General Anti-depressants Class

Question 1

What are some of the general ways anti depressants work?

Answer 1

Block NE or Serotonin (5-HT) reuptake to potentiate their effects, or inhibit monoamine oxidase (MAO) which would enhance neurotransmitter storage in vesicles.

Question 2

What is the job of MAO’s?

Answer 2

It degrades the monoamines, Nor-Epi, dopamine and serotonin.

Question 3

Explain the “Therapeutic Lag” associated with anti-depressants

Answer 3

It takes 3-4 weeks to have a Tx effect kick in, depending.

Question 4

What are the Serotonin and the Nor-Epi re-uptake transporters called?

Answer 4

SERT and NET (simply serotonin and nor-epi transporters)

Question 5

What are the inhibitory serotonin receptors? What’s their physiologic function?

Answer 5

5-HTR 1 subtypes, which are Gi receptors, they will inhibit the release of the serotonin from the nerve terminals.

Question 6

What else besides serotonin receptors can inhibit serotonin release?

Answer 6

Alpha 2 adrenergic receptor, which will serve the same function as the 5-HTR 1 receptors, which is to inhibit.

Question 7

General chemical feature of all anti-depressants?

Answer 7

Lipophilic, due to the need to cross the BBB. Also all oral.

Question 8

How are all the anti-depressants metabolized? Cleared?

Answer 8

Via CYP metabolism in liver, mainly 2D6, 3A family and 2C family. Renally cleared.

Question 9

What’s special about CYP2D6 and 2C19, in general?

Answer 9

Basically different people have different kinds of these enzymes due to genetic activity, some of them are more active than others, and lead to toxicity.

Question 10

What is the advantage of blocking MAO’s besides degrading the monoamines?

Answer 10

Since the monoamines will not be degraded we will be increasing their storage within the vesicles, there will be a build up of these transmitters (they aren’t degraded and its being synthesized at its normal rate) so that they can be secreted out again but this time in higher numbers than normal.

Question 11

Which anti-depressant is the most effacacious?

Answer 11

They are all similarly effective, but have different tox, price, etc etc.

Question 12

Which drug in this anti-depressant “class” is used for smoking cessation and what is its benefit?

Answer 12

Buproprion, its efficacy is debatable but it doesn’t induce weight gain and less mood swings from nicotine withdrawal.

Question 13

What are the side effects of stimulating the 5-HT2 excessively? Which is the big one?

Answer 13

Insomnia, anxiety, irritability, the big one is decreased libido and sexual dysfunction.

Question 14

AE of 5-HT3 excess stimulation?

Answer 14

CNS and periphery problems, GI effects.

Question 15

What is the black-box warning of all anti-depressants across the board?

Answer 15

Suicidal ideations, increased risk of this in children, adolescents and young adults.

Question 16

Why can we not cut these drugs cold turkey?

Answer 16

Withdrawal symptoms, which include a slew of things like dysphoria, irritability, agitation, dizziness, sensory disturbances, anxiety, confusion, headache, lethargy, emotional liability, insomnia, hypomania, tinnitus and seizures <— worst case scenario at large doses. Taper off slowly.

Question 17

Which anti-depressants are fatal in overdose?

Answer 17

TCA’s and MAOI’s.

Question 18

What is “Serotonin Syndrome?” What is its triad?

Answer 18

Excessive Serotonin activity, potentially lethal. Triad: cognitive (coma/seizures), autonomic (tachycaria, HTN) and somatic (myoclonus, tremor and hyperreflexia)

Question 19

Besides the triad, what other symptoms can we see in Serotonin syndrome?

Answer 19

Hyperthermia, metabolic acidosis, rhabdomyolysis (due to the myoclonus, tremors and hyperreflexia), renal failure (due to rhabdo damage depositing into the kidney), DIC.

Question 20

What are the drugs that can cause serotonin syndrome?

Answer 20

MAOI’s, SSRI’s (esp w/ MAOIs), 2nd gen antidepressants, linezolid (ABX), tramadol, meperidine, fentanyl, (all opoids or analgesics) ondansetron (anti-emetic), symatriptan (migranes), MDMA and LSD, St. John’s Wort, ginseng, alcohol.

Question 21

Which 2 drugs are associated with prolonged QT intervals leading to arrythmia’s when used with anti-depressants?

Answer 21

Thioridazine and Pimozide (both anti-psychotic drugs).

Question 22

Anti depressants and preggo? Can kids have it?

Answer 22

Avoid, especially in the 3rd trimester, enters breast milk. Some are, depends on the drugs.

Question 23

Problem with geriatics and anti-depressants?

Answer 23

Increased risk of falls. Excess CNS stimulations.

Question 24

What is the “start low go slow” method?

Answer 24

Start at a low dose and titrate up, do not increase dose before 5 half lives.