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Antidepressant drugs Flashcards

1
Q

name 7 antidepressant drug categories?

A
  1. MAO inhibitors
  2. TCA’s
  3. Serotonin selective reuptake inhibitors
  4. Dual serotonin & norepinephrine reuptake inhibitors
  5. 5-HT2 antagonists/reuptake inhibitors
  6. NEpi & dopamine reuptake inhibitors
  7. Antagonists at alpha2, 5-HT2 & 5-HT3 receptors
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2
Q

what are some MAO inhibitors?

A
  1. isocarboxazid
  2. phenelzine
  3. tranylcypromine
  4. selegline
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3
Q
  1. isocarboxazid
  2. phenelzine
  3. tranylcypromine
  4. selegline

MOA?

A

inhibit MAO-A

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4
Q

what are the two types of MAO’s?

A

MAO-A and MAO-B: metabolize dopamine and tyramine

MAO-A: metabolizes NEpi and serotonin

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5
Q

What are the two hydrazine deveratives of MAO?

A
  1. phenelzine

2. isocarboxazid

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6
Q

what are the two non-hydrazines derivatives of MAO?

A
  1. tranycypromine

2. selegiline

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7
Q
  1. isocarboxazid
  2. phenelzine
  3. tranylcypromine

MOA?

A

bind irreversibly and nonselectively to MAO-A and MAO-B.

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8
Q

which MAO is approved to treat Parkinson’s?

A

selegiline: MAO-B inhibitor.

high dose can inhibit MAO-A
avail as transdermal

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9
Q
  1. isocarboxazid
  2. phenelzine
  3. tranylcypromine
  4. selegline

Uses?

A

rarely used d/t toxicity and food/drug interactions

tx: depression unresponsive to other antidepressants

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10
Q
  1. isocarboxazid
  2. phenelzine
  3. tranylcypromine
  4. selegline

A.E?

A
  1. drowsiness
  2. insomnia
  3. nausea
  4. orthostatic hypotension
  5. weight gain
  6. muscle pain
  7. sexual dysfunction
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11
Q
  1. isocarboxazid
  2. phenelzine
  3. tranylcypromine
  4. selegline

two classes of Drug interactions?

A
  1. serotonin syndrome

2. cheese rxn.

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12
Q

What is serotonin syndrome?

A

combination of MAOI c a serotonergic agent.
Life-threatening

  1. hyperthermia
  2. muscle rigidity
  3. myoclonus

overstimulation of 5-HT1A and 5-HT2 receptors

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13
Q

What is the cheese rxn?

A

tyramine is contained in certain foods - cheese, chicken liver, soy, pickled fish and red wines.

tyramine inactivated by MAO in the gut.
Pts on MAOI cannot degrade tyramine -> release of catecholamines 
1. tachycardia
2. htn
3. arrhythmias
4. seizures
5. stroke
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14
Q

what are other MAOI drug interactions?

A
  1. sympathomimetic drugs

2. OTC cold preps contain pseudoephedrine and phenylpropanolamine.

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15
Q

What are two drugs help c cheese rxn?

A
  1. phentolamine
  2. prazosin

manage htn

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16
Q

Which MAOI’s is better tolerated and safer and unlikely to cause tyramine-induced htn?

A

selegiline transdermal patch

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17
Q

what is MAOI discontinuation syndrome?

A

abrupt d/c of MAOI’s

  1. worsening of depressive sx’s
  2. confusion
  3. disorientation
  4. psychosis
  5. anxiety
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18
Q

What are some TCAs?

A
  1. amitriptyline
  2. Clomipramine
  3. desipramine
  4. imipramine
  5. nortriptyline
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19
Q
  1. amitriptyline
  2. Clomipramine
  3. desipramine
  4. imipramine
  5. nortriptyline

mOA?

A

block SERT and NET -> increased monoamine conc in the cleft.

clomipramine = more selective for SERT
Desipramine and nortriptyline = more selective for NET

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20
Q
  1. amitriptyline
  2. Clomipramine
  3. desipramine
  4. imipramine
  5. nortriptyline

A.E?

A

block musc receptors:
- blurred vision, xerostomia, urinary retention, constipation and aggravation of narrow-angle glaucoma

alpha1-adrenoceptors:
- orthostatic hypotension, reflex tachycardia

H1 blockage:
- sedation and weight gain

Sexual effects:
- more in clomipramine

block cardiac fast Na channels -> arrythmias (COD)

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21
Q
  1. amitriptyline
  2. Clomipramine
  3. desipramine
  4. imipramine
  5. nortriptyline

Precautions?

A

narrow therapeutic index

pts c suicidal thoughts should be given only limited quantities and monitor closely

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22
Q
  1. amitriptyline
  2. Clomipramine
  3. desipramine
  4. imipramine
  5. nortriptyline

Overdose?

A

induce lethal arrythmias

Na bicarbonate = use to reverse conduction block.

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23
Q
  1. amitriptyline
  2. Clomipramine
  3. desipramine
  4. imipramine
  5. nortriptyline

discontinuation syndrome?

A
  1. flulike sx’s
  2. myalgia
  3. excessive sweating
  4. HA
  5. nausea
  6. insomnia
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24
Q

What are amoxapine and Maprotiline and their MOA?

A

TCAs

potent NET inhibitors and less potent SERT inhibitors.
Both posses anticholinergic properties.
Amoxapine is moderate antagonist of D2 receptors: antipsychotic properties.

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25
Q

What are some Selective Serotonin-reuptake inhibitors (SSRI)?

A
  1. citalopram
  2. escitalopram
  3. fluoxetine
  4. fluvoxamine
  5. paroxetine
  6. sertraline
26
Q
  1. citalopram
  2. escitalopram
  3. fluoxetine
  4. fluvoxamine
  5. paroxetine
  6. sertraline

MOA?

A

inhibit serotonin uptake

27
Q
  1. citalopram
  2. escitalopram
  3. fluoxetine
  4. fluvoxamine
  5. paroxetine
  6. sertraline

uses?

A
  1. depression (DOC)
  2. OCD
  3. PD
  4. GAD
  5. PTSD
  6. SAD
  7. PMDD
  8. bulimia
28
Q
  1. citalopram
  2. escitalopram
  3. fluoxetine
  4. fluvoxamine
  5. paroxetine
  6. sertraline

A.E?

A
  1. increased serotonergic activity in gut = nausea, GI upset, diarrhea
  2. increased serotonergic tone in CNS = diminished sex function/interest.
  3. weight gain (esp c paroxetine)
29
Q
  1. citalopram
  2. escitalopram
  3. fluoxetine
  4. fluvoxamine
  5. paroxetine
  6. sertraline

Drug interactions?

A
  1. fluoxetine and paroxetine inhibit CYP2D6
  2. Fluvoxamine inhibits CYP1A2, CYP2C9 and CYPT3A4
  3. citalopram, escitalopram and sertraline - low potential for interactions
  4. serotonin syndrome if used c MAOI or another serotonergic rx.
30
Q
  1. citalopram
  2. escitalopram
  3. fluoxetine
  4. fluvoxamine
  5. paroxetine
  6. sertraline

Overdoses?

A

fatality is low but can cause seizures.

31
Q
  1. citalopram
  2. escitalopram
  3. fluoxetine
  4. fluvoxamine
  5. paroxetine
  6. sertraline

D/c syndrome?

A
  1. nervousness
  2. anxiety
  3. irritability
  4. tearfulness
  5. electric shock sensations
  6. dizziness
  7. insomnia
  8. confusion
  9. confusion
  10. nausea
32
Q

Which SSRIs is most severe in d/c syndrome and which is least?

A

severe: paroxetine d/t short half life
least: fluoxetine d/t longer half life

33
Q

What are some Serotonin/NEpi reuptake inhibitors (SNRI)?

A
  1. venlafaxine

2. duloxetine

34
Q
  1. venlafaxine
  2. duloxetine

MOA?

A

block reuptake of serotonin and NEpi.

venlafaxine:
potent inhibitor of 5HT uptake
high doses: inhibits NEpi uptake
inhibit reuptake of dopamine weakly.

duloxetine:
inhibits serotonin and NEpi reuptake at all doses

35
Q
  1. venlafaxine
  2. duloxetine

drug interactions?

A

few CYP450 interactions

36
Q
  1. venlafaxine
  2. duloxetine

d/c syndrome?

A

vanlafaxine most d/t short half-life

37
Q

what is a NEpi & dopamine reuptake inhibitors (NDRI)?

38
Q

bupropion

MOA?

A

inhibits NEpi and dopamine uptake

increases NEpi and dopamine release.

39
Q

bupropion

overdose?

40
Q

what are two 5HT2 antagonists/reuptake inhibitors (SARI)?

A
  1. Nefazodone

2. Trazodone

41
Q
  1. Nefazodone
  2. Trazodone

MOA?

A

when 5HT reuptake is blocked by SSRIs, all 5HT recpetors are stimulated.
stimulation of 5HT1A receptors in raphe may help depression.
stimulation of 5HT2 receptors in forebrain = agitation/anxiety; spinal cord = sex dysfunction.

SARIs combine 5HT reuptake blockage c 5HT2 antagonism -> decrease undesired actions of stimulation of 5HT2 recptors.

42
Q
  1. Nefazodone
  2. Trazodone

A.E?

A

Nefazodone:
hepatotoxicity (no longer prescribed)

Trazodone:

  1. xtreme sedation
  2. hypnotic (main use)
  3. priapism (rare)
43
Q

What is a Noradrenergic & Specific serotonergic antidepressants (NASSA)?

A

Mirtazapine

44
Q

Mirtazapine

MOA?

A

antagonist of central presynaptic alpha2 receptors -> enhance release of NEpi and 5HT

antagonist at 5HT2 and 5HT3 recptors

H1 antagonist: sedation and weight gain

useful in insomnia or agitation

45
Q

What are some adjunctive tx of major depressive disorder?

A
  1. quetiapine
  2. aripiprazole
  3. olanzapine
46
Q

What are some clinical indications of antidepressants?

A
  1. depression (SSRI)
  2. anxiety disorders (SSRI first choice, bupropion least effective)
  3. chronic pain (TCAs and SNRI = neuropathic, SSRIs are not effective)
  4. eating disorders (help bulimia but not anorexia)
  5. Premenstrual dysphoric disorder (SSRIs)
  6. smoking cessation (bupropion)
47
Q

What are some antidepressants warnings/precautions?

A

Major Depressive Episode may be initial presentation of bipolar.

  • tx c antidepressant alone = precipitate mania
  • must screen for evidence of bipolar disorder.
48
Q

What are some drugs for bipolar disorder?

A
  1. lithium
  2. Valproate
  3. Carbamazepine
49
Q

Lithium

uses?

A

tx of manic-depressive pts and manic episodes

50
Q

Lithium

MOA?

A

inositol depletion theory:
G protein (Gq) activate PLC -> yield DAG and IP3
IP3 signal is terminated by conversion to IP2
IP2 is converted to IP1 by inositiol polyphosphatase
IP1 is converted to inositol by inositol monophosphatase

Lithium inhibits inositol polyphosphatase and monophosphatase = block regenration of inositol -> blcok signaling cascade in brain

Lithium inhibits central adrenergic, musc, and serotonergic neurotransmission.

ONLY affect neurons c active receptors!!

51
Q

Lithium

acute A.E?

A

narrow therapeutic window

  1. vomiting
  2. profuse diarrhea
  3. coarse tremor
  4. ataxia
  5. coma
  6. convulsions
  7. death (if plasma conc 3-5mM)
52
Q

Lithium

A.E?

A
  1. tremor, sedation, ataxia, aphasia = alleviate by propranolol or atenolol.
  2. seizures
  3. weight gain
  4. hypothyroidism
  5. nephrogenic diabetes insipidus
  6. edema
  7. dermatitis
  8. alopecia
  9. leukocytosis
53
Q

Lithium

in pregnancy?

A

increase incidence of congenital cardiac anomalies

Cat D

contraindicated in nursing mothers.

54
Q

Lithium

Monitoring?

A
  1. serum lithium conc
  2. thyroid function
  3. renal function
55
Q

Lithium

Drug interactions?

A
  1. thiazide diuretics
  2. NSAIDs
  3. ACE inhibitors
  4. ARBs
56
Q

What are alternatives to lithium?

A
  1. valproate

2. carbamazepine

57
Q
  1. valproate
  2. carbamazepine

Monitoring?

A

valproate: cbc and liver
carbamazepine: cbc

58
Q

what are some atypical antipsychotics can be used as lithium alternatives?

A
  1. olanzapine
  2. aripiprazole
  3. quetiapine
  4. risperidone
  5. ziprasidone
59
Q

what is an antiepileptic can be used as lithium alternative?

A

Lamotrigine

60
Q

What is the monoamine hypothesis?

A

deplete in monoamine = depression

Pharmacology (13 decks)

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