Epilepsy Flashcards
Definition of epilepsy
A neurological condition causing frequent seizures
Seizures are….
sudden changes in behaviour caused by electrical hypersynchronization of
neuronal networks in the cerebral cortex
Prevalence & Incidence of epilepsy
Prevalence between 2-7% of the population. COMMON
Incidence increased over the last 30-40 years
Diagnosis of epilepsy is done by
EEG - During the seizure will show increased frequency of waveforms.
MRI - detect underlying structural disease
Seizures can be split into
Generalised seizures by definition occur in both brain hemispheres.
Partial seizures happen in one focal brain area
define the following terms
tonic
clonic
atonic
tonic - muscle stiffening
clonic - jerking/twitching
atonic - Sudden loss of muscle control
what is the most common seizure in epilepsy. Describe it
Tonic clonic
loss of consciousness → muscle
stiffening (tonic) → jerking/twitching (clonic) → deep
sleep → wakes up.
define Absence seizures
Brief staring episodes with behavioural arrest
define Tonic/atonic seizures
Tonic Seizures: Sudden muscle stiffening (increased muscle tone)
Atonic Seizures: Sudden loss of muscle control. Muscles just
relax suddenly, patients will suddenly fall. (Remember the
helmets).
define myoclonic Seizures
sudden, brief muscle contractions
Patient may be eating cereal and suddenly gets an arm jerk
define Status epilepticus
> 5 min of continuous seizure activity
Medical emergency!!!
list Types of Generalised Seizures
Tonic-Clonic Absence Tonic/atonic Myoclonic Status epilepticus
categorise Partial/ focal Seizures
Simple: retained awareness/consciousness
Complex: impaired awareness/consciousness
what generally is anticonvulsant therapy based on
inhibit the glutamatergic system or
potentiate the GABAergic system
what allows vesicle attachment to presynaptic membrane
Synaptic vesicle associated (SV2A) protein
what receptors does glutamate activate
activates excitatory post-synaptic receptors
e.g. NMDA, AMPA & kainate receptors)
categorise how drugs inhibiting glutamatergic act - what do they act on
Voltage Gated Sodium
Channel
Voltage Gated Calcium
Channel
Exocytosis and Receptors
what drugs affect VGSCs on glutamatergic neurones and how
Carbamezapine - Stabilises inactive state of Na+ channel
Lamotrigine - Inactivates Na+ channels
pharmacokinetics of Carbamezapine
Enzyme inducer (drug-drug interactions)
Onset of activity within 1 hour
16-30 hour half-life
what is a potential issue/consideration with Carbamezapine
potential severe side-effects (Steven-Johnsons Syndrome and
Toxic Epidermal Necrolysis) in individuals with HLA-B*1502 allele
pharmacodynamics of Lamotrigine
Onset of activity within 1 hour
24-34 hour half-life
what drugs affect VGCCS and how
Ethosuximide - T-type (Transient calcium channel found in CNS) Ca2+ channel
antagonist
reduces activity in relay thalamic neurones
pharmacokinetics of Ethosuximide (t half)
Long half-life (50 hours)
what drugs affect exocytosis and receptors
Levetiracetam - Binds to SVA2
(preventing glutamate release)
Topiramate - Inhibits NMDA & kainate receptors
Topiramate pharmacokinetics
Fast-onset (1 hour); long half-life (20 hours)
how do you remember the indications for each drug acting on the Glutamatergic neurones
drugs acting on VGSC: Tonic-Clonic Seizures
drugs acting on T-type VGCC:
only useful in absence seizures
drugs on exocytosis and rc myoclonic seizures
what 2 ways can GABA be released
tonically and following neuronal stimulation
what does GABA activate
inhibitory post-synaptic GABAa rc
what are GABArc and what does activation of them cause
CL- channels
membrane hyperpolarisation
what is GABA taken up by and metabolised by
taken up: GAT
metabolised by: GABA transaminase (GABA - T)
what are the drugs affecting the GABAergic synapses and their mechanisms
Diazepam - Positive Allosteric Modulator (potentiator of GABAa receptor)
Sodium Valproate - Inhibits GABA transaminase
what are the drugs affecting the GABAergic synapses and their mechanisms
Diazepam - Positive Allosteric Modulator (potentiator of GABAa receptor)
Sodium Valproate - Inhibits GABA transaminase
BOTH INCREASES GABA MEDIATED INHIBITION
pharmacokinetics of diazepam
Rectal gel - Fast-onset (within 15 min); half-life (2 hours)
Indications of diazepam
Status epilepticus
emergency
why don’t you want people on diazepam for long time
dependancy, withdrawal symptoms, tolerance
pharmacokinetics of sodium valproate
Fast onset (1h); half-life (12h)
indications of sodium valproate
ALL forms of epilepsy. V commonly used drug.
