L18: Epilepsy Pharmacology Flashcards
What is epilepsy?
Recurring spontaneous seizures, could be 50 times a day, three time a week.
EEG voltage traces are usually flat, in epilepsy they’re not.
What are the two types of seizures?
focal and generalized
What is the difference between focal and generalized seizures?
Focal onset seizures start in one area and can spread across the brain and cause mild or severe symptoms, depending on how the electrical discharges spread, mostly stay in one location. Generalized seizures can start as focal seizures that spread to both sides of the brain (tonic-clonic and absence seizures)
Which part of the brain is most vulnerable to epilepsy?
Hippocampus (temporal lobe), plastic area that makes it vulnerable to epilepsy
What is absence seizure / epilepsy?
An absence seizure, which used to be called a “petit mal”, is where you lose awareness of your surroundings for a short time. They mainly affect children, but can happen at any age. Brief moments of losing consciousness.
Why do we not have seizures all the time? What is the security system?
- Pyramidal cells are excitatory, however they also have signals from excitatory and inhibitory cells coming from the side.
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Interneurons are inhibitory by nature, however, they have signals from excitatory and inhibitory synapses equally from both sides.
This means that in case of too much excitation or too much inhibition, the signal can be tweaked.
What is the age of most people affected by epilepsy?
Epilepsy happens to either very old or very young people.
What are the main reasons for epilepsy? Why does it appear?
- tumours (for old people)
- fevers (for young children, as fever increases overall activity in the brain)
- trauma (banging the head, neural circuits altered or cut)
- genetics (hundreds of genes identified)
however, it’s still not super clear, why does it happen
How can seizures be blocked pharmacologically?
- drugs that reduce excitation
- drugs that increase inhibition
- network activity modification
- indirectly modulating excitation and inhibition
What is Maximal Electroschock Seizure (MES) test? What is it used for?
MES is a model for generalized tonic-clonic seizures and provides an indication of a compound’s ability to prevent seizure spread when all neuronal circuits in the brain are maximally active.
What is Racine Scale? What is it used for?
The Racine scale is an often-used method of evaluating seizure severity in experimental models of epilepsy.
What is subcutaneous pentylenetetrazole (PTZ) acute seizure test? What is it used for?
The pentylenetetrazol (PTZ) or Metrazol test detects the ability of a test compound to raise the chemoconvulsant-induced seizure threshold of an animal and thus protect it from exhibiting a clonic, forebrain seizure.
Test of anti-seizure drugs for myoclonic and absence seizures.
What is the difference between Pentylenetetrazole (PTZ) and Maximal Electroshock Seizure (MES) tests?
PTZ models are often associated with absence seizures whilst MES models are associated with general tonic-clonic seizures.
What are 1st generation ASDs (anti-seizure drugs)? Give examples of their types and how does it act
Barbiturates:
- Mephobarbital (stimulate GABAergic)
- Phenytoin (Na channel blocker)
- Primidone (GABA and sodium (inhibits repetitive firing of APs))
- Trimethadone (GABA sodium)
Succinimides
- Phensuximide
- Methusiximide
- Ethosuximide
What are 2nd generation ASDs (anti-seizure drugs)? Give examples of their types and how does it act
- Carbamazepine - sodium channel blocker
- Valproate - sodium channel and N and L calcium channel blocker
- Benzodiazepines - positive allosteric modulators of GABA, increase its binding, but also slow activity of sodium channels
