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Therapeutics > Therapy of Schizophrenia > Flashcards

Therapy of Schizophrenia Flashcards

1
Q

Antipsychotics are similar regarding:

A

The beneficial effect

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2
Q

_____ are important for appropriate selection of an antipsychotic drug for an individual patient.

A

Adverse effect profiles

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3
Q

Pharmacotherapy guidelines emphasize antipsychotics:

A

Monotherapies with adequate benefit/risk ratios

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4
Q

When should antipsychotic combination regimens be used?

A

In the most treatment-resistant patients

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5
Q

Long-term maintenance antipsychotic treatment is needed for the vast majority of patients in order to:

A

Prevent relapse

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6
Q

______ should be used in combination with antipsychotic treatment to be effective.

A

Psychosocial rehabilitation programs

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7
Q

Most deterioration in psychosocial functioning occurs during:

A

The first 5 years after the initial psychotic episode

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8
Q

Patients with schizophrenia who continue to abuse alcohol or drugs usually have a __(good/poor) response to medications and a __(good/poor) prognosis.

A

Poor; Poor

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9
Q

Which drugs can induce psychosis?

A

1) Cannabis, Marijuana
2) Cocaine
3) Amphetamines: ecstasy (MDMA), methamphetamine, methylphenidate
4) LSD
5) Phencyclidine and ketamine
6) Alcohol

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10
Q

What are some medical causes of psychosis?

A

1) HIV (AIDS)
2) Malaria
3) Syphilis
4) Alzheimer’s disease
5) Parkinson’s disease
6) Hypoglycemia
7) SLE
8) Multiple sclerosis

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11
Q

What are the desired outcomes of schizophrenia therapy?

A

1) Avoiding unwanted adverse effects of therapy
2) Integrating the patient back into the community
3) Increasing adaptive functioning
4) Preventing relapse

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12
Q

Which drugs are First-Generation Antipsychotics (FGAs)?

A

1) Chlorpromazine
2) Haloperidol
3) Thiothixene
4) Loxapine

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13
Q

Which drugs are Second-Generation Antipsychotics (SGAs)?

A

1) Aripiprazole
2) Clozapine
3) Olanzapine
4) Quetiapine
5) Risperidone
6) Ziprasidone

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14
Q

First-Generation Antipsychotics (FGAs) mechanism of action?

A

1) Block dopaminergic neurotransmission
2) Block noradrenergic, cholinergic, and histaminergic action

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15
Q

Second-Generation Antipsychotics (SGAs) mechanism of action?

A

1) Block D2 dopamine receptors
2) Block 5-HT2A serotonin receptors

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16
Q

The major advantage of SGAs is:

A

Lower risk of neurologic adverse effects, particularly motor effects.

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17
Q

In first-episode psychotic patients, typical dosing ranges are about __% of the doses used in chronically ill individuals.

A

50%

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17
Q

The goals during the first 7 days of schizophrenia treatment should be:

A

1) Reduction of symptoms
2) Normalization of sleep and eating patterns

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17
Q

Some SGAs have increased risk of:

A

Metabolic adverse effects:
1) Weight gain
2) Hyperlipidemias
3) Diabetes mellitus

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18
Q

Why do we use lower doses in first-episode psychotic patients?

A

Because of increased susceptibility to extrapyramidal symptoms.

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19
Q

Which antipsychotic drugs have increased susceptibility to extrapyramidal symptoms?

A

1) Aripiprazole
2) Risperidone
3) Ziprasidone

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20
Q

In previously treated patients, use any antipsychotic EXCEPT:

A

1) Clozapine
2) Antipsychotics that were not effective or poorly tolerated by the patient

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21
Q

When can we try Clozapine?

A

1) Patients who were not responsive with 2 antipsychotic trials
2) Patients who were severely suicidal

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22
Q

If the patient begins to show adequate response at a particular dose, then the patient should ___(up/lower/continue) the dose.

A

Continue

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23
Q

Improvement is usually a slow but steady process over __-__ weeks or longer.

A

6-12

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24
Q

Increased socialization and improvement in self-care habits and mood take - weeks to occur.

A

2-3

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25
Q

Improvement in formal thought disorder can take an additional - weeks to occur.

A

6-8

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26
Q

What changes in patients taking antipsychotics take 2-3 weeks to occur?

A

1) Increased socialization
2) Improvement in self-care habits and mood

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27
Q

Chronically ill patients may need - months to improve.

A

3-6

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28
Q

What changes in patients taking antipsychotics take 6-8 weeks to occur?

A

Improvement in formal thought disorder

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29
Q

Before changing medications in a poorly responding schizophrenic patient, the
following should be considered:

A

1) Confirm the diagnosis of schizophrenia, or exclude a different diagnosis, a long-standing behavioral problem, a substance abuse disorder, or a general medical condition.

2) Check whether the patient has treatment-resistant schizophrenia.

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30
Q

Medications for schizophrenia
are __(palliative/curative).

A

Palliative

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31
Q

Maintenance drug therapy for schizophrenia prevents ___.

A

Relapse

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32
Q

After treatment of the first psychotic episode, medication should be continued for ____ after remission.

A

1-5 years

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33
Q

When starting a patient on multiple schizophrenia drugs, what should you do?

A

Antipsychotics should be tapered slowly over at least 1-2 weeks while the second antipsychotic is initiated and the dose titrated up.

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34
Q

Antipsychotic tapering needs to occur more slowly with ___.

A

Clozapine

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35
Q

Abrupt discontinuation, especially for clozapine, can result in ___.

A

Withdrawal symptoms

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36
Q

Abrupt discontinuation, especially for clozapine, can result in withdrawal symptoms such as:

A

1) Insomnia
2) Nightmares
3) Headaches
4) GI symptoms (abdominal cramps, stomach pain, nausea, vomiting, and diarrhea)
5) Restlessness
6) Increased salivation
7) Sweating

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37
Q

Long-Acting Injectable (LAI) Antipsychotics are used for:

A

Patients who are unreliable in taking oral medication on a daily basis

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38
Q

If medication nonadherence is due to adverse effects, what should you do?

A

Try an alternative medication with a more favorable adverse effect profile BEFORE a long-acting injectable antipsychotic is given

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39
Q

What is Paliperidone palmitate?

A

A long-acting injectable antipsychotic (once-monthly IM injection).

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40
Q

___ is available as once monthly injection that requires 2-3 weeks of oral antipsychotic overlap.

A

Aripiprazole

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41
Q

___ can be used as LAI administered every 2 - 4 weeks, but it may be associated with a post-injection delirium/sedation syndrome in 2% of patients.

A

Olanzapine

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42
Q

Olanzapine can be used as LAI administered every 2 - 4 weeks, but it may be associated with:

A

A post-injection delirium/sedation syndrome in 2% of patients.

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43
Q

What should you do after giving a patient Olanzapine injection?

A

1) Observe the patient for at least 3 hours after administration
2) Inform them they must not drive or operate machinery for that day

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44
Q

“Treatment Resistant” describes a patient who:

A

Has had inadequate response from multiple antipsychotic trials

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45
Q

What should you do in patients failing ≥ 2 pharmacotherapy trials?

A

1) Re-examine diagnosis
2) Exclude substance abuse
3) Medication non-adherence
4) Psychosocial stressors

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46
Q

Which drug may be effective in the management of treatment-resistant schizophrenia?

A

Clozapine

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47
Q

Clozapine has been effective in patients with:

A

1) Severe suicidality
2) Aggressive behavior
3) Those who cannot tolerate neurologic adverse effects of even low doses of other antipsychotics

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48
Q

Clozapine is monitored by:

A

1) Absolute Neutrophil Count (ANC)
2) Serum drug level
3) Norclozapine concentration

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49
Q

Because of the risk of _____, Clozapine is usually titrated more slowly than other antipsychotics, particularly on an outpatient basis.

A

Orthostatic hypotension

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50
Q

Clozapine dose should not exceed ___ daily.

A

900 mg

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51
Q

The Norclozapine level under normal circumstances is expected to be around ___ of the clozapine level.

A

Two-thirds

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52
Q

Antipsychotics are highly lipo(phobic/philic).

A

Lipophillic

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53
Q

Antipsychotics are highly bound to membranes and plasma proteins, and have __(low/large) volumes of distribution.

A

Large

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54
Q

Most antipsychotics are largely metabolized by ___.

A

CYPs

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55
Q

For antipsychotics metabolized by ___, metabolism is polymorphic as patients may be poor, intermediate, rapid, or ultrarapid metabolizers.

A

CYP2D6

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56
Q

Most antipsychotics have long elimination half-lives ≥ 24 hours, with the exception of __ and ___, which have shorter half-lives (2-10 hours).

A

Quetiapine and Ziprasidone

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57
Q

Antipsychotics cause weight (gain/loss).

A

Gain

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58
Q

Why do antipsychotics cause weight gain?

A

They’re associated with:
1) Antihistaminic effects
2) Antimuscarinic effects
3) Blockade of 5-HT2C receptors

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59
Q

Anti-Psychotics cause Hyperprolactinemia due to:

A

Dopamine blockade in the
tuberoinfundibular system.

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60
Q

Endocrine effects of antipsychotics are:

A

1) Gynecomastia
2) Galactorrhea
3) Menstrual irregularities
4) Decreased libido
5) Sexual dysfunction

61
Q

Cardiovascular system effects of antipsychotics are:

A

1) Orthostatic Hypotension (α-adrenergic blockade).
2) Sudden cardiac death
3) Elevation of serum triglycerides and cholesterol
4) Sinus tachycardia from anticholinergic effects
5) Reflex tachycardia from α-adrenergic blockade
6) Prolongation of QTc, which may be associated with polymorphic ventricular arrhythmias, including torsade de pointes syndrome.

62
Q

Which antipsychotic most commonly causes QT prolongation?

A

Thioridazine

63
Q

Anticholinergic effects of antipsychotics are:

A

1) Dry mouth
2) Constipation
3) Tachycardia
4) Blurred vision
5) Impairment of erection
6) Urinary retention
7) Impaired memory
8) Paralytic ileus
9) Necrotizing enterocolitis

64
Q

What are Extrapyramidal Symptoms?

A

Movement disorders due to excess dopamine blockade in the nigrostriatal pathway

65
Q

CNS effects of antipsychotics are:

A

1) Extrapyramidal Symptoms
2) Sedation
3) Seizures
4) Neuroleptic Malignant Syndrome (NMS)

66
Q

Which extrapyramidal symptoms are associated with antipsychotics?

A

1) Dystonia
2) Akathisia
3) Pseudoparkinsonism
4) Tardive Dyskinesia (TD)

67
Q

What is dystonia?

A

Prolonged tonic contractions

68
Q

When does dystonia occur with antipsychotics?

A

Usually within 1-4 days of initiating or increasing the dose of an antipsychotic

69
Q

Which type of dystonias are life-threatening?

A

Pharyngeal–laryngeal dystonias

70
Q

Are dystonias a reason for medication non-adherence?

A

YES

71
Q

What are the types of dystonias?

A

1) Trismus
2) Glossospasm
3) Tongue protrusion
4) Pharyngeal– laryngeal dystonia
5) Blepharospasm
6) Oculogyric crisis
7) Torticollis
8) Retrocollis

72
Q

What is oculogyric crisis?

A

Spasmodic movements of the eyeballs into a fixed position, usually upwards

73
Q

The risk of dystonia is greatly reduced with:

A

Second Generation Antipsychotics (SGAs)

74
Q

Dystonia may be treated with:

A

1) IM or IV anticholinergics
2) Benzodiazepines

75
Q

What is Akathisia?

A

The inability to sit still associated with functional motor restlessness (pacing, shifting, shuffling, or tapping feet)

76
Q

Akathisia is common with some ___, frequently accompanied
by dysphoria.

A

First Generation Antipsychotics (FGAs)

77
Q

Which antipsychotics appear to have the lowest risk of producing akathisia?

A

1) Quetiapine
2) Clozapine

78
Q

How is akathisia treated?

A

1) Benzodiazopines
2) Beta-Blockers
3) 5-HT2 receptor antagonist

79
Q

Which drugs can be used as protection against akathisia?

A

5-HT2 receptor antagonists:
1) Cyproheptadine
2) Mirtazapine
3) Trazodone

80
Q

Which Beta-Blockers can be used as treatment for akathisia?

A

1) Propranolol
2) Nadolol
3) Metoprolol

81
Q

When does Pseudoparkinsonism begin when taking antipsychotics?

A

Typically 1 - 2 weeks after initiation or a dose increase

82
Q

Pseudoparkinsonism can be treated with:

A

1) Anticholinergic drugs, but may produce euphoria.
2) Rotigotine

83
Q

Pseudoparkinsonism can be treated with which anticholinergic drugs?

A

1) Trihexyphenidyl
2) Benztropine
3) Orphenadrine

84
Q

Pseudoparkinsonism can be treated with which specific drug that has less effect on memory?

A

Amantadine

85
Q

What is the main cause of pseudoparkinsonism?

A

Due to D2 blockade in the nigrostriatum

86
Q

What is Rotigotine?

A

A dopamine agonist

87
Q

The risk of pseudoparkinsonism with SGAs is low, but may occur with ___ at relatively large doses.

A

Risperidone

88
Q

Which antipsychotics are reasonable alternatives in a patient experiencing extrapyramidal symptoms with other Second Gen. Antipsychotics?

A

1) Quetiapine
2) Aripiprazole
3) Clozapine

89
Q

What is Tardive Dyskinesia (TD)?

A

A syndrome characterized by abnormal involuntary movements buccal–lingual masticatory, or orofacial.

90
Q

Is the onset of tardive dyskinesia gradual or sudden?

A

Gradual

91
Q

The first detectable signs of tardive dyskinesia are:

A

Mild forward, backward, or lateral movements of the tongue

92
Q

Which extrapyramidal symptom is associated with higher overall morbidity and mortality?

A

Tardive dyskinesia

93
Q

Tardive dyskinesia is more prevalent with ___(FGAs/SGAs).

A

FGAs

94
Q

Short-term treatment of TD with which drugs may be effective?

A

1) Clonazepam
2) Ginkgo biloba
3) Clozapine

95
Q

What are the most sedating antipsychotics?

A

1) Chlorpromazine
2) Thioridazine
3) Clozapine
4) Olanzapine
5) Quetiapine

96
Q

Antipsychotics __(increase/decrease) the seizure threshold.

A

Decrease

96
Q

Sedation occurs __(early/late) in antipsychotic treatment and can __(increase/decrease) over time

A

Early; Decrease

97
Q

Which antipsychotics have the
highest seizure risk?

A

1) Clozapine
2) Chlorpromazine

98
Q

Which antipsychotics have the
lowest seizure risk?

A

1) Risperidone
2) Thioridazine
3) Haloperidol
4) Pimozide
5) Trifluoperazine
6) Fluphenazine

99
Q

Neuroleptic Malignant Syndrome (NMS) develops __(slowly/rapidly).

A

Rapidly

100
Q

True or False: Neuroleptic Malignant Syndrome (NMS) does not occur after stopping antipsychotics.

A

False; it can occur

101
Q

Possible mechanisms of Neuroleptic Malignant Syndrome (NMS) include:

A

1) Disruption of the central thermoregulatory process
2) Excess production of heat secondary to skeletal muscle contractions

102
Q

What are the signs and symptoms of Neuroleptic Malignant Syndrome (NMS)?

A

1) Temperature > 38°C
2) Loss of consciousness
3) Muscle rigidity
4) Autonomic dysfunction
a) Tachycardia
b) Labile blood pressure
c) Diaphoresis
d) Tachypnea
e) Urinary or fecal incontinence

103
Q

Which labs are associated with Neuroleptic Malignant Syndrome (NMS)?

A

Increased:
1) WBCs (Leukocytosis)
2) Creatine kinase (CK)
3) AST
4) ALT
5) LDH
6) Myoglobinuria

104
Q

How do you treat Neuroleptic Malignant Syndrome (NMS)?

A

First: Antipsychotic discontinuation and supportive care.
Second: Medications

105
Q

Which medications are used to treat Neuroleptic Malignant Syndrome (NMS)?

A

1) Bromocriptine
2) Amantadine
3) Dantrolene

106
Q

What is Dantrolene?

A

Skeletal muscle relaxant

107
Q

Ophthalmologic effects of antipsychotics are:

A

1) Exacerbation of narrow-angle (angle-closure) glaucoma
2) Opaque deposits in the cornea and lens
3) Cataract
4) Retinitis pigmentosa, due to
melanin deposits and can result in permanent visual impairment or blindness.

108
Q

Which antipsychotic causes opaque deposits in the cornea and lens?

A

Chlorpromazine

109
Q

Which antipsychotics cause cataracts?

A

1) Risperidone
2) Quetiapine

110
Q

Which antipsychotic causes retinitis pigmentosa?

A

Thioridazine doses > 800 mg daily

111
Q

Genitourinary System effects of antipsychotics are:

A

1) Urinary hesitancy and retention
2) Urinary incontinence
3) Sexual dysfunction
4) Priapism

112
Q

Which antipsychotic causes Urinary incontinence and why?

A

Clozapine; Due to α-blockade

113
Q

Which antipsychotics cause Urinary hesitancy and retention?

A

1) FGAs
2) Clozapine

114
Q

Why might antipsychotics cause Priapism?

A

Due to α1-adrenergic receptor blockade, leading to intracavernosal blood stasis

115
Q

Which antipsychotics typically cause agranulocytosis?

A

1) Clozapine (0.8%)
2) Chlorpromazine
3) Olanzapine

116
Q

The onset of agranulocytosis is usually within ____ of antipsychotic therapy.

A

The first 8 weeks

117
Q

If the absolute neutrophil count (ANC) is < ___, the antipsychotic should be discontinued and the ANC monitored closely until it returns to normal and also monitored closely for the development of infections.

A

500/μL

118
Q

The baseline ANC must be at least __/μL in order to start
clozapine.

A

1,500

119
Q

Weekly ANC monitoring for the first ___ of Clozapine therapy is
required.

A

6 months

120
Q

Effects of antipsychotics on the skin are:

A

1) Contact dermatitis
2) Skin reaction with Eosinophilia
3) Photosensitivity
4) Blue-gray or purplish skin coloration in areas exposed to sunlight (chlorpromazine), concurrent with corneal or lens pigmentation.

121
Q

Which antipsychotic can cause Skin reaction with Eosinophilia?

A

Ziprasidone

122
Q

All antipsychotics are known to cause photosensitivity, ESPECIALLY:

A

Chloropromazine

123
Q

Why should exposure to sunlight be limited (blocking sunscreen, hats, protective clothing, and sunglasses) when taking antipsychotics, such as Chlorpromazine?

A

It can cause blue-gray or purplish skin coloration in areas exposed to sunlight, concurrent with corneal or lens pigmentation.

124
Q

What is another miscellaneous effect of Clozapine?

A

Sialorrhea (drooling) in 54% of patients

125
Q

Sialorrhea (drooling) when taking Clozapine may happen due to:

A

Antagonistic effect on both α1- and α2-adrenergic receptors at the salivary glands = vasodilation and increased blood flow

126
Q

Which drugs may be used to treat clozapine-related
sialorrhea?

A

1) Anticholinergics (Benztropine and Atropine)
2) α2-agonists (Clonidine)

127
Q

___ is the best studied of all antipsychotics, and no relationship between its use and teratogenicity has been found.

A

Haloperidol

128
Q

Birth defects occur more often with __(FGAs/SGAs).

A

FGAs

129
Q

What are the postnatal and gestational complications of antipsychotics?

A

1) Weight gain
2) Increased risk of gestational diabetes
3) Risk of neonatal EPS (FGAs), with effects lasting for 3 - 12 months after birth
4) Increased risk of hypertension and VTEs

130
Q

Which antipsychotics cause weight gain?

A

1) Olanzapine
2) Clozapine

131
Q

Which antipsychotics cause increased risk of gestational diabetes?

A

1) Olanzapine
2) Clozapine

132
Q

The FDA issued a safety announcement that the pregnancy risk applies for which antipsychotics?

A

The entire antipsychotic class

133
Q

What risks are seen in newborns whose mothers were treated with antipsychotics during their third trimester?

A

1) EPS
2) Withdrawal symptoms

134
Q

Do antipsychotics appear in breast milk?

A

Yes

135
Q

Antipsychotics appear in breast milk with milk-to-plasma ratios of:

A

0.5:1

136
Q

1 week after delivery, ___ milk concentrations may reach 3X the plasma concentrations.

A

Clozapine

137
Q

Clozapine use during breast-feeding is NOT recommended due to:

A

The risk of bone marrow suppression

138
Q

Which antipsychotics are generally considered safe during breastfeeding?

A

1) Aripiprazole
2) Quetiapine

139
Q

Infants exposed to ___ through breast milk may become drowsy and lethargic.

A

Chlorpromazine

140
Q

Infants exposed to Chlorpromazine through breast milk may become:

A

1) Drowsy
2) Lethargic

141
Q

The co-administration of which 2 antipsychotics result in developmental delays at 12 - 18 months of age?

A

1) Chlorpromazine
2) Haloperidol

142
Q

What happens when antipsychotics are used with other sedatives?

A

Excess sedation

143
Q

What happens when antipsychotics are used with other antimuscarinic drugs?

A

Additive antimuscarinic effects

144
Q

Both combined sedative and anticholinergic effects from multiple medications can result in ____, particularly in the elderly.

A

Impaired cognition

145
Q

What happens when antipsychotics are used with other drugs that cause orthostasis?

A

More orthostatic hypotension

146
Q

What happens when antipsychotics are used with Metoclopramide?

A

1) Akathisia
2) Other EPS

147
Q

Careful monitoring is required when giving antipsychotics with diuretics that cause ___.

A

Hypokalemia

148
Q

Antipsychotics can __(shorten/prolong) the QT interval.

A

Prolong

149
Q

___ can precipitate akathisia or EPS when added to a patient stabilized on an antipsychotic.

A

SSRIs

150
Q

5-HT2 (Serotonin) receptor activation leads to:

A

Decreased dopamine release

151
Q

Antipsychotic drugs are metabolized by:

A

1) CYP2D6
2) CYP3A4
3) CYP1A2

Therapeutics (23 decks)

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