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Phys Pharm > Epilepsy > Flashcards

Epilepsy Flashcards

1
Q

What is epilepsy?

A

A disorder of the CNS characterised by recurren, sudden large increases in electrical activity (electrical seizures) that may be localised or generalised.

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2
Q

Prevalence of epilepsy?

A

How many people suffer!
- 2-5% of kids suffer 1 or more seizure (benign febreile convulsions) and of those 10% go onto to develop some form of adult epilepsy.

0.5 - 1% of adults have active epilepsy (men more likely as have jobs where more likely to bang head).

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3
Q

Incidence of epilepsy?

A

How many new cases per year?

0.1%
More common in children or elderly.

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4
Q

What do the symptoms of epilepsy depend on?

A

CNS region that the seizure occurs in.

Whether localised or general and if local - does it then spread?

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5
Q

Define partial.

A

Localised to a limited region.

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6
Q

Define primarily generalised.

A

Most CNS involved - no apparent focus.

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7
Q

Define secondarily generalised.

A

Most CNS involved - spread from initial focus.

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8
Q

Define simple.

A

Subject remains conscious.

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9
Q

Define complex.

A

Consciousness is impaired.

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10
Q

What tends to precede a seizure?

A

An aura - a smell, a tune.

These may be subcortical seizures.

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11
Q

What are absence seizures?

A

Primarily generalised, common in children, sudden loss of awareness for approx 30 seconds.

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12
Q

What are tonic clonic seizures?

A 
Primarily generalised, 2-5 minutes.
Sudden stiffening ('tonic') of muscles. A fall. Jerking ('clonic') movements.
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13
Q

What are simple partial seizures?

A

Focal cortical seizures…jerking movements beging in extremities —> body (jacksonian march). May be sensory rather than motor symptoms.

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14
Q

What is temporal lobe epilepsy?

A

Focal seizure of temporal lobe.

  • Simple focal; emotional, sensory or memory.
  • Complex focal - impairs conciousness…my be secondarily generalised to provoke tonic clonic.

Most common.

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15
Q

What is status epilepticus?

A

The seizure doesn’t spontaneously stop. 30 mins or more.

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16
Q

What are syndromes?

A

Collection of signs and symptoms to more closely identify a particular condition and optimise the theraputic approach.

Type and pattern
Frequency
Location of focus
Physical and mental symptoms.
Age of onset
Gender
Prognosis.
17
Q

What could the causes of seizures be?

A

1) Idiopathic - not known.
2) Cryptogenic - can’t be proved.
3) Symptomatic - band head, tumor, stroke or drug abuse.

18
Q

Does epilepsy have a genetic link?

A

Yes - 2-3x more likely if a close relative suffers.

19
Q

What channelopathy is present in benign febrile seizures?

A

Mutation in KCNQ2 and 3 - voltage gated potassium channel.

20
Q

What channelopathy is present in familial generalised epilepsy with febrile seizures plus (carries on into adulthood)?

A

Mutant SCN1B - encodes the Beta subunit of the Na+ channel.

21
Q

Explain the kainic acid injection model?

A

Leads to chronic epileptic behaviour.

22
Q

Explain kindling model.

A

Repeated low intensity electrical stimulation (to amygdala or hippocampus) that leads to chronic epileptic behaviour.

The frequency of stimulation is critical.

23
Q

Focal synchronous excitation that occur to initiate a seizure involve…

A

1) increased synaptic transmission

2) decreased surround inhibition

24
Q

What is the cellular mechanism that initiates a focal seizure?

A

Paroxysmal depolarising shift (PDS)
The mechanism is unknown but the ability of PDS to spread to neighbouring cells to generate a synchronous focus implies a failure of inhibitory feedback through local interneurones.

25
Q

What is epilepsy without surround inhibition?

A

spreading and blending of info from the nucleus.

26
Q

What is epilepsy WITH surround inhibition?

A

mediated by interneurones - through feedback pathways has the effect of limiting spread of input signalling. It has a focussing effect.
Causes greater inhibition on its neighbour than its neighbour causes on it.

27
Q

What are the 2 princicples for treating tonic clonic - partial, or temporal lobe seizures?
And what is the problem with them?

A

Enhance the activity of GABAergic system.
Use Dependant block of Voltage gated sodium channels.

May cause absence seizures.

28
Q

What drugs would you use to enhance the activity of the GABAergic system (and therefore treat tonic clonic, partial or temporal lobe seizures)?

A

Benzodiazepines - eg diazepamk. Bind to regulatory site on GABAa and increase the affinity of the receptor for GABA

Barbituates - phenobarbitone. Prolongs the time the GABA activated Cl- channel stays open.

Vigabatrin - inhibits GABAtransaminase

Tiagabin - inhibits GABA uptake.

29
Q

How would use block use dependent voltage gated sodium channels?

A

Carbamazepine, phenytoin - decrease likelihood of AP firing at high frequencies…little effect at low frequencies. (Bind to inactivated state and prolongs inactivation, decrease the max frequency they fire at).

30
Q

How would you treat status epilepticus?

A

Diazepam.

31
Q

How would you treat absence seizures?

A

Ethosuximide - mechanism is uncertain. Block t-type VOCC in thalamic neurones.

32
Q

What drugs would you use for both tonic-clonic and absence seizures.

A

Lamotrigine - used dependant block of sodium channels.

Sodium valproate - weak blocker of voltage operated sodium channels and weak inhibition of GABA transaminase.

33
Q

Gabapentin?

A

Binds to the alpha2delta subunit VOCC - comprimse NT release.

34
Q

Levetiracetam?

A

Binds to synaptic vesicle protein, SV2A, affects neurotransmission.

35
Q

Retigabine?

A

Provoke K+ channel opening.

36
Q

Premapanel?

A

AMPA antagonist.

37
Q

What are the non-therapeutic methods of treating epilepsy?

A

Ketogenic diet - high fat, low carb - to control seizures in kids.

Vagal stimulation - can abort impending or ongoing attacks.

Surgery - remove tissue that habours focus - limit spread of excitation.

Phys Pharm (18 decks)

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