Antiepileptic Flashcards
what are the circumstances where single seizure is provoked but may not necessarily be epilepsy? (What could trigger single seizure?)
- alcohol
- hypoglycaemia
- pyrexia
- sleep deprivation
2 different risk profiles of recurrent seizures
- lower risk (30-50%)
- single seizure
- normal EEG
- normal brain scan - higher risk (80%)
- previous (undiagnosed) seizures)
- epileptiform EEG
- abnormal brain scan
How do we diagnose someone w epilepsy?
based on:
- clinical Hx and examination
- blood test (liver function, blood chemistry)
- EEG,
- brain scan (CT/MRI)
to determine risk of recurrent seizures
epilepsy is
recurrent seizures
pathophysiology for seizures to occur
- neuronal depolarisation (firing) depends on membrane potential
- excessive synchronous depolarization, usually starting from defined regions (“foci”) and spreading to other regions
- unbalanced excitatory and inhibitory receptor/ ion channel function –> favouring DEPOLARIZATION –> dysregulated discharge
–> causes seizure
causes of epilepsy
- congenital or hereditary
- brain injury, scarring, tumor
- infections: meningitis or encephalitis
- blood glucose alteration
- metabolic disorder e.g. adrenal insufficiency leading to hyponatremia
what can be the differential diagnosis other than epilepsy
- patient can present w loss of awareness (present like seizure but wasn’t seizures)
- -> hypoglycaemia, panic attacks
- -> transient cardiac arrhythmia/ ischaemic attacks
- patient present w abnormal movement
- -> movement disorders
- -> tremor
- -> drop attacks
3 categories of seizures
- generalised seizures
- -> tonic clonic (grand mal)
- -> absence (petit mal)
- -> myoclonic (muscle jerking)
- -> atonic (paralytic; sudden loss of muscle strength) - partial seizures
- -> simple (consciousness not impaired)
- -> complex (consciousness impaired) - status epilepticus (never resolves)
difference between generalised and partial seizure based on EEG?
generalised: multi-foci (frontal, ocular, temporal)
partial: 1 or 2 out of the 3 foci mentioned
what can antiepileptic drug do (2 ways)
- decrease membrane excitability by altering Na+ and Ca2+ conductance during action potential
- enhance effect of inhibitory GABA neurotransmitters
MOA of phenytoin
- block voltage-dependent Na+ channels
Phenytoin can be used in what type of seizures
all types EXCEPT absence seizures
PK of phenytoin
- narrow therapeutic range (plasma conc 40-100um)
- saturation kinetics bet dose and plasma conc –> thus need titration and monitoring
- -> non-linear relationship bet dose and steady state plasma conc
Adverse effect/ danger of phenytoin
teratogenic - toxic for developing foetus
MOA of carbamazepine
- blockade of voltage-dependent Na+ channels
Carbamazepine can be used in what type of seizures and what are the exceptions?
- all types of seizure EXCEPT for absence seizures
PK of Carbamazepine
cyp450 inducer and cyp450 metabolite, thus HALF LIVE shortens with repeated doses
AND
increases the elimination of other drugs
SE/Adv effect/ Caution of Carbamazepine
aplastic anemia (2 per million per year)
MOA of Valproate
- blockage of voltage-dependent Na+ and Ca2+ channels
- inhibits GABA transaminase –> increases GABA
Valproate use in what type of seizures
for all type of seizures, including absence seizures
PK of valproate
strongly bound to plasma proteins, displaces other antiepileptics
what are the dose-related SE of anti-epileptics
Dose-related SE: drowsiness, confusion, slurred speech, nausea, unusual behaviour, mental changes, coma, nystagmus, ataxia
what are the non-dose related SE of anti-epileptics
- hirsutism, acne, gingival hyperplasia, folate deficiency, osteomalacia, hypersensitivity rxn (SJS)
BZDs use as an anti-epileptic MOA
enhances effects of inhibitory GABA neurotransmitters
GABA acts on the GABAa receptors CL- channels –> potentiates influx of CL- ions leading to hyperpolarisation –> neurons not firing
Names of the BZDs and their DOA for anti-epileptic purposes
- diazepam (long-acting)
- clonazepam (intermediate acting)
- lorazepam (intermediate-acting) (more for status epilepticus)
BZDs use in anti-epileptic is what line
last line of therapy
what factors need to be considered before the initial choosing of an antiepileptic drug
- seizure type
- epilpsy syndrome
- co-medication (esp cyp450)
- comorbidity
- lifestyle/preferences
how should anti-epileptic therapy start
- MONOtherapy first
- if patient have adverse rxn to the initial monotx,
- monotherapy of ANOTHER drug should be tried
which anti-epileptic drug is first line?
- carbamazepine
- phenytoin
- sodium valproate
for partial and generalised tonic clonic seizures
when do we test the anti-epileptic drug levels in a patient
- check for compliance in patient w refractory epilepsy (definition: medicine isn’t bringing your seizures under control)
- sx of drug toxicity
- titration of initial phenytoin dose
But routine checking w/o a clear indication is not required
reasons for increase risk for breakthrough seizures
- non-compliance
- interactions w antiepileptic med; lowering the blood lvls of antiepileptic drug
- alcohol abuse
- sleep deprivation
- concurrent illness
