pharmacology of anti convulsants Flashcards
primary mechanism of action of lamotrigene
blocks voltage gated sodium channels preventing sodium influx. Preventing depolarisation of glutaminergic neurons and reduces glutamate excitotoxicity
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.
primary mechanism of action of diazepam
GABA binds to GABA A receptor which increases chloride influx. Associated with hyperpolarisation of excitatory neurons
Primary mechanism of action of levetiracetam
inhibition of synaptic vesicle protein SV2A. Prevents vesicle exocytosis. causing reduction in glutamate secretion causing decreased glutamate excitotoxicity
drug target of lamotrigene
voltage gated sodium channels
drug target of sodium valproate
GABA transaminase
drug target of diazepam
benzodiazepine site on GABA A receptor
drug target of levetiracetam
synaptic vesicle protein SV2A
Common and less common side effects of lamotrigene
common: rash, drowsiness
less common but serious: steven johnson syndrone, suicidal thoughts
How to reduce severity and frequency of allergic reactions in lamotrigene
introduce gradually
Side effects of sodium valproate (common and serious)
Side effects (MANY):
Common: Stomach pain and diarrhoea, drowsiness, weight gain, hair loss
Serious:
hepatotoxicity, teratogenicity, pancreatitis
Important thing to consider for sodium valproate
Broad CYP enzyme inhibitor - increases serum concentration of many co-administered drugs
Serious but rare side effects of diazepam
haemolytic anaemia, jaundice
Common side effects of diazepam
Drowsiness, respiratory depression (if i.v. or at high dose)
Uncommon
Why is diazepam not used for long term treatment of seizures
development of tolerance
Levetiracetam side effects
dizziness, somnolence, fatigue and headache
Levetiracetam main benefit
The metabolism of levetiracetam has no effect on the cytochrome P450 enzyme system so it is favorable in terms of no drug–drug interactions.
Therapeutic objects of anti epilepsy drug therapy (3)
To eliminate seizures or reduce their frequency to the maximum degree possible
To avoid the adverse effects associated with long-term treatment
To aid patients in maintaining or restoring their usual psychosocial and vocational activities, and in maintaining a normal lifestyle.
How is sodium valproate teratogenic
Neural tube defects
Decreased IQ
Autism
(after in utero exposure)
Lamotrigene - OCP drug interaction
COC appears to have an impact on lamotrigine blood levels – coadministration leads to a reduced level of lamotrigine in the blood.
Lamotrigine does not appear to have an impact on blood ethinyl estradiol levels.
As COC increases UDPGA induction, which breaks down lamotrigene
