Seizure - J. Prunuske/Slattery Flashcards
What is the epidemiology of seizures?
- Incidence in US = 150,000 per year
- Prevalence:
- 2.3 million Adults
- 470,000 Children
- 1-2% of ER visits
- Direct + Indirect costs = $15.5 billion per year
What is the most common etiology of seizures?
Idiopathic
What is the most common etiology of seizures in people >60 yoa?
Stroke
What is the most common etiology of seizures in elderly patients?
Brain tumor
What etiologies cause provoked/secondary seizures?
- Metabolic disturbances
- sugar, sodium, calcium, azotemia
- Infections
- Focal neurologic lesions
- Medications/Withdrawal
- Toxins (EtOH, etc.)
What diagnostic evaulations are performed for a seizure?
- Neuroimaging (CT or MRI) - typically done with FIRST seizure, unless it is febrile seizure
- EEG in all patients
- LP - only if clinical concern for infection
- CBC, BMP
- Utox
- Pregnancy test - to rule out pre-eclampsia, avoid giving dangerous medications
What are the clinical hallmarks of Focal, Local, Simple, or Partial seizures?
- No LOC (retain awareness)
- Only involve one hemisphere
- symptoms based on specific area of the brain that is effected
What are the clinical hallmarks of Complex partial or Focal seizure with contralateral propagation or secondary generalization?q
- Initiates as a partial/local
- small seizure often undetected
- Becomes generalized → global disruption of both hemispheres
- LOC
- due to effects on reticular activating system
What are the clinical hallmarks of a General non-convulsive or Absence seizure?
- Diffuse
- Blank stare, then continue with previous action
- No postictal confusion
What are the clinical hallmarks of a convulsive, tonic-clonic, atonic, etc. seizure?
- Collapse at onset
- Clenching, extending, contracting, jerking movements
- LOC
- Drooling, incontinence
- Postictal confusion/amnesia
What are the clinical hallmarks of status epilepticus?
- Seizures that last for 5+ minutes
- 20% of people die (1 of 5)
- Not coming out of seizure, require IV medication
- Rapidly depletes glucose, starve brain, causes electrolyte imbalance
What anticonvulsant medications target pre-synaptic voltage-gated Na+ channels in order to decrease glutamate release?
- Phenytoin
- Carbamazepine
- Lacosamide
What anticonvulsant medications target pre-synaptic VG Ca2+ channels in order to decrease glutamate release?
- Ethosuximide
- Gabapentin
What anticonvulsant medication targets pre-synaptic K+ channels in order to diminish glutamate release?
Retigabine
What anticonvulsant medication targets pre-synaptic vesicle proteins (SV2A) in attempt to decrease glutamate release?
Levetiracetam
What anticonvulsant medication targets post-synaptic AMPA receptors?
- Phenobarbital
- Topiramate
What anticonvulsant medication targets post-synaptic NMDA receptors?
Valproic acid
What antiseizure drug targets GABA transporters (especially GAT-1)?
Tiagabine
What antiseizure medication targets GABA-transaminase (GABA-T)?
Valproic acid
What antiseizure medication targets GABAA receptors?
Benzodiazepines & Barbiturates
What antiseizure medications target synaptic vesicular proteins (SV2A)?
Levetiracetam
What is the pathogenesis of seizures according to Dr. Slattery?
- Imbalance between neuronal excitation and inhibition
- Increased extracellular K+ decreases neuronal hyperpolarization
- Decreased extracellular Ca2+/Mg2+ may increase excitability
- Increased glutamate
- Decreased GABA
What are the overarching principles of antiseizure drugs (i.e. what is their physiological purpose)?
- Decrease the effectiveness of glutamate transmission
AND/OR
- Increase the effectiveness of GABA transmission
What is the clinical treatment pearl for a focal seizure?
Lamotrigine
What is the clinical treatment pearl for a generalized seizure?
Valproic Acid
What is the clinical treatment pearl for a absence seizure?
Ethosuximide
What is the clinical treatment pearl for status epilepticus?
IV Lorazepam STAT!
What antiseizure drug is indicated in partial (focal) and secondarily generalized tonic-clonic seizures, is biotransformed by hepatic CYP3A4, is a strong inducer of multiple hepatic enzymes thus possibly reducing the effectiveness of many other drugs, has adverse side effects of mild leukopenia/hyponatremia, and has a risk of causing Stevens-Johnson Syndrome (if HLA-B*1502)?
Carbamezepine
What antiseizure drug is indicated for absence/generalized/non-convulsive seizures, is partially metabolized by CYP3A4 and partially excreted unchanged in the urine (25%), and has adverse effects of behavioral changes, psychotic behavior, and lupus (SLE)?
Ethosuximide
What antiseizure works for most seizures but is the drug of choice primarily for tonic-clonic seizures, undergoes hepatic metabolism mostly (95%) with 5% excreted unchanged in the urine, inhibits the metabolism of drugs that are substrates for CYP2C9 (Phenytoin & Phenobarbitol), also inhibits UGT (Lamotrigine & Lorazepam), and has adverse effects of alopecia, weight gain, and elevated AST ( liver damage)?
Valproic Acid
What antiseizure drug is indicated for partial and secondarily generalized tonic-clonic seizures, has varied rate of elimination depending on concentration, is metabolized primarily by CYP2C9/10 and to a lesser extent CYP2C19, reduces effectiveness of Carbamazepine and others, increases then decreases warfarin anticoagulant effect, and has adverse effects including nystagmus, cerebellar atrophy, gingival hyperplasia, coarsening of facial features, and hirsutism (male pattern growth in women)?
Phenytoin
What antiseizure drug is the primary therapy for focal seizures/primary or generalized tonic-clonic seizures/myoclonic seizures, is rapidly and almost completely absorbed (not plasma protein bound), excreted in the urine, has no drug interactions, and has adverse effects like behavioral changes and psychosis?
Levetiracetam
What antiseizure medication is used to treat focal and primarily generalized tonic clonic seizures, is mainly excreted unchanged in the urine, is a mild inducer of CYP3A, inhibits CYP2C19, can increase serum lithium levels, decreased by Carbamazepine/Phenytoin, requires increased doses of oral contraceptives due to reducing estradiol effects, and has adverse symptoms of psychomotor slowing, word-finding difficulty, impaired concentration, and memory interference?
Topirimate
(Topamax or “dopamax”)
