core drugs of epilepsy

Question 1

what are the main drugs used?

Answer 1

lamotrigine
sodium valproate
diazepam
levetiracetam

Question 2

what is the primary mechanism of action of lamotrigine?

Answer 2

Blocks voltage gated Na+ channels, preventing Na+ influx.
Prevents depolarisation of glutamatergic neurones and reduces glutamate excitotoxicity
reduces excitatory activity

Question 3

what is the target if lamotrigine?

Answer 3

Voltage gated Na+ channels

Question 4

what are the main side effects of lamotrigine?

Answer 4

Common: Rash, drowsiness


Less common but serious:

Steven-Johnson’s syndrome, suicidal thoughts

Question 5

what are some facts about lamotrigine?

Answer 5

Introducing lamotrigine gradually is one of the keys to reducing the frequency and severity of allergic skin reactions.

In 2020 – Lamotrigine was the 94th most commonly prescribed drug in West London area

Question 6

what is the primary mechanism of action of sodium valproate?

Answer 6

Inhibition of GABA transaminase prevents the breakdown of GABA.
This increases GABA concentrations directly in the synapse presynaptically and also indirectly prolongs GABA in the synapse, due to the fact that extraneuronal metabolism of GABA is slowed which also slows GABA removal from the synapse.

increases inhibitory activity

Question 7

what is the target of sodium valproate?

Answer 7

GABA transaminase

Question 8

what are the side effects of sodium valproate?

Answer 8

(MANY):

Common: Stomach pain and diarrhoea, drowsiness, weight gain, hair loss

Serious:
hepatotoxicity, teratogenicity, pancreatitis

Question 9

what are some facts about sodium valproate?

Answer 9

Broad CYP enzyme inhibitor - increases serum concentration of many co-administered drugs

In 2020 – Sodium valproate was the 78th most commonly prescribed drug in West London area

Question 10

what is the primary mechanism of action of diazepam?

Answer 10

Increases choride ion influx in response to GABA binding at the GABA A receptor.
Increased chloride ion influx associated with hyperpolarisation of excitatory neurones.

so increases inhibitory activity

Question 11

what is the target of diazepam?

Answer 11

Benzodiazepine site on the GABA A receptor

Question 12

what are side effects of diazepam?

Answer 12

Common: Drowsiness, respiratory depression (if i.v. or at high dose)

Uncommon but serious:
Haemolytic anaemia, jaundice



Question 13

what are some facts about diazepam?

Answer 13

Main reason that diazepam is not used for long term suppression of seizures is due to the development of tolerance.

Diazepam is a Schedule 4 controlled drug - addiction prone individuals more likely to become dependent on diazepam.

In 2020 – Diazepam was the 61st most commonly prescribed drug in West London area

Question 14

what is the primary mechanism of action of Levetiracetam?

Answer 14

Inhibition of the synaptic vesicle protein SV2A.
It inhibits this protein and prevents vesicle exocytosis.
A reduction in glutamate secretion is reduces glutamate excitotoxicity

prevents glutamate release from vesicles. decreases excitatory activity

Question 15

what is the target of Levetiracetam?

Answer 15

Synaptic vesicle protein SV2A

Question 16

what are the side effects of Levetiracetam?

Answer 16

Common:

dizziness, somnolence, fatigue and headache

Question 17

what are some facts about Levetiracetam?

Answer 17

The metabolism of levetiracetam has no effect on the cytochrome P450 enzyme system so it is favorable in terms of no drug–drug interactions.

In 2020 – Levetiracetam was the 74th most commonly prescribed drug in West London area