Pharma - Epilepsy

Question 1

What is the primary mechanism of action of lamotrigine?

Answer 1

→ Blocks voltage gated Na+ channels preventing Na+ influx.

→ Prevents depolarisation of glutamatergic neurones and reduces glutamate excitotoxicity

Question 2

What is the drug target of lamotrigine?

Answer 2

Voltage gated Na+ channels

Question 3

What are the side effects of lamotrigine?

Answer 3

Common: 
→ Rash
→ Drowsiness
Less common but serious:
→ Steven-Johnson's syndrome
→ suicidal thoughts

Question 4

How are the side effects of lamotrigine managed?

Answer 4

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

Question 5

What is the primary mechanism of action of sodium valproate?

Answer 5

→ Inhibition of GABA transaminase prevents the breakdown of GABA.
→ This increases GABA concentrations directly in the synapse presynaptically
→ 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 6

What is the drug target for sodium valproate?

Answer 6

GABA transaminase

Question 7

What are the side effects of sodium valproate?

Answer 7

Common: 
→ Stomach pain
→ diarrhoea
→ drowsiness
→ weight gain
→ hair loss
Serious:
→ hepatotoxicity
→ teratogenicity
→ pancreatitis

Question 8

What is an unprecedented side effect of sodium valproate?

Answer 8

→ Broad CYP enzyme inhibitor

→ increases serum concentration of many co-administered drugs

Question 9

What is the primary mechanism of action of diazepam?

Answer 9

→ 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 10

What is the drug target for diazepam?

Answer 10

Benzodiazepine site on the GABA A receptor

Question 11

What are the main 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 for long-term suppression of epilepsy?

Answer 12

→ 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.

Question 13

What is the primary mechanism of action of levetiracetam?

Answer 13

→ Inhibition of the synaptic vesicle protein SV2A
→ inhibits this protein and prevents vesicle exocytosis. → reduction in 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 side effects of levetiracetam?

Answer 15

→ dizziness
→ somnolence (drowsiness or desire for sleep)
→ fatigue
→ headache

Question 16

Why is levetiracetam especially favourable?

Answer 16

→ metabolism of levetiracetam has no effect on the cytochrome P450 enzyme system
→ favourable in terms of no drug–drug interactions

Question 17

What determines what anti-epileptic is given to a patient?

Answer 17

Type of seizure

Whether it’s a women of child-bearing potential

Question 18

Why is it important if a patient is a woman of child-bearing potential?

Answer 18

Certain anti-epileptics (sodium valproate) can’t be given to women of child-bearing potential

Question 19

Why can’t sodium valproate be given to women of child-bearing potential?

Answer 19

Can effect development of foetus in utero:

• neural tube defects
• decreased IQ
• autism