Antiepileptic Drugs (AED) Lecture Review

Comprehensive vocabulary flashcards covering antiepileptic drugs (AEDs), including their mechanisms of action, pharmacokinetics, clinical uses, and specific side effects as discussed in the lecture.

Epilepsy

A group of neurological disorders characterized by periodic seizures.

Seizures

An episodic high frequency discharge of impulses by a group of neurons in the brain.

Focal-to-bilateral tonic-clonic seizure

Also known as a secondarily generalized seizure, where a focal seizure spreads to involve both sides of the brain.

Focal Impaired Awareness Seizures

Previously known as complex focal seizures, where consciousness or awareness is affected during the episode.

Narrow Therapeutic Index

A property of several AEDs where there is a small margin between the therapeutic dose and toxic concentration, requiring close monitoring.

Carbamazepine

A sodium channel blocker used for focal, tonic-clonic, and focal-to-bilateral seizures that induces its own metabolism through hepatic enzymes like $CYP3A4$.

Auto-induction

The process where a drug like carbamazepine induces its own metabolism, causing serum concentrations to fall after a few weeks of treatment.

HLA-B*1502

An allele common in Asian populations that increases the risk of Stevens-Johnson syndrome when taking carbamazepine.

Oxcarbazepine

A prodrug of carbamazepine that is less potent but has a lower tendency to induce hepatic metabolizing enzymes.

Lacosamide

A sodium channel blocker approved for age $17+$ with minimal protein binding and no active metabolites, leading to minimal drug interactions.

Phenytoin

An old non-sedating AED that blocks $Na^+$ channels; it is $90\%$ bound to plasma proteins and follows non-linear (saturable) elimination kinetics.

Purple Glove Syndrome

A potential risk or complication associated with the use of the antiepileptic drug phenytoin.

Gingival Hyperplasia

A side effect of phenytoin characterized by the overgrowth of gum tissue.

Gabapentinoids

A class of drugs including gabapentin and pregabalin that target the auxiliary subunit of voltage-gated $Ca^+$ channels to decrease glutamate release.

Tiagabine

A GABA uptake inhibitor that targets the $GAT-1$ GABA transporter, the most abundant isoform in the brain.

Retigabine

A third-line treatment for focal seizures that acts as a $K^+$ channel opener and can cause pigment discoloration of the retina and skin.

Lamotrigine

A broad-spectrum AED that blocks sodium and potentially calcium channels; it is noted for having fewer fetal risks and causing insomnia instead of sedation.

Stevens-Johnson Syndrome

A potentially fatal rash that requires slow titration of drugs like lamotrigine to avoid risk.

Levetiracetam

A broad-spectrum AED that binds to the $SV2A$ synaptic vesicle protein to reduce the release of excitatory neurotransmitters like glutamate.

Perampanel

An $AMPA$ antagonist that blocks a subtype of glutamate receptors responsible for the neuron-to-neuron spread of excitation.

Valproic Acid

A broad-spectrum AED that blocks $Na^+$ channels, inhibits GABA transaminase, and blocks $T$-type $Ca^+$ channels; it is a potent teratogen.

Idiosyncratic Hepatotoxicity

A rare but potentially fatal side effect of valproate involving liver damage.

Topiramate

A multi-mechanism drug that inhibits $Na^+$ channels, enhances GABA, acts as a weak carbonic anhydrase inhibitor, and can cause cognitive impairment.

Oligohydrosis

A rare side effect of topiramate and zonisamide characterized by decreased sweating and potential hyperthermia, especially in children.

Zonisamide

A sulfonamide derivative that blocks $Na^+$ and $T$-type $Ca^+$ channels, used for focal and generalized seizures, and carries a risk of kidney stones.

Ethosuximide

The first-choice drug for generalized absence seizures, which works by inhibiting low-voltage-activated $T$-type $Ca^+$ channels in thalamocortical neurons.

Clobazam

A positive allosteric modulator of the $GABA_A$ receptor approved for focal and atonic seizures associated with Lennox-Gastaut syndrome.

Rufinamide

A voltage-gated $Na^+$ channel blocker used as adjunctive treatment for atonic seizures in Lennox-Gastaut syndrome; it may shorten the $QT$ interval.

Status Epilepticus

A medical emergency treated primarily with rapidly acting benzodiazepine formulations like IV diazepam or lorazepam.

Diazepam

A first-line benzodiazepine for status epilepticus (IV) and seizure clusters (rectal gel).

Lorazepam

A benzodiazepine used for status epilepticus, preferred for its prolonged action compared to other agents in its class.

Midazolam

The preferred benzodiazepine for the out-of-hospital treatment of status epilepticus.

Clonazepam

A long-acting benzodiazepine effective against absence, atonic, and myoclonic seizures.

Phenobarbital

A barbiturate used for drug-refractory status epilepticus; it acts as a positive allosteric $GABA$ receptor modulator and carries a risk of physical dependence.

Primidone

A derivative of phenobarbital that is metabolized into phenobarbital and two other active anti-seizure metabolites.

Dravet’s Syndrome

Severe myoclonic epilepsy of infancy often caused by an $SCN1A$ gene mutation of $Nav1.1$ sodium channels.

Stiripentol

A positive allosteric $GABA$ receptor modulator used specifically for Dravet’s syndrome in conjunction with clobazam or valproate.

Vigabatrin

An irreversible GABA transaminase inhibitor used for focal seizures and infantile spasms; it carries a risk of irreversible retinal dysfunction.

Infantile Spasms

Also known as West’s syndrome, typically treated with $ACTH$, oral corticoids, or vigabatrin.

Ganaxolone

A synthetic neuroactive steroid that acts as a $GABA_A$ positive allosteric modulator, approved for seizures in $CDKL5$ deficiency disorder.

CDKL5 Deficiency Disorder

A condition associated with seizures in patients $2$ years of age and older for which ganaxolone is an approved treatment.

T-type Calcium Channels

The specific molecular target in thalamocortical neurons inhibited by ethoxuximide to treat absence seizures.

AMPA Receptors

Glutamate receptors critical to the local generation of seizures and neuron-to-neuron spread of excitation, targeted by perampanel.

SV2A

A synaptic vesicle integral membrane protein targeted by levetiracetam and brivaracetam to reduce excitatory neurotransmitter release.

GAT-1

The specific GABA transporter isoform targeted by tiagabine to prolong inhibitory responses.

GABA Transaminase

An enzyme responsible for breaking down GABA; it is inhibited irreversibly by vigabatrin and also inhibited by valproate.

Typical CNS Side Effects

Common adverse effects of AEDs including sedation, dizziness, headache, ataxia, blurred vision, and GI disturbance.

Lennox-Gastaut Syndrome

A severe epilepsy syndrome often involving atonic seizures; treatments include clobazam, rufinamide, and topiramate.

Hirsutism

A side effect of phenytoin characterized by excessive hair growth.

Fatal Hyperammonemic Encephalopathy

A condition and contraindication for valproate in patients with genetic defects in urea metabolism.