Pharm of Epilepsy Flashcards
What are the excitatory neurotransmitters?
Glutamate and Aspartate
What neurotransmitter is inhibitory on neurons?
GABA
Explain the different states of the Voltage Na Channel
- Resting state- Activation gate closed; inactivation gate open
- Open state- both open and Na depolarizes cell
- Fast-Inactivation state- Inactivation gate closes but activation gate is open (refractory period)
- Inactivated Closed state- both closed
Which Na blockers prolong the fast inactivation state?
Carbamazepine Lamotrigine Phenytoin Topiramate Valproic Acid Lacosamide
Which Na blocker additionally can bind to the Na gate even in the closed state?
Lacosamide
AMPA receptor antagonists
Topiramate
Perampanel
Explain why blocking the AMPA receptor works to treat status epilepticus
Prevents glutamate from binding AMPA and allowing influx of Na (and Ca) into post synaptic neuron
NMDA receptor antagonist
Felbamate
Same MOA as AMPA antagonists
What type of seizure is treated with T-Type Ca2+ channel blocker?
Absence (petit mal) seizures
T-Type Ca2+ channel blockers
Ethosuximide
Zonisamide (additionally is a Na blocker)
SV2A Protein inhibitors
Levetiracetam
Brivaracetam
T-type Ca2+ channel a2d subunit blockers
Gabapentin
Pregabalin
Why does blocking the T-type Ca2+ channel work to suppress glutamate excitatory actions?
Once a neuronal signal reaches the pre-synaptic knob, depolarization allows Ca2+ into the knob which directs vesicles of glutamate to be released into the synaptic junction.
KCNQ Channel activator and MOA
Ezogabine
Hyperpolarizes presynaptic and post synaptic neuron to prevent release of Glutamate
Explain how GABA works to inhibit a neuronal signal
GABA is released from the presynaptic neuron.
It binds the B-subunit of the GABA receptor and allow efflux of Cl- which hyperpolarizes the post-synaptic neuron.
How is GABA made?
L-glutamate is converted to GABA via Glutamic Acid decarboxylase
What stimulates GAD (glutamic acid decarboxylase) and enhances inhibitory effects of GABA?
Valproic Acid
Gabapentin
Pregabalin
2 enzymes that breakdown GABA
GABA-T
SSD
GABA-T antagonists
Valproic Acid
Vigabatrin
SSD antagonist
Valproic Acid
What drug blocks the reuptake of GABA by GAT-1 in order to potentiate its effects?
Tiagabine
2 classes of drugs that enhance post-synaptic GABA-ergic transmission
- Barbiturates
2. Benzodiazepines
What is the most important difference between Benzo’s and Barbiturates?
Barbiturates are GABA-independent and therefore more lethal in toxicity
Common Benzos
- Lorazepam
- Diazepam
- Clonazepam
- Clobazam
Benzo MOA
Binds to allosteric site on GABA receptor and potentiates the Cl- efflux by allowing quicker recovery of the channel so it can open more frequently.
Barbiturate MOA
Binds allosteric site on GABA receptor WITHOUT GABA present and holds Cl- channel open
Name the 3 MOA of Topiramate
- Na blocker
- AMPA antagonist
- GABA receptor agonist
Name the 3 MOA of Valproic Acid
- Na blocker
- GAD stimulation (more GABA)
- GABA-T blocker (block reuptake)
Name the 2 MOA of Gabapentin and Pregabalin
1 a2d Ca channel blocker
2. GAD stimulator
2 syndromes associated with Cannabidiol
- Dravet Syndrome
2. lennox-gastaut syndrome
Black box warnings for all AEDs
- Abrupt withdrawal can cause seizures
2. Suicidal Ideation
Side effect of Phenytoin
Follow zero-order kinetics so can easily OD CYP inducer Gingival Hyperplasia Hypothyroidism Hypocalcemia
AED’s associated with osteopenia/osteoporosis
Carbamazepine
Phenytoin
Phenobarbital
Valproic acid
Carbamazepine side effects
CYP inducer
Bone Marrow suppression (get baseline CBC)
Vigabatrin Side effects
Loss of Vision
3 categories of drug-drug interactions to watch for with CYP inducing AED’s
- OCP
- Anticoags
- Antivirals (HIV meds)
Valproic acid and Lamotrigine inhibit what enzyme leading to increased concentration of other drugs?
UGT
What AED’s cause increased UGT activity and therefore increased clearance of drugs?
Phenobarbital
Phenytoin
CBZ
Standard of Care for a status epilepticus
- Benzo (Lorazepam)
2. SV2a blocker (Levetiracetam)
