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General Psychiatry Flashcards

1
Q

57-98% of patients with schizophrenia exhibit ________ meaning a lack of awareness or insight into their illness which strongly predicts non-adherence

A

Anosognosia

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1
Q

What type of s/sx of schizophrenia do antipsychotic have the most effect on?

A

Positive symptoms (hallucinations, delusions, paranoia, hostility, grandiosity, excitement, conceptual disorganization)

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2
Q

What are the four phases of schizophrenia?

A

Prodromal (gradual development that usually goes unnoticed) - example = isolation and loss of hygiene

Acute: + symptoms present often requiring hospitalization (unable to care for

Stabilization: Acute symptoms decrease (can last for months)

Stable: Positive symptoms lessened, negative symptoms may resolve. Anxiety/depression may still be present

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3
Q

What are the primary NTs involved with schizophrenia?

A

Dopamine (either overreactive or underreactive) and serotonin

Glutamate may also have a role

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4
Q

What are some risk factors for schizophrenia?

A

Family history, perinatal trauma, OB complications, being born in winter, stress

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5
Q

What are two other names for FGAs?

A

Typical or conventional antipsychotics

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6
Q

What effect on dopamine receptors (D2) do FGAs have that cause a split between low, intermediate, and high effect in the class?

A

Antagonistic effect

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7
Q

List FGAs with high potency as dopamine antagonists

A

Fluphenazine, haloperidol, pimozide

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8
Q

List FGAs with low potency as dopamine antagonists

A

Chlopromazine, thioridazine

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9
Q

Low potency FGAs (haloperidol, fluphenazine, pimozide) have what adverse effect profile?

A

Sedation (usually worse initially, better over time)
Anticholinergic effects (dry mouth, constipation, blurred vision, urinary hesitation) – dose dependent
Orthostatic hypotension (due to low-potency affecting the alpha-adrenergic receptor)

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10
Q

What receptors do low-potency FGAs effect?

A

Anticholinergic, antihistaminic, alpha-adrenergic blocking

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11
Q

What receptors do high-potency FGAs (chlorpromazine, thioridazine) effect?

A

Dopamine blocking

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12
Q

What are the main adverse effects with high-potency FGAs

A

Dopamine-related effects from it being blocked – extrapyramidal symptoms & hyperprolactinemia

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13
Q

What is another name for SGAs? What were they developed to prevent less of than FGAs?

A

Atypical antipsychotics

Developed to reduce EPS, improve efficacy, and reduce tardive dyskinesia

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14
Q

What receptor do SGAs have ability to block?

What effect does this have on symptoms of schizophrenia?

What is the benefit of this outside of schizophrenia?

A

Serotonin-2 receptors

Thought to improve negative symptoms (like blunted/flat affect, social withdrawal, ambivalence, etc) & reduce SGAs

Benefit = use of SGA for other mood disorders

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15
Q

What are some SGAs that have +++ effect on weight gain, glucose abnormality, and dyslipidemia? They are often associated with new-onset diabetes

A

Clozapine and olanzapine

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16
Q

What SGA has high potency at the D3 receptor which can lead to some benefit against - and cognitive symptoms?

A

Cariprazine (Vraylar)

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17
Q

D2 hyperactivity may be stabilized from partial agonism from which SGAs?

A

Aripirazole, brexpiprazole, cariprazine

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18
Q

What labs are required for patients starting SGAs?

A

BMI, BP, fasting glucose, lipids, waist circumference

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19
Q

What SGAs have highest risk of dyslipidemia?

A

Clozapine, olanzapine, quetipaine

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20
Q

What SGAs have highest risk of sedation?

A

Clozapine and quetiapine

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21
Q

What SGAs have low risk of sedation?

A

Aripiprazole (abilify)
Iloperidone (Fanapt)
Lumateperone (Caplyta)
Lurasidone (Latuda)
Paliperidone (Invega)

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22
Q

Which SGAs have higher risk of exhibiting Parkinsonism?

A

Lurasidone (Latuda)
Olanzapine (Zyprexa)
Paliperidone (Invega)
Risperidone (Risperdal)

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23
Q

Which SGAs have the most anticholinergic effects?

A

Cariprazine (Vraylar)
Clozapine (Clozaril)***
Olanzapine (Zyprexa)
Quetiapine (Seroquel)

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24
Q

What are adverse effects that all SGAs have to some degree?

A

Metabolic syndrome (weight gain, glucose abnormality, dyslipidemia)
Anticholinergic
Sedation
Orthostasis
EPS (Akathisia and parkinsonism)

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25
Q

Which SGAs have most effect at the serotonin-1A receptor that can increase dopamine in the prefrontal cortex (benefiting cognition)?

A

Aripiprazole
Brexpiprazole
Cariprazine

(Clozapine, quetiapine, and ziprasidone also have some effect)

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26
Q

All antipsychotics have a black box warning for what?

What do some have a BBW for?

A

Use in older adults with dementia

Some have it for increased risk of suicidal thoughts and behaviors in patients </= 24 years old (aripirzaole, brexpiprazole, cariprazine, lurasidone, and quetiapine)

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27
Q

Which type of antipsychotics have a higher mortality rate in older adults with dementia?

A

FGAs

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28
Q

What causes EPS?

What are the 4 manifestations?

A

Blockade of D2 receptors in the nigrostriatal pathway

Pseudoparkinsonism, dystonia, akathisia, tardive dyskinesia

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29
Q

EPS that manifests as bradykinesia, rigidity, tremor, or akinesia

A

Pseudoparkinsonism (often caused by Latuda, olanzapine, paliperidone, and risperidone)

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30
Q

Anticholinergic agents diphenhydramine, trihexyphenidyl, and benztropine are used to treat what EPS

A

Pseudoparkinsonism

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31
Q

What EPS is usually acute and treated with intramuscular anticholinergics

A

Dystonia (torticollis, laryngospasm, oculogyric crisis) – if longer, can treat with oral anticholinergics

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32
Q

What is akathisia?

A

A somatic restlessness – causes inability to stay calm or stay still

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33
Q

What type of drug does akathisia typically not respond to like other EPS? What is the treatment instead?

A

Anticholinergics

Treat akathisia with lipophilic beta blockers like propranolol
(second line = benzo)

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34
Q

Abnormal involuntary movements with long-term antipsychotic therapy typically involving orofacial muscles

A

Tardive dyskinesia

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35
Q

Which SGA is not associated with TD and may be a good option for patients with schiozophrenia with moderate-severe TD?

A

Clozapine

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36
Q

What drugs are used to treat tardive dyskinesia?

A

Valbenazine (Ingrezza)
Deutetrabenazine (Austedo)

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37
Q

How to valbenazine and deutetrabenazine work to treat TD?

A

Selectively inhibit vesicular monoamine transpoter 2 (VMAT 2) regulating dopamine released

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38
Q

Which CYP inhibitors is valbenazine adjusted for?

A

CYP3A4 and CYP2D6

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39
Q

Which CYP inhibitors is duetrabenazine dose adjusted for?

A

CYP2D6

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40
Q

Should anticholinergics be given to someone with TD for treating it?

A

No - it can worsen TD

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41
Q

Which emergency syndrome is associated with FGAs primarily (but can also occur with SGAs)? Describe its symptoms

A

Neuroleptic malignant syndrome (NMS)

Autonomic instability, rigidity, changing consciousness, fever, tachycardia

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42
Q

What is treatment for neuroleptic malignant syndrome?

A

Discontinue offending agent
Supportive fluids & cooling
Bromocriptine and dantrolene
Do not restart antipsychotic until at least 14 days after resolution of NMS

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43
Q

How do FGAs cause hyperprolactinemia?

A

Blocking effect of dopamine @ tuberoinfudibular pathway leading to higher prolactin (SGAs that can cause are risperidone and paliperidone)

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44
Q

Which antipsychotics have highest risk of QTc prolongation?

A

Chlorpromazine, haloperidol IV, and thioridazine

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45
Q

Which antipsychotics have highest risk of causing seizures?

A

Clozapine, chlopromazine, and cariprazine

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46
Q

Patients on antipsychotics should use caution with exposure to what type of weather?

A

High temps (due to risk of hyperthermia)
and low temps due to problems with thermoregulation

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47
Q

A patient with schizophrenia has stopped smoking (an inducer of CYP1A2). What antipsychotics need to be reduced in dose?

A

Clozapine, asenapine, olanzapine, ziprasidone

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48
Q

Intravenous haloperidol is not often recommended because it can lead to what?

A

Cardiac toxicity including torsades de pointes

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49
Q

What antipsychotic is available as an inhaled formulation? What is required for treatment with this?

A

Loxapine

REMS due to its association with bronchospasm (need to have albuterol nebs/neb solution)

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50
Q

When can clozapine be prescribed?

A

Patient has failed 2 or more adequate trials of antipsychotics (treatment resistant schizophrenia) or schizophrenia with suicidal ideation

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51
Q

What severe black box warning occurs with clozapine?

A

Severe neutropenia (agranulocytosis)

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52
Q

What is severe neutropenia defined as with treatment of clozapine?

A

ANC <500 cells/mm^3

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53
Q

What starting ANC does someone need with benign ethnic neutropenia for clozapine? Regular population?

A

BEN >1000 cells/mm3
Usual population >1500

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54
Q

What GI side effect is clozapine associated with?
Why is this important to monitor?

A

Constipation
Can lead to necrotizing colitis and/or intestinal ischemia

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55
Q

Asenapine is contraindicated with what condition

A

Severe hepatic impairment

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56
Q

Brexpiprazole must be adjusted for what condition(s)?

A

Renal and hepatic impairment

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57
Q

Cariprazine has a _______ half-life which means what?

A

Long half-life
May not see clinical reflections of dose for a long time

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58
Q

New 2019 treatment for schizophrenia with partial agonism and postynaptic antagonism for D2 receptors, 60x more affinicty for serotonin-2A leading to ««&laquo_space;EPS

A

Lumateperone (Caplyta)

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59
Q

Lumateperone should be avoided for use with what?

A

CYP3A4 inhibitors or inducers and mod/severe hepatic impairment

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60
Q

Lurasidone (Latuda) needs to be taken with what?

A

350 kcal of food

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61
Q

A patient is on lurasidone and is prescribed diltiazem (a CYP3a4 inhibitor). What should you do with the dose?

A

Taper the dose (also with severe renal impairment)

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62
Q

What LAI is part of a REMS program due to its risk of extreme sedation and delirium?

A

Olanzapine (Zyprexa Relprevv)

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63
Q

What is paliperidone in relation to risperidone?

A

The major active metabolite

64
Q

Olanzapine has structural similarity to what drug?

A

Clozapine

65
Q

Brexpiprazole is similar to what agent?

A

Aripirazole

66
Q

What drug is indicated only for psychosis associated with Parkinson disease? How does it work?

A

Pimavanserin (Nuplazid)

Inverse agonist at serotonin 2c receptors

67
Q

Pimvanserin should be avoided with what medications?

A

Strong CYP3A4 inducers

68
Q

Quetiapine has a high affinity for what receptor that leads to somnolence and weight gain?

A

histamine

69
Q

Quetiapine has a ____________ risk of EPS

A

low (antagonist at the d2 receptors)

70
Q

Risperidone has a _____________ risk of EPS

A

Low (antagonist at d2)

71
Q

Risperidone is associated with what adverse effects (paliperidone is similar)

A

Hyperprolactinemia, weight gain, OH, sexual dysfunction

72
Q

Olanzapine patients should be counseled on risk of what?

A

diabetes

73
Q

Patients with cariprazine (Vraylar) should be counseled on what?

A

Weight gain, GI symptoms, parkinsonism, risk of seizure

74
Q

Patients on pimavanserin should be counseled on what?

A

Headache, dizziness, edema, nausea, confusion

75
Q

Which SGA has low incidence of metabolic syndrome but has a high risk of QT prolongation?

A

Ziprasidone

76
Q

How should ziprasidone be taken?

A

With 500 kcal of food to increase absorption

77
Q

What risk does ziprasidone carry?

A

DRESS (drug reaction with eosinophilia and systemic symptoms) - rash, eosinophilia, fevere, lymphadenopathy can be fatal

78
Q

What is first line treatment for antipsychotics?

A

Typically an SGA

79
Q

What drug can be added to patients with clozapine who only have a partial response?

A

Lamotrigine

80
Q

What drug class may be useful during the acute phase of agitation and/or anxiety for patients with schizophrenia but is less effective for psychosis symptoms?

A

Benzodiazepines

81
Q

What are some medications/illicit drugs that can cause depression-like symptoms?

A

Interferons
Benzos
Barbiturates
Alcohol
CNS depressants
Withdrawal from stimulants
Cocaine
Amphetamines

82
Q

What are first-line medications for depression?

A

SSRIs
SNRIs
Bupropion
Mirtazapine
Vortioxetine

83
Q

How long is an adequate trial for an antidepressant?

A

4-8 weeks

84
Q

What symptoms of depression first improve? How does this affect suicidal ideation?

A

Physical (energy, sleep disturbances) before affective. Patients are increased suicidal risk because they may be able to carry out their plan during the phase where only physical has started to improve

85
Q

How long does it take to see full effect of an antidepressant?

A

4-6 weeks, but may be up to 8 weeks

86
Q

Can a patient who has failed an SSRI respond to another SSRI trial?

A

Yes - per the STAR*D trial

87
Q

After a patient has hit remission with an antidepressant, how much longer should the drug be continued for?

A

another 6-9 months OR if risk of recurrent depression treat for 2 years or longer

88
Q

Duloxetine is a CYP1A2 substrate. Smoking tobacco does what at this site? What about fluvoxamine

A

CYP1A2 inducer

CYP1A2 inhibitor

89
Q

Cyp2C19 substrates citalopram, escitalopram, fluoxetine, imipramine, and vilazodone are affected by what CYP2C19 inducer?

A

St John’s Wort

90
Q

Bupropion is a strong ________ inhibitor

A

CYP2D6

91
Q

Nefazodone is a strong _______ inhibitor

A

CYP3A4

92
Q

Fluvoxamine is a strong _________ inhibitor

A

CYP1A2
(is also a CYP3A4 inhibitor)

93
Q

What are CYP2D6 inhibitors that are antidepressants?

A

Bupropion
Duloxetine
Fluoxetine
paroxetine
sertraline

94
Q

SSRIs selectively inhibit the reuptake of what into the presynaptic neuron? This results in _______ serotonin concentrations

A

Serotonin

Increased

95
Q

What SSRI is primarily only used for OCD?

A

Fluvoxamine

96
Q

What SSRI has the longest half-life?

A

Fluoxetine (1-4 days)

97
Q

What are some similar side effects from the blockade of serotonin reuptake?

A

Insomnia
Restlessness
GI concerns
Sexual dysfunction
Headache

98
Q

What are the most sedating SSRIs?

A

Paroxetine, fluvoxamine

99
Q

What can be added to SSRI to treat sexual dysfunction of SSRIs?

A

Bupropion
PDE-5 inhibitor for ED
Weaker data: buspirone, mirtazapine

100
Q

What are the most activating SSRIs?

A

Fluoxetine, sertraline

101
Q

Why does SSRI causes serotonin sndrome with drugs like MAOIs, dextromethorphan, meperidine, sympathomimetics, linezolid, lithium, and SNRIs?

A

Because they have such potent serotonergic activity when they are with these other drugs that affect serotonin it can lead to serotonin syndrome

102
Q

List major interactions with SSRIs that can cause serotonin syndrome

A

MAOIs
TCAs
linezolid
dexamethasone
sympathomimetics
lithium
SNRIs
meperidine

103
Q

Why were triptans removed as a threat for serotonin syndrome with SSRIs and SNRIs?

A

because they bind to different serotonin receptors than these agents

104
Q

What are the three “clusters” of serotonin syndrome?

A

Neuromuscular hyperactivity (rigidity, tremors, myoclonus, incoordination)
Altered mental status (agitation, confusion, hypomania)
Autonomic instability (hyperthermia & diaphoresis)

105
Q

What is the most prominent side effect of serotonin syndrome?

A

Clonus

  • also tremor + hyperreflexia
106
Q

How is serotonin syndrome treated?

A

D/c the causative agent
Cool/supply respiratory assistance as necessary
Benzo for myoclonus
Anticonvulsant for seizures
Nifedipine for hypertension

107
Q

What adverse effect can occur with SSRIs particularly in older adults that requires monitoring?

A

Hyponatremia of the SIADH (syndrome of inappropriate hormone secretion type)

108
Q

What are some symptoms of SSRI withdrawal?

A

“Electric shock”
nausea
flu-like symptoms
chills
insomnia
anxiety
parasthesias

109
Q

What is the max dose of citalopram?

A

40 mg due to increased risk of QTc prolongation over this dose

110
Q

What are some reasons patients should not take citalopram?

A

Patients who have risk factors for QTc prolongation like congenital long QTc syndrome, bradycardia, hypokalemia, hypomagnesemia, recent MI, or uncompensated heart failure or taking meds that prolong QTc

111
Q

What is the max dose of citalopram for a patient who is over 60?

A

20 mg

112
Q

What is the max dose of citalopram for patients with hepatic impairment or taking CYP2C19 inhibitors (or are poor CYP2C19 metabolizers)?

A

20 mg

113
Q

Which SSRI has a once weekly dose/what is the dose?

A

Fluoxetine 90 mg weekly

114
Q

How does escitalopram related to citalopram?

A

It is the S isomer which is the active component of the racemic mixture

115
Q

What dose of escitalopram is equivalent to 20 mg of citalopram?

A

10 mg

116
Q

What benefit is there of escitalopram 10 mg over 20 mg citalopram?

A

Equal efficacy and less adverse effects

117
Q

SSRIs inhibit the serotonin reuptake into platelets. This causes an increased risk of?

A

Bleeding (as it leads to a decrease in serotonin-mediated platelet activation)

118
Q

What receptors do SNRIs block reuptake of?

A

Norepinephrine and serotonin

119
Q

Which SNRI is approved only for fibromyalgia?

A

Milnacipran

120
Q

Which SNRI has slightly higher incidence of anticholinergic symptoms?

A

Duloxetine

121
Q

When venlafaxine is a dose of less than 150 mg per day, what is it? What affect does this have on adverse effects?

A

A serotonin reuptake inhibitor only

AEs are more similar to SSRIs (especially GI)

122
Q

SNRIs have the adverse effect of ____________ blood pressure, but it is usually not significant

A

Increasing

123
Q

How does levomilnacripran related to milnacipran?

A

It is the more potent enantiomer

124
Q

Levomilnacipran has what counseling points>?

A

Do not use in renal failure
Do not crush or open
Only approved for depression, not fibromyalgia like milnacipran
Metabolized through CYP3A4 (interactions)
BP/OH can occur
can also cause increased heart rate and palpitations (main reason for d/c)

125
Q

Risk of death from overdose from highest to lowest with SNRI, TCA, and SSRI?

A

TCAs
SNRIs (especially duloxetine and venlafaxine)
SSRIs

126
Q

What SNRI is used for fibromyalgia, diabetic peripheral neuropathy, and chronic pain from lower back or osteoarthritis?

A

Duloxetine

127
Q

What is an advantage of desvenlafaxine (active metabolite) over venlafaxine?

A

Not much other than bypasses CYP metabolism so is advantageous for hepatic insufficiency or taking major CYP2D6 inducers/inhibitors

Needs to be dose reduced with renal insufficiency

128
Q

What type of drug is vilazodone?

A

SSRI with partial agonist at the serotonin-1A receptor

129
Q

Counsel on vilazodone

A

Usual/max dose is 40 mg daily
Take with food
AEs: Nausea and diarrhea, less incidence of sexual dysfunction
Do not use with seizure disorder hx
Decrease with CYP3A4 inhibitors
? pancreatitis, sleep paralysis

130
Q

What patient should not receive vilazodone (Vibbryd)

A

seizure history

131
Q

What type of medication is vortioxetine (Trintellix)

A

SSRI with partial agonist activity at serotonin-1b and antagonism at other serotonin receptors

132
Q

What are some counseling points on vortioxetine?

A

Usual dose 10 mg, max dose 20 mg
CYP2d6 metabolite (if on strong inhibitor, max dose is 10 mg)
less incidence of sexual dysfunction
AEs: N/V/D, constipation, xerostomia

133
Q

How does trazodone work?

A

Serotonin reuptake inhibitor that also blocks serotonin-2A receptors

134
Q

How does trazodone work for insomnia?

A

Histamine-1 antagonism

135
Q

What AES are associated with trazodone?

A

Sedation
OH
rare risk of priapism

136
Q

How does nefazodone (Serzone) work?

A

Serotonin-2A antagonist, blocks reuptake of serotonin and norepinephrine

137
Q

What are benefits of nefazodone over trazodone?

A

Less sexual dysfunction
Less risk OH
More effective for anxiety

138
Q

Counsel on how to take nefazodone and what is its black box warning?

A

Twice a day med
AEs: GI, dry mouth, light-headedness, sedation
Inhibits CYP3A4 potently caution when using drugs metabolized by CYP3A4

BBW: liver toxicity, so must be monitored

139
Q

Is nefazodone a first line agent for depression?

A

no, a second or 3rd line option due to its liver toxicity

140
Q

How does mirtazapine work?

A

Increase NE and serotonin in the synapse by antagonizing presynaptic alpha2 autoreceptors. Also blocks serotonin-2A (no sexual dysfunction, anxiety, or sedation), serotonin 3 (no nausea or GI disturbance) and serotonin 2c (weight gain)

141
Q

AEs of mirtazapine:?

A

Weight gain
Sedative effect
Abnormal liver function tests might occur
Low doses = sedating, high doses = insomnia

142
Q

How does bupropion work?

A

Inhibit dopamine and NE reuptake w/minimal serotonin effects

143
Q

What is the most important adverse effect of bupropion?

A

Lowered seizure threshold

144
Q

How can you minimize risk of seizures with bupropion?

A

Avoid in patients with eating disorders and seizure disorders
Max 150 mg/dose or 450 mg/day (IR or ER), max 400 mg/day SR
Space out dose titration by >4 days SR ER or 3 days IR
SR and ER have fewer adverse effects

145
Q

What are the most common AEs of bupropion?

A

Decreased appetite, insomnia, irritability, headache

146
Q

How do TCAs work?

A

Block serotonin and norepinephrine uptake

147
Q

Tertiary amines like amitriptyline and imipramine are more potent for ______ uptake than secondary amines like nortiptyline and desipramine which have more potent _____ activity

A

Serotonin

Norepinephrine

148
Q

What are AEs of TCAs?

A

Sexual dysfunction
orthostasis
Sedation
Anticholinergic symptoms
Cardiotoxicity in OD (QTc porlongation, torsades, eseziures)

149
Q

What should be monitored in patients>40 started on a TCA?

A

EKG

150
Q

A patient is actively suicidal, should he receive a TCA?

A

NO

151
Q

What are the two tertiary amines?

A

Amitriptyline and imipramine

152
Q

What are the two secondary amines?

A

Desipramine and nortriptyline

153
Q

Who are some patients that should not take TCAs?

A

Cardiac history
Seizure disorders
If at risk of OH at increased risk of falls

154
Q

What are some symptoms of withdrawing from TCAs?

A

Anticholinergic reversal effects like lacrimation, nausea, diarrhea, insomnia, balance problems, and restlessness

155
Q

How do MAOIs work?

A

Block the enzyme responsible for breakdown of certain NTs like norepi

156
Q

What are the MAOIs available in the US?

A

Isocarboxazid
Phenelzine
Tanylcypromine

157
Q
A

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