Epilepsy important content Flashcards
bolded things and just weird things that stand out
What drug has a boxed warning for aggression, hostility, irritability, anger, and homicidal ideation?
“Know this”
Perampanel
List the drugs that can induce seizures
will be on exam
BATHMIC
1) Bupropion
2) Alcohol, benzodiazepine or barbiturate withdrawal
3) Theophylline
4) Haloperidol and clozapine
5) Meperidine (opioid)
6) Illegal drug overdose (i.e., cocaine)
7) Carbapenem/ imipenem
What are the 6 categories of epilepsy?
1) Genetic
2) Structural
3) Infectious
4) Metabolic
5) Immune
6) Unknown
General pathophysiologic process underlying all epilepsies is what?
Disturbed regulation of electrical activity resulting in synchronized and excessive neuronal discharge
International League Against Epilepsy (ILAE)
Disorder + consequences of disorder
Can the patient drive a car?
What are the 3 genetic conditions that can cause epilepsy? What are the mutations of each?
1) Dravet syndrome; sodium channel
2) Childhood Absence Epilepsy (CAE); Ca2+ channels and GABA-receptor subunits
3) Juvenile Myoclonic Epilepsy (JME); many different mutations
Structural epilepsy etiologies
1) Cortical dysplasia is a common cause of what? What is it?
2) What is a common cause of Tx resistant adult-onset epilepsy? What causes this condition?
3) What is the third structural etiology discussed in class?
1) Childhood onset drug-resistant epilepsy
-exactly what it sounds like, cerebral cortex malformation
2) Mesial temporal lobe epilepsy; sclerosis occurs in the hippocampus
3) Traumatic brain injury epilepsy
What pathogen found in developing countries can cause infectious epilepsy?
Neurocysticercosis
Metabolic epilepsy may be caused by what? Why does this condition cause epilepsy?
Lafora disease; development of insoluble glycogen inclusion bodies
1) Immune epilepsy may be caused by what?
2) How does this condition cause epilepsy?
1) Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis
2) Central nervous system (CNS) inflammation
1) What is the pathophys of epilepsy?
2) What 4 ion channels are thought to play a significant role?
3) What are 2 other things that contribute to the pathophys?
1) Neuronal hyperexcitability and hypersynchronization
2) K+, Na+, Ca2+, and Cl–
3) Synaptic vesicle protein 2A (SV2A) and γ-aminobutyric acid (GABA)
Seizures are classified into an initial three categories depending on how they begin in the brain; what are they?
1) Focal seizures: one side of the brain
2) Generalized seizures: bilaterally
3) Unknown onset
Generalized-onset seizures usually always involve what?
Impaired awareness
What happens after the cessation of a typical absence seizure (blank stare seizure)?
The patient will often return to the previous activity as if nothing had happened
If the patient continues to have seizures at a maximum dose, or if the patient experiences intolerable adverse effects at any dose, what is appropriate?
Adding a second ASD and then tapering and discontinuing the ineffective or intolerable first ASD
Medication that induce lamotrigine glucuronidation include what?
Will be on exam
1) Carbamazepine
2) Phenobarbital
3) Phenytoin
4) Primidone
5) Rifampin
6) Lopinavir/ ritonavir
7) Atanazivir/ ritonavir
+ estrogen
What is the one med that inhibits lamotrigine glucuronidation?
will be on exam
Valproic acid
1) Oral contraceptives do what to lamotrigine metabolism?
2) What does this mean you need to do?
“big test thing”
1) Estrogen induces UGT and increases lamotrigine metabolism
2) Increase lamotrigine dose; may see doses of 150 mg to 200 mg PO BID
Lamictal
1) Must be re-titrated if a patient misses more than ____ half-lives duration of medication
2) Consider titration after missing _____ days of therapy w/ phenytoin, phenobarbital, primidone or carbamazepine
3) Consider after missing _______ days of therapy w/out valproic acid or an inducer
4) Consider after missing ______ days of therapy w/ valproic acid
“Know if you need to re-titrate”
1) 5
2) 2.5
3) 5
4) 10
What are the 3 different half lives of lamictal/ lamotrigine depending on concomitant therapies?
Concomitant:
1) Valproic acid therapy: 48 to 70 hours
2) Phenytoin, phenobarbital, primidone, or carbamazepine therapy: 13 to 14 hours
3) Phenytoin, phenobarbital, primidone, or carbamazepine plus valproate therapy: 27 hours
Drug of choice for absence seizures is what?
Ethosuximide (Zarontin)
What ASDs may cause folate deficiency (with megaloblastic anemia) with long term use?
Phenobarbital + Phenytoin + Primidone
What drug can cause purple glove syndrome with IV administration?
Phenytoin
Phenytoin: What are the weird long term adverse effects?
Connective tissue changes including skin thickening, gingival hyperplasia, coarsening of facial features, enlargement of lips; hirsutism; metabolic bone disease; cerebellar atrophy
Name a prodrug converted to active metabolite phenylethylmalon-amide (PEMA) and phenobarbital with same mechanism of action
Primidone (Mysoline)
What are the 3 weird contraindications of Valproate (injectable Divalproex (Depakote))?
1) Significant hepatic dysfunction
2) Mitochondrial disorders caused by DNA polymerase γ (POLG) mutations
3) Urea cycle disorders
Patients with porphyria [heme issue] should not take what?
Primidone (Mysoline)
Which drug can cause “intellectual blunting” w long term use?
Primidone
Levetiracetam/ Keppra is known for (rarely) causing what emotional issue?
Anger/ irritability/ etc (CNS related)
What can happen if you use topiramate and valproate/ divalproex together?
Hyperammonemia with and without encephalopathy
Valproate/ Divalproex has a boxed warning for what 3 things?
(important)
1) Hepatotoxicity; especially for children <2 years of age and with mitochondrial disorders
2) Fetal risk including neural tube defects, other major malformations, and decreased IQ
3) Pancreatitis including fatal hemorrhagic pancreatitis
What drug has all the following potential long term effects?: Hair and nail changes (alopecia, hirsutism); irregular menses and polycystic ovary-like syndrome; weight gain; cerebral pseudoatrophy; osteoporosis and osteopenia
Valproate/ Divalproex
Dose dependent thrombocytopenia is associated with ______________ concentrations >100 mcg/mL
valproate
Felbamate is a CYP______ inhibitor and CYP_______ inducer
2C19; 3A4
Felbamate has a boxed warning for what 2 things?
1) Fatal aplastic anemia
2) Acute liver failure
Lamotrigine (Lamictal)
1) Why is slow titration required?
2) What may it exacerbate?
1) To avoid rash including SJS
2) Myoclonus
What is the boxed warning for Lamotrigine that you need to esp. know for pediatric pts?
Rash including SJS, TEN with increased risk if given with valproate or if exceeding recommended initial dose or dose escalation
FDA issued special warning that requires the labeling of _________________ to include DRESS (Nov 2023)
Levetiracetam/ Keppra
Lamotrigine/ Lamictal: What are its weird common/ dose related adverse effects?
Rhinitis, pharyngitis, infection, fever
Which drug is assoc. with infection?
Lamictal/ lamitrigine
Which drug’s rare SEs include incapacitating generalized weakness + SJS?
Tiagabine
Levetiracetam (Keppra) and Brivaracetam (Briviact) both inhibit the release of what?
NTs
What can happen if you use both lamotrigine and valproate at the same time?
Rash including SJS, TEN
1) What medication has a higher incidence of hyponatremia (as high as 25%)?
2) For this same medication, who do you need to check HLA-B*1502 to predict SJS or TEN?
3) Is this medication safe in pregnancy?
1) Higher incidence of hyponatremia (as high as 25%)
2) Asian pts
3) May cause fetal harm
The possibility of long-term ophthalmologic effects exists with _________________.
Tiagabine
1) Oxcarbazepine inhibits what?
2) What 2 things does it induce?
1) CYP 2C19
2) CYP 3A4/5 & glucuronyltransferase (UGT)
Name 2 meds that can cause hyponatremia w long term use
Oxcarbazepine + Eslicarbazepine
What are 3 potential long term effects shared by topiramate and zonisamide?
Weight loss, renal stones, metabolic acidosis
Tiagabine can (rarely) increase generalized seizures and nonconvulsive SE in patients with ___________ epilepsy
refractory
Which drug is useful in tremors?
Zonisamide
Consider converting well-controlled patients from levetiracetam to ________________ if intolerable psychiatric side effects
Brivaracetam (Briviact)
What drug requires liver function and bilirubin monitoring before and at 1, 3, and 6 months of treatment specially if given with valproate?
Cannabidiol (Epidiolex) CV Solution
Describe how Cannabidiol may affect simultaneous ASDs
Induces CYP1A2, CYP2B6 & glucuronyltransferase (UGT); Inhibits CYP2C9 & CYP 2C19
Transaminase elevations may be seen in pts taking what?
Cannabidiol
Eslicarbazepine (Aptiom) Tablet is similar to what?
Carbazepine
Eslicarbazepine (Aptiom):
1) Should be avoided or dose adjusted when?
2) What 2 drugs should it NOT be taken with?
1) Avoid in severe hepatic impairment; dose adjustment in renal failure
2) Carbamazepine and oxcarbazepine
What drug is useful in mixed seizure types, but may cause aggressive behavior and can’t be used w hemodialysis/ severe hepatic impairment?
Perampanel (Fycompa)
Eslicarbazepine: list 3 rare SEs
PR interval, AV block; blood dyscrasias
Lacosamide (Vimpat)
1) Who should it be avoided in?
2) Who do you need to use caution for?
1) Third-degree heart block
2) Patients with underlying proarrhythmic conditions or on concomitant medications that affect cardiac conduction;
Prolonged PR interval may occur with what drug?
Lacosimide
What drug has a boxed warning for murder?
Perampanel
What drug is both useful to pts with neuropathy and doesn’t have many DDIs bc of renal excretion?
Pregabalin (Lyrica)
Rufinamide (Banzel):
1) Is contraindicated in what?
2) When should you use caution?
“unique”
1) Severe liver impairment or in familial short QT syndrome
2) With other drugs that shorten QT interval
Vigabatrin (Sabril): What’s the weird disadvantage? Explain
Permanent vision loss in most patients after a certain duration of exposure requiring eye exams Q3 months; requires REMS* program registration
*A Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program that the U.S. Food and Drug Administration (FDA) can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks.
Which med can cause the following side effects in pediatric pts?: aggression; infection including upper respiratory tract infection, bronchitis, ear infection, and acute otitis media
Vigabatrin
What drug has a boxed warning for progressive and permanent bilateral peripheral visual constriction including tunnel vision; reduced visual acuity?
Vigabatrin
What do you need to tell your pts taking Vigabatrin?
Onset of vision loss is unpredictable and can occur after weeks, months, or years
Generalized convulsive status epilepticus (GCSE) is defined as what?
Any recurrent or continuous seizure activity lasting longer than 30 minutes in which the patient does not regain baseline mental status.
Any seizure that does not stop within ____ minutes should be aggressively treated as impending SE.
5
IV _______________ is the preferred benzodiazepine for initial treatment of GCSE because of its efficacy and long duration of action in the central nervous system (CNS).
lorazepam
List the meds you need to give for status epilepticus in order
0-30 minutes: lorazepam IV
30-60 minutes: phenytoin IV
> 120 minutes: midazolam IV, phenobarbital IV or propofol IV
How do you dose lamotrigine/ Lamictal if the pt is on valproate?
1) Weeks 1 and 2: 25 mg QOD
2) Weeks 3 and 4: 25 mg Qday
