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MPharm Y3S2 > Clinical CNS Epilepsy > Flashcards

Clinical CNS Epilepsy Flashcards

1
Q

Define epilepsy from ILAE (international league against epilepsy):

A

A disease of the brain defined by any of the following conditions:
-at least 2 unprovoked (or reflex) seizures occurring more than 24hrs apart
-one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk after 2 unprovoked seizures (60%) over next 10 years
-diagnosis of epilepsy syndrome

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2
Q

What is convulsive status epilepticus?

A

The prolonged convulsive seizure lasting 5 mins or longer or recurrent seizures one after the other without recovery in between

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3
Q

Describe the location epidemiology of epilepsy:

A

Affects 70mil people worldwide and UK is thought to be 5-10/1000
Close to 80% of these people live in low-middle income countries, due to:
-indemic conditions, malaria, high traffic injuries, birth related injuries, 75% not receiving correct treatment

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4
Q

What is the person epidemiology of epilepsy?

A

Can affect people of all ages, race and gender
Highest in infants and people over 50
People who have learning difficulties also have higher rates of epilepsy in comparison to general population

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5
Q

Describe the mortality in epilepsy:

A

Increase risk of premature death in pts with epilepsy
Epilepsy related deaths are thought to be caused by:
-epileptic condition
-anti-epileptic condition
-co-morbidities
-unexplained- SUDEP

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6
Q

What is SUDEP?

A

Sudden Unexpected Death in Epilepsy
Most cases are thought to occur after a seizure
Normally happens unwitnessed at night whilst asleep

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7
Q

What are the risk factors for SUDEP?

A

Tonic seizures
Night time seizures
Not being on anti-epileptic drugs

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8
Q

Describe the aetiology of epilepsy:

A

2/3 of pts have unknown cause (idiopathic)
Structural- visible abnormalities in the brain using neuroimaging e.g stroke/trauma
Genetic- dravet syndrome
Infectious- infection where seizure is core symptom e.g TB, cerebral malaria
Metabolic- perforia, pyridoxine deficiency
Immune- evidence of AI mediated CNA inflammation, anti-NMDAr encephalitis

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9
Q

What are the risk factors for epilepsy?

A

Premature birth
Complicated febrile seizures (brought on by high temp)
Brain development malformation
FH of epilepsy or neurological disease
Head trauma
Infections (e.g meningitis and encephalitis)
Tumours
CVD/stroke
Dementia and neurodegenerative disorders
Drugs and alcohol withdrawl

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10
Q

What is the process for diagnosing epilepsy?

A

Referral to a specialist in epilepsy- all adults and children with first seizure should be seen asap
Detailed history from the pt and eye witness attack can help determine whether it was an epileptic seizure or not- recordings helpful

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11
Q

What are the investigations carried out when diagnosing epilepsy?

A

EEG (electroencephalogram)- to support diagnosis
Blood tests, U&E, ECG
Neuroimaging (MRI,CT)
Genetic testing (informed consent)
Antibody testing- new onset epilepsy if AI encephalitis suspected
Neurophysiological assessment- evaluate learning disabilities

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12
Q

What are the classifications of epilepsy?

A

Seizure type
Epilepsy type
Epileptic syndrome

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13
Q

What are the different seizure types?

A

Focal
Generalised
Unknown

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14
Q

What are the different epilepsy types?

A

Focal
Generalised
Combo
Unknown

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15
Q

Describe the classification of epilepsy in neonates:

A

Most common neurological emergency in neonatal period
Often provoked by an acute cause
Different classification as doesn’t fit into classifications for older children/adults
EEG used for diagnosis (gold standard)

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16
Q

How does ILAE classify seizures?

A

Classify due to humorous factors:
-where seizures start in the brain
Level of awareness pt had of seizure
Whether or not other symptoms e.g motor

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17
Q

What are focal seizures?

A

Increase in neuronal activity originating and remaining in one hemisphere of the brain
These are then subdivided into level of awareness:
-simple focal seizures (no loss of consciousness)
-complex or focal dyscognitive seizures (impaired awareness)

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18
Q

What are the aware+ impaired motor symptoms of focal seizures?

A

Automatisms (repeated/automatic movement)
Atonic (loss of muscle tone)
Clonic (jerking)
Epileptic spasms (extending of muscles in trunk/ close to trunk)
Hyperkinetic (irregular big movements)
Myoclonic
Tonic (stiffness)

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19
Q

What are the aware+ impaired non-motor symptoms of focal seizures?

A

Autonomic (changes in HR, breathing, colour)
Behaviour arrest (blank stare, stop talking/moving)
Cognitive (confusion, slowed thinking, problems talking)
Emotional (sudden fear, dread, anxiety, pleasure)
Sensory (change in vision, taste, tingling, pain)

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20
Q

What is the name of seizures have a focal onset but spread to other areas of the brain?

A

Focal to bilateral tonic clonic seizures

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21
Q

What is the difference between generalised and focal seizures?

A

Level of awareness isn’t looked into as much as with generalised the majority (not all) of these seizures have impaired awareness

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22
Q

What are generalised seizures?

A

Increase in neuronal activity that is widespread across both hemispheres of the brain, these are subdivided into:
-motor symptoms (physical movement)
-non motor aka absense (no physical movement)
-unknown onset- not sure where in the brain it starts
-unclassified- insufficient info to identify seizure type or nature of seizure

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23
Q

What are the motor symptoms in generalised seizures?

A

Tonic
Myoclonus
Atonic
Clonic
Tonic-clonic (ONLY IN GENERALISED)

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24
Q

What is tonic movement?

A

Sustained increase in muscle contraction (tense and rigid muscles)

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25
Q

What is myoclonus movement?

A

Muscle twitching (can involve single or multiple muscle groups)

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26
Q

What is atonic movement?

A

Muscle becoming limp (opposite to tonic)

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27
Q

What is clonic movement?

A

Jerking, rhythmic twitching movements

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28
Q

What is tonic-clonic movement?

A

Where the seizure starts off in tonic phase (muscle rigidity, loss of consciousness, rest stops, involuntary crying) into clonic phase where you have muscle twitching- relaxing and contracting with loss of control of bladder and/or bowels
After the seizure, some people will get a post ictal phase

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29
Q

What is a post ictal phase in seizures?

A

They have trouble remembering what has happened, feels tired, confused

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30
Q

What is absence in the non-motor symptoms?

A

Vacant starting, movement stops

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31
Q

What is epilepsy syndrome?

A

Epilepsies with specific signs and symptoms that can be clustered together
ILAE- 3 groups related to age of onset and separate group for idiopathic

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32
Q

What are factors used to help identify specific epilepsy syndromes?

A

Age of onset of seizures
Types of seizures
Specific EEG patterns and imaging
Associated co-morbidities (e.g learning difficulties)
Aetiology (cause) of the epilepsy if known

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33
Q

What is status epilepticus?

A

A prolonged convulsive seizure lasting 5 mins or longer OR recurrent seizures one after the other without recovery in between or more than 3 in an hour

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34
Q

Which patients could status epilepticus occur in?

A

Patients that have existing epilepsy
Patients that have never had seizures

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35
Q

What are the triggers of status epilepticus?

A

Head injury
Metabolic disturbance (hypoglycaemia)
Cerebrovascular event (stroke)
Alcohol withdrawal

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36
Q

What is the different type of status epilepticus?

A

Convulsive status epilepticus
Tonic-clonic seizures
Medical emergency as it increases likelihood of long term damage and even death

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37
Q

What should occur if a patient has a seizure in the community?

A

Note time of seizure
Provide first aid:
-protect patient from injury
-do not restrain them
-if/when seizure stops then check airways and place in recovery position

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38
Q

What should occur if a patient has a seizure lasting longer than 5 mins in the community?

A

Airways, respiratory and cardiac function must be secured
Buccal midazolam (first line) or rectal diazepam
This should only be administered by a trained personnel or specified individually agreed protocol draw up by specialist and family members

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39
Q

What should occur if a patient has a seizure in the hospital from 0-5 mins?

A

The seizure is timed from onset
Establish IV access
Airways must be secured and regular monitoring of cardiac and respiratory function set up
Give high conc oxygen
Give high potency thiamine (if suggestion of alcohol abuse) e.g pabrinex
Give glucose if patient is hypoglycaemic

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40
Q

What should occur if a patient has a seizure in the hospital from 5-20 mins?

A

Get a bit more info about the patient- if pre-hospital benzo given
Start setting up other investigations to help manage e.g chest x-ray, CT scan
Give IV lorazepam (0.1mg/kg, max 4mg) or IV diazepam if lorazepam not available, alternative to this is buccal midazolam if no IV access, max of 2 doses to be given including pre-hospital dose

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41
Q

What should occur if a patient has a seizure in the hospital from 20-40 mins?

A

Alert anaesthetist and ICU- if pt isn’t responding to treatment more intervention and care is needed
Give 2nd line IV anti epileptic drug (AED)- this will depend on hospital protocols in place (in NICE guidance they mention use of phenytoin, fosphenytoin sodium and phenobarbital, however newer AEDs such as SV/ levetiracetam can be used)

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42
Q

What should occur if a patient has a seizure in the hospital from 40-60 mins?

A

Transfer to ICU and general anaesthesia would be administered:
-propofol
-midzolam
-thiopental sodium
EEG monitoring needs to be set up when giving the anaesthetic
Anaesthetic continued for 12-24 hrs after last clinical/ electrographic seizure

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43
Q

What is the aim when treating patients with epilepsy?

A

Aim for monotherpay
Decrease likelihood of interactions and SEs
Usually doses are started low and then gradually titrated up until control is achieved

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44
Q

What should occur if a monotherpy of a first anti-epileptic drugs fails?

A

Treatment should be switched to another:
-this is done by adding the 2nd and titrating up, while 1st is titrated down
If the second AED fails, then combo therapy is considered:
-only considered when monotherapy has been tried and not resulted in seizure freedom

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45
Q

What is the therapeutic drug monitoring of anti-epileptic drugs?

A

Regular blood tests are not generally recommended and should only be undertaken if clinically needed and recommended by the specialist

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46
Q

What would be the main reasons a blood test is recommended for therapeutic monitoring of anti-epileptic drugs?

A

To identify non-adherence
Investigate suspected toxicity
Adjustment of phenytoin doses
Managing interactions with other meds
For specific clinal conditions e.g organ failure, pregnancy

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47
Q

What other the major points to be aware of with AEDs?

A

Suicidal behaviour- seek medical advice immediately
Anti-epileptic hypersensitivity syndrome- fatal- occur within 1-8 weeks of exposure
Vit D supplementation- if immobile/ low sun exposure

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48
Q

Name different types of AEDs:

A

Sodium valproate
Carbamazepine
Ethosuximide
Lamotrigine
Levetiracetam
Phenobarbital
Phenytoin
Many others

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49
Q

What is the safety update in sodium valproate?

A

Risk if birth defects and developmental disorders
In women who take SV while pregnant:
-1 in 9 babies will be at risk of birth defect (spina bifida, spinal and skull and organ malformation)
-4 in 10 will be at risk of developmental disorder (late to learn to talk/walk/learn)

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50
Q

What is the guidance for prescribing sodium valproate in accordance to the MRHA safety alert?

A

All products containing SV or valproic acid should not be started and prescribed to patients under 55 years old (male and female) unless 2 specialists independently consider and document that other treatments are ineffective or not tolerated or unless there is compelling reasons that reproductive risks do not apply
Girls and women need to have a pregnancy prevention programme

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51
Q

What should occur if patients are already prescribed sodium valproate?

A

They should be advised not to stop taking it unless they are advised by the specialist
It has been advised that their treatment is:
-reviewed with an annual risk acknowledgment form completed and
-if the treatment is to continue, a second opinion signature is required
-this process is also to be initiated for men as well as studies show it can affect male fertility

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52
Q

What is a pregnancy prevention programme?

A

Exclusion of pregnancy
Risk of acknowledgment form- also signed by patient and thoroughly counselled
Highly effective contraception

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53
Q

What is the primary indication of sodium valproate?

A

1st line- generalised tonic- clonic seizures, myoclonic, tonic or atonic seizures if pt not of child bearing age or on PPP
Can be used as 2nd line for absence (focal) seizures if other AED not suitable/ tolerated
Potential 1st line agent for Dravet’s syndrome, Lennox-Gastaut syndrome
Also add on therapy

54
Q

What is the age of a child who is not considered child bearing age?

A

Girls under 10

55
Q

What are the other indications of sodium valproate?

A

Migraine prophylaxis (unlicensed)
Mania bipolar disorder (either as SV or as a semi-sodium valproate)

56
Q

What are the SEs of sodium valproate?

A

Nausea, weight gain (monitor as factor for polycystic ovary syndrome)
Transient elevation of LFTs, blood dyscrasias (e.g anaemia)
Alopecia (hair loss)
Liver toxicity
Pancreatitis (very rare)

57
Q

What are the notable pharmacokinetics of sodium valproate?

A

Crossed in through the placenta
t1/2 ranges between 8-20 hours (usually shorter in children)
Metabolised through the liver via glucoronidation
Enzyme inhibitor of a few CYP enzymes (450,2C9)

58
Q

What are the monitoring requirements for sodium valproate?

A

LFTs- before starting and within 6 months of starting
FBC- before starting
Monitoring blood dyscrasia
Liver disorders-jaundice, non-specific symptoms e.g lethargy, drowsiness, loss of strength, N&V
Pancreatitis (N&V, abdominal pain)

59
Q

What is the primary indication of carbamazepine?

A

2nd line for focal seizures, other types of epilepsy that include benign epilepsy with centrotemporal spikes
Can be considered in last line generalised tonic-clonic seizures (but be aware it can exacerbate myoclonic and absence seizures if they are present it is not suitable)
Add on in focal seizures

60
Q

What are the other indications of carbamazepine?

A

Prophylaxis in bipolar disorder unresponsive to lithium
Trigeminal neuralgia (nerve pain in the face)
Adjunct to acute alcohol withdrawal (unlicensed)
Diabetic neuropathy (unlicensed)

61
Q

What are the adverse SEs of carbamazepine?

A

Drowsiness, dry mouth, nausea, vision disorders (all can be related to dose so can limit dose increase)
Blood disorders (leucopenia, eosinophilia, thrombocytopenia)
Hyponatraemia
Skin disorders

62
Q

What are the notable pharmacokinetics of carbamazepine?

A

Enzyme inducer, induces multiple CYP enzymes in liver
Multiple formulations (IR tabs, MR, liquid), different preps are not bio equivalent
It is metabolised in liver and clearance can be affected by other drugs causing enzyme induction/ inhibition AND also induction of its own metabolism thus altering t1/2 of the drug after continued admin
Interacts with other AEDs

63
Q

What are the monitoring requirements for carbamazepine?

A

Pre-treatment screening in pts of Han Chinese or Thai origin for the allele HLA-B*1502 allele- increased risk of Steven-johnson syndrome (severe skin reaction) with this allele
Plasma conc for optimum response 4-12mg after 1-2 weeks
Manufacturer recommends blood counts, liver and renal function
Monitor for any dyscrasia, liver or skin disorders

64
Q

What are the other AEDs that relate to carbamazepine?

A

Oxcarbazepine
Eslicarbazepine

65
Q

Describe oxcarbazepine:

A

Analogue of carbamazepine (pro-drug)- converted in liver
Weak enzyme inducer of CYP enzymes (3A4 and 3A5)
Enzyme inhibitor or CYP2C19
Pts have hypersensitivity to carbamazepine have a 25-30% chance of experiencing similar reaction to this
Has more linear pharmacokinetics- no self induction of metabolism so more preferable

66
Q

Describe eslicarbazepine:

A

Like that of oxcarbazepine- weak inhibitor or inducer of certain CYP
Doesn’t affect its own metabolism/ clearance
Long t1/2 so OD dosing
Risk of hypersensitivity
Similar SEs to oxcarbemazepine but can also prolong the PR interval

67
Q

What is the primary indication of ethosuximide?

A

1st line and adjunctive for absence seizures, including in childhood
3rd line for epilepsy with myoclonic- atonic seizures (Doose syndrome)
Also licensed for myoclonic seizures

68
Q

What are the other indications for ethosuximide?

A

No other indications

69
Q

What are the adverse SEs for ethosuximide?

A

GI discomfort (N&V, diarrhoea, constipation)
Anxiety
Sleep disturbances
Behavioural disorders
Ataxia (unco-ordinated movements and balance)
Drowsiness
Blood disorders
Rash (Steven-Johnson syndrome)

70
Q

What are the notable pharmacokinetics for ethosuximide?

A

Absorbed well orally, metabolised in the liver
Available in soft capsule or syrup form
Generally no notable interactions with AEDs

71
Q

What are the monitoring requirements for ethouximide?

A

Monitor for any blood dyscrasias
Should be taught to recognise signs e.g bruising, bleeding, fever, rash
Monitor for suicidal behaviours

72
Q

What is the primary indication for lamotrigine?

A

1st line and adjunctive for focal, generalised tonic-clonic seizures, absence seizures (if ethosuximide or SV not suitable/tolerated), tonic or atonic seizures, idiopathic generalised epilepsy
2nd or 3rd line for myoclonic seizures (caution as can exacerbate)

73
Q

What are the other indications for lamotrigine?

A

Bipolar disorder (monotherapy or as adjunctive)
Neuropathic pain

74
Q

What are the adverse SEs of lamotrigine?

A

Dizziness, drowsiness, headache, dry mouth, diplopia, rash (more common when given with other AEDs or in too rapid dose titration), hypersensitivity syndrome, suicidal ideation, blood disorders

75
Q

What are the notable pharmacokinetics of lamotrigine?

A

When given with drugs that are hepatic enzyme inducers or inhibitors, the t1/2 is altered, dosage of the drug needs to be adjusted for this
Does induce its own metabolism but doesn’t affect other AEDs

76
Q

What are the monitoring requirements for lamotrigine?

A

Counsel to patients:
Skin reactions- immediately to doctor
Bone marrow failure- anaemia, bruising, infection

77
Q

What is the primary indication for levetiracetam?

A

1st line for generalised tonic-clonic seizures, focal seizures, myotonic seizures, idiopathic generalised seizures
2nd line for absence seizures, myoclonic, idiopathic generalised seizures and other epilepsy syndromes
Adjunctive in focal, generalised tonic-clonic and myoclonic seizures

78
Q

What are the other indications of levetiracetam?

A

No other indications

79
Q

What are the adverse SEs of levetiracetam?

A

Drowsiness, dizziness, anxiety, GI discomfort, asthenia (lack of energy), insomnia, behavioural abnormalities (aggression/irritability), rash
Uncommon/rare- suicidal behaviours, thrombocytopenia, leukopenia

80
Q

What are the notable pharmacokinetics of levetiracetam?

A

Oral bioavailability is almost 100% with linear pharmacokinetic profile, allowing plasma levels to be more predictable therefore plasma monitoring not needed
It is not extensively metabolised in the body and a large proportion is excreted through the kidneys unchanged
Some of the drug is metabolised though hydrolysis and doesn’t require CYP450 hepatic isoforms

81
Q

What are the monitoring requirements for levetiracetam?

A

None except general counselling of AEDs

82
Q

What are the primary indications for phenobarbital?

A

No 1st line indications
NICE recommends its use as an adjunctive 2nd line option in generalised tonic-clonic seizures
3rd line add on in focal and myoclonic seizures
It is licensed for all epilepsy types except typical absence seizures, also in use in status epilepticus as IV

83
Q

What are the other indications of phenobarbital?

A

No other indications

84
Q

What are the adverse SEs of phenobarbital?

A

AED hypersensitivity syndrome (Steven-Johnson syndrome), bone fractures and bone disorders, blood disorders, folate deficiency, drowsiness, suicidal behaviour, hepatic disorders

85
Q

What are the notable pharmacokinetics of phenobarbital?

A

Metabolism of drug varies in neonates and children
Partly metabolised in liver, some is excreted unchanged from kidneys
Crosses the placenta barrier and is present in breast milk
Enzyme inducer of Cyp450 (potent)

86
Q

What are the monitoring requirements for phenobarbital?

A

Optimum plasma conc levels are 15-40mg/L however due to tolerance occurring with phenobarbital measuring these levels may not be as useful as other AEDs
Monitor for suicidal behaviours
Skin reactions-report signs and symptoms of rash or hypersensitivity syndrome

87
Q

What is the primary indication of phenytoin?

A

No 1st line indications
Adjunctive 3rd line in focal seizures
Use in tonic-clonic and focal seizures or absence seizures however NICE states that if myoclonic or absence seizures are present then phenytoin should not be used
The BNF also states use in the prevention of seizures during or following neurosurgery or severe head injury

88
Q

What are the other indications of phenytoin?

A

Trigeminal neuralgia (unlicensed and under specialist)

89
Q

What are the adverse SEs of phenytoin?

A

Drowsiness, confusion, hirsutism, gingival hyperplasia, cerebellar dysfunction, bone and bone marrow disorders, (can affect hematopoietic system formation of different blood types of cells resulting in megaloplastic anaemia, granulocytopenia)
Symptoms of phenytoin toxicity:
-nystagmus (rapid eye movement)
-diplopia
-slurred speech
-ataxia
-confusion
-hyperglycameia (inhibits glucose metabolism, stop insulin release)

90
Q

What are the notable pharmacokinetics of phenytoin?

A

Highly protein bound (around 90%)
Clearance of the drugs is through the liver but follows non-linear kinetics (saturation of the clearance pathways occurs at therapeutic doses) which can have knock on effects of half life
Available in various formulations- IV, caps, tabs, liquid
NOT all bioequivalent
Phenytoin sodium ≠ phenytoin base, 100mg PS=92mg PB
Enzyme inducer of CYP450

91
Q

What are the monitoring requirements for phenytoin?

A

Due to its pharmacokinetic profile monitoring may be needed in certain patient groups/situations where protein binding may be decreased (pre, elderly, when admin with other meds)
Free plasma phenytoin may be more appropriate
Monitor for any blood dyscrasia or skin disorders
With IV use monitor ECG and BP
Pre treatment- HBLA*B1502- Steven-Johnson

92
Q

Name other AEDs:

A

Clobazam
Lacosamide
Gabapentin
Pregabalin
Rufinamide
Vigabatrine
Tiagabine
Topiramate
Zonisamide
Perampenal
Brivaracetam

93
Q

What are the different categorises AEDs are put into?

A

Category 1,2,3

94
Q

What do category 1 AEDs mean?

A

Patients should be maintained on a specific manufacturer brand
Don’t switch

95
Q

Name examples of category 1 AEDs:

A

Carbamazepine
Phenobarbital
Phenytoin
Primidone

96
Q

What do category 2 AEDs mean?

A

The need for continued supply of a particular manufacturers product should be based on clinical judgement and consultation with pt/carer taking into account clinical and non clinical factors

97
Q

Name examples of category 2 AEDs:

A

Clobazam
Clonazepam
Zonisamide
Eslicarbazepine
Lamotrigine
Perampanel
Oxcarbazepine
Rufinamide
Topiramate
SV

98
Q

What do category 3 AEDs mean?

A

Usually unnecessary for pts to be maintained on specific manufactures brand as therapeutic equivalent is assured
Non clinical factors should be considered

99
Q

What are clinical factors relating to changing AEDs?

A

Relating to seizure freq
Treatment history
Complications of having a breakthrough seizure e.g if driving as a job, could lose job

100
Q

What are the non-clinical factors relating to changing AEDs?

A

Alternative medication could have a negative effect on pt/carer leading to anxiety, confusion, admin errors or changing adherence

101
Q

Describe the ketogenic diet in relation to treating epilepsy:

A

Non-pharmacological
High fat, low protein and carb diet and is mainly used with patients with difficult to treat epilepsy (intractable epilepsy)
NICE recommends it should only be used in 3º care epilepsy specialists

102
Q

How does the ketogenic diet work in relation to treating epilepsy?

A

The diet mimics the state of starvation for the brain, forcing the body to break down fat instead of carbs to produce energy
Ketones are produced so have anti convulsive properties

103
Q

Name the 3 different types of ketogenic diets:

A

Classical ketogenic diet
Modified ketogenic diet
Medium chain triglyceride diet

104
Q

What type of drugs can exacerbate epileptic seizures?

A

Prescription and illicit- including alcohol
Ways in which drugs can trigger seizures include:
-induction or inhibition of hepatic enzymes- alter pharmacokinetics (plasma conc affected)
-some AEDs can themselves worsen and/or precipitate seizures
-2º effects of other drugs used for other reasons e.g decrease in Na+ or serotonin syndrome
-renal/hepatic impairment
-co admin of other drug cautioned e.g theophylline

105
Q

Describe the withdrawal procedure for epilepsy patients on AEDs:

A

Aim for treatment to be discontinued in patients that have been seizure free for at least 2 years
The AED would be slowly withdrawn over 3 months, can be longer
Pts who are on barbiturates/ benzodiazepines, withdrawal must be much slower (6 months) de to withdrawal symptoms and potential seizure recurrence
If patients are on multiple AEDs one drug must be withdrawn at a time

106
Q

What factors should be taken into account by the specialist when deciding whether to withdraw AEDs?

A

Risk and benefits
Risk of seizure recurrent
Risk of SUDEP
Risk of job
Multi factorial risk factors:
-epilepsy surgery
-epilepsy type/syndrome
-cause of epilepsy
-abnormal MRI imaging

107
Q

Which 2 categories can AEDs be divided into?

A

Enzyme inducers
Non enzyme inducers

108
Q

Name the enzyme inducing AEDs:

A

Carbamazepine
Eslicarbazepine
Oxcarbazepine
Perempanel (doses over 12mg daily)
Phenobarbital
Phenytoin
Primidone
Rufinamide
Topiramate (doses over 200mg)

109
Q

Name the non enzyme inducing AEDs:

A

Acetazolamide
Clobazam
Clonazepam
Ethosuximide
Gabapentin
Lacosamide
Lamotrigine (COC can affect metabolism of this though)
Levetiracetam
Perampanel (doses below 12mg)
Pregabalin
SV
Tiagabine
Topiramate (doses below 200mg)
Vigabatrin
Zonisamide

110
Q

What are the contraceptives which are not effective in enzyme inducing AEDs?

A

Oral POP
Progesterone only implant
COC with less than 50mcg of ethinyestradiol

111
Q

What should occur even after an enzyme inducing AED is withdrawn?

A

The enzyme induction persists for 4 weeks after and therefore contraception methods must be continued during this time

112
Q

What is the guidance for emergency contraception with enzyme inducing AEDs?

A

1st- copper IUD (most effective)
2nd- Levonorgestrel 1.5 mg tabs- double dose should be taken to provide cover if copper IUD not suitable/ acceptable
3rd- ulipristal acetate 30mg tablet- effectiveness unknown

113
Q

What are the contraceptives used in non-enzyme inducing AEDs?

A

Normal contraceptive methods can be used
Except for lamotrigine

114
Q

Describe what measures need to be taken with contraception and lamotrigine?

A

COC can decrease the efficacy of lamotrigine (including glucornidation, decreases serum lamotrigine levels):
-increased risk of seizures 21 days
-increased risk of toxicity 7 day free period so continuous COC would be better
A POC desogestrel is also thought to potentially increase the exposure of lamotrigine
Additional barrier advised

115
Q

What contraceptions are not thought to be affected by lamotrigine?

A

Levonorgestrel IUD
Copper IUD
Injection
Still need to monitor lamotrigine levels

116
Q

What is the pre-conception advice for women who are planning to become pregnant with AEDs?

A

NICE recommend monitoring anti epileptic drug levels who are planning to become pregnant and are considered at risk of their seizures worsening- obtain baseline conc

117
Q

What are the medications that should be monitored pre/during conception of AEDs?

A

Phenytoin
Oxcarbamazepine
Phenobarbital
Carbamazepine
Lamotrigine
Levetriacetam

118
Q

What are the safest AEDs to use during pregnancy and why?

A

Lamotrigine and levetiracetam
They don’t increase the risk of birth abnormalities compared to the general population

119
Q

What are the AEDs that can affect babies during pregnancy and why?

A

Carbamazepine, phenobarbital, phenytoin or topiramate use during pregnancy increases the risk of physical birth abnormalities compared to the general population
Phenobarbital, topiramate or zonisamide during pregnancy increases the risk of baby born smaller than expected compared to general pop

120
Q

What are the AEDs that can affect babies after pregnancy and why?

A

Phenytoin or phenobarbital taking during pregnancy can increase the risk of child having difficulty with learning and thinking ability (neurodevelopmental adverse effects)

121
Q

List the AEDs and the physical number of birth defects they can have on babies:

A

General population 2-3/100
Carbamazepine 4-5/100
Phenobarbital 6-7/100
Phenytoin 6/100
Topiramate 4-5/ 100
Valproate 10/100

122
Q

What supplement does a pregnant women taking AED need to take and why?

A

5mg fold acid at least 1st trimester-often longer
To help prevent neural tube defects

123
Q

What are the factors that should occur when a patient with epilepsy is pregnant?

A

Notify the UK Epilepsy and Pregnancy register- pt choice
Care of women with epilepsy when pregnant should be shared with the epilepsy specialist, 1º care team and obstetrician/midwife
Some patients need more frequent review based on certain factors
Detailed ultrasound at 18-20 weeks to scan for structural abnormality

124
Q

Which patient factors would mean a pregnant patient with epilepsy would need to be reviewed more frequently?

A

Sleep deprivation
Patient adherence / compliance
Seizure type/frequency
Learning disabilities
Less than 16 years old
Active epilepsy (last 12 months)
Bilateral tonic-clonic seizures
Modifiable risk factors for SUDP

125
Q

What is the risk of seizures like in pregnancy for epileptic women?

A

Unlikely to experience an increase in seizure frequency or during first few months after birth
Increase risk in patients that have generalised tonic-clonic seizures (foetus may be at higher risk of harm)

126
Q

What is the risk of seizures like during labour for epileptic women?

A

Risk of seizure low but it is recommend to give birth in hospital
Patients would be kept under close observation in hospital
In an open bay and not a closed room alone as risk of SUDP

127
Q

What should be the procedure after birth for babies and mothers who have epilepsy?

A

Babies born to mothers who are on enzyme inducing AEDs are given 1mg vitamin K parentally at delivery
Patients are encouraged to breastfeed as it is generally safe- but always consult SPC

128
Q

What are the safety precautions advised for epileptic mothers and babies when back at home after pregnancy to decrease harm if the mother has a seizure?

A

Bathing- shower if washing alone, bath only if with someone
Feeding- sitting on the floor with mothers back against the wall, using cushions either side to decrease risk of child falling on hard floor
Changing nappies- change on the floor
Going outside- length of cord attached to pram to stop pram from rolling away

129
Q

Describe the correlation with epilepsy and bone health:

A

Related to long term use of AEDs increase the likelihood of bone loss, decreased bone density, risk of osteoporosis and fractures (at least in part as a result of fractures)
Thought to be due to metabolism of VitD by CYP450 enzymes
Risk of bone health increases if on multiple AEDs or for long periods of time

130
Q

What are the AEDs which can decrease bone health?

A

Enzyme inducers: carbamazepine, phenytoin, primidone
Non-enzyme inducers: SV

131
Q

What is the NICE guidance for bone health with AEDs?

A

Monitor VitD levels of patients on these AEDs and supplementation to those at risk
Other tools such as DEXA/FRAX
Counselling on bone health important:
-healthy diet, healthy sun exposure, exercise, smoking and alcohol cessation

132
Q

What are the rules when a patient has epilepsy and drives?

A

The patient must inform the DVLA if they have an epileptic seizure or blackout and stop driving immediately
-pts who fail to inform DVLA could face a fine of £1000 and be prosecuted
-informing DVLA can be done online or by filling in an FEP1 form
Tougher rules for bus, coach, lorry driving licenses

MPharm Y3S2 (22 decks)

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