Epilepsy Flashcards
What causes convulsions?
Imbalance between excitary and inhibitory neurotransmission
How is epilepsy characterised?
Unprovoked seizures
High frequency discharge by a group of neurons
Partial or generalised spread
Hyperexcitability of the CNS
What is used to diagnose epilepsy?
EEG
Where does loss of consciousness take place in the brain due to convulsions?
Reticular formation
What can cause epilepsy?
Head injuries
Lesions (bleeding from age)
Tumour
Infection
Genetics
Na/K channels
GABAa
Nicotinic receptors
Where do convulsions begin in the brain?
Motor cortex
Where does autonomic discharge take place in the brain?
Hypothalamus
What triggers are there for epilepsy?
Altered blood glucose/pH
Stress
Fatigue
Flashing lights/noise
What gain of function mutations are associated with epilepsy?
Voltage gated sodium channels
With partial seizures, where is brain activity localised?
One hemisphere of the brain
What are the two types of generalised seizures?
Clonic tonic (grand mal)
Absence seizures (petit mal)
What happens in focal seizures?
Brain activity is localised to one area an causes a change in sensation, such as strange taste or smell
What chemical models have been used to test epilepsy drugs on animals?
Penicillin crystals put directly onto the brain to inhibit GABAa activity
PTZ
Kainate
What is the kindling animal model for epilepsy?
Repeated low level electrical stimulation on genetically modified animals
How do benzodiazepines and barbiturates act as anti-epileptics?
Increase GABAa transmission
How does GABApentin work?
binds to α2/β subunit of voltage gated calcium channels, decreasing action potentials
How does tiagabine act as an anti-epileptic?
Inhibits GABA uptake
How do vigabatrin and valproate act as anti-epileptics?
Act as GABA transaminases
What do GABA transaminases do?
Convert GABA to succinate semialdehyde
What does sodium valproate do?
Inhibits Na+ and GABAa channels
Inhibits HDAC, responsible for histone binding which favours DNA transcription
Not sedative
What problems can Na+ channel inhibitors cause?
Complex pharmacodynamics
Vertigo
Ataxia
Headaches
What problems are associated with lamotrigine (Na+ channel blocker)?
Nausea
Dizziness
Ataxia
Rashes
What are 3-Ca2+ channel blockers used for?
Absence seizures
Give an example of a 3-Ca2+ channel blocker
Ethosuximide
What is the mechanism of 4-Ca2+ channel blockers
Bind to the a subunit of the Ca2+ channel which is used for inserting into the plasma membrane
Binds to a protein on synaptic vesicles which controls glutamate levels
Give 2 examples of 4-Ca2+ channel blockers
GABApentin
Pregabalin
