2.16: Anti Depress Flashcards
(61 cards)
1
Q
What is dysthymia?
A
Peristent depressive disorder
2
Q
Uses for antidepressants outside of depression?
A
- Anxiety
- PTSD
- Eating disorders
- OCD
3
Q
What is the monoamine hypothesis of depression?
A
- It was noted that reserpine depleted amines and inducted depression
- Noted that antidepressants enhanced monoamine systems
4
Q
What is the paradox in antidepressant treatments?
A
- Side effects will be noted from day one
2. Can take weeks to see impact on depression
5
Q
What are MAOIs?
A
“Monoamine Oxidase Inhibitors”
6
Q
What are TCAs?
A
“Tricyclic antidepressants”
7
Q
What are SNRIs?
A
“Serotonin Norepinephrine reuptake inhibitors”
8
Q
Where are monoamine oxidases found?
A
In BOTH Noradrenergic and Serotonergic PREsynaptic neurons
9
Q
What are MAOs? What do they do?
A
“Monoamine oxidase”
- Breakdown NE, 5HT, and Dopamine
- By inhibiting these, MAOIs increase NT in presynaptic neurons for release
10
Q
What is 5HT?
A
Serotonin
11
Q
What does MAO-A do?
A
Metabolizes the catecholamines:
- NE
- Epi
- 5HT
* **MAO-A is responsible for antidepressant effects
12
Q
What does MAO-B do?
A
Metabolizes trace amines:
1. 5HT at high []
13
Q
What are RIMAs?
A
“Reversible inhibitors of MonoAmine oxidase”
- Not available in the US
14
Q
How do the irreversible MAOIs work?
A
- Covalently bind to MAO permanently disabling
- Enzymes must be replaced to function again
- Replacement takes 10 -14
15
Q
What is special about selegiline?
A
- Irreversible BUT prefers MAO-B
- At high doses works on MAO-A as well
- **Only acts as antidepressant at high doses
16
Q
MAOI side effects?
A
- Nausea, constipation, appetite change
- Orthostatic hypotension
- Sedation
- Sleep disturbance
- Sexual dysfunction
- Weight gain
* *Rare/severe: - Hypertensive crisis
- Serotonin syndrome
17
Q
Foods that can cause hypertensive crisis in patient on MAOIs?
A
Those high in tyramine:
- Aged cheese
- Wine
- Cured meats
- Beer
- Fermented foods
18
Q
How does cheese rxn work?
A
- Tyramine found in cheese normally metabolized by liver MAOIs
- When not metabolized, becomes a pressor = HTN
- MAOIs stop it from being metabolized
19
Q
How is selegiline administered? Why is this important?
A
- Transdermal patch
- Hits brain first avoiding first pass metabolism = works at lower dose
- Does not have hypertensive crisis side effect
20
Q
Drugs that can cause hypertensive crisis with MAOIs?
A
- OTC cold medicines
- Cocaine
- Ecstasy
- Opioids
* **Brain aneurism / hemorrhagic stroke is fear
21
Q
What cause serotonin syndrome?
A
- MAOI: leads to serotonin build up
- SSRI: prevent serotonin reuptake
* ***Over abundance of serotonin in cleft stimulating post synaptic neuron
22
Q
Appearance of serotonin syndrome?
A
- Increased reflexes
- Myoclonus
- Disorientation
- Autonomic dysfunction: Increased temp and unstable BP
- Seizure
23
Q
Name the MAOIs?
A
MAOIs work well when you are in the “PITS”
- Phenelzine
- Isocarboxazid
- Tranylcypromine
- Selegiline
24
Q
MOA of TCAs?
A
- NE reuptake inhibitors
2. 5HT reuptake inhibitors
25
Name the TCAs?
TCAs taste like "CANDDI"
1. Clomipramine
2. Amitriptyline - Tertiary (Nortriptyline)
3. Nortriptyline
4. Desipramine
5. Doxepin
6. Imipramine - Tertiary (Desipramine)
26
Which are the tertiary TCAs and what to they become?
1. Imipramine - > Desipramine
| 2. Amitriptyline - > Nortriptyline
27
Difference in function between tertiary and secondary TCAs?
* Tertiary : NE = 5‐HT reuptake inhibitor;
| * Secondary : NE > 5‐HT re‐uptake inhibitor
28
Kinetics of TCAs?
- Highly lipid soluble
- High protein binding
- Large volume of distribution
- Significant first pass metabolism
- Rapid absorption
29
What does a high volume of distribution mean?
- Much more drug is found in tissue than in serum
30
Side effects of TCAs?
1. Antihistaminic: sedation / weight gain
2. Anti muscarinic: sedation and confusion
3. Increased 5HT: Sexual dysfunction
4. Increased NE: Sweating / hypertension
31
List receptor affinity for TCAs in order of most to least?
1. Histaminic receptors
2. Muscarinic receptors
3. Antidepressants (Target)
4. CNS toxicity (5x therapeutic dose)
5. CV toxicity (5x therapeutic dose)
32
Who should you not use TCAs in?
1. Elderly
2. Benzos / opiates / barbiturates
3. Alcoholics
33
Name the SSRIs?
SSRIs Make you want to "FFluox your PECS"
1. Fluoxetine
2. Fluvoxamine
3. Paroxetine
4. Escitalopram
5. Citalopram
6. Sertraline
34
Which SSRI has longest half life?
Fluoxetine: 1 - 4 days
| **Its metabolite has 7 - 15 day half life
35
Which SSRIs are CYP450 inhibitors?
1. Fluoxetine
2. Paroxetine
* **CYP 450-2d6
36
Which SSRIs have the shortest half lives?
1. Fluvoxamine
2. Paroxetine
* **Highest risk of discontinuation syndrome
37
What is discontinuation syndrome?
Withdrawal from a drug. Seen in SSRIs with shortest 1/2 life:
1. Fluvoxamine
2. Paroxetine
38
Relationship between Citalopram and Escitalopram?
Citalopram: R and S isomer of drug (S is active)
| "Es"citalopram: Only the active form (S Isomer)
39
What to tell patient about SSRI side effect?
1. May only happen once or intermittent
2. Can be dose dependent
3. If it is mild try to wait it out until benefit of antidepressant kicks in
40
Common side effects for SSRIs?
1. GI
2. Anxiety
3. CNS
4. Sexual dysfunction
41
What occurs in SSRI discontinuation syndrome?
Dizziness, nausea, fatigue, headache, insomnia, restlessness, unstable gait, brain zaps
***This is mild, annoying, and not life threatening
42
Which are the SNRIs?
1. Venlafaxine
2. Desvenlafaxine
3. Duloxetine
43
What do the SNRIs block?
Both the serotonin and NE reuptake pumps
44
Which pumps will venlafaxine block in order?
1. Serotonin
2. NE
3. Dopamine
* **Hits all 3 monoamines
45
Which SNRI has highest protein binding?
Duloxetine
46
Which SNRI has shortest 1/2 life?
Venlafaxine
| ***Highest risk of discontinuation syndrome
47
What is the metabolite of venlafaxine?
Desvenlafaxine
48
What are the atypical antidepressants? Mechanisms?
1. Bupropion: NE and dopamine reuptake inhibitor
| 2. Mirtazapine: blocks presynaptic A2 adrenergic autoreceptors on both NE and 5HT neurons = higher NE and 5HT [ ]s
49
What does Bupropion have highest affinity for?
1. Dopamine
| 2. NE
50
What is special about mirtazapines action on serotonin?
Also blocks the following serotonin receptors;
1. 5HT-2a
2. 5HT-2c
3. 5HT-3
* ***Prevents nausea, sexual dysfunction, insomnia, and anxiety that other serotonin RIs cause
51
Drawback of mirtazapine?
1. Weight gain
| 2. Sedative: take at night to help with sleep
52
What are bupropion and mirtazapine often combined with in the treatment of depression?
SSRIs and SNRIs
53
What is nefazodone?
- Blocks 5HT reuptake
| - 5HT-2a receptor antagonist *** No sexual side effects and mild sedation
54
What does antagonizing the 5HT-2a receptor result in?
Prevention of sexual side effects
55
What is vilazodone?
- 5HT reuptake inhibitor
- NO weight gain
- No Sexual side effects
56
What is Vortioxetine?
- 5HT reuptake inhibitor
- NO weight gain
- No Sexual side effects
57
How long do you have to wait after stopping MAOI to start another antidepressant?
~ 2 weeks to wait for neurons to regenerate MAO enzymes in neurons
***This is because of its long half life allowing its effects to persist in the system for long after use is stopped
58
How long do you have to wait after stopping RIMA to start another antidepressant?
Day or two, much shorter half life as these are reversible
59
How many half lives do you have to wait before starting MAOI when switching from another antidepressant?
- 5 1/2 lives
- This is usually about 1 week
* ***Since the 1/2 life of fluoxetine is so long you would need to wait closer to 5 weeks
60
What occurs if you do not wait long enough when switching to or from MOAI?
Risk of Serotonin syndrome or hypertensive crisis depending on what the mechanism of the other drug is
61
Which SSRIs are most likely to cause DDIs?
1. Fluvoxamine
| 2. Fluoxetine
