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Therapeutics > Epilepsy > Flashcards

Epilepsy Flashcards

1
Q

transient alteration of behavior, sensation, and/or consciousness due to disordered, synchronous, and rhythmic firing of neurons in the brain

A

seizure

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2
Q

disorder characterized by recurrent epileptic seizures

A

epilepsy

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3
Q

seizure localized to part of one cerebral hemisphere

A

focal onset/partial

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4
Q

seizure involving both hemispheres widely from the outset, generally associated with impaired awareness

A

generalized onset

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5
Q

generalized onset seizure characterized by sudden loss of consciousness, tonic phase followed by a clonic phase, interrupted respirations, tongue biting, headache, confusion

A

generalized tonic-clonic or grand mal

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6
Q

generalized onset seizure characterized by altered consciousness, staring with occasional eye blinking, brief twitching of the body/eyelids, enuresis

A

non-motor
petit mal or absence

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7
Q

pathophysiologic changes during a seizure

A

abnormal ion channel activity
decreased inhib neuron activity
increased excit neuron activity
rhythmic & repetitive neuron discharge

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8
Q

if you need to use polytherapy for ASMs, the 2nd med should have…

A

a different MOA

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9
Q

common AEs of ALL ASMs

A

CNS depression
fatigue, dizziness, unsteadiness, ataxia, diplopia, memory & thinking problems

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10
Q

what are the 1st generation ASMs (7)

A
  1. carbamazepine
  2. clonazepam
  3. ethosuximide
  4. phenobarbital
  5. phenytoin
  6. primidone
  7. valproate
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11
Q

what are the 2nd generation ASMs (8)

A
  1. felbamate
  2. gabapentin
  3. lamotrigine
  4. levetiracetam
  5. oxcarbazepine
  6. tiagabine
  7. topiramate
  8. zonisamide
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12
Q

what are the 3rd generation ASMs (7)

A
  1. brivaracetam (briviact)
  2. cenobamate (xcopri)
  3. eslicarbazepine (aptiom)
  4. lacosamide (vimpat)
  5. perampanel (fycompa)
  6. pregabalin (lyrica)
  7. vigabatrin (sabril)
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13
Q

which ASMs are Na channel blockers/modulators (7)

A

carbamazepine, oxcarbazepine, eslicarbazepine
cenobamate
lacosamide
lamotrigine
phenytoin

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14
Q

which ASMs are Ca channel modulators (3)

A

ethosuximide
gabapentin
pregabalin

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15
Q

which ASMs are GABA modulators (3)

A

valproate
tiagabine
vigabatrin

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16
Q

which ASMs are GABA receptor agonists (3)

A

clonazepam, phenobarbital, primidone
ALL 1ST GEN

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17
Q

which ASMs are glutamate blockers (2)

A

felbamate
parampanel

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18
Q

which ASMs are SV2A modulators (2)

A

levetiracetam, brivaracetam

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19
Q

which ASMs are highly protein bound (6)

A

carbamazepine, clonazepam, valproate, phenytoin, tiagabine, perampanel

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20
Q

which 2nd gen ASMs have high renal elimination (4)

A

felbamate, gabapentin, levetiracetam, topiramate

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21
Q

which 3rd gen ASMs have high renal elimination (4)

A

eslicarbazepine, lacosamide, pregabalin, vigabatrin

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22
Q

which ASMs have multiple MOAs (2)

A

topiramate and zonisamide

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23
Q

which seizure can carbamazepine NOT BE USED for? why?

A

absence
may worsen b/c of epoxide metabolite

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24
Q

which ASMs have a narrow therapeutic index (3)

A

carbamazepine
ethosuximide
phenytoin

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25
Q

carbamazepine induces

A

1A2, 2B6, 2C9, 2C19, 3A4
GT
ITSELF!!!!- AUTOINDUCER

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26
Q

carbamazepine is a substrate of

A

3A4

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27
Q

AEs of carbamazepine

A

hyponatremia due to SIADH
elevated LFTs
teratogenic

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28
Q

BBW for carbamazepine w/ increased risk depending on genetics

A

SJS/TEN

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29
Q

CIs for carbamazepine

A

bone marrow suppression, MAOIs, nefazodone, 3A4 sub NNRTIs

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30
Q

clonazepam 1/2 life is very?
it is a substrate of?

A

very long t1/2
3A4 substrate

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31
Q

AEs of clonazepam

A

pronounced sedation, paradoxical agitation, tolerance, withdrawal symptoms

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32
Q

clonazepam has a BBW for use with which drug class

A

opiates

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33
Q

this 1st gen ASM is choice for ABSENCE seizures only (may worsen other types)

A

ethosuximide

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34
Q

ethosuximide is a substrate of

A

3A4 & 2E1

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35
Q

ethosuximide AEs

A

GI related

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35
Q

phenobarbital & primidone induce

A

3A4, 2C9, 2C19. 1A2
GT

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36
Q

phenobarbital & primidone are substrates of

A

3A4 & 2C19

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37
Q

half life of phenobarbital/primidone?

A

very long t1/2

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38
Q

AE of phenobarbital

A

CNS depression/sedation

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39
Q

BBW for phenobarbital

A

risk of overdose with opioids
dependence

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40
Q

phenobarbital is contraindicated for? why?

A

respiratory disease w/ evidence of dyspnea or obstruction
due to AE of respiratory depression

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41
Q

what type of metabolism does phenytoin follow

A

saturable Michaelis-Menten

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42
Q

phenytoin induces

A

3A, 2C

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43
Q

phenytoin is a substrate of

A

2C9, 2C19

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44
Q

common AEs of phenytoin

A

gingival hyperplasia
teratogenic

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45
Q

serious AEs of phenytoin (rare)

A

SJS/TEN
blood dyscrasia
purple glove syndrome (severe inj site rxn)

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46
Q

BBW for phenytoin when given IV

A

hypotension & arrhythmias

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47
Q

prodrug converted to phenobarbital & PEMA

A

primidone

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48
Q

DDI with valproate that may increase its metabolism

A

oral contraceptives

49
Q

valproate inhibits

A

2C9, GT epoxide hydrolase

50
Q

valproate is a substrate of

A

UGT hepatic metabolism

51
Q

common AEs of valproate

A

tremor, weight gain, alopecia/hair text changes, nail disorders, hormone changes, osteoporosis.

52
Q

serious AEs of valproate??
leads to CI in??

A

hyperammonenia & encephalopathy, thrombocytopenia

CI in hepatic disease, urea cycle disorders

53
Q

BBW of valproate

A

hepatotoxicity, teratogenicity, mitochondrial disease, pancreatitis

54
Q

should valproate be used in WOCBP if avoidable?

A

no- teratogen

55
Q

felbamate induces

A

3A4

56
Q

felbamate inhibits

A

2C19

57
Q

felbamate is a substrate of

A

3A4 and 2E1

58
Q

BBW of felbamate
leads to CI in

A

irreversible fatal aplastic anemia
hepatic failure

CI in hx of blood dyscrasia or hepatic dysfunction

59
Q

felbamate is only used

A

for severe refractory cases

60
Q

gabapentin & pregabalin are labeled for use as??
primarily used for??

A

ADJUNCT for focal onset
used for other indications such as neuropathy

61
Q

how is lamotrigine dosed and why??

A

slow titration to mitigate the risk of TEN

62
Q

which drugs require dose titration adjustments for lamotrigine

A

valproate, carbamazepine, phenobarbital/primidone, phenytoin
all 1st gens

63
Q

which drugs may decrease lamotrigine levels

A

estrogen OCs

64
Q

BBW for lamotrigine

A

SJS/TEN
increased risk with valproate or rapid dose escalation

65
Q

in general, when lamotrigine is titrated with valproate, the dose is increased at a ____ rate than normal, and the maintenance dose is ___

A

slower, lower

66
Q

in general, when lamotrigine is titrated with carbamazepine, phenytoin, phenobarb/primidone, the dose is increased at a ___ rate than normal, and the maintenance dose is ___

A

faster, higher

67
Q

AEs of levetiracetam

A

mood related
irritability, anger, agitation, depression (can worsen pre-existing psych)

68
Q

2nd gen & 3rd gen ASMs that are analogues of carbamazepine??
they do not produce what metabolite??

A

2nd- oxcarbazepine
3rd- eslicarbazepine
NO epoxide metabolite

69
Q

oxcarbazepine induces

A

3A4/3A5
GT

70
Q

oxcarbazepine inhibits

A

2C19

71
Q

rare but serious AEs for oxcarbazepine

A

agranulocytosis
SJS/TEN

72
Q

tiagabine is a substrate of

A

3A4/1A2/2D6/2C19

73
Q

when is tiagabine used?
due to what AEs?

A

used for refractory epilepsy
serious AEs: new onset seizures, status epilepticus, exacerbation of EEG abnormalities

74
Q

topiramate induces

A

3A

75
Q

topiramate inhibits

A

2C19

76
Q

AEs of topiramate

A

notable cognitive impairment, bilateral paresthesias, weight loss, hyperhidrosis, kidney stones

77
Q

zonisamide is a substrate of

A

3A4

78
Q

AEs of zonisamide

A

notable cognitive impairment, weight loss, hyperhidrosis, kidney stones

79
Q

main benefit of zonisamide

A

ease of adherence- once daily dose

80
Q

3rd gen ASMs that is an analog of levetiracetam

A

brivaracetam (Briviact)

81
Q

brivaracetam inhibits

A

2C19, GT

82
Q

brivaracetam is a substrate of

A

2C19

83
Q

AEs of brivaracetam

A

mood & behavioral
better tolerated than levetiracetam

84
Q

dosing of cenobamate (xcopri)?
why is this done?

A

titrated no more quickly than Q2W
due to risk of dress

85
Q

cenobamate induces

A

2B6/2C/3A4

86
Q

cenobamate inhibits

A

2B6/2C19/3A

87
Q

cenobamate is a substrate of

A

UGT2B7/B7
2E1/2A6/2B6/2C19/3A4/3A5

88
Q

BBW for cenobamate

A

psychiatric, behavioral, mood, or personality changes which may be life threatening

89
Q

eslicarbazepine induces

A

GT

90
Q

eslicarbazepine inhibits

A

2C19

91
Q

AEs of eslicarbazepine (Aptiom)

A

tremor, hyponatremia due to SIADH, rash, likely teratogenic

92
Q

serious AEs of eslicarbazepine

A

SJS, DRESS, angioedema, cardiac effects, hepatotoxicity, blood dyscrasia

93
Q

benefit of eslicarbazepine

A

good for adherence- dosed once daily

94
Q

lacosamide inhibits

A

2C19

95
Q

lacosamide is a substrate of

A

2C19/2C9/3A4

96
Q

AEs of lacosamide (vimpat)

A

GI effects

97
Q

serious AEs of lacosamide

A

cardiac arrhythmias, syncope, DRESS, neutropenia, anemia

98
Q

perampanel induces

A

3A4/3A5/2B6, GT

99
Q

perampanel inhibits

A

3A4/3A5/2C8, GT

100
Q

perampanel is a substrate of

A

3A4/3A5/1A2/2B6

101
Q

AEs of perampanel (fycompa)??
1 of them leads to what BBW??

A

mood related, weight gain
BBW- aggression, hostility, irritability, anger, homicidal ideation

102
Q

AEs of pregabalin

A

cognitive impairment, edema, weight gain
potential for misuse with opiates

103
Q

vigabatrin induces

A

2C9

104
Q

AEs of vigabatrin

A

pronounced CNS depressive effects, weight gain, edema, peripheral neuropathy, neuropsychiatric effects, vision loss

105
Q

vigabatrin is used when??
why??

A

reserved for refractory cases
AE for risk of aggravating absence & myoclonic seizures & vision loss

106
Q

BBW w/ REMs for vigabatrin

A

progressive & permanent vision loss

107
Q

misc ASMs used for LGS or refractory epilepsies off label (3)

A

epidiolex
clobazam
rufinamide

108
Q

misc ASMs used for DRAVET SYNDROME or refractory epilepsies off label (2)

A

epidiolex
stiripentol

109
Q

3 rescue therapies to stop a cluster of seizures

A

diazepam rectal gel, nasal spray (diastat, valtoco)
midazolam nasal spray (nayzilam)

110
Q

3 nonpharm options for seizures

A

keto diet
vagus nerve stimulator
surgery

111
Q

children may be more susceptible to what AEs?

A

neuropsychiatric

112
Q

dosing method for children

A

weight based with higher mg/kg than adults

113
Q

caution in older adults for…

A

cognitive AEs
PKPD changes- renal, hepatic, hypoalbuminemia

114
Q

which ASMs can be used for migraine (3)

A

topiramate, valproate, zonisamide

115
Q

which ASMs can be used for bipolar disorder (4)

A

lamotrigine, valproate, carbamazepine, oxcarbazepine

116
Q

which populations have higher risk of HLA-B*1502 gene??
what does that put them at risk for

A

Asian populations
increased risk of SJS/TEN

117
Q

which ASMs recommend genetic testing for the HLA-B*1502 gene

A

carbamazepine + both analogs
phenytoin
lamotrigine

118
Q

which 2 ASMs are preferred in pregnancy

A

levetiracetam and lamotrigine

119
Q

which 3 ASMs are teratogens

A

valproic acid, carbamazepine, topiramate (among others)

120
Q

all WOCBP should supplement what?
what should women in 8th month of pregnancy supplement if on enzyme inducing AEDs?

A

WOCBP- folic acid
8 month pregnancy- vitamin K

121
Q

which ASMs can decrease effectiveness of OCs (8)

A

oxcarbazepine/carbamazepine
primidone/phenobarb
phenytoin
topiramate
felbamate
parampanel

Therapeutics (20 decks)

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