Lec 3: Antiepileptic Agents Flashcards by Jeff Lattman

what are the two different cellular mechanisms associated with seizures?

too much excitation (ions flowing inward like Na2+ and Ca2+) via the glutamate NT
too little inhibition (ions flowing outward like Cl- and K+) via the GABA NT

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“anti-seizure drugs” can be prescribed for other reasons such as?

migraines (prophylactic) and some pain conditions

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define what Epilepsy is

A CHRONIC disorder characterized by recurrent seizures

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what is Dravet Syndrome?

a mutation in a Na+ channel subunit SCN1A

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T/F the majority of people with epilepsy are resistant to treatments and usually try various treatments before finding one that is beneficial

False, only 30% of people are refractory to treatment

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what does SUDEP stand for?

sudden unexplained death in epilepsy

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list the first generation antiseizure medications

potassium bromide, phenobarbital, phenytoin, primidone, and ethosuximide

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what is phenytoin specifically classified as?

an Na2+ channel blocker

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what is primidone specifically classified as?

an Na2+ channel and GABA blocker

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what is ethosuximide specifically classified as?

T-type Ca2+ channel blocker

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list the second generation antiseizure medications

Benzos:
diazepam, carbamazepine, valproate, clonazepam, and clobazam

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T/F benzos have broad anti-seizure activity

True

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what is carbamazepine specifically classified as?

Na+ channel blocker

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what is valproate specifically classified as?

Na+ channel blocker

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what is clonazepam specifically classified as?

GABA potentiation

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what is clobazam specifically classified as?

GABA potentiation

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Vigabatrin:
drug class?
what does it do?

third generation antiseizure agent
irreversible GABA-T inhibitor

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Lamotrigine
drug class?
what does it do?

third generation antiseizure agent
Na+ channel blocker

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Oxcarbazepine
drug class?
what does it do?

third generation antiseizure agent
Na+ channel blocker

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Felbamate
drug class?
what does it do?

third generation antiseizure agent
multiple functions

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Gabapentin
drug class?
what does it do?

third generation antiseizure agent
binds presynaptic calcium channel α2δ subunit to modulate NT (Glutamate) release

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Topiramate
drug class?
what does it do?

third generation antiseizure agent
multiple functions

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Tiagabine
drug class?
what does it do?

third generation antiseizure agent
GABA potentiation; inhibits GABA reuptake

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Levetiracetam (Keppra)
drug class?
what does it do?

third generation antiseizure agent
Synaptic Vesicle Glycoprotein 2A (SV2A) modulation

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Zonisamide drug class? what does it do?

third generation antiseizure agent Na+ channel blocker

Pregablin drug class? what does it do?

third generation antiseizure agent presynaptic calcium channel α2δ subunit

Rufinamide drug class? what does it do?

third generation antiseizure agent Na+ channel blocker

Lacosamide (Vimpat) drug class? what does it do?

third generation antiseizure agent enhanced slow activation of sodium channels

Eslicarbazepine acetate drug class? what does it do?

third generation antiseizure agent a prodrug to Eslicarbazepine - Na+channel blocker

Retigabine drug class? what does it do?

third generation antiseizure agent K+ channel activator

Perampanel drug class? what does it do?

third generation antiseizure agent Glutamate (AMPA) antagonist

Brivaracetam drug class? what does it do?

third generation antiseizure agent SV2A modulation

Cannabidiol (CBD) drug class? what does it do?

third generation antiseizure agent CB1 negative allosteric modulator

Cenobamate drug class? what does it do?

third generation antiseizure agent Na+channel enhances inactivation and slows recovery; possible GABA receptor upregulation

Define a class I seizure

partial, focal, local seizures: seizure is confined to a local area

Define a class II seizure

generalized seizures: bilaterally symmetrical and without local onset

Define a class III seizure

unclassified seizures

Define a class IV seizure

special syndromes: syndromes characterized by the presence of seizures

Define a class I "simple partial" seizure

Consciousness is not impaired

Define a class I "complex partial" seizure

Impaired consciousness: begins as a simple partial seizure that progresses and is preceded by an aura. impaired memory occurs during seizure

Define a class I "Partial seizure evolving into secondarily generalized tonic-clonic seizure"

alternating contractions with relaxation causing loss of consciousness preceded by an aura

Define a class II "absence (petit mal)" seizure

sudden interruption of consciousness, blank stare, no aura

Define a class II "myoclonic" seizure (random discharges in motor cortex)

brief and sudden contractions of muscles

Define a class II "tonic-clonic (grand mal)" seizure

abrupt onset usually with no aura with contractions and relaxation/shaking followed by unconsciousness

define what status epilepticus is

either: -seizures occurring acutely in greater intensity, number, or length than usual -prolonged seizure lasting longer than 10 minutes or repeated seizures over the course of 30 minutes

is status epilepticus occurrence a major concern?

yes, it is life threatening and emergency care should begin immediately

how can we treat status epilepticus?

initially with benzos such as: IV diazepam IV lorazepam IM midazolam

**know the appearance of interictal EEG paroxysm, silent period, tonic seizure, clonic seizure, and prostictal depression

Slide 13

name the drugs that block voltage-dependent Na+ channels used for seizures. what specifically do they inhibit the channels from doing?

Phenytoin Carbamazepine Lamotrigine Valproate Topiramate Oxcarbazepine Primidone -- they inhibit high frequency repetitive firing and fast inactivation

what is Lacosamide's mechanism at voltage-dependent Na+ channels?

likely inhibits slow inactivation

what is Rufinamide's mechanism? what syndrome is it approved to treat?

may inhibit slow inactivation of voltage-dependent Na+ channels it is approved to treat Lennox-Gastaut syndrome (a childhood- onset epilepsy syndrome)

name the drugs that target GABAergic synapses and what specifically they each do

Valproate: modifies amino acid metabolism Vigabatrin: irreversible GABA-T inhibitor Tiagabine: preferentially binds GAT-1 (not GAT-2 or GAT-3) Benzodiazepenes: allosteric modulators of GABA A (enhance affinity/ increase frequency of channel opening) Barbiturates: allosteric modulators of GABA A (increase efficacy/ duration of opening) Topiramate: distinct modulator of GABA A

describe the mechanism of gabapentin and pregabalin and an additional thing they are used to treat

Bind a2dsubunit of voltage-operated Ca2+ channels and blocks (Anti seizure activity is most likely to decrease presynaptic release of glutamate) they are analgesics approved for nerve pain

describe the mechanism of Levetiracetam and Brivaracetam

bind synaptic vesicle protein SV2A and modify release of neurotransmitter (has clear anti-seizure efficacy)

Perampanel: monotherapy for what category of seizures? add on therapy for what category of seizures? drug class?

-Monotherapy for partial seizures -Add on therapy for generalized seizures -noncompetitive AMPA receptor antagonist

Felbamate: used for what category of seizures? what are the issues with this drug? when is it used for seizures?

partial seizures Causes high rate of aplastic anemia and severe hepatitis as a third-line drug for refractory cases

CBD: used for what category of seizures?

first in class for rare pediatric epilepsy syndromes

which 2 drugs block T-type Ca2+channels? what does the "T" mean?

Ethosuximide Valproate T = Low Voltage Activated Channel

what are the typical Anti-epileptic drug (AED) side effects?

drowsiness, fatigue/mental slowing, dizziness, blurred vision, mood changes, and Many idiosyncratic (individualistic) reactions (rash, gingival hyperplasia (oral condition that causes your gums to overgrow), bone density loss, hepatotoxicity

Vigabatrin has an FDA black box warning for what reason?

can cause permanent vision loss

what is a specific side effect lamotrigine may cause?

life-threatening skin rash

T/F AED may increase the risk of suicidal thoughts and changes in behavior

true

how do AED effect contraception?

increased oral contraception failure rate

what are the warnings of using AED during pregnancy?

Greater incidence of congenital defects