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T2 - Phase 3 - Brain, Mind, and Behavior > BMB 3 - Antidepressants & Anxiolytics; Antipsychotics; Sleep Aids > Flashcards

BMB 3 - Antidepressants & Anxiolytics; Antipsychotics; Sleep Aids Flashcards

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1
Q

What is the black box warning on all antidepressants?

A

Antidepressants increase the risk of suicidal thinking and suicide in patients < 24 years with major depressive disorder (MDD)

(NOTE: antidepressants may also “unmask” mania in patients with an underlying bipolar disorder.)

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2
Q

Name two of the hypotheses of the pathophysiology of major depressive disorder.

A

Amine hypothesis

Stress hypothesis

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3
Q

Describe the amine hypothesis of major depressive disorder.

A

Depression is caused by reduced levels of biogenic amines (e.g. 5-hydroxytrypatamine, dopamine, norepinephrine)

(_EVIDENCE_: reserpine depletes NE and 5-HT and can induce severe depression; TCAs and MAOIs have antidepressant effects.)

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4
Q

Describe the stress hypothesis of major depressive disorder.

A

Chronic stress →

↑ cortisol →

↓ brain-derived neurotrophic factor (BDNF) →

↓ neural plasticity →

depression

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5
Q

Why do antidepressants have a slow onset-of-action?

A

Monoamines stimulate signaling cascades →

↑ BDNF →

↑ neural plasticity

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6
Q

What is the onset-of-action of antidepressants?

A

> 3-4 weeks

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7
Q

How is resistant depression approached?

A

Increase dose,

switch type of antidepressant,

augment with a drug with a different mechanism

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8
Q

What pharmacological interactions put patients at greater risk of serotonin syndrome?

A

SSRIs or SNRIs combined with other serotonergic drugs (e.g. triptans or MAOIs)

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9
Q

Describe the symptoms of serotonin syndrome.

A

Hyperthermia,

hypertension,

muscle rigidity,

muscle jerks

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10
Q

How is serotonin syndrome treated?

A

Cyproheptadine

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11
Q

True/False.

Most antidepressants are CYP450 substrates or inhibitors.

A

True.

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12
Q

St. John’s Wort is commonly used as an antidepressant and is a P450 _________.

A

St. John’s Wort is commonly used as an antidepressant and is a P450 inducer.

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13
Q

Discontinuing antidepressants can cause withdrawal symptoms. How can this be mitigated?

A

Gradually reduce the dosage

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14
Q

What term refers to the fact that a period of several weeks may be needed before starting another drug after fluoxetine?

A

A washout period

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15
Q

What is the usual ratio of GABA to glutamate?

A

1 : 1

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16
Q

What happens if a person’s [glutamate] > [GABA]?

A

Hyperexcitability and anxiety

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17
Q

What happens if a person’s [GABA] > [glutamate]?

A

Hypoexcitability and sedation

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18
Q

What is the mechanism of action of tricyclic antidepressants?

A

Inhibits norepinephrine and 5-hydroxytryptamine reuptake

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19
Q

What is the mechanism of action of MAOIs?

A

Non-selectively increases monoamines

(5-hydroxytryptamine, dopamine, norepinephrine)

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20
Q

What is the mechanism of action of SSRIs?

A

Inhibits 5-hydroxytryptamine reuptake

(and some norepinephrine)

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21
Q

What is the mechanism of action of SNRIs?

A

Inhibits 5-hydroxytryptamine and norepinephrine reuptake

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22
Q

What is the mechanism of action of bupropion?

A

Inhibits dopamine and norepinephrine reuptake

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23
Q

What is the mechanism of action of lithium?

A

Inhibits phosphatidylinositol casade

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24
Q

What is the mechanism of action of barbituates?

A

Enhances GABA effect

(↑ duration of Cl- channel opening)

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25
Q

What is the mechanism of action of benzodiazepines?

A

Binds to GABA-A receptor + enhances GABA effect

(↑ frequency of Cl- channel opening)

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26
Q

Which medication type increases the frequency of Cl- channel opening?

Which medication type increases the duration of Cl-​ channel opening?

A

Benzodiazepines

Barbituates

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27
Q

What is the mechanism of action of buspirone?

A

5-HT1A partial agonism

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28
Q

What is the mechanism of action of Z drugs (zolpidem, zaleplon, eszopiclone)?

A

Binds to GABA-A receptors at α-1 subunit

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29
Q

What is the mechanism of action of suvorexant?

A

Orexin receptor antagonist

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30
Q

What is the mechanism of action of ramelteon?

A

Melatonin agonist

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31
Q

Tricyclic antidepressants should only be used with caution in what patient population?

A

The elderly

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32
Q

True/False.

Tricyclic antidepressants have a high overdose potential.

A

True.

33
Q

What antidepressant class is used for treating neuropathic pain?

A

Tricyclic antidepressants

34
Q

Name some of the treatment options for depression.

A

SSRIs

SNRIS

Tricyclic antidepressants

Bupropion

35
Q

MAOIs are mainly used in treating what condition(s)?

A

Atypical depression

(also, MDD and panic disorder)

36
Q

Name some of the major side effects of tricyclic antidepressant use.

A

Arrythmias, seizures, hypotension

37
Q

Name some of the major side effects of MAOI use.

A

Hypotension and seizures

38
Q

Name some of the major side effects of SSRI use.

A

Sexual dysfunction, serotonin syndrome

39
Q

What should be avoided in patients taking MAOIs?

A

Wine and cheeses;

SSRIs and SNRIs

40
Q

How long do SSRIs or SNRIs take for their onset of action?

A

3 - 4 weeks

41
Q

What is a major side effect of bupropion?

A

Seizures

42
Q

Bupropion should be avoided in what patient population(s)?

A

Bullemic or anorexic patients

43
Q

Which antidepressant is useful in smoking cessation?

A

Bupropion

44
Q

Lithium has a narrow ________ index.

A

Lithium has a narrow therapeutic index.

45
Q

Name some of the potential side effects of lithium use.

A

Nephrogenic diabetes inspidus;

weight gain, sedation, seizures;

teratogenic effects

46
Q

Buspirone is used to treat what condition(s)?

It is useful in what patient population(s)?

A

Anxiety;

those with histories of drug/alcohol abuse

47
Q

Which sleep aid should be avoided in patients with narcolepsy?

A

Suvorexant

48
Q

Describe the major four dopaminergic brain pathways with which antipsychotics interact.

A

Mesocortical - associated with positive symptoms

Mesolimbic - associated with negative symptoms

Nigrostriatal - involved in extrapyramidal side effects

Tuberohypophyseal - involved in prolactin side effects

49
Q

Which dopamine pathway is associated with positive symptoms of schizophrenia?

A

Mesocortical

50
Q

Which dopamine pathway is associated with negative symptoms of schizophrenia?

A

Mesolimbic

51
Q

Which dopamine pathway is associated with the extrapyramidal symptoms of antipsychotic use?

A

Nigrostriatal

52
Q

Which dopamine pathway is associated with the hyperprolactinemic symptoms of antipsychotic use?

A

Tuberohypophyseal

53
Q

What receptor type is upregulated in patients with schizophrenia?

A

D2 receptors

54
Q

Antipsychotics are ______ ___gonists that can treat psychosis,

A

Antipsychotics are D2 antagonists that can treat psychosis,

55
Q

Drugs that increase _______ergic activity worsen psychosis.

A

Drugs that increase dopaminergic activity worsen psychosis.

56
Q

Drugs that ___crease dopaminergic activity worsen psychosis.

A

Drugs that increase dopaminergic activity worsen psychosis.

57
Q

Name the three typical (1st -generation) antipsychotics (indicate high potency with asterisks).

A

Haloperidol**

chlorpromazine, thioridazine

**high potency

58
Q

Aside from D2 antagonism, what are the other incidental receptor interactions of typical (1st-generation) antipsychotics?

A

M1 antagonism

Alpha-1 antagonism

H1 antagonism

59
Q

Name some of the side effects of typical (1st-generation) antipsychotic use due to M1, alpha-1, and H1 antagonism.

A

M1 - Dry mouth, blurred vision, urinary retention

Alpha-1 - Orthostatic hypotension

H1 - Sedation

60
Q

The side effects of H1/M1/Alpha-1 antagonism are more associated with which form of typical antipyschotics, low potency (chlorpromazine and thioridazine) or high potency (haloperidol)?

A

Low potency

(chlorpromazine and thioridazine)

61
Q

Name some of the more severe side effects associated with haloperidol use.

A

QT prolongation;

extrapyramidal Syndromes

62
Q

List the extrapyramidal effects of haloperidol use.

A

Dystonia (after ≥ ~4 hours)

Akathisia (after ≥ ~4 days)

Bradykinesia

Tardive dyskinesia (after ≥ ~4 months)

63
Q

A patient presents with QT prolongation. You find out they recently started on an antipsychotic.

Which ones are the potential causes?

A

Haloperidol

or

a 2nd-generation antipsychotic

64
Q

A patient presents with altered mental status, an unstable HR and BP, and muscle rigidity.

They were recently started on haloperidol.

What is the diagnosis?

A

Neuroleptic malignant syndrome

65
Q

Name four atypical (2nd-generation) antipsychotics.

A

Clozapine,

olanzapine,

quetiapine,

risperidone

66
Q

The side effects of H1/M1/Alpha-1 antagonism are more associated with which form of antipyschotics, typical (1st-generation) or atypical (2nd-generation)?

A

Typical (1st-generation)

67
Q

The extrapyramidal side effects are more associated with which form of antipyschotics, typical (1st-generation) or atypical (2nd-generation)?

A

Typical (1st-generation)

68
Q

True/False.

Both typical and atypical antipsychotics are associated with QT prolongation.

A

True.

69
Q

What syndrome is associated with atypical antipsychotics but not typical antipsychotics?

A

Metabolic syndrome

(dyslipidemia, diabetes, weight gain)

70
Q

Which antipsychotic is especially associated with hyperprolactinemia?

A

Risperidone

71
Q

Which antipsychotic is the ultimate for treatment-resistant disease?

A

Clozapine

72
Q

Name some of the side effects associated specifically with clozapine.

A

Agranulocytosis,

myocarditis,

seizures

73
Q

How do you monitor a patient taking clozapine to check for agranulocytosis?

A

Monitor WBC count weekly for 6 months

74
Q

Besides D2, M1, H1, and alpha-1 antagonism, what other receptors are antagonized by atypical antipsychotics?

A

5-hydroxytryptamine2

75
Q

Name the indications for electroconvulsive therapy.

A

Treatment-resistant major depressive episodes or bipolar disorder

76
Q

___lateral lead placement in electroconvulsive therapy has less cognitive side effects.

A

Unilateral lead placement in electroconvulsive therapy has less cognitive side effects.

77
Q

What is the typical frequency and number of treatments in electroconvulsive therapy regimens?

A

2 - 3 / week

6 - 12

78
Q

What percentage of patients who failed medications respond to electroconvulsive therapy?

A

70%

(continuing antidepressants required to boost maintenance of improvements; maintenance ECT is an option)

T2 - Phase 3 - Brain, Mind, and Behavior (43 decks)

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