Antiepileptics Flashcards
Medication for epilepsy
Antiepileptics (I)
Phenytoin
carbamazepine
Valproate
Antiepileptics (II) Pregabalin Vigabatrin Lamotrigine Others eg, BZDs
BZD is additive therefore not a good choice coz epilepsy is lifelong
Seizure
A paroxysmal (“sudden attack”) event due to an abnormal discharge from a mass of CNS neurons.
• Diverse manifestations ranging from convulsion (observable) to an experience (subjective).
• Single seizure due to a correctable or avoidable circumstance (ie provoked) is not necessarily epilepsy: –Alcohol –Blood glucose alterations –Pyrexia (fever) –Sleep deprivation
Epilepsy and causes
• A chronic disorders characterized by recurrent seizures.
• Can be primary (congenital, hereditary)
or
secondary:
- Infection, eg, meningitis or encephalitis
- Brain injury, scarring or tumor
- Blood glucose alterations
- Metabolic disorders,
eg, adrenal insufficiency —> hyponatremia
Clinical features of Epilepsy
Recurrent seizures
• Lower Risk (30-50%)
•Single seizure
•Normal EEG
•Normal brain scan
- Higher Risk (80%)
- Previous (undiagnosed) seizures
- Epileptiform EEG
- Abnormal brain scan
clinical approach to epilepsy
Accurate diagnosis from clinical history and examination
Appropriate investigations
• Blood tests
• EEG
• Brain Scan (CT/MRI)
To determine risk of recurrent seizures
Classification of epilepsy
- Generalized seizures
a) Tonic clonic (Grand mal):
b) Absence (Petit mal):
c) Myoclonic
d) Atonic - Partial seizures
a) Simple (consciousness not impaired)
b) Complex (consciousness impaired) - Status epilepticus
pathophysiology of epilepsy
- Neuronal depolarization (“firing”) depends on membrane potential.
- A seizure occurs when there is excessive synchronous depolarization, usually starting from defined regions (“foci”) and spreading to other regions. • Due to unbalanced excitatory and inhibitory receptor / ion channel function which favour depolarization
Rational of AED
- Decrease membrane excitability by altering Na+ and Ca2+ conductance during action potentials.
- Enhance effects of inhibitory GABA neurotransmitters.
phenytoin
- Blockade of voltage-depedent Na+ channels.
- Suitable for all types of seizures except absence seizures.
- A relative narrow therapeutic range (plasma concentration 40-100 μM), saturation kinetics and consequent non-linear relationship between dose and plasma concentration necessitates titration and monitoring.
ADR of Phenytoin
Dose dependent systemic effect
- Endocrine gum
- neurological ——–> convulsion/cerebellar/vestibular
- skeletal
- haemotological —— B12, folate
Overdose
- convulsion/cerebellar/vestibular
- B12 folate
Hypersensitivity idiosyncratic
- Skin: morbilliform
- lupus-like bone marrow
- liver: necrosis
Teratogenic
Carbamazepine
- Blockade of voltage-depedent Na+ channels (like phenytoin).
- Suitable for all types of seizures except absence seizures.
- Hepatic enzyme (CYP450) inducer, T½ shortens with repeated doses —–> accelerates elimination of other drugs.
Carbamazepine ADR
Dose dependent
- GI Upset
- Diplopia
- nystamus
- drowsiness
- folate vit D def
- antidiuretic effect
Overdose
- Ataxia
- Confusion
- Behavioral-disturbance
hypersensitivity
- Bone marrow
- Rashes
- SLE
- SJS
- Lymphadenopathy
- Hepatitis
Teratogenic
- In animals
- In human??
Valproate
- Blockade of voltage-dependent Na+ and Ca2+ channels.
- Also inhibits GABA transaminase —-> increased GABA
- Suitable for all types of seizures, including absence seizures.
- Strongly bound to plasma proteins, displaces other antiepileptics.
Valproate ADR
Dose dependent
- GI upset
- Sedation
- wt gain
- hair loss
Hypersensitivity
- hepatotoxicity
- Thrombocytopenia
Teratogenic
- Spina bifida
- CVS
- Orofacial
- Digital
second gen AED
1) pregabalin
2) vigabatrin
3) Lamotrigine
4) BZDs
5) henobarbital
pregabalin
second gen AED
potentiate the release of GABA
–GABA analogue, increases synaptic GABA –> GABA receptor mediated Cl- currents resulting in hyperpolarization.
–Also acts on voltage-gated Ca2+channels.
–Besides GAD, also used as add-on therapy for partial seizures
–Adverse effects, mainly SEDATION, may be associated with emergence of worsening of SUICIDAL thoughts.
therefore not good for depression
vigabatrin
second gen AED
–Inhibits GABA transaminase —> increased synaptic GABA (» valproate).
–Useful in all types of seizures, including those refractory to other AEDs.
–Side effects: Sedation, behavioural and mood changes (occasionally psychosis), visual field defects.
Lamotrigine
second gen AED
- –Blockade of voltage-depedent Na+ channels.
–Also inhibits glutamate release.
–For all types of seizures.
–Side effects: Dizziness, sedation, rashes.
BZDs
potentiate GABA actions by increasing the frequency of GABA-induced channel opening
phenobarbital
increases frequency and duration of opening.
Which antiepileptic drug should be chosen initially
Antiepileptic drug treatment strategy should be individualised according to the
- seizure type,
- epilepsy syndrome,
- co-medication, comorbidity and the
- individual’s lifestyle and preferences (and/or those of their family and/or carers as appropriate).
Patients should be commenced on monotherapy initially. Should the patient develop an adverse reaction to the initial drug or if the initial monotherapy is unsuccessful, monotherapy using another drug should be tried
Monitoring: When are antiepileptic drug levels tested?
Physicians should be aware that the published “therapeutic range“ exists only as a guide. Patients may have good seizure control below this range, while others tolerate levels above the range.
“Treat the Patient, not the numbers”
Antiepileptic drug levels may help clinical management under the following clinical indications:
(1) assessment of compliance to drug treatment for patients with refractory epilepsy
(2) assessment of symptoms due to possible antiepileptic drug toxicity
(3) titration of phenytoin dose
Routine checking of antiepileptic drug levels without a clear clinical indication is not required, and is not cost effective.
Increased risk for breakthrough seizures
- Non-compliance to antiepileptic medication or drug
- Interactions with antiepileptic medications lowering blood levels of antiepileptic drugs.
- Alcohol abuse
- Sleep deprivation
- Concurrent illness
