Anti-seizure Drugs Flashcards Preview

Pharmacology > Anti-seizure Drugs > Flashcards

Flashcards in Anti-seizure Drugs Deck (19):

Two main categories of seizures

Partial (focus seizures)


2 types of generalized seizures

They affect the entire brain!
1. Tonic-clonic (grand mal)
2. Absence (petit mal) - looks like slow wave sleep


2 general mechanisms of seizures

Excitation (too much) - ionic inward Na/Ca currents, or glutamate
Inhibition (too little) - ionic inward Cl, outward K, GABA


3 mechanisms of antiepileptic drugs

Suppress the formation or spread of abnormal electrical discharges by:
1. Blocking ion channels (Na, Ca)
2. Enhance the action of GABAergic neurotransmission
3. Diminish the action of excitatory glutaminergic transmission (block NMDA or AMPA receptors)


Mechanism of drugs that block Na channels

Channels open when neuron is activated - causes depolarization
The Na channel is inactivated by closure of the inactivation gate
The inactivation gate must be opened before the next AP can occur
Drugs that block these channels prolong the inactivation state of the channel and increase the refractory period of the neuron (ones that bind the inactivate state have the most effect)


3 examples of Na channel blockers

Valproic Acid


Phenytoin (what is it used to treat and how does it work)

Used to treat tonic-clonic and partial seizures
Reduces sustained high frequency neuronal firing by binding to inactivated Na channels
Also effects Ca channels and inhibits the release of NTs and hormones
Can decrease the release of glutamate and increase release of GABA


Phenytoin PK/PD

Variable bioavailability due to differences in first pass mechanism
Elimination kinetics shift from first order to zero order at moderate-high doses (from little change in plasma concentration to massive change)
There are drug drug interactions


(what are they structurally similar to, how do they work, what do they treat)

Structurally related to tricyclic ADs
Reduces high frequency neuronal firing
Treats tonic-clonic and partial seizures
Blocks Na channels


Drugs that block Ca channels

Blockage of T-Type Ca channels in thalamic neurons blocks the rhythmic cortical discharge observed in absence seizures


Mechanism of Barbiturates on GABAa receptors

Bind to receptors at allosteric site
Prolong GAGA mediated chloride channel openings
Low concentrations: potentiate GABA that is there
High concentrations: direct agonist actions
Some blockage of VDSCs


Mechanism of BZs on GABAa receptors (and 2 examples of drugs)

Allosteric modulators of GABAa receptors
Increase frequency of GABA mediated Cl channel openings
1. Clonazepam - used to treat absence and myotonic seizures
2. Diazepam - used for status epileticus (recurrent tonic clonic seizures)


Enzyme that terminates the action of GABA

GABA transaminase


Depolarization shift

Prolongation of AP in postsynaptic nerve



Causes the depolarization of other neighbouring neurons too



Blocks voltage dependent Na channels firing at high frequencies
Antagonizes glutamate action at AMPA/KA receptors



Blocks voltage dependent Na channels at high firing frequencies
Modulates NMDA receptor (no depolarization shift)


NMDA channels

Need a strong depolarization via AMPA receptor in order to remove the Mg block and then get depolarization
Causes synaptic memory - get depolarized again and it is very fast


Toxicity of anti-seizure drugs

Overdose toxicity (most are CNS depressants so can get respiratory depression at high doses - also additive effects with other CNS depressants)
Teratogenicity (valproic acid associated neural tube defects, carbamazepine assocaited craniofacial abnormalities/spina bifida, phenytoin associated fetal hydrantoin syndrome)