Pharmacology of Epilepsy Flashcards
What is the primary mechanism of action of Lamotrigine?
- Blocks VGSCs, preventing sodium influx
- Prevents depolarisation of glutamatergic neurons
- reduced glutamate excitotoxicity
What is the drug target of Lamotrigine?
Voltage Gated Sodium Channels (VGSCs)
What are the main side effects of Lamotrigine?
Common: - rash - drowsiness Rare: - Steven-Johnson's Syndrome - Suicidal thoughts
What can be done to prevent the frequency and severity of allergic skin reactions when taking Lamotrigine?
introducing it gradually
What is the primary mechanism of action of Sodium Valproate?
- Inhibition of GABA transaminase, preventing the breakdown of GABA
- Increasing GABA concentration directly in the synapse, pre-synaptically
- Prolongs GABA in the synapse due to the extra-neuronal metabolism and removal being slowed
What is the drug target of Sodium Valproate?
GABA transaminase
What are the side effects of Sodium Valproate?
MANY Common: - stomach pain - diarrhoea - drowsiness - weight gain - hair loss SERIOUS: - hepatotoxicity - teratogenicity - pancreatitis
Why should a broad CYP enzyme inhibitor be prescribed in conjunction with Sodium Valproate?
Increases the serum concentration of many co-administered drugs
What is the primary mechanism of action of Diazepam?
- Increased Cl- influx to GABA binding to the GABA-A receptor
- hyperpolarisation of excitatory neurons
What is the drug target of Diazepam?
Benzodiazepine site on the GABA-A receptor
What are the side effects of Diazepam?
common: - drowsiness - respiratory depression (IV or high dose) SERIOUS: - hemolytic anaemia - jaundice
Why is Diazepam not used for the long term suppression of seizures?
- tolerance development
- Addictive, dependence likely (Schedule 4 controlled drug)
What is the primary mechanism of action of Levetiracetam?
- Inhibition of the synaptic vesicle protein SV2A
- prevents vesicle exocytosis
- reduces glutamate secretion
- reduces glutamate excitotoxicity
What is the drug target of Levetiracetam?
Synaptic Vesicle Protein, SV2A
What are the common side effects of Levetiracetam?
- dizziness
- somnolence
- fatigue
- headache
Why is Levetiracetam favorable?
- no effect on the cytochrome P450 enzyme system
- unlikely to have drug-drug interactions
What is important to note when prescribing therapeutic drugs for seizures?
- must tell pateint, they CANNOT drive
- they MUST tell the DVLA
Why does Lamotrigine cause drowsiness?
- acts on all presynaptic glutamate receptors
- non-specific
- slows down the whole brain
- depressant effect on the brain
When can Sodium Valproate be prescribed to those of child-bearing age?
ONLY when prescribed by a neurologist
Why can’t those of child-bearing age take Sodium Valproate?
teratogenic (reproductive toxicity)
What is the treatment of epilepsy dependent on?
- type of seizure
- the individual patient
What on an ECG can indicate an increased risk of seizure recurrance?
interictal epileptiform discharge (IED)
What are the main aims of antiepileptic drug (AED) therapy?
- eliminate seizures (or reduce frequency)
- avoid the adverse effects of LT treatment
- aid patients to maintain/restore a normal lifestyle
What must be done when Anti-Epileptic drug therapy is started?
must document advice to tell the DVLA that they cannot drive.
What is the first line and adjunctive treatment for those with absence seizures? (NOT CHILDBEARING)
First line: - ethosuximide - sodium valproate Adjunctive treatment: combine 2 of: - ethosuximide - sodium valproate - lamotrigine
What is the first line and adjunctive treatment for those with absence seizures? (CHILDBEARING)
First line: - ethosuximide Adjunctive treatment combine: - ethosuximide - lamotrigine
What is the first line and adjunctive treatment for those with focal seizures? (NOT CHILDBEARING)
First line: - carbamazepine - lamotrigine Adjunctive treatment -any
What is the first line and adjunctive treatment for those with focal seizures? (CHILDBEARING)
First line: - carbamazepine - levetiracetam Adjunctive treatment - any (NO SODIUM VALPROATE)
What is the first line and adjunctive treatment for those with generalised tonic-clonic seizures? (NOT CHILDBEARING)
First line: -sodium valproate Adjunctive treatment: combine 2 of: - sodium valproate - levetiracetam - topirimate
What is the first line and adjunctive treatment for those with generalised tonic-clonic seizures? (CHILDBEARING)
First line: - Lamotrigine - Carbamazepine Adjunctive treatment: combine: - levetiracetam - topirimate
What is the first line and adjunctive treatment for those with myoclonic seizures? (NOT CHILDBEARING)
First line: - sodium valproate Adjunctive treatment: - clobazam - lamotrigine - levetiracetam - topirimate
What is the first line and adjunctive treatment for those with myoclonic seizures? (CHILDBEARING)
First line: - levetiracetam - topiramate Adjunctive treatment: - clobazam - lamotrigine - levetiracetam - topirimate
What is the first line and adjunctive treatment for those with tonic or atonic seizures? (NOT CHILDBEARING)
First line:
- sodium valproate
Adjunctive treatment:
- lamotrigine
What is the first line and adjunctive treatment for those with tonic or atonic seizures? (CHILDBEARING)
First line: - sodium valproate (WITH PREGNANCY PREVENTION PLAN) Adjunctive treatment: - lamotrigine
What is the effect of sodium valproate with in utero exposure?
- neural tube defects
- decreased IQ
- autism
What is the impact of the combined oral contraceptive on lamotrigine blood levels?
- co-administration leads to low lamotrigine blood levels
- lamotrigine has no effect on blood ethinyl estradiol levels
- reduced seizure control
- NO contraceptive failure
Why does the combined oral contraceptive have an effect on lamotrigine levels?
may:
- reduce absorption
- enhance metabolism
- may enhance excretion
How do you combat the effect of COC pill on lamotrigine?
- change AED or contraception
OR - increase the dosage of lamotrigine
What do drug-drug interactions tend to involve?
- changes to liver metabolism
- AED commonly effect other drugs
