CNS Anti-Seizure Drugs - Kelly 6 Flashcards Preview

Pharmacology 3001 > CNS Anti-Seizure Drugs - Kelly 6 > Flashcards

Flashcards in CNS Anti-Seizure Drugs - Kelly 6 Deck (21)
1

Seizures

Episodes of abnormal electrical activity in the brain that cause involuntary movements, sensations or thoughts
May result from head trauma, broke, brain tumours, hypoxia, fever, brain infections and other conditions
Caused by synchronous neuronal discharged within seizure focus point, may spread

2

Epilepsy

Recurrent seizures that cannot be attributed to any proximal cause

3

Partial seizures

Focal

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Generalized seizures

Spread

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Cellular mechanisms of seizure generation

Excitation: ionic inward Na and Ca currents, Glutamate
Inhibition: ionic inward Cl and outward K, GABA

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Mechanisms of anti-epileptic drugs

1. Block ion channels
2. Augment action of GABAergic neurotransmission
3. Diminish action of excitatory glutaminergic transmission

7

Drugs that block Na channels

Voltage-sensitive Na channels rapidly open when membrane reaches threshold
Rapid depolarization, and NT release
Prolong inactivation state of the Na channel and increase the refractory period of the neutron
Have most effect on neurons that are firing repetitively and less effect on normal neurotransmission
Phenytoin, carbamazepine, valproic acid

8

Phenytoin

Used to treat tonic clonic seizures and partial seizures
Reduces sustained high frequency neon firing by binding to inactivated Na channels
Effects Ca channel
Inhibits the release of NT
Decreases release of glutamate and increases GABA
Variable bioavailability (first pass effect)
Elimination kinetics shift from first order to zero order at moderate to high doses
At higher concentrations, small changes in dose can produce larger changes in phenytoin concentrations

9

Carbamazepine

Prevent opening of Na channels
Closely related in structure of tricyclic antidepressants
Reduces high frequency neuronal firing
Used to treat tonic-clonic and partial seizures

10

Drugs that block Ca channels

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

11

Absence seizure

Caused by self-sustained cycle of activity generated between thalamic and cortical cells
Treated by ethosuximde and valproic acid which book T-Type Ca channels

12

Benzodiazepines

Enhance GABA activation of the GABA-chloride ionophore
Bind to different sites on the ionophore, facilitating GABA binding and increased frequency/duration of channel opening
Leads to hyper polarization and counteracts the depolarization effect of excitatory neurotransmission

13

Barbiturates

Bind to GABA receptors on allosteric site
Prolong GABA-mediated Cl channel openings
Potentiate GABA actions at GABA receptors at low concentrations
Have direct agonist actions at higher concentrations
Some blockade of VD Na channels

14

Clonazepam

BZ used in treatment of absence seizures and mythic seizures

15

Diazepam

BZ
Used intravenous for Status epilepticus

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GABA transaminase

Terminates actions of GABA
Inhibition of GABA transaminase increases levels of GABA
Blockade og GABA transporters in neurons and glia increases levels of GABA in the synaptic cleft

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Diminish action of excitatory glutaminergic transmission

Block NMDA or AMPA receptors

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Topiramate

Blocks voltage-dependent Na channels at high firing frequencies
Antagonizes glutamate action at AMPA/kainate receptor subtype

19

Felbamate

Blocks voltage dependent Na channels at high firing frequencies
Modulates NMDA receptor
Depolarization that allows receptor to be activated

20

Toxicity

Most AEDs are CNS depressants and at high doses, respiratory depression may occur
May be additive with other CNS depressants
Teratogenicity

21

Teratogenicity

Valproic acid associated neural tube defects
Carbamazepine associated craniofacial abnormalities and spina bifida
Phenytoin associated fetal hydrantoin syndrome