Antiepileptics Flashcards
Seizure Vs Epilepsey
Seizure: paroxysmal event caused by avoidable circumstance (E.g. alc, hypoglycemia).
Epilepsy: Chronic event
Factors that affect the risk of recurring seizures from Epilepsy (IMPT!!)
Lower risks:
- Single seizure
- Normal EEG
- Normal Brain scan
Higher risk: - Previous undiagnosed seizures - Epileptiform EEG - Abnormal brain scan (basically opposite of lower risk)
Possible causes of Epilepsy
- Congenital/Hereditary
- Brain injury/scarring/tumour (esp. those affecting brain structure)
- Brain Infections (e.g. meningitis)
- Blood glucose alterations (e.g. hypogly)
- Metabolic disorders (e.g. adrenal insufficiency leading to hyponatremia)
Three main classifications of epilepsy and their sub-categories if any
- Generalised:
- Tonic Clonic (dramatic)
- Absence (“zoning out”)
- Myoclonic (brief repetitive movements)
- Atonic (brief movements without muscle tone) - Partial
- Simple
- Complex (impaired consciousness) - Status Epilepticus (long seizures without recovery time)
The main rationale of Antiepileptics
- Seizures are caused by firing of neurons, involving Na & Ca ions
- Antiepileptics decrease membrane excitability by altering Na and Ca conductance during action potential
- They can also enhance effects of inhibitory GABA neurotransmitters
Drugs that only blocks voltage-dependent Na+ channels
1) Phenytoin
2) Carbamazepine
Disadvantages of Phenytoin
1) Teratogenic: unsuitable in pregnancy
2) Narrow-therapeutic range with non-linear PK requiring titration and monitoring
3) Not suitable for absence seizures
Can Carbamazepine be used for all types of seizures?
No, Carbamazepine cannot be used for absence seizures
Rare but significant fatal adverse effect of Carbamazepine
Aplastic anemia
What enzyme does Carbamazepine upregulates, leading to DDI?
CYP450
MoA of Valproate
1) Blocks BOTH Na and Ca voltage-dependent channels
2) Inhibits GABA transaminase, hence increasing GABA levels in synaptic space
Valproate can potentially interact with other drugs. Why is this so?
Valproate is strongly bound to plasma proteins and can displace drugs which are also bound to proteins such as other antiepileptics
What kind of seizure(s) is Valproate suitable for?
All types of absence
General Dose-related SE of antiepileptics?
- Drowsiness
- Confusion
- Nystagmus
- Ataxia
- Slurred speech
- Nausea
- Unusual Behaviour
- Mental Changes
- Coma
(i.e. a lot of CNS SE)
General Non-dose related SE of antiepileptics?
- Hypersensitivity rxn like SJS
2. Others: hirsutism, acne, gingival hyperplasia, folate deficiency, osteomalacia
BZDs can be used as Antiepileptics. However, why are they not the first-line drugs? What are they usually used for?
High potential for abuse, and causes death in overdose
Usual uses:
- Sedative, hypnotic
MoA of BZDs that confers them antiepileptic properties
- Binds to GABA receptors, enhancing action of the endogenous GABA
- Leads to greater entry of chloride ions
- Cells are now hyperpolarised and harder to excite
- Hence neurons cease to fire
There are short-acting, intermediate-acting and long-acting BZDs. Which BZD(s) is/are most suitable as antiepileptics and why?
Intermediate and long-acting
- Epilepsy is chronic conditions
- Important in refractory seizures and in status epilepticus as emergency use
- Duration for short-acting BZD is insufficient, and frequent use leads to addiction
Considerations when initiating antiepileptic drug
- Individualised according to seizure type, epilepsy syndrome, other meds, comorbidities, lifestyle and preferences
- Initiate monotherapy. If AE is encountered, or monotherapy is unsuccessful, try another monotherapy using another drug
- Initiate with lowest therapeutic dose
Antiepileptics that are considered first line treatments for newly diagnosed partial and generalised tonic clonic seizures (according to MOH guidelines)
Carbamazepine, Phenytoin, Valproate
- No specific preferences as they have similar effectiveness
When must the drug levels of antiepileptics be tested?
- Assessing compliance for refractory epilepsy
- Assessing sx for possible antiepileptic drug toxicity
- Titrating phenytoin dose
If patient is well-controlled, must the testing of antiepileptic drug levels continue?
No. Routine assessment w/o clear clinical indication is not cost-effective
Factors that increse the risk for breakthrough seizures (i.e. seizure episode in epileptic patients)
- Non-compliance to antiepileptics
- Interactions with antiepileptics causing lower concentration of antiepileptics
- Alc abuse
- Sleep deprivation
- Concurrent illness
