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Anti-depressants Flashcards

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1
Q

Anti-depressant uses

A 
Major depression
Persistent depressive disorder
Anxiety Disorders
Trauma and Stressor Related Disorders
Obsessive Compulsive Disorder
Eating Disorders
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2
Q

MAOIs (Monoamine Oxidase Inhibitors)

A

Tranylcypromine
Phenelzine
Isocarboxazid
Selegiline

“MAO Takes Pride in Shanghai”

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3
Q

TCAs (Tricyclic Antidepressants)

A 
Amitriptyline
Nortriptyline
Doxepin
Imipramine
Desipramine
Clomipramine
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4
Q

SSRIs (Selective Serotonin Reuptake Inhibitors)

A 
Fluoxetine
Sertraline
Paroxetine
Citalopram
Escitalopram
Fluvozamine
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5
Q

SNRIs (Serotonin Norepinephrine Reuptake Inhibitors)

A

Venlavaxine
Desvenlafaxine
Duloxetine

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6
Q

Atypical Antidepressants

A 
Mitazepine
Buproprion
Nefazodone
Vilazodone
Vortioxetine
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7
Q

Noradrenergic and serotoneric alpha 2 adrenergic antagonist

A

Mitazepine

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8
Q

NDRI: Norepinephrine and Dopamine reuptake inhibitor

A

Buproprion

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9
Q

Serotonin/NE reuptake inhibitor and serotonin 2A antagonist

A

Nefazodone

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10
Q

Serotonin reuptake blockade and serotonin 1A partial agonist

A

Vilazodone

Vortioxetine

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11
Q

MAOI MOA

A

Block the break down of serotonin, NE, and dopamine by MAO inside the presynaptic terminal

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12
Q

MAO-A MOA

A 
metabolizes catecholamine (NE, Epi), 5HT
metabolizes tyramine and DA
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13
Q

MAO-B MOA

A

metabolizes trace amines and 5HT (at high concentrations)

Metabolizes tyramine and DA

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14
Q

MAO irreversible inhibitors

A

Phenelzine
Tranylcypromine
Selegiline

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15
Q

MAOI irreversible inhibitor MOA

Phenelzine, Tranylcypromine

A

Block MAO-A and MAO B by covalently binding the enzyme, permanently disables the enzyme

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16
Q

MAOI irreversible inhibitor MOA

Selegiline

A

Preferentially inhibits MAO-B

At high doses can inhibit MAO-A

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17
Q

How long does it take an MAO enzyme to be replaced after irreversible inhibitors are stopped

A

10-14 days

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18
Q

How long does it take an MAO enzyme to be replaced after reversible inhibitors are stopped?

A

1 day

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19
Q

MAOI reversible inhibitors

RIMAs: reversible inhibitors of monoamine oxidase

A

Meclobemide

NOT FDA approved in the US

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20
Q

MAOI half-life

A

brief

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21
Q

MAOI side effects

A 
Due to excess serotonin and NE
GI (nausea, constipation, appetite change)
Sleep disturbances
Sexual dysfunction
Sedation
Weight gain
*Hypertensive Crisis
*Serotonin Syndrome
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22
Q

MOAI Hypertensive Crisis

A

Increased NE system

  • Food with high amounts of tyramine (aged cheeses, wines, cured meats); tyramine is metabolized by MAO, unmetabolized tyramine is a pressor
  • Sympathomimetics (cold medicine)
  • cocaine, ecstasy, opioids
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23
Q

How does Selegiline protect against a hypertensive crisis when given as a transdermal patch?

A

Drug goes 1st to brain (higher dose for anti-depressant effect), goes through 1st pass in liver, then goes to GI (lower dose)

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24
Q

MOAI Serotonin Syndrome

A

Increased Serotonin system
If give combo of MAOIs and SSRIs, SNRIs, or TCAs: prevent metabolism of serotonin and reuptake of serotonin > excess serotonin
-Increased reflexes, myoclonus, autonomic dysfunction (unstable BP, increased temp, disorientation)

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25
Food restrictions with MAOIs (severe):
``` Aged cheeses Aged meats All beers on tap Sauerkraut Fava or broad bean pods Banana peels Soy sauce ```
26
Food restrictions with MAOIs (Moderation):
``` Red wine (4 oz) White wine (4 oz) Bottle or canned beer (12 oz) ```
27
Food restrictions with MAOIs (mild to none):
``` Fresh/processed cheeses Fresh or processed meats Bouillon Chocolate Avocados Banana pulp ```
28
Which drugs put you at risk for Serotonin Syndrome when combined with a MAOI?
Analgesics/Opioids: Meperidine, Methadone, Pentazocine, Tramadol (weak serotonin reuptake inhibitors) Antidepressants: Mirtazepine, SNRIs, TCAs, SSRIs OTC cold remedy: Dextromethorphan (weak serotonin reuptake inhibitor)
29
Which drugs put you at risk for Hypertensive crisis when combined with a MAOI?
Analgesics/opioids: Tramadol Antidepressants: Buproprion, Other MAOIs, Mirtazepine, SNRIs, TCAs Sympathomimetics OTC cold remedies
30
Indication for MAOIs
Treatment resistant depression Treatment resistant anxiety disorders Treatment resistant atypical depression *Not used much anymore due to SE*
31
TCAs: Tricyclic Antidepressant MOA
NE and Serotonin reuptake inhibitors | Also block histamine, acetylcholine, alpha adrenergic receptors!
32
What is the secondary TCA metabolite of Imipramine?
Desipramine
33
What is the secondary TCA metabolite of Amitriptyline?
Nortriptyline
34
Tertiary TCA metabolite MOA
NE= 5-HT reuptake inhibitor
35
Secondary TCA metabolite MOA
NE > 5-HT reuptake inhibitor
36
What is unique about Clomipramine and Doxepine TCAs?
Tertiary but act like secondary
37
TCA Pharmacokinetics
``` High lipid solubility High protein binding Large volume of distribution Rapid absorption Significant 1st pass metabolism ```
38
TCA side effects
``` Block H1 rec: sedation, weight gain Block M1 rec: sedation, confusion, blurred vision, dry mouth, constipation Block a1 rec: sedation Increased serotonin: sexual dysfunction Increased NE: increased BP, sweating ```
39
TCA Contraindications
Elderly (65+) - risk of sedation and confusion, avoid polypharmacy CNS depressants: alcohol, barbituates, opiates, benzodiazepines Overdose- hypotension, respiratory depression, confusion, delirium, altered, severe arrhythmias
40
Serotonin Selective Reuptake Inhibitors (SSRIs) MOA
Selectively bind the serotonin reuptake pump (much less risk of side effects)
41
Which drug has the longest half life of the SSRIs?
Fluoxetine has the longest half life (7-15 days)- could take 5 weeks before completely gone!
42
Which SSRIs inhibit CYP450 2D6 enzymes?
Fluoxetine and paroxetine are strong inhibitors
43
Which SSRI has significantly less protein binding than the others?
Escitalopram (56%)
44
Which SSRIs have the shortest half lives?
Paroxetine and Fluvoxamine
45
Which SSRIs have the high risk for discontinuation syndrome?
Paroxetine and Fluvoxamine
46
Describe the relationship between Citalopram and escitalopram?
Escitalopram is purified S isomer of citalopram
47
Characteristics of SSRI side effects
Occur prior to onset of anti-depressant effect Are dose dependent May happen once, intermittently, or chronically May have different levels of severity
48
Common SSRI side effects
``` *Due to excessive serotonin* GI Anxiety CNS Sexual Dysfunction ```
49
Symptoms of SSRI discontinuation syndrome
Dizziness, nausea, fatigue, headache, insomnia, restlessness, unstable gait, brain zaps
50
Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)
Blocks serotonin and NE reuptake pumps | At high dose can block dopamine reuptake pump
51
What is the most commonly used SNRI?
Venlafaxine
52
Which SSRI has the highest affinity for the 5-HT transporter?
Paroxetine
53
Which SSRI is the least 5-HT selective?
Fluoxetine
54
Which SSRI is most likely to have drug-drug interactions due to inhibition of CYP enzymes?
Fluvoxamine
55
Which SNRI has the shortest half life?
Venlafaxine
56
Which SNRI has the greatest risk of causing discontinuation syndrome if stopped abruptly?
Venlafaxine | also Desvenlafaxine
57
What is the metabolite of Venlafaxine?
Desvenlafaxine
58
Mirtazapine MOA
Block a-2 presynaptic autoreceptors on NE and 5HT neurons, leads to increased NE and 5HT Also blocks Histamine, 5HT2A, 5HT2C, 5HT3
59
Mirtazapine Side effects (or lack thereof...)
Block histamine: weight gain, dry mouth, sedation | Block 5HT2A, 5HT2C, 5HT3: NO nausea, NO sexual dysfunction, NO insomnia, NO anxiety!
60
Buproprion MOA
NE and DA reuptake inhibitor No effects on 5HT, histamine
61
Burproprion side effects (or lack thereof...)
No 5HT related (sexual) No H1 related (sedation/weight gain) Increased seizure risk at high doses
62
Can Buproprion and Mirtazapine be used in combination with SSRIs and SNRIs?
Yes! Especially if you are only getting partial improvement in depression symptoms
63
Nefazodone MOA
Blocks 5-HT reuptake (SSRI effects) | 5-HT2A receptor antagonist: no sexual side effects
64
Nefazodone Side effects (or lack thereof...)
Mild sedation | No sexual side effects
65
Vilazodone MOA
Blocks 5HT reuptake (SSRI) | Partial agonist of 5-HT1A receptors (additional help for depression/anxiety)
66
Vilazodone side effects (or lack thereof...)
No weight gain No sexual side effects GI, nausea, vomiting, diarrhea Insomnia
67
Vortioxetine MOA
Blocks 5-HT reuptake (SSRI) Agonist at 5-HT1A Partial agonist at 5-HT1B Antagonist at 5-HT3 (less GI) and 5-HT7
68
Vortioxetine side effects (or lack thereof)
No weight gain No sexual side effects (except at high dose) GI (nausea > vomiting/diarrhea)
69
After stopping an MAOI, how long to wait until starting new antidepressant? What are you waiting for? What if MAOI is reversible?
10-14 days Neurons to regenerate MAO Only need to wait 1 day
70
After stopping other anti-depressants, how long wait until starting MAOI? What are you waiting for? Are there any anti-depressants that would require a longer wait before starting MAOI?
Need to wait ~1 week (5 half life for drug to clear) Drugs to clear Fluoxetine (~5 weeks)
71
What is the risk of overlapping an anti-depressant with an MAOI?
Risk of serotonin syndrome (increased serotonin) | Risk of hypertensive crisis (increased NE)
72
Which drug inhibits CYP 1A2?
Fluvoxamine
73
Which drugs inhibit CYP2C9 and CYP2C19?
Fluvoxamine | Fluoxetine
74
Which drugs inhibit CYP2D6?
Paroxetine Fluoxetine Buproprion
75
Which drugs inhibit CUP3A4?
Nefazadone | Fluxoxamine
76
Which 2 drugs are the MOST likely to produce interactions with other drugs?
Fluvoxamine | Fluoxetine

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