[PHARM] Pharmacology of Epilepsy [Segars] Flashcards
At the most basic level, what is the neuronal imbalance involved in epilepsy?
TOO MUCH glutamate, aspartate [excitation]
TOO LITTLE gaba [inhibition]
What are the (4) general MOAs of antiepileptic drugs?
- Suppress excitatory (glutamate) transmission
- Enhance inhibitory (GABA) transmission
- Block T-type Ca2+ channels
- Novel mechanisms
When are Na channel blockers most effective in exerting their effects?
Why does this make sense?
Most effective : Open state and Fast-inactivated state
If the activation gate is open, then the drugs can access the pore of the Na+ channel!
If the Na+ channel activation gate is OPEN… anti epileptic drugs __________
If the Na+ channel activation gate is CLOSED… anti epileptic drugs _________
If the Na+ channel activation gate is OPEN… anti epileptic drugs CAN access the pore
If the Na+ channel activation gate is CLOSED… anti epileptic drugs CANNOT access the pore
The probability of Na blockade is proportional to ___________________
The probability of Na blockade is proportional to the frequency of Nav channel opening and dose
What are the (6) drugs contained in the Na blockers that specifically prolong fast inactivation state?
Carbamazepine (oxcarbazepine/eslicarbasepine)
Lamotrigine
Phenytoin
Topiramate
Valproic acid
Lacosamide** (Zonisamide_, Rufin_amide**)
What is the one drug within the Na Blockers that prolong fast inactivation has an additional effect?
What is that effect?
Lacosamide
Enhance slow inactivation of Nav channels
What are the (2) AMPA receptor blockers?
Topiramate
Perampanel
What is the (1) NMDA receptor blocker?
Felbamate
What enzymes break down GABA endogenously?
GABA Transaminase : GABA-T
Succinic Semialdehyde Dehydrogenase : SSD
What is responsible for reuptake of GABA in the synaptic cleft?
GABA Transporter 1 (GAT-1)
What drugs (2) inhibits GABA-T?
Vigabatrin
Valproic acid
What drug inhibits GAT-1?
Tiagabine
What drug has dual action by inhibiting GABA-T AND SSD?
Valproic acid
GABA promoting agents
What are the (2) categories of pre-synaptic drugs?
GAT-1 inhibitor
GABA-T inhibitors
GABA Promoting agents
What is the (1) GAT-1 pre synaptic inhibitor?
Tiagabine
GABA promoting agents
What are the (2) GABA-T inhibitors?
Vigabatrin
Valproic acid
What are three classes of drugs that will enhance the post synaptic GABAergic neuronal transmisson?
- Barbiturates
- Benzodiazapines
- Topiramate