Neuro: Antiepileptic Drugs Flashcards
What neuronal imbalance causes seizures?
Glutamate/Aspartate overload= over-excitation
Need more GABA!
What state do Na-channel blockers work in? Open or closed?
Only in the open and inactivation; so it is state and use dependence
MOA of Lamotrigine
Prolong fast inactivation state of Na(v) ion channels
MOA of carbamazepine
Prolong fast inactivation state of Na(v) ion channels
MOA of penytoin
Prolong fast inactivation state of Na(v) ion channels
MOA of topiramate**
- Prolong fast inactivation state of Na(v) ion channels
- AMPA antagonist
- Activates GABAa receptor Cl channels on post-synaptic
MOA of Valproic acid***
- Prolong fast inactivation state of Na(v) ion channels
- Activates glutamic acid decarboxylase
- inhibits GABA transaminase and SSD
MOA of lacosamide**
- Prolong fast AND 2. slow inactivation state of Na(v) ion channels
different than other Na channel blockers
MOA of PerAMPAnel
Blocks the AMPA receptor
so Glutamate cannot excite the post-synaptic neuron
MOA of felbamate
NMDA receptor antagonist
so Glutamate cannot excite the post-synaptic neuron
What channels cause absence seizures?
T-type Ca+ channels in the thalamus
What wave types characterize absence seizures?
3-Hz spike and wave
-from T-type Ca channels
MOA of Ethosuximide
Blocks T-type Ca+ channels in Thalamus in Absence!
MOA of Zonisamide**
- Blocks T-type Ca+ channels in Thalamus
2. prolongs slow inactivation state of Na(v) ion channels
MOA of levetiracetam
inhibits synaptic vesicle 2A protein
-less Glutamate release
MOA of Brivaracetam
inhibits synaptic vesicle 2A protein
-less Glutamate release
MOA of Gabapentin**
- Blocks α2δ subunit of T-type Ca channels
2. Activates glutamic acid decarboxylase
MOA of Pregabalin**
- Blocks α2δ subunit of T-type Ca channels
2. Activates glutamic acid decarboxylase
MOA of ezogabine**
- KCNQ K+ Channel blocker on both pre- and post-synaptic
2. Activates GABAa receptor Cl channels on post-synaptic neurons
MOA of viGABATrin
Inhibits GABA transaminase
MOA of tiagabine
Inhibits GAT-1 reuptake channel
MOA of Benzodiazepines
Activates GABAa receptor Cl channels on post-synaptic neurons
MOA of Barbiturates (phenobarbitol)
Activates GABAa receptor Cl channels on post-synaptic
Suffix of all benzodiazapines
-azepam
Which GABAa receptor agonists are GABA independent?
Barbiturates
-simply bind and increase duration of Cl channel opening
Which Which GABAa receptor agonists are GABA dependent?
Benzodiazepine
-requires GABA in channel already and allows Cl to open more readily
What is a broad risk of all AEDs?
Abrupt withdrawl can cause status epilepticus
Suicidal behavior and ideation
Which drug is removed via Zero-order pharmacokinetics
Phenytoin
-saturable!
Which drugs are CYP450 and UGT conjugation inducers?
Phenytoin,
carbamazepine, and
phenobarbital
What two seizure syndromes may cannabidiol treat?
Lennox-Gastaut syndrome and Dravet syndrome
Adverse effects of Phenytoin (2)
Gingival hyperplasia
Hypocalcemia/osteoporosis
Adverse effects of carbamazepine
Agranulocytosis and aplastic anemia
-get CBC
What is unique about cabamazepines metabolism?
It induces auto-induction of Cyp450=self metabolism after 14 days
Why would you use oxcarbazepine instead of carbamazepine?
Does not generate the toxic epoxide that causes the aplastic anemia of carbamazepine
Adverse effects of Phenobarbitol
CNS depressant
Adverse effect of vigabatrin
Perminent concentric vision loss
What drugs inhibit conjugation by UGT?
Valproate and lamotrigine
=build up of drugs
What drugs are most affected use of CYP450 inducers (phenytoin,
carbamazepine, and
phenobarbital)?
Oral contraceptives
Anticoagulants (warfarin)
HIV Medications
How are the newer drugs cleared from the body?
Renal clearance
How do you initially treat status epilepticus? both first and second
1st IV: Lorazepam*
-oral midzaolam if no IV
2nd: Levetiracetam*, fosphenytoin, or valproate
