Pharmacology of antipsychotic medications Flashcards
(111 cards)
1
Q
What is the hallmark symptom of schizophrenia?
A
Psychosis, which includes experiencing auditory hallucinations (e.g., hearing voices) and delusions (fixed false beliefs).
2
Q
What are delusions in schizophrenia?
A
Fixed false beliefs that are not based in reality, such as paranoia or grandiosity.
3
Q
What are the three main categories of symptoms in schizophrenia?
A
Positive symptoms (e.g., hallucinations, delusions)
Negative symptoms (e.g., lack of motivation, social withdrawal)
Cognitive impairments (e.g., memory problems, difficulty concentrating)
4
Q
How many symptoms must a patient experience to meet the DSM-5 criteria for schizophrenia?
A
At least 2 of the 5 specified symptoms.
5
Q
What are the 5 symptoms listed in the DSM-5 criteria for schizophrenia?
A
Delusions
Hallucinations
Disorganized speech
Disorganized or catatonic behavior
Negative symptoms
6
Q
Which 3 symptoms must include at least one in the DSM-5 criteria for schizophrenia?
A
Delusions
Hallucinations
Disorganized speech
7
Q
What is disorganized or catatonic behavior in schizophrenia?
A
Disorganized behavior: Unpredictable or inappropriate actions.
Catatonic behavior: Lack of movement or response, or excessive and purposeless movement.
8
Q
How long must the symptoms persist to meet the DSM-5 criteria for schizophrenia?
A
The symptoms must be present for at least 6 months, with at least 1 month of active symptoms.
9
Q
What are the two main sets of risk factors for schizophrenia?
A
Genetic factors
Perinatal factors
10
Q
What are perinatal risk factors for schizophrenia?
A
Complications during pregnancy or birth, such as infections, malnutrition, or hypoxia.
11
Q
What are pre-morbid symptoms in schizophrenia?
A
Early signs or behaviors that appear before the full onset of schizophrenia, such as social withdrawal or cognitive difficulties.
12
Q
At what age did psychosis onset occur in teenagers who used cannabis from age 15-17?
A
At a mean age of 21.07 years.
13
Q
At what age did psychosis onset occur in teenagers who did not use cannabis from age 15-17?
A
At a mean age of 23.86 years.
14
Q
What is low cortical volume in schizophrenia?
A
A reduction in the volume of the brain’s cortex, associated with functional abnormalities.
15
Q
What is larger ventricle size in schizophrenia?
A
An increase in the size of the brain’s ventricles (fluid-filled spaces), often observed in schizophrenia patients.
16
Q
What brain regions are smaller in schizophrenia?
A
hippocampus and amygdala
17
Q
What is increased loss of gray matter in schizophrenia?
A
A reduction in gray matter volume, which affects brain regions involved in cognition, emotion, and behavior.
18
Q
How does cortical volume reduction in schizophrenia compare to Alzheimer’s and Huntington’s disease?
A
The reduction in cortical volume in schizophrenia is substantially less than in Alzheimer’s and Huntington’s disease.
19
Q
What is the relationship between cortical volume reduction and symptoms in schizophrenia?
A
The degree of cortical volume reduction correlates with the severity of cognitive impairments and negative symptoms in chronic schizophrenia.
20
Q
Why is gray matter loss significant in schizophrenia?
A
It affects brain regions involved in critical functions like cognition, emotion, and behavior, contributing to the disorder’s symptoms.
21
Q
What is the key takeaway about brain abnormalities in schizophrenia?
A
Structural and functional brain abnormalities, such as reduced cortical volume, larger ventricles, and smaller hippocampus/amygdala, are associated with cognitive impairments and negative symptoms in schizophrenia.
22
Q
How does dopamine (DA) from the ventral tegmental (VT) nucleus contribute to psychosis?
A
It increases the glutamate (Glu) response, leading to overstimulation of pyramidal neurons.
23
Q
what is the ventral tegmental (VT) nucleus?
A
brain region that produces dopamine (DA) .
24
Q
What is the dorsal raphe nucleus?
A
region that produces serotonin (5- HT).
25
What is the key takeaway about the neurobiological mechansims of psychosis?
Psychosis involves excessive activation of pyrimidal neurons due to increased glutamate release, driven by dopamine and serotonin, and insufficient regulation by GABA interneurons
26
What is the mesocortical dopamine system?
A dopamine pathway that projects from the ventral tegmental area (VTA) to the prefrontal cortex, involved in cognition and emotional regulation.
27
What is the mesolimbic dopamine system?
A dopamine pathway that projects from the ventral tegmental area (VTA) to the nucleus accumbens and other limbic regions, involved in reward and motivation.
28
What happens in the mesolimbic system in schizophrenia?
There is hyperdopaminergic activity (excessive dopamine signaling), which contributes to positive symptoms.
29
How does hyperdopaminergic activity in the mesolimbic system lead to positive symptoms?
Excessive dopamine signaling in the limbic regions overstimulates reward and perception pathways, causing hallucinations and delusions.
30
What is homovanillic acid (HVA)?
A major metabolite of dopamine, used as a marker for dopamine turnover in the brain.
31
Example of first-generation "typical antipsychotics"
Fluphenazine
Chlorpromazine
Haloperidol
Trifluoperazine
32
Example of 2-nd generation "atypical antipsychotics"
clozapine
olanzapine
quatipine
asenapine
risperidone
aripiprazole
33
what is the primary mechanism of action of first-generation (typical) antipsychotic?
D2 receptor antagonists
34
what is the primary mechanism of action of second- generation (atypical) antipsychotics?
5HT2/ D2 receptor antagonists.
35
what side effect is more commonly associated with second-generation (atypical) antipsychotics?
associated with higher risk of metabolic side effects (e.g., weight gain, diabetes, dyslipidemia.
36
High potency typical antipsychotics
haloperidol
fluphenazine
pimozide
thiothixene
37
Low potency typical antipsychotics
chlorrpromazine
prochlorperazine
Thioridazine
38
Besides D2 receptors, what other receptors do first-generation antipsychotics affect?
They also affect serotonin type 2 (5-HT2), alpha1, histaminic, and muscarinic receptors.
39
What symptoms of schizophrenia do first-generation antipsychotics effectively control?
They effectively control positive symptoms (e.g., hallucinations, delusions).
40
What is the primary mechanism of action of second-generation (atypical) antipsychotics?
They are 5HT2/D2 receptor antagonists.
41
Are second-generation antipsychotics significantly more effective than first-generation antipsychotics in treating cognitive and negative symptoms of schizophrenia?
No, there is no evidence that second-generation antipsychotics are significantly more effective than first-generation antipsychotics for these symptoms.
42
What happens to dopamine (DA) neurons during the initial phase of antipsychotic treatment?
Initially, dopamine neurons activate and release more dopamine.
43
What happens to dopamine neurons after repeated antipsychotic treatment?
They enter a state of physiological depolarization inactivation, leading to diminished production and release of dopamine, in addition to continued receptor blockade.
44
What happens to dopamine levels during the initial phase of antipsychotic treatment with D2 blockers?
Dopamine levels temporarily increase due to the removal of inhibitory feedback, leading to increased dopamine turnover and higher HVA levels.
45
What happens to dopamine levels with prolonged use of antipsychotics?
Dopamine levels can decrease due to receptor downregulation and compensatory mechanisms, leading to dopamine deficiency in certain brain regions.
46
What are the potential consequences of dopamine deficiency caused by prolonged antipsychotic use?
It can contribute to side effects such as negative symptoms and movement disorders (e.g., Parkinsonism, extrapyramidal symptoms [EPS]).
47
What is the effect of first-generation antipsychotics blocking D2 receptors in the mesolimbic pathway?
It results in reduced positive symptoms of schizophrenia.
48
What is the effect of first-generation antipsychotics blocking D2 receptors in the mesocortical pathway?
It can cause or worsen cognitive symptoms and negative symptoms, as this pathway is already deficient in schizophrenia.
49
What is the effect of first-generation antipsychotics blocking D2 receptors in the nigrostriatal pathway?
It produces extrapyramidal symptoms (EPS) such as motor abnormalities (parkinsonism), tardive dyskinesia, or hyperkinetic movement disorders.
50
What is the effect of first-generation antipsychotics blocking D2 receptors in the tuberoinfundibular pathway?
It causes hyperprolactinemia.
51
What are some common side effects of first-generation antipsychotics?
Dry mouth, blurred vision, drowsiness, weight gain, and EPS due to their anticholinergic properties.
52
What is dystonia in the context of extrapyramidal side effects (EPS)?
Dystonia involves sustained muscle contractions that cause twisting, repetitive movements, or abnormal postures.
53
What is akathisia in the context of extrapyramidal side effects (EPS)?
Akathisia is a restless feeling and the urge to move.
54
What are the symptoms of pseudoparkinsonism in the context of extrapyramidal side effects (EPS)?
Symptoms include rigidity, bradykinesia (slowed movement), tremor, and postural instability.
55
What is tardive dyskinesia in the context of extrapyramidal side effects (EPS)?
Tardive dyskinesia involves involuntary, repetitive movements, most commonly of the face, tongue, mouth, and limbs.
56
What is Neuroleptic Malignant Syndrome (NMS) in the context of extrapyramidal side effects (EPS)?
NMS is characterized by severe muscle rigidity, hyperthermia, autonomic dysregulation, and altered mental status.
57
What are "CPZ-equivalent dosages" in the context of first-generation antipsychotics (FGAs)?
CPZ-equivalent dosages refer to the equipotent dosage of an FGA compared with 100 mg of chlorpromazine (CPZ), and they are useful when switching from one FGA to another.
58
What type of antipsychotic is Fluphenazine, and what receptors does it block?
Fluphenazine is a high-potency typical antipsychotic that blocks postsynaptic dopaminergic D1 and D2 receptors. It also has some alpha-adrenergic and anticholinergic effects.
59
What is the dosing regimen for Fluphenazine decanoate?
The dosing for Fluphenazine decanoate is 12.5–100 mg IM every 3–4 weeks.
60
What is the mechanism of action of Haloperidol?
dopamine D2 antagonist with high potency and low potential for causing orthostasis.
61
What is a major drawback of Haloperidol?
It has a high potential for extrapyramidal symptoms (EPS) and dystonia.
62
Which cytochrome P450 enzymes are involved in Haloperidol metabolism, and what is the clinical significance?
Haloperidol interacts with CYP3A4 and CYP2D6 inhibitors and inducers, which can affect its metabolism and plasma levels.
63
What is a critical drug interaction to monitor with Haloperidol?
Haloperidol can interact with drugs that prolong QTc intervals, increasing the risk of arrhythmias.
64
What is the primary mechanism of action of most atypical antipsychotics?
Most atypical antipsychotics are dopamine antagonists and potently block 5-HT2A receptors, with greater blockade of 5-HT than dopamine.
65
What makes Aripiprazole unique among atypical antipsychotics?
Aripiprazole is a partial dopamine and 5-HT1A agonist and a 5-HT2A antagonist, unlike other atypical antipsychotics.
66
What receptors does Asenapine have a high affinity for?
Asenapine has high affinity for 5-HT, dopamine, alpha, and histaminergic receptors, but low affinity for muscarinic receptors.
67
What is unique about Iloperidone’s receptor activity?
Iloperidone acts on numerous 5-HT and dopamine receptors and has high affinity for alpha-1 receptors.
68
What is unique about Lurasidone’s receptor profile?
Lurasidone is a partial 5-HT1A agonist and has no affinity for muscarinic or histaminergic receptors.
69
What are MARTA (multi-acting receptor targeted agents) atypical antipsychotics?
Examples include Clozapine, Olanzapine, and Quetiapine. They act on multiple receptors (e.g., dopamine, serotonin, histamine, muscarinic).
70
What are SDA (serotonin-dopamine antagonist) atypical antipsychotics?
Examples include Risperidone, Ziprasidone, and Sertindole. They primarily block 5-HT2A and D2 receptors.
71
What are selective D2/D3 antagonist atypical antipsychotics?
Examples include Sulpiride and Amisulpiride. They specifically target D2 and D3 dopamine receptors.
72
What is the receptor activity profile of second-generation antipsychotics (SGAs)?
SGAs have weak D2 blocking but potent 5-HT2 antagonistic activity.
73
Which SGA is unique in fulfilling all criteria for receptor activity?
Clozapine is the only SGA that fulfills all criteria (e.g., weak D2 blockade, potent 5-HT2 antagonism, and other receptor effects).
74
What is the first-choice treatment for schizophrenia among SGAs, and why is Clozapine excluded?
Risperidone or Olanzapine are often first-choice SGAs for schizophrenia. Clozapine is reserved for treatment-resistant cases due to its risk of severe side effects (e.g., agranulocytosis).
75
What is the mechanism behind Clozapine-induced agranulocytosis?
Clozapine is metabolized into a toxic nitrenium ion, which damages bone marrow cells producing neutrophils, potentially triggering an immune response that destroys these cells, leading to agranulocytosis.
76
What is the primary mechanism of action of second-generation antipsychotics (except Aripiprazole)?
They are dopamine D2 antagonists but have lower rates of extrapyramidal symptoms (EPS) and tardive dyskinesia (TD) compared to first-generation antipsychotics.
77
What makes Aripiprazole unique among second-generation antipsychotics?
Aripiprazole is a partial dopamine and 5-HT1A agonist and a 5-HT2A antagonist, unlike other atypical antipsychotics.
78
What are the major adverse effects associated with second-generation antipsychotics?
They are associated with higher rates of metabolic adverse effects (e.g., weight gain, diabetes, dyslipidemia) compared to first-generation antipsychotics.
79
How does D2 receptor blockade in the mesolimbic pathway help in schizophrenia treatment?
D2 receptor blockade in the mesolimbic pathway is more robust than 5-HT2A antagonism, which helps reduce positive symptoms (e.g., hallucinations, delusions).
80
What causes negative and cognitive symptoms in schizophrenia?
Dopamine deficiency in the mesocortical pathway contributes to negative symptoms (e.g., apathy, social withdrawal) and cognitive symptoms (e.g., poor executive function).
81
Why is 5-HT2A antagonism more significant than D2 blockade in the mesocortical pathway?
The mesocortical pathway has more 5-HT2A receptors than D2 receptors, so 5-HT2A antagonism is more profound and may help improve negative symptoms.
82
How does 5-HT2A antagonism in the nigrostriatal pathway reduce extrapyramidal symptoms (EPS)?
5-HT2A antagonists block serotonin release, leading to increased dopamine release, which may help reduce EPS (e.g., parkinsonism, dystonia).
83
What is the role of dopamine in the tuberoinfundibular pathway?
Dopamine inhibits prolactin release, whereas 5-HT2A stimulation promotes prolactin release.
84
How do antipsychotics affect prolactin release in the tuberoinfundibular pathway?
Antipsychotics have antagonistic effects on both dopamine and 5-HT2A receptors, which can cancel each other out, leading to variable effects on prolactin levels.
85
What are D2-like receptors, and where are they primarily found?
D2-like receptors include D2, D3, and D4 receptors. They are primarily found in the mesolimbic, mesocortical, nigrostriatal, and tuberoinfundibular pathways and are key targets of antipsychotic medications.
86
What is the schedule for WBC monitoring in patients taking Clozapine?
Weekly for the first 6 months (highest risk period).
Every 2 weeks for the next 6 months.
Every 4 weeks thereafter, as long as the absolute neutrophil count (ANC) remains normal.
87
Which of the atypical antipsychotics has good superiority in persistence of maintainance therapy
Olanzapine
## Footnote
Why?
88
What is the mechanism of action of risperidone?
D2 and 5HT2 antagonism
89
What are serotonin- dopamine activity modulators?
Brexpiprazole
Aripiprazole
90
what is the mechanism of action of serotonin -Dopamine Activity Modulators (SDAMs)?
Partial agonists at 5-HT1A and dopamine D2 receptors (similar potency).
Antagonists at 5-HT2A and noradrenaline alpha1B/2C receptors.
91
What is the receptor profile and mechanism of action of Aripiprazole?
High affinity for D2, D3, 5-HT1A, and 5-HT2A receptors.
Moderate affinity for D4, 5-HT2C, 5-HT7, alpha1 adrenergic, H2 receptors, and serotonin reuptake transporter.
| partial agonist at D2 and 5-HT1A receptors and an antagonist at 5-HT2A.
## Footnote
partial agonist at D2 and 5-HT1A receptors and an antagonist at 5-HT2A, alpha1, and H1 receptors.
92
What are the anticholinergic effects of antipsychotics, and what causes them?
Anticholinergic effects include impaired memory, tachycardia, blurred vision, dry mouth, constipation, urinary retention, and inhibition of ejaculation.
## Footnote
These result from muscarinic cholinergic blockade.
93
Why are elderly patients particularly sensitive to anticholinergic side effects?
Elderly patients have reduced cholinergic function and are more prone to side effects like cognitive impairment, confusion, and delirium.
94
What causes postural hypotension in patients taking antipsychotics, and does tolerance develop?
Postural hypotension results from adrenergic blockade (alpha1 receptor antagonism)
## Footnote
Tolerance to this side effect can develop over time.
95
What are possible management strategies for antipsychotic-induced galactorrhea?
Switch to an SGA (e.g., olanzapine, quetiapine, aripiprazole, or ziprasidone).
Add bromocriptine (up to 15 mg daily).
Add amantadine (up to 300 mg daily).
| Bromocriptine is a dopamine receptor agonist- decreases prolactin.
## Footnote
Amantadine and bromocriptine are dopamine receptor agonists.
96
What is the primary treatment for Neuroleptic Malignant Syndrome (NMS)?
## Footnote
Severe muscle rigidity
Hyperthermia (high fever)
Autonomic instability (e.g., tachycardia, blood pressure fluctuations)
Altered mental status (e.g., confusion, delirium)
Immediate discontinuation of the antipsychotic.
Supportive care (e.g., cooling, hydration, managing autonomic instability).
Pharmacological interventions (e.g., dantrolene for muscle rigidity, bromocriptine or amantadine for dopamine agonism).
97
How do second-generation antipsychotics (SGAs) affect cognition in schizophrenia?
SGAs, as first-line treatment, have been shown to improve cognition over a 9-month period.
98
What is the course of sedation as a side effect of antipsychotics?
Sedation is initially considerable, but tolerance usually develops after a few weeks of therapy. Some patients may also experience dysphoria.
99
What is dystonia in the context of EPS?
A movement disorder with sustained muscle contractions causing twisting movements or abnormal postures
## Footnote
e.g., torticollis, oculogyric crisis
100
# pacing, rocking
What characterizes akathisia as an EPS?
Restlessness and an urge to move, leading to repetitive motions or inability to sit still.
101
What are the four key symptoms of pseudoparkinsonism?
Rigidity (muscle stiffness)
Bradykinesia (slowed movement)
Resting tremor (e.g., "pill-rolling")
Postural instability (balance issues, falls)
102
# lip-smacking, tongue protrusion, limb jerking
What defines tardive dyskinesia?
Involuntary, repetitive movements
103
When does acute dystonia typically occur after starting antipsychotics?
It occurs rapidly (within 24–96 hours) of initiating treatment or increasing the dose, especially with high-potency typical antipsychotics
## Footnote
e.g., haloperidol
104
Which patient population is at highest risk for acute dystonia?
Young men are most susceptible, particularly when using high doses of high-potency typical antipsychotics.
105
How is acute dystonia managed?
IM/IV anticholinergics (e.g., benztropine, diphenhydramine).
Benzodiazepines (if anticholinergics fail).
For severe cases (e.g., laryngeal dystonia), emergency intervention is required.
106
What is acute dystonia in the context of antipsychotic use?
Acute dystonia involves prolonged tonic muscle contractions, primarily affecting the eyes, neck, face, and throat
## Footnote
medical emergency if pharyngeal-laryngeal muscles are involved.
107
What are the treatment options for akathisia?
Reduce the antipsychotic dose.
Use lipophilic β-blockers (e.g., propranolol) or benzodiazepines.
Switch to an SGA (e.g., quetiapine, clozapine), which have the lowest risk of akathisia.
108
Why are anticholinergic agents not effective for treating akathisia?
Unlike dystonia/pseudoparkinsonism, akathisia is not mediated by cholinergic pathways, so anticholinergics (e.g., benztropine) are ineffective.
109
Which SGAs are least likely to cause akathisia?
Quetiapine and clozapine have the lowest risk of inducing akathisia among SGAs.
110
Why is close monitoring for TD critical in patients on antipsychotics?
TD is often irreversible, so early detection (e.g., using the Abnormal Involuntary Movement Scale [AIMS]) is key to preventing progression.
111
What are unproven but attempted treatments for TD?
Vitamin E (antioxidant).
Benzodiazepines (e.g., clonazepam).
Baclofen (GABA agonist).
Reserpine (dopamine depleter).
## Footnote
None have definitive evidence of efficacy.
