Anti-Epileptics

Question 1

What are the 2 main therapeutic mechanisms of anti-epileptics

Answer 1

• Voltage-gated sodium channel blockers

- Enhancement of GABA-mediated transmission

Question 2

Give 3 examples of voltage-gated sodium channel blockers

Answer 2

• Carbemazepine
• Lamotrigine
• Phenytoin

Question 3

What is the mechanism of action of voltage-gated sodium channel blockers?

Answer 3

• Enter cell and bind to VGSC from inside
• Can only bind when channels are open
• Once bound, prolong inactivated state - prevent repetitive APs and prevent their spread

Question 4

What is Carbemazipine used for?

Which other drug shares these uses?

Answer 4

Generalised tonic-clonic seizures, but not absence
All partial seizure types
Phenytoin

Question 5

Why is Lamotrigine a particularly useful VGSC blocker (3 reasons)

Answer 5

• Covers all seizure types, including absence seizure
• Ok in pregnancy
• Fewer DDIs than others as not a CYP inducer

Question 6

Why does Carbemazipine’s half-life decrease after prolonged use?

Answer 6

Induces its own metabolism

Question 7

What is important about Carbemazepine in terms of DDIs?

Answer 7

Induces CYP450 - decreases efficacy of many other drugs, including OCP

Question 8

Give 4 DDIs associated with Carbemazepine use

Answer 8

• CNS - dizziness, tingling
• GI upset
• Rashes
• Neutropenia

Question 9

Give 3 ADRs associated with phenytoin use

Answer 9

• Gingival hyperplasia
• Rashes
• CNS - dizziness

Question 10

Give 2 reasons why phenytoin is associated with lots of DDIs

Answer 10

• Highly protein bound - can be displaced - increases level of phenytoin
• Also a CYP450 inducer

Question 11

How do you monitor phenytoin levels?

Answer 11

Saliva

Question 12

What is the theory behind drugs enhancing GABA transmission?

Answer 12

GABA is a natural anticonvulsant - inhibits excitation in brain by increasing chloride current in neurones and hence making cell hyperpolarised - harder for AP

Question 13

Give 2 examples of drugs which enhance GABA transmission. How do each of them do this in broad terms?

Answer 13

• Benzos - bind to GABA receptor

- Sodium valproate - alter GABA metabolism

Question 14

What are the Benzos used for?

Give 2 named examples

Answer 14

Status epilepticus

Lorazepam, Diazepam

Question 15

Give 4 ADRs of Benzodiazepines

Answer 15

• Sedation
• Tolerance/dependence
• Confusion
• Aggression

Question 16

How does sodium valproate interfere with GABA metabolism?

Answer 16

• Weak inhibition of GABA inactivation enzymes

- Weak stimulation of GABA-synthesising enzymes

Question 17

What can sodium valproate be used for?

Answer 17

All seizure types

Question 18

Give some ADRs of sodium valproate

Answer 18

• CNS - sedation
• Weight gain
• Liver dysfunction

Question 19

What happens if you use sodium valproate with:

• Antidepressants?
• Antipsychotics?

Answer 19

• Antidepressants - inhibit Valproate

- Antipsychotics - antagonist Valproate

Question 20

What happens if you use sodium valproate in pregnancy?

Answer 20

Neural tube defects

Question 21

Which anti-epileptic is safest in pregnancy?

Which dietary supplements are beneficial in pregnancy alongside this?

Answer 21

Lamotrigine
Folic acid - decreases risk of neural tube defects
Vit K - AEDs can cause vit K deficiency