GABA and Epilepsy

Question 1

What diseases are caused when the balance of excitation and inhibition is imbalanced in favour of excitation?

Answer 1

Anxiety, Epilepsy, etc

Question 2

What is the relationship between the imbalance of excitation and inhibition and development?

Answer 2

The imbalance usually occurs early in development, correcting developmental problems could cure rather than treat epilepsy Most drugs are antiepileptic rather than anti-epileptogenic

Question 3

Basic outline of epilepsy

Answer 3

A common chronic neurological disorder characterised by unprovoked disturbance electrical rhythms typically manifested by seizures

Question 4

Epidemiology of epilepsy

Answer 4

Effects 0.5 to 1% of the population Variety causes (heritable, trauma, anaesthesia, unknown) Starts locally, progresses to other brain areas Site and degree of spread determines symptoms

Question 5

What is the most common cause of epilepsy?

Answer 5

heritability

Question 6

How long after head injury does the epileptogenic process take?

Answer 6

Around 4 or 5 years

Question 7

What the two major categories of seizure?

Answer 7

Generalised and partial

Question 8

What is difference between simple and complex partial seizures?

Answer 8

in simple partial seizures consciousness is preserved and in complex it is compromised

Question 9

What are the types of generalised seizure?

Answer 9

Absence, tonic-clonic, myotonic, myoclonic, atonic

Question 10

Absence seizures

Answer 10

Formerly petit mal Momentary lapses of consciousness/awareness

Question 11

Tonic-clonic seizures

Answer 11

Formerly grand mal Initial chronic phase resulting in rigid exteriors person (about one minute) followed by chronic stage (series of synchronous jerks; about 2 to 4 minutes)

Question 12

Myotonic seizures

Answer 12

Sudden muscle contractions

Question 13

Myoclonic seizures

Answer 13

Involuntary twitching of muscle

Question 14

Atonic seizures

Answer 14

Loss of all muscle tone and then collapse

Question 15

Partial seizures (in general)

Answer 15

Abnormal electrical activity localise one area of the brain, since his dependent brain regions involved, can be motor, sensory, aphasic cognitive, affective delusional, olfactory et cetera

Question 16

Incidence of epilepsy

Answer 16

Approximately 50 million people worldwide have epilepsy epilepsy is age-related 75% of people with epilepsy of the procedure before 18

Question 17

Underlying causes of epilepsy

Answer 17

Any changes in excitability have the potential to disrupt productivity and neural circuits, this disruption is what causes seizures

Question 18

What are the possible physiological causes epilepsy?

Answer 18

Enhance excitatory amino acid transmission impaired inhibitory transmission abnormal electrical properties affected cells

Question 19

What are the different mechanisms in which antiepileptic drugs can function?

Answer 19

Enhancing GABA action Inhibit sodium channel function Inhibit calcium channel function Unidentified non-specific effects

Question 20

Property of most antiepileptic drugs?

Answer 20

Use dependency

Question 21

Which drug classes enhance the action of GABA?

Answer 21

Barbiturates e.g. phenobarbitone; benzodiazepines e.g. clonazepam, diazepam

Question 22

What can barbiturates still used for today?

Answer 22

Preventing seizure induced mini-strokes

Question 23

What kind of channel is the GABAA receptor?

Answer 23

chloride

Question 24

What happens if the status epilepticus lasts for too long?

Answer 24

Effects of benzodiazepines or barbiturates can actually reverse due to build up chloride

Question 25

Vigabatrin

Answer 25

First design epilepsy; irreversibly inhibits GABA transaminase -> thus increases releasable pool of GABA short plasma half-life but long lasting effect -> oral administration once a day Rare side effects include depression and psychotic disturbances

Question 26

Tiagabine

Answer 26

GABA analogue; adjunctive therapy for partial seizures; inhibits reuptake of GABA into neurons and glia potentiates GABA transmission; side effects include drowsiness and confusion; effective in patients resistant to established drugs

Question 27

Sodium valproate

Answer 27

Effective in controlling tonic-clonic seizures drug of choice for: primary generalised epilepsy; absence seizures; myoclonic seizures; patients with both grand mal and petit mal also used for infantile epilepsy (low sedation and toxicity)

Question 28

Proposed mechanism(s) of action for sodium valproate

Answer 28

Mildly inhibits GABA inactivation enzymes GABA-transaminase and SSA dehydrogenase Some inhibition of sodium channels Enhance post-synaptic action of GABA

Question 29

Side effects of the sodium valproate

Answer 29

Relatively free of side effects but can cause: thinning and curling of hair in 10% of patients; hepatotoxicity; spina bifida (teratogenic)

Question 30

Gabapentin

Answer 30

Designed as. a lipid soluble analogue of GABA; effective anticonvulsants but properly not by the desired mechanism plasma half life is about six hours thus dosing is required 2 to 3 times a day excreted unchanged in urine and free from drug interactions; relatively free from side effects this will efficacy when used alone thus used as an adjunctive

Question 31

Gabapentin receptor

Answer 31

Question 32

Gabapentin and synapses

Answer 32

Appears to prevent excitatory synapses formation

Question 33

Reclassification of seizures as of 2017

Answer 33

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