Epilepsy important content

Question 1

What drug has a boxed warning for aggression, hostility, irritability, anger, and homicidal ideation?

“Know this”

Answer 1

Perampanel

Question 2

List the drugs that can induce seizures

will be on exam

Answer 2

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

Question 3

What are the 6 categories of epilepsy?

Answer 3

1) Genetic
2) Structural
3) Infectious
4) Metabolic
5) Immune
6) Unknown

Question 4

General pathophysiologic process underlying all epilepsies is what?

Answer 4

Disturbed regulation of electrical activity resulting in synchronized and excessive neuronal discharge

Question 5

International League Against Epilepsy (ILAE)

Answer 5

Disorder + consequences of disorder
Can the patient drive a car?

Question 6

What are the 3 genetic conditions that can cause epilepsy? What are the mutations of each?

Answer 6

1) Dravet syndrome; sodium channel
2) Childhood Absence Epilepsy (CAE); Ca2+ channels and GABA-receptor subunits
3) Juvenile Myoclonic Epilepsy (JME); many different mutations

Question 7

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?

Answer 7

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

Question 8

What pathogen found in developing countries can cause infectious epilepsy?

Answer 8

Neurocysticercosis

Question 9

Metabolic epilepsy may be caused by what? Why does this condition cause epilepsy?

Answer 9

Lafora disease; development of insoluble glycogen inclusion bodies

Question 10

1) Immune epilepsy may be caused by what?
2) How does this condition cause epilepsy?

Answer 10

1) Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis
2) Central nervous system (CNS) inflammation

Question 11

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?

Answer 11

1) Neuronal hyperexcitability and hypersynchronization
2) K+, Na+, Ca2+, and Cl–
3) Synaptic vesicle protein 2A (SV2A) and γ-aminobutyric acid (GABA)

Question 12

Seizures are classified into an initial three categories depending on how they begin in the brain; what are they?

Answer 12

1) Focal seizures: one side of the brain
2) Generalized seizures: bilaterally
3) Unknown onset

Question 13

Generalized-onset seizures usually always involve what?

Answer 13

Impaired awareness

Question 14

What happens after the cessation of a typical absence seizure (blank stare seizure)?

Answer 14

The patient will often return to the previous activity as if nothing had happened

Question 15

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?

Answer 15

Adding a second ASD and then tapering and discontinuing the ineffective or intolerable first ASD

Question 16

Medication that induce lamotrigine glucuronidation include what?

Will be on exam

Answer 16

1) Carbamazepine
2) Phenobarbital
3) Phenytoin
4) Primidone
5) Rifampin
6) Lopinavir/ ritonavir
7) Atanazivir/ ritonavir
+ estrogen

Question 17

What is the one med that inhibits lamotrigine glucuronidation?

will be on exam

Answer 17

Valproic acid

Question 18

1) Oral contraceptives do what to lamotrigine metabolism?
2) What does this mean you need to do?

“big test thing”

Answer 18

1) Estrogen induces UGT and increases lamotrigine metabolism
2) Increase lamotrigine dose; may see doses of 150 mg to 200 mg PO BID

Question 19

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”

Answer 19

1) 5
2) 2.5
3) 5
4) 10

Question 20

What are the 3 different half lives of lamictal/ lamotrigine depending on concomitant therapies?

Answer 20

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

Question 21

Drug of choice for absence seizures is what?

Answer 21

Ethosuximide (Zarontin)

Question 22

What ASDs may cause folate deficiency (with megaloblastic anemia) with long term use?

Answer 22

Phenobarbital + Phenytoin + Primidone

Question 23

What drug can cause purple glove syndrome with IV administration?

Answer 23

Phenytoin

Question 24

Phenytoin: What are the weird long term adverse effects?

Answer 24

Connective tissue changes including skin thickening, gingival hyperplasia, coarsening of facial features, enlargement of lips; hirsutism; metabolic bone disease; cerebellar atrophy

Question 25

Name a prodrug converted to active metabolite phenylethylmalon-amide (PEMA) and phenobarbital with same mechanism of action

Answer 25

Primidone (Mysoline)

Question 26

What are the 3 weird contraindications of Valproate (injectable Divalproex (Depakote))?

Answer 26

1) Significant hepatic dysfunction 2) Mitochondrial disorders caused by DNA polymerase γ (POLG) mutations 3) Urea cycle disorders

Question 27

Patients with porphyria [heme issue] should not take what?

Answer 27

Primidone (Mysoline)

Question 28

Which drug can cause "intellectual blunting" w long term use?

Answer 28

Primidone

Question 29

Levetiracetam/ Keppra is known for (rarely) causing what emotional issue?

Answer 29

Anger/ irritability/ etc (CNS related)

Question 30

What can happen if you use topiramate and valproate/ divalproex together?

Answer 30

Hyperammonemia with and without encephalopathy

Question 31

Valproate/ Divalproex has a boxed warning for what 3 things? (important)

Answer 31

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

Question 32

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

Answer 32

Valproate/ Divalproex

Question 33

Dose dependent thrombocytopenia is associated with ______________ concentrations >100 mcg/mL

Answer 33

valproate

Question 34

Felbamate is a CYP______ inhibitor and CYP_______ inducer

Answer 34

2C19; 3A4

Question 35

Felbamate has a boxed warning for what 2 things?

Answer 35

1) Fatal aplastic anemia 2) Acute liver failure

Question 36

Lamotrigine (Lamictal) 1) Why is slow titration required? 2) What may it exacerbate?

Answer 36

1) To avoid rash including SJS 2) Myoclonus

Question 37

What is the boxed warning for Lamotrigine that you need to esp. know for pediatric pts?

Answer 37

Rash including SJS, TEN with increased risk **if given with valproate** or if exceeding recommended initial dose or dose escalation

Question 38

FDA issued special warning that requires the labeling of _________________ to include DRESS (Nov 2023)

Answer 38

Levetiracetam/ Keppra

Question 39

Lamotrigine/ Lamictal: What are its weird common/ dose related adverse effects?

Answer 39

Rhinitis, pharyngitis, **infection**, fever

Question 40

Which drug is assoc. with infection?

Answer 40

Lamictal/ lamitrigine

Question 41

Which drug's rare SEs include incapacitating generalized weakness + SJS?

Answer 41

Tiagabine

Question 42

Levetiracetam (Keppra) and Brivaracetam (Briviact) both inhibit the release of what?

Answer 42

NTs

Question 43

What can happen if you use both lamotrigine and valproate at the same time?

Answer 43

Rash including SJS, TEN

Question 44

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?

Answer 44

1) Higher incidence of hyponatremia (as high as 25%) 2) Asian pts 3) May cause fetal harm

Question 45

The possibility of long-term ophthalmologic effects exists with _________________.

Answer 45

Tiagabine

Question 46

1) Oxcarbazepine inhibits what? 2) What 2 things does it induce?

Answer 46

1) CYP 2C19 2) CYP 3A4/5 & glucuronyltransferase (UGT)

Question 47

Name 2 meds that can cause hyponatremia w long term use

Answer 47

Oxcarbazepine + Eslicarbazepine

Question 48

What are 3 potential long term effects shared by topiramate and zonisamide?

Answer 48

Weight loss, renal stones, metabolic acidosis

Question 49

Tiagabine can (rarely) increase generalized seizures and nonconvulsive SE in patients with ___________ epilepsy

Answer 49

refractory

Question 50

Which drug is useful in tremors?

Answer 50

Zonisamide

Question 51

Consider converting well-controlled patients from levetiracetam to ________________ if intolerable psychiatric side effects

Answer 51

Brivaracetam (Briviact)

Question 52

What drug requires liver function and bilirubin monitoring before and at 1, 3, and 6 months of treatment specially if given with valproate?

Answer 52

Cannabidiol (Epidiolex) CV Solution

Question 53

Describe how Cannabidiol may affect simultaneous ASDs

Answer 53

Induces CYP1A2, CYP2B6 & glucuronyltransferase (UGT); Inhibits CYP2C9 & CYP 2C19

Question 54

Transaminase elevations may be seen in pts taking what?

Answer 54

Cannabidiol

Question 55

Eslicarbazepine (Aptiom) Tablet is similar to what?

Answer 55

Carbazepine

Question 56

Eslicarbazepine (Aptiom): 1) Should be avoided or dose adjusted when? 2) What 2 drugs should it NOT be taken with?

Answer 56

1) Avoid in severe hepatic impairment; dose adjustment in renal failure 2) Carbamazepine and oxcarbazepine

Question 57

What drug is useful in mixed seizure types, but may cause aggressive behavior and can't be used w hemodialysis/ severe hepatic impairment?

Answer 57

Perampanel (Fycompa)

Question 58

Eslicarbazepine: list 3 rare SEs

Answer 58

PR interval, AV block; blood dyscrasias

Question 59

Lacosamide (Vimpat) 1) Who should it be avoided in? 2) Who do you need to use caution for?

Answer 59

1) Third-degree heart block 2) Patients with underlying proarrhythmic conditions or on concomitant medications that affect cardiac conduction;

Question 60

Prolonged PR interval may occur with what drug?

Answer 60

Lacosimide

Question 61

What drug has a boxed warning for murder?

Answer 61

Perampanel

Question 62

What drug is both useful to pts with neuropathy and doesn't have many DDIs bc of renal excretion?

Answer 62

Pregabalin (Lyrica)

Question 63

Rufinamide (Banzel): 1) Is contraindicated in what? 2) When should you use caution? **"unique"**

Answer 63

1) Severe liver impairment or in familial short QT syndrome 2) With other drugs that shorten QT interval

Question 64

Vigabatrin (Sabril): What's the weird disadvantage? Explain

Answer 64

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.

Question 65

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

Answer 65

Vigabatrin

Question 66

What drug has a boxed warning for progressive and permanent bilateral peripheral visual constriction including tunnel vision; reduced visual acuity?

Answer 66

Vigabatrin

Question 67

What do you need to tell your pts taking Vigabatrin?

Answer 67

Onset of vision loss is unpredictable and can occur after weeks, months, or years

Question 68

Generalized convulsive status epilepticus (GCSE) is defined as what?

Answer 68

Any recurrent or continuous seizure activity lasting longer than 30 minutes in which the patient does not regain baseline mental status.

Question 69

Any seizure that does not stop within ____ minutes should be aggressively treated as impending SE.

Answer 69

5

Question 70

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).

Answer 70

lorazepam

Question 71

List the meds you need to give for status epilepticus in order

Answer 71

0-30 minutes: lorazepam IV 30-60 minutes: phenytoin IV >120 minutes: midazolam IV, phenobarbital IV or propofol IV

Question 72

How do you dose lamotrigine/ Lamictal if the pt is on valproate?

Answer 72

1) Weeks 1 and 2: 25 mg QOD 2) Weeks 3 and 4: 25 mg Qday