Epilepsy Flashcards
Antiepileptic hypersensitivity syndrome
Symptoms: fever, rash, lymphadenopathy
Within 1-8 weeks of exposure
Withdraw if presenting with signs or symptoms
What drugs can cause antiepileptic hypersensitivity syndrome?
Carbamazepine Lacosamide Lamotrigine Oxcarbazapine Phenobarbital Phenytoin Primidone Rufinamide
Risk of suicidal thoughts and behaviour
All antiepileptics carry this risk and may occur one week after starting treatment
Epilepsy and driving
Patients who have had a first unprovoked epileptic seizure/ single isolated seizure must not drive for 6 months.
If they have established epilepsy and they are compliant with treatment and follow up, they may drive and must be seizure free for a year and have no history of unprovoked seizures.
Should not drive during medication changes or withdrawal of medication and for 6 months after the last dose.
Epilepsy and pregnancy
Valproate- highest risk of serious developmental disorders- must be under the PPP
Increased risk of major congenital malformations- carbamazepine, phenobarbital, phenytoin, and topiramate.
The risk for carbamazepine, phenobarbital, and topiramate was shown to be dose dependent.
There is the possibility of adverse effects on neurodevelopment associated with the use of phenobarbital and phenytoin, and an increased risk of intra-uterine growth restriction with phenobarbital, topiramate, and zonisamide.
Epilepsy and breastfeeding
Women taking antiepileptic monotherapy should generally be encouraged to breast-feed, seek advice for combination therapy
All infants should be monitored for sedation, feeding difficulties, adequate weight gain, and developmental milestones.
Primidone, phenobarbital, and the benzodiazepines are associated with an established risk of drowsiness in breast-fed babies and caution is required.
Withdrawal effects may occur in infants if a mother suddenly stops breast-feeding, particularly if she is taking phenobarbital, primidone, or lamotrigine.
Antiepileptics that are readily transferred into breast milk and could cause high serum infant conc.
Ethosuximide, lamotrigine, primidone, and zonisamide
Antiepileptics that could cause drug accumulate through breastfeeding due to slower metabolism in infants
Phenobarbital and lamotrigine
Treatment of focal seizures
First line: carbamazepine and lamotrigine
Alternative: oxcarbazepine, sodium valproate, levetiracetam, pregabalin, gabapentin
What are the different types of generalised seizures?
Tonic-clonic seizures
Myoclonic seizures
Absence seizures
Atonic and tonic seizures
Which antiepileptic drugs may require dose changes during pregnancy?
Lamotrigine
Carbamazepine
Phenytoin
Treatment of tonic-clonic seizures
First line for newly diagnosed: sodium valproate (except in pre-menopausal women)
Alternative: lamotrigine- but may exacerbate myoclonic seizures- but can be given if established epilepsy with generalised tonic-clonic seizures only
Carbamazepine and oxcarbazepine may be considered- may exacerbate myoclonic and absence.
Treatment of absence seizures
First line: ethosuximide or sodium valproate (except in pre-menopausal women)
Alternative: lamotrigine
Not recommended: carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine and vigabatrin.
Treatment of myoclonic seizures
First line: sodium valproate (except in pre-menopausal women)
Alternative: levetiracetam or topiramate (which has a less-favourable side effect profile)
Sodium valproate+levetiracetam are effective in treating generalised tonic-clonic seizures that coexist with myoclonic in idiopathic generalised epilepsy.
Not recommended: carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine and vigabatrin.
Atonic and tonic seizures
Usually seen in childhood
May respond poorly to traditional drugs
First line: sodium valproate (except in pre-menopausal women)
Lamotrigine can be added as adjunct therapy
Epilepsy syndromes
Dravet syndrome: sodium valproate or topiramate
Lennox-Gastaut syndrome: sodium valproate or lamotrigine
Carbamazepine
Simple and complex focal seizures
Generalised tonic clonic seizures
May exacerbate absence, tonic, atonic and myoconic-avoid
Ethosuximide
Absence seizures
also licensed for myoclonic
Pregabalin and gabapentin
Focal seizures
Not recommended for absence, tonic, atonic and myoconic
Both also licensed for neuropathic pain and pregabalin is also licensed for generalised anxiety disorder
Lamotrigine
Focal seizures
Generalised tonic-clonic seizures
Typical absence seizures in children
Myoclonic seizures may be exacerbated by lamotrigine and it may cause serious rashes, especially in children
Lamotrigine-sodium valproate
Sodium valproate increases plasma-lamotrigine concentrations and other enzyme inducing antiepileptics may decrease them.
Levetiracetam
Focal seizures
Adjunct for myoclonic seizures in children and tonic-clonic seizures
Phenobarbital
Primidone
Tonic-clonic and focal seizures
Can be used in all seizures except absence
May have sedative effects in adults
Rebound seizures may occur on withdrawal
Primidone is mainly converted to phenobarbital
Phenytoin
Tonic-clonic and focal seizures
May exacerbate absence or myoclonic
Narrow therapeutic index
Parenteral administration: IV (fosphenytoin which is a pro-drug of phenytoin can be given intramuscularly)
Rufinamide
Adjunctive treatment of seizures in Lennox-Gastaut syndrome
Topiramate
Tonic-clonic and focal seizures
Sodium valproate
All seizure types
Monitor LFTs and FBC
Valproic acid- licensed for acute mania associated with bipolar disorder
Zonisamide
Focal seizures (for adults and children aged 6 years and above)
Clobazam (benzo)
Tonic-clonic and refractory focal seizures
Sedative side effects may be prominent
Clonazepam (benzo)
Refractory absence and myoclonic seizures
Sedative side effects may be prominent
Initial management of status epilepticus
Position patient to avoid injury
Support resp- provision of oxygen
Maintain bp
Correct hypoglycaemia
Parenteral thiamine- if alcohol abuse suspected
Pyridoxine hydrochloride- if pyridoxine deficiency suspected (particularly in children and infants)
Pharmacological treatment of status epilepticus
Seizures lasting longer than 5 minutes- IV lorazepam (repeat after 10 mins if seizures recur or fail to respond)
IV diazepam is effective but carries a high risk of thrombophlebitis (IM diazepam is too slow for status epilepticus)
Alternative would be rectal diazepam or buccal midazolam
If seizures recur or fail to respond 25 mins after onset, phenytoin (slow IV injection), fosphenytoin or phenobarbital should be used. Fosphenytoin can be given more rapidly and causes fewer injection site reactions than phenytoin.
If it’s been 45 mins after onset, anaesthesia with thiopental, midazolam or propofol (unlicensed)
Treating febrile convulsions
Brief febrile convulsions need no specific treatment; antipyretic medication (e.g. paracetamol), is commonly used to reduce fever and prevent further convulsions.
Prolonged febrile convulsions (those lasting 5 minutes or longer), or recurrent febrile convulsions without recovery must be treated actively (as for convulsive status epilepticus). Long-term anticonvulsant prophylaxis for febrile convulsions is rarely indicated.
Pre carbamazepine, oxcarbazepine and phenytoin treatment screening
HLA-B*1502 allele in patients of Han Chinese or Thai origin- risk of Steven Johnsons syndrome if this allele present
Plasma conc of carbamazepine
4-12mg/litre measured after 1-2 weeks