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BMSC2223 Neuropharmacology > Seizures and Epilepsy > Flashcards

Seizures and Epilepsy Flashcards

1
Q

What is the cause of a seizure?

A

Excessive and hypersynchronous activity in cerebrocortical neurones

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2
Q

What is epilepsy?

A

A condition that involves recurring seizures

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3
Q

How many people will experience a seizure in their lifetime?

A

Approx 9%

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4
Q

What is idiopathic epilepsy?

A

Epilepsy with no identifiable cause

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5
Q

What is symptomatic epilepsy?

A

Epilepsy with an identifiable cause

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6
Q

What is cryptogenic epilepsy?

A

Epilepsy where a cause is suspected but not confirmed

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7
Q

What is a generalised seizure?

A

A seizure that affects neurones in both cerebral hemispheres

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8
Q

What is a partial seizure?

A

A seizure that affects neurone in only one hemisphere

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9
Q

What is a secondary generalised seizure?

A

When a partial seizure which only affects one hemisphere spreads to involve both hemispheres

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10
Q

What is status epilepticus?

A

When a seizure occurs for more than 30 minutes without complete recovery

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11
Q

What is meant by a simple partial seizure?

A

A partial seizure where consciousness is retained

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12
Q

What is meant by a complex partial seizure?

A

A partial seizure where consciousness is impaired

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13
Q

Describe the Montreal procedure

A

A patient undergoes brain surgery using local anaesthetic. The surgeon stimulates different regions of the cortex to elicit a sensation. Any regions that elicit a sensation that usually precedes a seizure is surgically removed

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14
Q

Which neurones are typically affected during a generalised seizure?

A

Thalamocortical neurones

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15
Q

What are the symptoms of a generalised seizure?

A

Bilateral symmetrical muscle contractions and loss of consciousness

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16
Q

What are the types of generalised seizure?

A 
Absence
Myoclonic
Tonic-clonic
Tonic
Atonic
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17
Q

What is the most common type of seizure?

A

Complex partial

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18
Q

How can seizures be diagnosed?

A

Using electroencephalography to detect the synchronous firing of cortical neurones which reads as large waves

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19
Q

What type of EEG waves are typically seen during a seizure?

A

Delta waves

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20
Q

What may cause seizures?

A 
Hypoxia in utero
Brain injuries
Ischaemic or haemorrhagic strokes
Infections
Tumours
Congenital abnormalities
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21
Q

What typically causes genetic epilepsies that follow Mendelian patterns?

A

Ion channelopathies

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22
Q

What evidence is there to suggest polygenic inheritance of epilepsy?

A

The majority of people with epilepsy do not have relative with epilepsy, suggesting multiple genes and environmental factors are involved

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23
Q

Describe the excess excitation mechanism of seizure activity

A

Excessive inward sodium or calcium currents

Excessive release of glutamate or aspartate

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24
Q

Describe the insufficient inhibition mechanism of seizure activity

A

Excessive inward chloride or potassium currents

Insufficient GABA release

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25
Q

Which neurones typically prevent hyperexcitability?

A

Inhibitory interneurones

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26
Q

Which neurotransmitter is the main inhibitory neurotransmitter?

A

GABA

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27
Q

Which channel is mainly involved in seizures?

A

GABAa chloride ligand channel

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28
Q

How many proteins make up the GABAa receptor?

A

5 separate proteins

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29
Q

Which subunits make up the GABAa receptor?

A

Two alpha
Two beta
One gamma

30
Q

Describe how the Gamma-2 nonsense mutation results in Dravet syndrome

A

The nonsense mutation results in a premature stop codon which truncates the protein. The truncated protein is more hydrophilic so becomes a cytolic protein rather than a membranal protein, causing a lack of GABA receptors

31
Q

How is status epilepticus treated?

A

Diazepam

32
Q

What is the animal model for status epilepticus?

A

The animal is injected with pilocarpine which induces SE. 2 weeks post injection, epileptogenesis occurs where spontaneous seizures occur until death

33
Q

Describe the processes underlying epileptogenesis

A

Alpha-1 subunit expression decreases

The receptor subtypes may change to ones that desensitise more rapidly resulting in disinhibition

34
Q

What are the aims of antiepileptic drug treatment?

A

To suppress action potentials
To enhance GABA transmission
To suppress glutamatergic transmission

35
Q

Describe the mechanism of barbiturates

A

Enhance GABAa receptor action

36
Q

Give an example of a barbiturate

A

Phenobarbital, thiopental sodium

37
Q

Describe the mechanism of benzodiazepines

A

Increases GABA’s affinity for GABAa receptors to increase the chloride current and raise the action potential inhibition

38
Q

What are the actions of a benzodiazepine?

A

Sedation, hypnosis, anxiolysis, anticonvulsive, relaxation and amnesia

39
Q

Give an example of a benzodiazepine

A

Diazepam, clonazepam, clorazepate, lorazepam

40
Q

What seizures does clonazepam treat?

A

Tonic-clonic
Absence
Partial

41
Q

What seizures does clorazepate treat?

A

Partial

42
Q

What seizures does diazepam treat?

A

Status epilepticus

43
Q

What seizures does lorazepam treat?

A

Status epilepticus

44
Q

Which subunits may be rendered diazepam insensitive?

A

Alpha2, alpha3 and alpha5

Point mutation which substitutes histidine to arginine

45
Q

How can a benzodiazepine overdose be treated?

A

Patient given flumezanil

46
Q

Why are benzodiazepines preferred over barbiturates?

A

Barbiturates have a much narrower therapeutic window

47
Q

When could a dose of benzodiazepines become lethal?

A

If the drug is taken alongside another depressant drug, such as alcohol, oxycodone or doxylamine

48
Q

Why is treatment with benzodiazepines not preferred?

A

Benzodiazepines are addictive and tolerance is common

49
Q

What is the mechanism of GABA transaminase inhibitors?

A

They inhibit GABA transaminase to prevent GABA breakdown

50
Q

Give an example of a GABA transaminase inhibitor

A

Vigabatrin

51
Q

Give an example of a GABA reuptake inhibitor

A

Tiagabine

52
Q

What is the mechanism of a GABA reuptake inhibitor?

A

Prevent the reuptake of GABA into the neurone to increase the concentration in the synapse

53
Q

Describe the mechanism of sodium channel inhibitors?

A

Inhibit sodium channels to slow recovery and prevent reactivation

54
Q

Give an example of a sodium channel inhibitor?

A

Phenytoin, carbamazepine, lamotrigine

55
Q

When will phenytoin bind to a sodium channel?

A

Only when it is firing, resulting in use-dependent blockade

56
Q

How is phenytoin administered?

A

Orally

57
Q

Why should phenytoin not be prescribed with an albumin binding drug?

A

Phenytoin is largely albumin bound
Cotherapy with another albumin binding drug, results in unpredictable concentrations of free phenytoin and hepatic clearance making it difficult to dose

58
Q

What occurs to the half life of phenytoin as the dose increases?

A

The half life increases

59
Q

Why should phenyltoin not be prescribed during pregnancy?

A

Risk of foetal hydrantoin syndrome

60
Q

What are the symptoms of foetal hydrantoin syndrome

A 
Microcephaly
Dysmorphic craniofacial features
Limb defects
Developmental delays
Heart defects
Cleft lip
61
Q

What is the mechanism of valproic acid?

A

Inhibits sodium channels and succinic semialdehyde dehydrogenase. The inhibition of SSD indirectly inhibits GABA transminase
Inhibition of T-type calcium channels

62
Q

What is the risk of taking valproic acid during pregancy?

A

Foetal valproate syndrome causing congenital malformations

63
Q

What causes the congenital malformations in foetal valproate syndrome

A

Inhibition of histone deacetylases which results in hyperacetylation of chromatin and increases gene transcription

64
Q

What are the drug choices for partial seizures?

A

Carbamazepine
Phenytoin
Valproic acid

65
Q

What are the drug choices for tonic clonic seizures?

A

Carbamazepine
Phenytoin
Valproic acid

66
Q

What are the drug choices for absence seizures?

A

Ethosuximide, valproic acid

67
Q

What is the drug choice for atonic seizures?

A

Valproic acid

68
Q

What is the drug choice for myoclonic seizures?

A

Valproic acid

69
Q

What is the drug choice for febrile seizures?

A

Rectal diazepam

70
Q

Describe how optogenetics may be used experimentally to treat refractory epilepsy?

A

Halorhodopsins are a light activated chloride channel which cause hyperpolarisation in response to yellow light and can work as a GABA receptor if introduced to neurones

71
Q

Which epilepsy models have optogenetics been trialled and found to be successful in rodents?

A

Epilepsia partialis continua

Temporal lobe epilepsy

BMSC2223 Neuropharmacology (6 decks)

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