Exam 5 (final) - Watts Antidepressants

Question 1

brain-derived neurotrophic factor (BDNF) effect on depression (neurotrophic hypothesis)

Answer 1

stress and pain decrease BDNF levels in animals
-has antidepressant activities in animals
-depressed pts have less BDNF
-antidepressant meds increase BDNF
-some drugs cause decreased BDNF levels (glucocorticoids)

Question 2

targets of fluoxetine and trazodone

Answer 2

5HT-2 reuptake receptors

Question 3

targets of desipramine and maprotiline

Answer 3

NE reuptake receptors

Question 4

targets of MAOi

Answer 4

MAO (block conversion to metabolites?)

Question 5

Why is there a delay in clinical effect for some antidepressants?
-reason that therapy takes about 2-3 weeks before effectiveness

Answer 5

reason is not really known for sure

Question 6

mechanism of MAOis

Answer 6

inhibit Monoamine Oxydase in presynaptic neuron
-importance of this is NE and 5HT is normally degraded by MAO
-now more 5HT and NE is released from vesicles into synapse

Question 7

MAO inhibitors “severe” SE

Answer 7

HA
drowsiness
dry mouth
weight gain
orthostatic hypotension
sexual dysfxn

Question 8

MAOi clinical pearls

Answer 8

avoid foods with tyramine (many but some examples are cheeses, sour cream, liver, lots of meats like pepperoni, beer, red wine, avocados, bananas)

Question 9

tricyclic antidepressants (tertiary amines) MOA

Answer 9

inhibit both NE and 5HT reuptake via NET and SERT

Question 10

tricyclic antidepressants (tertiary amines) SE

Answer 10

sedation (most of any class for depression)
weight gain (most of any class for depression)
heart conduction disturbances

Question 11

tricyclic antidepressants (tertiary amines) options

Answer 11

imipramine (Tofranil)
amitriptyline (Elavil)
trimipramine (Surmontil)
clomipramine (Anafranil)
doxepin (Adapin, Sinequan)

Question 12

tricyclic antidepressants (secondary amines) options

Answer 12

desipramine (Norpramin)
nortriptyline (Pamelor)
pretriptyline (Vivactil)
maprotiline (Ludiomil)

Question 13

tricyclic antidepressants (secondary amines) SE

Answer 13

less but still some of:
sedation
weight gain
anticholinergic effects
autonomic effects
cardiovascular effects

Question 14

general all TCA SE

Answer 14

weight gain
anticholinergic effects
neuro
CV (in elderly)

Question 15

SSRIs MOA

Answer 15

inhibit 5HT presynaptic neuron receptors
-increases amount of 5HT in synapse
-5HT in synapse stays there longer and remains active longer

Question 16

SSRIs options

Answer 16

fluoxetine (Prozac)
fluvoxamine (Luvox)
paroxetine (Paxil)
sertraline (Zoloft)
citalopram (Celexa)
escitalopram oxalate (Lexapro)

Question 17

which SSRI has less autonomic SE and no sedation compared to other SSRIs

Answer 17

fluoxetine

Question 18

SSRI SE

Answer 18

NV
HA
sexual dysfxn
anxiety
insomnia
tremor

Question 19

abrupt SSRI d/c can lead to

Answer 19

withdrawal sx:
brain zaps
dizziness
sweating
N
insomnia
tremor
confusion
vertigo

Question 20

drugs when used in combo may cause serotonin syndrome

Answer 20

SSRIs
MAOis
TCAs
metoclopramide
tramadol
triptans
St. John’s Wort

Question 21

SSRI + 5HT1A partial agonists options

Answer 21

vilazodone (Viibryd)
vortioxetine (Brintellex)

Question 22

tetracyclic TCA

Answer 22

mirtazapine (Remeron)
-alpha2 antagonist
-5HT2 and 3 antagonist
-H1 antagonist

Question 23

unicyclic TCA

Answer 23

bupropion (Wellbutrin)
-DAT inhibitor
-NET and SERT inhibitor

Question 24

5HT2 antagonist/SERT inhibitor

Answer 24

trazodone (Dyserel)
-5HT2a antagonist
-weak SERT inhibitor

Question 25

SNRIs options

Answer 25

venlafaxine (Effexor) desvenlafaxine (Pristiq) duloxetine (Cymbalta) milnacipran (Ixel) levomilnacipran (Fetzima) reboxetine (Vestra, Edronax) atomoxetine (Straterra)

Question 26

more rapid acting antidepressants include what class

Answer 26

NMDA antagonists

Question 27

NMDA antagonists options

Answer 27

ketamine (subanesthetic doses) eskatamine (expensive)

Question 28

tx for postpartum depression (PPD)

Answer 28

SSRIs: fluoxetine, paroxetine SNRIs: venlafaxine GABA-A modulators: brexanolone (Zulresso) CBT

Question 29

brexanolone (Zulresso) MOA

Answer 29

-allopregnanolone levels increase during pregnancy -GABA-A receptors become desensitized -allopregnanolone levels return to normal postpartum -brexanolone resensitizes GABA-A receptors

Question 30

brexanolone (Zulresso) clinical pearls

Answer 30

REMS drug 60hr infusion $20,000-30,000 + hospital costs

Question 31

flibanserin (Addyi)

Answer 31

-developed as antidepressant but now use for hypoactive sexual desire disorder -agonist at 5HT1A -antagonist at 5HT2A/C

Question 32

how does reserpine cause depression ("biogenic amine" hypothesis)

Answer 32

depletes NE and 5HT from vesicles

Question 33

describe 3 steps of neuroendocrine hypothesis

Answer 33

changes in hypothalamic-pituitary-adrenal (HPA) axis -stress causes hypothalamus to release corticotropin releasing factor (CRF) -CRF promotes release of ACTH from pituitary -ACTH promotes release of cortisol from adrenal *just know elevated CRF causes depression*

Question 34

CRF acts on CRF1 receptors to cause:

Answer 34

arousal anxiety disruption of sexual behaviors disruption of sleep