Epilepsy Flashcards
Carbamazepine
Reduce excitation
Voltage gated sodium channel blocker
- Causes potassium channels to open
- Promotes GABA release (inhibitory neurotransmitter)
Partial or tonic-clinic seizures
Strong hepatic enzyme inducer - CYP3A4
Adverse reactions:
Hyponatraemia: SIADH
Bone marrow suppression and hepatic derangement
Phenytoin
Reduces excitation
Sodium channel blocker
Partial and tonic-clinic seizures
1st order to zero order kinetics: elimination from percentage of drug per unit time to amount
Hepatic enzyme inducer
Concentration can be reduced by carbamazepine and antacids (other enzyme inducers)
90% protein bound: valproate displaces it and inhibits metabolism - increases free phenytoin and toxicity
Side effects:
Acute: Ataxia, fatigue, diplopia, nystagmus, sedation at high levels
Chronic: Gum hyperplasia, coarse face, hirsutism, osteopenia, peripheral neuropathy
Idiosyncratic: fever, rash, lymphadenopathy, teratogenic
P450 enzyme inducer Hirsuitism Enlarged gums and lymphadenopathy Neuropathies (peripheral) Yellow-brown Teratogenic Osteopenia Interference with folate Nystagmus
Sodium Valproate
Reduces excitation and promotes inhibition
All seizure types
- Sodium a calcium channel blocker
- Increases GABA release
- Decreases Glutamate release
Hepatic metabolism
Teratogenic
Interacts with Lamotrigine
Valproate Appetite increase and weight gain Liver failure Pancreatitis Reversible hair loss Oedema Ataxia Teratogenic, tremor, thombocytopenia Encephalopathy - confusion as elevated ammonia
Levetiracetam
Reduces excitation
All seizure types but limited evidence in absence seizures
Acts via SV2A ligand - blocks synaptic vesicles release
NUMBER 1 choice for most seizure types
- Few side effects and no significant interactions
Common side effects: irritability, anxiety, fatigue, dizziness, behavioural changes and rarely psychosis and hepatic failure
Rapid and complete absorption
Renal excretion as an unchanged drug
NOT AN INHIBITOR OF CYP450 ENZYMES
Lamotrigine
Reduces excitation
All seizure types
Sodium channel modulator
BUT NO TERATOGENIC
Rash and STEVENS-JOHNSON SYNDROME (fatal)
Side effects: insomnia, less cognitive effects, mood stabilising effects
Topiramate
Multiple modes of action (same as valproate)
Used for migraines
Enzyme inducer and inhibitor
Hepatic elimination
Side effects: sedation, anorexia, and weight loss, psychiatric, word finding difficulties
Rare: kidney stones and acute angle closure glaucoma
Teratogenic
Drugs to avoid in psychiatric issues
Levetiracetam
Topiramate
Use: valproate, carbamazepine
Lamotrigine has use in bipolar
Drugs to avoid in poor bone health
Carbamazepine
Vitamin B catabolism
Drugs to avoid in obesity
Valproate, carbamazepine
Use: Topiramate - appetite suppressant, weight loss
Epilepsy and preganancy
Use: Levetiracetam and Lamotrigine
Valproate and valproate polytherapy: malformation and neurodevelopmental delay
AED Hypersensitivity syndrome
Rash, temps, tender nodes, hepatitis, eosinophilia, pharyngitis, organ failure
Aromatic AEDs phenytoin and carbamazepine show cross reactivity
Status of epilepticus
5 minutes of continuous seizure activity or briefer seizures with no recovery of consciousness in between times
Treatment:
5mins: 4mg Lorazepam: Repeat once at 10-15minutes
15mins: Phenytoin 20mg/kg - 50mg/min
15mins: Anaesthetic drugs in ICU with EEG monitoring
Prolonged seizure activity:
- Increases excitatory neurotransmitters
- Internalisation of GABAa receptors
- Less inhibitory signalling and excess excitatory transmission
- Propagation of seizure activity
- Increases NMDA receptors
Benzodiazepines
Diazepam, midazolam, lorazepam - pharmacokinetics make it the best choice
GABA agonists
IV most definitive
IM in pre-hospital status epilepticus
Epilepsy
Two recurrent unprovoked seizures
