Anti-epileptic Drugs

Question 1

What are anti-epileptic drugs used for?

Answer 1

• To restore excitatory - inhibitory balance
• To prevent/reduce frequency & severity of seizures in epilepsy

Question 2

Routes of anti-epileptic drugs administration

Answer 2

• oral
• IV

Question 3

True / False

Anti-epileptic drugs must be able to cross the blood-brain barrier to be effective.

Answer 3

True.

Question 4

Don’ts advice for anti-epileptic patients

Answer 4

• do not miss doses of epilepsy medicine
• do not change epilepsy treatment without advice from GP
• do not drink too much alcohol
• Important: DO NOT drive - inform DVLA

Question 5

5 mechanisms of Anti-epileptic drugs

Answer 5

1. Voltage-gated sodium channel inhibitors
2. Voltage-gated calcium channel inhibitors
3. GABA enhancing drugs
4. Anti-glutamate receptor drugs
5. Others

Question 6

Mechanism of action: Na⁺ channel inhibitors

Answer 6

Prolonge inactive state of Na⁺ channels → Reducing Na⁺ channel activity → hence, blocking entry of Na⁺ ions at pre-synaptic neurone → no action potential

Question 7

Examples of Na⁺ channel inhibitors

Answer 7

• phenytoin
• carbamazepine
• lamotrigine
• lacosamide
• topiramate

Question 8

Clinical use: Phenytoin

Answer 8

• focal seizures
• tonic-clonic seizures

❌ contraindicated in myoclonic

Question 9

Common side effects of Phenytoin

Answer 9

• gingival hyperplasia
• hirsutism
• dizziness
• nausea

Question 10

Severe side effects of Phenytoin

Answer 10

• Stevens-Johnson syndrome
  (flu-like symptoms + skin rash with blisters)
• Teratogenic

Question 11

Pharmacokinetics: Phenytoin

Answer 11

• narrow therapeutic index
• non-linear (i.e. large increase in plasma can cause toxicity)
• enzyme inducer (i.e. complex drug-drug interactions)

Question 12

Clinical use: Carbamazepine

Answer 12

• focal seizures
• generalised seizures

❌ contraindicated in myoclonic

Question 13

Common side effects of Carbamazepine

Answer 13

• dry mouth
• obesity
• dizziness
• nausea

Question 14

Severe side effects of Carbamazepine

Answer 14

• Stevens-Johnson syndrome
• Teratogenic

Question 15

Pharmacokinetics: Carbamazepine

Answer 15

• short half-life (hence take 3 times / day)
• enzyme inducer (drug-drug interactions)

Question 16

Clinical use: Sodium Valproate

Answer 16

• focal seizures
• generalised seizures

Question 17

Common side effects of Sodium Valproate

Answer 17

• GI symptoms (e.g. diarrhoea)
• weight gain
• amenorrhoea
• dizziness
• nausea

Question 18

Severe side effects of Sodium Valproate

Answer 18

Teratogenic !

• hepatotoxicity

Question 19

Pharmacokinetics: Sodium Valproate

Answer 19

• enzyme inhibitor
• well-tolerated within therapeutic window
• metabolised by liver

Question 20

Clinical use: Lamotrigine

Answer 20

• focal seizures
• absence seizures

✅ Non-Teratogenic

Question 21

Common side effects of Lamotrigine

Answer 21

• risk of osteoporosis
• dizziness
• nausea

Question 22

Severe side effects of Lamotrigine

Answer 22

Stevens-Johnson syndrome !

Question 23

Pharmacokinetics: Lamotrigine

Answer 23

• hepatic metabolism

Question 24

Clinical use: Lacosamide

Answer 24

• focal seizures
• combination therapy for tonic-clonic seizures

Question 25

Common side effects of *Lacosamide*

Answer 25

- vomiting - diarrhoea - dizziness

Question 26

**Severe** side effects of *Lacosamide*

Answer 26

- Stevens-Johnson syndrome - Suicidal ideation - Teratogenic

Question 27

Pharmacokinetics: *Lacosamide*

Answer 27

- minimal drug interactions - linear kinetics

Question 28

Clinical use: *Topiramate*

Answer 28

- focal seizures - absence seizures ✅ Non-Teratogenic

Question 29

Common side effects of *Topiramate*

Answer 29

- vomiting - diarrhoea - weight loss - dizziness

Question 30

**Severe** side effects of *Topiramate*

Answer 30

- renal stones - glaucoma - metabolic acidosis

Question 31

Pharmacokinetics: *Topiramate*

Answer 31

- enzyme inhibitor

Question 32

Examples of voltage-gated Ca²⁺ channel blockers

Answer 32

1. Ethosuximide 2. Pregabalin 3. Gabapentin

Question 33

Mechanism of action: *Ethosuximide*

Answer 33

Blocks T-type Ca²⁺ channels in thalamic neurones → reducing Ca²⁺ influx → decreasing neurone firing

Question 34

Clinical use: *Ethosuximide*

Answer 34

Absence seizures ✅ *Non-Teratogenic*

Question 35

Side effects of *Ethosuximide*

Answer 35

- headache - fatigue - GI upset - rash

Question 36

Mechanism of action: *Pregabalin* & *Gabapentin*

Answer 36

Binds to *alpha-2-delta* subunit of N-type Ca²⁺ channel → reducing neuronal transmission

Question 37

Clinical use: *Pregabalin* & *Gabapentin*

Answer 37

- focal seizures - neuropathic pain ❌ contraindicated in myoclonic

Question 38

Side effects of *Pregabalin* & *Gabapentin*

Answer 38

- dizziness - nausea - headache - weight gain

Question 39

Mechanism of action: **GABA-enhancing drugs**

Answer 39

bind to GABA-A receptor → increase activity of **GABA, a neurotransmitter that** promotes relaxation and reduces excitability in CNS

Question 40

Examples of **GABA-enhancing drugs**

Answer 40

- Barbiturates - Benzodiazepines - Z-class anxiolytic drugs *GABA-A receptor modulators*

Question 41

Examples of Benzodiazepines

Answer 41

- diazepam - lorazepam

Question 42

Clinical use: **GABA-enhancing drugs**

Question 43

Side effects of **GABA-enhancing drugs**

Question 44

**2** examples of **Anti-glutamate receptor drugs**

Answer 44

1. Felbamate 2. Perampanel