Antidepressants Flashcards
Which 1 class of antidepressants directly targets enzymes?
What enzymes, and what is their normal role in neurotransmission?
- MAOIs
- MAO A / B, deaminating (inactivating) monoamines
Which form MAO is also found in the gut, and what does it do there?
MAO-A, breaks down monoamines, mainly tyramine
What effect do the MAOIs have on enzyme function, and are they mostly reversible/irreversible?
inhibit, irreversible
Which 1 drug in this class is selective for MAO-B?
seligiline
What 3 neurotransmitters are affected by MAOIs, and do the drugs increase or decrease neurotransmission?
5-HT, NE, DA
increase neurotransmission
Which 3 classes of antidepressants work mainly by directly targeting monoamine reuptake transporters?
TCAs
SSRIs
SNRIs
What 3 transporters affected by TCAs, SSRIs, SNRIs and what is their normal role in neurotransmission
NET, DAT, SERT; Terminate activity of monoamines in the synapse by pumping MA from synapse back into presynaptic cell
Antidepressants have higher affinity for which 2 reuptake transporters
NET and SERT
Which 1 class selectively targets SERT, and which 2 target both SERT and NET?
SSRIs
TCAs and SNRIs
What is the effect of the antidepressants on these transporters, and does this increase or decrease monoaminergic neurotransmission?
Inhibit reuptake, increases neurotransmission
Which 1 class of antidepressants works mainly by directly targeting receptors and does it have some ability to inhibit SERT/NET?
5-HT2R antagonists
YES
What 1 class is most likely to be involved in food-drug interactions and what is the dietary element and enzyme involved?
MOAIs; tyramine; MAO-A, inhibited by MAOIs, stops breaking down tyramine
What is the mechanism underlying hypertensive crisis?
Excess tyramine displaces NE from storage sites, NE flood over-activates adrenergic receptors
Which 1 class has a narrow therapeutic index, and which 1 class has a wide (high) therapeutic index?
Lowest = TCAs, highest = SSRIs
Which 1 class can be cardiotoxic?
TCAs
Which 1 class has the highest rate of off-target receptor binding at muscarinic, histamine, adrenergic receptors, and which 1 class has the lowest rate of off-target receptor binding?
Highest = TCAs, lowest = SSRIs
What side effects are associated with off-target binding at histamine H1 receptors?
sedation, somnolence, weight gain
What side effects are associated with off-target binding muscarinic ACh receptors?
Dry mouth, constipation, dizziness, tachycardia, urinary retention, confusion
What side effect is associated with off-target binding at adrenergic α1 receptors?
Orthostatic hypotension
What 3 types of adverse effects are caused by excess serotonergic neurotransmission?
Serotonin syndrome, impaired sexual function, nausea/GI upset
Which 1 of these 3 adverse effects can be potentially fatal (may involve hyperthermia, hypertension, diarrhea, mydriasis, agitation and coma), and why is the risk especially problematic with MAOIs?
For the two remaining adverse effects that are not fatal, which class is most prone to producing those effects?
Which 1 class of antidepressants is least likely to cause any of these 3 effects, and why?
- Serotonin syndrome, MAOIs are irreversible- need to make new MAO enzymes to regain function
- SSRIs
- Tetracyclics / unicyclics, because they have essentially no direct effects on 5-HT
What types of side effects are related to excess noradrenergic neurotransmission?
Increased BP, HR, insomnia, anxiety, agitation
Which 1 drug can produce both fatal hepatotoxicity and priapism?
Nefazodone
Which 1 drug is a potent CYP3A4 inhibitor?
Nefazodone
Which 2 drugs produce significant sedation/hypnosis?
Trazodone, mirtazapine
Which 2 classes are usually reserved only for depression that does not respond to other drugs- and is this because of lower efficacy, or lower safety/tolerability?
MAOIs, 5HT2R antagonists; lower safety/tolerability
Is the overall efficacy of antidepressants better when used alone, or with psychotherapy?
with psychotherapy
How long should patients expect to wait for antidepressant effects to develop after beginning treatment- hours, days, several weeks - why?
Weeks (1-2 months) therapeutic effects likely come from chronic compensatory changes
Are antidepressants helpful for more than half of patients, or less than half?
more
Should a patient expect that the first drug they try will be effective, or is it a trial-and-error process?
trial and error
As patients try several drugs that are unsuccessful, do odds of success increase or decrease?
decrease
Is it possible for an antidepressant to stop working after a patient has been taking it for years?
yes
Which 2 classes of antidepressants are commonly used for treating many types of anxiety disorders?
SSRI and SNRI
What 2 classes of non-antidepressant drugs are also currently used for treating anxiety?
Benzodiazepines, B-adrenergic antagonists
Why are antidepressants preferred for long-term use?
Less risk of dependence, no hypotension
Does anti-anxiety effect develop right away, or slowly?
slowly
