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Y2 Pharmacology > Pharmacology of epilepsy > Flashcards

Pharmacology of epilepsy Flashcards

1
Q

what are the drug options for epilepsy

A

levetiracetam, diazepam, sodium valproate, lamotrigine

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2
Q

what is the primary mechanism of action for lamotrigine

A

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

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3
Q

what is the drug target for lamotrigine

A

voltage gated sodium channels

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4
Q

what are the side effects of lamotrigine

A

Side effects:
Common: Rash, drowsiness

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

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5
Q

introducing lamotrigine gradually is one of the keys to what

A

reducing frequency and severity of allergic skin reaction

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6
Q

what is the primary mechanism of action for sodium valproate

A

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.

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6
Q

drug target for sodium valproate

A

GABA transaminase

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7
Q

side effects of sodium valproate

A

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

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7
Q

what does broad CYP enzyme inhibitor do with sodium valproate

A

it increases the serum concentration of many co administered drugs

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8
Q

primary mechanism of diazepam

A

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

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9
Q

drug target of diazepam

A

Benzodiazepine site on the GABA A receptor

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10
Q

side effects of diaepam

A

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

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11
Q

why is diazepam not used for long term suppression of seizures

A

due to development of tolerance

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12
Q

how controlled is diazepam and why

A

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

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13
Q

primary mechanism of action for levetiracetam

A

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

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14
Q

drug target of levetiracetam

A

Synaptic vesicle protein SV2A

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15
Q

side effects of levetiracetam

A

Common:
dizziness, somnolence, fatigue and headache

16
Q

why is levetiracetam in favour of no drug-drug interactions

A

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

17
Q

what is P450

A

key enzyme involved in metabolism of drugs

18
Q

what are possible types of seizures

A

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

19
Q

what are absence seizures

A

staring off at nothing, where you stop focussing

20
Q

what are focal seizures

A

repetitive movements such as tapping finger or blinking
typically one side

21
Q

what are generalised tonic-clonic seizures

A

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

22
Q

what are myoclonic seizures

A

jerking spasms

23
Q

what are atonic seizures

A

going ‘floppy’

24
Q

what are tonic seizures

A

stiffening

25
Q

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

A

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

26
Q

who do u also need to contact upon epilepsy diagnosis

A

the DVLA as you cannot drive

27
Q

what is first line for absence seizures

A

those not of child bearing potential - ethosuximide or sodium valproate

child bearing potential - ethosuximide

28
Q

what is adjunctive treatment for absence seizures

A

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

child bearing potential - combine lamotrigine and ethosuximide

29
Q

what is the first line for focal seizures

A

those not of child bearing potential - carbamazepine or lamotrigine

child bearing potential - carbamazepine or levetiracetam

30
Q

what is adjunctive treatment for focal seizures

A

those not of child bearing potential - any

child bearing potential - any but not sodium valproate

31
Q

what is first line for generalised tonic clonic seizures

A

those not of child bearing potential - sodium valproate

child bearing potential - lamotrigine (or carbamazepine)

32
Q

what is adjunctive treatment for generalised tonic clonic seizures

A

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

child bearing potential - combine levetiracetam and topirimate

33
Q

what is the first line for myoclonic seizures

A

those not of child bearing potential - sodium valproate

child bearing potential - levetiracetam or topirimate

34
Q

what is adjunctive for myoclonic seizures

A

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

child bearing potential - clobazam, lamotrigine, levetiracetam, topirimate

35
Q

what is first line for tonic or atonic seizures

A

those not of child bearing potential - sodium valproate

child bearing potential - sodium valproate (pregnancy prevention programme)

36
Q

what is the adjunctive treatment for tonic or atonic seizures

A

those not of child bearing potential - lamotrigine

child bearing potential - lamotrigine

37
Q

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

A

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

38
Q

what is COC and how does it impact lamotrigine levels

A

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

39
Q

why might COC affect lamotrigine like this

A

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

40
Q

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

A

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

Y2 Pharmacology (8 decks)

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