Pharmacology of Anticonvulsants (Epilepsy) Flashcards
What are the core drugs used to treat Epilepsy?
Lamotrigine
Sodium Valproate
Diazepam
Levetiracetam
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 the main side effects of Lamotrigine?
Common: Rash, drowsiness
Less common but serious: Steven-Johnson’s syndrome, suicidal thoughts
How should you introduce Lamotrigine to a patient?
Introducing lamotrigine gradually is one of the keys to reducing the frequency and severity of allergic skin reactions.
What is the primary mechanism of action of 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.
What is the drug target of sodium valproate?
GABA transaminase
What are the main side effects of Sodium Valproate?
Common: Stomach pain and diarrhoea, drowsiness, weight gain, hair loss
Serious: hepatotoxicity, teratogenicity, pancreatitis
What effect does Sodium Valproate have on other drugs?
Broad CYP enzyme inhibitor - increases serum concentration of many co-administered drugs
What is the primary mechanism of action 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.
What is the drug target of Diazepam?
Benzodiazepine site on the GABA A receptor
What are the main side effects of Diazepam?
Common: Drowsiness, respiratory depression (if i.v. or at high dose)
Uncommon but serious: Haemolytic anaemia, jaundice
Can Diazepam used long-term? Why?
No: Main reason that diazepam is not used for long term suppression of seizures is due to the development of tolerance.
Diazepam is a Schedule 4 controlled drug - addiction prone individuals more likely to become dependent on diazepam.
What is the primary mechanism of action of 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
What is the drug target of Levetiracetam?
Synaptic vesicle protein SV2A
What are the main side effects of Levetiracetam?
Common: dizziness, somnolence, fatigue and headache
What are some benefits of Levetiracetam?
The metabolism of levetiracetam has no effect on the cytochrome P450 enzyme system so it is favorable in terms of no drug–drug interactions.
What is “the seven steps” approach to prescribing treatment?
- Identify the patient’s problem
- Specify the therapeutic objective
- Select a drug on the basis of comparative efficacy, safety, cost and suitability
- Discuss choice of medication with patient (and carer) and make a shared decision about treatment
- Write a correct prescription
- Counsel the patient on appropriate use of the medicine
- Make appropriate arrangements for follow up (Monitor/stop the treatment)
What 2 things affect the type of treatment patients receive for epilepsy?
Treatment dependent on type of seizure and individual patient
Why is there a difference in treatment between men (and post-menopausal women) and women of child-bearing potential for the drug prescribed?
Drugs can have effects on a fetus:
“Valproate” causes:
- Neural tube defects
- Decreased IQ
- Autism
(after in utero exposure)
How can Lamotrigine affect the combined oral contraceptive pill (COC)?
COC appears to have an impact on lamotrigine blood levels – coadministration leads to a reduced level of lamotrigine in the blood.
- REDUCED SEIZURE CONTROL
*COC may reduce lamotrigine absorbtion so less gets into the blood in the first place
*COC may enhance lamotrigine metabolism and so more is cleared from the blood
*COC may enhance lamotrigine excretion and thus enhance clearance from the blood
Lamotrigine does not appear to have an impact on blood ethinyl estradiol levels.
-NO CONTRACEPTIVE FAILURE
Why does the combined oral contraceptive (COC) pill affect the levels of Lamotrigine in our blood?
(COC appears to have an impact on lamotrigine blood levels – coadministration leads to a reduced level of lamotrigine in the blood.)
There is an enzyme “uridine diphosphate glucuronic acid (UDPGA)” that converts Lamotrigine into its inactive form, Lamotrigine N2-glucuronide (LTG-Gluc)
The COC pill induces this enzyme; less active lamotrigine
How would you tackle the issue of reduced Lamotrigine, if prescribing it to a patient on the COC pill?
COC= combined oral contraceptive pill
1. Increase dose of lamotrigine
2. Change contraception
What is a common issue with AED’s?
AED= anti-epileptic drugs
- Drug-drug interactions are common
- Frequently involve drug-induced changes in liver metabolism
- Antiepileptic drugs commonly interfere with metabolism of other drugs (incl COC)
