Exam 3 - Lec 48-49 Seizures Ott Flashcards
risk factors for seizure recurrence (9 of them; slide 8)
< 2 years seizure free
-onset of seizure after age 12
-history of atypical febrile seizures
-2-6 yrs before good seizure control in tx
> 30 episodes before control achieved
-partial seizures
-abnormal EEG throughout tx
-organic neuro disorder (brain injury, dementia)
-withdrawal of phenytoin or valproate
what medications/drug classes lower the seizure threshold at normal doses? (6 of them)
-bupropion
-clozapine
-theophylline
-varenicline
-phenothiazine antipsychotics
-CNS stimulants (amphetamines)
what medications/drug classes lower the seizure threshold at high doses and impaired renal function? (6 of them)
-carbapenems (**imipenem)
-lithium
-meperidine
-penicillin
-quinolones
-tramadol
possible reasons for tx failure for drug-resistant epilepsy (3 of them)
-failure to reach CNS target
-alteration of drug targets in CNS
-drugs missing the real target
management of drug-resistant epilepsy (3 things bolded)
-rule out pseudo-resistance (wrong drug/diagnosis)
-combination therapy
-electrical/surgical intervention
status epilepticus definition
continuous seizure activity lasting 5 min or more, or two or more discrete seizure with incomplete recovery between
possible drug therapy for status epilepticus (bolded)
benzodiazepines, most commonly lorazepam or midazolam
for status epilepticus tx, what is given if seizure continues 5-20 minutes after (initial tx phase)? (2 options)
IV lorazepam or IV midazolam
why does phenytoin have a limited infusion rate?
it can cause hypotension due to propylene glycol diluent
fosphenytoin dosing
20 mg PE (phenytoin equivs)/kg IV, may give additional dose 10 min after load
why does fosphenytoin have better IV tolerance of dosing than phenytoin?
bc fosphenytoin is a prodrug of phenytoin
phenytoin/fosphenytoin administration requires cardiac monitoring, and may also cause what local reaction?
purple glove syndrome
for oral phenytoin dosing, we must obtain what two things in the same blood draw?
-phenytoin serum conc
-serum albumin
(these are used in the equation to calculate dose)
therapeutic serum conc range for phenytoin
a. 5-10 mcg/mL
b. 10-20 mcg/mL
c. 20-40 mcg/mL
d. 50-100 mcg/mL
b. 10-20 mcg/mL
IV to PO conversion for valproate
1:1 conversion
desired serum conc range for valproate
50-125 mcg/mL (~80 mcg/mL)
carbamazepine, phenobarbital, and phenytoin are inducers of which 3 CYPS?
1A2, 2C9, 3A4
lamotrigine, oxcarbazepine, and topiramate induce which CYP?
a. 1A2
b. 2C9
c. 3A4
c. 3A4
which drug is a UGT inhibitor?
a. carbamazepine
b. phenobarbital
c. phenytoin
d. lamotrigine
e. oxcarbazepine
f. valproate
g. topiramate
f. valproate
boxed warning for lamotrigine
Stevens-Johnson Syndrome
lamotrigine dosing without concomitant UGT drug interactions (4 doses to know)
-25 mg once daily x 14 days
-50 mg once daily x 14 days
-100 mg once daily x 7 days
-200 mg once daily
(if given with UGT inhibitor, dec doses by half; if given with UGT inducer, double the doses)
what must be screened prior to starting carbamazepine or like derivatives?
screen for HLA-B*1502 allele
(it is assoc with SJ syndrome and anticonvulsant hypersensitivity syndrome; if positive, pt should not be treated with these drugs unless benefits outweigh risk)
true or false: there is strong correlation for positive HLA-B*1502 allele and AHS in Asian pts
true
which allele in pts of Northern European and Asian descent may confer similar risk for AHS to HLA-B*1502?
a. HLA-B1330
b. HLA-A3101
c. HLA-B1503
d. HLA-A3151
b. HLA-A*3101
mortality rate of DRESS syndrome
10%
true or false: DRESS syndrome is less likely in pts positive for HLA-A*1301
false (more likely)
DRESS syndrome usually occurs ___-___ weeks after start of drug therapy
2-6 weeks
DRESS syndrome is associated with which drugs? (7 of them in bold)
-carbamazepine
-phenobarbital
-phenytoin
-cenobamate
-lamotrigine
-valproate
-zonisamide
antiseizure drug withdrawal syndrome (2 things in bold)
-associated with abrupt discontinuation of antiseizure med
-may cause recurrence of seizures, always taper
drug serum conc for antiseizure drugs may be altered in pregnancy due to changes in ?
volume of distribution
why is valproate not recommended in pregnancy?
causes neural tube defects and is assoc with dec IQ of the offspring (consider supplemental folic acid 5 mg daily)
which antiseizure drugs are teratogenic risks? (7 of them)
-carbamazepine
-phenobarbital
-phenytoin
-fosphenytoin
-clonazepam
-primidone
-topiramate
infants should receive what dose of vitamin K at birth to dec risk of hemorrhagic disease?
a. 1 mg
b. 2 mg
c. 3 mg
d. 5 mg
a. 1 mg
why do antiseizure drugs dec efficacy of estrogen-containing contraceptives?
estrogen compounds are major 3A4 substrates; need to use higher dose estrogen contraceptives, or can use progestin-only - depot formulation, or IUDs are also recommended
_________ can dec lamotrigine serum conc (50%) and vice versa
estrogen
which medications have an AE of arrhythmias? (2 of them)
a. lamotrigine
b. lacosamide
c. pregabalin
d. phenytoin/fosphenytoin
e. fenfluramine
a. lamotrigine
d. phenytoin/fosphenytoin
which medications have an AE of PR interval changes? (2 of them)
a. lamotrigine
b. lacosamide
c. pregabalin
d. phenytoin/fosphenytoin
e. fenfluramine
b. lacosamide
c. pregabalin
which medication has an AE of heart block?
a. lamotrigine
b. lacosamide
c. pregabalin
d. phenytoin/fosphenytoin
e. fenfluramine
b. lacosamide
which medication has an AE of valvular heart disease?
a. lamotrigine
b. lacosamide
c. pregabalin
d. phenytoin/fosphenytoin
e. fenfluramine
e. fenfluramine
which drug(s) are assoc with hyponatremia and SIADH?
a. carbamazepine
b. zonisamide
c. phenytoin
d. topiramate
a. carbamazepine
(also eslicarbazepine/oxcarbazepine)
which drug(s) alters vitamin D metab and can lead to osteoporosis?
a. carbamazepine
b. zonisamide
c. phenytoin
d. topiramate
c. phenytoin
which drug(s) are assoc with dec serum bicarb leading to metabolic acidosis, as well as decreased sweating, heat intolerance, oligohydrosis, and nephrolithiasis?
a. carbamazepine
b. zonisamide
c. phenytoin
d. topiramate
d. topiramate
psychiatric SE: psychosis, suicidal thoughts/behaviors, unusual mood changes, worsening depression (usually seen in children and adolescents)
a. levetiracetam
b. perampanel
c. valproate
d. topiramate
a. levetiracetam
psychiatric SE: acute mental status changes related to hyperammonemia (differentiate from sedation)
a. levetiracetam
b. perampanel
c. valproate
d. topiramate
c. valproate
psychiatric SE: associated with cognitive dysfunction if dose is inc too rapidly, use a slow titration
a. levetiracetam
b. perampanel
c. valproate
d. topiramate
d. topiramate
boxed warning for perampanel
dose-related serious/life-threatening neuropsychiatric events; use caution with pre-existing psychosis
post-marketing warning for topiramate
vision loss, myopia, retinal detachment
vigabatrin is CI in which pts?
pts who have other risk factors for irreversible vision loss
gabapentin/pregabalin should be evaluated before use in pts with risk for __________ _________ in pt who is taking other CNS depressants, has pulmonary disease, or is elderly
respiratory depression
_________ can cause thrombocytopenia, as well as PCOS, weight gain, and sedation
a. carbamazepine
b. oxcarbazepine
c. valproate
d. zonisamide
e. felbamate
c. valproate
carbamazepine induces p-glycoprotein, as well as which 4 cyps?
1A2
2C9
2C19
3A4
(oxcarbazepine induces 3A4)
which is CI if there is a sulfa allergy?
a. topiramate
b. zonisamide
c. phenobarbital
d. phenytoin
b. zonisamide
topiramate and zonisamide clinical pearls (3 of them)
-weight loss
-oligohydrosis (decreased sweating)
-nephrolithiasis
_________ absorption is dec when given with enteral feedings, hold feedings 1-2 hours before and after administration. It can also cause gingival hyperplasia and hirsutism
a. topiramate
b. zonisamide
c. phenobarbital
d. phenytoin
d. phenytoin
which drug can cause gingival hyperplasia and hirsutism?
phenytoin
How is gabapentin/pregabalin eliminated? How should we adjust the dose?
renally elim; dec dose in renal impairment
what drug is indicated for Dravet Syndrome and Lennox Gastaut Syndrome?
Epidiolex (oral CBD)
multiple seizure types that develop in childhood, usually accompanied by intellectual disability, sometimes responsive to combination of some AEDs
a. Lennox-Gastaut Syndrome
b. Dravet Syndrome
a. Lennox-Gastaut Syndrome
rare genetic epileptic encephalopathy with normal childhood development until seizures begin in 1st year of life leading to multiple seizure types and developmental disability
a. Lennox-Gastaut Syndrome
b. Dravet Syndrome
b. Dravet Syndrome
what is the fats:carbs/protein ratio in the “keto diet”?
3:1 or 4:1
true or false: children respond only while on the keto diet, the effects in adults may continue after the diet is discontinued
false (adults only respond while on the keto diet, effects in children may continue after diet is discontinued)
all antiseizure drugs carry what warning?
inc risk of suicidal thinking/behaviors
antidepressants carry a warning for inc risk of suicidal thinking during tx in pts < ____ years of age
< 24
use of _________ should be avoided in pts with uncontrolled seizure disorders, as it can inc risk of seizures and frequency
bupropion
what condition is a common co-morbidity for epilepsy/seizure disorders?
depression
which drug is indicated only for absence seizures?
a. clonazepam
b. carbamazepine
c. lamotrigine
d. ethosuximide
d. ethosuximide
