Epilepsy Flashcards
There’s a _____% US prevalence of epilepsy
1.2%
When does genetic epilepsy usually present?
In young children
True or false: Infectious epilepsy does not include when a patient experiences seizures in the setting of acute infection such as meningitis or encephalitis
True; only occurs when a patient develops epilepsy as the sequelae of an infection
What is neurocysticercosis?
Parasitic infection of the brain that results from ingestion of eggs from a pork tapeworm
A protein responsible for the fusion of vesicles to the membrane has been found to be upregulated in certain models of epilepsy.
1) What is it called?
2) What does it cause?
1) Synaptic vesicle protein 2A (SV2A)
2) Dysfunction of SVA2 impairs synaptic GABA release
γ-aminobutyric acid (GABA) is an inhibitory neurotransmitter, and _______________ is an irreversible inhibitor of γ-aminobutyric acid transaminase (GABA-T)
vigabatrin
True or false: Seizures can manifest physically in a variety of ways
True
Seizures are classified into an initial three categories depending on how they begin in the brain; what are they? How does each begin?
1) Focal seizures: Start in a network of cells on only one side of the brain
2) Generalized seizures: Start in a bilaterally distributed network
3) Unknown onset: Can later be recategorized when it becomes clear how seizures begin in a particular patient’s brain
What are the two types of focal seizures? Differentiate them
1) Focal aware seizure: Cognizant during seizure (doesn’t mean they can respond to questions)
2) Focal impaired seizure: Loss of awareness may occur at any point
1) What are 3 different motor signs of focal seizures?
2) What are nonmotor signs?
1) Myoclonus (e.g., twitching and jerking)
Tonic contraction (e.g., stiffening)
Automatisms (e.g., smacking lips or rubbing hands)
2) Changes in sensation, emotions, thinking or experience
What are focal to bilateral tonic–clonic seizures?
Focal seizures that propagate beyond the brain’s one hemisphere to the contralateral hemisphere
Feelings of fear, depression, joy, anger, or memory phenomena such as feelings of familiarity (déjà vu) or unfamiliarity (jamais vu) may indicate what type of focal seizure?
Temporal lobe seizure activity
Describe the presentation of a tonic-clonic seizure
1) Sudden sharp tonic contraction
2) Subsequent period of rigidity and clonic movements
3) Pt may cry or moan or may lose sphincter control with bladder and/or bowel incontinence or bite their tongue
4) Postictal Sx: confusion, drowsiness, lack of coordination, soreness throughout the body, and amnesia
Atonic seizures:
1) How may they present?
2) What are they a hallmark feature of?
1) Head drop, the dropping of a limb, or slumping to the ground.
2) Lennox–Gastaut syndrome
How do typical absence seizures present?
Blank stare
What are some examples of generalized nonmotor seizures that aren’t typical absence?
Atypical absence
Absence seizures with myoclonia
Absence seizures with eyelid myoclonia
What are the 2 types of seizures of unknown onset?
Motor and nonmotor
After establishing the epilepsy type, what should be determined if possible?
An epilepsy syndrome
1) What is the gold standard for diagnosing epilepsy?
2) What is commonly performed in a patient who presents after their first seizure, as a way to evaluate for a brain tumor, cerebral bleeding, or gross anatomical injury?
1) Video EEG
2) CT
True or false: Some clinicians choose to start an antiseizure drug (ASD) treatment after one seizure with a definite abnormal MRI or epileptiform EEG while others do not initiate treatment until a second seizure has occurred
True
What is the general recommendation as far as treating first seizures goes?
Don’t Tx unless recurrent seizures likely
For childhood absence epilepsy (CAE):
1) What works?
2) What is detrimental?
1) Efficacious = ethosuximide
2) Detrimental = phenytoin or carbamazepine
Comorbidity Tx:
1) Epilepsy + migraine?
2) Epilepsy + bipolar disorder?
3) Epilepsy + neuropathy
1) Topiramate
2) Lamotrigine
3) Pregabalin
1) What is the general guideline for treating epilepsy?
2) How do you know if optimal dose has been achieved and no further increase is necessary?
3) When may further titration to a maximum dose may be needed for optimal seizure control be needed?
1) Start low and titrate
2) If the patient is seizure free with no adverse effects at a minimal therapeutic dose
3) If the patient continues to have seizures at a minimal or moderate-therapeutic dose
Is monotherapy preferred for epilepsy or not? Explain
Monotherapy is preferred; may consider additional drugs for therapy failure at max dose or intolerable side effects
List the factors to consider when selecting an ASD (anti seizure drug)
1) Efficacy for the specific seizure type, epilepsy, or syndrome
2) Most tolerable SE profile (considering age and gender)
3) Choosing one that’ll also treat comorbid conditions
4) Drug-drug interactions with other meds
5) Compliance + insurance
6) Need for therapeutic levels to be reached quickly
List the 4 first generation ASDs and their target concentration ranges in mcg/ml
1) Carbamazepine: 4-12
2) Phenobarbital: 10-40
3) Phenytoin: total = 10-20
-Unbound: .5-3 mcg
4) Valproic acid (divalproex): 50-100
List the second generation ASDs (8)
1) Felbamate
2) Gabapentin
3) Lamotrigine
4) Levetiracetam
5) Oxcarbazepine
6) Tiagabine
7) Topiramate
8) Zonisamide
List the third generation ASDs (9)
1) Brivaracetam
2) Cannabidiol
3) Clobazam
4) Eslicarbazepine
5) Lacosimide
6) Perampanel
7) Pregabalin
8) Rufinamide
9) Vigabatrin
Describe the escalation regimen for Lamictal >12 y/o
Describe dosing when taking valproate and lamotrigine (Lamictal):
1) During weeks 1 and 2, a dose of 25 mg every other day may be given instead of 25 mg once daily dose.
2) During weeks 3 and 4, a dose of 25 mg once a day may be given instead of the 25 mg twice daily dose (total daily dose of 50 mg).
List 3 nonpharmacologic therapies for epilepsy, and specify when to use each
1) Ketogenic diet (↑ fat / ↓ carb)
2) Vagus nerve stimulation (VNS): For refractory epilepsy
3) Surgery: Tx of choice for refractory focal epilepsy
Teratogenicity of ASDs:
1) What should you avoid in pregnancy? (2 things)
2) What should you do to prevent an adverse effect?
3) What should you consider?
1) Valproic acid and carbamazepine
2) High-dose folic acid (4-5 mg daily) to reduce neural tube defects
3) Using copper or levonorgestrel IUD
1) What is an adverse effect of chronic ASD therapy? Why?
2) What are 2 things you should do abt it?
3) Give examples of drugs that can do this
1) Osteomalacia and osteoporosis: Interference of vitamin D metabolism
2) Supplement vitamin D and calcium
-Bone mineral density testing
3) Phenytoin, phenobarbital, carbamazepine, oxcarbazepine, felbamate and valproate
List 3 nonpharmacologic therapies for epilepsy, and specify when to use each
1) Ketogenic diet (↑ fat / ↓ carb)
2) Vagus nerve stimulation (VNS): For refractory epilepsy
3) Surgery: Tx of choice for refractory focal epilepsy
Carbamazepine (Tegretol):
1) What 3 forms does it come in?
2) MOA?
3) What 2 comorbidities is it useful for?
1) Chewable, ER tablet, suspension
2) Na+; Enhances fast inactivation of voltage-gated sodium channels
3) Comorbid bipolar disorder or trigeminal neuralgia
Carbamazepine (Tegretol):
1) What can it make worse?
2) What severe SE is a risk with this med?
3) Is it safe in pregnancty?
1) Other seizure types in patients with absence epilepsy
2) Increased risk of SJS/TEN in HLA-B1502 and HLA-A3101 allele in Asians
3) Can cause fetal harm
Carbamazepine is a __________ and ____________ inducer and can cause __________ effects
CYP and UGT; CNS effects
Carbamazepine is a potential inducer of what 4 CYPs and what else?
1) CYPs: 3A4, 1A2, 2B6, 2C9/19 &
2) Glucuronyltransferase(UGT)
1) Carbamazepine has a boxed warning for what increased risk of 3 things?
1) SJS/TEN and HLA-B*1502 allele; aplastic anemia and agranulocytosis
List some rare and serious adverse effects of Carbamazepine
1) Other blood dycrasias incl.: DRESS*; hyponatremia; increased intraocular pressure
2) AV heart block
3) Hepatotoxicity
4) Nephrotoxicity
Long-term adverse effects of carbamazepine include __________________, as well as _____________ disease including osteoporosis, osteopenia, osteomalacia
Hyponatremia; metabolic bone
Clonazepam (Klonopin) (CIV/ continuous intravenous infusion, tablet, ODT):
1) What is the MOA?
2) What other Dx is this useful for?
3) When may it increase TC (tonic clonic) seizures?
1) Cl-: binds GABAA receptor and potentiates GABA by modulating chloride conductance
2) Panic disorder
3) When used in mixed seizure types
Clonazepam (Klonopin):
1) What 2 Dxs is it contraindicated in?
2) What may occur after discontinuation?
3) Is it safe in pregnancy?
4) What types of effects can it have?
1) Acute narrow angle glaucoma and severe liver impairment
2) Withdrawal symptoms
3) May cause fetal harm
4) CNS
1) What is the boxed warning for Clonazepam (and all benzos)?
2) What is a long term effect?
1) Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death; overdose & death; abuse and addiction; dependence and withdrawal
2) Physiologic dependence
Ethosuximide (Zarontin) (capsule, solution):
1) MOA?
2) What is it the DOC for?
1) Ca2+; inhibition of T-type calcium channels
2) Absence seizures*
Ethosuximide (Zarontin) (capsule, solution):
1) What does it make worse?
2) When should you use w caution?
3) Is it safe in pregnancy?
1) Generalized TC seizures and other seizure types
2) In hepatic/renal dysfunction
3) May cause fetal harm
Ethosuximide
1) Common and dose-related adverse effects include what?
2) What is a long term adverse effect?
3) What are some rare and serious adverse effects?
1) Anorexia and weight loss; CNS effects
2) Behavioral changes (CNS related)
3) Blood dyscrasias; SJS; DRESS; hepatic/renal dysfunction; lupus erythematosus
Phenobarbital (Luminal) (CIII, Tablet, elixir, injectable) has the exact same MOA as what?
Benzos
(Cl-; binds GABAA receptor and potentiates GABA by modulating chloride conductance)
1) What ASD is not FDA approved (grandfathered)?
2) What may happen when this ASD is used w other CNS depressants? What else may it cause?
3) Is this drug safe in pregnancy?
1) Phenobarbital
2) May produce additive CNS effects; may cause respiratory depression
3) Can cause fetal harm
Phenobarbital:
1) Is it an inducer or inhibitor?
2) What are the Common and Dose-Related Adverse Effects?
1) CYP and UGT Inducer: induces CYP3A4/2C9/2C19/1A2 and glucuronyltransferase(UGT)
2) Paroxysmal effects including excitement, irritability and hyperactivity in elderly and children;
Phenobarbital:
1) What is the Boxed warning (Sezaby)?
2) What are the rare and serious adverse effects?
3) What are 3 long term effects?
1) Respiratory depression with opioids, dependence and withdrawal; abuse and addiction
2) Rash (SJS, TEN); cardiac effects including bradycardia, hypotension, syncope; hepatotoxicity
3) Behavioral changes; metabolic bone disease; folate deficiency (with megaloblastic anemia)
Phenytoin (Dilantin)
(ER capsule, liquid, injectable, chewable tablet)
1) MOA?
2) What are injectable phenytoin and fosphenytoin approved for?
3) What 2 conditions can it make worse?
1) Na+: Enhances fast inactivation of voltage-gated sodium channels; inhibits persistent sodium current (INAP) and increases threshold for action potential firing
2) Prevention or treatment of seizures during or after neurosurgical procedures, severe TBI, status epilepticus
3) May aggravate seizures in patients with absence seizures; can increase blood sugar levels in diabetes;
Monitoring of free _____________ levels required in pregnancy, elderly, or low albumin; compromised absorption with concomitant tube feeds
phenytoin
Phenytoin:
1) What does it induce?
2) What is a common or dose related adverse effect?
1) CYP3A4/2C9/2C19/1A2 & glucuronyltransferase(UGT)
2) CNS effects
Phenytoin:
1) What is the boxed warning?
2) What are some other rare/ serious adverse effects?
1) Hypotension and arrhythmias when exceeding infusion rates greater than 50 mg / min for adults and 1 to 3 mg / kg / min (of 50 mg / min – whichever is slower) for pediatrics
2) Blood dyscrasias; (SJS/TEN); DRESS; hepatotoxicity; purple glove syndrome with IV administration
Primidone (Mysoline; Tablet)
1) MOA?
2) What other condition is it useful in treating?
3) **Who is it contraindicated in?*
1) Cl-; Prodrug converted to active metabolite phenylethylmalon-amide (PEMA) and phenobarbital with same mechanism of action
2) Essential tremor
3) Patients with porphyria
1) Is Primidone an inducer or inhibitor?
2) Common and dose-related adverse effects include what?
1) Induces CYP3A4/2C9/2C19/1A2 and glucuronyltransferase(UGT)
2) CNS effects; anorexia; emotional disturbances
Primidone:
1) What are some rare and serious adverse effects?
2) What abt long term adverse effects?
1) Blood dyscrasias; SJS/ TEN
2) Behavioral changes; intellectual blunting; metabolic bone disease; folate deficiency (with megaloblastic anemia)
Valproate (injectable as Divalproex (Depakote)):
1) MOA?
2) What 2 comorbidities can it Tx?
1) GABA?? likely potentiates GABAergic transmission among multiple other unknown mechanisms
2) Bipolar disorder and migraine
” pregnancy category D—contraindicated in women of childbearing potential and pregnancy category X for pregnant patients treated for migraine prophylaxis”
This describes which drug?
Valproate (injectable as Divalproex (Depakote))
Valproate/ Divalproex:
1) Inducer or inhibitor?
2) _____________ OCPs may decrease valproic levels
3) Common and dose-related adverse effects include what?
1) Inhibits CYP2C9 & glucuronyltransferase
2) estrogen
3) GI effects; CNS effects, dose dependent thrombocytopenia (associated with valproate concentrations >100 mcg/mL)
Valproate/ Divalproex: Rare and serious adverse effects include what?
Hyperammonemia with and without encephalopathy; DRESS
Felbamate (Felbatol; Tablet, liquid):
1) MOA?
2) When should it be used?
3) What pts is it contraindicated in?
1) Antagonizes NMDA glutamate receptor
Binds to GABAA receptor and augments GABAergic transmission
2) For severe refractory epilepsy ONLY
3) Patients with hepatic dysfunction, history of blood dyscrasias
Felbamate has what 2 common/ dose related adverse effects?
Anorexia + CNS effects
When might the SEs of Felbamate occur?
Aplastic anemia with reported onset between 5-30 weeks; acute liver failure with reported onset occurring in 5 weeks
Gabapentin (Neurontin; Tablet, capsule, liquid):
1) MOA?
2) What are the advantages of it?
1) Ca2+; binds to presynaptic α2δ subunit of calcium channels with unknown antiseizure effect
2) Useful in postherpetic neuralgia, chronic pain, and neuropathy; few drug–drug interactions
Gabapentin:
1) 2 disadvantages?
2) What is a common/ dose related effect?
3) What are the 2 rare/ serious adverse effects?
4) What are 2 long term effects?
1) Withdrawal rxn + may cause fetal harm
2) CNS effects
3) DRESS + neuropsychiatric symptoms in children 3 to 12 years of age
4) Weight gain, peripheral edema
Lamotrigine (Lamictal; Tablet, chewable, ODT, XR tablet):
1) MOA?
2) What other Dx can it Tx?
3) Is it safe in pregnancy?
1) Na+; enhances fast inactivation of voltage-gated sodium channels
2) Bipolar disorder
3) May cause fetal harm
What drug only induces UGT?
Lamotrigine/ Lamictal
Lamotrigine:
1) Is it an inducer or inhibitor?
2) Estrogen OCPs decrease lamotrigine by _____%
3) What are some common and dose-related adverse effects?
1) UGT inducer
2) 50%
3) CNS effects; other effects including rhinitis, pharyngitis, infection, fever
Lamotrigine:
1) Boxed warning?
2) What are 2 other rare/ serious effects?
3) Long term effects?
1) Rash including SJS, TEN with increased risk if given with valproate, exceeding recommended initial dose or dose escalation
-more common in kids
2) DRESS; blood dyscrasias
3) Rash usually appears after 3-4 weeks of therapy
Levetiracetam (Keppra; Tablet, XR tablet, injectable)
1) MOA?
2) Advantage?
3) 2 disadvantages?
4) What are the common/ dose related effects?
1) Binds to and selectively inhibits synaptic vesicle SV2A protein thereby preventing neurotransmitter release
2) Minimal drug–drug interactions
3) May worsen depression, PTSD, anxiety, thought disorders
-Dose adjustment in dialysis/renal failure is necessary
4) CNS effects (incl. behavioral/ anger issues)
Levetiracetam (Keppra) What are 2 rare and serious adverse effects?
Psychosis, hallucinations
Oxcarbazepine (Trileptal; Tablet, ER tablet, liquid )
1) MOA?
2) Advantage?
1) Na+; Enhances fast inactivation of voltage-gated sodium channels
2) Useful in bipolar
Oxcarbazepine:
1) What does it decrease?
2) What is a common SE?
1) Estrogen OCP levels
2) CNS effects
Oxcarbazepine:
1) Rare and serious SEs?
2) Long term use SE?
1) Hyponatremia; rash (SJS, TEN); DRESS; blood dyscrasias
2) Hyponatremia
Tiagabine (Gabatril):
1) MOA?
2) What has it been associated with in those w existing epilepsy?
3) Common/ dose related SEs?
1) Inhibitor of GABA reuptake transporter GAT1
2) New-onset seizure, status epilepticus, and exacerbation of EEG abnormalities
3) CNS effects + behavior effects
Topiramate:
1) List the rare adverse effects
2) What are 3 potential long term effects?
1) Glaucoma; oligohidrosis and hyperthermia; metabolic acidosis; rash (SJS, TEN); hypothermia and hyperammonemia with and without encephalopathy when used with valproate.
2) Weight loss, renal stones, metabolic acidosis
Zonisamide (Zonegran) Capsule: What are the 3 MOAs?
1) Enhances fast inactivation of voltage-gated sodium channels
2) Inhibits T-type calcium channels
3) Weak carbonic anhydrase inhibitor
Zonisamide (Zonegran) Capsule:
1) Who is it theoretically contraindicated in?
2) Should not be used in renal failure due to what?
3) Common SE?
1) Those with sulfa allergy
2) Increases in SCr and BUN and possible effects on GFR.
3) CNS effects
Zonisamide:
1) Rare and serious adverse effects include what?
2) Long term adverse SEs? (hint: same as topiramate)
1) Oligohidrosis and hyperthermia; SJS/TEN; DRESS; fulminant hepatic necrosis; blood dyscrasias
2) Weight loss, renal stones, metabolic acidosis
Brivaracetam (Briviact) CV (Tablet, liquid, injectable):
1) MOA?
2) Disadvantage?
1) Binds to and selectively inhibits synaptic vesicle SV2A protein thereby preventing NT release
2) Dosage adjustments required in hepatic impairment
Brivaracetam
1) Inducer or inhibitor?
2) Common SEs?
3) Rare SE?
1) Inhibits CYP2C19 & glucuronyltransferase
2) CNS + behavioral
3) Psychosis
Cannabidiol (Epidiolex) CV Solution:
1) MOA?
2) How does the FDA designate it?
3) What is it useful in?
4) Is it safe in pregnancy?
1) Unknown
2) Orphan drug
3) Refractory seizures in LGS and Dravet syndrome
4) May cause fetal harm
A rare disease is defined as a disease that affects fewer than 200,000 people in the United States; prior to passage of the _________________ Act, private industry had little incentive to invest money in the development of treatments for small patient populations.
Orphan Drug
Orphan Drug Act provides what 2 things?
1) 7-year marketing exclusivity to sponsors
-Exclusive marketing rights limit competition
2) Tax credit of 50 percent of the cost
Cannabidiol:
1) MOA?
2) “Common” SEs?
1) Induces CYP1A2, CYP2B6 & glucuronyltransferase (UGT); Inhibits CYP2C9 & CYP 2C19;
2) CNS effects (not rlly common); transaminase elevations
Clobazam (Onfi) CIV (Tablet, suspension)
1) MOA?
2) Use with other CNS depressant may produce what?
3) Is it safe in pregnancy?
1) Cl-; binds GABAA receptor and potentiates GABA by modulating chloride conductance
2) Additive CNS effects; may cause respiratory depression, coma, and death
3) May cause fetal harm
Clobazam:
1) What does it inhibit and induce? (how can it affect other ASDs?)
2) What does it decrease?
3) What is a common SE?
1) Inhibitor of CYP 2C9 and inducer of CYP 3A4
2) Decreases estrogen OCP levels
3) CNS effects
What is the boxed warning Clobazam and all other benzos have?
Concomitant use with opioids increases risk of death; overdose death; physical dependence;
Eslicarbazepine:
1) Induces and inhibits what?
2) What else does it interact with?
3) Common SE?
1) Induces glucuronyltransferase (UGT); Inhibitor of CYP2C19
2) Decreases estrogen OCP levels
3) CNS effects
Eslicarbazepine: rare SEs?
Hyponatremia; SJS; DRESS; cardiac effects including prolonged PR interval, AV block; hepatotoxicity; blood dyscrasias
Lacosamide (Vimpat) CV (Tablet, liquid, injectable)
1) MOA?
2) Advantage?
3) Common SE?
1) Na+; Selectively enhances slow inactivation of voltage-gated sodium channels
2) Minimal drug–drug interactions
3) CNS effects
Lacosamide (Vimpat): there’s some weird rare/ serious adverse effects with this one, what are they?
Cardiac effects including: AV conduction abnormalities, prolonged PR interval, atrial arrhythmias, syncope (especially in patients with diabetes)
Perampanel (Fycompa) CIII (Tablet, liquid):
1) MOA?
2) Advantage?
3) Who should you avoid using it in?
1) Selectively and noncompetitively antagonizes AMPA glutamate receptor on postsynaptic neuron
2) Useful in mixed seizure types
3) Avoid in active psychosis or unstable recurrent affective disorders with significant hostility or aggressive behavior; -Avoid in severe hepatic/renal impairment or hemodialysis
Perampanel:
1) What does it induce?
2) What does it inhibit?
3) What does it decrease?
4) Common SEs?
1) CYP3A4, CYP2B6, glucuronyltransferase (UGT)
2) CYP3A4 & glucuronyltransferase(UGT)
3) Estrogen OCP levels
4) CNS + behavioral effects
Perampanel:
1) Rare and serious SE?
2) Common SE?
1) Boxed warning for aggression
2) Weight gain
Pregabalin (Lyrica) CV (Tablet CR, capsule, liquid)
1) MOA?
2) Advantages? (2)
3) Common SE?
4) Long term SEs? (2)
1) Ca2+; binds to presynaptic α2δ subunit of calcium channels
2) Useful in patients with neuropathy + minimal DDIs due to renal excretion
3) CNS effects
4) Weight gain, edema
Rufinamide (Banzel; Tablet, liquid):
1) MOA?
2) What does it interact with?
1) Na+; Selectively enhances fast inactivation of voltage-gated sodium channels
2) Decreases estrogen OCP levels
Rufinamide: Rare/ serious adverse effects?
DRESS; rash (SJS); status epilepticus; leukopenia; QT interval shortening
Vigabatrin (Sabril; Tablet, powder pack)
1) MOA?
2) What does it induce?
3) Common SEs?
1) Binds to and irreversibly inhibits GABA transaminase
2) CYP 2C9
3) CNS effects
-In peds: aggression; infection including upper respiratory tract infection, bronchitis, ear infection, and acute otitis media
Vigabatrin:
1) Rare/ serious SEs? (besides vision)
2) Long-term adverse effects?
1) Seizure exacerbation, particularly absence and myoclonic seizures in patients with generalized epilepsies; anemia
2) Onset of vision loss is unpredictable and can occur after weeks, months, or years with risk increasing in a dose-related and life exposure-related manner; abnormal MRI signal changes in infants treated for infantile spasms strongly suggestive of intramyelinic edema in select brain areas
What are 2 options for at-home Tx of seizures?
1) Diazepam (Diastat): Rectal gel
2) Diazepam (Valtoco): Nasal spray
Describe deciding whether or not you should d/c therapy
(probably not on exam)
Patients may remain on therapy for their lifetime
Some patients may discontinue therapy
Seizure free for 2 to 5 years
History of a single type of focal seizure or primary generalized seizures
Normal neurologic exam and normal IQ, and an EEG that has normalized with treatment
