BMB 3 - Antidepressants & Anxiolytics; Antipsychotics; Sleep Aids Flashcards by Jason Worley

What is the black box warning on all antidepressants?

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

Amine hypothesis

Stress hypothesis

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Describe the amine hypothesis of major depressive disorder.

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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Describe the stress hypothesis of major depressive disorder.

Chronic stress →

↑ cortisol →

↓ brain-derived neurotrophic factor (BDNF) →

↓ neural plasticity →

depression

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

Monoamines stimulate signaling cascades →

↑ BDNF →

↑ neural plasticity

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What is the onset-of-action of antidepressants?

> 3-4 weeks

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How is resistant depression approached?

Increase dose,

switch type of antidepressant,

augment with a drug with a different mechanism

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

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

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Describe the symptoms of serotonin syndrome.

Hyperthermia,

hypertension,

muscle rigidity,

muscle jerks

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How is serotonin syndrome treated?

Cyproheptadine

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True/False.

Most antidepressants are CYP450 substrates or inhibitors.

True.

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

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

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

Gradually reduce the dosage

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

A washout period

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What is the usual ratio of GABA to glutamate?

1 : 1

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

Hyperexcitability and anxiety

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

Hypoexcitability and sedation

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What is the mechanism of action of tricyclic antidepressants?

Inhibits norepinephrine and 5-hydroxytryptamine reuptake

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What is the mechanism of action of MAOIs?

Non-selectively increases monoamines

(5-hydroxytryptamine, dopamine, norepinephrine)

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What is the mechanism of action of SSRIs?

Inhibits 5-hydroxytryptamine reuptake

(and some norepinephrine)

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What is the mechanism of action of SNRIs?

Inhibits 5-hydroxytryptamine and norepinephrine reuptake

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What is the mechanism of action of bupropion?

Inhibits dopamine and norepinephrine reuptake

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What is the mechanism of action of lithium?

Inhibits phosphatidylinositol casade

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What is the mechanism of action of barbituates?

Enhances GABA effect

(↑ duration of Cl^- channel opening)

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What is the mechanism of action of benzodiazepines?

**Binds to** _GABA-A_ **receptor** + **enhances** _GABA_ **effect** (↑ frequency of Cl^- channel opening)

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

Benzodiazepines Barbituates

What is the mechanism of action of buspirone?

_5-HT_1A_ **partial agonism**

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

Binds to GABA-A receptors at α-1 subunit

What is the mechanism of action of suvorexant?

Orexin receptor antagonist

What is the mechanism of action of ramelteon?

Melatonin agonist

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

The elderly

**True/False**. Tricyclic antidepressants have a high overdose potential.

True.

What antidepressant class is used for treating neuropathic pain?

Tricyclic antidepressants

Name some of the treatment options for depression.

SSRIs SNRIS Tricyclic antidepressants Bupropion

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

Atypical depression | (also, MDD and panic disorder)

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

Arrythmias, seizures, hypotension

Name some of the major side effects of MAOI use.

Hypotension and seizures

Name some of the major side effects of SSRI use.

Sexual dysfunction, serotonin syndrome

What should be avoided in patients taking MAOIs?

Wine and cheeses; SSRIs and SNRIs

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

3 - 4 weeks

What is a major side effect of bupropion?

Seizures

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

Bullemic or anorexic patients

Which antidepressant is useful in smoking cessation?

Bupropion

Lithium has a narrow ________ index.

Lithium has a narrow **_therapeutic_** index.

Name some of the potential side effects of lithium use.

Nephrogenic diabetes inspidus; weight gain, sedation, seizures; teratogenic effects

Buspirone is used to treat what condition(s)? It is useful in what patient population(s)?

Anxiety; those with histories of drug/alcohol abuse

Which sleep aid should be avoided in patients with narcolepsy?

Suvorexant

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

**Mesocortical** - associated with _positive_ symptoms **Mesolimbic** - associated with _negative_ symptoms **Nigrostriatal** - involved in _extrapyramidal_ side effects **Tuberohypophyseal** - involved in _prolactin_ side effects

Which dopamine pathway is associated with positive symptoms of schizophrenia?

Mesocortical

Which dopamine pathway is associated with negative symptoms of schizophrenia?

Mesolimbic

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

Nigrostriatal

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

Tuberohypophyseal

What receptor type is upregulated in patients with schizophrenia?

**D2** receptors

Antipsychotics are ______ \_\_\_gonists that can treat psychosis,

Antipsychotics are **_D2_** **_anta_**gonists that can treat psychosis,

Drugs that increase \_\_\_\_\_\_\_ergic activity worsen psychosis.

Drugs that increase **_dopamin_**ergic activity worsen psychosis.

Drugs that \_\_\_crease dopaminergic activity worsen psychosis.

Drugs that **_in_**crease dopaminergic activity worsen psychosis.

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

**Haloperidol**\*\* **chlorpromazine**, **thioridazine** \*\*high potency

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

**M1** antagonism **Alpha-1** antagonism **H1** antagonism

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

**M1** - Dry mouth, blurred vision, urinary retention **Alpha-1** - Orthostatic hypotension **H1** - Sedation

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)?

**Low potency** | (chlorpromazine and thioridazine)

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

QT prolongation; extrapyramidal Syndromes

List the extrapyramidal effects of haloperidol use.

**Dystonia** (after ≥ ~4 hours) **Akathisia** (after ≥ ~4 days) **Bradykinesia** **Tardive** **dyskinesia** (after ≥ ~4 months)

A patient presents with QT prolongation. You find out they recently started on an antipsychotic. Which ones are the potential causes?

Haloperidol _or_ a 2^nd-generation antipsychotic

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?

Neuroleptic malignant syndrome

Name four atypical (2^nd-generation) antipsychotics.

Clozapine, olanzapine, quetiapine, risperidone

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

Typical (1^st-generation)

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

Typical (1^st-generation)

**True/False**. Both typical and atypical antipsychotics are associated with QT prolongation.

True.

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

**Metabolic syndrome** | (dyslipidemia, diabetes, weight gain)

Which antipsychotic is especially associated with hyperprolactinemia?

Risperidone

Which antipsychotic is the ultimate for treatment-resistant disease?

Clozapine

Name some of the side effects associated specifically with clozapine.

Agranulocytosis, myocarditis, seizures

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

Monitor WBC count weekly for 6 months

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

5-hydroxytryptamine₂

Name the indications for electroconvulsive therapy.

Treatment-resistant **major depressive episodes** or **bipolar disorder**

\_\_\_lateral lead placement in electroconvulsive therapy has less cognitive side effects.

**_Uni_**lateral lead placement in electroconvulsive therapy has less cognitive side effects.

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

2 - 3 / week 6 - 12

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

**70%** (continuing antidepressants required to boost maintenance of improvements; maintenance ECT is an option)