Pharmacology of anticonvulsants

Question 1

What are examples of anticonvulsants?

Answer 1

• Lamatrogine
• Sodium valproate
• Diazepam
• Levetiracetam

Question 2

What is the primary mechanism of action of Lamotrigine?

Answer 2

Blocks voltage gated Na+ channels -> prevents Na+ influx

Prevents depolarisation of glutamatergic neurones and reduces glutamate excitotoxicity

Question 3

What is the drug target for Lamotrigine?

Answer 3

Voltage gated Na+ channels

Question 4

What are the side effects of Lamotrigine?

Answer 4

Common: Rash, drowsiness

Less common but serious:
Steven-Johnson’s syndrome, suicidal thoughts

Question 5

What is key ro reducing the frequency and severity of allergic skin reactions?

Answer 5

Introducing lamotrigine gradually

Question 6

What is the target of sodium valproate?

Answer 6

GABA transaminase

Question 7

What is the primary mechanism of action of sodium valproate?

Answer 7

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 metanolism of GABA is slowed which also slows GABA removal from the synapse.

Question 8

What are the side effects of sodium valproate?

Answer 8

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

Serious:

hepatotoxicity, teratogenicity, pancreatitis

Question 9

What is the drug target of diazepam?

Answer 9

Benzodiazepine site on the GABA A receptor

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.

Question 11

What are the side effects of diazepam?

Answer 11

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

Uncommon but serious:

Haemolytic anaemia, jaundice



Question 12

Why is diazepam not used lon term?

Answer 12

development of tolerance

Question 13

What is the target for levetiracetam?

Answer 13

Synaptic vesicle protein SV2A

Question 14

What is the primary mechanism 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

Question 15

What are the side effects of levetiracetam?

Answer 15

dizziness, somnolence, fatigue and headache

Question 16

Why is levertiracetam favorable?

Answer 16

Has no effect on the cytochrome P450 enzyme system so it is favorable in terms of no drug–drug interactions.

Question 17

What is the key to reducing frequency of allergic reactions in lamotrigine?

Answer 17

Gradual introduction

Question 18

What effect can sodium valproate have on other drugs?

Answer 18

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

Question 19

Why is diazepam not used for long term seizure suppression?

Answer 19

Development of tolerance

Question 20

What is the risk with diazepam?

Answer 20

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