Anti-epileptics Flashcards
1
Q
Differences between seizures and epilepsy
A
Frequency:
Seizures - a paroxysmal event due to an abnormal, hypersynchronous discharge from a mass of CNS neurons.
Epilepsy - chronic or repeated episodes of seizures
Causes: Seizures - usually due to a correctable or avoidable circumstance: - Alcohol - Hypoglycemia - Pyrexia - Sleep deprivation
Epilepsy - causes may be unavoidable/cannot be corrected:
- Congenital or hereditary
- Brain injury, scarring or tumor
- Infections: meningitis or encephalitis
- Blood glucose alterations
- Metabolic disorders (e.g. adrenal insufficiency leading to hyponatremia)
2
Q
What are the different risk levels of epilepsy?
A
Lower Risk (30-50%)
- Single seizure
- Normal EEG
- Normal brain scan
Higher Risk (80%)
- Previous (undiagnosed) seizures
- Epileptiform EEG
- Abnormal brain scan
3
Q
What are the methods of diagnosis of epilepsy?
A
- Accurate diagnosis from clinical history and examination
- Appropriate investigations
» Blood tests (Liver function, blood chemistry)
» Electroencephalogram (EEG)
» Brain Scan (CT/MRI) - To determine risk of recurrent seizures
4
Q
What is the pathophysiology of epilepsy?
A
- 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 -> dysregulated discharge
5
Q
What are the differential diagnoses for epilepsy?
A
Based on seizure frequency
- Patient presents with loss of awareness
- Transient cardiac arrythmia
- Transient ischaemic attacks
- Hypoglycemia
- Panic attacks - Patient presents with abnormal movement
6
Q
Classification of seizures
A
- Generalized seizures
A. Tonic clonic (Grand mal)
- Triggered by musical tone around the 9-10s mark
- A lot of jerking, but will eventually subside
- Most dramatic presentation type of seizure
B. Absence (Petit mal)
- Triggered by physical exertion (blowing at tissue)
- Person is zoning out, then comes back at full awareness
C. Myoclonic
- Involves clonus or repetitive movement of muscles
D. Atonic
- No muscle tone (person flops out) - Partial seizures
- Simple (consciousness not impaired)
- Complex (consciousness impaired) - Status epilepticus
7
Q
What is the therapeutic rationale of antiepileptics?
A
- Decrease membrane excitability by altering Na+ and Ca2+ conductance during action potentials.
- Enhance effects of inhibitory GABA neurotransmitters.
- Some compounds are effective only against select type of seizures.
8
Q
Phenytoin:
- MOA
- Seizures covered
- Therapeutic range, saturation kinetics, drug interactions
- Side effects
A
- Blockade of voltage-dependent Na+ channels
- Suitable for all types of seizures except absence seizures.
- Relatively narrow therapeutic range, saturation kinetics. Consequent non-linear relationship between dose and plasma concentration necessitates titration and monitoring.
- Teratogenic
9
Q
Carbamazepine:
- MOA
- Seizures covered
- Therapeutic range, saturation kinetics, drug interactions
- Side effects
A
- Blockade of voltage-dependent Na+ channels (like phenytoin).
- Suitable for all types of seizures except absence seizures.
- Hepatic enzyme (CYP450) inducer, half-life shortens with repeated doses -> accelerates elimination of other drugs.
- Aplastic anemia
10
Q
Valproate:
- MOA
- Seizures covered
- Therapeutic range, saturation kinetics, drug interactions
- Side effects
A
- 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
11
Q
General adverse effects of antiepileptics
A
- Dose-related side effects:
» Drowsiness, confusion, nystagmus, ataxia, slurred speech, nausea, unusual behavior, mental changes, coma - Non-Dose Related:
» Hirsutism, acne, gingival hyperplasia, folate deficiency, osteomalacia, hypersensitivity reactions (including Stevens-Johnson syndrome)
12
Q
Benzodiazepines MOA
A
Enhance effects of GABA neurotransmitters, by potentiating the influx of Cl- ions leading to hyperpolarization -> neurons not firing
13
Q
Onset of action, side effects of:
- Clonazepam
- Lorazepam
- Diazepam
A
- Intermediate acting | Panic, disorder, seizure
- Intermediate acting | Anxiety, insomnia, status epilepticus
- Long acting | alcohol withdrawal symptoms, status epilepticus, refractory seizure, adjunct skeletal muscle spasm
14
Q
Treatment considerations - which antiepileptic drug should be chosen initially?
A
- Treatment strategy should be personalised
- Patients should be commenced on monotherapy initially. Add on drugs if the patient develops an adverse effect to the initial drug, or the initial monotherapy is unsuccessful.
- All antiepileptic drugs licensed for monotherapy have similar efficacy in the newly diagnosed epilepsy
15
Q
When are antiepileptic drug levels tested?
A
- Assessment of compliance to drug treatment for patients with refractory epilepsy.
- Assessment of symptoms due to possible antiepileptic drug toxicity.
- Titration of phenytoin dose.
- Routine checking of antiepileptic drug levels without a clear clinical indication is not required, and is not cost-effective.
