Antiseizure meds Flashcards by Alex Alanis

Mechanisms of seizures

Paroxysmal discharges –> synchronization and recruitment of large population of cortical/thalamic neurons

Enhanced glutamate/deficient GABA –> propagation of abnormal activity

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Seizure sequence

focal epileptogenesis –> synchronization –> propagation

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Primary causes of seizure

genetic, idiopathic

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Secondary causes of seizure

mechanical (trauma, tumor), metabolic (hypoxia, hypoglycemia, hypocalcemia, alkalosis), withdrawal from CNS depressant, toxins

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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)

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Tonic-clonic mechanism

Initiation: loss of GABA
Propagation: loss of GABA, increased glu response, Na channel excitation

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Absence seizures

petit mal. 3 Hz EEG. Children.

Normal muscle tone; impaired consciousness with staring spells; no postictal state

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Absence seizure mechanism

inappropriate activation of low-threshold T-type Ca channels

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Simple partial seizure

preserved consciousness

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Complex partial seizure

loss/impaired consciousness, psychomotor (limbic, temporal/frontal cortex)

can develop to secondary generalized

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Partial seizure mechanism

involves initiation instead of propogation –> more difficult to treat

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Primary generalized tonic-clonic seizure drug choice

Valproate or lamotrigine or levetiracetam

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Partial seizure treatment

carbamazepine or lamotrigine or levetiracetam

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Absence seizure treatment

Ethosuximide or valproate

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Atypical absence, myoclonic, atonic seizure treatment

valproate or lamotrigine, or leviteracetam

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Use of VSSC blockers

Tonic-clonic seizures. block high-frequency, repetitive firing of APs. Use-dependent

Phenytoin, carbamazepine, lamotrigine, topiramate, valproate,

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T-type Ca channel blockers

ethosuximide

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Use of high-voltage activated Ca channel blockers (N-type)

blocks neurotransmitter release

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Benzos and phenobarbital action

facilitate GABA-mediated opening of Cl channels

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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