Schizophrenia Alma Flashcards
1
Q
Who publishes the DSM-5-TR
A
The American Psychiatric Association (APA)
2
Q
What is the DSM NOT based on?
A
It is NOT based on objective standards or biological paramaters.
3
Q
What is the primary function of the DSM-5-TR?
A
Provides diagnostic criteria and classifications for mental disorders.
4
Q
What are the key clinical characteristics typically addressed when studying schizohrenia?
A
Symptoms, Diagnostic Criteria, and the clinical course of the disorder
5
Q
How are the symptoms of schizophrenia generally categorized?
A
They are divided into POSITIVE symptoms (eg delusions, hallucinations), negative symptoms (eg; flat affect, avolition) and disorganized symptoms (eg., disorganized speech and behavior)
6
Q
What do diagnostic criteria for schizophrenia usually involve?
A
At least one month of active-phase symptoms (positive negative, or disorganized), significant social/occupational dysfunction, and total duration of at least SIX months (including prodromal or residual phases).
7
Q
What is meant by the “clinical course” of schizophrenia?
A
It refers to the progression of the disorder, typically including prodromal, active, residual phases, with symptoms severity and functional impairment varying over time.
8
Q
Which genetic factors are associated with an increased risk of developing schizophrenia?
A
A strong family history, higher concordance rates in identical twins, and various gene variants that may predispose individuals to the disorder.
9
Q
What are some known environmental risk factors for schizophrenia?
A
A: Prenatal exposures (e.g., infections, malnutrition), psychosocial stressors, urban living, substance use (especially cannabis), and childhood trauma.
10
Q
Q: How do sex differences manifest in schizophrenia?
A
A: Men often have an earlier onset and may experience more severe symptoms, whereas women tend to have a later onset and may exhibit slightly different symptom profiles.
11
Q
Q: What role does the dopaminergic system play in schizophrenia?
A
A: Dysregulation in dopamine pathways—particularly the mesolimbic pathway (linked to positive symptoms) and the mesocortical pathway (linked to negative symptoms)—is strongly implicated in the disorder.
12
Q
Q: How do NMDA receptors and glutamate contribute to the pathophysiology of schizophrenia?
A
A: Reduced NMDA receptor function and disrupted glutamate signaling are thought to contribute to both positive and negative symptoms, adding complexity to the neurochemical imbalance.
13
Q
Q: How do typical (first-generation) antipsychotics work, and what are their main drawbacks?
A
A: They primarily block D2 dopamine receptors to reduce positive symptoms but often cause extrapyramidal side effects (e.g., dystonia, akathisia, parkinsonism) and can lead to tardive dyskinesia with long-term use.
14
Q
Q: How do atypical (second-generation) antipsychotics differ from typical antipsychotics?
A
A: They target both dopamine (D2) and serotonin (5-HT2A) receptors, aiming to address positive and negative symptoms with a lower risk of extrapyramidal side effects, though they can increase the risk of metabolic syndrome.
15
Q
Q: What are some common side effects of antipsychotic therapy?
A
A: Side effects can include sedation, weight gain, metabolic disturbances, extrapyramidal symptoms (more common with typical antipsychotics), and possible endocrine changes (e.g., hyperprolactinemia).
16
Q
Q: What are “positive” symptoms in schizophrenia-spectrum disorders, and why are they sometimes called “productive” symptoms?
A
A: They involve excesses or distortions of normal functioning, such as hallucinations or delusions, and are called “productive” because they represent added experiences or behaviors.
17
Q
Q: What are “negative” symptoms in schizophrenia-spectrum disorders?
A
A: They are characterized by deficits in normal functioning, including reduced emotional expression, lack of motivation, or diminished speech.
18
Q
Q: What are “cognitive” symptoms in schizophrenia-spectrum disorders?
A
A: They often involve disorganized thinking, poor executive functioning, difficulty with attention, and impaired memory.
19
Q
Q: How can “motor” symptoms manifest in schizophrenia-spectrum disorders?
A
A: Motor symptoms can include catatonia, which involves unusual motor behaviors such as immobility, waxy flexibility, or repetitive, purposeless movements.
20
Q
Q: What are hallucinations?
A
A: Perceptions that occur without an external stimulus.
21
Q
Q: Which type of hallucination is most common, and which ones might suggest a neurological issue?
A
A: Auditory hallucinations are most common; olfactory or gustatory hallucinations may point to a neurological cause.
22
Q
Q: What defines a delusion?
A
A: A fixed belief that does not change when presented with contradictory evidence.
23
Q
Q: How are delusions classified as bizarre or non-bizarre?
A
A: Bizarre delusions are clearly implausible; non-bizarre delusions could occur in real life.
24
Q
Q: What are some common types of delusions?
A
A: Persecutory, referential, grandiose, erotomanic, nihilistic, and somatic.
25
Q: What are persecutory delusions?
A: Fixed beliefs of being harmed, harassed, or conspired against.
26
Q: What are referential delusions?
A: Fixed beliefs that certain gestures, comments, or cues are aimed at oneself.
27
Q: What are grandiose delusions?
A: Fixed beliefs of having extraordinary abilities, wealth, or importance.
28
Q: What are erotomanic delusions?
A: Fixed beliefs that another person is in love with the individual.
29
Q: What are nihilistic delusions?
A: Fixed beliefs that a major catastrophe will occur or that reality does not exist.
30
Q: What are somatic delusions?
A: Fixed beliefs involving bodily functions or health, such as thinking one is severely ill despite no medical evidence.
31
Q: What are negative symptoms in the context of schizophrenia?
A: They are characterized by diminished or absent emotional, motivational, and social functioning.
32
Q: What is affective flattening or blunting?
A: A reduction in emotional expression and reactivity.
33
Q: What is alogia?
A: Poverty of speech, typically manifesting as brief, empty replies.
34
Q: What is avolition?
A: A lack of motivation to pursue goal-directed activities.
35
Q: What is anhedonia?
A: An inability to experience pleasure in normally enjoyable activities.
36
Q: What is asociality?
A: A lack of interest or engagement in social interactions.
37
Q: What are common cognitive issues with information processing in schizophrenia?
A: Difficulty filtering stimuli and encoding new information.
38
Q: What are the main executive deficits seen in schizophrenia?
A: Attention deficits and working memory problems.
39
Q: What is derailment in the context of thought disorders?
A: Inability to maintain a coherent train of thought.
40
Q: What is tangentiality?
A: Providing oblique or indirect answers that don’t directly address the topic.
41
Q: What is incoherence or “word salad”?
A: Speech that is so disorganized it becomes nearly impossible to understand.
42
Q: What is circumstantiality?
A: Speech that includes unnecessary details before finally reaching the point.
43
Q: What is echolalia?
A: Repetition of another person’s words or phrases.
44
Q: What is clanging?
A: Speaking in words linked by sound or rhyme rather than meaning.
45
Q: What is thought blocking?
A: A sudden interruption in the flow of thought.
46
Q: What is perseveration?
A: Persistent repetition of a word, phrase, or topic despite changes in the conversation.
47
Q: What are disorganized movements in the context of schizophrenia?
A: Unpredictable, agitated motor behaviors that lack a clear pattern or purpose.
48
Q: What does psychomotor slowing involve?
A: Prolonged reaction times, difficulties with motor coordination, and impaired performance on complex motor tasks.
49
Q: What is catatonia?
A: A state characterized by waxy flexibility, minimal movement, and often automatic obedience, typically accompanied by reduced goal-directed behavior and social withdrawal.
50
Q: How long must symptoms persist for a diagnosis of schizophrenia?
A: Over 6 months.
51
Q: Which symptom categories can qualify for a schizophrenia diagnosis (at least two are required)?
A: Delusions, hallucinations, disorganized speech/thoughts, disorganized or catatonic behavior, and negative symptoms.
52
Q: What differentiates Brief Psychotic Disorder from Schizophrenia in terms of duration?
A: Brief Psychotic Disorder lasts under 1 month, while Schizophrenia requires over 6 months.
53
Q: Give examples of negative symptoms relevant to schizophrenia diagnosis.
A: Flattened affect, alogia, avolition, and anhedonia.
54
Q: What is Schizophreniform Disorder in terms of duration?
A: It is characterized by symptoms lasting between 1 and 6 months.
55
Q: What are the typical stages of schizophrenia?
A: Premorbid, prodromal, active, and residual/stable.
56
Q: What characterizes the premorbid stage of schizophrenia?
A: Minimal or no symptoms and relatively normal functioning.
57
Q: What typically happens during the prodromal stage?
A: Gradual appearance of mild symptoms and a noticeable decline in functioning.
58
Q: What defines the active stage?
A: Full-blown psychotic symptoms and significant impairment in daily functioning.
59
Q: What is the residual/stable stage?
A: A phase where symptoms lessen or stabilize compared to the active stage, but functioning may not fully return to premorbid levels.
60
61
What characterizes the premorbid stage of schizophrenia?
Normal functioning with mild behavioral changes.
62
Which personality traits are commonly seen in the premorbid stage?
Quiet, passive, introverted, and avoidant traits.
63
What additional issues might appear in the premorbid stage?
Anxiety, obsessive-compulsive features, and sleep disturbances.
64
Why is family history relevant in the premorbid stage?
This stage is more commonly observed in relatives of individuals with serious mental illnesses.
65
How does severe psychosocial stress relate to the premorbid stage?
It can increase the risk of progression to more pronounced symptoms.
66
What typically happens to premorbid symptoms during the prodromal stage?
They tend to worsen.
67
Which functional declines often occur in the prodromal stage?
Declines in occupational and interpersonal functioning.
68
What unusual interests might develop during the prodromal stage?
Sudden focus on abstract ideas such as philosophy or religion.
69
Which behaviors indicate the prodromal stage?
Bizarre behavior and unusual speech patterns.
70
What typically happens to psychotic symptoms during the residual stage?
They subside, though oddities of thought and behavior may persist.
71
Which symptoms become more prominent in the residual stage?
Negative symptoms, such as flattened affect, avolition, or anhedonia.
72
How is overall functioning affected in the residual stage?
It often remains low, even though some symptoms lessen.
73
What onset pattern is associated with a better prognosis in schizophrenia?
A later onset and an acute presentation.
74
What personal or family history factors are linked to a better prognosis?
Good premorbid history, being married, and a family history of mood disorders.
75
Which type of symptoms generally predict a more favorable outcome?
Predominantly positive symptoms (e.g., hallucinations, delusions).
76
Which onset pattern is linked to a poorer prognosis?
An earlier onset with an insidious (gradual) course.
77
What family history and marital status factors are often associated with worse outcomes?
A family history of schizophrenia and being single, divorced, or widowed.
78
Which type of symptoms generally predict a worse outcome?
Predominantly negative symptoms (e.g., avolition, alogia).
79
How does gender influence the course of schizophrenia?
Males typically have an earlier onset, more negative symptoms, and a poorer prognosis.
80
What is the approximate global prevalence of schizophrenia?
About 0.3% (up to 1% for schizophrenia-spectrum disorders).
81
In what type of location is schizophrenia more common, and why?
Large cities, likely due to higher psychosocial stress and possible environmental factors.
82
How does schizophrenia’s distribution compare across different countries?
It is generally similar worldwide, but the impact can be more severe in developing nations.
83
What role do cultural factors play in schizophrenia?
They can shape both the presentation and severity of symptoms.
84
What two main factors contribute to the development of schizophrenia?
Environmental insults and genetic susceptibility.
85
Which periods of development are most relevant for environmental risk factors in schizophrenia?
Prenatal, perinatal, and adolescence.
86
Give examples of environmental insults that may increase the risk of schizophrenia.
Infections, hypoxia, drug abuse, and stress.
87
Name some genes implicated in schizophrenia susceptibility.
KCNH2, DTNBP1, NRG1, DISC1, and RGS4.
88
89
Which relatives have the highest risk of developing schizophrenia?
Identical twins, with around a 48% risk.
90
What is the approximate risk for fraternal twins?
About 17%.(2nd most to identical twins)
## Footnote
2nd most to identical twins.
91
92
Which birth-related factors are linked to a higher risk of schizophrenia?
Winter births and urban environments.
93
Name some infections associated with an increased risk of schizophrenia.
Influenza, respiratory infections, rubella, poliovirus, and CNS infections.
94
Which prenatal stressors can elevate the likelihood of schizophrenia?
Famine, maternal bereavement, flooding, unwanted pregnancy, maternal depression, Rh incompatibility, and hypoxia.
95
What obstetric complications are commonly linked to higher odds of developing schizophrenia?
CNS damage, low birth weight, and pre-eclampsia.
96
Which structural brain changes are commonly observed in schizophrenia?
Enlarged lateral ventricles and reduced volume in the dorsolateral prefrontal cortex and temporal lobes.
97
What functions are disrupted by prefrontal cortex dysfunction in schizophrenia?
Interpreting environmental stimuli, decision making, social cue recognition, attention, working memory, and understanding abstract rules.
98
Which symptom domains are most closely linked to prefrontal cortex deficits?
Negative and cognitive symptoms.
99
How does temporal cortex dysfunction contribute to schizophrenia symptoms?
It leads to inappropriate activation/inactivation that facilitates auditory hallucinations and cognitive deficits.
100
Which brain areas show hyperactivity during auditory hallucinations in schizophrenia?
The inferior colliculi, bilateral inferior frontal/insular cortex, right lateral temporal cortex, thalamus, and left hippocampus.
101
What post-mortem findings in schizophrenia suggest it is not a neurodegenerative disorder?
Subtle architectural changes in pyramidal neurons without evidence of gliosis.
102
Which cortical neurons show structural alterations in schizophrenia?
Pyramidal cells, which have smaller soma, reduced dendritic length, and lower spine density.
103
How does NMDA receptor hypofunction affect schizophrenia symptoms?
Reduced glutamate signaling in the prefrontal and temporal cortex contributes to negative and cognitive symptoms.
104
What role does dopamine play in positive versus negative symptoms?
Overactive D₂ receptors in the nucleus accumbens lead to positive symptoms, while reduced dopamine in the prefrontal cortex underlies negative and cognitive symptoms.
105
How does overactivation of 5-HT₂A receptors impact schizophrenia?
It is linked to negative symptoms and may exacerbate other symptom domains.
106
Which two NMDA receptor antagonists produce symptoms similar to schizophrenia?
Phencyclidine (PCP) and ketamine.
107
What autoimmune disorder targets NMDA receptors and can present with acute psychosis?
Anti-NMDA receptor encephalitis.
108
What do postmortem and imaging studies reveal about NMDA receptor function in schizophrenia?
Altered glutamate enzyme levels and reduced NMDA receptor binding in regions like the prefrontal cortex, thalamus, and hippocampus.
109
How do early NMDA receptor impairments affect brain development?
They disrupt neuronal migration, dendritic spine formation, and pruning.
110
What do genetic studies suggest about NMDA receptors in schizophrenia?
Many schizophrenia-linked genes affect NMDA receptor function, supporting the role of glutamate dysregulation.
111
Why is the ON–OFF contrast between adjacent groups of pyramidal neurons important?
It ensures proper cortical function, creating salience maps and preventing sensory overload.
112
Which receptors coordinate the activation of pyramidal neurons and interneurons?
NMDA glutamate receptors.
113
How does NMDA receptor dysfunction affect information processing?
It leads to improper activation and inactivation of cortical areas, resulting in a loss of sensory coherence and contributing to schizophrenia symptoms.
114
Which brain regions are notably impacted by NMDA receptor hypofunction?
The temporal and prefrontal cortex.
115
What role do the mesolimbic and mesocortical dopamine systems play in schizophrenia?
They regulate motivational functions by modulating salience, influencing both positive and negative symptoms.
116
What happens to cortical pyramidal cells when NMDA receptors are dysfunctional?
They become hyperactivated.
117
How does mesolimbic pathway overactivity contribute to schizophrenia symptoms?
It increases dopamine in the nucleus accumbens, facilitating positive symptoms like hallucinations and delusions.
118
Why does hypoactivation of the mesocortical pathway lead to negative and cognitive symptoms?
It results in lower dopamine levels in the prefrontal cortex, which underlies apathy, lack of motivation, and impaired thinking.
119
Which neurotransmitter imbalance is central to these altered pathways in schizophrenia?
Dopamine (high in the mesolimbic pathway and low in the mesocortical pathway).
120
Which class of drugs can induce psychotic states by overstimulating dopamine receptors?
Chronic dopamine agonists such as amphetamine.
121
How can dopamine agonist-induced psychosis be reversed?
By using dopamine receptor blockers.
122
What have studies shown about dopamine receptor density in some untreated patients with schizophrenia?
They exhibit upregulated (increased) dopamine receptors in certain brain regions.
123
How is antipsychotic potency related to D₂ receptor affinity?
Higher D₂ receptor affinity generally means higher antipsychotic potency.
124
What effect do 5-HT₂A receptor agonists typically have?
They are hallucinogenic.
125
Why are 5-HT₂A receptor antagonists useful in treating schizophrenia?
They help reduce psychotic symptoms, often addressing both positive and negative symptom domains.
126
What are the main treatment modalities for schizophrenia?
Pharmacotherapy, psychosocial interventions, and psychotherapeutic approaches.
127
What are the primary therapeutic goals in managing schizophrenia?
To minimize symptoms, reduce medication side effects, prevent relapse, and optimize functioning.
128
Which psychosocial approach is often highlighted for schizophrenia treatment?
Assertive Community Treatment (ACT), which provides comprehensive, community-based support.
129
What role can family education play in schizophrenia treatment?
It helps relatives understand the disorder, improving support and potentially enhancing treatment adherence.
130
Name some common challenges faced in treating schizophrenia.
Social stigma, treatment noncompliance, substance abuse comorbidity, and increased risk of violence or suicide.
131
Why are medical comorbidities sometimes overlooked in schizophrenia?
They can be overshadowed by psychiatric symptoms, leading to underdiagnosis or undertreatment.
132
What is the primary pharmacological action of antipsychotic drugs?
They mainly antagonize dopamine D₂ receptors.
133
Besides schizophrenia, where else are antipsychotics commonly used?
They can be used in other neuropsychiatric conditions, such as bipolar disorder or severe agitation.
134
How are typical (first-generation) antipsychotics generally characterized?
By highly selective D₂ blockade, often categorized by potency (e.g., haloperidol is high potency).
135
What additional mechanisms distinguish atypical (second-/third-generation) antipsychotics?
They often target multiple receptors, including serotonin (5-HT₂A) and may act as partial dopamine agonists.
136
Give examples of different atypical antipsychotic classes.
MARTA: Clozapine, Olanzapine, Quetiapine
SDA: Risperidone, Paliperidone, Ziprasidone
Dopamine stabilizers: Aripiprazole, Brexpiprazole, Cariprazine
137
How does D₂ receptor binding affinity correlate with antipsychotic dose?
Drugs with higher D₂ affinity generally require lower doses to achieve therapeutic effects.
138
Which classes of drugs are included under typical (first-generation) antipsychotics?
Phenothiazines, diphenylbutylpiperidines, thioxanthenes, butyrophenones, dibenzoxazepines, and dihydroindolones.
139
What is the primary mechanism of action for typical antipsychotics?
They mainly block D₂ dopamine receptors.
140
Which symptom domain do typical antipsychotics most effectively treat?
Positive symptoms such as delusions and hallucinations.
141
Name four extrapyramidal side effects associated with typical antipsychotics.
Parkinsonism, akathisia, acute dystonia, and tardive dyskinesia.
142
Why can typical antipsychotics lead to hyperthermia?
Because D₂ receptors are involved in body temperature regulation.
143
How do typical antipsychotics exhibit antiemetic effects?
They block D₂ receptors in the chemoreceptor trigger zone (CTZ), reducing the vomiting reflex.
144
Which dopamine pathway blockade leads to increased prolactin release?
The tuberoinfundibular pathway.
145
What are the main extrapyramidal symptoms caused by typical antipsychotics?
Parkinsonism, akathisia, acute dystonia, and tardive dyskinesia.
146
What is the usual treatment for acute dystonia?
Intramuscular benztropine or diphenhydramine.
147
Which factors increase the risk of tardive dyskinesia?
Older age, female sex, and prolonged use of typical antipsychotics.
148
How is tardive dyskinesia commonly managed?
By using VMAT2 inhibitors (e.g., deutetrabenazine, valbenazine), reducing the dose, or switching to an atypical antipsychotic.
149
Why might typical antipsychotics contribute to hyperthermia?
They block D₂ receptors, which are involved in regulating body temperature.
150
What are the hallmark signs of NMS?
High fever, severe muscle rigidity, autonomic instability, and altered mental status/delirium.
151
Which lab finding strongly suggests muscle breakdown in NMS?
Elevated creatine phosphokinase (CPK).
152
Name two pharmacologic treatments often used for NMS.
Dantrolene (a muscle relaxant) and bromocriptine (a dopamine agonist).
153
What immediate action should be taken if NMS is suspected?
Stop the offending antipsychotic and provide intensive supportive care.
154
Approximately what percentage of patients show poor or incomplete response to typical antipsychotics?
Around 30% show poor response, and an additional 30% or more have incomplete response.
155
Why might typical antipsychotics fail to improve negative and cognitive symptoms?
They primarily target D₂ receptors (improving positive symptoms), but negative and cognitive symptoms involve other neurotransmitter pathways and cortical dysfunction not addressed by simple dopamine blockade.
156
Which atypical antipsychotic is especially indicated for treatment-resistant schizophrenia?
Clozapine.
157
What does MARTA stand for, and which receptors do these agents typically target?
Multi-Acting Receptor Targeted Agents; they target dopamine, serotonin, histamine, muscarinic, and other receptors.
158
Why does clozapine require regular blood monitoring?
It carries a risk of agranulocytosis, requiring frequent WBC/ANC checks to prevent severe neutropenia.
159
What is a major metabolic concern with olanzapine?
Significant weight gain and increased risk of metabolic syndrome (diabetes, hyperlipidemia).
160
Which MARTA drug is especially sedating and may be useful for patients with sleep disturbances?
Quetiapine.
161
How do SDA antipsychotics differ mechanistically from typical antipsychotics?
They block both D₂ and 5-HT₂A receptors, improving efficacy for negative symptoms and reducing EPS risk.
162
Which SDA is known for potentially elevating prolactin levels?
Risperidone (and its active metabolite paliperidone).
163
Why might ziprasidone be chosen over other antipsychotics for certain patients?
It has a lower risk of metabolic side effects but can prolong the QT interval, so cardiac monitoring may be needed.
164
What are the advantages of lurasidone?
It generally has a favorable metabolic profile and is taken once daily with food, potentially improving adherence.
165
What is the unique mechanism of action for drugs like aripiprazole and brexpiprazole?
They are partial D₂ agonists, providing a 'stabilizing' effect on dopamine activity.
166
How does partial D₂ agonism reduce the likelihood of EPS?
By not fully blocking dopamine receptors, it avoids severe dopamine deficiency in the nigrostriatal pathway.
167
Which side effect is relatively common with aripiprazole, despite its lower risk for EPS?
Akathisia (restlessness).
168
Name two additional dopamine stabilizers besides aripiprazole.
Brexpiprazole and cariprazine.
169
Why are third-generation antipsychotics often considered helpful for negative symptoms?
Their partial agonist profile may support dopamine function in the prefrontal cortex, improving motivation and cognition.
170
What general advantages do atypical antipsychotics have over typical antipsychotics?
Lower risk of EPS and tardive dyskinesia, better efficacy against negative symptoms, and some improvement in cognitive symptoms.
171
Which atypical antipsychotic is most strongly associated with agranulocytosis and seizures?
Clozapine.
172
Which atypical antipsychotic is known for the highest risk of hyperprolactinemia?
Risperidone.
173
Why might some atypical antipsychotics cause metabolic issues like weight gain or diabetes?
They often have affinity for histamine H₁ and certain serotonin receptors that can increase appetite and alter metabolism.
174
In clinical practice, what is a common strategy if patients develop significant metabolic side effects on a MARTA agent?
Switch to an agent with a lower metabolic risk profile (e.g., ziprasidone or lurasidone) and address lifestyle factors (diet, exercise).
175
Q: What is the primary pharmacological feature that confers “atypicality” to antipsychotics?
A: Concurrent D₂ and 5-HT₂A antagonism, allowing lower D₂ blockade and reduced EPS.
176
Q: How does partial or loose binding at D₂ receptors help minimize EPS?
A: It reduces the chance of severe nigrostriatal dopamine blockade, which is responsible for extrapyramidal symptoms.
177
Q: Which unique receptor actions differentiate clozapine from other atypical agents?
A: Potential effects on the glycine site of NMDA receptors and D₄ receptor antagonism.
178
Q: Which receptors, when blocked, are most associated with sedation and weight gain?
A: H₁-histamine receptors (and 5-HT₂C blockade also contributes to increased appetite).
179
Q: What side effects are typically linked to muscarinic (M₁) receptor blockade?
A: Dry mouth, blurred vision, constipation, urinary retention, and confusion (especially in older adults).
180
Q: Which receptor blockade can lead to orthostatic hypotension and dizziness?
A: α₁-adrenergic receptor blockade.
181
Q: Why does clozapine sometimes cause hypersalivation, despite antimuscarinic effects?
A: It partially agonizes M₄ receptors, which can increase salivation.
182
Q: How can 5-HT₂C receptor antagonism affect a patient’s metabolic profile?
A: It can increase appetite, contributing to weight gain and potential obesity.
183
Q: Which three major drugs are classified as MARTA?
A: Clozapine, Olanzapine, and Quetiapine.
184
Q: Which MARTA agent is known for significant metabolic side effects (e.g., weight gain, hyperglycemia)?
A: Olanzapine.
184
Q: Why is clozapine reserved for treatment-resistant schizophrenia?
A: It has superior efficacy but carries risks like agranulocytosis, myocarditis, and seizures, requiring regular blood monitoring.
185
Q: Why might quetiapine be chosen for patients who have trouble sleeping?
A: It is sedating and can help with insomnia but also causes orthostatic hypotension and potential metabolic issues.
185
Q: What is the main pharmacological action of SDA antipsychotic
A: They block both D₂ and 5-HT₂A receptors, improving efficacy and reducing EPS compared to typicals.
186
Q: Which SDA is most associated with increased prolactin levels?
A: Risperidone (and its active metabolite, paliperidone).
187
Q: Why might ziprasidone be preferred in patients concerned about weight gain?
A: It has a relatively low metabolic risk, though it can prolong the QT interval.
188
Q: Which SDA is known for a good metabolic profile and must be taken with food to enhance absorption?
A: Lurasidone.
189
Q: Name three dopamine stabilizers (third-generation atypical antipsychotics).
A: Aripiprazole, Brexpiprazole, and Cariprazine.
190
Q: How does partial D₂ agonism reduce the risk of EPS and hyperprolactinemia?
A: It does not fully block dopamine receptors, allowing some normal dopamine activity in the nigrostriatal and tuberoinfundibular pathways.
191
Q: Which side effect is relatively common with aripiprazole despite its favorable EPS profile?
A: Akathisia (subjective restlessness).
192
Q: Why might partial D₂ agonists be more beneficial for negative symptoms?
A: They can support dopaminergic activity in the prefrontal cortex, potentially improving motivation and cognition.
193
Q: How does 5-HT₂A antagonism help reduce EPS?
A: Serotonin blockade in certain pathways can enhance dopamine release in the striatum, offsetting D₂ blockade-induced EPS
194
Q: Which atypical antipsychotic is considered the “gold standard” for refractory schizophrenia, and what are its major risks?
A: Clozapine; agranulocytosis, seizures, myocarditis, and severe metabolic issues.
195
Q: Among atypical antipsychotics, which agent(s) are best known for minimal weight gain?
A: Ziprasidone (though it requires caution regarding QT prolongation) and, to a lesser extent, lurasidone.
196
Q: Which receptors, when antagonized, are most commonly implicated in metabolic syndrome associated with some atypicals?
A: Primarily H₁ and 5-HT₂C blockade, which increase appetite and can alter energy expenditure.
197
Q: How can α₁ blockade contribute to sedation beyond orthostatic hypotension?
A: Reduced sympathetic tone can lower alertness, especially when combined with H₁ blockade.
198
Q: What makes clozapine particularly effective for treatment-resistant schizophrenia?
A: It has a unique receptor profile (D₄ > D₂, multiple serotonin receptors) and can address both positive and negative symptoms more effectively than many other agents.
199
Q: Which serious side effect requires weekly or biweekly blood monitoring for patients on clozapine?
A: Agranulocytosis, a potentially life-threatening drop in white blood cells.
199
Q: Which common side effects can be particularly troublesome for patient comfort on clozapine?
A: Hypersalivation, sedation, weight gain, and constipation.
200
Q: Why is risperidone sometimes considered “less atypical” than other second-generation antipsychotics?
A: Its relatively stronger D₂ blockade can lead to higher rates of EPS and hyperprolactinemia.
200
Q: Besides agranulocytosis, name two other major risks of clozapine.
A: Seizures (especially at higher doses) and myocarditis.
201
Q: Which metabolite of risperidone is available as a separate drug formulation?
A: Paliperidone, which shares many of risperidone’s properties.
202
Q: Why might risperidone be preferred over more sedating atypicals for certain patients?
A: It has lower sedation and less anticholinergic activity compared to agents like clozapine or quetiapine.
203
Q: What distinguishes aripiprazole’s mechanism of action from that of other antipsychotics?
A: It is a partial agonist at D₂ receptors, acting as an agonist or antagonist depending on local dopamine levels.
204
Q: Which common side effect may occur despite aripiprazole’s generally mild profile
A: Akathisia (subjective restlessness and an urge to move).
205
Q: How can partial D₂ agonism help reduce the risk of hyperprolactinemia?
A: By not fully blocking dopamine in the tuberoinfundibular pathway, allowing normal prolactin regulation.
206
Q: Which concerning behavioral changes have been reported with aripiprazole in rare cases?
A: Impulse-control problems, such as pathological gambling or hypersexuality.
207
Q: Name one reason atypical antipsychotics are better tolerated than typicals.
A: They cause fewer extrapyramidal symptoms due to lower or modulated D₂ blockade.
208
Q: Which atypical antipsychotic is considered the “gold standard” for patients with persistent suicidality or aggression?
A: Clozapine, due to its unique efficacy profile.
209
Q: What is a key disadvantage shared by many second-generation antipsychotics, especially olanzapine and clozapine?
A: Metabolic syndrome, including significant weight gain and risk of diabetes.
210
Q: Why might atypical antipsychotics be more expensive overall?
A: They are newer agents, some require regular blood monitoring (clozapine), and they often have higher acquisition costs.
211
Q: Which atypicals have the highest risk for sedation and anticholinergic side effects?
A: Clozapine, olanzapine, quetiapine (and older typicals like chlorpromazine).
212
Q: Which second-generation agent is most notable for QTc prolongation?
A: Ziprasidone.
213
Q: If a patient develops high prolactin levels on risperidone, what alternative atypical might help?
A: Aripiprazole, which can lower prolactin by partial D₂ agonism.
214
Q: Among the atypicals, which drug is associated with minimal weight gain and metabolic risk?
A: Ziprasidone (though caution is needed regarding QT interval).
215
Q: Which side effects do typical antipsychotics still rank highest for compared to atypicals?
A: EPS, tardive dyskinesia, and hyperprolactinemia.
216
Q: Why are second-generation antipsychotics preferred as first-line therapy over typical antipsychotics?
A: They are chosen for their lower risk of extrapyramidal symptoms (EPS) and tardive dyskinesia.
217
Q: What is the next step if a patient does not respond or has intolerable side effects to an initial atypical antipsychotic?
A: The clinician may switch to another second-generation antipsychotic or consider a high-potency first-generation antipsychotic, balancing efficacy with side-effect risks.
218
Q: What is considered the third-line treatment option for treatment-resistant schizophrenia?
A: Clozapine is reserved for patients who have failed at least two adequate trials of other antipsychotics.
219
Q: Which antipsychotic options may be more beneficial for patients with predominant negative symptoms?
A: Partial D₂ agonists (e.g., aripiprazole) or dopamine stabilizers (e.g., cariprazine) may be beneficial, and clozapine is effective in refractory cases.
220
Q: What antipsychotic choices are preferred for patients at high risk for metabolic side effects?
A: Agents with a lower metabolic burden, such as ziprasidone, aripiprazole, or lurasidone, are preferred.
221
Q: What special dosing considerations apply when treating older adults with antipsychotics?
A: Use the lowest effective doses due to increased sensitivity to sedation, anticholinergic effects, and orthostatic hypotension.
222
Q: Which antipsychotics are commonly used in pediatric and adolescent populations?
A: Risperidone and aripiprazole are commonly used, with careful dose titration and monitoring of growth and metabolic parameters.
223
Q: How can non-adherence to antipsychotic medication be addressed?
A: Long-acting injectable (LAI) formulations (e.g., risperidone LAI, paliperidone palmitate, aripiprazole LAI) can help ensure consistent dosing.
224
Q: What are important considerations for antipsychotic use during pregnancy and lactation?
A: Risk–benefit assessments are essential; some clinicians may favor agents with more safety data (e.g., haloperidol), while certain atypicals may be used cautiously.
225
Q: Which antipsychotic is specifically approved for treating psychosis in Parkinson’s disease?
A: Pimavanserin, a 5-HT₂A inverse agonist, is FDA-approved for Parkinson’s disease psychosis.
226
Q: Why might clozapine be chosen for patients with persistent suicidality or aggression?
A: Clozapine is highly effective in treatment-resistant cases and is known to reduce both suicidality and aggressive behaviors.
