Lecture 13 - anti-convulsants (epliepsy) Flashcards
what is epilepsy?
- involves hyperexcitability of CNS and diagnosed by EEG trace.
what is epilepsy caused by?
- head injury
- local lesions
- tumours
- mutations in channels involved with generating AP
what are symptoms characterised by?
by location of the brain affected and how it spreads through these different areas of the brain
what is partial epilepsy?
where spread is limited to a particular part of the brain
what is generalised epilepsy
both hemisphere of the brain are affected
what can epilepsy be triggered by?
- changes in blood glucose levels or pH
- stress
- fatigue
- overwhelmed by sensory input
- results in neuronal death.
gainer mutations of voltage-gated sodium channels
gainer mutations for depolarisation causes hyperexcitability of neurons where they fire action potentials inappropriately.
how do mutations effect potassium channels?
causes a loss of function
what do partial seizures look like on EEG?
causes involuntary muscle contraction, abnormal sensory experience with effects on mood, known as psychomotor epilepsy. confined to one hemisphere
generalised seizure on an EEG
- whole brain is affected and immediate loss of consciousness.
- includes tonic-clonic (grand mal) and absence seizures.
- treated with drugs involving calcium channels
chemical animal model for epilepsy
- penicillin applied directly on brain will cause seizures as it inhibits GABAa receptors
- kainic injections causes excitotoxicity and local damage of inhibitory neurons
electrical animal model of epilepsy
kindling model involves repeated low electrical stimulation to cause localised hypersensitivity
genetic animal model for epilepsy
genetically modified animals that carry mutations in the receptors involved in action potential generation
how do anti-epileptic drugs work?
- increasing activity of GABAa receptor
- inhibiting GABA uptake
- inhibiting metabolism of GABA
drugs that increase GABA transmission
- Benzodiazepines and barbiturates (causes sedation)
- uptake inhibitors e.g. tiagabine
- metabolic inhibitors e.g. valproate
what is the action of valproate?
increases brain levels of GABA through inhibition of GABA aminotransferase. also effects sodium channels and NMDA receptor-mediated actions further
how is GABA synthesised?
- from a precursor of glutamate which is one of metabolites in Krebs cycle. GAD converts glutamate into GABA
what does GABA transaminase do?
inhibits GABA production
what drug increases the transcription of GAD?
valproate by increasing the open DNA
target for anti-epileptic drugs
drugs that target sodium channels prevents action potentials from occurring to decrease excitatory neurotransmission to limit the spread
what is the problem for anti-epileptic drugs that target sodium channels?
- sodium channels found in all nerves and muscle so selectivity for specific effected neurons is not possible so there are side effects
what are the three states of a sodium channel?
- resting where channel is closed
- activated where channel is open caused by depolarisation
- inactive due to blockage of channel by a protein.
sodium channel inhibitors used in treatment of epilepsy
- phenytoin (dilantin) to treat partial seziures and grand mal
- carbamazepine (tegretol) is most used and works with partial and generalised
- Lamotrigine (lamictal) used in combination with other drugs for partial
what are the problems with phenytoin (dilantin)
has limited solubility so given orally and causes vertigo, ataxia and headaches. has difficulty to control levels
what are the problems with carbamazepine (tegretol)?
has limited water solubility and slow absorption so has antidiuretic effects. should not be combined with other drugs.
antiepileptic drugs (calcium channel blockers)
- ethosuximide (zarontin) T calcium channel blocker and used for abscence seizures. long half life
- GABApentin acts on subunit of calcium channels
