Tutorial 2 - Epilepsy Flashcards
What is epilepsy?
A disorder of brain function characterized by the periodic and unpredictable occurrence of seizures.
What is a seizure?
A transient alteration of behaviour due to the disordered, synchronous, and rhythmic firing of populations of brain neurones.
What drugs are used to inhibit seizures?
Anticonvulsant or antiepileptic drugs
Where do seizures arise from?
The cerebral cortex
What are the 2 categories of seizure?
Partial (focal) seizures - those beginning focally at a cortical site.
Generalised seizures - those that involve both hemispheres widely from the outset.
The behavioural manifestations of a seizure depend on what?
They are determined by the functions normally served by the cortical site at which the seizure arises.
What would happen if someone had a seizure in the motor cortex?
Clonic jerking of the body part controlled by this region of the cortex.
What is a partial simple seizure?
Preservation of consciousness
What is a complex partial seizure?
Impairment of consciousness
Give 3 examples of generalised seizures.
Absence (lack of awareness), myoclonic (jerk/twitch) and tonic-clonic seizures (whole body shakes).
What neurotransmitters are involved in epilepsy that cause seizures?
A decrease in GABA mediated inhibition
An increase in glutamate-mediated excitation in the brain.
Both glutamate and GABA are thought to play key roles in the brain mechanisms causing epilepsy & seizures.
What pharmacological evidence is there to show neurotransmitters are involved in epilepsy? 6 things.
- Impairment of GABA-mediated inhibition causes seizures in animals.
- Enhancement of GABA-mediated inhibition leads to seizure suppression.
- Many clinically useful anticonvulsant drugs are known to act, by increasing the effect of central GABA-mediated inhibition.
- Central (i.c.v.; focal) administration of glutamate or glutamate receptor agonists causes seizure-like activity in animals.
- Glutamate receptor antagonists are anticonvulsant in experimental models of epilepsy.
- Some therapeutically effective anticonvulsant drugs act partly by blocking glutamate-mediated excitation in the brain e.g. phenobarbital.
What does i.c.v. mean?
Intracerebroventricular administration of drug - means lots of drug goes straight to the central part of the brain.
What biochemical evidence is there for the role of neurotransmitters in epilepsy?
- Cobalt-induced seizures in rodents are associated with ↑ glutamate release and with ↓ GABA concentration, ↓ GAD activity and ↓ GABA uptake (probably reflecting GABA neurone loss) at the seizure focus.
- Audiogenic seizures in mice (DBA/2 mice) are associated with ↑ glutamate receptor binding in the brain and with ↓ GABA release from depolarized brain slices.
- The baboon Papio papio, which is highly sensitive to photicallyinduced seizures, has a lower than normal CSF (Cerebral spinal fluid) GABA concentration.
Name 5 antiepileptic drugs.
Valproate Phenobarbital Benzodiazepines (Clonazepam and diazepam) Vigabatrin Tiagabine
How does valproate work?
Effects gaba transaminase and Na+ channels.
Stops absence seizures
How does phenobarbital work?
Enhances GABA action. Inhibition of synaptic excitation.
Helps all seizures EXCEPT absence seizures.
How do Benzodiazepines (Clonazepam and diazepam) work?
Enhance GABA action. Works on all types of seizures.
How does Vigabatrin work?
Inhibits GABA transaminase. Works for all types and good for patients resistant to other drugs.
How does Tiagabine work?
Inhibits GABA reuptake. Works for focal seizures.
Draw a diagram showing a GABA synapse and the effects of -Benzodiazepines -Phenobarbital -Vigabatrin -Tiagabine on the synapse.
Diagram
