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Therapeutics Module 2 > Depression > Flashcards

Depression Flashcards

1
Q

What are the 5 SSRI medications?

A

Sertraline
Escitalopram
Citalopram
Fluoxetine
Paroxetine

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2
Q

What are the 2 SNRI medicaitons?

A

Duloxetine
Venlafaxine

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3
Q

What is the NDRI?

A

bupropion

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4
Q

What is the 1 A2 agonist 5ht2 antagonist?

A

Mirtazipine

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5
Q

What is the MOA of SSRI

A

Inhibition of presynaptic 5-HT reuptake by inhibition of the 5Ht transporter CNS Neurons
Increased 5Ht is then present in the synaptic cleft

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6
Q

What happens the 1st few days of SSRI?

A

Decreased agitation and anxiety

Improved sleep and appetite

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7
Q

What is important when someone first starts and SSRI

A

Higher incidence of energy may make someone more inclined to act upon their suicide ideation thoughts

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8
Q

What happens the first 1-3 weeks of SSRI medication start?

A

Increased activity and sex drive

Improved self care and concentration memory thinking and movement

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9
Q

What happens the first 2-4 weeks of starting an SSRI?

A

Relief of depressed mood, return or experiencing pleasure, fewer hopeless feelings, subsiding suicidial thoughts

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10
Q

What are the adverse reaction of SSRI?

A

Aconym HANDS
Headache
Anxiety
Nausea
Diarrhea and GI pset
Sleep disturbances

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11
Q

What is the acronym HANDS and what does it relate to?

A

Headache
Anxiety
Nausea
Diarrhea
Sleep disturbances

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12
Q

What are other AE of SSRIs?

A

Male/Female sexual/dysfunction

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13
Q

How do we deal with the adverse reactions of SSRI?

A

dose adjustment usually decreased

For Sexual dysfunction we may need to consider PDE5 inhibitors

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14
Q

What is emotional blunting/detachment?

A

Reported phenomenon in SSRI but hard to study accurately

We can switch to antidepressant with increase NE/DA activity such as bupropion or decrease the dose

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15
Q

What are the warnings of SSRI?

A

similar to all antidepressant where their is increased usage in children. adolescents and young adults

Increased fracture risk and decreased bone mineral density

QT prolongation
- Especially Escitalopram

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16
Q

What is an especially important note that we need to be aware of with respect to Citalopram and escitalopram?

A

Dose dependant QTc prolongation

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17
Q

Which SSRI usually are the most sedating (Still low)?

A

sertraline, citalopram, but paroxetine has the most sedating

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18
Q

Which SSRI has been associated with weight gain?

A

Paroxetine

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19
Q

What SSRI leads to more sweating and sedation?

A

paroxetine

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20
Q

Which SSRS is most stimulating and have a long 1/2 life

A

Fluoxetine

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21
Q

Which SSRI has the most GI side effects?

A

Fluvoxamine

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22
Q

Which SSRI generally has the best tolerability?

A

Escitalopram and sertraline

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23
Q

Which SSRI has the least tolerability?

A

Fluvoxamine which can lead to nausea, sedation, constipation

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24
Q

Which enzyme is inhibited by fluvoxamine***

A

1A2

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25
Q

Enzyme 1A2 is inhibited by?

A

Which enzyme is inhibited by fluvoxamine***

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26
Q

Which enzyme is inhibited by fluoxetine and paroxetine?

A

2D6

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27
Q

Enzyme 2D6 is inhibited by

A

Which enzyme is inhibited by fluoxetine and paroxetine?

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28
Q

What happens when you increase NSAID usage with SSRI usage?

A

Increases risk of bleeding and decreases platelet aggregation effects of SSRIs

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29
Q

What risk increases when taking an SSRI

A

Serotonergic agents increase risk of serotonin syndrome

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30
Q

What are the relevant PK of SSRIs (AM)

A

A= adequate with or without food,
Metabolism: Hepatically metabolized by CYP

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31
Q

Which SSRI drug increases in absorption with food?

A

Sertraline

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32
Q

Which SSRI form active metabolites? (3)

A

Fluoxetine, Citalopram, Sertraline

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33
Q

How often is an SSRI taken?

A

Once daily

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34
Q

What is Vortioxetine?

A

It is an SSRI that has mixed receptor effects, and ahas been shown to have a reduced side effect profile as comparred to other SSRI

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35
Q

What are the two SNRIS

A

Duloxetine
Venlafaxine

Desvenlafaxine (Pristiq)

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36
Q

What is the MOA of SNRI

A

Inhibits the presynaptic 5-HT and NE reuptake by inhibiting 5-HT and NE transporters in CNS neurons

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37
Q

What is a possible MOA of SNRI as comparred to SSRI

A

It may be effective for the treatment of neuropathic pain

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38
Q

Which SNRI is dose dependant for the amount of binding capacity to 5-HT

A

Venlafaxine
<150mg/dau binds to 5-HT
>150 binds to NE and 5HT

Weakly inhibits DA transporter A 450mg/dayu

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39
Q

Which SNRI have about equal affinity for NE and 5HT trasnporters?

A

Duloxetine and desvenlafaxine

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40
Q

What is the onset of action for SSRI

A

SAME AS SSRI

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41
Q

What are the anticholinergic-like effects of SNRIs?

A

Increase NE/anticholinergic effect. hence possible increase in dry mouth constipation sedation and urinary retention

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42
Q

Which SNRI has lower sexual dysfunction as comparred to SSRI

A

Desvenlafaxine, duloxetine

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43
Q

Which SNRI has similar rates of sexual dysfunction comparred to SSRI?

A

Venlafaxine

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44
Q

Which SNRI can cause hyponatremia

A

Venlafaxine is the highest

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45
Q

What is the adverse drug effects of SNRI?

A

Dose related BP/HR and sweating

Dont appear to be associated with increased risk of fractures
May less emotional blunting than SSRIs

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46
Q

SNRIs relevant PK

A

No effects from food

Dose adjustment for renal impairment
Venlafaxine and duloxetine are hepatically metabolized

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47
Q

Which drug interaction should know for duloxetine?

A

Moderate inhibitor and substrate for Cyp2D6

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48
Q

What disease is Duloxetine CI with?

A

Narrow Angle Glaucoma

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49
Q

What is the black box warning for SNRI?

A

Increase suicide if age is below 24

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50
Q

What should be monitored while on an SSRI?

A

Blood pressure

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51
Q

Should you stop SNRIs immediately?

A

No They need to be tapered

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52
Q

Which disease states should you avoid taking duloxetine in?

A

Hepatic impairment or risk of urinary retention due to anticholingeric effects

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53
Q

Which SNRI is more serotonergic effect?

A

Venlafaxine

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54
Q

What is the NDRI ( Norepinephrine and dopamine reuptake inhibitors) we should know?

A

Buproprion

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55
Q

What is the MOA of buproprion?

A
56
Q

What is buproprion useful in?

A
57
Q

What can bupropion augment?

A
58
Q

What does risk of sexual dysfunction do in relation to bupropion?

A

Less risk and may alleviate the actually alleviate the sx

59
Q

What is the onset of bupropion?

A

Similar to SSRIs and SNRIs

60
Q

Which liver enzyme is bupropion metabolized by?

A

CYP2B6

61
Q

Where is bupropion primarily eliminated?

A

Kidneys, hence renal dosing adjustments are recommended

62
Q

Can Zyban be used concurrently for MDD and smoking cessation?

A

Yes

63
Q

What drug class is contraindicated with buproprion?

A

MAOI therapy

64
Q

Which Cyp enzyme does bupropion inhibit?

A

CYP2d6

65
Q

What is the usual dose of Buproprion?

A

100-300mg

66
Q

What is the two formulations for bupropion?

A

Sr and XL

67
Q

What medical conditions is Bupropion contraindicated for?

A

Seizure
Eating disorder
Abrupt discontinuation of alcohol or sedatives

68
Q

What are the black box warnings of bupropion?

A

Increase risk of suicide if less then 24 years old (as with all ADs)

69
Q

What is the ⍺2-antagonist 5-HT2antagonist we should know?

A

Mirtazipine

70
Q

What is the mechanism of Mirtazipine?

A

antagonism at: 5HT2A, 5HT2C, 5HT3, α2-adrenergic, H1

71
Q

What occurs at low doses of mirtazipine <30mg

A

HI receptor blocking

72
Q

What does the H1 receptor do when activated in terms of symptom side effectds

A

Weight gain and sedation

73
Q

What happens at dose of >15mg with mirtazipine?

A

increased release of NE and 5HT

74
Q

What is Mirtazipine especially considered for? Patients with?

A

insomnia, anxiety, reduced appetite

75
Q

Is mirtazipine usually dosed together or separetley?

A

Both mono and adjunctive

76
Q

Mirtazipine compared to other meds is it safer in overdose?

A

Yes

77
Q

What are the three AD effects of mirtazipine?

A

Sedation
Increased Triglycerides and weight gain due to increased appetite

Less sexual dysfunction as compared to ssri/snri

78
Q

Where is mirtazipine generally excreted?

A

Kidneys and liver, but no renal/hepatic adjustment required

79
Q

When should mirtazapine be taken?

A

Night because of sedation

80
Q

The sedation effect is typically lost (or at least much less pronounced) with doses starting at ___ (Mirtazapine)

A

> 30mg

81
Q

What are the black box warnings for mirtazapine?

A

Increased suicide risk if <24

82
Q

What are the TCAs?

A

Tertiary amines
* Amitriptyline (Elavil)
* Clomipramine
* Doxepin
* Imipramine
Secondary amines
* Nortriptyline (Aventyl)
* Desipramine

83
Q

What are the MOA of TCAs?

A

Inhibit presynaptic 5-HT and NE reuptake by inhibiting 5-HT and NE transporters in CNS neurons

DIRTY ANTIDEPRESSANTS

84
Q

What activity does tertiary amines have?

A

more 5-HT activity

85
Q

What activity does Secondary amines have?

A

More NE activity and better tolerated

86
Q

What are the Secondary amines? TCAs

A
  • Nortriptyline (Aventyl)
  • Desipramine
87
Q

What are the teriary amines TCAs?

A
  • Amitriptyline (Elavil)
  • Clomipramine
  • Doxepin
  • Imipramine
88
Q

What places for therapy does TCAs have?

A

MDD with additonal disease states such as
* Insomnia
* Anxiety
* Chronic, non-cancer pain (low back pain, neuropathic)
* Migraines/headaches
* OCD (clomipramine)

89
Q

What are TCAs contraindicated in?

A
  • Acute MI, heart block, CHF * Severe liver impairment
90
Q

What are the adverse drug effects of TCAs?

A

Sedation
Anticholinergic effects
Cardiovascular effects

91
Q

What is the cardiovascular effects of TCAs?

A

Lethal in overdose
QT prolongation

92
Q

What dose range are TCAs lethal?

A

only 3x the therapeutic dose

93
Q

What are the additional ADEs with TCAS? (Not as major)

A
94
Q

What is trazodone?

A

Serotonin reuptake inhibitor/
5-HT2 antagonist

95
Q

What is the MOA of trazodone?

A

Weak inhibition of SERT and NET

96
Q

At doses of greater then 200mg what is the MOA of trazodone?

A

5-HT2A and 5-HT2C receptor antagonism

97
Q

At doses of 25-200mg what is the MOA of trazodone?

A

Antagonist at alpha-1 adrenergic receptors and H1 histamine receptors

98
Q

At doses of alpha-1 adrengergic receptors and H1 histamine receptors with respect to trazodone what are the common S/E

A

Sedation
Not as well tolerated

99
Q

What are the ADEs of trazodone?

A

dizziness, sedation, headache, nausea, constipation, drymouth

100
Q

What is the usual dose range of trazodone for depression?

A

200-400mg/dau

101
Q

What is the usualy dosage for sedative for trazodone?

A

50mg-200mg

102
Q

What does food do to trazodone?

A

Food enhances, although delays peak concentration

103
Q

Which CYP enzyme metabolizes trazodone?

A

CYP3A4

104
Q

Where is trazodone primarily excreeted?

A

Kidney

105
Q

Which drugs are CI with does trazodone?

A

Dyp3A4 inducers and inhibitors

Antihypertensives (Since trazodone has alpha-1 antagonism

106
Q

What is the atypical antipsychotic?

A

Quetiapine (Seroquel)

107
Q

What is the MOA of Quetiapine

A

Antagonist at 5HT-1 & 2, D1 & 2, H1, alpha-1 & 2

108
Q

What is the usual dosage of quetiapine

A

150-300mg/day, requires a gradual increase in dosage

109
Q

What are doses of 300-600 generally reserved for with quetiapine?

A

Psychotic depression

110
Q

What dosage forms of Quetiapine are there?

A

IR or XR(ER)

111
Q

What is the usual dosage range of quetiapine?

A

150-300mg/day

112
Q

What is moclobemine?

A

Reversible MAOI

113
Q

What is the MOA of moclobemine?

A

Short- acting reversible inhibitor of MAO-A to ↓ metabolism of 5-HT, NE, DA

114
Q

What is the dosage regimen of Moclobemide?

A

300mg/day in 2 divided doses

115
Q

What is the issue with higher doses of Moclobemide

A

Specificity for MAO-A is list hence, caution regarding tyramine is required

116
Q

What is the tyramine reaction?

A

Where food containing tyramine increases the levels of norepinephrine

117
Q

Which enzymes metabolize Moclobemide?

A

CYP2C19, CYP2D6, most of the urine contains metabolites

118
Q

What are the DI with Moclobemide?

A

Serotonergic drugs need to be stopped 2 weeks before starting MAOI to avoid precipitating a hypertensive reaction or serotonin syndrome

119
Q

Which SSRI specifically needs to be stopped before starting a MAOI?

A

Stop Fluoxetine 5 weeks prior to starting MAOI

120
Q

If stopping MAOI how long do you need to wait before starting another antidepressant?

A

2 weeks

121
Q

Stop MAOI at least _______ prior to local or general anesthesia

A

2 days

122
Q

What ADE is there with MAOI/Moclobemide?

A
  • Tachycardia
  • Hypotension
  • Sleep disturbance, agitation, nervousness, anxiety
  • Less frequent than SSRI, SNRI * N/V/D
  • Sexual dysfunction (low incidence compared to SSRI) * Anticholinergic effects
123
Q

What is phenelzine and tranylcypromine?

A

Irreversible MOAI

124
Q

What is the MOA of phenelzine

A

Irreversibly bind and inhibit MAO-A and MAO-B non-selectively increasing 5-HT, NE, DA

125
Q

What is the MOA of Tranylcypromine

A
  • Irreversibly binds and inhibits MAO-A and MAO-B
  • Additional action similar to amphetamines:
    • Increased 5-HT, DA, NE release in
      synapse
    • Inhibits DA and NE transporters
126
Q

What is the duration of action with I-MAOI?

A

Duration of Action: matches timeframe to synthesize new MAO enzymes (2-3 weeks)

127
Q

What is CI with I-MAOI

A
  • Concurrent use of serotonergic or sympathomimetic agents

Tyramine containing foods

128
Q

Which medication counselling points are important with MOAI?

A

Adherence to diet and medication restrictions

Disclose MAOI use to all HCPS

129
Q

What are the 5 first line SSRI?

A

Sertraline Escitalopram Citalopram Fluoxetine Paroxetine

130
Q

What are the 2 first line SNRIs?

A

Duloxetine Venlafaxine

131
Q

What is the 5ht Modulator?

A

Vortioxetine

132
Q

What is the first line 1 NDRI?

A

Bupropion

133
Q

What is the first line 1 A2-agonist 5-ht2 antagonist

A

Mirtazapine

134
Q

What are the odds of remittance with antidepressant treatment?

A

1/3 remit after first treatment, 1/3 after second, and 2/3 after four treatment steps

135
Q
A

Therapeutics Module 2 (4 decks)

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