Pharmacology of epilepsy

Question 1

what are the drug options for epilepsy

Answer 1

levetiracetam, diazepam, sodium valproate, lamotrigine

Question 2

what is the primary mechanism of action for lamotrigine

Answer 2

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

Question 3

what is the drug target for lamotrigine

Answer 3

voltage gated sodium channels

Question 4

what are the side effects of lamotrigine

Answer 4

Side effects:
Common: Rash, drowsiness

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

Question 5

introducing lamotrigine gradually is one of the keys to what

Answer 5

reducing frequency and severity of allergic skin reaction

Question 6

what is the primary mechanism of action for 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 metanolism of GABA is slowed which also slows GABA removal from the synapse.

Question 6

drug target for sodium valproate

Answer 6

GABA transaminase

Question 7

side effects of sodium valproate

Answer 7

Side effects (MANY):
Common: Stomach pain and diarrhoea, drowsiness, weight gain, hair loss
Serious:
hepatotoxicity, teratogenicity, pancreatitis

Question 7

what does broad CYP enzyme inhibitor do with sodium valproate

Answer 7

it increases the serum concentration of many co administered drugs

Question 8

primary mechanism of diazepam

Answer 8

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 9

drug target of diazepam

Answer 9

Benzodiazepine site on the GABA A receptor

Question 10

side effects of diaepam

Answer 10

Common: Drowsiness, respiratory depression (if i.v. or at high dose)
Uncommon but serious:
Haemolytic anaemia, jaundice

Question 11

why is diazepam not used for long term suppression of seizures

Answer 11

due to development of tolerance

Question 12

how controlled is diazepam and why

Answer 12

diazepam is a Schedule 4 controlled drug bc addiction prone individuals are more likely to become dependent on diazepam

Question 13

primary mechanism of action for levetiracetam

Answer 13

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 14

drug target of levetiracetam

Answer 14

Synaptic vesicle protein SV2A

Question 15

side effects of levetiracetam

Answer 15

Common:
dizziness, somnolence, fatigue and headache

Question 16

why is levetiracetam in favour of no drug-drug interactions

Answer 16

bc metabolism of levetiracetam has no effect on the cytochrome P450 enzyme system

Question 17

what is P450

Answer 17

key enzyme involved in metabolism of drugs

Question 18

what are possible types of seizures

Answer 18

absence, focal, generalised tonic-clonic, myoclonic, tonic, atonic

Question 19

what are absence seizures

Answer 19

staring off at nothing, where you stop focussing

Question 20

what are focal seizures

Answer 20

repetitive movements such as tapping finger or blinking
typically one side

Question 21

what are generalised tonic-clonic seizures

Answer 21

2 phases
tonic where you lose consciousness and fall
clonic where there is muscle spasms

Question 22

what are myoclonic seizures

Answer 22

jerking spasms

Question 23

what are atonic seizures

Answer 23

going 'floppy'

Question 24

what are tonic seizures

Answer 24

stiffening

Question 25

what is interictal epileptiform discharge (IED) and what is the risk with it

Answer 25

large intermittent spikes observed between seizures in epilepsy, there is risk of increased seizure recurrence

Question 26

who do u also need to contact upon epilepsy diagnosis

Answer 26

the DVLA as you cannot drive

Question 27

what is first line for absence seizures

Answer 27

those not of child bearing potential - ethosuximide or sodium valproate child bearing potential - ethosuximide

Question 28

what is adjunctive treatment for absence seizures

Answer 28

those not of child bearing potential - combine 2 of ethosuximide, sodium valproate and lamotrigine child bearing potential - combine lamotrigine and ethosuximide

Question 29

what is the first line for focal seizures

Answer 29

those not of child bearing potential - carbamazepine or lamotrigine child bearing potential - carbamazepine or levetiracetam

Question 30

what is adjunctive treatment for focal seizures

Answer 30

those not of child bearing potential - any child bearing potential - any but not sodium valproate

Question 31

what is first line for generalised tonic clonic seizures

Answer 31

those not of child bearing potential - sodium valproate child bearing potential - lamotrigine (or carbamazepine)

Question 32

what is adjunctive treatment for generalised tonic clonic seizures

Answer 32

those not of child bearing potential - combine 2 of sodium valproate, levetiracetam, topirimate child bearing potential - combine levetiracetam and topirimate

Question 33

what is the first line for myoclonic seizures

Answer 33

those not of child bearing potential - sodium valproate child bearing potential - levetiracetam or topirimate

Question 34

what is adjunctive for myoclonic seizures

Answer 34

those not of child bearing potential - clobazam, lamotrigine, levetiracetam, topirimate child bearing potential - clobazam, lamotrigine, levetiracetam, topirimate

Question 35

what is first line for tonic or atonic seizures

Answer 35

those not of child bearing potential - sodium valproate child bearing potential - sodium valproate (pregnancy prevention programme)

Question 36

what is the adjunctive treatment for tonic or atonic seizures

Answer 36

those not of child bearing potential - lamotrigine child bearing potential - lamotrigine

Question 37

why is there a difference in treatment between child bearing potential individuals and others

Answer 37

valproate causes neural tube defects, decreased IQ and autism after in utero exposure

Question 38

what is COC and how does it impact lamotrigine levels

Answer 38

combined oral contraceptive coadministration leads to reduced levels in blood, lamotrigine does not appear to impact on blood ethinyl estradiol levels, this drug-drug interaction causes reduced seizure control but no contraceptive failure

Question 39

why might COC affect lamotrigine like this

Answer 39

COC may reduce lamotrigine absorption so less gets into the blood in the first place, or may enhance metabolism so more is cleared or may enhance excretion

Question 40

why might a patient experience drowsiness on week 4 of contraceptive cycle if on lamotrigine and COC

Answer 40

GP increased lamotrigine dose to combat the reducing effects of COC but in the 4th week of cycle the COC does not contain the active drug, therefore the COC does not affect the liver enzymes and lamotrigine levels increase causing drowsiness