Epilepsy

Question 1

Phenytoin MOA

Answer 1

GLUTAMATE
- decrease voltage-sensitive Na channel opening -> decreased repetitive firing in depolarised neurones > decrease glut released

• decreased Ca chan opening
• may also have other effects

Question 2

Carbamazepine MOA

Answer 2

GLUTAMATE
- decrease voltage-sensitive Na channel opening -> decreased repetitive firing in depolarised neurones > decrease glut released

• Antag NMDA and AMPA receptors (post synaptic) > decrease glut binding

Question 3

Oxcarbazepine MOA

Answer 3

GLUTAMATE
- decrease voltage-sensitive Na channel opening -> decreased repetitive firing in depolarised neurones > decrease glut released

• MAY increase K conductance + modulate Ca channels

Question 4

Lacosamide MOA

Answer 4

GLUTAMATE
- decrease voltage-sensitive Na channel opening -> decreased repetitive firing in depolarised neurones > decrease glut released

• modulates CRMP-2 (involved in neuronal differentiation and axonal growth), mech unclear
  * MAY prevent aberrant synaptic connectivity and/or rearrangements seen in epilepsy.

Question 5

Zonisamide MOA

Answer 5

GLUTAMATE
- decrease voltage-sensitive Na channel opening -> decreased repetitive firing in depolarised neurones > decrease glut released

• decrease T type Ca channels opening
• antagonism at kainate/AMPA receptor sites

Question 6

Valproate MOA

Answer 6

GABA (mainly)

• increase GABA synth
• decrease GABA metabolism

GLUTAMATE (to some extent)

• decrease voltage-sensitive Na channel opening
• decrease glut binding to AMPA and NMDA
• inhibits T type Ca channels opening

OTHER
- inhibits GSK-3 (like lithium) - may be neuroprotective

Question 7

Lamotrigine MOA

Answer 7

Broad spectrum
GABA
- inhibits GABA metabolism

GLUTAMATE

• decrease voltage-sensitive Na and Ca channel opening
• **MAY AGGRAVATE SEIZURES IN PTS WITH SPECIFIC NA CHANNEL MUTATIONS

Question 8

Topiramate MOA

Answer 8

Broad spectrum
GABA
- enhances GABA binding at GABA-A receptors

GLUTAMATE

• decrease voltage-sensitive Na and Ca channel opening
• antag at kainate/AMPA receptor sites

Question 9

Felbamate MOA

Answer 9

Broad spectrum
GABA
- enhances GABA binding at GABA-A receptors

GLUTAMATE

• decrease voltage-sensitive Na and Ca channel opening
• antag at kainate/AMPA receptor sites

Question 10

Levetiracetam MOA

Answer 10

novel drug -potential as add on due to diff moa

SV2A

• main moa
• binds to presyn SV2A protein on memb of synaptic vesicles (thought to control vesicle exocytosis) > decrease exocytotic vesicle release > decrease neurotransmitter release
• *does not alter normal neurotransmitters, only decreases hippocampal excitation during repetitive stimulation

OTHER
- SOME evidence of GABA modulation and decrease Ca chan opening as well

Question 11

Gabapentin MOA

Answer 11

GLUTAMATE
- binds to alpha2delta subunit of voltage-gated Ca channels > decrease channel opening > decrease Ca influx

**LITTLE GABA activity

Question 12

Pregabalin MOA

Answer 12

GLUTAMATE
- binds to alpha2delta subunit of voltage-gated Ca channels > decrease channel opening > decrease Ca influx

**NO GABA activity

Question 13

Tiagabine MOA

Answer 13

GABA

• inhibits GABA reuptake > more GABA available for binding
• *NO glutamate effect

Question 14

Vigabatrin MOA

Answer 14

GABA

- inhibits GABA transaminase (responsible for inactivating GABA)

Question 15

Ethosuximide MOA

Answer 15

• inhibits T type Ca channels

* *really only used for absence seizures.