Antiepileptics/ anticonvulsants Flashcards
General definition of epilepsy
Unprovoked seizures caused by high frequency discharge from group of neurones in particular part of brain
Can be Partial or generalised
Diagnosis with EEG
What is a partial seizure?
Where the spread of electrical activity is limited to one part of the brain
What is a generalised seizure?
Where electrical activity spreads to both hemispheres of the brain
What are the categories of generalised seizures?
Simple generalised seizure (petit mal)= no loss of consciousness, absence seizures
Complex generalised seizure (grand mal)= loss of consciousness, tonic-chlonic seizures
Difference between a partial and generalised epilepsy EEG
Partial epilepsy EEG there is only electrical activity in certain lobes of the brain not all
Generalised epilepsy EEG has rhythmic activity across all lobes
What are the three brain lobes?
Frontal, Temporal, Occipital
Name 3 types of animal models of epilepsy
Genetic, chemical and kindling model
What can happen if a grand mal seizure is uncontrolled?
Leads to neuronal death
Describe the EEG of an absence petit mal seizure
Characteristic oscillatory waves in all lobes of the brain
What can give rise to different types of epilepsy?
Mutations in voltage gated ion channels
Mutations in ligand gated ion channels
What 2 types of mutations can lead to epilepsy?
Gain of function mutations- Increased depolarisation leading to more action potentials
Loss of function mutations- Reduced hyperpolarisation leading to more action potentials as the membrane potential doesn’t polarise (become positive)
Name 2 ligand gated ion channels that if mutated can lead to epilepsy
Nicotinic receptors and GABA receptors in the brain
Describe three chemical animal models of epilepsy
- Penicillin applied directly to the brain inhibits GABA receptors and leads to increased electrical activity
- PTZ added to water causes abnormal swimming patterns in zebrafish (blocks GABA receptors)
- Kainate is agonist of glutamate receptors, excess kainate increases glutamate receptor activation leading to seizures
Describe the kindling model of epilepsy
Mainly in rodents
Apply low level electrical current to certain area of the brain repeatedly over several weeks
Animal develops partial epilepsy in that part of brain
Used for drug testing
What can an anti-convulsant targeting GABA do?
- Work directly to target the GABA receptor, increase it’s affinity for GABA
- Inhibit GABA reuptake, GABA stays in synaptic cleft for longer therefore increasing stimulation of GABA on post synaptic receptors
- Block enzymes from metabolising GABA into succinate
