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Pharmacy Year 3 > Epilepsy > Flashcards

Epilepsy Flashcards

1
Q

Why do epilepsy patients have a higher mortality rate?

A

Accidents
Falling from heights
Head injuries etc

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2
Q

What is Sudden Unexpected Death in Epilepsy?

A

Thought to be due to impaired cardiac or respiratory function
More common in generalised tonic-clonic seizures or poor seizure control (high freq.)

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3
Q

What is the pharmacist role in Sudden Unexpected Death in Epilepsy?

A

Increases adherence and manage side effects to try and control seizures

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4
Q

Define a seizure

A

Episode of neurological dysfunction of abnormal firing of neurones, manifesting as changes in motor control, sensory perception, behaviour, autonomic function

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5
Q

What affects the symptoms exhibited in a seizure?

A

The location of the neurones

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6
Q

When can seizures be classed as epilepsy?

A

Two or more seizures separated in time

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7
Q

What could be potential causes of epilepsy?

A

Idiopathic - Genetic
Symptomatic - Head injury etc
Provoked - Drug abuse etc

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8
Q

What tests should be done in the diagnosis of epilepsy and why?

A

Bloods - Infection markers, electrolyte imbalances
ECG - Arrhythmias
MRI - Structural abnormalities
EEGs - May show epileptic activity to confirm diagnosis

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9
Q

Which medications can lower the seizure threshold?

A 
SSRIs
Tricyclics
Quinolones
Tramadol
Overdoses of medications
Illicit drugs
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10
Q

What other tools can be used in diagnosis of epilepsy?

A

Family history

Description of attack - witnesses?

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11
Q

What could mimic a seizure?

A

Non-Epileptic Attack Disorder

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12
Q

Why is it important to properly classify seizures?

A

For appropriate treatment and management

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13
Q

What are partial seizures?

A

Abnormal firing in one area of brain, location is manifestation

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14
Q

What is secondary generalisation?

A

Starts as partial seizure, then moves into other regions of the brain

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15
Q

Describe a simple partial seizure

A

Maintains consciousness
Limb twitching
Sensory changes
Aggression

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16
Q

Describe a complex partial seizure

A

Lose consciousness
May experience aura (ensure safety)
Automatisms (rhythmic, purposeless movements)
Can be dangerous if unaware of surroundings

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17
Q

Describe a generalised tonic/clonic seizure

A 
Tonic - Muscles tense
Clonic - Limb shaking, self terminates in 1-2 mins
Bite tongue
Lose continence
Fatigue and confusion after
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18
Q

Describe a generalised absence seizure

A

Lasts for seconds

Like zoning out

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19
Q

Describe a generalised myoclonic seizure

A

Limb jerking
Usually during working hours
Awake and aware
Interferes with day-to-day life

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20
Q

Describe a generalised atonic seizure

A

Patient loses all tone

Collapses

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21
Q

What are potential triggers of seizures?

A 
Fatigues, lack of sleep
Stress
Excess alcohol
Flashing lights (~5%)
Menstruation (catamenial epilepsy)
Excitement
Medicines
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22
Q

When would combination therapy be used for epilepsy?

A

After 2-3 drugs have been tried as mono therapy without seizure control

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23
Q

How is treatment for epilepsy initiated?

A

Start at lowest dose, titrate up until seizures controlled or side effects are limiting

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24
Q

When would treatment be started after first case seizure?

A

If EEG shows clear epileptic activity or a structural abnormality

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25
Q

What is the treatment aim of epilepsy drugs?

A

Seizure control at lowest dose with minimum side effects

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26
Q

What factors should be considered when choosing an anti epileptic drug?

A 
Syndrome and seizure type
Comorbidities
Lifestyle
Gender
Age
Preference
Drug factors - Formulation, dose, interactions, side effects etc.
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27
Q

Which drugs are first line for generalised tonic/clonic seizures?

A

Carbamazepine
Lamotrigine
Sodium Valproate
Oxcarbazepine

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28
Q

Which drugs are adjuncts in generalised tonic/clonic seizures?

A 
Clobazam
Lamotrigine
Levetiracetam
Sodium Valproate
Topiramate
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29
Q

Which drugs may worsen generalised tonic/clonic seizures?

A 
Carbamazepine
Gabapentin
Oxcarbazepine
Phenytoin
Pregabalin
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30
Q

Which drug is first line for tonic or atonic seizures?

A

Sodium Valproate

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31
Q

Which drug is adjunct for tonic or atonic seizures?

A

Lamotrigine

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32
Q

Which drugs may worsen tonic or atonic seizures?

A

Carbamazepine
Gabapentin
Oxcarbazepine
Pregabalin

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33
Q

Which drugs are first line and adjunct in absence seizures?

A

Ethosuximide
Lamotrigine
Sodium Valproate

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34
Q

Which drugs may worsen absence seizures?

A 
Carbamazepine
Gabapentin
Oxcarbazepine
Phenytoin
Pregabalin
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35
Q

Which drugs are first line and adjunct for myoclonic seizures?

A

Levetiracetam
Sodium Valproate
Topiramate

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36
Q

Which drugs may worsen myoclonic seizures?

A 
Carbamazepine
Gabapentin
Oxcarbazepine
Phenytoin
Pregabalin
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37
Q

Which drugs are first line for partial seizures?

A 
Carbamazepine
Lamotrigine
Levetiracetam
Oxcarbazepine
Sodium Valproate
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38
Q

Which drugs are adjunct for partial seizures?

A 
Carbamazepine
Lamotrigine
Levetiracetam
Oxcarbazepine
Sodium Valproate
Clobazam
Gabapentin
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39
Q

What is the initial dosing routine for sodium valproate?

What dosage forms are available?

A

Initially 600mg a day in 1-2 divided doses
Gradually increase every 3 days until seizures controlled
Dosage forms: EC, MR tabs, liquids, granules, IV

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40
Q

What are the monitoring requirements for sodium valproate?

A

Signs of liver, blood and pancreatic disorders

Platelet monitoring for clotting disorders and thrombocytopenia

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41
Q

When is sodium valproate contraindicated?

A

Women of childbearing potential (unless completely necessary) due to teratogenic effects

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42
Q

What are the side effects of sodium valproate?

A 
Nausea
Gastric irritation
Diarrhoea
Weight gain
Hair loss
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43
Q

What is the initial dosing routine for carbamazepine?

What are the dosage forms?

A

Initially 100-200mg 1-2 times a day
Increase every 2 weeks
Dosage Forms: Oral or suppositories

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44
Q

What is the conversion between carbamazepine dosage forms?

A

125mg suppository = 100mg oral formulation

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45
Q

What are the monitoring requirements for carbamazepine?

A 
Signs of blood, skin and liver disorders
Leukopenia
LFT changes/liver failure
Rash
Steven-Johnson Syndrome
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46
Q

What interactions may occur with carbamazepine and why?

A 
CYP3A4 substrates (e.g. reduces efficacy of the pill)
Potent enzyme inducer
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47
Q

What are the side effects of carbamazepine?

A 
Headaches
Nausea and vomiting
Drowsiness
Dizziness
Rash
Ataxia (Discoordinated movements)
Hyponatraemia
48
Q

What is the initial dosing routine for lamotrigine?

What are the available dosage forms?

A

Initially 25mg daily
Increase every 2 weeks to avoid rash
Dosage Forms: Oral formulations (normal, dispersible)

49
Q

What is the dosing regime for lamotrigine as an adjunct?

A

25mg every other day if taken with valproate

50
Q

When is lamotrigine an alternative to sodium valproate?

A

In young women as it is safer in pregnancy

51
Q

What are the side effects of lamotrigine?

A

Nausea and vomiting
Dry mouth
Skin reactions

52
Q

When should a patient consult their doctor if on lamotrigine?

A

If they get a rash within the first 8 weeks, treatment may be withdrawn

53
Q

What is the initial dosing routine for levetiracetam?

What are the dosage forms available?

A

250mg daily
Increase every 1-2 weeks
Max. 1.5g twice a day
Oral, IV

54
Q

What are the side effects of levetiracetam?

A 
Nasopharyngitis
Somnolence
Fatigue
Dizziness
Headache
55
Q

When may levetiracetam be discontinued and when is it contraindicated?

A

If experiencing symptoms of depression or low mood

Avoid in patients with a history of severe depression

56
Q

When is phenytoin used?

A

If everything else has been tried and hasn’t worked
Refractory seizures and status epilepticus
Seizures caused by brain tumours and head injuries

57
Q

What is the dosing regimen for phenytoin?

What are the available dosage forms?

A

3-4mg/kg/day loading dose - adjust according to levels
Then 200-500mg daily
Capsules and IV phenytoin base, liquid and chewable tabs phenytoin base

58
Q

How long does it take to reach steady state concentrations with phenytoin?
What is the steady state concentration?

A

7-10 days

10-20mg/L

59
Q

What does phenytoin interact with?

A

CYP450 inhibitors and inducers

Enteral feeding

60
Q

When may patients need a lower dose of phenytoin?

A

Low albumin patients - highly protein bound usually

61
Q

What is the conversion between phenytoin sodium and phenytoin base?

A

100mg phenytoin sodium = 92mg phenytoin base

62
Q

What are the side effects of phenytoin?

A 
Nausea and vomiting
Constipation
Drowsiness
Parasthesia
Gum hypertrophy 
Acne
Excessive hair growth 
Coarsening of facial features
63
Q

What are the symptoms of an overdose of phenytoin?

A 
Eye flickering
Ataxia
Double vision
Blurred vision
Confusion
Hyperglycaemia
64
Q

What are the categories of antiepileptics and what do they mean?

A

Categorised on bioavailability
Category 1 - Use specific brands to prevent loss of seizure control
Category 2 - Supply based on advice of a specialist, if brand switched and seizures uncontrolled specialist may prescribe specific brand
Category 3 - No specific measures

65
Q

Which drugs are category 1?

A

Phenytoin
Carbamazepine
Phenobarbital

66
Q

Which drugs are category 2?

A

Sodium Valproate
Oxcarbazepine
Lamotrigine

67
Q

Which drugs are category 3?

A

Levetiracetam
Lacosamide
Gabapentin

68
Q

Which drug may require an increase in dose if on EHC?

A

Lamotrigine

69
Q

What should be given to women on antiepileptics before pregnancy?

A

5mg folic acid once a day

70
Q

Why may treatment with antiepileptics be changed in the elderly and how?

A 
May have a smaller volume of distribution
Impaired metabolism
Number of medications
Comorbidities
May require lower dose
71
Q

How would carbamazepine be altered when given to the elderly?

A

Give MR release formulation

72
Q

What is status epilepticus?

A

Prolonged seizures lasting more than 30 minutes (or multiple within 30 minutes)
Convulsive seizures
Breathing may be impaired

73
Q

What is the treatment for status epilepticus?

A

IV lorazepam 0.1mg/kg
Repeat once after 10-20mins if seizure continues
If unavailable, IV diazepam or buccal midazolam
Give normal antiepileptics if possible
If lorazepam hasn’t worked give IV phenytoin 20mg/kg over 20 minutes
If already on phenytoin, give phenobarbital, sodium valproate, lacosamide or levetiracetam
If still not working call anaesthetist for GA

74
Q

What are the possible reasons for treatment failure?

A 
Check compliance
Brand/formulation changes
Wrong seizure type diagnosis
Brain tumours 
Alcohol/drug misuse
75
Q

How should drugs be switched in epilepsy treatment?

A

Start second line, titrate to therapeutic dose and wean off first drug

76
Q

What could be the result of abrupt withdrawal of antiepileptics?

A

Rebound seizures

77
Q

What should be done if combination therapy doesn’t work?

A

Revert to regimen that gave best balance of efficacy and tolerability (may be combination or monotherapy)

78
Q

What are the issues surrounding combination therapy of antiepileptics?

A

Drug interactions
DDIs between antiepileptics
Similar ADRs make cause difficult to determine
Compliance issues with complex drug regimes

79
Q

How is treatment withdrawn and when?

A

Slowly withdrawn over months
Withdraw one drug at a time if combination therapy
If seizures recur reverse last dose reduction
Can only withdraw once seizure free for 2 years

80
Q

What counselling points should be given to patients on antiepileptics?

A 
Importance of compliance
Advise against swimming/bathing - SUDEP
Dosing schedule and titrations
Signs and symptoms of ADRs - Bruising, bleeding, liver dysfunction, rashes
OTC and other medications
81
Q

What are the social aspects to be aware of?

A

Health and safety risk for employers
Have to inform DVLA, cannot drive until one year seizure free
Avoid binge drinking

82
Q

What are some causes of seizures in children?

A 
Cardiac defects
Low blood flow to brain
Structural defects in brain
Congenital problems in brain
Metabolic reasons (build up of noxious chemicals in blood)
83
Q

Describe febrile seizures

A

Temperature rises rapidly causing child to fit
Usually family history
High incidence
Generalised tonic/clonic seizure

84
Q

How are febrile seizures managed?

A

Environmental interventions - Turn heating down, open windows
Hold child with head down to allow blood to reach brain while sleeping

85
Q

Describe trauma seizures

A

Usually after hitting head/accidents

Tonic/clonic or clonic seizures

86
Q

What are paroxysms?

A

Anoxic tonic/clonic seizures resulting from child holding their breath

87
Q

What are reflex anoxic seizures?

A

From cold food, head trauma, fright

88
Q

What can cause metabolic seizures?

A

Hypoglycaemia

Hyponatraemia

89
Q

What are the causes of epileptic seizures in children?

A

Depolarisation on EEG
Genetics
Seconday causes - Tumour, neural damage
Neurodegenerative disorders

90
Q

What is Dravet’s Syndrome?

A

SCN1A mutations
Intractable seizures in first year of life
Doesn’t respond to conventional antiepileptics
Developmental delays - walking, talking learning
Child doesn’t grow properly
Lower normal body temperature

91
Q

What are the treatment options for Dravet’s Syndrome?

A

1st Line - Sodium Valproate (high dose)
2nd Line - Clobazam (orally)
3rd Line - Stiripentol (reduce doses of first 2) - if child > 3years

92
Q

How does Stiripentol work?

A

Increases GABA to down regulate transmission in brain and inhibits metabolism of other antiepileptics

93
Q

What are the dosage forms for Stiripentol?

A

Capsule

Sachet for oral suspension

94
Q

What are the doses for Stiripentol?

A

10mg/kg BD for 1 week, then 15mg/kg BD for 1 week

Then:
<6years - Increase to 25mg/kg BD over 3 weeks
6-12years - Increase to 25mg/kg BD over 4 weeks
>12 years - Increase slowly to maximum tolerated dose

95
Q

What is the goal of treatment in Dravet’s Syndrome?

A

Reduce frequency and severity of seizures

96
Q

What is Lennox-Gastaut Syndrome?

A

Most common form of intractable epilepsy
“Drop attacks” - Generalised absence seizures
Focal tonic seizures
Developmental delay and learning difficulties
May progress to generalised tonic seizures

97
Q

What are the treatment options for Lennox-Gastaut Syndrome?

A

1st Line - Sodium Valproate

2nd Line - Lamotrigine, Topiramate, Clobazam, Phenytoin (depends on age and tolerance)

98
Q

What is the purpose of corticosteroid use in Lennox-Gastaut Syndrome?

A

May reduce inflammation and neuronal damage
Reduce longevity and spreading of seizures
Prolong functional life

99
Q

What is a non-pharmacological treatment option for Lennox-Gastaut Syndrome?

A

Surgery for focal seizures - identify causal structure and remove

100
Q

What are the pharmacokinetics of Sodium Valproate?

A

Half life: 4-8hrs (child), 8-20hrs (adult)
90% protein bound
Renally cleared
“Therapeutic Concentration” 40-100mg/L (more about toxicity)

101
Q

What are the possible teratogenic effects of Sodium Valproate?

A 
Neural tube defects - Cleft lip, spina bifida
Congenital Heart Disease
Hole in Heart
Renal Defects
Developmental delay
102
Q

What should be done if a patient on Sodium Valproate falls pregnant?

A

Give smallest dose more frequently or prolonged release formulation
5mg Folic acid

103
Q

How does Sodium Valproate work?

A

Inhibits GABA reuptake in CNS

104
Q

How does Carbamazepine work?

A

Voltage gated sodium channel antagonist - prevents repetitive action potentials
GABA agonist

105
Q

When is Carbamazepine contraindicated?

A

Dravet’s Syndrome

Myoclonic Seizure Disorders

106
Q

What are the pharmacokinetics of Carbamazepine?

A 
30hr half life after single dose, 15hr after repeated dosing
12hr half life if given with phenytoin
65% protein bound
Extensive hepatic metabolism
Therapeutic level 4-12mg/L
107
Q

How does Lamotrigine interact with other antiepileptics?

A

Can result in increased Sodium Valproate or decreased Carbamazepine

108
Q

When is Lamotrigine used 1st line?

A

Focal seizures
Generalised tonic/clonic seizures
Girls and women of childbearing age

109
Q

How does gastric pH vary in children?

A

Increased if <2years (prevents denaturing of proteins in milk)

110
Q

What effect does childhood gastric pH have on Phenytoin?

A

Lower oral bioavailability
Phenytoin is a prodrug - no activation
Give higher doses

111
Q

How does gastric motility vary in children?

A

Slower than in adults

112
Q

What effect does childhood gastric motility have on Phenobarbital and Carbamazepine?

A

Reduced peak levels of Phenobarbital - Rapid absorption through GIT
Slower time to reach peak levels of Carbamazepine - Absorbed in GIT

113
Q

How does a milk-based diet affect Phenytoin dosing?

A

Raise dose by 50%

If enteral feeding, Phenytoin absorption reduced by 35%

114
Q

How does metabolism vary in children?

A

Increased hepatic extraction (large SA ratio)
Increased first pass
Higher CYP1A2, 2C9 and 3A4 expression

115
Q

How should antiepileptics be started in children?

A

Slow increase of dose to prevent reaching toxic levels

Pharmacy Year 3 (15 decks)

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