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
outline the sequence of events that occur at a GABAergic synapse
- it can be released tonically or it can be released following neuronal stimulation
- it activates inhibitory post-synaptic GABAa receptors
- GABAa receptors are Cl- channels
- this leads to membrane hyperpolarisation
- GABA is taken up by the GAT transporter
- it is then metabolised by GABA transaminase (GABA-T)
- it is broken down back into glutamate
what is diazepam and what does it do?
it is a positive allosteric modulator of GABAa receptors
it increases the activity of the GABA that binds to the channel but doesn’t increase the amount of GABA in the synapse
outline the pharmacokinetics of diazepam
administered as a rectal gel
it has a fast-onset (within 15mins) but a short half-life (2hrs)
what type of epilepsy is diazepam used to treat?
status epilepticus
what is used to inhibit the GABA transaminase enzyme? how does it work?
sodium valproate
it increases GABA-mediated inhibition
by increasing GABA-t it is increasing the amount of GABA, and also reducing the amount of glutamate being formed
what has a similar method of action to sodium valproate?
vigabatrin
outline the pharmacokinetics of sodium valproate
fast onset (1hr) and a half-life of 12hrs
what forms of epilepsy is sodium valproate used to treat?
all forms except status epilepticus
what is the pharmacological treatment of tonic-clonic seizures?
carbamazepine
lamotrigine
valproate
