Epilepsy Flashcards
Why do epilepsy patients have a higher mortality rate?
Accidents
Falling from heights
Head injuries etc
What is Sudden Unexpected Death in Epilepsy?
Thought to be due to impaired cardiac or respiratory function
More common in generalised tonic-clonic seizures or poor seizure control (high freq.)
What is the pharmacist role in Sudden Unexpected Death in Epilepsy?
Increases adherence and manage side effects to try and control seizures
Define a seizure
Episode of neurological dysfunction of abnormal firing of neurones, manifesting as changes in motor control, sensory perception, behaviour, autonomic function
What affects the symptoms exhibited in a seizure?
The location of the neurones
When can seizures be classed as epilepsy?
Two or more seizures separated in time
What could be potential causes of epilepsy?
Idiopathic - Genetic
Symptomatic - Head injury etc
Provoked - Drug abuse etc
What tests should be done in the diagnosis of epilepsy and why?
Bloods - Infection markers, electrolyte imbalances
ECG - Arrhythmias
MRI - Structural abnormalities
EEGs - May show epileptic activity to confirm diagnosis
Which medications can lower the seizure threshold?
SSRIs Tricyclics Quinolones Tramadol Overdoses of medications Illicit drugs
What other tools can be used in diagnosis of epilepsy?
Family history
Description of attack - witnesses?
What could mimic a seizure?
Non-Epileptic Attack Disorder
Why is it important to properly classify seizures?
For appropriate treatment and management
What are partial seizures?
Abnormal firing in one area of brain, location is manifestation
What is secondary generalisation?
Starts as partial seizure, then moves into other regions of the brain
Describe a simple partial seizure
Maintains consciousness
Limb twitching
Sensory changes
Aggression
Describe a complex partial seizure
Lose consciousness
May experience aura (ensure safety)
Automatisms (rhythmic, purposeless movements)
Can be dangerous if unaware of surroundings
Describe a generalised tonic/clonic seizure
Tonic - Muscles tense Clonic - Limb shaking, self terminates in 1-2 mins Bite tongue Lose continence Fatigue and confusion after
Describe a generalised absence seizure
Lasts for seconds
Like zoning out
Describe a generalised myoclonic seizure
Limb jerking
Usually during working hours
Awake and aware
Interferes with day-to-day life
Describe a generalised atonic seizure
Patient loses all tone
Collapses
What are potential triggers of seizures?
Fatigues, lack of sleep Stress Excess alcohol Flashing lights (~5%) Menstruation (catamenial epilepsy) Excitement Medicines
When would combination therapy be used for epilepsy?
After 2-3 drugs have been tried as mono therapy without seizure control
How is treatment for epilepsy initiated?
Start at lowest dose, titrate up until seizures controlled or side effects are limiting
When would treatment be started after first case seizure?
If EEG shows clear epileptic activity or a structural abnormality
What is the treatment aim of epilepsy drugs?
Seizure control at lowest dose with minimum side effects
What factors should be considered when choosing an anti epileptic drug?
Syndrome and seizure type Comorbidities Lifestyle Gender Age Preference Drug factors - Formulation, dose, interactions, side effects etc.
Which drugs are first line for generalised tonic/clonic seizures?
Carbamazepine
Lamotrigine
Sodium Valproate
Oxcarbazepine
Which drugs are adjuncts in generalised tonic/clonic seizures?
Clobazam Lamotrigine Levetiracetam Sodium Valproate Topiramate
Which drugs may worsen generalised tonic/clonic seizures?
Carbamazepine Gabapentin Oxcarbazepine Phenytoin Pregabalin
Which drug is first line for tonic or atonic seizures?
Sodium Valproate
Which drug is adjunct for tonic or atonic seizures?
Lamotrigine
Which drugs may worsen tonic or atonic seizures?
Carbamazepine
Gabapentin
Oxcarbazepine
Pregabalin
Which drugs are first line and adjunct in absence seizures?
Ethosuximide
Lamotrigine
Sodium Valproate
Which drugs may worsen absence seizures?
Carbamazepine Gabapentin Oxcarbazepine Phenytoin Pregabalin
Which drugs are first line and adjunct for myoclonic seizures?
Levetiracetam
Sodium Valproate
Topiramate
Which drugs may worsen myoclonic seizures?
Carbamazepine Gabapentin Oxcarbazepine Phenytoin Pregabalin
Which drugs are first line for partial seizures?
Carbamazepine Lamotrigine Levetiracetam Oxcarbazepine Sodium Valproate
Which drugs are adjunct for partial seizures?
Carbamazepine Lamotrigine Levetiracetam Oxcarbazepine Sodium Valproate Clobazam Gabapentin
What is the initial dosing routine for sodium valproate?
What dosage forms are available?
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
What are the monitoring requirements for sodium valproate?
Signs of liver, blood and pancreatic disorders
Platelet monitoring for clotting disorders and thrombocytopenia
When is sodium valproate contraindicated?
Women of childbearing potential (unless completely necessary) due to teratogenic effects
What are the side effects of sodium valproate?
Nausea Gastric irritation Diarrhoea Weight gain Hair loss
What is the initial dosing routine for carbamazepine?
What are the dosage forms?
Initially 100-200mg 1-2 times a day
Increase every 2 weeks
Dosage Forms: Oral or suppositories
What is the conversion between carbamazepine dosage forms?
125mg suppository = 100mg oral formulation
What are the monitoring requirements for carbamazepine?
Signs of blood, skin and liver disorders Leukopenia LFT changes/liver failure Rash Steven-Johnson Syndrome
What interactions may occur with carbamazepine and why?
CYP3A4 substrates (e.g. reduces efficacy of the pill) Potent enzyme inducer
What are the side effects of carbamazepine?
Headaches Nausea and vomiting Drowsiness Dizziness Rash Ataxia (Discoordinated movements) Hyponatraemia
What is the initial dosing routine for lamotrigine?
What are the available dosage forms?
Initially 25mg daily
Increase every 2 weeks to avoid rash
Dosage Forms: Oral formulations (normal, dispersible)
What is the dosing regime for lamotrigine as an adjunct?
25mg every other day if taken with valproate
When is lamotrigine an alternative to sodium valproate?
In young women as it is safer in pregnancy
What are the side effects of lamotrigine?
Nausea and vomiting
Dry mouth
Skin reactions
When should a patient consult their doctor if on lamotrigine?
If they get a rash within the first 8 weeks, treatment may be withdrawn
What is the initial dosing routine for levetiracetam?
What are the dosage forms available?
250mg daily
Increase every 1-2 weeks
Max. 1.5g twice a day
Oral, IV
What are the side effects of levetiracetam?
Nasopharyngitis Somnolence Fatigue Dizziness Headache
When may levetiracetam be discontinued and when is it contraindicated?
If experiencing symptoms of depression or low mood
Avoid in patients with a history of severe depression
When is phenytoin used?
If everything else has been tried and hasn’t worked
Refractory seizures and status epilepticus
Seizures caused by brain tumours and head injuries
What is the dosing regimen for phenytoin?
What are the available dosage forms?
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
How long does it take to reach steady state concentrations with phenytoin?
What is the steady state concentration?
7-10 days
10-20mg/L
What does phenytoin interact with?
CYP450 inhibitors and inducers
Enteral feeding
When may patients need a lower dose of phenytoin?
Low albumin patients - highly protein bound usually
What is the conversion between phenytoin sodium and phenytoin base?
100mg phenytoin sodium = 92mg phenytoin base
What are the side effects of phenytoin?
Nausea and vomiting Constipation Drowsiness Parasthesia Gum hypertrophy Acne Excessive hair growth Coarsening of facial features
What are the symptoms of an overdose of phenytoin?
Eye flickering Ataxia Double vision Blurred vision Confusion Hyperglycaemia
What are the categories of antiepileptics and what do they mean?
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
Which drugs are category 1?
Phenytoin
Carbamazepine
Phenobarbital
Which drugs are category 2?
Sodium Valproate
Oxcarbazepine
Lamotrigine
Which drugs are category 3?
Levetiracetam
Lacosamide
Gabapentin
Which drug may require an increase in dose if on EHC?
Lamotrigine
What should be given to women on antiepileptics before pregnancy?
5mg folic acid once a day
Why may treatment with antiepileptics be changed in the elderly and how?
May have a smaller volume of distribution Impaired metabolism Number of medications Comorbidities May require lower dose
How would carbamazepine be altered when given to the elderly?
Give MR release formulation
What is status epilepticus?
Prolonged seizures lasting more than 30 minutes (or multiple within 30 minutes)
Convulsive seizures
Breathing may be impaired
What is the treatment for status epilepticus?
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
What are the possible reasons for treatment failure?
Check compliance Brand/formulation changes Wrong seizure type diagnosis Brain tumours Alcohol/drug misuse
How should drugs be switched in epilepsy treatment?
Start second line, titrate to therapeutic dose and wean off first drug
What could be the result of abrupt withdrawal of antiepileptics?
Rebound seizures
What should be done if combination therapy doesn’t work?
Revert to regimen that gave best balance of efficacy and tolerability (may be combination or monotherapy)
What are the issues surrounding combination therapy of antiepileptics?
Drug interactions
DDIs between antiepileptics
Similar ADRs make cause difficult to determine
Compliance issues with complex drug regimes
How is treatment withdrawn and when?
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
What counselling points should be given to patients on antiepileptics?
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
What are the social aspects to be aware of?
Health and safety risk for employers
Have to inform DVLA, cannot drive until one year seizure free
Avoid binge drinking
What are some causes of seizures in children?
Cardiac defects Low blood flow to brain Structural defects in brain Congenital problems in brain Metabolic reasons (build up of noxious chemicals in blood)
Describe febrile seizures
Temperature rises rapidly causing child to fit
Usually family history
High incidence
Generalised tonic/clonic seizure
How are febrile seizures managed?
Environmental interventions - Turn heating down, open windows
Hold child with head down to allow blood to reach brain while sleeping
Describe trauma seizures
Usually after hitting head/accidents
Tonic/clonic or clonic seizures
What are paroxysms?
Anoxic tonic/clonic seizures resulting from child holding their breath
What are reflex anoxic seizures?
From cold food, head trauma, fright
What can cause metabolic seizures?
Hypoglycaemia
Hyponatraemia
What are the causes of epileptic seizures in children?
Depolarisation on EEG
Genetics
Seconday causes - Tumour, neural damage
Neurodegenerative disorders
What is Dravet’s Syndrome?
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
What are the treatment options for Dravet’s Syndrome?
1st Line - Sodium Valproate (high dose)
2nd Line - Clobazam (orally)
3rd Line - Stiripentol (reduce doses of first 2) - if child > 3years
How does Stiripentol work?
Increases GABA to down regulate transmission in brain and inhibits metabolism of other antiepileptics
What are the dosage forms for Stiripentol?
Capsule
Sachet for oral suspension
What are the doses for Stiripentol?
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
What is the goal of treatment in Dravet’s Syndrome?
Reduce frequency and severity of seizures
What is Lennox-Gastaut Syndrome?
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
What are the treatment options for Lennox-Gastaut Syndrome?
1st Line - Sodium Valproate
2nd Line - Lamotrigine, Topiramate, Clobazam, Phenytoin (depends on age and tolerance)
What is the purpose of corticosteroid use in Lennox-Gastaut Syndrome?
May reduce inflammation and neuronal damage
Reduce longevity and spreading of seizures
Prolong functional life
What is a non-pharmacological treatment option for Lennox-Gastaut Syndrome?
Surgery for focal seizures - identify causal structure and remove
What are the pharmacokinetics of Sodium Valproate?
Half life: 4-8hrs (child), 8-20hrs (adult)
90% protein bound
Renally cleared
“Therapeutic Concentration” 40-100mg/L (more about toxicity)
What are the possible teratogenic effects of Sodium Valproate?
Neural tube defects - Cleft lip, spina bifida Congenital Heart Disease Hole in Heart Renal Defects Developmental delay
What should be done if a patient on Sodium Valproate falls pregnant?
Give smallest dose more frequently or prolonged release formulation
5mg Folic acid
How does Sodium Valproate work?
Inhibits GABA reuptake in CNS
How does Carbamazepine work?
Voltage gated sodium channel antagonist - prevents repetitive action potentials
GABA agonist
When is Carbamazepine contraindicated?
Dravet’s Syndrome
Myoclonic Seizure Disorders
What are the pharmacokinetics of Carbamazepine?
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
How does Lamotrigine interact with other antiepileptics?
Can result in increased Sodium Valproate or decreased Carbamazepine
When is Lamotrigine used 1st line?
Focal seizures
Generalised tonic/clonic seizures
Girls and women of childbearing age
How does gastric pH vary in children?
Increased if <2years (prevents denaturing of proteins in milk)
What effect does childhood gastric pH have on Phenytoin?
Lower oral bioavailability
Phenytoin is a prodrug - no activation
Give higher doses
How does gastric motility vary in children?
Slower than in adults
What effect does childhood gastric motility have on Phenobarbital and Carbamazepine?
Reduced peak levels of Phenobarbital - Rapid absorption through GIT
Slower time to reach peak levels of Carbamazepine - Absorbed in GIT
How does a milk-based diet affect Phenytoin dosing?
Raise dose by 50%
If enteral feeding, Phenytoin absorption reduced by 35%
How does metabolism vary in children?
Increased hepatic extraction (large SA ratio)
Increased first pass
Higher CYP1A2, 2C9 and 3A4 expression
How should antiepileptics be started in children?
Slow increase of dose to prevent reaching toxic levels
