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Flashcards in Anti-depressants Deck (76):
1

Anti-depressant uses

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

2

MAOIs (Monoamine Oxidase Inhibitors)

Tranylcypromine
Phenelzine
Isocarboxazid
Selegiline

"MAO Takes Pride in Shanghai"

3

TCAs (Tricyclic Antidepressants)

Amitriptyline
Nortriptyline
Doxepin
Imipramine
Desipramine
Clomipramine

4

SSRIs (Selective Serotonin Reuptake Inhibitors)

Fluoxetine
Sertraline
Paroxetine
Citalopram
Escitalopram
Fluvozamine

5

SNRIs (Serotonin Norepinephrine Reuptake Inhibitors)

Venlavaxine
Desvenlafaxine
Duloxetine

6

Atypical Antidepressants

Mitazepine
Buproprion
Nefazodone
Vilazodone
Vortioxetine

7

Noradrenergic and serotoneric alpha 2 adrenergic antagonist

Mitazepine

8

NDRI: Norepinephrine and Dopamine reuptake inhibitor

Buproprion

9

Serotonin/NE reuptake inhibitor and serotonin 2A antagonist

Nefazodone

10

Serotonin reuptake blockade and serotonin 1A partial agonist

Vilazodone
Vortioxetine

11

MAOI MOA

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

12

MAO-A MOA

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

13

MAO-B MOA

metabolizes trace amines and 5HT (at high concentrations)
Metabolizes tyramine and DA

14

MAO irreversible inhibitors

Phenelzine
Tranylcypromine
Selegiline

15

MAOI irreversible inhibitor MOA
(Phenelzine, Tranylcypromine)

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

16

MAOI irreversible inhibitor MOA
(Selegiline)

Preferentially inhibits MAO-B
At high doses can inhibit MAO-A

17

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

10-14 days

18

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

1 day

19

MAOI reversible inhibitors
(RIMAs: reversible inhibitors of monoamine oxidase)

Meclobemide
NOT FDA approved in the US

20

MAOI half-life

brief

21

MAOI side effects

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

22

MOAI Hypertensive Crisis

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

23

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

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

24

MOAI Serotonin Syndrome

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)

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