Antiepileptic Drugs Flashcards
Membrane depolarization leads to enhanced ________ receptor function & reduced _______ function. Epileptic seizures involve neurons firing at higher frequency than normal.
Membrane depolarization leads to enhanced excitatory (⬆︎ glutamate and aspartate) receptor function & reduced GABA function
4 mechanisms of AEDs (Anti-Epileptic Drugs)
- Supress excitatory (glutamate) transmission
- Enhance inhibitory (GABA) transmission
- Block low-threshold T-type Ca2+ channels
- Novel mechanism
How can we suppress excitatory (glutamate) transmission?
- Supress VGNav channels
- Supress ligand-gated AMPA/NMDA channels
Antiepileptic drugs that block pre-synaptic VGNa2+ by prolonging fast- inactivation state.
- 1-3) Carbamazepine, Oxcarbazepine, Eliscarbazepine
- 4-6) Lacosamide, Rufinamide, Zonisamide
- 7) Lamotrigine
- 8) Phenytoin
- 9) Topiramate
- 10) Valproic acid
![](https://s3.amazonaws.com/brainscape-prod/system/cm/302/343/718/a_image_thumb.png?1581572490)
Which AED is unique in that it can prolonging fast inactivationAND enhancing slow inactivation of VGNav2+ channels?
Lacosamide
![](https://s3.amazonaws.com/brainscape-prod/system/cm/302/343/824/a_image_thumb.png?1581575634)
AMPA-R ANT
MOA
- 1. Topiramate
- 2. Perampanel
MOA = bind to post-synaptic AMPA receptor and block glutamate binding; channel doesn’t open –> AP does not propogate downstream
![](https://s3.amazonaws.com/brainscape-prod/system/cm/302/343/871/a_image_thumb.png?1581572441)
NMDA-R ANT
MOA
Felbamate
- MOA = bind to post-synaptic NMDA-R and block glutamate binding; channel doesn’t open –> AP does not propogate downstream
![](https://s3.amazonaws.com/brainscape-prod/system/cm/302/344/032/a_image_thumb.png?1581572523)
Describe VGNa channels during depolarization
-
Resting state:
- Activation gate = CLOSED,
- Inactivation gate = OPEN
-
Open state:
- Both gates OPEN
-
Fast-inactivated state (cannot be reactived)
- Activation gate = OPEN
- Inactivation gate = CLOSED
-
Inactivated-closed state
- Both gates CLOSED
![](https://s3.amazonaws.com/brainscape-prod/system/cm/302/345/298/a_image_thumb.png?1581573702)
The pharmacological activity of AED Nav channel blockers is _______ and ________-dependent
State and Use-dependent
AED’s binding site is at the _________ side Nav channel ‘pore’
Inside; activation gate must be open
![](https://s3.amazonaws.com/brainscape-prod/system/cm/302/344/184/a_image_thumb.png?1581572644)
- If the _________ gate is open, AEDs can NTR pore and bind.
- Which states can this occur?
- Activation gate
- Open state and Fast-inactivated state
![](https://s3.amazonaws.com/brainscape-prod/system/cm/302/344/251/a_image_thumb.png?1581573920)
Why do the AED’s that are VGNav+ blockers act preferentially on the neurons involved in epileptic seizures?
The probability of Na+ blockade is proportional to FREQUENCY of Nav channel opening and dose, The neurons involved in epilepsy will be firing at ⬆︎ frequency than normal, allowing more chances for these drugs to slip right in and bind
How can we enhance inhibitory (GABA) transmission?
- Presynaptic: Block GABA reputake or metabolism
- Post-synaptic: Poteniate GABA-A-R Cl-currents
- Nothing bound to GABAA -R = ____________.
- Binding to GABAA–R = ______________.
- Nothing bound to post-synaptic GABAA -R = inactive Cl- channel closed.
- Binding to post-synaptic GABAA–R = Cl- channel opens => hyperpolization = ⬇︎ AP propagation
![](https://s3.amazonaws.com/brainscape-prod/system/cm/302/347/477/a_image_thumb.png?1581577087)
MOA of the AED, Tiagabine?
- Blocks pre-synaptic reuptake of GABA by blocking the GABA transporter, GAT-1 =>⬆︎ GABA => bing to post-synaptic GABAA-R => hyperpolarization => ⬇︎ AP propogation
![](https://s3.amazonaws.com/brainscape-prod/system/cm/302/347/910/a_image_thumb.png?1581577336)
MOA of Valproic Acid
- ⬆︎ activity of glutamic acid decarboxylase => ⬆︎ presynaptic GABA
- Inhibit GABA-T, which typically metabolizes GABA
- Inhibit SSD (Succinic Semialdehyde Decarboxylase), which typically metabolized GABA
- *T-type Ca2+ channel ANT
- Prolongs fast inactivation of Na channels
![](https://s3.amazonaws.com/brainscape-prod/system/cm/302/347/969/a_image_thumb.png?1581577532)
MOA of Vigabatrin
- Inhibit GABA-T => prevents metabolism of GABA
![](https://s3.amazonaws.com/brainscape-prod/system/cm/302/348/134/a_image_thumb.png?1581577608)
Which 2 AED’s inhibit the metabolism of GABA by inhibiting GABA-T?
1. Valproic acid
2. Vigabatrin
Post-synpatic GABA-A AGO (enhance transmission)
MOA of each
-
Barbituates (PB) (phenobarbital & primidone)
- Bind to allosteric site on GABA-A R => ⬆︎ DURATION of Cl- channel opening
-
Benzos (Lorazepam, Diazepam, Clonazepam)
- Bind to allosteric site on GABA-A-R => potentiate effects of GABA by ⬆︎ FREQUENCY of Cl- channel opening
- Topiramate
![](https://s3.amazonaws.com/brainscape-prod/system/cm/302/348/144/a_image_thumb.png?1581577741)
Which drug in the barbiturate family gets metabolized to phenobarbital in the body?
Primidone