Pharmacology of Epilepsy - Core Drugs & Case Study Flashcards
What are the 4 core drug (class) used in the treatment of epilepsy?
- Lamotrigine
- Sodium valproate
- Diazepam
- Levetiracetam
In 2020 - lamotrigine was the 94th most commonly prescribed drug in West London area.
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 is the drug target of Lamotrigine?
Voltage gated Na+ channels
What are some of the potential side effects of taking Lamotrigine?
Common:
- Rash
- Drowsiness
Less common but serious:
- Steven-Johnson’s syndrome
- Suicidal thoughts
What is one of the keys to reducing the frequency and severity of allergic skin reactions when prescribing lamotrigine to treat epilepsy?
Introducing lamotrigine gradually
What is the benefit of introducing lamotrigine gradually when treating epilepsy?
It’s one of the keys to reducing the frequency and severity of allergic skin reactions
In 2020 - sodium valproate was the 78th most commonly prescribed drug in West London
What is the primary mechanism of action of sodium valproate?
Inhibition of GABA transaminase
Prevents breakdown of GABA
Increases GABA concentrations directly in synapse presynaptically
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 is the function of GABA?
Reduces neuronal excitability by inhibiting nerve transmission
= Primary inhibitory neurotransmitter for CNS
What is the drug target for sodium valproate?
GABA transaminase
What are the potential side effects of taking sodium valproate?
Many side effects inc.
Common:
- Stomach pain
- Diarrhoea
- Drowsiness
- Weight gain
- Hair loss
Serious:
- Hepatotoxicity
- Teratogenicity
- Pancreatitis
Sodium valproate is a broad CYP enzyme inhibitor. How might this affect co-administered drugs?
It increases serum concentration of many co-administered drugs
In 2020 - Diazepam was 61st most commonly prescribed drug in West London
What is the primary mechanism of action of Diazepam?
Increases chloride ion influx in response to GABA binding at the GABA-A receptor
Increased Cl- influx associated with hyperpolarisation of excitatory neurones
What is the drug site and target for Diazepam?
Benzodiazepine site on the GABA-A receptor
What are some potential side effects of taking diazepam?
Common:
- Drowsiness
- Respiratory depression (if i.v. or at high dose)
Uncommon but serious:
- Haemolytic anaemia
- Jaundice
What is a common side effect that one might consider when taking diazepam at a high dose or through an I.V.?
Respiratory depression
What is the main reason for diazepam not being used for long term suppression of seizures?
The development of tolerance
Diazepam is a Schedule 4 controlled drug. What is the significance of this?
Addiction prone individuals more likely to become dependent on diazepam
In 2020 - Levetiracetam was the 74th most commonly prescribed drug in West London area.
What is the primary mechanism of action of Levetiracetam?
Inhibition of the synaptic vesicle protein SV2A
This prevents vesicle exocytosis
Leads to a reduction in glutamate secretion which reduces glutamate excitotoxicity
What is the drug target of Levetiracetam?
Synaptic vesicle protein SV2A
What are some potential side effects of taking Levetiracetam?
Common:
- Dizziness
- Somnolence
- Fatigue
- Headache
Levetiracetam is favourable in terms of no drug-drug interactions.
Why is this?
Its metabolism has no effect on the cytochrome P450 enzyme system
The metabolism of levetiracetam has no effect on the cytochrome P450 enzyme.
What is the significance of this?
It’s favourable in terms of no drug-drug interactions
What does the treatment of epilepsy depend on?
The type of seizure
The individual patient
How might you classify epilepsy seizures?
- Absence
- Focal
- Generalised tonic-clonic
- Myoclonic
- Tonic or atonic