ASMs

Carbamazepine

MOA: Sodium channel blocker/modulator

PK: 

• Potent inducer of 2C19, 2C9, 3A4→ affects the effectiveness of other antiepileptics 

• Is an autoinducer 

• Forms a toxic epoxide→leads to ADRs

BBW: Agranulocytosis; aplastic anemia; SJS/TEN (Higher with risk of HLA-B 1502 positive

Contraindications: History of bone marrow depression, 3A4 metabolized drugs 

Should not use in children

Clonazepam

MOA: GABA agonist

BBW: Use with opiates may result in sedation, respiratory depression, coma, death

ADRs: Pronounced sedation, paradoxical agitation, tolerance; severe withdrawal symptoms

Contraindications: Acute narrow-angle glaucoma, advanced liver disease

Ethosuximide

MOA: Inhibition of T-type calcium channels

Phenobarbital

MOA: GABA Agonist

PK: 

• Inducer of 3A4,2C9,2C19,1A2

BBW: Risk of overdose when used with opioids, dependence and withdrawal, abuse

ADRs: Prominent CNS depression/sedation

Contraindications: respiratory disease with evidence of dyspnea or obstruction

Phenytoin

MOA: Sodium Channel Blocker/Modulator

PK: 

• Exhibits Michaelis-Menten PK→metabolism is saturable

• Highly protein bound 

BBW: Hypotension and arrhythmias with IV administration

ADRs: SJS/TEN, Blood dyscrasias, Hepatotoxicity, Severe local injection site reaction (“purple glove syndrome”), Gingival Hyperplasia(w/long term use)

Contraindications: Sinus bradycardia, AV blocks

Should avoid in children 

Valproate

MOA: GABA modulator, blocks voltage-gated sodium channels.

PK:

• Substrate of UGT hepatic metabolism

• oral contraceptives may cause increased valproate metabolism and subsequent increased risk in seizures

• highly protein bound 

Black Box Warning: Hepatotoxicity, teratogenicity, patients with mitochondrial disease, pancreatitis

ADRs: Hyperammonemia and encephalopathy (higher risk when used with topiramate), thrombocytopenia, Tremor, weight gain, alopecia or hair texture changes, nail and nail bed disorders, hormone changes, osteomalacia/osteoporosis

Contraindications: Hepatic disease, urea cycle disorders

Felbamate

MOA: Glutamate blocker, may also augment GABA neurotransmission

BBW: Irreversible aplastic anemia, hepatic failure

Contraindications: History of any blood dyscrasia or hepatic dysfunction

Gabapentin(Neurotonin) 

MOA:Calcium channel modulator

PK: renal elimination 

Should avoid in children 

Lamotrigine (Lamictal)

MOA: Sodium Channel Blocker/Modulator

PK/PD: Substrate of UGT hepatic metabolism

• Dose recommendations differ if on valproate, carbamazepine, phenobarbital, phenytoin, primidone, or valproate

  • If on valproate:  decrease dose; 25 mg every other day

  • If on carbamazepine, phenobarbital, etc: increase dose; 50mg/day

• Estrogen OCs may decrease lamotrigine levels by 50%

BBW:SJS/TEN

ADRs:  tremors  

Levetiracetam (Keppra)

MOA: Modulates SV2A protein → helps stabilize neurotransmitter release

Adverse Effects: Psychosis, hallucinations, DRESS,  Mood problems → irritability, agitation, anger, depression (“Kepp-Rage”)

• can worsen psychiatric conditions

Oxcarbazepine (Trileptal)

MOA: Sodium channel blocker/modulator, analogue of carbamazepine

PK: 

• Does not produce epoxide metabolite→better tolerability than carbamazepine

ADRs: Agranulocytosis, SJS/TEN (higher risk in HLA B*1502 positive)

• Should avoid in children 

Tiagabine (Gabitril)

MOA: GABA modulator

ADRs: New onset seizures, status epilepticus, exacerbation of EEG abnormalities

Should avoid in children 

PK: high protein binding 

Note: Generally reserved for refractory epilepsies due to risk of serious AE

Topiramate (Topamax) 

MOA: Sodium Channel Modulator, GABA agonist, Glutamate antagonist, Carbonic anhydrase inhibitor

PK:  

• Induces CYP3A at high doses

ADRs: Notable cognitive impairment (“Dope Amax”), bilateral paresthesias, weight loss, hypohidrosis, kidney stones

Contraindications: Alcohol use for the ER formulation (within 6 h prior to and 6 h after administration)

Zonisamide(Zonegran)

MOA: Sodium Channel Modulator, Calcium Channel Modulator, weak carbonic anhydrase inhibitor

PK: Cyp3A4 Substrate

ADRs: Notable cognitive impairment, weight loss, hypohidrosis, kidney stones

Contraindications: Sulfa allergy

Brivaracetam (Briviact)

MOA: SV2A inhibitor (similar to levetiracetam, chemical analog).

PK: Weak inhibitor of CYP2C19 and glucuronidation; substrate of CYP2C19.

ADRs: Mood and behavioral issues similar to levetiracetam.

Cenobamate (Xcopri)

MOA: Sodium channel blocker + positive allosteric modulator of GABA.

Contraindications: Familial short QT syndrome

BBW: psychiatric/behavioral/mood/personality changes (can be life-threatening).

Eslicarbazepine (Aptiom)

MOA: Sodium channel blocker; prodrug to licarbazepine and carbamazepine.

PK:No epoxide metabolite (better tolerated than carbamazepine).

Adverse effects:

• Rare/serious: SJS, DRESS, angioedema, AV block, hepatotoxicity, blood dyscrasias.

• Common: Tremor, hyponatremia (via SIADH), rash.

Lacosamide (Vimpat)

MOA: Sodium channel blocker/modulator.

ADRs: Cardiac Arrhythmias, syncope, DRESS, neutropenia and anemia

Perampanel (Fycompa)

MOA: Glutamate AMPA receptor blocker.

PK: highly protein bound 

Pregablin

MOA: Calcium channel modulator (similar to gabapentin).

Adverse effects:

• Serious: Misuse potential, especially with opioids.

• Common: Cognitive impairment, edema, weight gain.

Vigabatrin (Sabril)

MOA: Irreversible inhibitor of GABA transaminase → increases GABA.

Black box / REMS: Progressive, permanent vision loss (dose and exposure-related).

ADRS: 

• Can worsen absence or myoclonic seizures in generalized epilepsies, anemia.

• Common: Sedation, weight gain, edema, neuropsychiatric issues (psychosis, depression, behavioral changes), neuropathy.

Avoid in children 

What ASMs are highly protein bound?

Cows Value Pretty Tight Proteins”

• C = Clonazepam

• V = Valproate

• P = Phenytoin

• T = Tiagabine(GABA modulator)

• P = Perampanel(Glutamate AMPA receptor blocker)

👉 Think: “These drugs stick tightly to protein—handle with care!”

What medications should I avoid in children with epilepsy?

“Children Get Overly Prone To Vicious Seizures”

• C = Carbamazepine

• G = Gabapentin

• O = Oxcarbazepine

• P = Phenytoin

• T = Tiagabine

• V = Vigabatrin(Irreversible inhibitor of GABA transaminase → increases GABA.)

What ASM are preferred in pregnancy?

Levetiracetam and lamotrigine

Genetic testing for SJS is needed for what

“Careful People Of East Asia, Listen!”

• C = Carbamazepine

• P = Phenytoin

• O = Oxcarbazepine

• E = Eslicarbazepine

• L = Lamotrigine