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Psychopharm > Antidepressant MoAs > Flashcards

Antidepressant MoAs Flashcards

1
Q

List the tertiary amines

A

“AICD”

Amitryptiline

Amoxapine

Imipramine

Clomipramine

Doxepin

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2
Q

List the secondary amines

A

Desipramine

Maprotiline

Nortryptiline

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3
Q

Imipramine, the first TCA, is closely related to which other psych med (non-TCA)?

A

Chlorpromazine

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4
Q

Imipramine was derived from?

A

Methylene blue (antihistamine)

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5
Q

Tertiary TCAs have highest affinity for ___

A

blocking 5HT reuptake

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6
Q

Secondary amines have high affinity for _____

A

blocking NE reuptake

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7
Q

Tertiary amines are metabolized to ____

A

secondary amines in the liver

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8
Q

TCA association: Panic disorder with agoraphobia

A

Imipramine

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9
Q

TCA assocation: GAD

A

Impirapmine and doxepin

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10
Q

TCA Association: OCD

A

clomipramine (FDA approved)

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11
Q

TCA assocation: enuresis

A

Imipramine (NOT FIRST LINE)

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12
Q

Cardiac side effects of TCAs are mediated by ___

A

Na and Calcium channels

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13
Q

Compared to SSRIs, TCAs are less likely to cause …

A

sexual side effects, weight gain, and sleep disturbance

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14
Q

Most serotonergic TCA

A

Clomipramine

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15
Q

Most anticholinergic and alpha TCA

A

Amitriptyline

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16
Q

Most noradrenergic, low anticholinergic TCA

A

Desipramine

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17
Q

Low anticholinergic TCA

A

Nortriptyline

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18
Q

Most antihistamine TCA

A

Doxepin

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19
Q

Closest TCA to nortriptyline but may be more noradrenergic

A

Protriptyline

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20
Q

TCA Pharmacokinetics

A

fast absorption in small intestine. T1/2 vary from 10-70 hours (once qd).

Nortriptyline and doxepin exist in liquid solutions.

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21
Q

The tertiary TCAs are ________ and other enzymes, leading to the formation of secondary TCAs

A

demethylated by 2C19

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22
Q

In the case of amitriptyline and imipramine, they are converted to the secondary TCAs ________

A

nortriptyline and desipramine

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23
Q

delirium due to anticholinergic and antihistamine effects, especially with _______

A

amitriptyline

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24
Q

Increased risk of seizures, up to 2% with ———

A

clomipramine

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25
Q

Which class of meds: avoid in narrow- angle glaucoma (is fine in chronic open-angle glaucoma)

A

TCAs

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26
Q

Least orthostatic TCA

A

Nortryptiline

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27
Q

increased LFTs are associated with ——— (TCAs)

A

imipramine and desipramine

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28
Q

Usual cause of death in TCA overdose

A

cardiac arrhythmia

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29
Q

Which are the tetracyclic antidepressants?

A

Amoxapine and Maprotiline

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30
Q

Amoxapine (Asendin)

A

derived from mid-potency antipsychotic, loxapine. May have TD and may have greater risk of seizures than other TCAs.

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31
Q

Amoxapine mechanism

A

Increases 5-HT, NE, and blocks DA.

It is the only TCA/tetracyclic with both antidepressant and antipsychotic properties.

Has an active metabolite.

Half-life is 8 hours, but the active metabolite has a half-life of >30 hours.

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32
Q

Maprotiline (Ludiomil)

A

greatly differs from the others in that it lacks 5-HT reuptake inhibition and primarily acts to inhibit NE reuptake.

Is a strong antihistamine, is sedating. Is less anticholinergic and alpha blocking than amitriptyline.

Half-life is 30–60 hours.

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33
Q

Fun fact: first SSRI was actually ———

A

zimelidine (now banned for causing Guillain- Barre syndrome and other sometimes fatal side effects)

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34
Q

Best SSRI in pregnancy?

A

Fluoxetine has most data

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35
Q

SSRIs approved for OCD

A

fluvoxamine, paroxetine, sertraline, and fluoxetine Use higher doses than in MDD

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36
Q

SSRIs approved for use in panic disorder

A

People’S Freaking

Paroxetine, Sertraline, Fluoxetine

(But you can try other SSRIs, and don’t forget benzos)

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37
Q

SSRIs approved for bulemia and anorexia

A

Fluoxetine

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38
Q

SSRI FDA Approvals in children

A

fluoxetine for the treatment of depression fluoxetine, fluvoxamine, and sertraline for the treatment of OCD.

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39
Q

FDA Antidepressant black Box Warning

A

under the age of 24. This was based upon meta-analyses that showed increased risk of suicidal thoughts and behaviors, in addition to aggression and hostility in children treated with SSRIs.

40
Q

SSRI Pharmacokinetic takeaways:

A

Regarding CYP interaction, fluvoxamine has the most interaction with 1A2, 2C, and 3A inhibition (with minimal 2D6 inhibition).

Fluoxetine and paroxetine are the strongest 2D6 inhibitors, with sertraline having moderate inhibition.

41
Q

SSRI Pharmacodynamic takeaways

A

citalopram and escitalopram are the most selective inhibitor of 5-HT reuptake, having little inhibition of DA, NE, histamine, or GABA.

Fluoxetine weakly inhibits NE reuptake and binds to 5-HT2C.

Sertraline weakly inhibits NE and DA reuptake.

Paroxetine has significant anticholinergic activity at higher doses.

42
Q

Which SSRIs are most selective for blocking only serotonin reuptake?

A

citalopram and escitalopram are the most selective inhibitor of 5-HT reuptake

43
Q

SSRI drug interactions - Big picture

A

2D6 inhibitors will slow the metabolism of carbamazepine, diazepam, phenytoin, and antineoplastic agents.

Sertraline may displace warfarin from proteins, leading to increased PTT.

Fluvoxamine increases concentrations of multiple BZD, warfarin, clozapine, carbamazepine, methadone, propranolol, and diltiazem. It has little interaction with lorazepam.

44
Q

Incidence of sexual dysfunction on SSRIs

A

50-80%

45
Q

Common treatment for SSRI-induced sexual dysfunction

A

decreasing the dose, adding bupropion (increases DA) or buspirone (antagonism of 5-HT via autoreceptor), or use of sildenafil

46
Q

SSRIs with most GI side effects

A
  • Sertraline and Fluvoxamine - nausea, diarrhea, vomiting are most common with these. Mediated through 5-HT3.
  • Paroxetine is associated with constipation (anticholinergic).
47
Q

SSRI that commonly causes anxiety

A

fluoxetine

48
Q

SSRI that commonly causes insomnia

A

fluoxetine

49
Q

Common SE of SSRIs

A

Sexual, GI, anxiety, insomnia, sedation, emotional blunting. More rarely, seizures (0.2%), platelet issues (binding),

50
Q

Best SSRI in breast feeding mothers?

A

Sertraline (data?)

51
Q

Which SSRI should make you think about getting an EKG to look at the QTc

A

Citalopram is known to cause QTc prolongation. Do not higher than 40mg.

52
Q

Sertraline generic quirks

A

Commonly has bruising and hair loss. The original medication was often sedating, leading to pm dosing. The generic often has the opposite effect, with patients initially experiencing feelings of restlessness, anxiety, and hypervigilance (which are problematic considering sertraline is used for anxiety). Have seen a couple cases of bruxism which improves with buspirone. Seen Torsades and neutropenia x1 recently with sertraline.

53
Q

Medication associated with pulmonary hypertension in newborns of mothers who took it.

A

Paroxetine

54
Q

Paroxetine generic quirks

A

I avoided this medication for a long time due to fear of weight gain and sexual side effects. Now that the side effects of citalopram are more apparent, I am less hesitant to use paroxetine (a medication that may have better efficacy than citalopram).

55
Q

Vilazodone is like an SSRI with ____

A

5-HT1A agonism (like buspirone). Similar to combining citalopram + buspirone.

56
Q

Vilazodone side effect profile

A

Fewer sexual side effects and weight gain than other SSRIs.

Discontinuation symptoms may occur if stopping quickly.

Watch out for QTc prolongation at high doses.

57
Q

Vilazodone is metabolized by ____

A

CYP 3A4

58
Q

Vilazodone dosing

A

Start at 10mg, up by 10 mg per week. Goal of 40mg daily. Max dose ~80mg.

59
Q

Venlafaxine indications

A

FDA approved for MDD, GAD, Panic Disorder, Social Anxiety Disorder. Has been used for diminishing symptoms of menopause, treating chronic pain, and dual diagnosis of MDD and cocaine dependence.

60
Q

Venlafaxine is metabolized by _____

A

2D6

61
Q

Venlafaxine is metabolized to ____

A

desvenlafaxine

62
Q

Venlafaxine dosing

A

IR is most associated with nausea and often is started in low doses of 37.5 mg twice daily (use in the am and at 1pm due to risk of insomnia if taken at bedtime).

As dose increases, affinity for NE transporter increases. As a result, HTN and anxiety are more associated with higher doses of the medication.

When taken as the XR, the maximum dose is 375 mg

63
Q

Desvenlafaxine dosing

A

therapeutic dose of 50 mg (which happens to be the starting dose) with no significant data to support improved efficacy of 100 mg.

64
Q

Venlafaxine dosing (and side effect) pearl

A

As dose increases, affinity for NE transporter increases. As a result, HTN and anxiety are more associated with higher doses of the medication.

65
Q

Duloxetine indications

A

FDA approved for MDD, Diabetic peripheral neuropathy, fibromyalgia, GAD, Chronic musculoskeletal pain.

Also used for stress urinary continence (duloxetine increases the tone of the urethral sphincter and will be marketed as Yantreve), neuropathic pain/chronic pain, other anxiety disorders.

66
Q

Duloxetine mechanism

A

similar to venlafaxine (5-HT and NE reuptake blockade) but has equal affinity for 5-HT and NE transporters at all doses.

67
Q

Duloxetine dosing

A

There is little data to show greater clinical efficacy in doses above 60 mg for the treatment of depression. BID dosing may reduce side effects seen with once-daily dosing. Starting dose is 20 or 30 mg.

68
Q

Duloxetine side effects

A

similar to venlafaxine, including nausea, dizziness, constipation, insomnia, and sexual dysfunction. Less likely to cause HTN. May increase Hgb A1c in long term treatment. Potentially increases LFTs (especially in hepatically compromised patients). Discontinuation syndrome can occur.

69
Q

Is bupropion generic less effective?

A

We don’t know, but - In 2007, in response to multiple patient reports about the generic Bupropion XL having more side effects and being less efficacious than Wellbutrin XL, the FDA concluded that the discrepancy was due to “natural mood variation.”

70
Q

Bupropion indications

A

FDA approved for MDD, seasonal affective disorder, nicotine addiction (smoking cessation under Zyban brand name, generally used in combination with nicotine substitutes),

Also used for BMD (less likely to precipitate mania in BMD I than TCAs and in BMD II than most other antidepressants), ADHD, cocaine detoxification (reducing cravings), hypoactive sexual desire disorder due to SSRIs.

71
Q

Bupropion dosing

A

available in immediate release IR (BID or TID), sustained release SR (used BID), and extended release ER (once daily). The active ingredient is the same in each. The IR reaches peak concentration in 2 hours, SR in 3 hours and ER in 5 hours. The half-life is 12 hours

72
Q

Bupropion mechanism of action

A

Mechanistically, bupropion inhibits the reuptake of DA and NE.

73
Q

Bupropion pharmacodynamics

A

Is metabolized to active metabolite hydroxybupropion by CYP2B6 (inhibited by fluoxetine).

Hydroxybupropion itself inhibits 2D6. Bupropion has affinity for DA transporters while hydroxybupropion has more selective affinity for NE transporters

74
Q

Bupropion and utox

A

Bupropion may have a false positive UDS for amphetamines

75
Q

Bupropion side effects

A

seizure risk is 2% with 600 mg and 0.1% with 300-450 mg (the SR and ER at same doses has risk of 0.05%, equivalent to the other antidepressants). Side effects most common include headache, insomnia, dry mouth, tremor, and nausea. Severe anxiety and panic disorder can be worsened by bupropion. Can worsen psychosis and delirium due to dopaminergic activity.

76
Q

Mirtazapine mechanism (general)

A

Uknown exactly how - a tetracyclic antidepressant that is both serotonergic and noradrenergic through a mechanism different from serotonin reuptake blockade or monoamine oxidase inhibition.

77
Q

Mirtazapine half-life

A

30 hours

78
Q

Mirtazapine mechanism (detailed)

A

Works to increase 5-HT at the 1A receptor (the main site for the antidepressant actions of most antidepressants).

It does this by blocking the 5-HT2A, 5-HT2C and 5-HT3 receptors, resulting in all serotonin being directed to the 5-HT1A receptor.

As a result, there are less sexual and GI side effects than other antidepressants.

Additionally, it increases NE and DA transmission (recall 5-HT2C normally inhibits DA—think atypical antipsychotic mechanism of action).

Strong histamine affinity causes sedation and weight gain. There is minimal anticholinergic effect

79
Q

Mirtazapine dosing tips

A

Starting dose ranges from 7.5 to 15 mg.

Increasing dose above 30 mg leads to higher NE effects and less sedation

80
Q

Mirtazapine side effects

A

Somnolence occurs in >50% (worsened by alcohol or other sedatives), increases appetite and cholesterol, reduction of ANC (monitor for fever, chills, sore throat), and agranulocytosis.

81
Q

levomilnacipran (Fetzima) indication

A

MDD

82
Q

Levomilnacipran (Fetzima) MOA

A

The L-enantiomer of Milnacipran (Savella, FDA approved for fibromyalgia)), levomilnacipran is also dual serotonin and norepinephrine reuptake inhibitor.

However, it has much higher selectivity for reuptake blockade of NE than 5-HT reuptake blockade

83
Q

levomilnacipran side effects

A

HTN, tachycardia, GI symptoms (N/V, constipation), hyperhidrosis, urinary hesitancy/retention, erectile dysfunction

84
Q

Iproniazid (trivia)

A

Was the first MAOi (1958-1961), but was pulled from the market because of hepatotoxicity

85
Q

List the MAOIs

A

STRIP’M

selegiline (Eldepryl)

tranylcypromine (Parnate)

rasagiline (Azilect)

isocarboxazid (Marplan)

phenelzine (Nardil)

moclobemide (Manerix)

86
Q

Which MAOI is available transdermally?

A

Selegiline

87
Q

What is MAO and what does it do?

A

It is found on the outer mitochondrial membrane, where it degrades monoamine neurotransmitters (NE, 5HT, DA, Epi, Tyramine).

88
Q

MAO-A breaks down what?

A

Think MOA-A = “All” (unlike B, which only does a couple)

Breaks down: NE, Epinephrine, 5-HT, DA and tyramine

89
Q

MAO-B breaks down

A

DT

dopamine and tyramine

90
Q

MAO indications

A

MDD

  • Some data may show that phenelzine may better treat atypical depression (hypersomnia and hyperphagia) than TCAs
  • May treat depression in Bipolar Disorder better than TCAs with less hypomania/mania
  • Depression associated with TBI
  • Tranylcypromine was included in the STAR*D trials as an effective option in treatment-resistant depression.

anxiety, phobias, pain, migraines, depression associated with TBI.

91
Q

Which TCAs are structurally related to amphetamines and may have a stimulant effect on the brain?

A

Stimulating The Persons

  • Selegiline
  • Tranylcypromine
  • Phenelzine
92
Q

MAO half-life pearls

A

Serum half-lives can be ~2-3 hours but have tissue half-lives with longer times.

HOWEVER - They irreversibly inactivate MAOIs, thus the effect can last up to 2 weeks, even with a single dose.

93
Q

What is Moclobemide?

A

Moclobemide is a reversible MAO-A inhibitor and has fewer side effects and less dietary restrictions. It is not approved for use in the United States at this time

94
Q

What % of patients on SSRIs gain weight?

A

Up to 30%, especially with paroxetine

95
Q

Vortioxetine dosing

A

Most of my patients are on 20mg, some did better on 30, and none (so far) did better (or worse) on 40 vs. 30. 10 is ok, kinda like 10 of Prozac or 50-75 of Zoloft.

There is definitely data in GAD, not yet in OCD, though there is no reason to anticipate it would not help in OCD. It’s just an SSRI with mild 1a partial agonism like Buspar and some fancy blocking of serotonin receptors subtypes.

It has antagonistic action at 5-HT3, like ondansetron, which is thought to have efficacy in OCD augmentation indirectly through blocking of 5-HT3. Not that this means much from a clinical standpoint.

Psychopharm (9 decks)

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