Epilepsy Flashcards
What is a seizure?
A SEIZURE is an episode of neurological dysfunction of abnormal firing of neurones manifesting as changes in motor control/sensory perception/behaviour/autonomic function.
What is epilepsy?
EPILEPSY is the condition of recurrent, spontaneous seizures arising from abnormal, synchronous and sustained electrical activity in the brain.
Aetiology of epilepsy?
- Idiopathic epilepsy – genetic cause
- Symptomatic epilepsy (e.g. Head injury/stroke)
- Up to 50% have no apparent cause
- Up to 40% may have a genetic component
Diagnosis of epilepsy?
First step of diagnosis is to establish if paroxysmal event was actually a seizure or something else.
Good history taking and witnesses are useful
Epilepsy is spontaneous and recurrent.
Diagnosis should be made by a specialist (NICE, 2012)
There is no single diagnostic tool, good history taking is key
Clinical diagnosis decision is based upon:
- Description of attack – witness accounts/video footage
- Family history – Genetic cause?
- Blood tests – low Na
- ECG – cardiac cause? Syncope?
- Medication history
- -> Legal and illicit drugs can cause seizures
- -> Overdose of some drugs can lead to seizures
- -> Many commonly prescribed drugs can lower seizure threshold
Neuroimaging and EEGs for epilepsy:
- MRI is better than CT
- Visualisation of structural abnormalities
- Important in those <2 years or adults who develop seizures, and those refractory to AEDs
- NICE recommend should be performed within 4 weeks
- EEGs should never be used in isolation
- Main role is to classify epilepsy
- 10% of epileptic patients never show changes
- 2-4% of healthy people can have abnormal EEGs.
Classification of Seizures:
- May have more than one type of epilepsy
- Depend on the location and focus on the pathways involved
- Failure to classify can lead to inappropriate treatment and treatment failure.
Two Main Types:
1) Partial seizures
- Simple partial seizures – maintain consciousness
- Complex partial seizures – don’t maintain consciousness, aura
- With Secondary Generalisation
2) Generalised seizures
- Tonic (muscle tense)/Clonic (limb shaking, biting tongue)
- Absence – short
- Myoclonic – limb jerking
- Atonic – drop attacks
Seizure triggers:
- Fatigue
- Lack of sleep
- Stress
- Alcohol
- Flashing lights (photosensitive epilepsy)
- Excitement
- Menstruation
- Missing meals
- Some medications
Nice guidelines on PHARMACOLOGICAL MANAGEMENT in epilepsy:
- Always initiated by a specialist, after a diagnosis
- Monotherapy should be used where possible
Start low, go slow - Adjunctive (add on) treatment should only be considered when monotherapy has failed
- AEDs are not usually started after a first seizure (except if quite clear abnormality
Aim of Therapy in epilepsy?
- Single Agent
- Lowest Dose
- Minimum Side Effects
Treatment should be tailored to the individual taking into account:
Patient factors
- Epilepsy syndrome
- Seizure type
- Co-morbidity
- Lifestyle
- Gender
- Age
- Preferences of individual/family/carers
Drug Factors
- Side effect profile
- Dose
- Treatment schedule
- Formulation
- Interactions
Generalised Tonic/Clonic 1st line treatment:
Carbamazepine, Lamotrigine, Na Valproate, Oxcarbazepine
Tonic or Atonic 1st line treatment:
Na Valproate
Absense siezure 1st line treatment:
Ethosuximide, Lamotrigine, Na Valproate
Myoclonic seizure 1st line treatment:
Levetiracetam, Na Valproate, Topiramate
Focal seizure type 1st line treatment:
Carbamazepine, Lamotrigine, Levetiracetam, Oxcarbazepine, Na Valproate
Describe sodium valproate:
1st line therapy in multiple seizure types
Initially 600mg/day in 1 - 2 divided doses increased gradually every 3 days
MHRA: Should be avoided in pregnant women and women of childbearing potential due to risk of neurodevelopmental defects.
Dosage forms = EC tablets, MR tablets, liquid, granules, IV
IV dose = Oral doses
Monitor for signs of liver, blood, pancreatic disorders
Side Effects – nausea, gastric irritation, diarrhoea, weight gain, hair loss
Describe carbamazepine:
- 1st line treatment for focal seizures
- Initially 100-200mg 1-2times daily increased slowly every 2 weeks.
- Monitor for blood, liver or skin disorders
- Available via PO and PR routes: 125mg suppository is equivalent to 100mg orally
- Metabolism at CYP3A4 – potent inducer (interactions)
- Side effects – Headache, N+V, drowsiness, dizziness, rash, ataxia, hyponatraemia
- -> Dose related, can be dose limiting
- -> Can be reduced by using MR tabs
Describe lamotrigine:
- Used for focal and generalised seizures
- Initially 25mg/day and slowly titrated every two weeks
- Serious skin reactions
- -> Increase dose slowly
- -> More common when also on valproate or in first 8 weeks of treatment
- Lamotrigine considered one of safest AEDs in pregnancy
- Oral route only
- Side effects – nausea, vomiting, diarrhoea, dry mouth, skin reactions
Describe Levetiracetam:
- Used for partial seizures and adjunctive therapy for myoclonic seizures and tonic-clonic seizures
- 250mg/day, increased every 1-2 weeks to max 1.5g BD
Little metabolism, not affecting CYP450
–> Therefore few interactions - Good oral bioavailability, therefore no dose alteration between oral and IV
- Side effects: Nasopharyngitis, somnolence, fatigue, dizziness, headache
- -> Low mood, irritability, depression are common reasons for discontinuation
Describe phenytoin:
- Not recommended by NICE for first line
- Role in refractory seizures and status epilepticus
- Initially 3-4mg/kg/day (usual dose 200-500mg/day)
Dose adjusted according to levels and effect - Narrow therapeutic index with saturable kinetics
- Half life 4-72 hours (depends on dose). Steady state reached after 7-10days
- Extensive hepatic metabolism
- Strong inducer of CYP450 - interactions
- Highly protein bound – albumin
- Interactions with enteral feeding
- Capsules and IV = Phenytoin sodium
- Liquid, chewable tablets = phenytoin base
- -> 100mg phenytoin sodium = 92mg phenytoin
- -> Need to be careful when switching formulations
Side effects – N+V, constipation, drowsiness, parasthesia, gingival hyperplasia, acne, hirsuitism, coarsening of facial features.
Signs of overdose - Nystagmus, ataxia, diplopia, slurred speech, confusion, hyperglycaemia
- Desirable plasma-phenytoin concentration = 10-20mg/litre
Antiepileptics are divided into three categories according to the importance of maintaining a consistent supply of a particular manufacturers product/brand:
Category 1: Includes phenytoin, carbamazepine, phenobarbital,
Specific measures are necessary to ensure consistent supply of a particular product
Category 2: Includes sodium valproate, lamotrigine, oxcarbazepine
The need for continued supply based on clinical judgement
Category 3: Includes levetiracetam, lacosamide, gabapentin
No specific measures required
Women and epilepsy:
Antiepileptics interact with hormonal medications
- Can reduce effectiveness as enzyme inducers. E.g. Carbamazepine, phenytoin
- Oral contraceptives and EHC can reduce effectiveness of lamotrigine.
- May need to increase dose of lamotrigine
- Some AEDs are teratogens/can cause birth/developmental defects
- These drugs are to be avoided in women of childbearing potential and pregnant women
- Pharmacokinetics can be altered in pregnancy
- All women on AEDs should be offered folic acid 5mg OD before any possibility of pregnancy
- Some women have increased seizure frequency around menstruation
- Side effects of some AEDs may be undesirable
Epilepsy and Older People: Pharmacokinetic and pharmacodynamic issues
Polypharmacy
Co-morbidity
Consider using lower doses of AEDs
If on carbamazepine, this should be modified release
