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Psychopharmacology > Chapter 7: treating mood disorders > Flashcards

Chapter 7: treating mood disorders Flashcards

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1
Q

what is classified as a “response”

A

at least 50% reduction in symptoms

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2
Q

what are the 6 SSRIs

A

fluoxetine (Prozac)
Sertraline (Zoloft)
Paroxetine (Paxil)
Fluvoxamine (Luvox)
citalopram (Celexa)
escitalopram (Lexapro)

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3
Q

what is the SPARI used in clinical practice

A

Vilazodone (Viibryd)

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4
Q

what does SPARI stand for

A

serotonin partial agonist reuptake inhibitor

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5
Q

what are the 5 SNRIs

A

venlafaxine (Effexor)
desvenlafaxine (Pristiq)
duloxetine (Cymbalta)
milnacipran (Toledomen)
levomilnacipran (Fetzima)

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6
Q

what does NDRI stand-for and what is the NDRI used in clinical practice

A

Norepinephrine-dopamine reuptake inhibitor
Buproprion (Wellbutrin)

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7
Q

what is agomelatine (Valdoxen) used for

A

exerts antidepressant effect by correcting circadian rhythm by acting as a substitute melatonin

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8
Q

mechanism of action for agomelatine (Valdoxen)

A

agonist at melatonin 1 (MT1) and 2 (MT2)
antagonist at 5HT2C

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9
Q

4 principle mechanisms of action for mirtazapine

A

antagonism of 5HT2A, 5HT2C, a2-adrenergic, H1 receptors

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10
Q

what does SARI stand for and what are the SARIs used in clinical practice

A

serotonin antagonist reuptake inhibitors
nefazodone (Dutonin)
trazadone (Deseryl)

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11
Q

5 mechanisms of action for vortioxetine

A

inhibits SERT
antagonist ar 5HT3 and 5HT7
agonist at 5HT1A
weak partial agonism at 5HT1B/1D

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12
Q

name of the neuroactive steroid used in clinical practice

A

brexanolone

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13
Q

drugs most often used as augmentation agents in treatment-resistant unipolar depression

A

olanzapine/fluoxetine combo
quetiapine (seroquel)
aripiprazole (abilify)
brexpiprazole (rexulti)
cariprazine (Vraylar)

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14
Q

second line monotherapies for treatment-resistant depression

A

tricyclics
MAOIs

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15
Q

what is 1st line treatment for bipolar disorder

A

serotonin/dopamine blocker rather than monoamine inhibitor

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16
Q

drugs typically prescribed as 1st line treatment for bipolar disorder

A

olanzapine-fluoxetine combo
quetiapine (seroquel)
lurasidone (Latuda)
cariprazine (Vraylar)

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17
Q

what is the “classic” mood stabilizer

A

Lithium

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18
Q

how are anticonvulsants categorized as mood stabilizers

A

“mania minded” (tx/stabilize from above)
“depression minded” tx/stabilize from below

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19
Q

anticonvulsants proven effective in bipolar disorder

A

valproic acid (Depakote)
carbamazepine (Tegretol)
lamotrigine (Lamictal)

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20
Q

is monotherapy or combination therapy the standard for treating bipolar disorder

A

combination therapy

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21
Q

what % of SERTs need to be occupied to achieve antidepressant effect with SSRIs

A

80-90%

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22
Q

how do SSRIs work in general (common to all 6)

A

serotonin levels rise d/t SERT blockade.
There is an immediate increase of serotonin in the somatodendritic area which causes stimulation of 5HT1A autoreceptors. 5HT1A receptors downregulate (desensitized) after prolonged exposure to increased 5HT levels (correlates with time to therapeutic effect). Once autoreceptors are desensitized the neuron is disinhibited and releases 5HT at the axon terminal. Eventually, postsynaptic 5HT receptors desensitize which reduces side effects as tolerance develops

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23
Q

what is the only SSRI approved for treatment of eating disorders

A

fluoxetine (Prozac)

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24
Q

what is the mechanism of action of fluoxetine (Prozac) other than SERT inhibition

A

5HT2C antagonism

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25
what neurotransmitters are increased by 5HT and 5HT2C antagonism
norepinephrine and dopamine
26
is 5HT2C antagonism generally activating or sedating
activating (energizing for increased concentration/attention)
27
half-life and available dosing options for fluoxetine
2-3 days once daily or once weekly (active metabolite has a half-life of 2-3 weeks
28
binding profile of sertraline (Zoloft)
SERT inhibition with weaker DAT inhibition and σ1binding
29
binding porperties of stimulants like cocaine and meth
high-impact DAT inhibition
30
"well-oft"
adds weak DAT inhibition of wellbutrin and zoloft together
31
binding profile of paroxetine
NET and muscarinic inhibition and enzyme nitric oxide synthase
32
withdrawal rxns for paroxetine (Paxil)
akathisia, restlessness, GI symptoms, dizziness, tingling
33
binding properties of fluvoxemine (Luvox)
5HT inhibition and σ1binding properties (agonist)
34
what is Fluvoxamine approved for
OCD, not depression
35
available dosing options for fluvoxemine
IR (BID) ER (QD)
36
one of the better tolerated SSRIs that are favorable for the elderly
Citalopram (Celexa)
37
enantiomers of citalopram
S and R
38
function of R enantiomer in citalopram
mild antihistaminic properties activity may interfere with S enantiomer's ability to inhibit SERT
39
whats important to remember about dosing citalopram
high doses can cause QTc prolongation
40
advantages of escitalopram over citalopram
only contains S enantiomer no high dose restriction removes antihistaminic properties
41
BEST tolerated SSRI
escitalopram
42
drugs typically used to augment SSRIs/SNRIs to add 5HT1A partial agonism
buspirone aripiprazole/brexpiprazole/cariprazine quetiapine
43
SPARI binding of buspirone
5HT1A partial agonist
44
SPARI binding profile of aripiprazole, brexpiprazole, cariprazine
5HT1A/D2 partial agonist
45
SPARI binding profile of quetiapine
5HT/D2 antagonist w/ 5HT1A partial agonist properties
46
how does wellbutrin work
occupation of SERT and 5HT1A receptors increase 5HT in somatodendritic area. This causes 5HT1A autoreceptors to downregulate/desensitize after prolonged exposure to increased levels of 5HT. downregulated autoreceptors to increased neuronal firing and 5HT release at axon terminal
47
48
binding profile of vilazodone
SERT inhibition with 5HT1A partial agonism
49
what is an advantage of SNRIs over SSRIs
ability to treat pain
50
where do SNRIs increase dopamine levels and how do they do it
in the PFC NET inhibition increases the diffusion radius of NET. There are not very many DATs in the PFC so dopamine uses NET for reuptake. When NET is inhibited it increases dopamine levels in PFC
51
which SNRI is approved for fibromyalgia but not depression
milnacipran
52
which enzyme converts venlafaxine to its active metabolite desvenlafaxine
2D6
53
Is venlafaxine more potent for SERT or NET
SERT. Dose-dependent NET inhibition
54
which enzyme is desvenlafaxine a substrate for
2D6
55
Is desvenlafaxine more potent for SERT or NET
SERT
56
Is duloxetine more potent for SERT or NET
SERT (slightly)
57
Should duloxetine be dosed daily or BID
BID at first then transition to daily once patient is tolerant of dose
58
which of mirtazapine's mechanisms of action increases the downstream release of dopamine in the PFC
antagonism of 5HT2A also improves sleep
59
what is the result of mirtazapine's 5HT2C antagonism
enhanced release of norepinephrine and dopamine
60
what is the MAIN mechanism of action for mirtazapine
a2-adrenergic antagonism
61
how does mirtazapine's a-2 adrenergic antagonism work
a2 are norepinephrine auto receptors so when they are blocked, norepinephrine can't shut itself off and release is increased
62
which SNRI is approved for fibromyalgia but not depression
milnacipran
63
which of mirtazapine's mechanisms of action enhances the release of norepinephrine and dopamine in the PFC
antagonism of 5HT2C
64
what is the main mechanism of action of mirtazapine
antagonism of a2 adrenergic receptors this makes it so norepinephrine cannot turn itself off at its autoreceptors on noradrenergic neurons
65
where are 5HT3 receptors usually located
on GABA interneurons
66
how doe 5HT3 antagonist action work
when serotonin stimulates it it causes GABA to inhibit whatever neuron is downstream from it
67
Is 5HT3 antagonism activating or sedating
always activating
68
mechanism of action for nefazadone
5HT2A antagonism (robust) 5HT2C antagonism (weaker) SERT inhibition
69
why is nefazadone not really used anymore
liver toxicity
70
what is the difference between high and low doses of trazodone
hypnotic at low doses (5HT2A blockade), antidepressant at higher doses
71
Is 5HT2A action generally activating or sedating
sedating
72
Mechanism of action of vortioxetine
SERT inhibition 5HT3 and 5HT7 antagonism 5HT1A antagonism
73
cognitive domains treated by vortioxetine
attention executive function memory processing speed
74
what happens with SERT inhibition and 5HT1B/D (vortioxetine)
5HT1B/D autoreceptors typically turn off 5HT, when they are not inhibited it increases 5HT more than just SERT inhibition alone
75
SERT inhibition and 5HT3 antagonism (vortioxetine)
Removes GABAs inhibition of dopamine and acetylcholine neurons causing increased neurotransmitter release
76
SERT inhibition and 5HT7 antagonism
Prevents GABA from inhibiting downstream neurotransmitters resulting in increased serotonin in the PFC
77
what does brexanolone typically treat
postpartum depression (60-hour continuous infusion)
78
what are the typical augmenting agents for treatment-resistant unipolar depression
olanzapine-fluoxetine combo quetiapine aripiprazole brexpiprazole cariprazine
79
What binding property of brexpiprazole contributes to efficacy for agitation in dementia
a1 antagonism
80
How does brexpiprazole enhance dopamine release in the PFC
simultaneous a1 and 5HT2A blockade (antagonism)
81
what is California rocket fuel
NRI with mirtazapine
82
how does California rocket fuel work
blocks serotonin/norepinephrine reuptake disinhibits serotonin and norepinephrine release
83
How do you achieve triple monoamine action with an attention to dopamine
stimulant/modafinil (DAT inhibitor) with SNRI
84
2nd line therapy for treatment-resistant depression
TCAs MAOIs
85
Lethal dose of a TCA
1 month supply
86
TCAs are very effective for depression. What is their downfall
side effects
87
what are TCA side effects caused by
blockade of: muscarinic cholinergic receptors H1 histamine receptors a1 adrenergic receptors VSSCs
88
Class of medication for MAOIs
irreversible enzyme inhibitors enzyme activity only returns when another one is synthesized in 2-3 weeks
89
MAOA
enzyme that preferentially metabolizes monoamines associated with depression (5HT/NE)
90
MAOI and tyramine
may develop HTN crisis after ingesting tyramine (especially cheese) since tyramine causes NE release that is destroyed by MAOA. When that is inhibited NE is not destroyed and BP rises
91
5HT/DA blockers used for bipolar
olanzapine-fluoxetine combo quetiapine lurasidone cariprazine
92
1st line treatment for bipolar
5HT/DA blocker
93
what is olanzapine-fluoxetine combo approved for
schizophrenia bipolar mania treatment-resistant unipolar depression bipolar depression
94
how does olanzapine-fluoxetine combo work in bipolar
antagonism of 5HT2A/5HT2C responsible for antidepressant action D2 antagonism keeps antidepression from spilling over into mania
95
what is quetiapine approved for
schizophrenia bipolar mania bipolar depression augmenting SSRI/SNRI for tx-resistant depression
96
how does quetiapine work in bipolar
antagonist at 5HT2A. 5HT2C, and a2 agonism at 5HT1A D2 antagonism keeps it from spilling over into mania
97
what is Lurasidone NOT approved for
bipolar mania
98
what med is most often prescribed for bipolar depression
lurasidone
99
what is cariprazine approved for
bipolar mania and depression
100
what receptors does cariprazine work at
partial agonist at D3, D2, 5HT1A
101
what sets cariprazine apart from other D2/5HT blockers used for bipolar
highly potent action at D3 as a partial agonist
102
how potent is cariprazine's action at D3
more potent than dopamine itself
103
anticonvulsants used in bipolar disorder
valproic acid (depakote) carbamazepine (tegretol) lamotrigine (Lamictal)
104
what are the three hypotheses for valproic acid's mechanism of action
-inhibits VSSCs boost action of neurotransmitter GABA -regulating downstream signal transduction cascades
105
typical side effects of valproic acid
hair loss, weight gain, sedation, metabolic disturbance, tremor
106
what warnings does valproic acid have
bone marrow suppression, liver, pancreatic, and fetal toxicities
107
what risks does valproic acid pose to women of childbearing age
amenorrhea, polycystic ovaries, hyperandrogenism, obesity, insulin-resistance
108
what tests should you order when starting valproic acid
pregnancy test, LFTs, platelet count
109
What enzyme is induced by carbamazepine
3A4
110
What additional indication is carbamazepine useful for
neuropathic pain

Psychopharmacology (13 decks)

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