Definitions, Etiology & Pathophysiology
What is the minimum duration for a seizure to be classified as status epilepticus?
Bonus: What was the previous duration definition?
5 minutes
What is the maximum loading dose of levetiracetam (in mg)?
4500 mg
What is the first-line agent for status epilepticus?
Bonus: Name the routes of administration
Benzodiazepines
Bonus: lorazepam is IV, diazepam is PR/IV, midazolam is IM, IN, buccal
What IV fluid should be avoided in patients on a ketogenic diet?
Dextrose
What is the preferred agent for pediatric refractory SE according to the NYP algorithm?
Midazolam infusion
What is the definition of super-refractory SE?
SE that continues or recurs 24 hours or more after the onset of anesthesia, including those cases in which SE recurs on the reduction or withdrawal of analgesia
What is the target total phenytoin level for status epilepticus?
Bonus: What about non-SE seizures?
15-25 mcg/mL
10-20 mcg/mL
What was the conclusion of the ESETT trial?
Levetiracetam, fosphenytoin and valproate were found to be equally efficacious in improving patient responsiveness for status epilepticus
True or False: Suspensions are preferred over tablets for pediatric patients on a ketogenic diet.
FALSE
What is the FDA-approved antiepileptic for neonatal seizures?
Bonus: What type of formulation is used in neonates?
Phenobarbital
Bonus: preservative-free
Provide one potential etiology of seizures in each of the following populations: neonatal, pediatric, adult.
Neonates: HIE, stroke, congenital, metabolic, infectious, drug-induced
Pediatric: genetic, trauma, febrile, metabolic, autoimmune
Adult: trauma, tumor, stroke, encephalitis, meningitis, metabolic, drug/alcohol induced
What are the benefits of fosphenytoin over phenytoin?
Faster infusion rate, safer side effect profile (no purple glove syndrome), better compatibility
What are the alternative options for urgent control according to the NYP Adults SE algorithm?
Lacosamide, brivaracetam, phenobarbital
In a ketogenic diet, what % of calories should come from fat, protein, and carbohydrates each?
65-75% fat, 20-25% protein, 5-10% carbohydrates
What are the risk factors for febrile seizures?
NICU stays > 28 days, developmental delays, infection, family history of seizures
Name two neurotransmitters involved in the pathophysiology of seizures and classify them as inhibitory or excitatory.
Glutamate: excitatory
GABA: inhibitory
Identify the site of action for the following medications: phenytoin, lorazepam, levetiracetam, ketamine
What other medication can ketamine be combined with to lower dose requirements?
Simultaneous benzodiazepine infusion
Name two of the proposed mechanisms of a ketogenic diet in the management of epilepsy.
Increased levels of GABA, decreased levels of glutamate, increased production of BDNF, remodeling of gut microbiome, improvement of mitochondrial action, antagonize AMPA receptors, activation of KATP currents
Name two treatment options for infantile spasms, and the side effect that requires a REMS program for one of them.
Adrenocorticotropic hormone, vigabatrin
REMS for vision loss caused by vigabatrin
Describe the pathophysiology of status epilepticus.
•After repeated seizures, GABA-a receptors are internalized
•GABA-a receptors become inactive because they are no longer within reach of the neurotransmitter
•In contrast, NMDA subunits are mobilized to the synaptic membrane and assemble into additional receptors
•As a result, the number of functional NMDA receptors per synapse increases, whereas the number of functional GABA-a receptors decreases
What are the major side effects of propofol and what monitoring parameters should be used?
Side effects: PRIS, hypotension, hypertriglyceridemia, pancreatitis
Monitor: TG, pH, HCO3, CPK, lipase, BP
Provide a treatment option and dosing for emergent initial therapy, urgent control, refractory SE, and super-refractory SE.
emergent: lorazepam, diazepam or midazolam
urgent: levetiracetam, valproate, fosphenytoin
refractory: midazolam, propofol
super-refractory: ketamine, pentobarbital
Identify two interventions a pharmacist can make during order verification for the following med list for a patient on a ketogenic diet:
- acetaminophen chewable tablet
- senna tablets
- phenytoin suspension
- albuterol nebulizer
- amoxicillin suspension
acetaminophen to non-chewable tablet, phenytoin suspension to capsules, amoxicillin suspension to capsules
A 3-year-old child (15 kg) with history of epilepsy presents to the ED in status epilepticus. The patient already received rectal diazepam at home, followed by IV lorazepam on arrival in ED, with no response. The team orders levetiracetam 150 mg po. What is wrong with this order?