Antiseizure meds Flashcards
Mechanisms of seizures
Paroxysmal discharges –> synchronization and recruitment of large population of cortical/thalamic neurons
Enhanced glutamate/deficient GABA –> propagation of abnormal activity
Seizure sequence
focal epileptogenesis –> synchronization –> propagation
Primary causes of seizure
genetic, idiopathic
Secondary causes of seizure
mechanical (trauma, tumor), metabolic (hypoxia, hypoglycemia, hypocalcemia, alkalosis), withdrawal from CNS depressant, toxins
Tonic-clonic seizures
Grand mal. 30%. High amplitude EEG spikes at 15-40 Hz
loss of postural control; LOC; tonic phase (rigid extension of trunk and limbs), clonic phase (rhythmic contraction of arms and legs)
Tonic-clonic mechanism
Initiation: loss of GABA
Propagation: loss of GABA, increased glu response, Na channel excitation
Absence seizures
petit mal. 3 Hz EEG. Children.
Normal muscle tone; impaired consciousness with staring spells; no postictal state
Absence seizure mechanism
inappropriate activation of low-threshold T-type Ca channels
Simple partial seizure
preserved consciousness
Complex partial seizure
loss/impaired consciousness, psychomotor (limbic, temporal/frontal cortex)
can develop to secondary generalized
Partial seizure mechanism
involves initiation instead of propogation –> more difficult to treat
Primary generalized tonic-clonic seizure drug choice
Valproate or lamotrigine or levetiracetam
Partial seizure treatment
carbamazepine or lamotrigine or levetiracetam
Absence seizure treatment
Ethosuximide or valproate
Atypical absence, myoclonic, atonic seizure treatment
valproate or lamotrigine, or leviteracetam
Use of VSSC blockers
Tonic-clonic seizures. block high-frequency, repetitive firing of APs. Use-dependent
Phenytoin, carbamazepine, lamotrigine, topiramate, valproate,
T-type Ca channel blockers
ethosuximide
Use of high-voltage activated Ca channel blockers (N-type)
blocks neurotransmitter release
Benzos and phenobarbital action
facilitate GABA-mediated opening of Cl channels
Vigabatrin action
inhibits inactivation of GABA by GABA transaminase
Tiagabine action
blocks GABA reuptake
Gabapentin action
alters GABA metabolism, release, reuptake
Carbamazepine (Tegretol) pharmacokinetics
complete oral absorption. P450 inducer –> 2-fold increase in clearance in first month
Carbamazepine side effects
diplopia, ataxia, nausea/vomiting, drowsiness (higher doses)
Stevens-Johnson syndrome (associated with HLA-B 1502 allele–Asians)
Rare: aplastic anemia, agranulocytosis, hepatotoxicity
Phenytoin (Dilantin) absorption
absorption dependent on formulation. Erratic IM absorption (fosphenytoin for IM/IV)
Food –> enhanced absorption, reduced GI upset
Phenytoin metabolism
hepatic. P450 inducer. Zero-order kinetics
Phenytoin adverse effects
nystagmus, diplopia and ataxia. Sedation at higher doses
rash most common. Gingival hyperplasia develops gradually
Long-term use –> mild peripheral neuropathy, osteomalacia
Leviteracetam (Keppra) mechanism
Ca channel effects
Keppra pharmacokinetics
rapid oral absorption, urinary excretion. PO/IV formulations
Keppra ADRs
fatigue, somnolence, asthenia, dizziness
Lamotrigine (Lamictal) pharmacokinetics
complete oral absorption. Phase II hepatic metabolism (high loading doses, rapid increase in dose –> increased side effect risk)
Lamictal ADRs
similar to phenytoin, but lower rate of occurance
Stevens-Johnson syndrome
Lamictal use
monotherapy for newly diagnosed partial or generalized seizures. Better tolerated than tegretol and dilantin
maintenance tx of bipolar
migraines
Topiramate pharmacokinetics
Urinary excretion
Topiramate ADRs
dose-related dizziness, somnolence, psychomotor slowing, impaired concentration, interference with memory
teratogenic
Topiramate use
adjunctive therapy in partial seizures
Zonisamide pharmacokinetics
complete oral absorption, long half life, excreted unchanged by kidneys and metabolized by CYP450
Zonisamide ADRs
very well tolerated
Renal stones possible (mild carbonic anhydrase inhibitor)
Zonisamide use
broad spectrum activity. Add-on for partial and generalized seizures
Lacosamide pharmacokinetics
rapid, complete oral absorption, hepatic metabolism, but negligible DDIs
Lasosamide ADRs
dizziness, headache, nausea, diplopia
Lacosamide use
adjunct in partial seizures
Ethosuximide pharmacokinetics
complete oral absorption, completely metabolized by CYP3A4 –> DDIs with inhibitors/inducers
Ethosuximide ADRs
gastric distress
less common: headache, dizziness
Valproic acid mechanism
potentiates GABA function, limits activity of T-type Ca channels
Valproic acid pharmacokinetics
food delays absorption. can inhibit its own metabolism. extended release and IV formulations available
Valproic acid ADRs
GI complaints (avoided when taken with food)
Rare: hepatotoxicity
contraindicated in pregnancy
gabapentin use
certain treatment resistant epilepsies
management of status epilepticus
Initial: IV lorazepam
If seizures persist: IV phenobarbital, then pentobarbital until they stop
If seizures still persist: propofol infusion with pressor support
