SE
Contraindications
MOA: Na ch blocker
PK: hepatic, inducer
RX: partial
SE: fatigue, dizziness, somnolence, ataxia, double vision, hyponatremia, rash
Contraindications: Dravet syndrome, absence epilepsy, myoclonic epilepsy
Lacosamide
MOA
PK
RX
SE
Contraindications
MOA: Na ch blocker (slow)
PK: renal excretion
RX: partial
SE: dizziness, ataxia, diplopia, nausea, depression
Contraindications: Cardiac conduction disease (prolongs PR interval, can worsen Brugada syndrome)
Vigabatrin
MOA
PK
RX
SE
MOA: inhibits GABA transaminase
PK: renal excretion
RX: partial, infantile spasms w tuberous sclerosis
SE: somnolence, ha, depression, agitation, fatigue, visual field loss
Tiagabine
MOA
PK
RX
SE
MOA: GABA uptake inhibitor
PK: hepatic, inducer
RX: partial
SE: dizziness, somnolence, depression, confusion, ataxia
Gabapentin / Pregabalin
MOA
PK
RX
SE
MOA: Ca ch blocker, GABA enhancer?
PK: renal excretion
RX: partial, neuropathic pain
SE: somnolence, dizziness, ataxia, tremor, edema, weight gain
Clobazam
MOA
PK
RX
SE
MOA: GABA enhancer
PK: hepatic
RX: partial, myoclonic seizures
SE: ataxia, somnolence, diplopia and dysarthria, SJS, TEN
Rufinamide
MOA
PK
RX
SE
Contraindications
MOA: Na ch blocker
PK: hepatic
RX: partial, LGS
SE: dizziness, drowsiness, nausea, ha, rash, mood changes
Contraindications: QT shortening syndromes (may worsen cardiac conduction abnormalities)
Peramanel
MOA
PK
RX
SE
MOA: AMPA receptor blocker
PK: hepatic
RX: partial
SE: fatigue, dizziness, ataxia FDA warning: homocidal and suicidal ideation
Ezogabine or retigabine
MOA
PK
RX
SE
MOA: K ch opener
PK: hepatic
RX: partial
SE: dizziness, drowsiness, slurred speech, FDA warning: skin discoloration and retinal pigment changes
Safest AED pregnancy:
lamotrigine, levetiracetam, oxcarbazepine
Least safe AED pregnancy
valproate: cardiac and CNS, oral cleft, club foot, hypospadias
Carbamazepine, Phenobarbital, Topiramate, Phenytoin
all AEDs teratogenic
AED with no/minimal hepatic metabolism: 6
(safer in liver disease and less drug interactions)
Levetiracetam
Brivaracetam
Gabapentin
Pregabalin
Lacosamide
Vigabatrin
Levitating Gabby playing Lacrosse with Vi(gabatrin) jersey shooting into a urinal (renal exretion)
OCPs lower the levels of which AED significantly?
Lamotrigine
Estrogen-containing OCs lower lamotrigine levels by ~50% due to increased glucuronidation, potentially leading to breakthrough seizures.
AEDs that lower OCP effectivenss
Strong CYP3A4 Inducers (Highest Risk of OC Failure)
Phenytoin – CYP3A4 inducer
Carbamazepine – CYP3A4 inducer (autoinduction)
Phenobarbital – CYP3A4 inducer
Primidone – CYP3A4 inducer (metabolized to phenobarbital)
Rufinamide – CYP3A4 metabolism, weak inducer
Felbamate – CYP3A4 inducer, also inhibits CYP2C19
Topiramate (≥200 mg/day) – Moderate CYP3A4 induction
💡 Board Exam Tip: Topiramate at lower doses (<200 mg/day) has minimal effect, but doses ≥200 mg/day significantly reduce OC effectiveness.
AEDs that directly or indirectly increase GABA
Benzodiazepines (Diazepam, Lorazepam, Clonazepam, Midazolam, Clobazam) Allosteric modulators of GABA_A receptors, increasing frequency of Cl⁻ channel opening
Barbiturates (Phenobarbital, Primidone), Prolong duration of Cl⁻ channel opening at GABA_A receptors
Vigabatrin Irreversible inhibitor of GABA transaminase (GABA-T), increasing GABA levels
Tiagabine Inhibits GABA reuptake (GAT-1 inhibitor), prolonging synaptic GABA action
Valproic Acid (VPA) Inhibits GABA transaminase (GABA-T) and increases GABA synthesis
Gabapentin & Pregabalin Binds α2δ subunit of voltage-gated Ca²⁺ channels → indirectly affects GABA release but does NOT act as a direct GABA agonist
💡 Board Exam Tip: Gabapentin & Pregabalin do not directly activate GABA receptors but were originally designed as “GABA analogs.” They primarily modulate Ca²⁺ channels, reducing excitatory neurotransmitter release.
Clinical Implications
Benzodiazepines & Barbiturates – Used for status epilepticus, but risk of sedation and tolerance.
Vigabatrin – Risk of permanent visual field loss (requires vision monitoring).
Tiagabine – Can worsen generalized epilepsy and cause nonconvulsive status epilepticus.
Valproic Acid – Broad-spectrum, but teratogenic (contraindicated in pregnancy).
Gabapentin/Pregabalin – Primarily for neuropathic pain, not first-line for epilepsy.
Eslicarbazepine
MOA
PK
RX
SE
Contraindications
Contraindications: Generalized epilepsy, absence, myoclonic seizures
Fosphenytoin
MOA
PK
RX
SE
Contraindications
MOA
PK
RX
SE
Contraindications: same as phenytoin: Dravet syndrome, absence epilepsy, myoclonic epilepsy (Worsens seizures)
9 Sodium Channel blockers
Carbamazepine, Oxcarbazepine, Eslicarbazepine, Phenytoin, Fosphenytoin, Lacosamide, Lamotrigine, Rufinamide, Zonisamide
A football player tackles, a large body of salt, picks it up and puts it in the trunk of a black supercar with an S on the door, an oxygen tanks mounted on the roof to make it go faster. He jumps in the driver seat and starts chasing a clown who is rough riding a lamb, while holding a lacrosse stick in his right hand and sticking his left foot big toe out as he rides into the end zone.
Sodium channel blockers exacerbate which two types of seizures?
absence and myoclonic seizures
Which six sodium channel blockers sould be avoided in Dravet syndrome, JME, and LGS?
carbazepine, oxcarbazepine, eslicarbazepine, phenytoin, lacosamide, rufinamide
