Antidepressants

Question 1

Which 1 class of antidepressants directly targets enzymes?
What enzymes, and what is their normal role in neurotransmission?

Answer 1

1. MAOIs
2. MAO A / B, deaminating (inactivating) monoamines

Question 2

Which form MAO is also found in the gut, and what does it do there?

Answer 2

MAO-A, breaks down monoamines, mainly tyramine

Question 3

What effect do the MAOIs have on enzyme function, and are they mostly reversible/irreversible?

Answer 3

inhibit, irreversible

Question 4

Which 1 drug in this class is selective for MAO-B?

Answer 4

seligiline

Question 5

What 3 neurotransmitters are affected by MAOIs, and do the drugs increase or decrease neurotransmission?

Answer 5

5-HT, NE, DA
increase neurotransmission

Question 6

Which 3 classes of antidepressants work mainly by directly targeting monoamine reuptake transporters?

Answer 6

TCAs
SSRIs
SNRIs

Question 7

What 3 transporters affected by TCAs, SSRIs, SNRIs and what is their normal role in neurotransmission

Answer 7

NET, DAT, SERT; Terminate activity of monoamines in the synapse by pumping MA from synapse back into presynaptic cell

Question 8

Antidepressants have higher affinity for which 2 reuptake transporters

Answer 8

NET and SERT

Question 9

Which 1 class selectively targets SERT, and which 2 target both SERT and NET?

Answer 9

SSRIs
TCAs and SNRIs

Question 10

What is the effect of the antidepressants on these transporters, and does this increase or decrease monoaminergic neurotransmission?

Answer 10

Inhibit reuptake, increases neurotransmission

Question 11

Which 1 class of antidepressants works mainly by directly targeting receptors and does it have some ability to inhibit SERT/NET?

Answer 11

5-HT2R antagonists
YES

Question 12

What 1 class is most likely to be involved in food-drug interactions and what is the dietary element and enzyme involved?

Answer 12

MOAIs; tyramine; MAO-A, inhibited by MAOIs, stops breaking down tyramine

Question 13

What is the mechanism underlying hypertensive crisis?

Answer 13

Excess tyramine displaces NE from storage sites, NE flood over-activates adrenergic receptors

Question 14

Which 1 class has a narrow therapeutic index, and which 1 class has a wide (high) therapeutic index?

Answer 14

Lowest = TCAs, highest = SSRIs

Question 15

Which 1 class can be cardiotoxic?

Answer 15

TCAs

Question 16

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?

Answer 16

Highest = TCAs, lowest = SSRIs

Question 17

What side effects are associated with off-target binding at histamine H1 receptors?

Answer 17

sedation, somnolence, weight gain

Question 18

What side effects are associated with off-target binding muscarinic ACh receptors?

Answer 18

Dry mouth, constipation, dizziness, tachycardia, urinary retention, confusion

Question 19

What side effect is associated with off-target binding at adrenergic α1 receptors?

Answer 19

Orthostatic hypotension

Question 20

What 3 types of adverse effects are caused by excess serotonergic neurotransmission?

Answer 20

Serotonin syndrome, impaired sexual function, nausea/GI upset

Question 21

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?

Answer 21

1. Serotonin syndrome, MAOIs are irreversible- need to make new MAO enzymes to regain function
2. SSRIs
3. Tetracyclics / unicyclics, because they have essentially no direct effects on 5-HT

Question 22

What types of side effects are related to excess noradrenergic neurotransmission?

Answer 22

Increased BP, HR, insomnia, anxiety, agitation

Question 23

Which 1 drug can produce both fatal hepatotoxicity and priapism?

Answer 23

Nefazodone

Question 24

Which 1 drug is a potent CYP3A4 inhibitor?

Answer 24

Nefazodone

Question 25

Which 2 drugs produce significant sedation/hypnosis?

Answer 25

Trazodone, mirtazapine

Question 26

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?

Answer 26

MAOIs, 5HT2R antagonists; lower safety/tolerability

Question 27

Is the overall efficacy of antidepressants better when used alone, or with psychotherapy?

Answer 27

with psychotherapy

Question 28

How long should patients expect to wait for antidepressant effects to develop after beginning treatment- hours, days, several weeks - why?

Answer 28

Weeks (1-2 months) therapeutic effects likely come from chronic compensatory changes

Question 29

Are antidepressants helpful for more than half of patients, or less than half?

Answer 29

more

Question 30

Should a patient expect that the first drug they try will be effective, or is it a trial-and-error process?

Answer 30

trial and error

Question 31

As patients try several drugs that are unsuccessful, do odds of success increase or decrease?

Answer 31

decrease

Question 32

Is it possible for an antidepressant to stop working after a patient has been taking it for years?

Answer 32

yes

Question 33

Which 2 classes of antidepressants are commonly used for treating many types of anxiety disorders?

Answer 33

SSRI and SNRI

Question 34

What 2 classes of non-antidepressant drugs are also currently used for treating anxiety?

Answer 34

Benzodiazepines, B-adrenergic antagonists

Question 35

Why are antidepressants preferred for long-term use?

Answer 35

Less risk of dependence, no hypotension

Question 36

Does anti-anxiety effect develop right away, or slowly?

Answer 36

slowly