Seizures

Question 1

Absence Seizure Medication

Answer 1

• anticonvulsants: ethosuximide (most effective), valproate

- tx for comorbidities

Question 2

Absence Seizure Epidemiology

Answer 2

• 3-10% childhood epilepsies

- females>males

Question 3

Absence Seizure Clinical Features

Answer 3

• 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

Question 4

EEG of Absence Seizure

Answer 4

-generalized 3 Hz spike and wave

Question 5

Absence Seizure Etiology

Answer 5

• 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

Question 6

Divalproex MOA

Answer 6

• mania tx

- principal mechanism of action believed to be inhibition of transamination of GABA

Question 7

Divalproex Pros and Cons

Answer 7

• Pros: individualized tx, rapid loading, safe and effective

- Cons: not proven as preventative, weight gain, not effective in bipolar depression, super curly hair

Question 8

Phenytoin

Answer 8

• 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

Question 9

Carbamazepine

Answer 9

• 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

Question 10

Valproate

Answer 10

• 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

Question 11

Levetiracetam

Answer 11

• 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

Question 12

Phenobarbital

Answer 12

• 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

Question 13

Diazepam

Answer 13

• drug of choice for status epilepticus
• broad spectrum seizure tx
• enhancement of GABA activity

Question 14

Divalproex

Answer 14

• broad spectrum seizure tx

- depakote

Question 15

Ethosuximide

Answer 15

• 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)

Question 16

Tx for Status Epilepticus

Answer 16

• first diazepam/lorazepam/midazolam
• next phenytoin or forphenytoin
• if seizures persist, phenobarbital
• if still continue, pentobarbitol or propofol with pressor support

Question 17

Simple Partial Seizures

Answer 17

• preservation of consciousness is key feature

- usually of cortical origin

Question 18

Complex Partial Seizures

Answer 18

• loss of or impaired consciousness

- involves limbic as well as temporal/frontal cortex

Question 19

Mechanisms of Antiseizure Drugs

Answer 19

• 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)

Question 20

Which antiseizure meds cause inhibition of Na channel function?

Answer 20

• phenytoin
• carbamazepine
• lamotrigine
• block of sustained high frequency repetitive firing of APs that can initiate seizure fomation
• blockade is use-dependent

Question 21

Which antiseizure meds cause enhancement of GABA?

Answer 21

• BDZs and phenobarbital (open Cl channels)

- Valproate (acts partly by this mechanism)

Question 22

Which antiseizure drugs cause dec. in low-threshold Ca T type current?

Answer 22

-ethosuximide

Question 23

Which antiseizure meds inhibit function of synaptic vesicle protein SV2A

Answer 23

• levetiracetam

- SV2A impairs Ca mediated NT release

Question 24

Status Epilepticus

Answer 24

• state of recurrent motor seizures between which pt does not regain consciousness
• mortality of 25%

Question 25

Febrile

Answer 25

• 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

Question 26

When to tx seizures:

Answer 26

-if someone has > 2 seizures, begin tx

Question 27

Non-medication tx for seizure

Answer 27

• ketogenic diet
• vagal nerve stimulation
• surgery