Epilepsy Flashcards Preview

Yr 2 - Pharmacology > Epilepsy > Flashcards

Flashcards in Epilepsy Deck (92):
1

What is epilepsy?

A group of neurological disorders marked by sudden and recurrent episodes of sensory disturbance, loss of conciousness or convulsions associated with abnormal electrical activity in the brain

2

On this pet scan which areas are coloured blue?(temporal lobe epilepsy)

The area of hypo-metabolism between seizures

3

How long between seizures in epilepsy?

It varies -> they are usually intermittent

4

What causes the seizures?

Excessive and abnormal cortical nerve cell activity

5

What 6 things can precipitate seizures?

- altered blood glucose and pH

- stress (going to dentist)

- fatigue

- flashing lights

- noise

- no apparent cause

6

How is epilepsy diagnosed (2)?

- ruling out other conditions that might cause similar symptoms

- confirmation with an electroencephalogram (EEG)

7

What are the major causes of epilepsy (10)?

- birth and perinatal injuries

- congenital malformations

- genetic (ion channels)

- idiopathic (unknown)

- Vascular insults

- Head trauma

- Severe metabolic disturbances

- drug/alcohol abuse

- Neoplasia

- Infection

8

What is the treatment when seizures are caused by something else i.e. tumours/infection?

Treat the underlying cause

NO ANTI-EPILEPTICS!!

9

What can epilepsy be confused with in children?

Febrile convulsion

(hyperthermia)

10

What are the NICE guidelines for epilepsy?

You must have 2 seizures and investigations prior to treatment

11

What are the two types of epilepsy?

Partial/focal/localised

Generalised/global

12

What are the different categories of localised seizures?

Simple (no loss of conciousness)

Complex (impairment of conciousness)

13

What are the different categories of Generalised seizures (6)?

Absence

Myclonic

Tonic clonic

Tonic

Atonic

Status epilepticus

14

What is a localised seizure?

It affects a specific region of a single hemisphere- includes psychomotor epilepsy

15

What % of seizures are accounted for by localised seizures?

60%

16

What can cause localised seizures?

Cortical lesions (tumours, developmental malformation, damage due to trauma or stroke)

Genetic

17

What are generalised seizures?

Discharges from both hemispheres

18

What % of seizures are accounted for by generalised seizures?

40%

19

What are generalised seizures often caused by?

Genetics

20

What are Absence seizures?

= look like daydreaming

21

What are Myclonic seizures?

= muscle twitch

22

What are Tonic clonic seizures?

= muscle convulsions

23

What are Tonic seizures?

= becoming stiff

24

What are Atonic seizures?

= drop seizures

25

What is Status epilepticus?

epileptic fits follow one another without recovery of conciousness between them

26

What are the two proposed mechanisms of epilepsy?

  1. Decreased inhibitory synaptic activity (insufficient GABA/ GABA-A receptor not working)
  2. increased excitatory synaptic activity (too much Glutamate (NMDA, Kainate or AMPA receptor)

27

What are the 3 proposed mechanisms for partial seizures?

  1. Selective loss of (inhibitory) interneurones = decreased feed forward/backward inhibiton of dendate gyrus cells
  2. Injury = synaptic reorganisation (axonal sprouting of remaining neurones) & recurrent excitatory connections
  3. Loss of excitatory neurones =usually inhibit dendate granule cells

28

What is an epileptic focus?

A high frequency burst of action potentials

(n.b. this is not a problem but its also not quite right)

29

How do epileptic foci develop into a seizure?

Hyper-synchronisation of neuronal populations = paroxysmal depolarising shift (PDS) = seizure

30

What is paroxysmal depolarising shift?

activation of AMPA (excitatory) receptors

-> e.g. by glutamate= NMDA receptor activation = increased intracellular K, accumulating Ca in pre-synaptic terminal (enhanced neurotransmitter release) & depolarisation induced NMDA receptor activation (increased Ca influx)

31

What follows the PDS and is used to help localise the brain region where seizures originate:

Interical spike

32

What is epileptigenesis?

The development of epilepsy (e.g. due to trauma)

33

What are the 3 stages of epileptigenesis?

  1. normal network becomes hyper-excitable = not working properly
  2. often a silent period after injury = gradual change of network
  3. full blown epilepsy

34

What is the kindling model?

Animal model of epilepsy produced by electrical stimulation= alters glutamate channel properties, increase neuron loss

35

What is the general seizure mechanism?

Widespread cortical areas

- genetic (e.g. juvenile myoclonic epilepsy = JME)

- idiopathic gene mutations/change in ion channels (Ca, Na, K, Cl) & GABA/ACh gated channels

36

What is the seizure mechanism for absence seizures?

- spike wave complexes on EEG

- GABA-B receptors, Ca & K channels within thalamus = oscillations

37

In which % of patients is the current epilepsy therapy are effective?

75%

38

Which specific type of epilepsy is not well controlled?

Psychomotor epilepsy

39

How do anti epilepsy drugs work?

They target the symptoms (they do NOT cure epilepsy!)

40

The ideal anti-epileptic drug should be able to...(4):

-orally active

-allow normal function (not sedative) so can still work

- non-toxic

- low incidence of interactions with other drugs e.g. NSAIDs

41

What are the two aims of pharmacological intervention in epilepsy?

  • Block activity in the focus
  • Block spread of activity (no synchronisation)

42

What are the actions of pharmacological intervention in epilepsy?

- increase inhibitory influences (decrease neuronal firing rates (Na channels) & increase neurotransmitter release (Ca channels))

- decrease excitatory synaptic transmission (decrease glutamate release & decrease glutamate's actions)

43

What does AED stand for?

Anti-epileptic drugs

44

How many generations of AED are there?

3 (the first generation was the first discovered etc. etc.)

45

Name 3 first generation AEDs:

Phenytoin

Phenobarbitone

Ethosuximide

46

What is the mechanism of action for Phenytoin?

Inhibits voltage gated Na & Ca channels

47

What is the mechanism of action for Phenobarbitone?

Potentiates GABA at GABA-A receptors

48

What is the mechanism of Ethosuximide?

Inhibits Ca channels (T-type)

49

Name 3 second generation AEDs:

Carbamazepine

Valproate

Diazepam

50

What is the mechanism of action of Carbamazepine?

Inhibits Na channels

51

What is the mechanism of action for Valproate?

  • Potentiates GABA at GABA-A receptors
  • Inhibits GABA-T, SSA dehydrogenase & Na channels

52

What is the mechanism of action of Diazepam?

Potentiates GABA at GABA-A receptors

53

Name 4 third generation AEDs:

Lamotrigine

Gabapentin

Vigabatrin

Tiagabine

54

What is the mechanism of action of Lamotrigine?

Inhibits Na channel

Inhibits Ca channels

55

What is the mechanism of action of gabapentin?

Initially synthesised to be a GABA-mimetic

Inhibits voltage-gated Ca channels

Modulates action of GAD

56

What is the mechanism of action of Vigabatrin?

Inhibition of GABA-T

57

What is the mechanism of action of Tiagabine?

Inhibits GABA reuptake by blocking the GABA transporter

58

What is the mechanism of action of Talampenel and Tezampanel?

AMPA antagonist

59

Which anti-epileptic drug is not used for epilepsy as it does not work in the way expected?

Gabapentin

- instead it binds Ca channel subunit = used for neuropathic pain and other disorders= INCREASE INHIBITORY INFLUENCES

60

Which drugs potentiate GABA at GABA-A receptors (3)?

Benzodiazepines (Diazepam)

Phenobarbitone

Valproate

 

= INCREASE INHIBITORY INFLUENCES

61

Which drugs inhibit GABA break down (2)?

& which enzymes do they inhibit?

Inhibit GABA-T

= vigabatrin & valproate

 

Inhibit SSA dehydrogenase

= valproate

= INCREASE INHIBITORY INFLUENCES

62

Which drugs inhibit GABA reuptake (in both neurones & glial cells)?

Tagabine= INCREASE INHIBITORY INFLUENCES

63

Which 4 antiepileptic drugs work by blocking volatge-activated sodium channels?

Carbamazepine

Phenytoin

Valproate

Lamotrigine

 

= INCREASE INHIBITORY INFLUENCES

64

What are the three main conformations of sodium channels?

Resting

Open

Inactivated

65

Which conformation of sodium channels does phenytoin preferentially bind?

Inactive form (once bound it holds the channel in the inactivated form)

66

How does blocking voltage gated sodium channels are used to treat epilepsy?

Reduces the amplitude of sodium-dependent action potentials

-> has a greater block of rapidly firing neurons (e.g. high frequency firing = stops synchronicity)

= works along side GABA= INCREASE INHIBITORY INFLUENCES

67

Name three drugs used to treat epilepsy that block voltage gated calcium channels:

Ethosuximide

Lamotrigine

Gabapentin

68

How does Ethosuximide work?

Binds T-Type voltage gated Ca channel = low threshold Ca currents = modulates firing patterns of neurons= INCREASE INHIBITORY INFLUENCES

69

How does Lamotrigine work?

Inhibits voltage sensitive Na and/or Ca channels = modulates glutamate release= INCREASE INHIBITORY INFLUENCES

70

How does Gabapentin work?

Binds α2δ subunit of Ca channel (prevents trafficking to plasma membrane)= increases synaptic GABA = enhanced GABA response at non-synaptic sites of neuronal tissue & reduces release of mono amine neurotransmitters)= INCREASE INHIBITORY INFLUENCES

71

Which antiepileptic drugs are used to increase inhibitory influences (10)?

  • Gabapentine
  • Benzodiazepines (Diazepam)
  • Phenobarbitone
  • Valproate
  • Vigabatrin
  • Tigabine
  • Carbamazepine
  • Phenytoin
  • Valproate
  • Lamotrigine

72

Which anti-epileptic drugs are used to reduce Glutamate actions?

AMPA antagonists (talampanel & tezamapanel)

Kainate or NMDA receptor antagonist

73

What is Glutamate?

Major fast excitatory neurotransmitter

74

Which neurones does Glutamate act at?

AMPA, kainate & NMDA receptors

Metabotropic glutamate receptors

75

Which 5 drug treatments are preferred in Partial seizures?

Carbamazepine/ Lamotrigine

Sodium valproate (often not used as teratogenic)

Phenytoin

Phenobarbitone

Ritagabine (adjunct)

76

Which type of epilepsy is poorly treated with current drugs?

Psychomotor epilepsy

77

Which 5 drug treatments are preferred in General seizures?

  • Carbamazepine,
  • valproate,
  • Phenytoin,
  • Phenobarbitone,
  • Lamotrigene (not in myclonic)

78

Which 7 drugs can NOT be used in myoclonic or absence seizures?

- Carbamazepine

- gabapentine

- oxcarbazepine

- phenytoin

- Pregabalin

- tiagabine

- Vigabatrin

79

Which 2 drug treaments are used to treat status epilepticus/ seixures in children?

Buccal midazolam

Rectal diazepam

80

Which 3 drug treatments are used to treat absence seizures?

Ethosuximide

Valproate

Lamotrigine

81

Which 3 drug treatments are used to treat myclonic seizures?

Sodium valproate

Levetiracetam

topiramate

82

Which 3 antiepileptic drugs can also be used to for migraines and neuropathic pain?

Topiramate

gabapentin

Levetiracetam

83

Which antiepileptic drug can also be used for trigeminal neuralgia?

Carbamazepine

84

Which 3 antiepileptic drugs can also be used to treat bipolar disorders and anxiety?

Clonazepam

Lamotrigine

Divalproex

85

 

2 Key things that should be taken into account with an epileptic patient:

  • falls increase risk of dental injuries, soft tissue damage and misalignment of TMJ
  • fixed dental replacements (e.g. tooth implants) are recommended to reduce the risk of aspiration

86

Which dental side effects does Phenytoin have?

Causes gingival hyperplasia in 50% -60% of patients

87

Which 4 dental side effects does carbamazepine have?

Xerostomia

Ulcer

Glossitis

Stomatitis

88

Which dental side effects does sodium valproate have?

reduce blood clotting mechanism

89

Which dental side effects does phenytoin and phenobarbital have?

Accelerates the excretion and metabolism of Vitamin D = increased risk of fractures (recommend vitamin D + Ca supplements)

90

Which other drugs affect the metabolism of Carbamazepine, sodium valproate and phenytoin negatively?

NSAIDs and some antifungals (metronidiazole, fluconazole & miconazole)

91

Which types of local anaesthetic should be used in an epileptic patient?

NO ADDED ADRENALINE!!

e.g. Mepivacain & Articain

92

Which local anaesthetic possess both proconvulsant & anticonvulsant properties (3)?

Enflurane

High dose opioids

Lidocane