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Neuroscience > Neuroscience Week 8: Depression Drugs > Flashcards

Neuroscience Week 8: Depression Drugs Flashcards

1
Q

Learning issues

A
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2
Q

Mood Disorder drugs: Prototypes

12 listed

A
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3
Q

Antidepressants: prototypes

8 listed

A
  • Fluoxetine
  • Venlafaxine
  • Bupropion
  • Buspirone
  • Mirtazepine
  • Amitryptyline
  • Nortyptyline
  • Tranylcypromine
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4
Q

Mood Stabilizers: Prototypes

4 listed

A
  • Lithium
  • Valproic Acid
  • Lamotrigine
  • Olanzepine
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5
Q

Mood Stabilizers: classes

3 listed

A
  • Lithium
  • Anticonvulsants
  • Antipsychotics
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6
Q

Antidepressants: Classes

8 listed

A
  • SSRIs
  • SNRIs
  • Amphetamine-related
  • 5HT1A/α1 partial agonist
  • 5HT2/α2 Antagonists
  • Tertiary Amine TCAD’s
  • Secondary Amine TCAD’s
  • MAOIs
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7
Q

Antidepressants: Fluoxetine related agents

5 listed

A
  • Paroxetine
  • Setraline
  • Fluvoxamine
  • Citalopram
  • Escitalopram
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8
Q

Antidepressants: Fluoxetine Class

A

SSRI

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9
Q

Antidepressants: Venlafaxine related agents

4 listed

A
  • Descenlafaxine
  • Duloxetine
  • Levomilnacipran
  • Milnicipran
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10
Q

Antidepressants: Venlafaxine Class

A

SNRI

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11
Q

Antidepressants: Bupropion class

A

Amphetamine-related

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12
Q

Antidepressants: Buspirone class

A

5HT1A/α1 partial agonist

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13
Q

Antidepressants: Mirtazapine related agents

A

Trazodone

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14
Q

Antidepressants: Mirtazapine Class

A

5HT2/α2 Antagonists

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15
Q

Antidepressants: Amitriptyline Class

A

Tertiary Amine TCAD

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16
Q

Antidepressants: Amitriptyline related agents

3 listed

A
  • imipramine
  • Clomipramine
  • Doxepin
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17
Q

Antidepressants: Nortriptyline related agents

A
  • Desipramine
  • Amoxapine
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18
Q

Antidepressants: Nortriptyline Class

A

Secondary Amine TCAD

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19
Q

Antidepressants: Tranylcypromine Class

A

MAOI

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20
Q

Antidepressants: Tranylcypromine Related agents

3 listed

A
  • Selegiline
  • Phenelzine
  • Isocarboxazid
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21
Q

Mood Stabilizers: Lithium Class

A

Lithium

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22
Q

Mood Stabilizers: Valproic acid class

A

Anticonvulsants

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23
Q

Mood Stabilizers: Valproic acid related agents

2 listed

A
  • Carbamazepine
  • Oxcarbazepine
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24
Q

Mood Stabilizers: Valproic acid use

A

Mania-normal

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25
Q

Mood Stabilizers: Lamotrigine Class

A

Anticonvulsants

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26
Q

Mood Stabilizers: Lamotrigine use

A

Depression-normal

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27
Q

Mood Stabilizers: Olanzapine Class

A

Antipsychotics

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28
Q

Mood Stabilizers: Olanzapine related agents

3 listed

A
  • Quetiapine
  • Lurasidone
  • Aripiprazole
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29
Q

Reserpine and propranolol can cause?

A

Depression

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30
Q

Depression chemical imbalance theory

A
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31
Q

Monoamine hypothesis is overly simplistic

A
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32
Q

Neuroendocrine factors in the pathophysiology of depression

3 listed

A
  • Dysregulation of the HPA axis: ↑ CRF, ↑ Cortisol
  • Dysregulation of the thyroid axis: ↓TSH, ↓Thyroxine
  • Gonadotropin deficiencies
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33
Q

Stress increases evoked _________ release and chronic antidepressant treatment can diminish ___________ release.

A

Glutamate

Glutamate

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34
Q

Ketamine as an antidepressant

A
  • rapid antidepressant effect that can last up to one week after administration - but arent really practical
  • NMDA receptor partial agonists OR allosteric modulators of mGluRs
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35
Q

Glucocorticoids depress the synthesis of __________, decreasing neurogenesis

A

BDNF

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36
Q

Some antidepressants and electroconvulsive therapy can increase BDNF levels and thereby increase?

A

Neurogenesis in the dentate gyrus and enhance synaptic connectivity

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37
Q

Neurotrophic hypothesis of depression

A
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38
Q

MOA of common antidepressant medications

A
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39
Q

SNRI MOA

A

blocks NET reuptake thereby increasing noradrenergic transmission

SNRIs

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40
Q

Fluoxetine and related agents MOA

A

SSRI

block 5HT reuptake transporter thereby increasing

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41
Q

Mirtazepine MOA

A

5HT2/α2 Antagonists which block autoreceptor response to increase the release of NE and SE

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42
Q

Buproprion MOA

A

enhances noradrenergic release

and

dopamine

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43
Q

Buspirone MOA

A

5HT1A/α1 partial agonist so they are NE and SE partial agonists

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44
Q

Fill in the table

A
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45
Q

Side effects of SSRIs organ systems

3 listed

A
  • Gut
  • Spinal/Supraspinal
  • CNS
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46
Q

Side effects of SSRIs: Gut

3 listed

A
  • Nausea
  • GI Upset
  • Diarrhea
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47
Q

Side effects of SSRIs: spinal/supraspinal

3 listed

A
  • sexual dysfunction (30-40%) (some tolerance, takes longer)
  • ↓ libido, ↓ decreased arousal
  • ↓ or delayed orgasm
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48
Q

Side effects of SSRIs: Higher CNS

3 listed

A
  • Headaches / insomnia / somnolence
  • Anxiety / agitation
  • Weight gain (especially with paroxetine)
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49
Q

Discontinuation Syndrome of SSRIs

A
  • Nausea
  • dizziness
  • anxiety
  • tremor
  • palpitations
  • less pronounces with longer-acting agents such as fluoxetine and sertraline
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50
Q

Teratogenic potential of SSRIs

A
  • teratogenic potential remains unresolved
  • Sertraline is preferred among the class during pregnancy and nursing
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51
Q

SSRIs Drug interactions

A
  • High plasma protein binding (80-90%)
  • Inhibit drug metabolism by CYP450s: (1A2, 2C19, 2D6, 3A4)
  • MAOIs contraindicated - 5HT syndrome
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52
Q

Serotonin Syndrome

A

occurs when the excess of serotonin

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53
Q

Serotonin Syndrome symptoms

A
  • Cognitive (delirium, coma)
  • Autonomic (hypertension, tachycardia, hyperthermia)
  • Somatic (myoclonus, hypereflexia, tremor, muscle rigidity)
  • Treatment with benzodiazepines
54
Q

Other complications of SSRIs overview

4 listed

A
55
Q

Buspirone MOA

A
56
Q

Buspirone effects at MCRs or H1 receptors

A

no relevant effects

57
Q

Buspirone contraindicated with

A

MAOIs

58
Q

Buspirone side effects

4 listed

A
  • Tachycardia
  • Tremors
  • Insomnia
  • Constipation
59
Q

Buspirone clinical use

A

not first-line but has some utility as an adjunct for use with SSRIs to offset sexual and anxiogenic side effects of SSRIs

60
Q

SNRI MOA

A
61
Q

SNRIs side effects

A

SSRI side effects +

  • CNS activation / agitation
  • can elevate HR and BP
62
Q

SNRI Efficacy

A

similar to SSRIs but better response in some patients who do not respond to or tolerate SSRIs

63
Q

SNRI other complications

A

also discontinuation syndrome and SSRI complications

64
Q

SNRI plasma binding

A

lower plasma protein binding (27%)

65
Q

SNRI half-life

A

shorter half-life than SSRIs or TCADs

66
Q

SNRI caveat

A

can be helpful with concomitant pain syndromes

67
Q

Buproprion MOA

A

Hydroxybuproprion (active metabolite) enhances NE (and DA) release

68
Q

Buproprion adrenergic (muscarinic) and noradrenergic (α1) or H1

A

no relevant effects

69
Q

Buproprion caveats

A
  • lower incidence of sexual dysfunction and weight gain
  • can be combined with SSRI to reduce sexual and weight effects
70
Q

Buproprion contraindications

A
  • higher incidence of tremors and seizures (dose-dependent)
  • Can aggravate propensity for psychosis
  • Not used when depressive symptoms are accompanied with anxiety
  • MAOIs
71
Q

Buproprion drug interactions

A

high plasma protein binding (84%)

72
Q

Buproprion efficacy for depression

A

efficacy similar to SSRIs as a monotherapy

73
Q

Buproprion contraindicated with MAOIs

A

yes it is contraindicated

74
Q

Buproprion overview

A
75
Q

Mirtazapine Overview

A
76
Q

Mirtazapine MOA

A
  • 5HT2/α2 adrenergic receptor Antagonists
  • (enhances 5HT and NE release via “autoreceptors” blockade)
77
Q

Mirtazapine muscarinic or α1 activity

A

no effects

78
Q

Mirtazapine H1 receptor effects

A

Very potent H1 receptor antagonist

So it (↑appetite, weight gain, altered lipid profile)

79
Q

Mirtazepine can offset some SSRI/SNRI side effects

A
  • Drowsiness
  • Weight gain
  • Dry mouth
  • Increased appetite
  • Constipation
  • Lack of energy
  • Weakness
  • Dizziness
  • Serum triglycerides increased
  • Dream disorders
  • Disturbance in thinking
  • ALT increased
  • Swelling of extremities
  • Muscle pain
  • Confusion
  • Urinary frequency
  • Tremor
  • Back pain
  • Shortness of breath
80
Q

Mirtazapine can offset some?

A

SSRI/SNRI side effects

81
Q

Mirtazapine discontinuation syndrome?

A

Yes

82
Q

Mirtazapine drug interactions

A

high plasma protein binding (85%)

83
Q

Mirtazapine safety profile

A

similar to SSRIs

84
Q

Mirtazapine contraindicated with?

A

MAOIs

85
Q

Mirtazapine efficacy

A
  • better than SSRIs / SNRIs/ Buproprion
  • but less than TCADs or MAOIs
  • Has a substantial anxiolytic effects
86
Q

Mirtazapine caveats

A
  • H1 receptor antagonists
  • substantial anxiolytic effect
  • can offset some SSRI/SNRI side effects
87
Q

Tricyclic Antidepressants overview

A
88
Q

Tricyclic Antidepressants AKA

A

TCADs

89
Q

Tricyclic Antidepressants subtypes

A
  • Tertiary amine TCADs
  • Secondary amine TCADs
90
Q

TCAD: Tertiary amine MOA

A

1o preference as a 5HT reuptake inhibitor

2o Muscarinic, α1 adrenergic & H1 receptor antagonist

91
Q

TCAD: secondary amine MOA

A
  • 1o preference as a NE reuptake inhibitor
  • 2o Reduced affinity as Muscarinic antagonists BUT similar affinity to α1 adrenergic & H1 receptors as antagonist
92
Q

TCAD: secondary amine example

A

Nortriptyline

93
Q

TCAD: Tertiary amine example

A

Amitriptyline

94
Q

TCAD Side effects organ systems

A
  • GI distress
  • Sexual dysfunction
  • Sedation
  • Weight gain
  • Cardiovascular (orthostatic hypotension → tachycardia)
95
Q

Which subtype of TCAD have more pronounced side effects

A

3o amine TCADs

96
Q

TCADs toxic range

A
  • incorporate into excitable membranes
  • Cardiovascular (arrythmias / AV block / Cardiac arrest)
  • CNS (confused states / seizures / coma)
97
Q

TCADs drug interactions

A

High plasma protein binding >85%

98
Q

TCAD discontinuation syndrome

A

Yes

99
Q

TCAD side effects overview

A
100
Q

CNS & autonomic system effects

  • Muscarinic antagonism
  • α1 antagonism
  • H1 antagonism
A
101
Q

MAOIs subtypes

A

irreversible MAOIs

reversible MAOIs

with selectivity

102
Q

Non-selective MAOIs

A
  • Phenelzine
  • Iproniazide
103
Q

Irreversible Type A MAOIs MOA

A

NE/5HT/DA

104
Q

Irreversible Type A MAOIs

A

Clorgyline

105
Q

Irreversible Type B MAOIs

A

Selegiline

106
Q

Irreversible Type B MAOIs MOA

A

DA

107
Q

Reversible Non-selective MAOI

A

Tranylcypromine

108
Q

Reversible Type A MAOI

A

Moclobemide

109
Q

Reversible Type A MAOI MOA

A

NE/5HT/DA

110
Q

MAOI Acute side effects therapeutic range

A
  • Acute:
  • sexual dysfunction (worst of all classes)
  • Restlessness / insomnia (amphetamine-like effects
111
Q

MAOI long-term side effects therapeutic range

A
  • weight gain
  • postural hypotension
  • reflex tachycardia via downregulation of α1 adrenergic receptors
112
Q

MAOI side effects toxic range

A
  • CV: hypotension/Arrhythmias
  • CNS: ataxia / confused states / convulsions / coma
113
Q

MAOIs Drug interactions overview

A
114
Q

MAOIs plasma binding

A

High plasma protein binding

115
Q

MAOIs serotonin syndrome

A

YES

116
Q

MAOIs hypertensive crisis

A

especially with irreversible MAOIs

  • tyramine containing foods (some cheeses, beers, soy products)
  • Decongestants in cold medications (ephedrine, pseudoephedrine, phenylprolamine)
117
Q

MAOIs clinical use

A
  • limited to treatment-resistant cases of depression
  • because of intense side effects
  • but
  • advent of newer selective reversible agents?
  • Development of transdermal preps would avoid the 1st pass metabolism
118
Q

St. Johns Wort

A
119
Q

St John’s Wort active agents

A
  • Hypericin
  • Hyperforin
  • Flavinoids
  • and other active agents
120
Q

St John’s Wort MOA

A

weak NE, DA & 5HT reuptake inhibitor

Weak MAO inhibition (types a & B)

glutamate, GABA & adenosine receptor antagonism

121
Q

St John’s Wort plasma protein binding

A

potential for drug interactions

122
Q

St John’s Wort efficacy

A

some efficacy for mild to moderate depression

123
Q

St John’s Wort dosing issue

A

continuing problem of variable dosing

124
Q

St John’s Wort contraindications

A

Antidepressants

125
Q

Treating Major Depressive disorder I

A
126
Q

considered a disease of 3rds

A

Major Depressive disorder I

  • 1/3 are properly diagnosed
  • 1/3 of the diagnosed are properly treated
  • 1/3 of the treated don’t respond significantly
127
Q

Major Depressive disorder I adjuncts or switching drugs

A

adding an adjunct or switching can increase efficacy

128
Q

Treatment of Major Depressive disorder I concerns

A
  • need to ensure sufficient dose
  • Non-pharmacological interventions in milder cases
  • Drugs more effective in more depressed patients
  • some agents are more effective with certain types of depression
  • Consider side effects you most want to avoid
  • Greater efficacy & compliance when combined with other therapies
129
Q

Treating Major Depressive disorder II

A
130
Q

Depression comorbidity

A
131
Q

Challenges with Antidepressant therapy

A
132
Q

Other uses of antidepressants

A

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