Antidepressants Flashcards
What are the core elements of depression (MDD)
emotional, behavioral, cognitive
emotional elements of MDD
sadness, anhedonia, lack of motivation,
behavioral elements of MDD
anergia, psychomotor slowing
cognitive elements of MDD
helplessness, distortions (maladaptive thoughts)
monoamine theory for MDD
result of below-normal levels of DA, NE, and 5-HT
Key to treating depression
restore monoamine levels
what causes monoamine depletion
reserpine
antidepressants pharmacodynamic effect
boosting monoamine levels
MDD is a
neurohormonal disorder
MDD frequently appears in the aftermath of events (loss and failure), which are experienced as
uncontrollably stressful
uncontrollably stressful events are associated with
excessive output of the hormone cortisol
The tendency to interpret loss/failure events as uncontrollably stressful probably lies in
pre-existing ways of processing information
Dexamethasone suppression test in non-depressed people
DXM suppresses release of cortisol for about 24 hours, and then cortisol slowly comes back to its relatively low levels
Dexamethasone suppression test in depressed people
DXM suppresses release of cortisol for just a few hours, and then cortisol bounces back to its relatively high levels
HPAC system during stress (CNS stress system)
hypothalamus activates pituitary gland with CRH, pituitary gland activates adrenal cortex with ACTH, adrenal cortex activates cortisol release, cortisol activates hippocampus, hippocampus stops hypothalamus
what does the hypothalamus also do in the HPAC system during stress
stops CNS positive motivation system (BAS)
what is CRH
corticotropin releasing hormone
what is ACTH
adrenocorticotropic hormone
what does the hippocampus do in the HPAC system during stress specifically
sends signal to hypothalamus to stop cortisol release
when the HPAC system is activated, what happens to the brains positive motivation system (BAS)?
decreases in activity
where are the adrenal glands located
kidneys
behavioral activation system (reward based system)
BAS
what do high levels of cortisol do to the hippocampus
kill it
what happens in HPAC dysregulation
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
first true antidepressant medications
MAOIs: Marplan (isocarboxazid), Nardil (phenelzine), Parnate (tranylcypromine), MAO-B only: Emsam transdermal patch (selegiline, deprenyl)
T1/2 elimination of MAOIs
a couple of hours
nonselective inhibitors of both MAO-A and MAO-B
reduce breakdown of DA, NE, and 5-HT, do NOT have adverse effects on ACh activity
issues of MAOI antidepressants
-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
cheese syndrome
tyramine, found in food and beverages gone under fermentation can be fatal in people taking MAOI antidepressants
why can taking an MAO-A inhibiter lead to cheese syndrome
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
what would be preferable instead of an MAO-A inhibitor to reduce risk of cheese syndrome
A RIMA (reversible inhibitor of MAO-A), doesn’t bind permanently
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
Aurorix (moclobemide), a better RIMA
the second type of ADM
tricyclic antidepressants (TCAs)
Good absorption after PO admin, blood levels peak after ~60 minutes
Tricyclic antidepressants (TCAs)
TCA T1/2
around 24 hours, daily usage
main mechanism of TCA
reuptake blockade of NE and 5-HT
TCAs have what kind of side effects
anti-cholinergic, blocks Ach activity
