Epilepsy Flashcards
(188 cards)
1
Q
epilepsy is characterized by
A
recurrent and unpredictable seizures
2
Q
seizures are associated with
A
episodic high frequency discharge of impulses by large groups of neurons
3
Q
*seizures in the motor cortex will cause
A
convulsions
4
Q
*seizures involving the hypothalamus will cause
A
peripheral autonomic discharge
5
Q
*seizures involving reticular formation will cause
A
LOC
6
Q
simple partial seizures are characterized by
A
not causing altered consciousness
7
Q
complex partial seizures are characterized by
A
impaired or altered consciousness
8
Q
simple and complex partial seizures can
A
transition to a tonic clonic. this is called a secondarily generalized seizure.
9
Q
primary generalized seizures always involve
A
LOC
both hemispheres
10
Q
primary generalized seizures are classified as
A
tonic clonic
absence
myoclonic
atonic
11
Q
absence seizures are characterized by
A
blanking out for a few seconds at a time. no convulsions.
12
Q
myoclonic seizures involve
A
intense muscle contractions
13
Q
atonic seizures involve
A
loss of muscle tone
14
Q
gold standard drug for partial seizures
A
carbamazepine
15
Q
*conventional anti seizure drugs for partial seizures
A
carbamazepine
phenytoin
valproate
16
Q
conventional drugs used depend on
A
type of seizure
17
Q
*absence seizure gold standard drug
A
ethosuximide
18
Q
*absence seizure med options (4)
A
ethosuximide
valproate
clonazepam
lamotrigine
19
Q
if patient is suffering from absence seizures only, what would be a good choice?
A
ethosuximide
20
Q
if your patient is suffering from absence seizures concomitant with tonic clonic seizures, what do you need?
A
a med with a broader spectrum of activity.
valproic acid
21
Q
myoclonic seizure med options (3)
A
valproic acid
clonazepam
levetiracetam
lamo
22
Q
what to be aware of when prescribing benzos to patients for seizure?
A
tolerance develops in long term use
23
Q
tonic clonic seizure med options
A
carbamazepine phenobarbital phenytoin primidone valproate lamotrigine levetiracetam topiramate
24
Q
why is it so important to ID the type of seizure?
A
certain meds will exacerbate certain seizures
25
what meds to avoid in absence or myoclonic seizures
carbamazepine
| phenytoin
26
ethosuximide is only used for
absence seizures
27
valproic acid may be used for
All
28
clonazepam may be used for what kind of generalized seizures?
absence
| myoclonic
29
carbamazepine is used for which complex seizure?
tonic clonic seizures
30
phenobarbital is used for
tonic clonic seizures
31
phenytoin is used for
all partials
| tonic clonic seizures
32
primidone is used for
tonic clonic seizures
33
lamotrigine may be used for
partials and tonic clonic
| *absence
34
levetiracetam may be used for
myoclonic or tonic clonic
35
topiramate may be used for
tonic clonic seizures
36
anti epileptic drugs function to
balance out over excitation in the brain
37
effects of anti epileptic (2)
by suppressing discharge of neurons within a seizure focus
| by suppressing propagation of seizure activity from the focus to other areas of the brain
38
mechanisms of action of different anti epileptics (5)
```
suppression of sodium influx
suppression of calcium influx
promotion of potassium efflux
antagonism of glutamate receptors
potentiation of GABA (inhibitory)
```
39
all MoAs of anti epileptics
function to reduce excitation
40
Which 3 anti epileptics function at voltage gated Na channels?
carbamazepine
phenytoin
valproic
41
how do carbamazepine, phenytoin, and topiramate work
they bind to the inactive state of voltage gated sodium channels, keeping them inactive for a slightly longer period. In doing so, they inhibit APs from neurons.
42
what 3 anti epileptics function at the level of GABA signaling
benzodiazepines
barbituates
valproic acid*
43
benzos and barbs bind at
gaba a receptors, potentiating the effects of gaba at these receptors. this increases inhibitory gaba signaling in the brain.
44
how do benzos and barbs work
they bind to gaba A, promote chloride influx into the cell making it hyper polarized and less likely to fire.
45
how does valproate work
goes into pre synaptic terminals and inhibits the enzymes that metabolize gaba, allowing a greater mount of gaba to be able to be released into the synaptic cleft.
46
which anti epileptic drugs
47
which anti epileptic drugs function at the level of T-type calcium channels?
valproate
| ethosuximide
48
where are t-type calcium channels located?
thalamus
49
what two things should we be associating with t-type calcium channels?
thalamus
| absence seizures
50
drugs that bind to voltage gated Na channels function to reduce high freq discharges in which synapses of the brain?
glutamate
51
drugs that act on GABA
benzos
| barbituates
52
4 most commonly used drugs for tonic-clonic seizures that we will be focusing on
carbamazepine
phenobarbital
gabapentin
phenytoin
53
true or false: carbamazepine is the most widely used AED
true
54
why is carbamazepine preferred to phenytoin and phenobarbital? (3)
- less sedating
- mood stabilizing effects
- does not cause cognitive impairments
55
carbamazepine is first line for
all forms of partial seizures
| tonic clonic general seizure
56
MoA carbamazepine
stabilizes the inactive state of voltage dependent Na channels, limiting the repetitive firing evoked why sustained depolarization.
57
bioavailability of PO carbamazepine
85%
58
peak plasma time of carbamazepine
4.5 hr
59
metabolism of carbamazepine
primarily phase I hepatic metabolism via CYP3A4
60
what enzymes do carbamazepine induce?
CYP1A2
CYP2C9
CYP3A4
61
Carbamazepine is metabolized by and induces CYP3A4. what does this mean for elimination?
initially the half life is 25-65 hours
once dose is chronic and induction of CYP3A4 continues, the half-life decreases. at this point, the half life decreases to 10-20 hours.
62
unique metabolism/elimination of carbamazepine means what in terms of dosing?
dose monitoring and dose adjusting in the first 3-5 weeks of using the drug.
63
initial half life of carbamazepine
25-65 hr
64
chronic half life of carbamazepine
10-20 hr
65
UGT is a
phase II enzyme
66
carbamazepine induces what phase II enzyme?
UGT
67
pharmacokinetics of phenytoin and phenobarbital
they induce phase I enzymes as well as phase II enzymes, like carbamazepine
68
the only 3 AEDs that avoid many of these pharmacokinetic considerations in regard to metabolism
levetiracetam
gabapentin
pregabalin
69
ACUTE intoxication of carbamazepine
hyper irritability
stupor/coma
convulsions
respiratory depression
70
if a patient on carbamazepine presents with ataxia and diplopia...
dose should be decreased
71
you know you should decrease a patient's dose of carbamazepine if they present with
ataxia
| diplopia
72
other adverse effects of carbamazepine, which usually disappear with tolerance, are
drowsiness
vertigo
blurred vision
73
serious long term implication of carbamazepine
hematological toxicities like aplastic anemia, agranulocytosis, and *leukopenia*
74
carbamazepine pregnancy category
D
| benefits have to outweigh risks
75
why is it critical to monitor WBC in carbamazepine?
because of risk for transient leukopenia could become a chronic or prolonged issue.
76
required monitoring while on carbamazepine
renal
hepatic
CBC * transient leukopenia
77
drug interactions with carbamazepine
many because of its potent inducing effects of CYPs.
78
which AEDs may you see decreased plasma conc/dec clinical effect of when also taking carbazepine (related to induction of CYP enzymes?)
phenytoin
valproate
phenobarbital
79
which non AED drugs may you see dec plasma conc/dec clinical effect of when taking carbamazepine
PO contraceptives
warfarin
corticosteroids
80
if your patient were taking either phenytoin, valproate, or pheno barb as a mono therapy and then you introduced carbamazepine, what may happen?
seizures may reappear.
81
birth control and carbamazepine
increase doses of contraceptives or change method of birth control
82
carbamazepine black box warnings
- serious dermatological reactions
| - aplastic anemia/agranulocytosis
83
aplastic anemia/agranulocytosis as a rare adverse effect of carbamazepine which typically occurs
in elderly patients taking the med for trigeminal neuralgia
84
anticonvulsants structurally related to carbamazepine (2)
oxcarbazepine
| esilcarbazepine acetate
85
active metabolite of oxcarbazpine
eslicarbazepine
86
benefit of oxcarbazepine over carbamazepine
not as potent of a CYP inducer
| some decreased in hematologic effects
87
increased risk in oxcarbazepine as opposed to carbamazepine
hyponatremia
88
eslicarbazepine acetate
pro drug with active metabolite of eslicarbazepine
89
phenytoin is the oldest
non sedating AED
90
for which seizure types is phenytoin indicated?
all partials
| tonic clonic
91
phenytoin MoA
stabilizes the inactivated state of voltage dependent sodium channels
92
drugs that stabilize the inactivated state of voltage dependent sodium channels may be used for
all partial types and tonic clonic
93
protein binding of phenytoin
highly protein bound
94
low Vd of phenytoin tells you
its primary bound in plasma proteins
95
metabolism of phenytoin
CYP 2C9
| CYP 2C19
96
phenytoin induces which CYPs?
CYP2C's
| CYP3A's
97
elimination for zero order drugs is
dose dependent
98
phenytoin metabolism/plasma levels
as plasma lvls approach min effective dose, CYPs become saturated. those enzymes become fully saturated in therapeutic levels. as consequence, plasma levels shoot up into toxic range bc CYPs are saturated and can't metabolize any more.
99
therapeutic window for phenytoin
10 - 20 mcg/mL
100
if you have a patient on phenytoin who is not well controlled, what do you do INSTEAD of just raising the dose? and why
increasing the dose as you would with a first order drug will shoot them into the toxic range
because it is a zero order drug, you'd have to make a very small incremental dose change.
101
ataxia and diplopia in phenytoin use is a sign that
the dose is too high
102
dose related effects of phenytoin
ataxia
diplopia
drowsiness
sedation
103
idiosyncratic adverse effects of phenytoin
```
gingival hyperplasia
hirsutism
anemia
lymphadenopathy
osteoporosis
rash
```
104
pregnancy category of phenytoin
D
| benefit must outweigh risk
105
phenytoin will decrease the concentrations of which drugs, due to CYP induction?
carbamazepine
PO contraceptives
warfarin
corticosteroids
106
black box warning of phenytoin
severe hypotension/arrhythmias with rapid infusion
107
pro drug version of phenytoin
fosphenytoin
108
advantage of fosphenytoin
water soluble for parenteral administration
| can be administered IV for rapid loading
109
disadvantage of fosphenytoin
10x more expensive than phenytoin
110
gabapentin is appropriate for which kind of seizures?
all forms of partial seizures
111
MoA gabapentin
bind to alpha2delta1 subunit of Ca channels in cortical membrane, likely to inhibit Ca channel activity.
112
unique thing about gabapentin
it requires active transport to get from GI to systemic circulation, meaning it is difficult to overdose on or become toxic from because the transporter gets saturated.
113
metabolism of gabapentin
it is not metabolized. it is excreted unchanged in the urine
114
caution with gabapentin
renal function, as it is excreted unchanged in urine.
115
clearance of gabapentin correlates
directly with renal function
116
adverse effects of gabapentin usually resolve within 2 weeks. they are: (6)
```
somnolence
dizziness
ataxia
fatigue
headache
tremor
```
117
pregnancy category of gabapentin
c
118
advantages of gabapentin
well tolerated
no protein binding
not metabolized
no enzyme induction
119
anticonvulsant structurally related to gabapentin
pregabalin
120
prcegablin is the only AED with
potential for abuse
121
mixed pharmacology of pregabalin which enables it to be used for epilepsy and neuropathic/functional pain
reduces glutamate, norepinephrine, and substance P
122
pregabalin may be combined with (4)
valproate
lamotrigine
phenytoin
carbamazepine
123
pregabalin for pain relief
for neuropathic and functional pain
124
phenobarbital is the drug of choice for
seizures in infants
125
phenobarbital may be used for what types of seizures?
all partials
| tonic clonic
126
while phenobarbital is the drug of choice for neonatal seizures, it
is not effective as a mono therapy and will likely need an adjunct med as well
127
adverse effects of phenbarbital
```
resp depression
sedation
physical dependence
hyperactivity
cognitive impairments
```
128
use levetiracetam with caution in patients with
mood disorders
129
valproic acid may be used for what types of seizures?
all partial seizures
| all generalized seizures
130
MoA valproic acid (3)
stabilizes the inactivation state of sodium channels,
produces small reductions in T-type Calcium activity,
and increases GABA through inhibition of GABA transaminase activity
131
bioavailability of valproic acid
90%
132
protein binding of valproic acid
high
133
what needs to be kept in mind when using phenytoin and valproic acid together?
they are both highly protein bound drugs
134
metabolism of valproic acid
CYP 2C9
| CYP 2C19
135
what metabolic enzymes does valproic acid effect and how?
inhibits CYP 2C9 and UGT
136
valproic acid is a potent inhibitor of
phase I and phase II
137
adverse effects of valproic acid usually diminish after a few weeks because of tolerance, but what are they?
GI symptoms: anorexia, N/V
CNS: sedation, ataxia, tremor
Rash, alopecia, appetite stimulation/weight gain
138
CNS adverse effects in valproic acid
respond to dose reduction
139
pregnancy category of valproic acid*
D
* 4x more likely to have neural tube defects with valproic acid than other AEDs
* lower IQs in children
140
what needs to be monitored in valproic acid use?
liver function
141
LFT elevation in valproic acid
is common for the first few months of therapy
142
fatal complication of valproic acid
fulminant hepatitis
143
black box warning: valproic acid
hepatic failure
| teratogenicity
144
drug:drug interactions with valproic acid in relation to phase I metabolism
valproic acid inhibits CYP2C9, you'll see an increase in the conc of certain drugs
145
which phase I drugs will valproic acid interact with and how
increased plasma concentration of
| phenytoin, phenobarbital, ethosuximide
146
drug:drug interactions with valproic acid in terms of phase II metabolism
valproic acid inhibits UGT, which means increased levels of certain drugs
147
which phase II drugs will valproic acid interact with and how?
by inhibiting UGT, it'll increase plasma concentration of lamotrigine and lorazepam.
148
high concentrations of valproic acid will result in displacement of what?
phenytoin and other drugs from albumin
149
lamotrigine may be used for which types of seizures? (FDA)
all partials
| tonic-clonic
150
lamotrigine may be used off label for what type of seizures?
absence
myoclonic
tonic
atonic
151
MoA lamotrigine*
stabilizes the inactivation state of Na channels
as well as additional, unknown MoA.
because it does help with absence seizures, we can guess that it also has activity with T type calcium channels.
152
protein binding of lamotrigine
none
153
metabolism of lamotrigine
phase I, extensive CYPs
154
lamotrigine affects metabolism of other drugs by
inducing UGT
155
half life of lamotrigine is reduced by
phenytoin, carbamazepine, phenobarbital
156
half life of lamotrigine is increased by
valproate
157
adverse effect you want to be careful to monitor for in lamotrigine and why
rash, as it can transition into stevens-johnson syndrome and even DIC.
158
incidence of lamotrigine rash is more likely
in children than adults
159
black box: lamotrigine
life threatening rash, especially in combo with valproic acid.
more likely in high doses or in rapid dose escalation.
more likely in children.
160
using lamotrigine and valproic acid together
should be avoided
161
ethosuximide is indicated for which types of seizures?
absence only
162
MoA ethosuximide
reduces low threshold calcium currents in T-type channels in thalamus.
163
metabolism of ethosuximide
CYP3A4
164
does ethosuximide induce or inhibit any other metabolic enzymes?
no
165
ethosuximide most common side effets
nausea, vomiting, anorexia
166
pregnancy category: ethosuximide
D
167
if a woman who is taking ethosuximide is trying to get pregnant, you should
switch her to lamotrigine
168
teratogenicity of AEDs
somewhat increased risk of congenital malformations
169
most teratogenic AED
valproic acid
170
when a woman is going to become pregnant and is on an AED, you want to
evaluate if there is a safer choice
| if so, withdraw her from current drug and begin new drug.
171
supervised withdrawal from AED
typically done over the course of months with monitoring for reappearance of seizures
172
when is a trial of gradual discontinuation of AED warranted?
when pt is seizure free for 3-4 years
173
if a patient is on multiple AEDs, how is withdrawal done?
gradual withdrawal from one drug at a time
174
if a patient is able to gradually withdraw from one of their AEDs and seizures have not reappeared,
can initiate gradual withdrawal of other drug
175
suicidality is officially increased with what AEDs?
lamotrigine
| topirimate
176
anti seizure drug class black box warning
suicidality
177
Rescue AEDs may be administered during active seizure. What drug class is used?
benzos
178
benzos for rescue AED (3)
clonazepam
lorazepam
diazepam
179
rectally administered rescue AED
diazepam
180
buccally administered rescue AED
midazolam
181
sublingual rescue AED
SL clonazepam
182
monitor for what after rescue benzo?
respiratory depression
183
alcohol withdrawal induced seizures are
generalized tonic clonic seizures that typically occur within 12-48 hours after last drink. potentially fatal.
184
why do tonic clonic seizures happen in AWS?
prolonged exposure to high levels of alcohol leads to reduced alpha1-GABAA receptors. when alcohol is removed, there is a decrease in the inhibitory tone of the brain. brain is predisposed to excitation.
abrupt discontinuation of alcohol leads to up-regulation of alpha4-GABAA receptors. These receptors deactivate quickly leading to a reduced inhibitory tone and increased susceptibility to w/d seizures.
decrease in alpha1 gaba receptors, increase in alpha4 gaba receptors. this makes you susceptible. you are not as responsive to GABA anymore.
185
issues with benzos for AWS
synergistic sedative effects with alcohol - potentially fatal
186
why may shorter acting benzos be safer for inpatient AWS?
because when the pt is d/c, they will likely drink again. you don't want the synergistic effects to occur.
187
which AEDs are NOT efficacious in preventing alcohol withdrawal seizures? (2)
carbamazepine
| phenytoin
188
advantage of using traditional AEDs for AWS?
no abuse liability or synergistic effect with alcohol
