Depression/Anxiety Flashcards
1
Q
3 monoamines
A
dopamine
seratonin
norepinephrine
2
Q
inhibitors of monoamine uptake: 4 examples
A
SSRI
SNRI
NDRI
TCA
3
Q
SSRI
A
selective serotonin reuptake inhibitors
4
Q
SNRIs
A
serotonin and norepinpheinr reuptake inhibitors
5
Q
NDRIs
A
norepinephrine and dopamine reuptake inhibitors
6
Q
TCA
A
tricyclic anti depressants
7
Q
MAOI stands for
A
monoamine oxidase inhibitors
8
Q
NDRI example
A
duloxetine
9
Q
etiology of MDD: monoamine hypothesis
A
deficiency in the amount or function of 5HT/Serotonin, norepinephrine, and or dopamaine.
10
Q
etiology of depression: neurotrophic hypothesis
A
deficiency in neurotrophic factors, especially BDNF (brain derived neurotrophic factor)
11
Q
in depression or chronic stress, you’ll have a decrease in (2)
A
synapses
BDNF
12
Q
increased dendritic arbors is associated with
A
increased bdnf
13
Q
most proximal cause of depressive symptoms
A
neural apoptosis in hippocampus/pre frontal cortex
14
Q
stress mechanisms underlying neural apoptosis
A
- sustained high levels of cortisol which promotes neural apoptosis
- excessive glutamate levels which are high enough to be cytotoxic. leads to apoptosis.
15
Q
what counteracts this neural apoptosis contributing to depressive symptoms?
A
monoamines and neurotrophic factors
16
Q
monoamines and their receptors counteract cytotoxic effects of stress. what do they promote?
A
genes which facilitate neurogenesis in hippocampus, producing an anti depressant response.
17
Q
depression results in an imbalance of opposing signals.
too much _____ or _____
too little _____, _____, and or ______
A
too much glutamate or cortisol
or too little norepinephrine, serotonin, and or BDNF.
18
Q
the way to counter depression is to reduce _______ or increase _______
A
reduce stress related signaling
increase monoamine NTs or BDNF
19
Q
antidepressant strategy
A
increase synaptic concentrations of norepinephrine / serotonin in the hippocampus and prefrontal cortex
20
Q
if an antidepressant strategy is increase synaptic concentrations of norepinephrine / serotonin in the hippocampus and prefrontal cortex, how can we go about doing that? (3)
A
- inhibit reuptake of the monoamines once released from presynaptic neurons
- prevent degradation of the monoamines once released
- block pre synaptic forms of negative feedback regulation
21
Q
anti depressants may also work by mimicking the actions of
A
NE / serotonin and postsynaptic receptors (beta adrenergic or serotonin 1A receptors)
22
Q
time course of response: anti depressants
A
initial response: 1-3 weeks
max response: 12 weeks
23
Q
when can an anti depressant be considered failed?
A
after 1 month with no success
24
Q
selecting an anti depressant is
A
patient specific. they’re nearly all the same efficacy.
25
early treatment management of the patient on anti depressant
assess for suicidal tendencies
26
SSRI drugs (6)
```
fluoxetine
paroxetine
citalopram
escitalopram
sertraline
fluvoxamine
```
27
action of SSRI
selectively inhibiting the serotonin reuptake transporter SERT
28
efficacy of SSRIs is attributed to
subsequent actions of elevated 5HT at 5HT1A receptors
29
5HT 1A receptor activation
anti depressant response
30
AEs of SSRIs are all serotonin mediated. They are (4)
nausea
agitation
insomnia
sexual dysfunction
31
AE of nausea from SSRI is due to which receptor activation
5HT3
32
sexual dysfunction is due to activation of what receptor in SSRI use?
5HT2
33
drug interactions with SSRIs can be due to
their inhibition of the metabolism of other drugs
34
risk of overdose with SSRI is
low
35
SSRIs must not be combined with
MAOIs
36
SSRIs are potent inhibitors of
CYP 2D6
37
SSRIs inhibit which transporter
SERT
38
which serotonin receptors are particularly problematic when stimulated re: adverse effects?
5HT2
| 5HT3
39
which other SSRIs inhibit metabolism of other drugs the most?
fluoxetine
| paroxetine
40
which SSRIs probduce active metabolites?
fluoxetine
| sertraline
41
stimulating 5HT14 in the wrong region of the brain
leads to undesired effects
42
by inhibiting CYP 1D6 AND 3A4, SSRIs can
increase plasma concentrations of many drugs
43
which SSRI has the longest half life?
fluoxetine
44
half life of fluoxetine's metabolite's half life?
3 days
45
washout period
t1/2 of med's active metabolites.
46
SSRIs have high Vd because
lipophilic
47
SSRI with high protein binding, like fluoxetine, plus phenytoin
could cause phenytoin toxicity because they'd compete for protein binding and there would be more free phenytoin circulating
48
anti depressant actions of SSRIs are similar in efficacy and time course to
TCAs
49
acute toxicity/cardiotoxicity in anti depressant use is seen more in/less in which drugs?
more often in MAO Is and TCAs
| less often in SSRIs
50
SSRI side effects
nausea
insomnia
sexual dysfunction
51
sedation in antidepressants is seen more in/less in
more in TCAs
| less in SSRIs
52
SSRIs + MAOIs in comvination
risk for serotonin syndrome
53
serotonin syndrome s/s
tremor
hyperthermia
CV collapse
54
paroxetine or fluoxetine in combination with TCAs
should not be combined.
| these SSRIs inhibit CYP2D6 --> inc risk for TCA toxicity
55
which SSRIs are FDA approved for adolescents?
fluoxetine
| escitalopram
56
With regards to pregnancy, SSRIs are mainly
category C
57
which SSRI do you want to avoid the most in pregnancy?
paroxetine - category D
58
SSRIs may also treat (6)
```
GAD
panic
social anxiety
OCD
premenstrual dysphoric syndrome
PTSD
```
59
interactions between hydrocodone and fluoxetine or paroxetine
hydrocodone is a prodrug converted by CYP2D6 into hydromorphone, a much more potent opioid. fluoxetine or paroxetine will inhibit CYP2D6, which may decrease pain relief in those taking hydrocodone.
60
SNRIs (4)
duloxetine
venlafaxine
desvenlafaxine
milnacipran
61
desvenlafaxine
active metabolite of venlafaxine, can be prescribed on its own
62
SNRIs inhibit which transporters?
SERT
| NET
63
the antidepressant effects of SNRIs are due to
activating 5HT1a receptors
| activating beta adrenergic receptors
64
adverse effects of SNRIs are similar to SSRIs, plus
dose related elevation of bp
65
risk of SSRI/SNRI overdose is
low
66
SNRIs cannot be used in combo with
MAOIs
67
why do you get elevated bp with SNRI?
activation of alpha adrenergic receptors in vasculature
68
SNRIs have a greater affinity for
SERT
69
Are SNRIs more efficacious than SSRIs or TCAs?
no
70
inhibiting SERT and NET leads to
increases in serotonin and norepinephrine signaling
71
bioavailability of SSRI and SNRIs
pretty good
72
half life of SNRIs is ____ than SSRIs
shorter
73
active metabolites / washout periods SNRIs
not a concern
74
protein binding of SNRIs
varies between the drugs
75
duloxetine protein binding as compared to other SNRIs
much higher, 90%
76
if you're concerned about drug:drug interactions but need to prescribe an anti depressant, what would be a good choice?
venlafaxine or milnacipran SNRIs because of low protein binding
77
SNRIs are mainly metabolized by _____ except for
CYP 2D6
| except for desvenlafaxine
78
metabolism of desvenlafaxine
phase II - conjugation
79
SNRIs noradrenergic related adverse effects
inc bp
tachy
CNS activation
80
like SSRIs, SNRIs may also be used to treat
anxiety disorders
fibromyalgia
neuropathic pain
81
SNRIs are thought to help fibromyalgia and neurpathic pain, unlike SSRIs, because of
increased noradrenergic signaling
82
TCA examples (5)
```
amitryptaline
clomipramine
dose-in
imipramine
trimipramine
```
83
why have TCAs fallen out of of favor (2)
not very well tolerated in regards to AE
| risk for fatal cardiac arrhythmia with high doses
84
TCA MoA
inhibit 5HT and NE uptake
85
antidepressant effects of TCAs can be attributed to
effects on 5HT1a receptors and beta adrenergic receptors
86
TCAs and active metabolites
they do have active metabolites that work at 5HT and norepinephrine receptors, but their affinity may defer. you can have varied response to TCAs depending on the active metabolites.
87
why aren't TCAs as well tolerated as SSRIs/SNRIs?
they affect additional receptors unrelated to therapeutic efficacy
88
what other receptors do TCAs antagonize, unrelated to therapeutic efficacy? (3)
muscarinic acetylcholine receptors
histamine H1 receptors
alpha1 adrenergic receptors
89
TCA half lives
long
90
TCA washout periods
important to pay attention to bc they do have active metabolites with long half lives
91
TCa protein binding
high
92
TCA lipophilicity
high
93
metabolite half lives of TCAs as compared to just the half life of TCAs
longer
94
washout period of TCA
long because of active metabolite half lives
95
TCAs are metabolized by
CYP 2D6
96
poor metabolizers of CYP 2D6 can have a _ fold difference in plasma conch
30 fold difference
97
what actions are warranted to avoid toxicity when a pt who is a PM of CYP2D6 is taking a TCA?
plasma level monitoring
| dose reduction
98
a`
99
AEs of TCAs r/t to antagonism of muscarinic receptors (4)
dry mouth
blurred vision
constipation
urinary retention
100
AEs of TCA r/t antagonism of H1 histamine receptors? (2)
sedation
| weight gain
101
A Es of TCAs r/t antagonism of alpha1 adrenergic receptors (1)
postural hypotension
102
potentially fatal A E of TCAs, particularly in overdose?
ventricular dyshythmias
103
therapeutic index of TCA
narrow
104
TCAs are only prescribed in 1 week intervals, why?
because they may be used for suicide in OD
105
drug interactions and TCAs
likely to cause adverse effects bc they rely on CYPs
106
TCAs potentiate the effects of (2)
alcohol
| anesthetic
107
TCAs interfere with the actions of _____ and may require _____
anti hypertensive drugs
| may require dose adjustments up, as TCAs can cause hypertension
108
efficacy and time course of TCAs as compared to SSRI and SNRI
identical
109
at the present time, TCAs are used if
depression is unresponsive to more commonly used agents like SSRIs or SNRIs
110
TCAs and chronic or neuropathic pain
efficacy
111
first choice for patient with depression and chronic pain and what is your next choice if they don't respond to it?
1st - SNRI
| 2nd - TCA
112
acute TCA overdose s/s (3)
confusion
mania
cardiac dysrhythmias
113
TCAs are likely to interact with drugs which
are metabolized by, inhibit, or induce CYPs
114
(3) things that TCAs will interact with
alcohol
anesthetics
MAOIs
115
monoamine receptor antagonists (2)
mirtazapine
| trazodone
116
monoamine receptor antagonist MoA
mirtazapine antagonizes 5HT2c and 5HT3 receptors, while also blocking a2 adrenergic receptors
117
mirtazapine differs in its anti depressant response because it blocks __&__ instead of activating _______.
blocks 5HT2c and 5HT3 instead of activating 5HT1a.
118
how do monoamine receptor antagonists, like mirtazapine, work? (2)
activation of 5HT2c and 5HT3 is actually depressive, so blocking them is anti depressive.
they also block a2 adrenergic receptors on NE and 5HT terminals, increasing the amount of NE and 5HT available for release to synaptic cleft.
119
what non therapeutic receptors do monoamine receptor antagonists also bind to and block, and what is the effect?
histamine h1 receptors, resulting in sedation.
120
MAOI for depression are
no longer preferred
121
how do MAOIs work
irreversibly bind to monoamine oxidase and inhibit it, preventing metabolism/breakdown of NE, 5HT, and DA in the brain.
122
MAOI effectiveness as compared to TCAs and SSRIs/SNRIs
as effective but more hazardous
123
MAOIs will be considered for depression if
a patient is treatment resistant
124
MAOIs are irreversible inhibitors of
MAO A and MAO B
125
MAOI dietary restrictions
need to restrict tyramine
| risk for HTN crisis
126
seizure risk and MAOIs/SSRIs/SNRIs
seizure threshold is lowered
127
adverse effects of MAOIs
CNS stimulation
| orthostatic hypotension
128
if you eat tyramine rich foods on an MAOI
htn crisis
129
why is tyramine so dangerous on an MAOI?
inhibiting MOA in the liver makes tyramine able to enter the systemic circulation. when tyramine hits NE containing terminals in the CNS, it causes a massive dump of NE. this increases sympathetic tone to the point of htn crisis and possibly death.
130
atypical antidepressant example
buproprion
131
MoA of buprioprion
binds to and inhibits NET and DAT, increasing NE and DA signaling.
also functions as a partial agonist of nicotinic Act receptors, underlying its efficacy for smoking cessation.
132
bupropion is a derivative of
amphetiamine
133
most notable adverse effect of buproprion
seizure
134
choosing an antidepressant is based on (6)
```
cost
availability
adverse effects
drug interactions
pt history of response
pt preference
```
135
choosing an anti depressant for an individual with depression who is also having insomnia
choose mirtazapine bc of sedating effects
| avoid SSRI bc of excitatory effects
136
if a patient is depressed and experiencing extreme fatigue, what would be a good choice?
buproprion
137
if a patient is experiencing depression and decrease in libido, which would be 2 better anti depressant choices?
bupropion (atypical)
| mirtazipine (monoamine receptor antagonist)
138
most commonly prescribed first line agent in MDD
SSRI
139
second or third line choices are
TCAs
| MAOIs
140
non pharmacological approaches may be preferred to
MAOIs
141
patient teaching for antidepressants
3-4 week lag time exists between initiation of therapy and measurable therapeutic response
142
if a pt doesn't respond to a given antidepressant after a 12 week trial, what is the reasonable next step?
stopping and switching to another antidepressant, but you have to be mindful of washout periods in this instance
143
if a partial response is observed on an SSRI or SNRI,
other drugs can be added concomitantly
144
what is a typical maintenance treatment phase of antidepressants?
6-12 months
145
when is lifelong treatment advisable? (2)
if a patient has experienced 2-3 separate episodes of major depression
if a patient is chronically depressed
146
why don't we withdraw antidepressants once remission occurs?
because they're still at risk for relapse. the 6-12 month maintenance is recommended. you want to avoid episodes of MD because they get more severe as they come and treatment resistance becomes more likely with each episode.
147
the most safe anti depressants in pregnancy (3)
fluoxetine (SSRI)
citalopram (SSRI)
TCAs
148
antidepressants and breastfeeding
benefits of breastfeeding outweigh the risks of infant antidepressant exposure
149
blackbox warning for antidepressants in children and young adults
increased risk in suicidality
150
patients on antidepressants should be monitored
at least twice a year to assess if the drug is still needed or if the dose needs adjustment
151
withdrawing of antidepressants
needs to be a slow, supervised taper over months or longer to minimize withdrawal symptoms like rebound anxiety/depression
152
early warning signs of relapse and what you should do
insomnia
avoiding social engagement
adjust or restart treatment
153
for those who are treatment resistant, what are non pharm treatment options? (3)
vagus nerve stimulation
ECT
transcranial magnetic stimulation
154
new generation of anti depressants being introduced in clinical practice
NMDA receptor antagonist (ketamine)
155
how does ketamine work?
rapidly increases glutamate levels in the brain by blocking NMDA receptors on gaba terminals.
156
when you block glutamate signaling on a gaba terminal,
you reduce gaba release at the synapse. this increases glutamate signaling at the synapse, resulting in an increase of glutamate and brain neurotrophic signaling. this is all anti depressant.
157
doses of ketamine for anti depression
much lower than doses taken recreationally
158
ketamine's antidepressant effect is
rapid
159
obstacles to using ketamine as an antidepressant
abuse liability
| potential for dissociative effects
160
esketamine
intranasal ketamine
| first FDA approved fast acting antidepressant
161
therapeutic onset of esketamine
hours
162
prescribed doses of esketamine can produce
```
sedation
inattention
dissociation
abuse potential
suicidal behaviors
```
163
to prevent abuse of esketamine, it is only available
at approved treatment centers. it cannot be taken home. patients go 2-3 times a week to get their treatment under supervision.
164
brexanolone
| what is it
new FDA Approved Drug for postpartum depression
allopregnanolone, a neuroactive metabolite of progesterone which typically drops right after delivery (this triggers depression/anxiety for some women). when given as a continuous IV over 60 hours immediately after delivery. goal is to reduce or prevent PPD.
165
adverse effects of brexanolone
```
sedation
headache
dizziness
dry mouth
hot flashes
LOC
```
166
blackbox warning: brexanolone
for LOC
| need to be supervised while on this med
167
drugs used in anxiety disorders (5)
```
SSRI
SNRI
benzodiazepines
buspirone
beta blockers
```
168
types of anxiety disorders (5)
```
GAD
OCD
panic disorder
PTSD
social anxiety disorder
```
169
if acute relief is needed for anxiety, what is the drug of choice and for how long?
benzodiazepine
| 2-4 weeks
170
if adequate acute response is not achieved in 2-4 weeks of benzodiazepine for anxiety, what will you try next?
SSRI or SNRI
171
if SNRI or SSRI doesn't provide an adequate for anxiety,
switch to another SSRI/SNRI
| or switch to a different agent
172
benzodiazepines bind to
gaba-A receptors
173
benzos and barbiturates both
bind to and potentiate the effects of gaba
174
if your benzodiazepine expresses an alpha 1 unit,
sedation
175
if your benzodiazepine expresses an alpha 2 and 3 subunit,
decreased anxiety
176
alpha 1 subunits
sedation
177
alpha 2 and alpha 3 subunits
decrease anxiety
178
other general effects from benzos (3)
anti convulsant activity
hypnosis
anterograde amnesia
179
advantages of benzos for treating anxiety. (3)
rapid action
high therapeutic index
little or no induction of liver enzymes, so lower risk for drug interactions in terms of phase I metabolism
180
disadvantages of benzos (4)
impairment of psychomotor performance
amnesia
dependence/withdrawal after long term treatment
rebound anxiety after short term treatment
181
what to worry about after long term treatment of benzos
dependence
| withdrawal
182
what to worry about after short term benzo treatment
rebound anxiety
183
pharmacokinetic considerations of benzos
long half lives
| metabolites with long half lives
184
desmethyldiazepam
active metabolite of multiple benzos which has a very long half life. It then is metabolized to oxazepam, which is also active.
185
complicated metabolism of benzos
some have active metabolites who then have their own active metabolites. there are potentially many different wash out periods that we need to be aware of.
186
if hepatic function is compromised in a patient who needs benzos
you'd want to select a benzo that only undergoes phase II metabolism. ie: lorazepam
187
buspirone vs benzo
reduces symptoms of anxiety less effectively than benzos but has no risk of dependence
188
MoA buspirone (2)
mysterious
likely blocks 5HT1a autoreceptors, increasing 5HT signaling in the brain
stimulates 5HT1a post synaptic receptors as a partial agonist
189
Buspirone can be used as an adjunct
to SSRI/SNRIs if they've experienced only partial response. Its MoA allows an anti depressant effect as well.
190
buspirone duration of onset
longer than benzos
| similar to SSRIs
