33. Anticonvulsants Flashcards
what is epilepsy?
a neurological condition causing frequent seizures
what are seizures?
“sudden changes in behaviour caused by electrical hypersynchronisation of neuronal networks in the cerebral cortex”
essentially over-excitation due to too much glutamatergic activity (glutamate is the main excitatory NT within the CNS)
what is the prevalence and incidence of epilepsy?
prevalence: 2-7% of the population
incidence has been increasing over the last 30-40 years
how is epilepsy diagnosed?
by measuring brain activity via:
- electroencephalography
- magnetic resonance imaging
what are the 2 categories of seizure seen in epilepsy?
generalised seizure: when the increased synchronisation begins simultaneously in both hemispheres of the brain
partial/focal seizure: begin within a particular area of the brain, and may spread out
what are the different types of generalised seizure and what are their symptoms?
- tonic-clonic seizures: loss of consciousness –> muscle stiffening –> jerking/twitching –> deep sleep –> wakes up
- absence seizures: brief staring episodes with behavioural arrest
- tonic/atonic seizures: sudden muscle stiffening (tonic)/ sudden loss of muscle control (atonic)
- myoclonic seizures: sudden, brief muscle contractions - lots of muscle movement seen
- status epilepticus: over 5mins of continuous seizure activity (most dangerous)
what are the different types of partial/focal seizure and what are their symptoms?
- simple: retained awareness/consciousness
2. complex: impaired awareness/consciousness
outline the sequence of events that occur at a glutamatergic synapse
- AP arrives at the presynaptic terminal
- VGSC opens –> membrane depolarisation
- VGKC opens –> membrane repolarisation
- Ca2+ influx through VGCCs –> vesicle exocytosis
- synaptic vesicle associated (SV2A) protein allows vesicle (containing glutamate) attachment to the presynaptic membrane (it is a docking protein)
- glutamate is released into the synapse
- glutamate activates excitatory post-synaptic receptors (e.g. NMDA, AMPA, kainate receptors)
what is carbamazepine and what does it do?
VGSC blocker
it stabilised the inactive state of the Na+ channel –> more likely to remain in an inactive state –> reduced neuronal activity
- enzyme inducer
- fast onset of activity
- long half-life (16-30hrs)
when is carbamazepine used? what are the potential side effects?
tonic-clonic seizures and partial seizures
because it is an enzyme inducer of the cytochrome P450 pathways, it reduces the activity of a number of other drugs
it can potentially have severe skin side effects
what is lamotrigine and what does it do?
VGSC blocker
directly inactivates Na+ channel –> reduces glutamate neuronal activity
onset of activity is within an hour and half life is long (24-34hrs)
it is more selective for glutamatergic neurones
when is lamotrigine used?
tonic-clonic seizures and absence seizures
name a VGCC inhibitor used to treat seizures and outline what type of seizures it is used for and how it works
ethosuximide is a T-type (found in CNS) calcium channel antagonist
it reduces activity in relay thalamic neurones (prevents the propagation of an AP –> decreased neurotransmission) and it has a long half-life (50hrs)
it is only useful for absence seizures
what is levetiracetam? when is it used?
a drug that binds to synaptic vesicle associated protein (SV2A) and prevents glutamate exocytosis
it has a fast onset (1hr) and short half life (10hrs)
it is used for myoclonic seizures
what is topiramate? when is it used?
a drug that inhibits NMDA and kainate receptors and also affects VGSCs and GABA receptors
it has a fast onset (1hr) and long half life (20hrs)
it is used for myoclonic seizures
