Antiepileptics Flashcards
How does sodium valproate work?
Increase GABA concentration (by inhibiting GABA transaminase)
Also blocks voltage gated sodium channels and T type calcium channels.
Inhibitor of enzyme histone deacetylase 1 (HDAC1) - histone deacetylase inhibitor.
What is the rate of teratogenicity with valproate? What kind of defects do babies get?
6-9%
They get all kinds of defects: Neural tube defects. Trigonocephaly Facial - Tall forehead with bifrontal narrowing, Epicanthic folds, Medial deficiency of eyebrows Flat nasal bridge, Anteverted nares Cardiac defects Limb defects Genitourinary defects Brain defects Eye anomalies Respiratory tract anomalies DD Behavioural problems
When is carbamazepine used? When should it be avoided?
First line for focal seizures, focal seizures with secondary generalisation and benign rolandic epilepsy
May worsen seizures in JME and CAE
Side effects of carbamazepine?
Common:
- Ataxia, drowsiness, diplopia, headache. (dose related and usually transient. Commencing slowly lessen side effects)
- Rash - in particular SJS, within 4-6 weeks. Increased risk of SJS in Han Chinese ethnicity with HLA B1502 allele. and HLA A3101 allele. Also multiorgan hypersensitivity (DRESS)
- Other side effects: aplastic anemia (avoid if on clozapine, known neutropenia) transaminitis SIADH arrhythmias exacerbate hypothyroidism auditory side effects Increases risk of SLE Teratogenic
- CYP 450 INDUCER so can lower valproate and phenytoin levels.
- Can also reduce efficacy of OCP
- Avoid macrolides - can cause toxicity
- Avoided in 1st year of life due to poor absorption
What is the main side effect of ethosuxamide?
Abdominal pain. (GI symptoms ie anorexia, weight loss, ataxia, eurphoria)
(Rare: depression, psychosis, rash, SJS, SLE, aplastic anaemia)
C/I in porphyria, diabetes (has sucros), or mixed seizure types.
What are the main side effects of topiramate?
- Weight loss (anorexia) **
- Sedation (high doses)
- Mood disturbance
- Language impairment
- Metabolic acidosis (CA inhibitor). Monitor HCO3.
- Heat intolerance (from reduced sweating)
- Paraesthesia (uncommon)
- Nephrocalcinosis (need monitoring)
Topiramate stabilises presynaptic neuronal membranes by blocking voltage-dependent sodium channels. enhances activity of GABA on postsynaptic chloride channels
Which antiepileptics are best in Childhood absence epilepsy? Which ones are to be avoided?
Use ethosuximide or sodium valproate.
2nd line: lamotrigine.
Avoid carbamazepine, oxcarbazepine, phenytoin, tiagabine, vigabatrin.
Which antiepileptics are best in juvenile absence epilepsy?
Sodium valproate
2nd line: lamotrigine (may increase myoclonic jerks), ethosuximide, clobazam.
Avoid: carbamazepine, oxcarbazepine, phenytoin, tiagabine, vigabatrin.
Which antiepileptics are best in juvenile myoclonic epilepsy?
Sodium valproate
2nd line: clobazem, levetiracetam, topiramate, lamotrigine.
Avoid: carbamazepine, oxcarbazepine, phenytoin, tiagabine, vigabatrin.
Which antiepileptics are best for focal epilepsies?
carbamazepine or sodium valproate.
2nd line: clobazem, keppra, lamotrigine, oxcarbazepine, topiramate
What is best treatment for infantile spasms?
Steroids and vigabatrin.
Avoid carbamazepine, oxcarbazepine.
What is best for benign epilepsy with centrotemporal spikes?
Carbamazepine, sodium valproate
What is best antiepileptic for Dravet’s?
Sodium valproate
Avoid carbamazepine, lamotrigine, oxcarbazepine, vigabatrin.
What is best antiepileptic for lennox-gastaut syndrome
sodium valproate
Avoid carbamazepine, oxcarbazepine.
What is side effect of sodium valproate
common: weight gain
Others: Hepatotoxicity (idiosyncratic, not dose related) Rash Thrombocytopenia Pancreatitis Teratogenicity Sedation Dystonia/tremor
