Epilepsy Flashcards
How does epilepsy occur?
uncontrolled neuronal firing/inhibition - no balance between them
Too much Na, Ca, glutamate, aspartate = excitation
Too much Cl, K, GABA = inhibition
inhibitory inter-neuron surround excitatory cells in the brain - allow activity to only spread in one direction and not disperse by releasing GABA
in epilepsy this mechanism doesn’t work properly, leading to spreading of hyperexcitabilty
What is the definition of epilepsy?
a condition in which seizures recur, usually spontaneously
2 or more unprovoked seizures
By what modes to anti-epileptic drugs work?
decreases the frequency and/or severity of seizures in people with epilepsy
- Suppress action potential - Na channel blocker or modulator K channel opener
- Enhance GABA transmission -GABA uptake inhibitor, GABA mimetics
- Suppression of excitatory transmission - Glutamate receptor antagonist
How are seizures classified?
Generalized - with initial activation of neurones throughout both hemispheres
Partial - with the initial activation of a limited number of neurones in a part of 1 hemisphere. Where it starts can determine symptoms
Secondary generalized (a partial seizure that later spreads to involve the majority of the 2 cerebral hemispheres)
can then be classified further depending on what the person does during the seizure e.g. absence = staring and blinking without falling
fefWhat is a seizure and how does it occur?
Clinical manifestation of an abnormally excessive and hypersynchronous activity of neurones located predominantly in the cerebral cortex
cortical discharges can be transmitted to the muscles, causing twitches or convulsions
epileptic seizures manifest themselves in different ways depending on their site of origin and subsequent spread
What is an EEG and what does it show in a seizure?
Electroencephalography uses scalp electrodes to record the electrical activity along the scalp produced by the firing of neurones within the brain
high spikes during seizure
all over brain = generalised
one part of brain = partial
What is status epilepticus?
life-threatening condition
brain is in a state of persistent seizure
More than 30 mins continuous seizure activity OR
Two or more sequential seizures spanning this period without full recovery between seizures
medical emergency
SE confers greater risk for future unprovoked seizures
What is a treatment option for status epilepticus?
Diazepam - GABA(A) receptor agonist
What is GABA?
Major inhibitory neurotransmitter
Acts via:
GABA(A) receptors - ligand gated Cl receptor
GABA(B) receptors - G protein coupled receptor
normally made from 2 alpha, 2 beta, 1 gamma, 1 delta
Which epilepsies are caused by mutations in GABA(A) receptors?
CAE (childhood absence epilepsy)
FS (pure febrile seizures)
GEFS+ (generalized epilepsy with febrile seizures plus)
JME (juvenile myoclonic epilepsy)
DS (Dravet syndrome – also know as SMEI (severe myoclonic epilepsy in infancy))
What are the drugs of choice for partial and generalised seizures?
Carbamazepine
Phenytoin
Valproic Acid
What are the drugs of choice for febrile seizures?
Diazepam rectally
What drugs enhance the action of GABA(A)?
barbiturates e.g. phenobarbital
benzodiazepines e.g. clonazepam - increases Cl current
What drugs are benzodiazepines and what seizures are they most effective against?
Clonazepam - Effective in generalized tonic-clonic, absence and partial seizures
Clorazepate
- Effective against partial seizures
Diazepam (Valium) and lorazepam -
Effective against status epilepticus (IV)
What are the side effects of benzodiazepines?
Sedation
Significant problem of tolerance and dependence - Avoid long-term use
Can get respiratory depression if used i.v.
