Epilespy Flashcards
What is a seizures?
The clinical manifestation of an abnormally excessive and hypersynchronous activity of neurones located predominantly in the cerebral cortex
Why do epileptic seizures manifest in different ways?
It depends on their site of origion and subsequent spread.
How does epileptic seuizures occur?
The cortical discharges can be transmitted to the muscles, causing twitches or convulsions
What are the 3 classification of seizures?
Generalized (
Partial
Secondary generalized
What is the generalized classification of seizures?
With initial activation of neurones throughout both hemispheres
What is the partial classification of seizures?
With the initial activation of a limited number of neurones in a part of 1 hemisphere
What is secondary generalized seizures?
A partial seizure that later spreads to involve the majority of the 2 cerebral hemispheres)
What is a tonic-clonic seizure?
Typical type with stiffening, fallng and jerking of the body –> example of generalized seizure
What occurs with a complex seizure?
Type of partial seizure were there is seizure activity with change in awareness of surroudnings
What is the manifestation of partial seizuredependent on?
Depends on the site of origion
What is electroencephalogram?
Electroencephalography (EEG) uses scalp electrodes to record the electrical activity along the scalp produced by the firing of neurones within the brain.
What is status epolepticus?
Status epilepticus (SE) is a life-threatening condition in which the brain is in a state of persistent seizure
What has to occur for a person to be defined as having status epilepticus?
More than 30 mins continuous seizure activity OR
Two or more sequential seizures spanning this period without full recovery between seizures
What is the complication of status epilepticus?
SE is a medical emergency because the longer a seizure lasts, the less likely it is to stop on its own
SE confers greater risk for future unprovoked seizures
What is the treatment for status epilepticus?
Injection of GABAa receptor agonist
What is a definition of epilepsy?
Epilepsy can then be defined as a condition in which seizures recur, usually spontaneously; a single seizure episode is not considered as epilepsy, i.e. 2 or more unprovoked seizures
What caues to much neuronal activity and therefore seizures?
Excitation –> to much
Ionic—Na+, Ca2+ influx
Neurotransmitter—glutamate, aspartate release
Or
Inhibition (too little)
Ionic—CI- influx, K+ efflux
Neurotransmitter—GABA release
What is the normal status quo of the brain?
Normally in the brain very small numbers of brain cells are active at any given time –> tightly focused the activity and not allowed to spread.
What allows brain activity to spread in one direction but not to spread out sideways?
A group of brain cells called inhibitory interneurones
They release the inhibitory neurotransmitter GABA
What percentage of neurones are interneurones?
Just 10–20%
What happens in the absence of inhibitory nternurones?
The initially localized hyperexcitability spreads into surrounding neuronal networks after involving more and more neurones, cause a clinically visible seizure
GABA is a major inhibitory neurotransmitter found in 30% of syanapses and acts on two different receptors. What are they and which one is targete dby epileptic drugs?
GABAa–> affects ligand gated chloride channel receptor
GABAb –> G protein coupled receptor
Epileptic drugs act on to GABAa to prevent the brain waves and seizures
What are the normal 5 subunits of GABAa receptor?
Pentameric: typical in vivo subunit composition is two α, two β and one γ or δ subunit
What determines the intrinisc properties of the GABAa channels? What is the implications of this?
It is effected by the GABAa subunit composition –> which effects the ability of different drugs on the receptor
What are the different types of known epilepsies causes by GABAa receptor mutation?
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 is the characteristic of Dravet syndrome?
Patients experience frequent seizures, poor seizure control, and developmental delays. -
What is the action of antiepileptic drugs?
A drug which decreases the frequency and/or severity of seizures in people with epilepsy
Treats the symptom of seizures, not the underlying epileptic condition
Correct classification of seizures leads to correct Anti epileptic drug selection
What are the mode of actions of antiepileptic drugs?
1)Suppress action potential:
Sodium channel blocker or modulator
Potassium channel opener
- Enhance GABA transmission
GABA uptake inhibitor
GABA mimetics - Suppression of excitatory transmission
Glutamate receptor antagonist
What are the different actions that a anticonvulsant can have?
Enhancement of GABAergic transmission
Inhibition of Na+ channels
Mixed actions–> Combination of some or all of the above and also inhibiting neurotransmitter release
What is the choice of drug for partial or partial complex seizure?
Carbamazepine
Phenytoin
Valproic Acid
What is the choice of drug for generalised tonic clonic seizure?
Carbamazepine
Phenytoin
Valproic Acid
What is the choice of drug for absence seizure?
Ethosuximide
Valproic Acid
What is the choice of drug for Atypical absence
Atonic, myoclonic
seizure?
Valproic Acid
What is the choice of drug for febrile seizures?
Diazepam and rectal
What are the various methods of enhancing GABA action?
Enhance action of GABAA receptors with barbiturates e.g. phenobarbital
Enhance action of GABAA receptors with benzodiazepines e.g. clonazepam
Inhibit GABA transaminase - vigabatrin
Inhibit GABA uptake – tiagabine
Give examples of different types of Benzodiazepines and there action?
Clonazepam
Effective in generalized tonic-clonic, absence and partial seizures
Clorazepate
Effective against partial seizures
Used in conjunction with other drugs
Diazepam (Valium) and lorazepam
Effective against status
epilepticus when given i.v.
What is the mode of action of benzodiazepines?
Increase affinity of GABA for
its receptor by:
Increases Cl- current (opening frequency)
Suppresses seizure focus by raising action potential threshold
Strengthens surround inhibition – prevents spread
What is the side effect of benzodiazepine?
Sedation
What is the complications of taking benzodiazepines?
Significant problem of tolerance and dependence
Avoid long-term use
Can get respiratory depression if used i.v.
Gve 4 examples of drugs that inhibit sodium channels?
Phenytoin
Carbamazepine and oxcarbamazepine
Lamotrigine
Common way in which epileptic drugs act
What is the mechanism of action of phenytoin?
Phenytoin binds to the inactivated state and slows down its recovery
What occurs during action potential of voltage dependent sodium channel?
Closed – before activation
Open – during depolarisation
Inactivated – shortly after the peak of depolarisation
Na+ channels do not recover from the inactivated state until the membrane has repolarised
Give 3 examples of AED that have mixed actions?
Gabapentin
Valproate (valproic acid)
Levetiracetam
what is unusual about valproate?
Not related chemically to the other classes of anti-epileptics
Unusual in that it is effective against both tonic-clonic and absence
What other illness can valproate be used in?
Useful in bipolar depressive illness
How is valproate taken?
Taken orally
Well absorbed
What is the different mechanisms of Valproate? (3)
Inhibits Na+ channels but weaker than phenytoin
Decreased GABA turnover
Inhibition of succinic semialdehyde dehydrogenase and thereby indirectly inhibiting GABA transaminase
May lead to increased synaptic GABA levels
Blocks neurotransmitter release by blocking T-type Ca2+ channels
Should antiepileptics drugs be given in pregnancy?
Seizure very harmful for pregnant women
Monotherapy usually better than drug combination
Folic acid is recommended to be given for every pregnant women with epilepsy
What AED should definetly not be given to a pregnant lady?
Phenytoin, valproic acid are absolutely contraindicated and oxcarbamazepine is better than carbamazepine
What drug mainly causes Foetal hydantoin sydndrome?
Up to 30% of children whose mothers are taking phenytoin during pregnancy develop FHS
What is the presentation of foetal hydantoin syndrome?
Intrauterine growth restriction with microcephaly
Minor dysmorphic craniofacial features and limb defects including hypoplastic nails and distal phalanges (birth defects)
A smaller population will have growth problems and developmental delay, or mental retardation
Heart defects and cleft lip may also be featured
What other drug may cause Foetal hydantoin syndrome?
Carbamazepine can cause this but reports have been less common
What is the increase chance of developing Foetal Valproate Syndrome (FVS) if the mother is taking valporic acid?
There is a 6-9% risk of congenital malformations in infants exposed to VPA prenatally, compared to 2-3% in the general population
What is optogenetic stimulation?
It is the introduction of halorhopdsins into the brain taht reacts to yellow light and allows the chlordie to enter the cell and hyperpolarize the neurones.
What is Epilepsia partialis continua?
A rare type of brain disorder
Patient experiences recurrent motor epileptic seizures that are focal (hands and face)
Recur every few seconds or minutes for extended periods (days or years)
What is the cause of Epilepsia partialis continua?
Usually due to large, acute brain lesions resulting from strokes in adults and focal cortical inflammatory processes in children
Is there any treatment for epilepsia partialis continua?
They are very medication and therapy-resistant, and the primary therapeutic goal is to stop secondary generalization
