Exam 3 - Rochet/Ott (Seizures) Flashcards
1
Q
3 main ways to classify seizures
A
Focal Onset
Generalized Onset
Unknown Onset
2
Q
how to classify Focal Onset Seizures
A
Aware or Impaired awareness
and
Motor or Nonmotor onset
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
4
Q
common reason for generalized seizures
A
NOT due to lesion—- presumed to be genetic!
5
Q
Generalized seizures are known to cause the patient to be aware or non-aware?
A
non-aware — pt lose consciousness
6
Q
Focal seizures can progress to secondary generalized seizures via projections to the ______
A
thalamus
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
8
Q
what are automatisms?
A
repetitive motor behaviors
swallowing, chewing, lip smacking
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
10
Q
what is postictal state
A
after seizure —- pt will not recover a normal level of consciousness immediately
11
Q
symptoms of postictal state
A
confusion
disorientation
anterograde amnesia
12
Q
Generalized Seizures:
Absence —- can be ______ or _______
A
atypical
or
typical
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)
14
Q
Describe Atypical Absence Generalized Seizures
A
SLOWER ONSET
more difficult to control pharmacologically than typical
15
Q
Generalized Seizures – two main subgroupings
A
Abscence or Non-Abscence
16
Q
What are Non-Abscence Generalized Seizures?
A
Myoclonic Tonic Clonic Atonic Tonic-Clonic Status Epilepticus
17
Q
which Non-Abscence Generalized Seizures?
shock-like contraction of muscles
and
isolated jerking of head, trunk, and body
A
Myoclonic
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…
19
Q
which Non-Abscence Generalized Seizures?
involve rapid/repetitive motor activity
occur in babies/young kids
A
clonic
20
Q
which Non-Abscence Generalized Seizures?
sudden loss of muscle tone
and
patients fall if standing “drop attacks”
A
Atonic
21
Q
which Non-Abscence Generalized Seizures?
referred to as grand mal
A
tonic-clonic
22
Q
which Non-Abscence Generalized Seizures?
known as single prolonged seizure
A
status epilepticus
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
24
Q
Drug therapy can be GRADUALLY withdrawn in pts who have been clinically free of seizures for _______(how long…?)
A
2 - 5 years
25
what is PDS
paroxysmal depolarizing shift
| it is large depolarization that triggers burt of action potentials
26
Pathophysiology of Seizures:
| Depolarization involves activation of _____ and _____ channels also _______ channels
AMPA; NMDA; voltage gated Ca2+
27
Pathophysiology of Seizures:
| Depolarization activates channels by the ________ neurotransmitter (known as ______) and and leads to _____ influx
excitatory; glutamate; Ca2+
28
Pathophysiology of Seizures:
| Hyperpolarization involves activation of ______ receptors and ______ channels
GABA; and calcium gated POTASSIUM channels
29
Pathophysiology of Seizures:
| Hyperpolarization leads to a ____ efflux
K+
30
Pathophysiology of Seizures:
_____ neurons are used to dampen neuronal signaling
by feed forward or feedback inhibition
GABAergic
31
Pathophysiology of Seizures:
| what is inhibitory surround
it is hella GABA neurons connected to glutamate to inhibit an electrical discharge from spreading
32
Pathophysiology of Seizures:
| Tonic Phase Seizures --- _______ mediated inhibition dissapears
GABA
33
Pathophysiology of Seizures:
| Tonic Phase Seizures ---- ________ mediated activity increases
glutamate
| AMPA and NMDA receptor
34
Pathophysiology of Seizures:
| In Clonic Phase: ______ mediated inhibition gradually ______ which causes a period of _______
GABA; gradually returns; period of Oscillation
35
Pathophysiology of Seizures:
| In the tonic phase --- when ______ mediated inhibition breaks down ---- the action potentials do what?
GABA mediated;
| action potentials propagate to distant neurons
36
allllllll the potential triggers of status epilepticus
```
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
```
37
Drugs that may increase the risk of seizures
```
alcohol
theophylline
bupropion
oral contraceptives
withdrawal from depressants
CNS stimulants
clozapine
```
38
why is clozapine related to increase risk of seizures
clozapine converted to norclozapine via CYP1A2 and norclozapine increases seizure risk
39
what is the definition of seizure
paroxysmal disorder of CNS ---- abnormal neruonal discharges with or without loss of consciousness
40
what is the definition of convulsion
specific seizure where attack is manifested by involuntary muscle contractions
41
what is the definition of epilepsy
repeated seizures due to damage/irritation and or chemical imbalances in brain
42
Two synapses are targeted for Anticonvulsant drugs --- what are the two synapses
Glutamate (excitatory) and GABA (inhibitory)
43
For Excitatory Synapse Drug Targets:
What are the Presynaptic targets
and
what are the postsynaptic targets
pre: Na+ channels and Ca2+ channels
post: NMDA and AMPA receptors
44
For Inhibitory Synapse Drug Targets:
What are the Presynaptic targets
and
what are the postsynaptic targets
Pre: GABA transporter (GAT-1) and GABA transaminase (GABA-T)
Post: GABA(A) receptors and GABA(B) receptors
45
List the drugs that decrease sodium influx
```
carbamazepine
oxcarbazepine
phenytoin
lacosamide
lamotrigine
valproate
```
46
List the drugs that decrease calcium influx
| **This is CRITICAL for abscence seizures!!
ethosuximide
lamotrigine
valproate
47
List the drugs that enhance GABA mediated inhibition
```
BZDs
barbituates
valproate
gabapentin
viganatrin
tiagabine
```
48
List the drugs that antagonize excitatory tranxmitters (ex: glutatmate)
felbamate
| topiramate
49
what drugs activate the GABA(A) receptor
barbituates
and
benzodiazepines
50
what drugs increase GABA levels
valproate
51
what drugs increase GABA release
gabapentin
52
what drugs inhibit GABA transaminase
vigabatrin
53
what drugs inhibit GAT-1
tiagabine
54
what drug is a NMDA receptor antagonist
felbamate
55
what drug is an antagonist of AMPA receptors
topiramate
56
MOA of phenytoin
binds and stabilizes the inactivated state of Na+ Channel
57
what is the therapeutic plasma level for phenytoin
7.5 - 20 ug/mL
58
Phenytoin has (linear or non-linear) pharmacokinetics
NON-linear!
59
drug interactions with Phenytoin
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
60
ADEs of Phenytoin
```
Arrhthymia
Ataxia
GI symptoms
Sedation (@ high doses)
Gingival Hyperplasia
Nystagmus or Diplopia
Hisutism
hypersensitivity reactions
```
61
which drug(s) is a part of the Hydantoin class
phenytoin
62
which drug(s) is a part of the Iminostilbene class
carbamazepine
and
oxcarbamazepine
63
which one has reduced toxicity?
oxcarbamazepine
or
carbamazepine
oxcarbamazepine
64
MOA of Carbamazepine
bind and stabilize Na+ channel into inactivated state
65
ADEs of Carbamazepine
```
blurred vision
ataxia
GI disturbances
sedation at high doses
serious skin rash
DRESS hypersensitivity reaction
```
66
what is the brand of Lacosamide
Vimpat
67
what is MOA of Lacosamide
(aka Vimpat)
| enhances inactivation of voltage gated Na+ Channels
68
Barbituates and BZDs binds to active site or allosteric site?
ALLOSTERIC
69
Barbituates and BZDs bind to an allosteric regulatory site on the _______ receptor
GABA(A)
70
what drugs are barbituates
phenobarbital
and
primidone
71
MOA of phenobarbital
bind to allosteric regulatory site on GABA(A) receptors to INCREASE duration of Cl- channel opening events
(aka enhance GABA inhibitory signaling)
72
Diazepam is especially useful for what types of seizures?
tonic clonic status epilepticus
73
MOA of BZDs
increases FREQUENCY of Cl- channel opening events by binding to allosteric regulatory site on GABA(A) receptors
74
BZDs or Barbituates?
| increase FREQUENCY of Cl- Channels
BZDs
75
BZDs or Barbituates?
| increase DURATION of Cl- channels
barbituates
76
Clonazepam is useful for what kinds of seizures?
absence seizures
77
MOA of gabapentin:
increase GABA release by being analog of GABA
78
what is the MOA of Vigabatrin:
irrevers. inhibitor of GABA-T (GABA transaminase)
79
what is the role of GABA-T
it degrades GABA
80
what is the MOA of Tiagabine
inhibits GAT-1 (GABA transporter)
81
NMDA and AMPA receptors --- what binds to it and cause a trigger?
glutamate
82
NMDA and AMPA receptors ---- excitatory or inhibitory recetors?
excitatory because they are glutamate receptors
83
NMDA or AMPA receptors ---
| which one causes a Na+ AND Ca2+ influx when glutamate binds
NMDA
| NMDA has letters of AND in it... so both Na+ and Ca2+..
84
NMDA or AMPA receptors ---
| which one causes a Na+ only influx when glutamate binds
AMPA
85
T or F: NMDA and AMPA receptors cause an influx of K+ when glutamate binds
FALSE ---- EFFLUX of K+
86
MOA of Felbamate?
NMDA receptor antagonist
87
MOA of Topiramate
AMPA receptor antagonist
88
main toxicity of Felbamate
hepatic toxicity!! --> 3rd line drug
89
what is MOA of Ethosuximide
blocks T-Type Ca2+ channels in thalamic neurons
90
Ethosuximide is used only for ______ seizures and that is because why?
Abscence;
| T-Type Ca2+ channels thought to be involved in cortical discharge of an absence attack
91
MOA of lamotrigine
inhibits Na+ and Ca2+ voltage gated channel
92
MOA of Valproate
inhibits Na+ and Ca2+ channels
93
drug interactions of Valproate
displaces phenyotin from plasma proteins
and
inhibits metab. of phenytoin, CBZ, phenobarbital, lamotrigine
94
MOA of Keppra
interferes with synaptic vesicle release and neurotransmission (bind binding to SV2A protein)
and
interferes w/ Ca2+ entry through Ca2+ channels
95
Tx Status Epilepticus:
| what are the phases broken into? (times too..)
0 - 5 mins: Stabilization phase
5 - 20 mins: Initial Phase
20 - 40 mins: Second Phase
40 - 60 mins: Third Phase
96
Tx Status Epilepticus:
| what do you during the stabilization phase?
```
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
if Txing status epilepticus AND the blood glucose is < 60 mg/dL --- how do you treat it?
100 mg IV thiamine and 50 mL D5W
98
```
Tx Status Epilepticus:
what drug class is most commonly used first in the initial phase
```
BZDs (Midazolam, Lorazepam, Diazepam)
| ALL IV!!!
99
Tx Status Epilepticus:
| during INITIAL PHASE: what drug do you use if there are no BZDs available?
Phenobarbital (IV!!)
100
Tx Status Epilepticus:
| what drugs are used during SECOND PHASE
```
IV ---
fosphenytoin
or
Valproic Acid
or
Levetiracetam
```
(or phenobarbitol)
(no preferred choice b/w agents!!)
101
Tx Status Epilepticus:
| what do you do during THIRD PHASE?
repeat second line therapy
Then use Anesthetic Dose of the Following and keep doing EEG monitoring!!
Thiopental, Midazolam, Phenobarbitol, and Propofol
102
Loading Dose of Phenytoin for Tx of Status Epilepticus:
| and MAX?
20 mg/kg IV
(may give additional doses 10 minutes after load)
Up to 50 mg/minute IV infusion
103
Loading Dose of Fosphenytoin for Tx of Status Epilepticus:
| and MAX?
20 mg PE/kg IV
(may give additional doses 10 minutes after load)
Up to 150 mg PE/minute IV infusion
104
Phenytoin or Fosphenyotin has better IV tolerance?
Fosphenytoin
105
what kind of monitoring is required with Phenytoin/Fosphenytoin
Cardiac monitoring
106
what kind of local reaction can be seen with Phenytoin/Fosphenytoin
Purple glove syndrome
| blood flow issues ---- purple hands
107
How do you switch from IV phenytoin to oral?
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
what is the phenytoin adjusted concentration
Observed Concentration
(DIVIDED BY)
(0.25 x albumin) +0.1
109
Tx of Status Epilepticus:
Valproate Loading Dose
and
Subsequent doses
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
Switching from IV Valproate to Oral -- how to?
1:1 conversion
111
Desired therapeutic concentration of Phenytoin
10 - 20 mcg/mL
112
Desired therapeutic concen. of Valproate
80 mcg/mL
| 50 - 125
113
What Drugs are Usual 1st Line Tx for Absence Seizure?
Ethosuximide
Lamotrigine
Valproate
114
What Drugs are Usual 1st Line Tx for Myoclonic Seizure
Levetiracetem
Topiramate
Valproate
115
What Drugs are Usual 1st Line Tx for Lennox-Gastuat Syndrome
Valproate
| Lamotrigine
116
What Drugs are Usual 1st Line Tx for Partial Onset Seizures
```
Carbamazepine
Lamotrigine
Levetiracetam
Oxcarbazepine
Valproate
```
117
What Drugs are Usual 1st Line Tx for Tonic-Clonic Seizures
Carbamazepine
lamotrigine
Oxcarbamazepine
Valproate
118
what drug has be titrated v slowly/specifically due to drug interactions and a severe ADE
Lamotrigine!!
| UGT drug interactions and can lead to DRESS hypersensitivity or SJS
119
what drug causes the lamotrigine dose to be lower (cut in half) during titration (and why?)
Valproate
| b/c it is a UGT inhibitor
120
what drug causes the lamotrigine dose to be higher (doubled) during titration (and why?)
CBZ and Phenytoin
| b/c UGT inducer
121
what is the dosing titration schedule for lamotrigine (with not UGT interactions present)
25 mg x 14 days
50 mg x 14 days
100 mg x 7 days
200 mg QD
122
what genetic variant has a black box warning because it puts a patient at a higher hypersensitivity risk when on CBZ/oxvarbamazepine
HLA-B*1502
123
what antidepression med actually should be avoided in pts with uncontrolled seizure disorders
bupropion
124
Cardiovascular ADEs:
| what anticonvulsant med causes heart block
lacosamide
125
Cardiovascular ADEs:
| what anticonvulsant med cause arrhythmias
phenytoin/fosphenytoin
126
Cardiovascular ADEs:
| what anticonvulsant med causes PR interval changes
Lacosamide; Pregabalin
127
Cardiovascular ADEs:
| what anticonvulsant med causes peripheral edema (aka caution in HF)
Pregabalin
| also gabapentin
128
Electrolyte Abnormality ADEs:
| what anticonvulsant meds can cause HYPONATREMIA/SIADH
Carbamazepine; Oxcarbamazepine
129
what anticonvulsant med can cause osteoporosis from long term use (happens bc it laters vitamin D metabolism)
phenytoin
130
what anticonvulsant leads to hyperammonia (and mechanism behind this?)
Valproate
| Mechanism: Valproate cause CARNITINE deficiency --- Carnitine is used to keep ammonia in check
131
what anticonvulsants should be avoided because of psychosis
levetiracetam
and
perampanel
132
what drugs have renal dosing
```
Keppra
Ezobagine
Felbamate
Gabapentin
Pregabalin
Topiramate
Vigabatrin
```
133
what drugs are controlled substances
```
Clobazam
Clonazepam
Ezobagine
Perampanel
Phenobarbitol
Pregabalin
Brivatacatem
```
134
contraindication for phenytoin?
Sinus bradycardia or 2nd/3rd degree heart block
135
Oxcarbamazpeine is ____ times the dose of carbamazepine if converting
1.5
136
Fosphenytoin to Phenytoin conversion occurs in ____ hour post dose
0.5 - 1
137
what drug is converted to phenobarbital
primidone
138
what drug has a boxed warning for vision loss
Vigabatrin
| Ezobagine (from retinal abnormalities)
139
what drug is contraindicated in sulfa hypersensitivity
Zonisamide
140
what drugs have serum concentrations to monitor for?
```
Valproate
Carbamazepine
Phenobarbital
Phenytoin
Tiagabine
```
141
What drugs are renally cleared 100%?
Gabapentin and Pregabalin
142
what drugs have black box warnings about vision loss
Ezobagine
| Vigabatrin
143
what drug has a contraindication for Familial short QT Sydnrome
Rufinamide
144
ADEs of Pregabalin
Angioedema
Peripheral Edema
PR interval prolongation
145
what drug can cause PCOS
valproate
146
what drug can cause alopecia
valproate
147
what drugs can cause metabolic acidosis
topiamate
| Zonisamide
148
what drug can cause hyperammonia
valproate
149
what drugs can cause hyponatremia
Carbamazepine
Eslicarbamazepine
Oxcarbamazepine
150
which drug can cause grey-blue/brown skin
Ezobagine
151
what drugs increase PR interval
Lacosamide
| Pregabalin
152
which one can decrease bone mineral density
phenytoin
| alters vit. D metabolism --- osteoporosis
153
what drugs have boxed warning for aplastic anemia
carbamazepine
| Felbamate
154
what drug can cause renal canculis
zonisamide
155
ADEs of Zonisamide
sulfa allergy
metabolic acidosis
renal calculi
156
which drug causes hirustism
phenytoin
157
which drug causes gingival hyperplasia
phenytoin
158
which drug causes SLE
Ethosuximide
159
which drug causes anterograde amnesia
Clonazepam
160
what drugs cause peripheral edema
pregabalin
| gabapentin
161
which drug causes hiccups
ethosuximide
162
what drug causes leukopenia
ethosuximide
163
what drugs cause weight gain (ones Ott highlighted)
Vigabatrin
| Valproate
164
what drugs cause Nystagmus
phenytoin
| Brivarecetam
165
which drug causes secondary angle closure glaucoma
topiramate
