Epilepsy and Anti-Epileptic Drugs

Question 1

What is a paroxysmal depolarising shift and what is its cause?

Answer 1

Sustained suprathreshold depolarisation - due to Na+ and Ca2+ entry - Ca2+ entry causes K+ channel opening - prolonged afterhyperpolarisation after PDS - failure of Ca2+-dependent K+ current in transition from PDS to seizure

Question 2

Which traditional drugs are used to inhibit voltage-gated Na+ channels in PDS?

Answer 2

Phenytoin
Carbemazepine
Valproate

Question 3

Which traditional drug is used to block voltage-gated Ca2+ channels in PDS?

Answer 3

Ethosuximide

Question 4

What is the action of valproate?

Answer 4

Inhibits GABA transaminase - prevents GABA breakdown

Blocks Na+ channels

Question 5

Which newer AEDs are used to block voltage-gated Na+ channels?

Answer 5

Lamotrigine

Topiramate

Question 6

What is the action of felbamate?

Answer 6

Blocks glycine site of NMDARs - not used clinically

Question 7

What is the action of perampanel?

Answer 7

Non-competitive AMPAR antagonist

Question 8

What is the action of leveritacetam?

Answer 8

Decreases glutamate release - synaptic depression

Question 9

What is the action of tiagabine?

Answer 9

Selective GAT-1 inhibitor - prevents GABA reuptake into pre-synaptic terminal and glial cells

Question 10

What is the 1st line drug for partial seizures?

Answer 10

Carbemazepine

Question 11

What is the 1st line drug for generalised tonic-clonic seizures?

Answer 11

Valproate

Question 12

What is the 1st line drug for generalised absence seizures?

Answer 12

Ethosuximide

Question 13

What is the 1st line drug for status epilepticus?

Answer 13

Clonazepam

Question 14

What is a disadvantage of carbemazepine?

Answer 14

Affects enzyme activity - changes oral contraceptive metabolism

Question 15

What is a disadvantage of valproate?

Answer 15

Developmental toxicity - use lamotrigine in women of childbearing potential