Seizures Flashcards
Absence Seizure Medication
- anticonvulsants: ethosuximide (most effective), valproate
- tx for comorbidities
Absence Seizure Epidemiology
- 3-10% childhood epilepsies
- females>males
Absence Seizure Clinical Features
- simple seizures: impairment of consiousness, minimal motor activity, 5-15 seconds, many per day, normal muscle tone
- complex seizures: impairment of consiousness, prominent motor activity
EEG of Absence Seizure
-generalized 3 Hz spike and wave
Absence Seizure Etiology
- genetic mutation in genes encoding T-type Ca++ channels
- T type Ca gate does not close at -55mV like it should
- oscillatory stimulation of thalamic-cortical circuitry -> activation of low-threshold T-type Ca channels
Divalproex MOA
- mania tx
- principal mechanism of action believed to be inhibition of transamination of GABA
Divalproex Pros and Cons
- Pros: individualized tx, rapid loading, safe and effective
- Cons: not proven as preventative, weight gain, not effective in bipolar depression, super curly hair
Phenytoin
- dilantin
- very effective against of tonic/clonic and partial seizures
- targets Na channels
- blocks VSSC, suppresses repetitive action potential
- pts should be monitored for gingival hyperplasia
- strong inducer of CYP450 -> DDIs
- ADRs: nystagmus, diplopia, ataxia, rash, osteomalacia, peripheral neuropathy
Carbamazepine
- tx of grand mal (tonic/clonic) seizures and for partial seizures
- targets Na channels
- block of VSSC to suppress repetitive action potential
- anticonvulsant, antimanic, neuropathic pain
- pharmacokinetics: strong inducer of CYP450 enzymes
- ADRs: dipolpia, ataxia, sedation, GI upset, aplastic anemia, agranulocytosis, hepatotoxicity
Valproate
- depakote
- Broadspectrum: first line tx for tonic/clinic seizures, tx of absence seizures
- targets VSSC, dec. axonal flow
- enhancement of GABA activity
- anticonvulsant, antimanic, mood stabalizer, antimigraine
- no CYP450 metabolism- minimal DDI
- inhibits metabolism of other AEDs (antiepileptic drugs)
- ADIs: weight gain, GI upset, hepatic failure, pancreatitis, teratogenic
Levetiracetam
- keppra
- tx of grand mal seizures
- tx of partial seizures
- block of Ca mediated release of glutimate activity
- approved as add-on agent to carbamazepine/phenytoin but often used as monotherapy
- inhibits function of synaptic vesicle protein SV2A
- ADRs: somnolence, asthenia, dizziness, low incidence of cognitive side effects, no CYP450 metabolism- minimal DDIs
Phenobarbital
- broad spectrum seizure tx
- used in neonatal status epilepticus
- adjunct for partial and tonic/clonic seizures
- best choice for neonates and pregnant women
- pharmacokinetics: classic enzyme inducer
Diazepam
- drug of choice for status epilepticus
- broad spectrum seizure tx
- enhancement of GABA activity
Divalproex
- broad spectrum seizure tx
- depakote
Ethosuximide
- drug of choice for absence seizures
- block of T-type Ca channels in thalamocortical pathways
- ADRs: possible DDIs with CYP inhibitors or inducers, dose related gastric distress most common (N/V)
Tx for Status Epilepticus
- first diazepam/lorazepam/midazolam
- next phenytoin or forphenytoin
- if seizures persist, phenobarbital
- if still continue, pentobarbitol or propofol with pressor support
Simple Partial Seizures
- preservation of consciousness is key feature
- usually of cortical origin
Complex Partial Seizures
- loss of or impaired consciousness
- involves limbic as well as temporal/frontal cortex
Mechanisms of Antiseizure Drugs
- elevating seizure threshold- stabilize membrane
- limiting propagation- reduce synaptic transmission or nerve conduction
- drugs are more effective in limiting propagation (generalized seizures) than in preventing initiation (partial seizures)
Which antiseizure meds cause inhibition of Na channel function?
- phenytoin
- carbamazepine
- lamotrigine
- block of sustained high frequency repetitive firing of APs that can initiate seizure fomation
- blockade is use-dependent
Which antiseizure meds cause enhancement of GABA?
- BDZs and phenobarbital (open Cl channels)
- Valproate (acts partly by this mechanism)
Which antiseizure drugs cause dec. in low-threshold Ca T type current?
-ethosuximide
Which antiseizure meds inhibit function of synaptic vesicle protein SV2A
- levetiracetam
- SV2A impairs Ca mediated NT release
Status Epilepticus
- state of recurrent motor seizures between which pt does not regain consciousness
- mortality of 25%
Febrile
- most common childhood seizure
- usual age 6 months to 3 years
- usually within first 24 hours of illness
- no proof of occurrence with rise of fever
- nearly all children will have normal cognition
When to tx seizures:
-if someone has > 2 seizures, begin tx
Non-medication tx for seizure
- ketogenic diet
- vagal nerve stimulation
- surgery
