Seizures and Epilepsy Flashcards
Neurons
The functional unit of the brain
Extraordinarily complex network of billions of nerve cells
Communicate using electrical potentials
Action Potentials
Series of channels that selectively let charged elements in and out of cells
Channels for Na, K and Ca are particular important in seizures
All or nothing
Neurotransmitters
complex compounds that signal neighboring cells on or off
What is a seizure?
Seizure: a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain
Types of Seizures
convulsive (generalized, shaking)
non convulsive
Generalized seizures
typical of genetic causes and usually diagnosed in childhood
Seizure semiology – “the study of signs”
Most seizures (adults) start as a focal seizure
Partial seizures (start in small part of brain) ↔️ complex partial seizures causing confusion ↔️ secondarily generalized seizures (convulsive)
The First Seizure
Is it a seizure? (Any provoking cause)
MRI or CT
EEG or brain wave testing
Everyone can have a seizure - was it provoked
Patient with first unprovoked seizure: normal imaging and EEG – most neurologist DO NOT prescribe daily prophylactic medication
If second seizure occurs…
…likelihood of third seizure very high
start daily medications!
Epilepsy
At least two unprovoked seizures occurring greater than 24 hours apart
Young children may have genetic causes of epilepsy, Some are outgrown
Incidence of epilepsy is roughly 1% of the population
Cause of Epilepsy
Varies by age
most adults have lesional epilepsy
Long Term Care for Epilepsy
Months to years: trial and error period (to find ideal medication)
Patient care giver support is essential, care giver burden is tremendously high
Minimizing risk of injuries – swimming and bathing are particularly dangerous. Heights are also worrisome.
Many people have concurrent psychiatric and/or substance abuse disease and history.
Treatment of Epilepsy
Uncontrolled epilepsy is a severely disabling condition impacting all facets of life
Impairs ability to work, develop relationships and has a rather severe and destructive impact on psychiatric health
Patients who have had a seizure should not be driving until 1 year seizure free
First line therapy for epilepsy is medical to prevent ongoing seizures
Lorazepam (Ativan)
USE: FIRST LINE treatment in emergency seizure treatment (in ER or ambulance)
Not rapidly redistributed into tissue (half life is 24 hrs)
Rapid onset and Strong sedative
Not practical for daily use, can lead to withdrawal seizures with long term use
Midazolam (Versed)
USE: continuous infusion in ICU for severe/prolonged seizures
Very rapid onset (IV)
Half life 2 hours
Very strong sedative, most patients in ventilator while receiving drug
Clonazepam (Klonopin)
MOA: Work by facilitation of GABA mediated inhibition
USE: Some efficacy with all seizures, particularly useful in myoclonic types
AE: sedation, slow cognition, drooling
Watch for tolerance
Half life 24-48 hours
Clobazam (Onfi)
MOA: GABAA receptor agonist
USE: approved in last 5 years here in the US for Lennox-Gastaut syndrome, Adjunctive, “add on” therapy
Half life 10-46 hours
Dosed twice daily
Tolerance common, may need escalating doses to maintain control
Phenobarbital (Luminal)
MOA: Prolongs the open state of the GABA receptor, depresses normal excitatory activity
Most drug eliminated by liver, half life is 70-130 hours
Strong enzyme inducer
AE: sedation, confusion, insomnia, interferes with Vitamin D metabolism, very high risk of withdrawal
Primidone (Mysoline)
MOA: Metabolized to phenobarbital
USE: drug itself may also have anti seizure properties, tremor
AE: similar to phenobarbital
Phenytoin (Dilantin)
MOA: membrane stabilizing effect, multiple actions sites on Na channels, extensively protein bound, inducer of P450 system
USE: status epilepticus
Complicated first order and zero order
AE: cerebellar atrophy, sensory neuropathy, gingival hyperplasia, bone density loss (due to altered metabolism of vitamin D), risk of serious arrhythmia and bradycardia during IV administration
Drug interactions: phenobarbital, carbamazepine and valproic acid
Carbamazepine (Tegretol, Carbatrol ER)
MOA: stabilizing effect on membrane, particularly related to Na currents
USE: Focal onset seizures
Strong hepatic enzyme inducer with clinically significant drug-drug interactions
AE: GI upset, allergic reactions, and persistent leukopenia with long term usage
Oxcarbazepine (trileptal)
MOA: similar to carbamazepine
USE: focal onset seizures
AE: allergic reactions and hyponatremia
Better tolerated than carbamazepine, fewer drug-drug interactions
No IV
Lamotrigine (Lamictal)
MOA: similar to phenytoin and carbamazepine, voltage dependent blockade of Na channels
USE: all seizure types with exception of myoclonic seizures
AE: Stevens-Johnson’s Syndrome, can be life threatening
Start at very low doses to limit likelihood of skin reactions → Escalate over a period of weeks to months.
Not a good choice for patients with poor compliance
Topiramate (Topamax)
MOA: inhibits voltage activated Na channels, decreases glutamate-mediated excitatory transmission, also effects Ca currents, GABA mediated channels and as weak inhibitory CA activity.
USE: some efficacy against all seizure types, also commonly used in migraine, psychiatry and neuropathic pain
AE: cognitive slowing, word finding difficulty, renal stones, weight loss
Valproic acid, Divalproex (Depakote, Depakene)
MOA: increase GABA concentrations, modulate GABA receptor expression on cell surfaces. Some metabolites also active.
P450 enzyme inhibitor
USE: primary generalized seizures (think JME), effective in absence and myoclonic seizures. Less effective for focal onset.
prolongs half life of lamotrigine, may act synergistically
AE: weight gain, tremor, alopecia, hyperammonemia with encephalopathy, platelet function, PCOS, major risk of teratogenicity
Risk for hepatic failure in children under 10, especially those with certain genetic conditions.
Gabapentin (Neurontin)
MOA: Unique binding site in neocortex and hippocampus voltage gated Ca channel
USE: partial onset seizures, “weak” anti seizure drug, add on for patients with neuropathic pain and seizures
AE: drowsiness, dizziness and sensory changes
Levetiracetam (Keppra)
MOA: binds to synaptic vesicle protein 2a, unclear how this is effective
USE: non-neurologists for seizures, all seizure types and may be particularly useful in temporal lobe epilepsy
AE: agitation or mood changes, concern in patients with underlying psychiatric disease
Well tolerated and has no drug interactions
Ethosuximide (Zarontin)
MOA: module Ca channels in the thalamus
USE: exclusively in absence seizures
AE: GI disturbance , very safe, can worsen non-absence seizures
Vigabatrin (Sabril)
MOA: Irreversible inhibitor of GABA transaminase, long acting drug
USE: infantile spasms
AE: retinal toxicity manifested as concentric visual field constriction
Limits use for a duration of 6 months
Imperative baseline visual field and follow ups
Cannabidiol (Epidiolex)
MOA: Low affinity for CB1 and CB2 receptors, Serotonergic
USE: Dravet Syndrome and LGS
No psychotropic properties
AE: GI and liver side effects most common
Status Epilepticus
True neurological emergency
Seizures lasting longer than 5 minutes with or without rescue therapy and unlikely to spontaneously terminate
Need respiratory support (intubation) and ICU level care
Rapid and aggressive medication adjustments
Medications During prolonged Seizures
Rescue vs prophylactic medication
IV preferable, can give IM as well
If seizure does not terminate repeat
Continue benzodiazepine administration while preparing ‘prophylactic’ medication
Plan to intubate patient
Dosing
Depends on half life
Drugs with long half-life (phenytoin, phenobarbital) can be given once a day
Drugs with short half-life (valproate, carbamazepine) require more frequent dosing
The less frequent the dose, the greater the compliance
Enzyme Induction
A subset of the p450 isoenzymes (1C2, 2C9, 2C19, 3A4) and uridine glucuronal transferase (UGT) are upregulated by phenytoin, phenobarb, primidone and carbamazepine
an increased rate of clearance for all compounds that utilize this pathway
Enzyme Inhibition
Results in a decreased rate of drug clearance
Usually affect only one or two pathways = Depakote
More rapid effect than enzyme inducers
