IP7 EXAM 1- GABA Modulators/Glutamate Signaling Inhibitors/Ca2+ Channel Blockers

What AEDs are GABA modulators?

Phenobarbital, Lorazepam, Diazepam, Midazolam, Clonazepam, Chlorazepate

Binding to GABA causes what?

influx of Cl- which triggers depolarization

What is different about Phenobarbital when comparing them to the other GABA modulators (benzodiazepines)?

Can cause influx of Cl- without binding to GABA

What are the benzodiazepines that are GABA modulators?

Lorazepam, Diazepam, Midazolam, Clonazepam, Chlorazepate

What is the MOA of GABA modulators?

allosterically binds to GABA, which promotes the opening of the Cl- channel, which leads to hyper polarization of the neuron

Clonazepam brand name

Klonopin

Chlorazepate brand name

Tranxene

When are Clonazepam and Chlorazepate indicated in seizures?

long term treatment of seizures

Lorazepam brand name

Ativan

Diazepam brand name

Valium, Diastat

Midazolam brand name

Versed

When are Lorazepam, Diazepam, and Midazolam indicated in seizures?

short term, status epilepticus

What is the boxed waring for the benzodiazepines?

avoid use with opioids, may cause respiratory depression--> death

What barbiturates are used in epilepsy?

Phenobarbital

Phenobarbital brand name

Luminal

When is phenobarbital indicated?

narrow spectrum, used in status epilepticus

What is a special trait of phenobarbital?

auto-inducer, dose changes often

Can you combine phenobarbital with other AEDs?

No

What AEDs inhibit glutamate signaling?

Levetiracetam

Levetiracetam brand name

Keppra

How does Levetiracetam stop glutamate signaling?

binds to the presynaptic vesicle protein SV2A, inhibits glutamate signaling

What does Levetiracetam also inhibit?

N-type Ca2+ channels

How is Keppra metabolized?

95% renal, amide hydrolysis

What are the idiosyncratic side effects of Levetiracetam?

increase in suicidal thoughts, psychosis, SJS/TENS

What AED blocks Ca2+ channels?

Ethosuximide

Ethosuximide brand name

Zarontin

What is the MOA of Ethosuxumide?

Block post-synaptic T-type Ca2+ channels in thalamic neurons

When is Ethosuximide indicated?

first line therapy for absence seizures