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Therapeutics 3 - Spring 2018 > Exam 3 - Rochet/Ott (Seizures) > Flashcards

Exam 3 - Rochet/Ott (Seizures) Flashcards

1
Q

3 main ways to classify seizures

A

Focal Onset
Generalized Onset
Unknown Onset

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2
Q

how to classify Focal Onset Seizures

A

Aware or Impaired awareness
and
Motor or Nonmotor onset

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3
Q

common reason for causes of focal seizures

A

usually due to a lesion

head trauma/tumor/stroke/hypoxia at birth/metabolic disorder/ infection/malformations

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4
Q

common reason for generalized seizures

A

NOT due to lesion—- presumed to be genetic!

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5
Q

Generalized seizures are known to cause the patient to be aware or non-aware?

A

non-aware — pt lose consciousness

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6
Q

Focal seizures can progress to secondary generalized seizures via projections to the ______

A

thalamus

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7
Q

what are possible symptoms of an aura before a seizure

A

abdominal discomfort
sense of fear
unpleasant smell
result of abnormal electrical activity

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8
Q

what are automatisms?

A

repetitive motor behaviors

swallowing, chewing, lip smacking

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9
Q

special aspects of impaired awareness focal seizures:

A

repetitive motor behaviors
disturbances of visceral/emotional/autonomic
seizure followed by confusion/fatigue/throbbing HA

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10
Q

what is postictal state

A

after seizure —- pt will not recover a normal level of consciousness immediately

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11
Q

symptoms of postictal state

A

confusion
disorientation
anterograde amnesia

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12
Q

Generalized Seizures:

Absence —- can be ______ or _______

A

atypical
or
typical

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13
Q

Describe Typical Absence Generalized Seizures

A 
brief loss of consciousness
staring or eye flickering
begins ABRUPTLY
often repetitive
(NO convulsions, aura, or postical period)
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14
Q

Describe Atypical Absence Generalized Seizures

A

SLOWER ONSET

more difficult to control pharmacologically than typical

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15
Q

Generalized Seizures – two main subgroupings

A

Abscence or Non-Abscence

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16
Q

What are Non-Abscence Generalized Seizures?

A 
Myoclonic
Tonic
Clonic
Atonic
Tonic-Clonic
Status Epilepticus
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17
Q

which Non-Abscence Generalized Seizures?

shock-like contraction of muscles
and
isolated jerking of head, trunk, and body

A

Myoclonic

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18
Q

which Non-Abscence Generalized Seizures?
involve rigidity as a result of increased tone in extensor muscles
and
occur in children

A

tonic

increased tone = tonic…

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19
Q

which Non-Abscence Generalized Seizures?
involve rapid/repetitive motor activity
occur in babies/young kids

A

clonic

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20
Q

which Non-Abscence Generalized Seizures?
sudden loss of muscle tone
and
patients fall if standing “drop attacks”

A

Atonic

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21
Q

which Non-Abscence Generalized Seizures?

referred to as grand mal

A

tonic-clonic

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22
Q

which Non-Abscence Generalized Seizures?

known as single prolonged seizure

A

status epilepticus

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23
Q

Describe Tonic Clonic Seizure

A

Tonic: 15 - 30 seconds of tonic rigidity in all extremities (happens abruptly — NO aura)
Clonic: 1 - 2 minutes —involves violent jerking

may bite tongue or cheek
urinary incontinence is common

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24
Q

Drug therapy can be GRADUALLY withdrawn in pts who have been clinically free of seizures for _______(how long…?)

A

2 - 5 years

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25
Q

what is PDS

A

paroxysmal depolarizing shift

it is large depolarization that triggers burt of action potentials

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26
Q

Pathophysiology of Seizures:

Depolarization involves activation of _____ and _____ channels also _______ channels

A

AMPA; NMDA; voltage gated Ca2+

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27
Q

Pathophysiology of Seizures:

Depolarization activates channels by the ________ neurotransmitter (known as ______) and and leads to _____ influx

A

excitatory; glutamate; Ca2+

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28
Q

Pathophysiology of Seizures:

Hyperpolarization involves activation of ______ receptors and ______ channels

A

GABA; and calcium gated POTASSIUM channels

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29
Q

Pathophysiology of Seizures:

Hyperpolarization leads to a ____ efflux

A

K+

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30
Q

Pathophysiology of Seizures:
_____ neurons are used to dampen neuronal signaling
by feed forward or feedback inhibition

A

GABAergic

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31
Q

Pathophysiology of Seizures:

what is inhibitory surround

A

it is hella GABA neurons connected to glutamate to inhibit an electrical discharge from spreading

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32
Q

Pathophysiology of Seizures:

Tonic Phase Seizures — _______ mediated inhibition dissapears

A

GABA

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33
Q

Pathophysiology of Seizures:

Tonic Phase Seizures —- ________ mediated activity increases

A

glutamate

AMPA and NMDA receptor

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34
Q

Pathophysiology of Seizures:

In Clonic Phase: ______ mediated inhibition gradually ______ which causes a period of _______

A

GABA; gradually returns; period of Oscillation

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35
Q

Pathophysiology of Seizures:

In the tonic phase — when ______ mediated inhibition breaks down —- the action potentials do what?

A

GABA mediated;

action potentials propagate to distant neurons

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36
Q

allllllll the potential triggers of status epilepticus

A 
prenatal injury
cerebrovascular disease
brain tumors
head trauma
infection
hemorrhage
anoxia
drugs
metabolic disturbances
sleep deprivation
stress
alcohol withdrawal
withdrawal from AEDs (especially quickly)
repetitive light stimluation
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37
Q

Drugs that may increase the risk of seizures

A 
alcohol
theophylline
bupropion
oral contraceptives
withdrawal from depressants
CNS stimulants
clozapine
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38
Q

why is clozapine related to increase risk of seizures

A

clozapine converted to norclozapine via CYP1A2 and norclozapine increases seizure risk

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39
Q

what is the definition of seizure

A

paroxysmal disorder of CNS —- abnormal neruonal discharges with or without loss of consciousness

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40
Q

what is the definition of convulsion

A

specific seizure where attack is manifested by involuntary muscle contractions

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41
Q

what is the definition of epilepsy

A

repeated seizures due to damage/irritation and or chemical imbalances in brain

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42
Q

Two synapses are targeted for Anticonvulsant drugs — what are the two synapses

A

Glutamate (excitatory) and GABA (inhibitory)

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43
Q

For Excitatory Synapse Drug Targets:
What are the Presynaptic targets
and
what are the postsynaptic targets

A

pre: Na+ channels and Ca2+ channels
post: NMDA and AMPA receptors

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44
Q

For Inhibitory Synapse Drug Targets:
What are the Presynaptic targets
and
what are the postsynaptic targets

A

Pre: GABA transporter (GAT-1) and GABA transaminase (GABA-T)

Post: GABA(A) receptors and GABA(B) receptors

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45
Q

List the drugs that decrease sodium influx

A 
carbamazepine
oxcarbazepine
phenytoin
lacosamide
lamotrigine
valproate
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46
Q

List the drugs that decrease calcium influx

**This is CRITICAL for abscence seizures!!

A

ethosuximide
lamotrigine
valproate

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47
Q

List the drugs that enhance GABA mediated inhibition

A 
BZDs
barbituates
valproate
gabapentin
viganatrin
tiagabine
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48
Q

List the drugs that antagonize excitatory tranxmitters (ex: glutatmate)

A

felbamate

topiramate

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49
Q

what drugs activate the GABA(A) receptor

A

barbituates
and
benzodiazepines

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50
Q

what drugs increase GABA levels

A

valproate

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51
Q

what drugs increase GABA release

A

gabapentin

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52
Q

what drugs inhibit GABA transaminase

A

vigabatrin

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53
Q

what drugs inhibit GAT-1

A

tiagabine

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54
Q

what drug is a NMDA receptor antagonist

A

felbamate

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55
Q

what drug is an antagonist of AMPA receptors

A

topiramate

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56
Q

MOA of phenytoin

A

binds and stabilizes the inactivated state of Na+ Channel

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57
Q

what is the therapeutic plasma level for phenytoin

A

7.5 - 20 ug/mL

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58
Q

Phenytoin has (linear or non-linear) pharmacokinetics

A

NON-linear!

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59
Q

drug interactions with Phenytoin

A

can be displaced from plasma proteins by other drugs (which leads to increase in phenytoin concen.)

and it induces CYP450 - increases metab of other drugs

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60
Q

ADEs of Phenytoin

A 
Arrhthymia
Ataxia
GI symptoms
Sedation (@ high doses)
Gingival Hyperplasia
Nystagmus or Diplopia
Hisutism
hypersensitivity reactions
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61
Q

which drug(s) is a part of the Hydantoin class

A

phenytoin

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62
Q

which drug(s) is a part of the Iminostilbene class

A

carbamazepine
and
oxcarbamazepine

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63
Q

which one has reduced toxicity?
oxcarbamazepine
or
carbamazepine

A

oxcarbamazepine

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64
Q

MOA of Carbamazepine

A

bind and stabilize Na+ channel into inactivated state

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65
Q

ADEs of Carbamazepine

A 
blurred vision
ataxia
GI disturbances
sedation at high doses
serious skin rash
DRESS hypersensitivity reaction
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66
Q

what is the brand of Lacosamide

A

Vimpat

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67
Q

what is MOA of Lacosamide

A

(aka Vimpat)

enhances inactivation of voltage gated Na+ Channels

68
Q

Barbituates and BZDs binds to active site or allosteric site?

A

ALLOSTERIC

69
Q

Barbituates and BZDs bind to an allosteric regulatory site on the _______ receptor

70
Q

what drugs are barbituates

A

phenobarbital
and
primidone

71
Q

MOA of phenobarbital

A

bind to allosteric regulatory site on GABA(A) receptors to INCREASE duration of Cl- channel opening events
(aka enhance GABA inhibitory signaling)

72
Q

Diazepam is especially useful for what types of seizures?

A

tonic clonic status epilepticus

73
Q

MOA of BZDs

A

increases FREQUENCY of Cl- channel opening events by binding to allosteric regulatory site on GABA(A) receptors

74
Q

BZDs or Barbituates?

increase FREQUENCY of Cl- Channels

75
Q

BZDs or Barbituates?

increase DURATION of Cl- channels

A

barbituates

76
Q

Clonazepam is useful for what kinds of seizures?

A

absence seizures

77
Q

MOA of gabapentin:

A

increase GABA release by being analog of GABA

78
Q

what is the MOA of Vigabatrin:

A

irrevers. inhibitor of GABA-T (GABA transaminase)

79
Q

what is the role of GABA-T

A

it degrades GABA

80
Q

what is the MOA of Tiagabine

A

inhibits GAT-1 (GABA transporter)

81
Q

NMDA and AMPA receptors — what binds to it and cause a trigger?

82
Q

NMDA and AMPA receptors —- excitatory or inhibitory recetors?

A

excitatory because they are glutamate receptors

83
Q

NMDA or AMPA receptors —

which one causes a Na+ AND Ca2+ influx when glutamate binds

A

NMDA

NMDA has letters of AND in it… so both Na+ and Ca2+..

84
Q

NMDA or AMPA receptors —

which one causes a Na+ only influx when glutamate binds

85
Q

T or F: NMDA and AMPA receptors cause an influx of K+ when glutamate binds

A

FALSE —- EFFLUX of K+

86
Q

MOA of Felbamate?

A

NMDA receptor antagonist

87
Q

MOA of Topiramate

A

AMPA receptor antagonist

88
Q

main toxicity of Felbamate

A

hepatic toxicity!! –> 3rd line drug

89
Q

what is MOA of Ethosuximide

A

blocks T-Type Ca2+ channels in thalamic neurons

90
Q

Ethosuximide is used only for ______ seizures and that is because why?

A

Abscence;

T-Type Ca2+ channels thought to be involved in cortical discharge of an absence attack

91
Q

MOA of lamotrigine

A

inhibits Na+ and Ca2+ voltage gated channel

92
Q

MOA of Valproate

A

inhibits Na+ and Ca2+ channels

93
Q

drug interactions of Valproate

A

displaces phenyotin from plasma proteins
and
inhibits metab. of phenytoin, CBZ, phenobarbital, lamotrigine

94
Q

MOA of Keppra

A

interferes with synaptic vesicle release and neurotransmission (bind binding to SV2A protein)
and
interferes w/ Ca2+ entry through Ca2+ channels

95
Q

Tx Status Epilepticus:

what are the phases broken into? (times too..)

A

0 - 5 mins: Stabilization phase
5 - 20 mins: Initial Phase
20 - 40 mins: Second Phase
40 - 60 mins: Third Phase

96
Q

Tx Status Epilepticus:

what do you during the stabilization phase?

A 
stabilize pt (ABCs)
time seizure from onset
assess oxygenation
initiate EEG monitoring
Check blood glucose (fingerstick)
obtain IV access to get CBC w/ differential; CMP; tox screen
97
Q

if Txing status epilepticus AND the blood glucose is < 60 mg/dL — how do you treat it?

A

100 mg IV thiamine and 50 mL D5W

98
Q 
Tx Status Epilepticus: 
what drug class is most commonly used first in the initial phase
A

BZDs (Midazolam, Lorazepam, Diazepam)

ALL IV!!!

99
Q

Tx Status Epilepticus:

during INITIAL PHASE: what drug do you use if there are no BZDs available?

A

Phenobarbital (IV!!)

100
Q

Tx Status Epilepticus:

what drugs are used during SECOND PHASE

A 
IV ---
fosphenytoin
or
Valproic Acid
or 
Levetiracetam

(or phenobarbitol)

(no preferred choice b/w agents!!)

101
Q

Tx Status Epilepticus:

what do you do during THIRD PHASE?

A

repeat second line therapy

Then use Anesthetic Dose of the Following and keep doing EEG monitoring!!
Thiopental, Midazolam, Phenobarbitol, and Propofol

102
Q

Loading Dose of Phenytoin for Tx of Status Epilepticus:

and MAX?

A

20 mg/kg IV
(may give additional doses 10 minutes after load)

Up to 50 mg/minute IV infusion

103
Q

Loading Dose of Fosphenytoin for Tx of Status Epilepticus:

and MAX?

A

20 mg PE/kg IV
(may give additional doses 10 minutes after load)

Up to 150 mg PE/minute IV infusion

104
Q

Phenytoin or Fosphenyotin has better IV tolerance?

A

Fosphenytoin

105
Q

what kind of monitoring is required with Phenytoin/Fosphenytoin

A

Cardiac monitoring

106
Q

what kind of local reaction can be seen with Phenytoin/Fosphenytoin

A

Purple glove syndrome

blood flow issues —- purple hands

107
Q

How do you switch from IV phenytoin to oral?

A

obtain BOTH phenytoin serum concen. and serum albumin at the SAME TIME!!! and calculate adjusted concentration

Want serum concentration range to be 10 - 20 mcg/mL

108
Q

what is the phenytoin adjusted concentration

A

Observed Concentration
(DIVIDED BY)
(0.25 x albumin) +0.1

109
Q

Tx of Status Epilepticus:
Valproate Loading Dose
and
Subsequent doses

A

LD: 15 - 30 mg/kg
and
Subsequent Doses: 15 mg/kg/day titrated to 60 mg/kg/day (MAX)

(IV dosed Q6H after loading dose)

110
Q

Switching from IV Valproate to Oral – how to?

A

1:1 conversion

111
Q

Desired therapeutic concentration of Phenytoin

A

10 - 20 mcg/mL

112
Q

Desired therapeutic concen. of Valproate

A

80 mcg/mL

50 - 125

113
Q

What Drugs are Usual 1st Line Tx for Absence Seizure?

A

Ethosuximide
Lamotrigine
Valproate

114
Q

What Drugs are Usual 1st Line Tx for Myoclonic Seizure

A

Levetiracetem
Topiramate
Valproate

115
Q

What Drugs are Usual 1st Line Tx for Lennox-Gastuat Syndrome

A

Valproate

Lamotrigine

116
Q

What Drugs are Usual 1st Line Tx for Partial Onset Seizures

A 
Carbamazepine
Lamotrigine
Levetiracetam
Oxcarbazepine
Valproate
117
Q

What Drugs are Usual 1st Line Tx for Tonic-Clonic Seizures

A

Carbamazepine
lamotrigine
Oxcarbamazepine
Valproate

118
Q

what drug has be titrated v slowly/specifically due to drug interactions and a severe ADE

A

Lamotrigine!!

UGT drug interactions and can lead to DRESS hypersensitivity or SJS

119
Q

what drug causes the lamotrigine dose to be lower (cut in half) during titration (and why?)

A

Valproate

b/c it is a UGT inhibitor

120
Q

what drug causes the lamotrigine dose to be higher (doubled) during titration (and why?)

A

CBZ and Phenytoin

b/c UGT inducer

121
Q

what is the dosing titration schedule for lamotrigine (with not UGT interactions present)

A

25 mg x 14 days
50 mg x 14 days
100 mg x 7 days
200 mg QD

122
Q

what genetic variant has a black box warning because it puts a patient at a higher hypersensitivity risk when on CBZ/oxvarbamazepine

A

HLA-B*1502

123
Q

what antidepression med actually should be avoided in pts with uncontrolled seizure disorders

124
Q

Cardiovascular ADEs:

what anticonvulsant med causes heart block

A

lacosamide

125
Q

Cardiovascular ADEs:

what anticonvulsant med cause arrhythmias

A

phenytoin/fosphenytoin

126
Q

Cardiovascular ADEs:

what anticonvulsant med causes PR interval changes

A

Lacosamide; Pregabalin

127
Q

Cardiovascular ADEs:

what anticonvulsant med causes peripheral edema (aka caution in HF)

A

Pregabalin

also gabapentin

128
Q

Electrolyte Abnormality ADEs:

what anticonvulsant meds can cause HYPONATREMIA/SIADH

A

Carbamazepine; Oxcarbamazepine

129
Q

what anticonvulsant med can cause osteoporosis from long term use (happens bc it laters vitamin D metabolism)

130
Q

what anticonvulsant leads to hyperammonia (and mechanism behind this?)

A

Valproate

Mechanism: Valproate cause CARNITINE deficiency — Carnitine is used to keep ammonia in check

131
Q

what anticonvulsants should be avoided because of psychosis

A

levetiracetam
and
perampanel

132
Q

what drugs have renal dosing

A 
Keppra
Ezobagine
Felbamate
Gabapentin
Pregabalin
Topiramate
Vigabatrin
133
Q

what drugs are controlled substances

A 
Clobazam
Clonazepam
Ezobagine
Perampanel
Phenobarbitol
Pregabalin
Brivatacatem
134
Q

contraindication for phenytoin?

A

Sinus bradycardia or 2nd/3rd degree heart block

135
Q

Oxcarbamazpeine is ____ times the dose of carbamazepine if converting

136
Q

Fosphenytoin to Phenytoin conversion occurs in ____ hour post dose

137
Q

what drug is converted to phenobarbital

138
Q

what drug has a boxed warning for vision loss

A

Vigabatrin

Ezobagine (from retinal abnormalities)

139
Q

what drug is contraindicated in sulfa hypersensitivity

A

Zonisamide

140
Q

what drugs have serum concentrations to monitor for?

A 
Valproate
Carbamazepine
Phenobarbital
Phenytoin
Tiagabine
141
Q

What drugs are renally cleared 100%?

A

Gabapentin and Pregabalin

142
Q

what drugs have black box warnings about vision loss

A

Ezobagine

Vigabatrin

143
Q

what drug has a contraindication for Familial short QT Sydnrome

A

Rufinamide

144
Q

ADEs of Pregabalin

A

Angioedema
Peripheral Edema
PR interval prolongation

145
Q

what drug can cause PCOS

146
Q

what drug can cause alopecia

147
Q

what drugs can cause metabolic acidosis

A

topiamate

Zonisamide

148
Q

what drug can cause hyperammonia

149
Q

what drugs can cause hyponatremia

A

Carbamazepine
Eslicarbamazepine
Oxcarbamazepine

150
Q

which drug can cause grey-blue/brown skin

151
Q

what drugs increase PR interval

A

Lacosamide

Pregabalin

152
Q

which one can decrease bone mineral density

A

phenytoin

alters vit. D metabolism — osteoporosis

153
Q

what drugs have boxed warning for aplastic anemia

A

carbamazepine

Felbamate

154
Q

what drug can cause renal canculis

A

zonisamide

155
Q

ADEs of Zonisamide

A

sulfa allergy
metabolic acidosis
renal calculi

156
Q

which drug causes hirustism

157
Q

which drug causes gingival hyperplasia

158
Q

which drug causes SLE

A

Ethosuximide

159
Q

which drug causes anterograde amnesia

A

Clonazepam

160
Q

what drugs cause peripheral edema

A

pregabalin

gabapentin

161
Q

which drug causes hiccups

A

ethosuximide

162
Q

what drug causes leukopenia

A

ethosuximide

163
Q

what drugs cause weight gain (ones Ott highlighted)

A

Vigabatrin

Valproate

164
Q

what drugs cause Nystagmus

A

phenytoin

Brivarecetam

165
Q

which drug causes secondary angle closure glaucoma

A

topiramate

Therapeutics 3 - Spring 2018 (20 decks)

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