10. Anti-Seizure Medications and GABA Modulators

What does ASM stand for?

Anti-Seizure Medication.

What is the goal of seizure treatment?

Prevent all seizures.

When is surgery considered for seizures?

In drug-resistant epilepsy after failure of ≥3 ASMs.

What are two neurostimulation options for epilepsy?

Vagus nerve stimulator (VNS) and responsive nerve stimulator (RNS).

What are complications of undertreated epilepsy?

Seizure focus strengthening, cortical injury, status epilepticus, and SUDEP.

What is SUDEP?

Sudden unexplained death in epilepsy, often due to cardiac or respiratory compromise.

What factors influence ASM choice?

Seizure type, patient factors, titration speed, and side effects.

Why combine ASMs with different mechanisms?

To broaden seizure coverage and reduce resistance.

When is polytherapy considered?

If a single ASM fails or is poorly tolerated.

What is drug-resistant epilepsy?

Failure of 3 or more ASMs to control seizures.

What is the most common mechanism of ASMs?

Sodium channel antagonism.

What does sodium channel antagonism do?

Blocks action potential propagation in neurons.

Which ASMs are sodium channel blockers?

Carbamazepine, lamotrigine, phenytoin.

What does ethosuximide target?

T-type calcium channels in the thalamus.

Which seizure type is ethosuximide used for?

Absence seizures.

What protein does levetiracetam bind to?

SV2A protein in the SNARE complex.

What is the effect of SV2A binding by levetiracetam?

Reduces synaptic vesicle release of neurotransmitters.

What do benzodiazepines do at GABA-A receptors?

Increase frequency of chloride channel opening.

What are benzodiazepines used for besides seizures?

Sedation, anxiolysis, alcohol withdrawal.

What is a side effect of benzodiazepines?

Abuse potential and withdrawal seizures.

What do barbiturates do at GABA-A receptors?

Increase duration of chloride channel opening.

What is a downside of barbiturates?

Sedation, bone loss, addiction risk.

What is the mechanism of valproic acid?

Na channel block, Ca channel block, and ↑ GABA.

What is the mechanism of topiramate?

Na channel block, GABA modulation, and glutamate antagonism.

What are the actions of propofol?

GABA modulation and glutamate antagonism.

What is propofol used for in epilepsy?

Third-line treatment for status epilepticus and general anesthesia.

Why must the airway be protected with propofol?

It causes respiratory depression and requires intubation.

What defines status epilepticus?

A seizure lasting >5 minutes or multiple seizures without return to baseline.

What is the first-line treatment for status epilepticus?

A short-acting benzodiazepine like lorazepam.

What is the second-line treatment for status epilepticus?

A second benzodiazepine dose + long-acting IV ASM (e.g., levetiracetam, valproic acid, or phenytoin).

What is the third-line treatment for status epilepticus?

Anesthetic agent like propofol.

Why is propofol third-line in status epilepticus?

It requires intubation due to respiratory depression.

What is the mechanism of lorazepam?

GABA-A receptor agonist that increases frequency of channel opening.

Which ASMs are used IV for status epilepticus second-line?

Levetiracetam, valproic acid, phenytoin.

What is the main concern in prolonged status epilepticus?

Risk of neuronal injury, cortical necrosis, and SUDEP.

What is the mechanism of carbamazepine?

Sodium channel antagonist.

What is carbamazepine used for?

Focal or generalized epilepsy; trigeminal neuralgia.

What are key adverse effects of carbamazepine?

SJS/DRESS, hepatotoxicity, aplastic anemia.

What teratogenic effect is associated with carbamazepine?

↓ folate → spina bifida.

What is the mechanism of lamotrigine?

Sodium channel antagonist.

What is lamotrigine used for?

Focal or generalized epilepsy; bipolar disorder.

What is the major adverse effect of lamotrigine?

SJS/DRESS (worst of all ASMs).

What is the mechanism of phenytoin?

Sodium channel antagonist.

What is phenytoin used for?

Focal or generalized epilepsy; status epilepticus (2nd line).

What are phenytoin's IV side effects?

Bradycardia and arrhythmias.

What are chronic phenytoin side effects?

Osteoporosis, gingival hyperplasia.

What are phenytoin's teratogenic effects?

Facial anomalies, developmental delay.

What is the mechanism of lorazepam?

GABA-A agonist (↑ frequency of channel opening).

What is lorazepam used for?

Seizure abortion; first-line for status epilepticus.

What are side effects of lorazepam?

Drowsiness, incoordination, dysarthria, withdrawal seizures.

What is the mechanism of phenobarbital?

GABA-A agonist (↑ duration of channel opening).

What is phenobarbital used for?

Focal/generalized epilepsy; refractory status epilepticus.

What are side effects of phenobarbital?

Sedation, low bone density, addiction.

What teratogenic effect is associated with phenobarbital?

Cardiac malformations, developmental delay.

What is the mechanism of ethosuximide?

T-type calcium channel antagonist.

What is ethosuximide used for?

Absence seizures.

What are side effects of ethosuximide?

SJS, aplastic anemia.

What is the mechanism of levetiracetam?

SV2A (SNARE) antagonist.

What is levetiracetam used for?

Focal/generalized epilepsy; 2nd-line status epilepticus.

What are side effects of levetiracetam?

Irritability and depression.

What is the mechanism of valproic acid?

↑ GABA, Na and Ca channel antagonism.

What is valproic acid used for?

Focal/generalized epilepsy, migraines, bipolar disorder, 2nd-line status epilepticus.

What are side effects of valproic acid?

Hepatotoxicity, pancreatitis, thrombocytopenia.

What teratogenic effects are associated with valproic acid?

Low IQ and autism (worst teratogen).

What is the mechanism of topiramate?

Na channel block, GABA modulation, glutamate antagonism.

What is topiramate used for?

Focal/generalized epilepsy, migraines, bipolar disorder, weight loss.

What are side effects of topiramate?

Renal stones, glaucoma, word-finding difficulty.

What is the teratogenic risk of topiramate?

Oral clefts.

What is the mechanism of propofol?

GABA modulation and glutamate antagonism.

What is propofol used for?

Status epilepticus (3rd line), anesthesia induction.

What are side effects of propofol?

Respiratory depression and hypotension.