Epilepsy Flashcards
Sodium Valproate
AED: Acute liver failure, hyperammonaemia. Tremor and ataxia.
Mitochondrialopathies.
Carbemazepine
AED: SJS
Auto-induces CYP3A4 for which it is a substrate. Therefore do not take levels too early.
Lamotrigine
AED: Na channels
Dosing: Very slow up-titration of doses.
Ethosuximide
First line for pure absence seizures.
If absence seizures + genetic generalised epilepsy use sodium valproate.
Management of status epilepticus
1st line: Benzodiazepine (Lorazepam 2-4mg IV, Midazolam 10mg IM, repeat if needed)
2nd line (equal): Phenytoin, Levetiracetam, Phenobarbital, Sodium valproate.
Genetic Generalised Epilepsy
Childhood and Juvenile Absence Epilepsies:
- Onset 8-12 years, otherwise normal development.
- Absence seizures and occasional GTCS
- Cease by late teens in 80%
- Sodium valproate most effective
Juvenile Myoclonic Epilepsy:
- 2nd most common form of epilepsy
- 7% heterozygotes for intestinal cell kinase (ICK)
- 8-12 years, otherwise normal development
- 90% GTCS, 30% absence seizures
- myoclonic jerks on waking, worse with ETOH and sleep deprivation.
- EEG: 3Hz spike and wave
- Treatment: Valproate (men), Lamotrigine (women)
- Prognosis for remission is poor.
Mesial Temporal Lobe Epilepsy
- Most common form of epilepsy:
- Risk factors: febrile seizures as child, CNS infections –> hippocampal sclerosis.
- Typical aura (deja vu, jamais vu, gustatory or olfactory hallucinations, epigastric rising), focal seizure with imapired awareness with or without automatisms. May evolve to GTCS.
- MRI: Unilateral hippocampal atrophy with T2 increase.
- Tx: Trial of focal agents (carbamazepine, lamotrigine), often drug refractory and requires surgery.
When to start treatment of epilepsy?
Risk of further seizure:
- After 1st seizure = 46%
- After 2nd seizure = 70%
Therefore treat after 2nd unprovoked seizure, or if additional risk factors present after 1st seizure.
- EEG abnormalities, MRI abnormalities, examination abnormalities with presumed structural cause.
Treatment of Focal Seizure
1 - Carbamazepine
2 - Lamotrigine
Others:
Levetiracetam, Valproate, Phenytoin, Lacosamide.
Treatment of Generalised epilepsy
Absense - Valproate or Ethosuximide
Genetic (ideopathic) generalised epilepsy - Valproate, Lamotrigine (in women), Zonisamide.
GTCS - Valproate. Levetiracetam is inferior and more expensive
Unknown seizure type - valproate (broad spectrum)
Carbamazepine
AED: SJS
Auto-induces CYP3A4 for which it is a substrate. Therefore do not take levels too early.
3 AED that can be loaded for rapid response…
Phenytoin, Valproate, Levetiracetam
Titrating AEDs
- Slow titration, aiming for lowest efficacious dose.
- Once at desired clinical effect, take trough level to set baseline for future.
- If not controlled with 1 drug, change to a different drug.
- Limited evidence for dual therapy, if required need 2 difference mechanisms (commonly lamotrigine and valproate).
Epilepsy in Women
Oestrogen promotes neuroexcitation –> increased seizures. Progesterone promoted neuroinhibition.
Most AEDs are CYP induces and will increased clearence of hormonal contraception (the exception is lamotrigine, which will increase levels). Therefore consider progestin implant or IUD.
No change in seizure frequency during pregnancy compared with non-pregnant controls.
AEDs in pregnancy
Defects:
- Valproate - neural tube defects, facial cleft, hypospadias.
- Phenytoin - hypospadias, cardiac defects
- Carbamazepine, lamotrigine, phenobarbital - cardiac defect risk.
General rules:
- Aim for mono-therapy, aim for lowest efficacious dose.
- Avoid: Valproate
- Best tolerated: Carbamazepine, Lamotrigine
- Frequent levels required and may need significant dose increase to maintain levels.
