Epilepsy drugs

Question 1

Carbamazepine

Answer 1

METHOD OF ACTION:
- inhibits voltage sensitive Na+ channel opening and thus repetitive firing of APs in neurones reducing glutamate release.
- decreases glutamate binding to NMDA & AMPA receptors.
ADVERSE EFFECTS:
- >10% –> dizziness, sedation, dizziness, fatigue, leukopenia, nausea, vomiting.
- 1-10% –> double vision (diplopia), accommodation disorder, dry mouth, oedema, weight gain
- CYP interactions

Question 2

Phenytoin

Answer 2

METHOD OF ACTION:
- inhibits voltage sensitive Na+ channel opening thus repetitive firing of APs in neurones reducing glutamate release.
- Also decreases Ca2+ channel opening
ADVERSE EFFECTS:
- vertigo, ataxia, headache, nystagmus
- Hyperplasia of the gums, hirtuism & coarsening of features.
- at higher doses confusion with intellectual disorientation.
- CYP450 inducer.

Question 3

Levetiracetam (Keppra)

Answer 3

MECHANISM OF ACTION:
- binds to synaptic vesicle protein 2A (SV2A) located in membranes of synaptic vesicles, and consequently reduces exocytotic vesicle release of glutamate.
ADVERSE EFFECTS:
- somnolence, dizziness, nervousness, decreases haematocrit and WBCs, depression.

Question 4

lamotrigine

Answer 4

MECHANISM OF ACTION:
- potentiates GABA by inhibiting GABA transaminase & succinic semialdehyde dehydrogenase.
- reduces voltage sensitive Na+ (and Ca2+) channel opening reducing glutamate release.
ADVERSE EFFECTS:
- somnolence (20%), asthenia (24%), headache (17%), dizziness (14%), Rash (14%), Nausea (10%)

Question 5

sodium valproate (Epilim)

Answer 5

MECHANISM OF ACTION:
- Increases GABA levels via enhancing GABA synthesis, inhibiting GABA metabolism and possibly inhibiting GABA reuptake.
- reduces sensitive Na+ channel opening (weakly) and therefore reduces glutamate release
- reduces glutamate binding to AMPA & NMDA receptors
- inhibits T type Ca2+ channels –> used in absence seizures
- inhibits GSK-3 like Li+, (can be used for bipolar disorder.) meaning it may be neuroprotective.
ADVERSE EFFECTS:
- GI disturbances
- somnolence, potentiates effects of alcohol
- appetite stimulation & weight gain, thinning of hair, ankle swelling.
- inhibits CYP450

Question 6

zonisamide

Answer 6

MECHANISM OF ACTION:
- reduces voltage sensitive Na+ channel opening therefore reducing repetitive firing of APs and glutamate release.
- Also decreases T type Ca2+ channel opening (good for abscence seizures).
- Antagonism at kainate/AMPA receptor sites (non NMDA excitatory receptors).
ADVERSE EFFECTS:
- Drowsiness (17%), Loss of apetite (13%), headache (10%), agitation/irritability (9%), Nausea (9%), fatigue (8%).