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Pharm: Psych > 2.16: Anti Depress > Flashcards

2.16: Anti Depress Flashcards

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1
Q

What is dysthymia?

A

Peristent depressive disorder

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2
Q

Uses for antidepressants outside of depression?

A
  1. Anxiety
  2. PTSD
  3. Eating disorders
  4. OCD
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3
Q

What is the monoamine hypothesis of depression?

A
  • It was noted that reserpine depleted amines and inducted depression
  • Noted that antidepressants enhanced monoamine systems
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4
Q

What is the paradox in antidepressant treatments?

A
  1. Side effects will be noted from day one

2. Can take weeks to see impact on depression

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5
Q

What are MAOIs?

A

“Monoamine Oxidase Inhibitors”

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6
Q

What are TCAs?

A

“Tricyclic antidepressants”

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7
Q

What are SNRIs?

A

“Serotonin Norepinephrine reuptake inhibitors”

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8
Q

Where are monoamine oxidases found?

A

In BOTH Noradrenergic and Serotonergic PREsynaptic neurons

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9
Q

What are MAOs? What do they do?

A

“Monoamine oxidase”

  • Breakdown NE, 5HT, and Dopamine
  • By inhibiting these, MAOIs increase NT in presynaptic neurons for release
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10
Q

What is 5HT?

A

Serotonin

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11
Q

What does MAO-A do?

A

Metabolizes the catecholamines:

  1. NE
  2. Epi
  3. 5HT
    * **MAO-A is responsible for antidepressant effects
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12
Q

What does MAO-B do?

A

Metabolizes trace amines:

1. 5HT at high []

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13
Q

What are RIMAs?

A

“Reversible inhibitors of MonoAmine oxidase”

- Not available in the US

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14
Q

How do the irreversible MAOIs work?

A
  • Covalently bind to MAO permanently disabling
  • Enzymes must be replaced to function again
  • Replacement takes 10 -14
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15
Q

What is special about selegiline?

A
  • Irreversible BUT prefers MAO-B
  • At high doses works on MAO-A as well
  • **Only acts as antidepressant at high doses
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16
Q

MAOI side effects?

A
  1. Nausea, constipation, appetite change
  2. Orthostatic hypotension
  3. Sedation
  4. Sleep disturbance
  5. Sexual dysfunction
  6. Weight gain
    * *Rare/severe:
  7. Hypertensive crisis
  8. Serotonin syndrome
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17
Q

Foods that can cause hypertensive crisis in patient on MAOIs?

A

Those high in tyramine:

  1. Aged cheese
  2. Wine
  3. Cured meats
  4. Beer
  5. Fermented foods
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18
Q

How does cheese rxn work?

A
  • Tyramine found in cheese normally metabolized by liver MAOIs
  • When not metabolized, becomes a pressor = HTN
  • MAOIs stop it from being metabolized
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19
Q

How is selegiline administered? Why is this important?

A
  • Transdermal patch
  • Hits brain first avoiding first pass metabolism = works at lower dose
  • Does not have hypertensive crisis side effect
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20
Q

Drugs that can cause hypertensive crisis with MAOIs?

A
  1. OTC cold medicines
  2. Cocaine
  3. Ecstasy
  4. Opioids
    * **Brain aneurism / hemorrhagic stroke is fear
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21
Q

What cause serotonin syndrome?

A
  1. MAOI: leads to serotonin build up
  2. SSRI: prevent serotonin reuptake
    * ***Over abundance of serotonin in cleft stimulating post synaptic neuron
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22
Q

Appearance of serotonin syndrome?

A
  1. Increased reflexes
  2. Myoclonus
  3. Disorientation
  4. Autonomic dysfunction: Increased temp and unstable BP
  5. Seizure
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23
Q

Name the MAOIs?

A

MAOIs work well when you are in the “PITS”

  1. Phenelzine
  2. Isocarboxazid
  3. Tranylcypromine
  4. Selegiline
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24
Q

MOA of TCAs?

A
  1. NE reuptake inhibitors

2. 5HT reuptake inhibitors

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25
Q

Name the TCAs?

A

TCAs taste like “CANDDI”

  1. Clomipramine
  2. Amitriptyline - Tertiary (Nortriptyline)
  3. Nortriptyline
  4. Desipramine
  5. Doxepin
  6. Imipramine - Tertiary (Desipramine)
26
Q

Which are the tertiary TCAs and what to they become?

A
  1. Imipramine - > Desipramine

2. Amitriptyline - > Nortriptyline

27
Q

Difference in function between tertiary and secondary TCAs?

A
  • Tertiary :NE=5‐HT reuptake inhibitor;

* Secondary :NE>5‐HT re‐uptake inhibitor

28
Q

Kinetics of TCAs?

A
  • Highly lipid soluble
  • High protein binding
  • Large volume of distribution
  • Significant first pass metabolism
  • Rapid absorption
29
Q

What does a high volume of distribution mean?

A
  • Much more drug is found in tissue than in serum
30
Q

Side effects of TCAs?

A
  1. Antihistaminic: sedation / weight gain
  2. Anti muscarinic: sedation and confusion
  3. Increased 5HT: Sexual dysfunction
  4. Increased NE: Sweating / hypertension
31
Q

List receptor affinity for TCAs in order of most to least?

A
  1. Histaminic receptors
  2. Muscarinic receptors
  3. Antidepressants (Target)
  4. CNS toxicity (5x therapeutic dose)
  5. CV toxicity (5x therapeutic dose)
32
Q

Who should you not use TCAs in?

A
  1. Elderly
  2. Benzos / opiates / barbiturates
  3. Alcoholics
33
Q

Name the SSRIs?

A

SSRIs Make you want to “FFluox your PECS”

  1. Fluoxetine
  2. Fluvoxamine
  3. Paroxetine
  4. Escitalopram
  5. Citalopram
  6. Sertraline
34
Q

Which SSRI has longest half life?

A

Fluoxetine: 1 - 4 days

**Its metabolite has 7 - 15 day half life

35
Q

Which SSRIs are CYP450 inhibitors?

A
  1. Fluoxetine
  2. Paroxetine
    * **CYP 450-2d6
36
Q

Which SSRIs have the shortest half lives?

A
  1. Fluvoxamine
  2. Paroxetine
    * **Highest risk of discontinuation syndrome
37
Q

What is discontinuation syndrome?

A

Withdrawal from a drug. Seen in SSRIs with shortest 1/2 life:

  1. Fluvoxamine
  2. Paroxetine
38
Q

Relationship between Citalopram and Escitalopram?

A

Citalopram: R and S isomer of drug (S is active)

“Es”citalopram: Only the active form (S Isomer)

39
Q

What to tell patient about SSRI side effect?

A
  1. May only happen once or intermittent
  2. Can be dose dependent
  3. If it is mild try to wait it out until benefit of antidepressant kicks in
40
Q

Common side effects for SSRIs?

A
  1. GI
  2. Anxiety
  3. CNS
  4. Sexual dysfunction
41
Q

What occurs in SSRI discontinuation syndrome?

A

Dizziness, nausea, fatigue, headache, insomnia, restlessness, unstable gait, brain zaps
***This is mild, annoying, and not life threatening

42
Q

Which are the SNRIs?

A
  1. Venlafaxine
  2. Desvenlafaxine
  3. Duloxetine
43
Q

What do the SNRIs block?

A

Both the serotonin and NE reuptake pumps

44
Q

Which pumps will venlafaxine block in order?

A
  1. Serotonin
  2. NE
  3. Dopamine
    * **Hits all 3 monoamines
45
Q

Which SNRI has highest protein binding?

A

Duloxetine

46
Q

Which SNRI has shortest 1/2 life?

A

Venlafaxine

***Highest risk of discontinuation syndrome

47
Q

What is the metabolite of venlafaxine?

A

Desvenlafaxine

48
Q

What are the atypical antidepressants? Mechanisms?

A
  1. Bupropion: NE and dopamine reuptake inhibitor

2. Mirtazapine: blocks presynaptic A2 adrenergic autoreceptors on both NE and 5HT neurons = higher NE and 5HT [ ]s

49
Q

What does Bupropion have highest affinity for?

A
  1. Dopamine

2. NE

50
Q

What is special about mirtazapines action on serotonin?

A

Also blocks the following serotonin receptors;

  1. 5HT-2a
  2. 5HT-2c
  3. 5HT-3
    * ***Prevents nausea, sexual dysfunction, insomnia, and anxiety that other serotonin RIs cause
51
Q

Drawback of mirtazapine?

A
  1. Weight gain

2. Sedative: take at night to help with sleep

52
Q

What are bupropion and mirtazapine often combined with in the treatment of depression?

A

SSRIs and SNRIs

53
Q

What is nefazodone?

A
  • Blocks 5HT reuptake

- 5HT-2a receptor antagonist *** No sexual side effects and mild sedation

54
Q

What does antagonizing the 5HT-2a receptor result in?

A

Prevention of sexual side effects

55
Q

What is vilazodone?

A
  • 5HT reuptake inhibitor
  • NO weight gain
  • No Sexual side effects
56
Q

What is Vortioxetine?

A
  • 5HT reuptake inhibitor
  • NO weight gain
  • No Sexual side effects
57
Q

How long do you have to wait after stopping MAOI to start another antidepressant?

A

~ 2 weeks to wait for neurons to regenerate MAO enzymes in neurons
***This is because of its long half life allowing its effects to persist in the system for long after use is stopped

58
Q

How long do you have to wait after stopping RIMA to start another antidepressant?

A

Day or two, much shorter half life as these are reversible

59
Q

How many half lives do you have to wait before starting MAOI when switching from another antidepressant?

A
  • 5 1/2 lives
  • This is usually about 1 week
  • ***Since the 1/2 life of fluoxetine is so long you would need to wait closer to 5 weeks
60
Q

What occurs if you do not wait long enough when switching to or from MOAI?

A

Risk of Serotonin syndrome or hypertensive crisis depending on what the mechanism of the other drug is

61
Q

Which SSRIs are most likely to cause DDIs?

A
  1. Fluvoxamine

2. Fluoxetine

Pharm: Psych (7 decks)

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