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L2 pharmacology > CNS 2 - Antiepileptics > Flashcards

CNS 2 - Antiepileptics Flashcards

1
Q

What are partial seizures?

A

When the abnormal electrical activity is limited to a certain area of the brain

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2
Q

What are generalised seizures?

A

When the abnormal electrical activity involves both hemispheres of the brain

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3
Q

What are simple generalised seizures?

A

Don’t involve loss of consciousness

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4
Q

What are the 2 main categories of seizures?

A
  • Partial
  • Generalised
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5
Q

What are the 2 types of generalised seizures?

A
  • Simple
  • Complex
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6
Q

What are complex generalised seizures?

A

Always involve loss of consciousness

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7
Q

What symptoms would be seen during a seizure affecting the motor cortex?

A

Body convulsions

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8
Q

What symptoms would be seen during a seizure affecting the hypothalamus?

A

Autonomic reflexes e.g. salivating, sweating

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9
Q

What symptoms would be seen during a seizure affecting the reticular formation?

A

Loss of consciousness

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10
Q

What factors are triggers for seizures? (4)

A
  • Change in blood glucose/pH
  • Stress
  • Fatigue
  • High sensory input e.g. flashing lights
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11
Q

What can cause the development of epilepsy? (5)

A
  • Head injury
  • Local lesion (e.g. bleed)
  • Tumour
  • Infection
  • Genetics
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12
Q

How is epilepsy diagnosed

A

EEG

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13
Q

What is a grand mal seizure?

A
  • Typical loss of consciousness and violent convulsions
  • Also known as tonic-clonic seizure
  • Generalised
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14
Q

What is a petit mal seizure?

A
  • Absence seizure
  • Characteristic oscillatory trace on EEG
  • Generalised
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15
Q

What can happen when grand mal seizures are uncontrolled?

A

Neuronal death

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16
Q

What mutations can cause inherited forms of epilepsy? (4)

A
  • Na+ channels (gain of function)
  • K+ channels (loss of function)
  • Nicotinic receptors
  • GABA receptors
17
Q

What animal models are used to study epilepsy? (3)

A
  • Genetic models
  • Chemical models
  • Kindling model
18
Q

What are genetic models for epilepsy?

A

Genetically modify rodents/zebrafish to introduce mutations which are associated with epilepsy in humans in order to study drug effects

19
Q

What chemical models are used to study epilepsy? (3)

A
  • Penicillin crystals cause seizures when applied directly to the brain by blocking GABA receptors
  • PTZ blocks GABA receptors and causes seizures
  • Kainate is an agonist for glutamate receptors which can cause seizures
20
Q

What is the kindling model for epilepsy?

A
  • Repeatedly apply electrical stimulus to an area of the brain over time
  • Animal develops partial seizures in that area
21
Q

Which drugs treat epilepsy by increasing inhibitory GABA transmission? (4)

A
  • Benzodiazepines (emergency)
  • Barbiturates (rarely used)
  • GABA uptake inhibitors e.g. tiagabine
  • Metabolic inhibitors e.g. valproate, vigabatrin
22
Q

What is status epilepticus?

A

An emergency situation where a seizure doesn’t end

23
Q

How is status epilepticus treated?

A

IV diazepam

24
Q

How is GABA made?

A

Glutamate converted into GABA by GAD enzyme

25
Q

How can GABAergic neurones be identified?

A

Expression of GAD

26
Q

What is the main excitatory neurotransmitter in the CNS?

27
Q

What is the target of GABA metabolic inhibitors valproate and vigabatrin?

A

GABA transaminase

28
Q

Which enzymes are involved in GABA metabolism? (2)

A
  • GABA transaminase
  • Succinate-semialdehyde dehydrogenase
29
Q

How might valproate be working at the level of transcription?

A

By inhibiting HDACs, the uncoiled form of DNA is favoured so transcription factors can bind meaning more transcription of GAD

30
Q

Which drugs treat epilepsy by decreasing excitatory glutamate transmission?

A

Use-dependent Na+ channel inhibitors

31
Q

How do use-dependent Na+ channel inhibitors work?

A
  • Bind to Na+ channels in the inactivated state and prolong this phase to reduce the number of channels available to generate action potentials
  • Targets only the hyperexcitable neurons because they will have the most channels in the inactivated state
32
Q

What are examples of use-dependent Na+ channel inhibitors? (3)

A
  • Carbamazepine
  • Phenytoin (older)
  • Lamotrigine
33
Q

What is the most widely used anti-epileptic drug?

A

Carbamazepine

34
Q

How are absence seizures treated?

A

T-type Ca2+ channel inhibitor ethosuximide

35
Q

How do Gabapentin and pregabalin work?

A

Bind to a subunit of voltage gated Ca2+ channel and prevent trafficking to the membrane

36
Q

What is a new drug being used for epilepsy?

A

Levetiracetam

37
Q

How does Levetiracetam work?

A

Binds to a protein on synaptic vesicles involved in controlling glutamate levels inside vesicles and reduces the amount of glutamate released by neurons

38
Q

What drugs are being developed for epilepsy treatment? (2)

A
  • Glutamate receptor antagonists
  • Cannabidiol (CBD)

L2 pharmacology (9 decks)

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