Anticonvulsants COPY Flashcards
Define epilepsy
A neurological condition causing frequent seizures
Define seizure
Seizures are “sudden changes in behaviour caused by electrical hypersynchronization of neuronal networks in the cerebral cortex”
Prevalence and incidence of epilspesy
Prevalence between 2-7% of the population Incidence increased over the last 30-40 years
How is epilepsy diagnosed
Brain activity can be measured using: -Electroencephalography (EEG) -Magnetic resonance imaging (MRI)… more specific
Two Main Seizure types
General Partial/focal
Distinguish types of general seizures
Tonic-clonic Absence Tonic/atonic Myoclonic Status epilepticus
Distingish partial/focal seizures
Simple Complex
What are general seizures
Begins simultaneously in both hemispheres of brain
Outline tonic-clonic seizure
loss of consciousness –> muscle stiffening (=tonic part) –> rhythmic jerking/twitching (=clonic part) –> deep sleep –> wakes up
Outlin absence seizures
brief staring episodes with behavioural arrest
Tonic/atonic seizure
sudden muscle stiffening/sudden loss of muscle control (similar but doesn’t have the phases in tonic-clonic)
Outline myoclonic seizure
sudden, brief muscle contractions
Outline status epilepticus
> 5 min of continuous seizure activity
What are partial/focus seizues
Begins within a particular area of brain and may spread out
Simple vs complex partial/focus seizure
Simple: retained awareness/consciousness Complex: impaired awareness/consciousness
Activity at the glutamaterig synapse
- VGSC open –> depolarization 2. VGKC opens –> repolarisation 3. Ca2+ influx through VGCC –> vesicle exocytosis 4. Glutatmate activates post synaptic receptors
How are synpatic vesicles attached to presynaptic membrane for glutamate
Synaptic vesicle associated (SV2A) protein allows vesicle attachment to presynaptic membrane (a docking protein)
Which receptors fores glutatmate bind to on the post-synaptic receptors
Glutamate activates excitatory post-synaptic receptors (e.g. NMDA, AMPA & kainate receptors)
Outline the morphooy of the Na+ channel
Closed, open then inactive
Outline mechanism of carbamezapine
Pharmacodynamics: Stabilises inactive state of Na+ channel –> reducing neuronal activity
PK of carbamazapine
Enzyme inducer Onset of activity within 1 hour 16-30 hour half-life Basically all have fast onset, and long duration of action
Indication of carbamazapine
Tonic-clonic seizures; partial seizures
What are the very dangerous side effects of the carbamazepine
NB: potential severe side-effects (SJS (stephen-johnson syndrome) & TEN) in individuals with HLA-B*1502 allele Especially Han chinese
What is the mechanism of lamotrigine action
Inactivates Na+ channels reducing glutamate neuronal activity
What is the PK of lamotrigine
Onset of activity within 1 hour 24-34 hour half-life (again, fast onset, long duration of action)
Indication of lamotrigine
Tonic-clonic seizures; absence seizures
Which drug blocks calcium channel
Ethosuximide
Mechanism of Ethasuximide action
T-type Ca2+ channel antagonist –> reduces activity in relay thalamic neurones (as opposed to dihydropyridines, which are used in treatment of HTN)
Half life of ethasuximide
Long half life (50 hrs)
What is the infication of ethosuximide
Absence seizures
What drug inhibits SV2A
Levetiracetam
What is the mechanism of levetiracetam
Binds to synaptic vesicle associated protein (SV2A) preventing glutamate release
PK of levetiracetam
Fast onset, half life 10hrs
Infications of levetiracetam
Myoclonic
What drugs block postsynaptic membane receptors
Topiramate
What is the mechanism of topiramate action
Inhibits NMDA & kainate receptors Also affects VGSCs & GABA receptors
What is the PK of topiramate
Fast-onset (1 hour); long half-life (20 hours)
Indication of topiramate
Myoclonic seizures and neuropathic pain (more)
Action at GABA receptor
DIFFERENCE TO OTHERS: there is always a small amount of GABA released as the brain is always in an inhibitory mode GABA can be released tonically & also following neuronal stimulation
How does GABA get released and work on receptor
GABA activates inhibitory post-synaptic GABAA receptors GABAA receptors are chloride (Cl-) channels–> membrane hyperpolarisation GABA is taken up by GAT & metabolised by GABA transaminase (GABA-T)
What is the acton of diazepam
GABA receptor, PAM –> increases GABA-mediated inhibition POSITIVE ALLOSTERIC MODULATOR I.e. BDZs cannot activate the GABA-A receptor without the normal GABA ligand bindin
What is the indication of diazepam in epilepsy + how it is administered in this case
Rectal gel - Fast-onset (within 15 min); half-life (2 hours) for Status epilepticus
Function of sodium valproate
Inhibits GABA transaminase –> increases GABA-mediated inhibition
What does GABA transaminase do
Converts GABA-A to glutamate So with sodium valproate, a GAT inhibitor, you will have less Glu and more GABA :)
What is the infication for sodium valproate
Indicated for ALL forms of epilepsy
