Seizures & Anti-epiletics CA Flashcards
What is a seizure?
A paroxysmal event due to an abnormal hyper-synchronous discharge from a mass of CNS neurons.
What is epilepsy?
A disorder of the brain characterised by repeated seizures.
What indicates a lower risk of recurrence of seizure?
- Single seizure
- Normal EEG
- Normal brain scan
What indicates a higher risk of recurrence of seizure?
- Previous (undiagnosed) seizures
- Epileptiform (abnormal) EEG
- Abnormal brain scan
Causes of epilepsy
- congenital/hereditary
- brain injury, scarring or tumour
- infections: meningitis or encephalitis
- blood glucose alterations: chronic hypoglycemia
- metabolic disorders: adrenal insufficiency leading to hyponatremia
Investigations to be ordered for epilepsy
- Blood tests (Liver function, blood chemistry– electrolytes, glucose, calcium & magnesium)
- EEG
- Brain scan (CT/MRI)
(to determine risk of recurrent seizures)
Epilepsy/seizure classification
- Generalised seizure: grand mal/tonic, petit mal/absence, myoclonic, atonic
- Partial seizure: simple, complex
- Status epilepticus: severe form, medical emergency
Rationale for the use of anti-epileptics
- Decrease membrane excitability by altering Na+ and Ca2+ conductance during action potentials.
- Enhance effects of inhibitory GABA neurotransmitters.
What are some common drugs used in the treatment of seizures and epilepsy?
Phenytoin, Carbamazepine, Valproate, Diazepam
What is the MOA of phenytoin?
Reduces excitatory sodium signals by acting as a blockade of voltage-dependent Na+ channels
Note: Narrow therapeutic range (<40 no effect, >100 becomes toxic)
Which anti-epileptic drug should be given first-line for newly diagnosed partial and generalised tonic clonic seizures?
- Carbamazepine
- Phenytoin
- Sodium valproate
Which anti-epileptic drug should be given first-line for absence seizure?
ONLY sodium valproate
Important contraindication of Phenytoin
Teratogenic: leads to birth defects in fetus, contraindicated in pregnant women!
What is the MOA of carbamazepine
Similar to phenytoin:
Reduces excitatory sodium signals by acting as a blockade of voltage-dependent Na+ channels
Important considerations on the use of Carbamazepine
- Drug interactions: Hepatic enzyme (CYP450) inducer, lead to reduced efficacy of other drugs metabolised by these enzymes, hence dosage of other drugs needs to be increased
- Side effects: Aplastic anemia due to inability of bone marrow to produce all kinds of blood cells
What is the MOA of valproate?
- Acts as a blockade of voltage-dependent Na+ and Ca2+ channels hence decrease excitatory tone
- Inhibits GABA transaminase (which breaks down GABA), hence increase GABA, increase inhibitory tone
What kinds of seizures is valproate used for?
All types of seizures, including absence seizure
Important considerations on the use of Valproate
- Valproate binds strongly to plasma proteins and displaces other anti-epileptics, causing them to be unbound and active, increasing the effects of other drugs—hence need to readjust dose of other anti-epileptic medications
What are some dose-related adverse effects of anti-epileptics in general?
- Drowsiness, confusion
- Nystagmus (involuntary, rapid, and repetitive movements of the eyes, can be horizontal, vertical, or rotational)
- Ataxia (poor muscle control)
- Slurred speech
- Nausea
- Unusual behaviour
- Mental changes
- Coma
What are some non-dose related effects of anti-epileptics in general? (may arise even if very low dose given)
- Hirsutism (excessive hair growth)
- Acne
- Gingival hyperplasia (gums overgrowth)
- Folate deficiency
- Osteomalacia (bone softening)
- Hypersensitivity reactions (including SJS)
MOA of benzodiazepines. How are benzodiazepines used in the context of epilepsy?
MOA: increase effect of inhibitory GABA neurotransmitters, potentiates influx of Cl- ions, lead to hyperpolarization, inhibit firing of neurons
Used as a sedative for anti-anxiety effects
Which types of benzodiazepines are used a anti-epileptics? SA or LA?
Short Acting (SA) benzodiazepines are not usually used for anti-epileptic purposes (NO Midazolam/Triazolam)
Epilepsy is a chronic illness. More frequent doses = more adverse effects.
What benzodiazepines are used for anti-epileptics purposes?
Intermediate acting: Clonazepam, Lorazepam
Long acting: Diazepam
Note: Used for refractory seizures (which are not effectively controlled by first-line medications (carbamazepine, valproate, phenytoin), also used during status epilepticus
When are anti-epileptic drug levels tested?
- Assessment of compliance to drug treatment for pts with refractory epilepsy
- Assessment of symptoms due to possible antiepileptic drug toxicity
- Titration of phenytoin dose (due to narrow therapeutic window)
Note: Routine checking not required and not cost effective