Epilepsy Pharmacology Flashcards
What are the drugs for epilepsy? (4)
lamotrigine
sodium valproate
diazepam
levetiracetam
What is the drug target for lamotrigine?
Voltage gated Na+ channels
What is 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 are the main side effects of lamotrigine?
Side effects:
Common: Rash, drowsiness
Less common but serious:
Steven-Johnson’s syndrome, suicidal thoughts
What is the key with reducing the frequency and severity of allergic skin reactions?
Introducing lamotrigine gradually is one of the keys to reducing the frequency and severity of allergic skin reactions.
What is the drug target for sodium valproate?
GABA transaminase
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 metabolism of GABA is slowed which also slows GABA removal from the synapse.
What are side effects of sodium valproate?
Side effects (MANY):
Common: Stomach pain and diarrhoea, drowsiness, weight gain, hair loss
Serious:
hepatotoxicity, teratogenicity, pancreatitis
What are CYP enzymes?
Human cytochrome P450 (CYP) enzymes
What increases serum concentration of many co-administered drugs?
broad CYP enzyme inhibitors
What is the drug target of diazepam?
Benzodiazepine site on the GABA A receptor
What is the primary mechanism of action for diazepam?
Increases chloride ion influx in response to GABA binding at the GABA A receptor. Increased chloride ion influx associated with hyperpolarisation of excitatory neurones.
What are the side effects of diazepam?
Side effects:
Common: Drowsiness, respiratory depression (if i.v. or at high dose)
Uncommon but serious:
Haemolytic anaemia, jaundice
Why is diazepam not used longterm?
Main reason that diazepam is not used for long term suppression of seizures is due to the development of tolerance.
Why is diazepam a schedule 4 controlled drug?
Diazepam is a Schedule 4 controlled drug - addiction prone individuals more likely to become dependent on diazepam.
What is the patient’s problem?
generalised tonic-clonic epilepsy
Generalised tonic clonic seizures
EEG shows interictal epileptiform discharge (IED) – risk of seizure recurrence
What is the therapeutic objective for this patient?
Must document advice to
contact DVLA that they cannot drive
What drug treatment do you give for different epilepsies?
Absence
Focal
Generalised tonic-clonic
Myoclonic
Tonic or atonic
Which drug treatment should you offer for generalised tonic-clonic epilepsy in a female of child bearing age in the first instance and explain the mechanism of action of your drug of choice?
it prevents sodium influx which inhibits glutamate
- voltage gated sodium channel on glutamatergic excitatory neurons in brain
Why do we think there is a difference in treatment between men (and post-menopausal women) and women of child-bearing potential?
Valproate:
Neural tube defects
Decreased IQ
Autism
(after in utero exposure)
COC= combined oral contraceptives
Either 1) Increase dose of lamotrigine (COC can reduce lamotrigine by 50%) Or 2) Change contraception
in reality…
- Change AED or change contraception. (Better to stick with AED if it works)
What do you think is going on?
COC taken over four weeks:
First three weeks: active drug
Fourth week: nothing or ‘dummy’
So, fourth week - no COC affecting liver enzymes:
Liver enzymes normalise Lamotrigine levels increase
Using the BMJ Best Practice link, which drug would you administer first. Route of administration is different depending on whether Essie is in hospital (in this case) or out of hospital. Can you explain why?
What is the key mechanism of action of benzodiazepines (Target/Location/Effect)?
