(pharm) pharmacology of anticonvulsants Flashcards
what are the most common drugs prescribed for epilepsy?
lamotrigine
sodium valproate
diazepam
levetiracetam
explain the primary mechanism of action of 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 Na+ channels
what are the most common side effects of lamotrigine?
rash, drowsiness
what are the less common side effects of lamotrigine?
Steven-Johnson’s syndrome, suicidal thoughts
how is lamotrigine used to prevent allergic skin reactions?
introducing lamotrigine gradually is one of the keys to reducing the frequency and severity of allergic skin reactions
explain the primary mechanism of action of sodium valproate
inhibition of GABA transaminase prevents the breakdown of GABA = increases GABA concentrations directly presynaptically + indirectly prolongs GABA in the synapse due to the fact that extraneuronal metabolism of GABA is slowed (which also slows GABA removal from the synapse) = overstimulation of inhibitory neurones due to prolonged presence of GABA in the synapse
what is the drug target for sodium valproate?
GABA transaminase
what are the common side effects of sodium valproate?
stomach pain
diarrhoea
drowsiness
weight gain
hair loss
what are the less common side effects of sodium valproate?
hepatotoxicity
teratogenicity
pancreatitis
what is the broad classification of sodium valproate?
braod CYP enzyme inhibitor
increases the serum concentration of many co-administered drugs
what is the drug target for diazepam?
benzodiazepine site on the GABA A receptor
what are the most common side effects of diazepam?
drowsiness, respiratory depression (if IV or at high dose)
what are the less common side effects of diazepam?
haemolytic anaemia, jaundice
when can respiratory depression occur when diazepam is administered?
if diazepam is given at high doses or if IV diazepam is administered
what is the main reason that diazepam is not used for the long-term suppression of seizures?
due to the development of tolerance
diazepam is a schedule 4 controlled drug - what does this mean?
addicition-prone
individuals are more likely to become dependent on diazepam
diazepam is a schedule 4 controlled drug - what does this mean?
addiction-prone
individuals are more likely to become dependent on diazepam
explain the mechanism of action of levetiracetam
inhibition of the synaptic vesicle protein SV2A = prevents vesicle exocytosis
so less glutamate secretion reduces glutamate excitotoxicity
what is the drug target for levetiracetam?
synaptice vesicle protein SV2A
what are the common side effects of levetiracetam?
dizziness
somnolence (i.e. drowsiness)
fatigue
headaches
why is levetiracetam favourable?
has no effect on the cytochrome P450 enzyme system = favourable in terms of no drug-drug interactions
how do you rule out that a seizure is not just a one-off episode?
do an EEG (electroencephalogram)
what will appear on an EEG if there is increased brain activity in between seizures?
IEDs = interictal epilepriform discharge
what are IEDs?
interictal epilepriform discharge
= sharp waves that are characteristic of epilepsy
appear as hyperactivity in specific areas
what does the presence of IEDs on an EEG suggest?
increase risk of seizures within next two years (increased risk of recurrence) = pharmacological treatment advised
what must you ensure to do when a patient presents to A&E with recurrent seizures?
must inform DVLA that they cannot drive
MUST MAKE A NOTE IN MEDICAL NOTES
what is the therapeutic objective for patients that present with recurrent seizures?
reduce risk of recurrence of seizures (drugs to reduce the risk of seizures in the future)
reduce severity of the seizure in the moment (drugs to stop seizure in the moment)
tackle the triggers (stress from university and lack of sleep)
avoid adverse effects associated w long-term treatment (fertility etc)
maintain a normal lifestyles
why can sodium valproate not be given to women with potential fertility?
as it is teratogenic (can cause neural tube defects and decreased IQ in foetuses)
which drug is administered to patients when they have a seizure in hospital?
IV diazepam or IV lorazepam
why is diazepam/lorazepam administered intravenously during a seizure?
patients cannot swallow and drug needs to act fast (administer as close to site of action as possible)
how does lamotrigine interact with the combine oral contraceptive pill?
taking both lamotrigine and the COC will reduce lamotrigine concentrations in the blood (reduced efficacy) however the plasma COC levels are unaffected
how is the problem of lamotrigine and combine oral contraceptive pill interaction overcome?
taking both lamotrigine and the COC will reduce lamotrigine concentrations in the blood (reduced efficacy)
SO increase the dose of lamotrigine (can also offer alternative contraceptive)
why are benzodiazepines given to address seizures in hospital but not in the community?
as repeated/prolonged intake of benzodiazepines = increased risk of dependency and tolerance so can have withdrawal symptoms
how do oestrogens and progesterones affect seizures?
oestrogens = seizure promoting
progesterones = seizure inhibiting
how and why can seizures be affected by pregnancy?
(lamotrigine) dose may be reduced due to fears of harming the unborn child
pregnancy may lead to changes in liver metabolism = (lamotrigine) levels may decrease and be associated with increased seizures
how can the anticonvulsant dose be determined for patients during pregnancy?
monitor patient and their response to drug dose during the beginning of the pregnancy
dose can be adjusted to suit the second and third trimester
briefly explain the mechanism of action of benzodiazepines
target = benzodiazepine site on the GABA A receptor
location = GABA A receptor
effect = positive allosteric modulator so stimulates an even greater chloride ion influx into the cell, accentuating the hyperpolarisation
