Antiepileptics Flashcards
What is a seizure?
- Paroxysmal event due to an abnormal hypersynchronous discharge from a mass of CNS neurons
- Diverse manifestations from convulsion (observable) to an experience (subjective)
Note: Single seizure due to correctable/avoidable circumstance not necessarily epilepsy
- -> Alcohol
- -> Hypoglycemia
- -> Pyrexia
- -> Sleep deprivation
Risks of Epilepsy
Lower risk (30-50%)
- single seizure
- normal EEG & brain scan
Higher risk (80%)
- previous (undiagnosed) seizures
- epileptiform EEG
- abnormal brain scan
How is Epilepsy investigated??
- accurate diagnosis from clinical hx & examination
- blood tests (liver function, blood chemistry)
- EEG
- Brain scan (CT/MRI)
- Determine risk of recurrent seizures
Pathophysiology of Epilepsy
- Unbalanced excitation & inhibitory receptor/ion function favouring depolarisation -> dysregulated discharge*
- Seizure occurs when there is excessive synchronous depolarisation (usually starting from defined regions “foci” & spreads to other regions)
Causes of Epilepsy
- Congenital/hereditary
- Brain injury, scarring/tumour
- Infections (meningitis/encephalitis)
- Blood glucose alterations
- Metabolic disorders (eg. adrenal insufficiency leading to hyponatremia - trigger balance between excitation & inhibition)
Possible differential diagnosis of Epilepsy
Pt presents with loss of awareness…
- Transient cardiac arrhythmia/ischaemic attack
- Hypoglycemia
- Panic attack
Pt presents with abnormal movement…
- Movement disorders in sleep & wake
- Tremor/ paroxysymal choreoathetosis/ dystonia
- Drop attacks & cataplexy
Classification of Epilepsy
1) Generalised seizures (altered consciousness, entire brain)
i) Tonic clonic (grand mal)
ii) Absence (petit mal)
iii) Myoclonic (muscle related…)
iv) Atonic (paralytic kind of seizure)
2) Partial seizures (focuses on 1 area of the brain)
i) Simple (conscious)
ii) Complex (consciousness impaired)
3) Status epilepticus (multiple repeated seizures that don’t stop???)
Rationale of Antiepileptic Treatment
To decrease membrane excitability by altering Na+ & Ca2+ conductance during action potentials
Enhance effect of inhibitory GABA neurotransmitter
[Antiepileptic] Phenytoin
MOA: Blocks voltage-dependent Na+ channels
Use: All seizures EXCEPT absence seizures
- Narrow TW
- Saturation kinetics (need titration & monitoring)
- -> Non-linear r/s between daily dose of phenytoin & steady-state [plasma]
- Teratogenic (NOT for use in pregnancy)
[Antiepileptic] Carbamazepine
MOA: Blocks voltage-dependent Na+ channels
Use: All seizures EXCEPT absence seizures
- Hepatic CYP450 inducer -> Accelerates elimination of other drugs
- Aplastic anaemia (rare but serious)
[Antiepileptic] Valproate
MOA: Blocks voltage-dependent Na+ & Ca2+ channels
Inhibits GABA transaminase -> Increase GABA
Use: All seizures
- Strongly bound to plasma proteins, displace other antiepileptics
Side effects of Antiepileptics
Dose-related
- Drowsiness, confusion, nystagamus (crossed eye), ataxia (movement disorder), slurred speech, nausea, unusual behaviour, mental changes, coma
Non-dose related
- Hirsutism (overgrowing of hair), gingival hyperplasia (overgrowth of gum tissue) , folate deficiency, osteomalacia (softened bone), hypersensitivity rxs (including SJS)
[Antiepileptic] Benzodiazepines
(An anxiolytic: Can have abuse potential but if no choice in emergency can still use)
MOA: Potentiates influx of Cl- ions leading to hyperpolarization -> neurons not firing -> Enhance effects of inhibitory GABA neurotransmitters
Choice:
Clomazepam - Seizure
Lorazepam - Status epilepticus
Diazepam - Seizure, Status epilepticus
How to choose treatment of choice for Epilepsy
Note: Always MONOTHERAPY initially
- Try another drug if unsuccessful/ ADR
Individualised according to seizure type, epilepsy syndrome, co-medication, comorbidities, indv’s lifestyle & preferences
- 1st line: Carbamazepine/ Phenytoin/ Valproate for newly diagnosed partial & generalised tonic clonic seziures
(Absence seizures can only use valproate)
When are Antiepileptic drug levels tested?
1) Assess compliance of treatment for pts with refractory epilepsy
2) Assess symptoms due to possible antiepileptic drug toxicity
3) Titration of phenytoin dose
- Routine checking not required & not cost effective
