Lecture 13 - anti-convulsants (epliepsy)

Question 1

what is epilepsy?

Answer 1

• involves hyperexcitability of CNS and diagnosed by EEG trace.

Question 2

what is epilepsy caused by?

Answer 2

• head injury
• local lesions
• tumours
• mutations in channels involved with generating AP

Question 3

what are symptoms characterised by?

Answer 3

by location of the brain affected and how it spreads through these different areas of the brain

Question 4

what is partial epilepsy?

Answer 4

where spread is limited to a particular part of the brain

Question 5

what is generalised epilepsy

Answer 5

both hemisphere of the brain are affected

Question 6

what can epilepsy be triggered by?

Answer 6

• changes in blood glucose levels or pH
• stress
• fatigue
• overwhelmed by sensory input
• results in neuronal death.

Question 7

gainer mutations of voltage-gated sodium channels

Answer 7

gainer mutations for depolarisation causes hyperexcitability of neurons where they fire action potentials inappropriately.

Question 8

how do mutations effect potassium channels?

Answer 8

causes a loss of function

Question 9

what do partial seizures look like on EEG?

Answer 9

causes involuntary muscle contraction, abnormal sensory experience with effects on mood, known as psychomotor epilepsy. confined to one hemisphere

Question 10

generalised seizure on an EEG

Answer 10

• whole brain is affected and immediate loss of consciousness.
• includes tonic-clonic (grand mal) and absence seizures.
• treated with drugs involving calcium channels

Question 11

chemical animal model for epilepsy

Answer 11

• penicillin applied directly on brain will cause seizures as it inhibits GABAa receptors
• kainic injections causes excitotoxicity and local damage of inhibitory neurons

Question 12

electrical animal model of epilepsy

Answer 12

kindling model involves repeated low electrical stimulation to cause localised hypersensitivity

Question 13

genetic animal model for epilepsy

Answer 13

genetically modified animals that carry mutations in the receptors involved in action potential generation

Question 14

how do anti-epileptic drugs work?

Answer 14

1. increasing activity of GABAa receptor
2. inhibiting GABA uptake
3. inhibiting metabolism of GABA

Question 15

drugs that increase GABA transmission

Answer 15

1. Benzodiazepines and barbiturates (causes sedation)
2. uptake inhibitors e.g. tiagabine
3. metabolic inhibitors e.g. valproate

Question 16

what is the action of valproate?

Answer 16

increases brain levels of GABA through inhibition of GABA aminotransferase. also effects sodium channels and NMDA receptor-mediated actions further

Question 17

how is GABA synthesised?

Answer 17

• from a precursor of glutamate which is one of metabolites in Krebs cycle. GAD converts glutamate into GABA

Question 18

what does GABA transaminase do?

Answer 18

inhibits GABA production

Question 19

what drug increases the transcription of GAD?

Answer 19

valproate by increasing the open DNA

Question 20

target for anti-epileptic drugs

Answer 20

drugs that target sodium channels prevents action potentials from occurring to decrease excitatory neurotransmission to limit the spread

Question 21

what is the problem for anti-epileptic drugs that target sodium channels?

Answer 21

• sodium channels found in all nerves and muscle so selectivity for specific effected neurons is not possible so there are side effects

Question 22

what are the three states of a sodium channel?

Answer 22

1. resting where channel is closed
2. activated where channel is open caused by depolarisation
3. inactive due to blockage of channel by a protein.

Question 23

sodium channel inhibitors used in treatment of epilepsy

Answer 23

1. phenytoin (dilantin) to treat partial seziures and grand mal
2. carbamazepine (tegretol) is most used and works with partial and generalised
3. Lamotrigine (lamictal) used in combination with other drugs for partial

Question 24

what are the problems with phenytoin (dilantin)

Answer 24

has limited solubility so given orally and causes vertigo, ataxia and headaches. has difficulty to control levels

Question 25

what are the problems with carbamazepine (tegretol)?

Answer 25

has limited water solubility and slow absorption so has antidiuretic effects. should not be combined with other drugs.

Question 26

antiepileptic drugs (calcium channel blockers)

Answer 26

1. ethosuximide (zarontin) T calcium channel blocker and used for abscence seizures. long half life
2. GABApentin acts on subunit of calcium channels