pharmacology of anti convulsants

Question 1

primary mechanism of action of lamotrigene

Answer 1

blocks voltage gated sodium channels preventing sodium influx. Preventing depolarisation of glutaminergic neurons and reduces glutamate excitotoxicity

Question 2

primary mechanism of action of sodium valproate

Answer 2

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 3

primary mechanism of action of diazepam

Answer 3

GABA binds to GABA A receptor which increases chloride influx. Associated with hyperpolarisation of excitatory neurons

Question 4

Primary mechanism of action of levetiracetam

Answer 4

inhibition of synaptic vesicle protein SV2A. Prevents vesicle exocytosis. causing reduction in glutamate secretion causing decreased glutamate excitotoxicity

Question 5

drug target of lamotrigene

Answer 5

voltage gated sodium channels

Question 6

drug target of sodium valproate

Answer 6

GABA transaminase

Question 7

drug target of diazepam

Answer 7

benzodiazepine site on GABA A receptor

Question 8

drug target of levetiracetam

Answer 8

synaptic vesicle protein SV2A

Question 9

Common and less common side effects of lamotrigene

Answer 9

common: rash, drowsiness

less common but serious: steven johnson syndrone, suicidal thoughts

Question 10

How to reduce severity and frequency of allergic reactions in lamotrigene

Answer 10

introduce gradually

Question 11

Side effects of sodium valproate (common and serious)

Answer 11

Side effects (MANY):

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

Serious:

hepatotoxicity, teratogenicity, pancreatitis

Question 12

Important thing to consider for sodium valproate

Answer 12

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

Question 13

Serious but rare side effects of diazepam

Answer 13

haemolytic anaemia, jaundice

Question 14

Common side effects of diazepam

Answer 14

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

Uncommon

Question 15

Why is diazepam not used for long term treatment of seizures

Answer 15

development of tolerance

Question 16

Levetiracetam side effects

Answer 16

dizziness, somnolence, fatigue and headache

Question 17

Levetiracetam main benefit

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.

Question 18

Therapeutic objects of anti epilepsy drug therapy (3)

Answer 18

To eliminate seizures or reduce their frequency to the maximum degree possible
To avoid the adverse effects associated with long-term treatment
To aid patients in maintaining or restoring their usual psychosocial and vocational activities, and in maintaining a normal lifestyle.

Question 19

How is sodium valproate teratogenic

Answer 19

Neural tube defects
Decreased IQ
Autism
(after in utero exposure)

Question 20

Lamotrigene - OCP drug interaction

Answer 20

COC appears to have an impact on lamotrigine blood levels – coadministration leads to a reduced level of lamotrigine in the blood.

Lamotrigine does not appear to have an impact on blood ethinyl estradiol levels.

As COC increases UDPGA induction, which breaks down lamotrigene