Pharmacology of Epilepsy

Question 1

What is the primary mechanism of action of Lamotrigine?

Answer 1

• Blocks VGSCs, preventing sodium influx
• Prevents depolarisation of glutamatergic neurons
• reduced glutamate excitotoxicity

Question 2

What is the drug target of Lamotrigine?

Answer 2

Voltage Gated Sodium Channels (VGSCs)

Question 3

What are the main side effects of Lamotrigine?

Answer 3

Common:
- rash
- drowsiness
Rare:
- Steven-Johnson's Syndrome
- Suicidal thoughts

Question 4

What can be done to prevent the frequency and severity of allergic skin reactions when taking Lamotrigine?

Answer 4

introducing it gradually

Question 5

What is the primary mechanism of action of Sodium Valproate?

Answer 5

• Inhibition of GABA transaminase, preventing the breakdown of GABA
• Increasing GABA concentration directly in the synapse, pre-synaptically
• Prolongs GABA in the synapse due to the extra-neuronal metabolism and removal being slowed

Question 6

What is the drug target of Sodium Valproate?

Answer 6

GABA transaminase

Question 7

What are the side effects of Sodium Valproate?

Answer 7

MANY
Common:
- stomach pain
- diarrhoea
- drowsiness
- weight gain
- hair loss
SERIOUS:
- hepatotoxicity
- teratogenicity
- pancreatitis

Question 8

Why should a broad CYP enzyme inhibitor be prescribed in conjunction with Sodium Valproate?

Answer 8

Increases the serum concentration of many co-administered drugs

Question 9

What is the primary mechanism of action of Diazepam?

Answer 9

• Increased Cl- influx to GABA binding to the GABA-A receptor
• hyperpolarisation of excitatory neurons

Question 10

What is the drug target of Diazepam?

Answer 10

Benzodiazepine site on the GABA-A receptor

Question 11

What are the side effects of Diazepam?

Answer 11

common:
- drowsiness
- respiratory depression (IV or high dose)
SERIOUS:
- hemolytic anaemia
- jaundice

Question 12

Why is Diazepam not used for the long term suppression of seizures?

Answer 12

• tolerance development

- Addictive, dependence likely (Schedule 4 controlled drug)

Question 13

What is the primary mechanism of action of Levetiracetam?

Answer 13

• Inhibition of the synaptic vesicle protein SV2A
• prevents vesicle exocytosis
• reduces glutamate secretion
• reduces glutamate excitotoxicity

Question 14

What is the drug target of Levetiracetam?

Answer 14

Synaptic Vesicle Protein, SV2A

Question 15

What are the common side effects of Levetiracetam?

Answer 15

• dizziness
• somnolence
• fatigue
• headache

Question 16

Why is Levetiracetam favorable?

Answer 16

• no effect on the cytochrome P450 enzyme system

- unlikely to have drug-drug interactions

Question 17

What is important to note when prescribing therapeutic drugs for seizures?

Answer 17

• must tell pateint, they CANNOT drive

- they MUST tell the DVLA

Question 18

Why does Lamotrigine cause drowsiness?

Answer 18

• acts on all presynaptic glutamate receptors
• non-specific
• slows down the whole brain
• depressant effect on the brain

Question 19

When can Sodium Valproate be prescribed to those of child-bearing age?

Answer 19

ONLY when prescribed by a neurologist

Question 20

Why can’t those of child-bearing age take Sodium Valproate?

Answer 20

teratogenic (reproductive toxicity)

Question 21

What is the treatment of epilepsy dependent on?

Answer 21

• type of seizure

- the individual patient

Question 22

What on an ECG can indicate an increased risk of seizure recurrance?

Answer 22

interictal epileptiform discharge (IED)

Question 23

What are the main aims of antiepileptic drug (AED) therapy?

Answer 23

• eliminate seizures (or reduce frequency)
• avoid the adverse effects of LT treatment
• aid patients to maintain/restore a normal lifestyle

Question 24

What must be done when Anti-Epileptic drug therapy is started?

Answer 24

must document advice to tell the DVLA that they cannot drive.

Question 25

What is the first line and adjunctive treatment for those with absence seizures? (NOT CHILDBEARING)

Answer 25

``` First line: - ethosuximide - sodium valproate Adjunctive treatment: combine 2 of: - ethosuximide - sodium valproate - lamotrigine ```

Question 26

What is the first line and adjunctive treatment for those with absence seizures? (CHILDBEARING)

Answer 26

``` First line: - ethosuximide Adjunctive treatment combine: - ethosuximide - lamotrigine ```

Question 27

What is the first line and adjunctive treatment for those with focal seizures? (NOT CHILDBEARING)

Answer 27

``` First line: - carbamazepine - lamotrigine Adjunctive treatment -any ```

Question 28

What is the first line and adjunctive treatment for those with focal seizures? (CHILDBEARING)

Answer 28

``` First line: - carbamazepine - levetiracetam Adjunctive treatment - any (NO SODIUM VALPROATE) ```

Question 29

What is the first line and adjunctive treatment for those with generalised tonic-clonic seizures? (NOT CHILDBEARING)

Answer 29

``` First line: -sodium valproate Adjunctive treatment: combine 2 of: - sodium valproate - levetiracetam - topirimate ```

Question 30

What is the first line and adjunctive treatment for those with generalised tonic-clonic seizures? (CHILDBEARING)

Answer 30

``` First line: - Lamotrigine - Carbamazepine Adjunctive treatment: combine: - levetiracetam - topirimate ```

Question 31

What is the first line and adjunctive treatment for those with myoclonic seizures? (NOT CHILDBEARING)

Answer 31

``` First line: - sodium valproate Adjunctive treatment: - clobazam - lamotrigine - levetiracetam - topirimate ```

Question 32

What is the first line and adjunctive treatment for those with myoclonic seizures? (CHILDBEARING)

Answer 32

``` First line: - levetiracetam - topiramate Adjunctive treatment: - clobazam - lamotrigine - levetiracetam - topirimate ```

Question 33

What is the first line and adjunctive treatment for those with tonic or atonic seizures? (NOT CHILDBEARING)

Answer 33

First line: - sodium valproate Adjunctive treatment: - lamotrigine

Question 34

What is the first line and adjunctive treatment for those with tonic or atonic seizures? (CHILDBEARING)

Answer 34

``` First line: - sodium valproate (WITH PREGNANCY PREVENTION PLAN) Adjunctive treatment: - lamotrigine ```

Question 35

What is the effect of sodium valproate with in utero exposure?

Answer 35

- neural tube defects - decreased IQ - autism

Question 36

What is the impact of the combined oral contraceptive on lamotrigine blood levels?

Answer 36

- co-administration leads to low lamotrigine blood levels - lamotrigine has no effect on blood ethinyl estradiol levels - reduced seizure control - NO contraceptive failure

Question 37

Why does the combined oral contraceptive have an effect on lamotrigine levels?

Answer 37

may: - reduce absorption - enhance metabolism - may enhance excretion

Question 38

How do you combat the effect of COC pill on lamotrigine?

Answer 38

- change AED or contraception OR - increase the dosage of lamotrigine

Question 39

What do drug-drug interactions tend to involve?

Answer 39

- changes to liver metabolism | - AED commonly effect other drugs