Pharmacology of epilepsy Flashcards
what are the drug options for epilepsy
levetiracetam, diazepam, sodium valproate, lamotrigine
what is the primary mechanism of action for lamotrigine
Blocks voltage gated Na+ channels preventing Na+ influx. Prevents depolarisation of glutamatergic neurones and reduces glutamate excitotoxicity
what is the drug target for lamotrigine
voltage gated sodium channels
what are the side effects of lamotrigine
Side effects:
Common: Rash, drowsiness
Less common but serious:
Steven-Johnson’s syndrome, suicidal thoughts
introducing lamotrigine gradually is one of the keys to what
reducing frequency and severity of allergic skin reaction
what is the primary mechanism of action for sodium valproate
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.
drug target for sodium valproate
GABA transaminase
side effects of sodium valproate
Side effects (MANY):
Common: Stomach pain and diarrhoea, drowsiness, weight gain, hair loss
Serious:
hepatotoxicity, teratogenicity, pancreatitis
what does broad CYP enzyme inhibitor do with sodium valproate
it increases the serum concentration of many co administered drugs
primary mechanism of diazepam
Increases choride ion influx in response to GABA binding at the GABA A receptor. Increased chloride ion influx associated with hyperpolarisation of excitatory neurones
drug target of diazepam
Benzodiazepine site on the GABA A receptor
side effects of diaepam
Common: Drowsiness, respiratory depression (if i.v. or at high dose)
Uncommon but serious:
Haemolytic anaemia, jaundice
why is diazepam not used for long term suppression of seizures
due to development of tolerance
how controlled is diazepam and why
diazepam is a Schedule 4 controlled drug bc addiction prone individuals are more likely to become dependent on diazepam
primary mechanism of action for levetiracetam
Inhibition of the synaptic vesicle protein SV2A. It inhibits this protein and prevents vesicle exocytosis. A reduction in glutamate secretion is reduces glutamate excitotoxicity
drug target of levetiracetam
Synaptic vesicle protein SV2A
side effects of levetiracetam
Common:
dizziness, somnolence, fatigue and headache
why is levetiracetam in favour of no drug-drug interactions
bc metabolism of levetiracetam has no effect on the cytochrome P450 enzyme system
what is P450
key enzyme involved in metabolism of drugs
what are possible types of seizures
absence, focal, generalised tonic-clonic, myoclonic, tonic, atonic
what are absence seizures
staring off at nothing, where you stop focussing
what are focal seizures
repetitive movements such as tapping finger or blinking
typically one side
what are generalised tonic-clonic seizures
2 phases
tonic where you lose consciousness and fall
clonic where there is muscle spasms
what are myoclonic seizures
jerking spasms
what are atonic seizures
going ‘floppy’
what are tonic seizures
stiffening
what is interictal epileptiform discharge (IED) and what is the risk with it
large intermittent spikes observed between seizures in epilepsy, there is risk of increased seizure recurrence
who do u also need to contact upon epilepsy diagnosis
the DVLA as you cannot drive
what is first line for absence seizures
those not of child bearing potential - ethosuximide or sodium valproate
child bearing potential - ethosuximide
what is adjunctive treatment for absence seizures
those not of child bearing potential - combine 2 of ethosuximide, sodium valproate and lamotrigine
child bearing potential - combine lamotrigine and ethosuximide
what is the first line for focal seizures
those not of child bearing potential - carbamazepine or lamotrigine
child bearing potential - carbamazepine or levetiracetam
what is adjunctive treatment for focal seizures
those not of child bearing potential - any
child bearing potential - any but not sodium valproate
what is first line for generalised tonic clonic seizures
those not of child bearing potential - sodium valproate
child bearing potential - lamotrigine (or carbamazepine)
what is adjunctive treatment for generalised tonic clonic seizures
those not of child bearing potential - combine 2 of sodium valproate, levetiracetam, topirimate
child bearing potential - combine levetiracetam and topirimate
what is the first line for myoclonic seizures
those not of child bearing potential - sodium valproate
child bearing potential - levetiracetam or topirimate
what is adjunctive for myoclonic seizures
those not of child bearing potential - clobazam, lamotrigine, levetiracetam, topirimate
child bearing potential - clobazam, lamotrigine, levetiracetam, topirimate
what is first line for tonic or atonic seizures
those not of child bearing potential - sodium valproate
child bearing potential - sodium valproate (pregnancy prevention programme)
what is the adjunctive treatment for tonic or atonic seizures
those not of child bearing potential - lamotrigine
child bearing potential - lamotrigine
why is there a difference in treatment between child bearing potential individuals and others
valproate causes neural tube defects, decreased IQ and autism after in utero exposure
what is COC and how does it impact lamotrigine levels
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
why might COC affect lamotrigine like this
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
why might a patient experience drowsiness on week 4 of contraceptive cycle if on lamotrigine and COC
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
