Antidepressants

Question 1

What are the core elements of depression (MDD)

Answer 1

emotional, behavioral, cognitive

Question 2

emotional elements of MDD

Answer 2

sadness, anhedonia, lack of motivation,

Question 3

behavioral elements of MDD

Answer 3

anergia, psychomotor slowing

Question 4

cognitive elements of MDD

Answer 4

helplessness, distortions (maladaptive thoughts)

Question 5

monoamine theory for MDD

Answer 5

result of below-normal levels of DA, NE, and 5-HT

Question 6

Key to treating depression

Answer 6

restore monoamine levels

Question 7

what causes monoamine depletion

Answer 7

reserpine

Question 8

antidepressants pharmacodynamic effect

Answer 8

boosting monoamine levels

Question 9

MDD is a

Answer 9

neurohormonal disorder

Question 10

MDD frequently appears in the aftermath of events (loss and failure), which are experienced as

Answer 10

uncontrollably stressful

Question 11

uncontrollably stressful events are associated with

Answer 11

excessive output of the hormone cortisol

Question 12

The tendency to interpret loss/failure events as uncontrollably stressful probably lies in

Answer 12

pre-existing ways of processing information

Question 13

Dexamethasone suppression test in non-depressed people

Answer 13

DXM suppresses release of cortisol for about 24 hours, and then cortisol slowly comes back to its relatively low levels

Question 14

Dexamethasone suppression test in depressed people

Answer 14

DXM suppresses release of cortisol for just a few hours, and then cortisol bounces back to its relatively high levels

Question 15

HPAC system during stress (CNS stress system)

Answer 15

hypothalamus activates pituitary gland with CRH, pituitary gland activates adrenal cortex with ACTH, adrenal cortex activates cortisol release, cortisol activates hippocampus, hippocampus stops hypothalamus

Question 16

what does the hypothalamus also do in the HPAC system during stress

Answer 16

stops CNS positive motivation system (BAS)

Question 17

what is CRH

Answer 17

corticotropin releasing hormone

Question 18

what is ACTH

Answer 18

adrenocorticotropic hormone

Question 19

what does the hippocampus do in the HPAC system during stress specifically

Answer 19

sends signal to hypothalamus to stop cortisol release

Question 20

when the HPAC system is activated, what happens to the brains positive motivation system (BAS)?

Answer 20

decreases in activity

Question 21

where are the adrenal glands located

Answer 21

kidneys

Question 22

behavioral activation system (reward based system)

Answer 22

BAS

Question 23

what do high levels of cortisol do to the hippocampus

Answer 23

kill it

Question 24

what happens in HPAC dysregulation

Answer 24

excess levels of cortisol are released causing the hippocampus to deteriorate, leading to the hippocampus no longer being able to tell the hypothalamus to stop producing cortisol

Question 25

first true antidepressant medications

Answer 25

MAOIs: Marplan (isocarboxazid), Nardil (phenelzine), Parnate (tranylcypromine), MAO-B only: Emsam transdermal patch (selegiline, deprenyl)

Question 26

T1/2 elimination of MAOIs

Answer 26

a couple of hours

Question 27

nonselective inhibitors of both MAO-A and MAO-B

Answer 27

reduce breakdown of DA, NE, and 5-HT, do NOT have adverse effects on ACh activity

Question 28

issues of MAOI antidepressants

Answer 28

-Excess DA levels can precipitate psychotic symptoms and agitation -MAOIs bind to MAO and block its activity permanently = drug effect lasts even after discontinuation, until new MAO is synthesized (1-2 weeks) -Cheese syndrome

Question 29

cheese syndrome

Answer 29

tyramine, found in food and beverages gone under fermentation can be fatal in people taking MAOI antidepressants

Question 30

why can taking an MAO-A inhibiter lead to cheese syndrome

Answer 30

MAO-A in the gut breaks down tyramine, when taking an MAO-A inhibitor, tyramine has sympathetic effects (mimics sympathetic nervous system, fight/flight), which increases heart rate and blood pressure, and can trigger hypertensive crisis which can be fatal

Question 31

what would be preferable instead of an MAO-A inhibitor to reduce risk of cheese syndrome

Answer 31

A RIMA (reversible inhibitor of MAO-A), doesn't bind permanently

Question 32

what RIMA is available worldwide except in USA because it would have to go through FDA approval process, and no one will make money off of it

Answer 32

Aurorix (moclobemide), a better RIMA

Question 33

the second type of ADM

Answer 33

tricyclic antidepressants (TCAs)

Question 34

Good absorption after PO admin, blood levels peak after ~60 minutes

Answer 34

Tricyclic antidepressants (TCAs)

Question 35

TCA T1/2

Answer 35

around 24 hours, daily usage

Question 36

main mechanism of TCA

Answer 36

reuptake blockade of NE and 5-HT

Question 37

TCAs have what kind of side effects

Answer 37

anti-cholinergic, blocks Ach activity