Mood Disorder Pharmacology Flashcards Preview

Pharmacology Test #6 > Mood Disorder Pharmacology > Flashcards

Flashcards in Mood Disorder Pharmacology Deck (76)
Loading flashcards...
1

Criteria for major depressive disorders

1. Depressed mood for 2+ weeks
2. Anhedonia
3. Anxiety
4. Disrupted sleep/appetite
5. Cognitive deficits
6. Loss of self-worth
7. Suicidal thoughts

2

Co-morbid medical/psychiatric conditions with major depressive disorders

CAD, diabetes, stroke, chronic pain, drug abuse

3

Monoamine hypothesis

MDD caused by a deficiency in cortical/limbic 5HT, NE, DA

4

Two theories of depression that are non-mutually exclusive

the monoamine hypothesis and the neurotrophic hypothesis

5

Evidence for the monoamine hypothesis

1. Reserprine (monoamine depleter) causes depression
2. Dietary changes: patients treated with AD relapse when tryptophan is withdrawn from diet
3. Genetics: SNPs in SERT associated with MDD
4. 5HT, NE receptors are decreased in MDD patients
5. 5HT/NE/DA agents work

6

Neurotrophic hypothesis

MDD is caused by loss of neurotrophic support and ADs restore neurogenesis and lost synaptic connectivity

7

Brain-derived neurotropic factor (BDNF) and neurons in a normal state

cell receives input from monoamine and BDNF stimulation, which supports neurotrophy and synaptic connectivity

8

BDNF and neurons in a depressed state

in part due to interference via glucocorticoids, BDNF is reduced and results in hypotrophy and loss of connectivity

9

BDNF and neurons in a treated state

monoamines result in increased CREB expression and results in resumption of normal BDNF secretion, re-gained connectivity

10

BDNF is critical for

neurotrophic support and required for the action of ADs

11

Evidence for the neurotrophic hypothesis:

1. BDNF changes in MDD: stress/pain reduces BDNF, causing structural changes in hippocampus similar to that seen in MDD
2. BDNF has AD properties: direct infusion of BDNF in rodent has AD effect
3. ADs cause increased BDNF/neurogenesis
4. Human MDD and BDNF: MDD associated with drop in BDNF

12

Why do antidepressants exhibit a delayed onset of several weeks compared to when their biochemical effects are thought to occur?

Time for monoamines to changes synthesis of BDNF, time for restored synaptic connectivity, and time for changes to occur such as up-or down-resgulation in signal transduction machinery

13

Antidepressant drug classes:

1. SSRIs
2. SNRIs (Serotonin-NE Reuptake Inhibitors)
3. 5-HT2 Antagonists
4. Tetracyclic/Unicyclic antidepressants
5. MAOIs

14

SSRIs

1. Fluoxetine (Proxac)
2. Paroxetine (Paxil)
3. Fluvoxamine (Luvox)
4. Sertraline (Zoloft)
5. Citalopram (Celexa)
6. Escitalopram (Lexapro)

15

Which SSRIs inhibit P450s?

1. Fluoxetine (Proxac)
2. Paroxetine (Paxil)
3. Fluvoxamine (Luvox)

16

What are SSRIs selective for?

more selective for SERT over NET

17

First choice for treatment of MDD due to safety and efficacy considerations

SSRIs

18

SSRIs Indications

MDD; Anxiety disorders; Premenopausal Dysphoric disorder; Eating disorders (bulimia only)

19

GAD

generalized, free-floating anxiety/undue worry

20

OCD

chronic anxiety-provoking thoughts (obsessions) and temporary anxiolytic actions (compulsions) taken to alleviate the anxiogenic thoughts

21

PTSD

anxious thoughts, hypervigilance from a traumatic event

22

Adverse effects of SSRIs

1. Sexual dysfunciton
2. Weight gain/loss
3. Serotonin syndrome
4. Adolescent suicide
5. Withdrawal sndrome
6. Effects on newborns

23

SSRI withdrawal

dizziness, paresthesias

24

Effects on newborns when mothers are on SSRIs

persistent pulmonary HTN (serious, fatal sometimes); withdrawal signs in infants; congenital malformations

25

Newer SNRIs

1. Duloxetine (Cymbalta)
2. Venlafaxine (Effexor)
3. Desvenlafaxine (Pristiq)

26

Two classes of SNRIs

the older TCAs and a newer group of pure re-uptake inhibitors that hit NET with high affinity

27

Tricyclic Antidepressants (TCA)

1. Amitriptyline (many receptors hit)
2. Nortriptyline (secondary amine)
3. Imipramine (anticholinergic)
4. Desipramine (metabolite of imipramine)
5. Clomipramine

28

Clinical use of TCAs

Used only in refractory MDD (not responsive to SSRIs)

29

Indications of SNRIs

Refractory MDD; anxiety disorders; pain (diabetic neuropathy, fibromyalgia); enuresis (bed wetting); insomnia

30

Adverse effects of SNRIs (most apply to the TCAs)

1. Cardiotoxicity
2. Sexual dysfunction
3. Weight loss
4. Serotonin syndrome (TCA and MAOI co-admin)
5. Suicidal thoughts
6. Withdrawal syndrome
7. Sedation