Antipsychotic Agents Flashcards
1
Q
____ is due to too much neurotransmission due to too many neurotransmitters binding to postsynaptic receptors
A
Psychosis
2
Q
The therapeutic goal of psychosis is to block access to post-synaptic receptors by administering a ___ ___
A
Receptor agonist
3
Q
Antipsychotics, also known as neuroleptics take control of the _____
A
Neuron
4
Q
Prior to 1950, psychotic patients were often ____
A
Institutionalized
5
Q
What are three classifications of antipsychotics?
A
-Traditional or classic agents (1950-1990)
-Atypical agents (or second-generation antipsychotics)
-Third-generation antipsychotics
6
Q
What are clinical indications for antipsychotics?
A
-Schizophrenia
-Schizoaffective disorder
-Bipolar disorder
-Acute psychotic symptoms (violence/agitation) or behavioral disturbances related to Tourettes, Senile Dementia, Alzheimer’s disease, etc)
7
Q
Other uses for phenothiazines and related antipsychotic drugs include…
A
-Antiemetic/antinausea
-Antihistamine/antipruritic activity
-Potentiation of analgesics, sedatives, and general anesthetics
8
Q
Schizophrenia is a ____ disease
A
Debilitating
9
Q
What are symptoms of Schizophrenia?
A
-Delusions
-Hallucinations
-Disorganized speech
-Catatonia
-Deficits in attention, memory, or executive function
-Comorbidities (Mood disorders, substance use disorders, anxiety, aggression)
-Depression
-Anxiety
-Aggression
-Hostility
-Hopelessness
-Suicidality
-Flat affect
-Poverty of speech
-Lack of energy
-Lack of interest
-Social withdrawal
10
Q
All of the symptoms of Schizophrenia lead to ____ and ____ dysfunction
A
Social and occupational
11
Q
Excessive _____ activity underlies Schizophrenia
A
Dopaminergic
12
Q
Drugs that increase dopaminergic activity (levodopa, amphetamines) ____ schizophrenia or induce a ____
A
Aggravate; psychosis
13
Q
Traditional antipsychotics block the ____ receptor and clinical efficacy is directly proportional to affinity
A
D2
14
Q
Postmortem, there has been found to be an ____ in dopamine receptor density in those with untreated schizophrenia
A
Increase
15
Q
The clinical response of schizophrenia is correlated with a decrease in a dopamine metabolite, ____ ____, in the cerebrospinal fluid, plasma, and urine
A
Homovanillic acid
16
Q
We know that serotonin is also involved with neurotransmitters because LSD, which produces hallucinations (like seen in schizophrenia), is a ___ ____
A
Serotonin agonist
17
Q
We know that glutamate is involved in schizophrenia because PCP, which produces a psychosis similar to schizophrenia, is a ____ ___ at NMDA (glutamate) receptors
A
Glutamate antagonist
18
Q
NMDA hypofunction causes glutamate ____ and the destruction of cortical neurons
A
Toxicity
19
Q
Glutamate is like the “___ ___” in your car for neuronal transmission
A
Gas pedal
20
Q
Traditional antipsychotics principally act via the blockage of ____ ____
A
Dopamine receptors
21
Q
____ subtypes of dopamine receptors have been described
A
5
22
Q
Antipsychotic activity of the classical agents correlates best with the ____ receptor blockade
A
DA2
23
Q
Dopamine receptor blockade in the extrapyramidal tracts and the hypothalamus/pituitary account for many side effects of antipsychotics such as…
A
-Movement disorders
-Endocrine imbalances
24
Q
Other side effects of traditional antipsychotics are related to interactions with other _____
A
Neurotransmitters
25
Atypical or second-generation antipsychotics block more than one type of _____
Receptor
26
Atypical/second-generation antipsychotics have a greater affinity for ____ than ____
Serotonin; dopamine
27
Atypical/second-generation antipsychotics can alleviate positive and negative symptoms and possibly help _____ deficits
Neurocognitive
28
Atypical or second-generation antipsychotics cause less or no ___ ___ or ___ ___
-Extrapyramidal symptoms
-Tardive dyskinesia
29
Atypical or second-generation antipsychotics can generally be started ____ in the disease
Earlier
30
In 2003, Ariprprazole (Abilify) was introduced as the ___ atypically antipsychotic
7th
31
Aripiprazole (Abilify) has unique synaptic actions, making it the first of a ___ generation of antipsychotic drugs
Third
32
Aripiprazole (Abilify) is not a dopamine antagonist, but rather a ___ ____ of dopamine receptors; it "stabilizes" hyper and hypoactivity
Partial agonist
33
Aripiprazole (Abilify) is also 5HT2 ____ and partial ____ at 5HT1A
Antagonist; agonist
34
Antipsychotics are absorbed ___, but incompletely
Readily
35
Antipsychotics are significantly affected by ___-___ metabolism
First-pass
36
Antipsychotics are ____% protein-bound
95
37
Antipsychotics have a much ____ clinical duration of action than estimated from the plasma half-life due to sequestration in fat tissue
Longer
38
Antipsychotics are mainly metabolized by ____ ____ and ____
Hepatic oxidation and glucoronidation
39
Active metabolite formation is not important except for with what drug, that produces a metabolite that is more potent than the parent drug?
Thioridazine
40
The ability to metabolize and eliminate antipsychotics diminishes with ____
Age
41
The typical half-life of an antipsychotic is from ___-___ hours
12-24
42
Smoking decreases plasma levels of what 4 antipsychotic drugs?
-Clozapine
-Olanzapine
-Haloperidol
-Fluphenazine
43
Antipsychotics are pure ____ blockers
D2
44
Chlorpromazine (Thorazine) should be given at a dose between ____-___ mg/day
200-1,000
45
Chlorpromazine (Thorazine) is rarely used due to its low ____
Potency
46
Chlorpromazine (Thorazine) causes significant central and peripheral alpha-1 adrenergic blockage, causing ___ and ____
Sedation and hypotension
47
Chlorpromazine (Thorazine) may cause some extrapyramidal symptoms due to ____ blockage in basal ganglia
Dopamine
48
Thioridazine (Mellaril) should be given at a dose between ____-____ mg/day
20-800
49
Thioridazine (Mellaril) has a greater potency than Aliphatics like _____, but causes a similar alpha-1 adrenergic blockage
Chlorpromazine
50
Thioridazine (Mallaril) causes less extrapyramidal symptoms due to significant ____ activity, but causes increased incidence of cardiac arrhythmias
Anticholinergic
51
Fluphenazine (Prolixin) should be given in doses of __-__ mg/day
5-40
52
Fluphenazine (Prolixin) is also available in ____ formulation
Intramuscular
53
Perphenazine (Trilafon) should be given in doses between ___-___ mg/day
8-64
54
Thiothixene (Navane) should be given in doses between ___-___ mg/day
6-60
55
Phenothiazines and Thioxanthenes cause potent ____ blockages, leading to significant extrapyramidal symptoms
D2 (dopamine)
56
Phenothiazines and Thioxanthenes cause less of an ____ adrenergic blockade, meaning less sedation and hypotension
Alpha-1
57
Haloperidol (Haldol) is an example of what drug class?
Butyrophenones
58
Haloperidol (Haldol) was the first alternative to ____
Phenothiazines
59
Haloperidol (Haldol) should be given in doses between ___-___ mg/day
5-40
60
Butyrophenones like Haloperidol (Haldol) are _____ unrelated to phenothiazines, though the pharmacological and side effects are similar
Structurally
61
Butyrophenones like Haloperidol (Haldol) cause high incidence of ____ ____ and ____, but less weight gain, anticholinergic effects, and hypotension than older phenothiazines
Extrapyramidal symptoms and sedation
62
What are three Phenothiazine alternatives of the 1970s?
-Molindone (Moban)
-Pimozide (Orap)
-Loxapine (Loxitane)
63
Molindone (Moban) and Pimozide (Orap) are ____ antagonists and are structurally unrelated to the phenothiazines/thioxanthenes; they have no apparent clinical advantages
D2 (dopamine)
64
Loxapine (Loxitane) has a similar structure to ____ ____
Tricyclic anitdepressants
65
Loxapine (Loxitane) has mixed ____ and ____ activity
Antipsychotic and antidepressant
66
What is a metabolite of Loxapine (Loxitane)?
Amoxapine
67
Loxapine (Loxitane) binds ____ and ____ receptors
Dopaminergic and serotonergic
68
Loxapine causes less ____ symptoms than piperazine phenothiazines
Extrapyramidal
69
Traditional antipsychotic agents have a ____ therapeutic index with respect to mortality
High
70
Overdoses with traditional antipsychotics are rarely fatal, except for ____ which can be cardiotoxic
Thioridazine
71
Side effects of traditional antipsychotic agents routinely occur at therapeutic doses as they are extensions of pharmacological actions; these include...
-Sedation
-Extrapyramidal symptoms (dystonia, akathisia, parkinsonism)
-Tardive Dyskinesia
72
Tardive Dyskinesia occurs in ___-___% of chronically treated patients
20-40
73
Tardive Dyskinesia causes abnormal, jerky movements of the ____ and ____
Face and tongue
74
The mechanism of tardive dyskinesia is poorly understood and unpredictable, but thought to be due to ___ ___ ____
D2 (dopamine) receptor supersensitivity
75
There is no treatment for tardive dyskinesia and it may be _____
Irreversible
76
If signs of tardive dyskinesia develop, reduce dose or discontinue the antipsychotic and eliminate all drugs with central anticholinergic action (antidepressants) OR switch to ___
Clozapine
77
Prevention of tardive dyskinesia is key; give minimal ____ doses for a limited time if possible
Effective
78
____ ____ syndrome is a rare medical emergency that affects 1% of patients, but 10% of cases are fatal
Neuroleptic malignant
79
Neuroleptic malignant syndrome is more common in what gender?
Males
80
80% of cases of neuroleptic malignant syndrome occur in patients under ____ years old
40
81
What are symptoms of neuroleptic malignant syndrome?
-Hyperthermia or fever
-Diffuse muscular rigidity
-Severe extrapyramidal symptoms
-Fluctuating levels of consciousness
82
Treatment for neuroleptic malignant syndrome is ____, and consists of rehydration, body cooling, and discontinuing with the antipsychotic
Supportive
83
Traditional antipsychotics might be contraindicated in patients with...
-Parkinson's disease
-Hepatic failure
-Hypotension
-Bone marrow depression
-Those prescribed CNS depressants
84
Traditional antipsychotic drugs can have additive effects when taken with what types of drugs?
-CNS depressants
-Anticholinergic medications
85
Traditional antipsychotics have the potential for increased metabolism when administered with agents that include ____ ____, like cigarette smoking
Hepatic enzymes
86
What are other adverse effects of traditional antipsychotics?
-Autonomic and endocrine effects
-Cholestatic jaundice due to biliary obstruction
-Dermatological reactions: allergic reaction, photosensitivity
-Ocular effects
-Reproductive effects
87
What are examples of ocular effects that could result from traditional antipsychotics?
-Opacities of the cornea and lens with chlorpromazine
-Decreased vision or blindness with high-dose thioridazine
88
What are examples of reproductive effects that could result from traditional antipsychotics?
-In women: amenorrhea and increased libido
-In men: decreased libido and gynecomastia
89
From 1975-____, not a single new antipsychotic was marketed in the US
1989
90
What are examples of second-generation antipsychotics?
-Clozapine
-Risperidone
-Olanzapine
-Quetiapine
-Ziprasidone
-Lurasidone
91
What is one third-generation antipsychotic?
Aripiprazole
92
Compared to classical/traditional antipsychotics, atypical antipsychotics have...
-Wider range of CNS receptor interactions (particularly with 5-HT2 (serotonin) receptors)
-Different adverse effect profile
93
As a group, atypical antipsychotics all produce less ___ ___ and are less likely to produce tardive dyskinesia
Extrapyramidal symptoms
94
Atypical antipsychotics are more effective in reducing "____" symptoms of schizophrenia than older agents
Negative
95
Haloperidol has its main effect on what receptor?
D2
96
Clozapine has its main effect on what 3 receptors?
-Muscarinic
-5-HT2
-Alpha1
97
Risperidone has its main effect on what 2 receptors?
-D2
-5-HT2
98
Olanzapine has its main effect on what 3 receptors?
-Muscarinic
-D2
-5-HT2
99
Ziprasidone has its main effect on what 2 receptors?
-D2
-5-HT2
100
D1-antagonism has ____ effects, but potent agents may impair cognitive function
Unknown
101
D2-antagonism has ____ effects; it causes relief of positive symptoms, induction of extrapyramidal symptoms, and increased prolactin levels
Antipsychotic
102
5-HT1a-agonist has possible ___/___ effects
Antidepressant/anxiolytic
103
5-HT2a-antagonism causes improvement in negative symptoms and ____ ____; this may reduce extrapyramidal symptoms
Cognitive impairment
104
5-HT2c-antagonism may cause ____ as well as attenuate increases in prolactin levels; this contributes to weight gain and there is limited evidence for the mediation of antipsychotic effects
Anxiolysis
105
5-HT3-antagonism has an ____ effect and this is normally lacking in antipsychotic agents
Antiemetic
106
Alpha1-antagonism causes what clinical effects?
-Sedation
-Hypotension
-Reflex tachycardia
107
Alpha2-antagonism causes what clinical effects?
-May improve depression and negative effects
108
H1-antagonism causes what clinical effects?
-Sedation
-Contribution to weight gain
109
m1-antagonism causes what clinical effects?
-Anticholinergic effects
-May attenuate extrapyramidal symptoms
110
____ is the prototype "atypical" antipsychotic which the FDA approved in 1989
Clozapine (Clozaril)
111
What is the mechanism of action for Clozapine (Clozaril)?
-Binds to multiple receptors (dopamine, serotonin, acetylcholine)
-Greater 5-HT2 (serotonin) than D2 (dopamine) blockade defines "atypical"
112
Clozapine (Clozaril) is not indicated as first-line for schizophrenia due to _____ effects
Hematological
113
To be prescribed Clozapine (Clozaril), a patient must have failed a minimum of ____ other antipsychotics due to insufficient effectiveness or signs of toxic dose/other intolerable side-effects
2
114
Clozapine (Clozaril) salvages ____ of those patients who are considered treatment refractory
Half
115
Clozapine can cause ____, so patients must register for a program and have bloodwork before refill
Agranulocytosis
116
Side effects of Clozapine (Clozaril) include...
-Sedation (40%)
-Weight gain (80%)-> can be up to 20 pounds
-Constipation (30%)
-Agranulocytosis (1-2%)
-Seizures (3.5%)
117
Agranulocytosis from Clozapine (Clozaril) usually develops within the first ___ months of treatment
3
118
If someone is taking Clozapine (Clozaril), they need weekly monitoring of ___ ___ cell counts
White blood
119
What are signs of agranulocytosis?
-Fever
-Sore throat
-Cellulitis
120
Risperidone (Risperdal) has a unique _____ structure
Chemical
121
Risperidone (Risperdal) causes a potent blockage of ___ and ____ receptors
D2 (dopamine) and 5HT2 (serotonin)
122
Risperidone (Risperdal) improves control of psychotic symptoms with minimal ____ symptoms at therapeutic doses
Extrapyramidal
123
Risperidone (Risperdal) is not associated with the ____ and ____ risks of clozapine
Hematological and seizure
124
The initial dose of Risperidone (Risperdal) is ___ mg, twice a day
1
125
Dosage of Risperidone (Risperdal) should be increased by ___-___ mg until the dose reaches 3mg twice per day
1-2
126
Typical dosing of Risperidone (Risperdal) is less than ____ mg/day; doses above this may result in extrapyramidal symptoms and increased prolactin
8
127
Doses above ___ mg twice per day are no more effective and cause more extrapyramidal symptoms
6
128
Risperidone ____ is a long-acting depot form (25 mg, 37.5mg, and 50mg injections)
Consta
129
The initial dose of Risperidone Consta is ____ mg IM every 2 weeks
25
130
The max dose of Risperidone Consta is ___ mg IM every 2 weeks
50
131
With Risperidone Consta, there is a ___ week lag in effect; this requires an overlap of oral risperidone
3
132
There are no real ____ doses between oral and injection Risperidone Consta
Equivalent
133
Dose adjustments for Risperidone Consta should not be made more than once per ____
Month
134
Once mixed, Risperidone Consta is stable for ____ hours
6
135
Paliperidone (Invega) is an active metabolite of _____
Risperidone (9-hydroxy)
136
Paliperidone (Invega) utilizes a _____ delivery system
OROS
137
Paliperidone (Invega) is a selective ____ antagonist
Monoaminergic
138
The therapeutic effect of selective monoaminergic antagonists like Paliperidone is antagonism activity of ___ and ____ receptors
5HT2A (serotonin) and DA2 (dopamine)
139
Selective monoaminergic antagonists cause enhanced affinity of...
-alpha1
-alpha2
-Histamine1
140
Paliperidone (Invega) has been approved for ____ and ____ treatment of schizophrenia
Acute and maintenance
141
Paliperidone (Invega) should be avoided in patients with...
-Gastrointestinal narrowing
-Concurrent medications known to prolong the QTc interval
-Congenital long QTc syndrome
-History of cardiac arrhythmias
142
What are some drug interactions with Paliperidone (Invega)?
-Levodopa and other dopaminergic agents
-Centrally acting agents
-Agents causing orthostatic hypotension
143
Paliperidone (Invega) should be given in a ____ mg dose once per day
6
144
Initial dose ____ is not required with Paliperidone (Invega)
Titration
145
Incremental adjustments of ____ mg/day at 5 or more day intervals are recommended for Paliperidone (Invega)
3
146
The maximum dose of Paliperidone (Invega) is ___ mg/day
12
147
For those with mild renal impairment (CrCl 50-80 mL/min), the maximum dose of Paliperidone (Invega) should be ___ mg/day
6
148
For those with moderate to severe renal impairment (CrCl 10-50 mL/min), the maximum dose of Paliperidone (Invega) should be ___ mg/day
3
149
No dose adjustment is required in patients with mild-moderate ____ impairment
Hepatic
150
Olanzapine (Zyprexa) is structurally and pharmacologically similar to Clozapine, but _____ has not been reported with it
Agranulocytosis
151
What is the mechanism of action with Olanzapine (Zyprexa)?
-Completely blocks 5HT2 (serotonin) at low doses (5 mg)
-D2 (dopamine) blockage increases with higher doses
152
Olanzapine (Zyprexa) is available in doses of 2.5, 5, 7.5, 15, and 20 mg and should not be ____, since it breaks the drug down
Cut
153
What are side effects of Olanzapine (Zyprexa)?
-Mild sedation
-Occasional extrapyramidal symptoms
-Weight gain/Diabetes
154
Olanzapine (Zyprexa) has less impact on ___ and does not cause agranulocytosis
Prolactin
155
The efficacy of Olanzapine (Zyprexa) is ____ to Lorazepam (Ativan) or Haloperidol (Haldol)
Superior
156
What are the two dosage forms of Zyprexa?
-Disintegrating tablets
-Injectable IM
157
Zyprexa ____ is the disintegrating tablet form of Zyprexa, and can be given in doses of 5, 10, 15, or 20 mg
Zydis
158
The injectable IM dosage form of Zyprexa is indicated for acute ____ in patients already on another oral antipsychotic, but is not a substitute for oral Zyprexa
Agitation
159
Injectable Zyprexa should be given in ___ mg doses every 2 hours, up to 3 doses in 24 hours
10
160
A single dose of injectable Zyprexa should not exceed ____ mg
10
161
Dosing of injectable Zyprexa in the elderly can be ___ or ___ mg
5 or 2.5
162
Vias of Zyprexa are single-dose only and must be ____ prior to administration
Mixed
163
There is a greater association with increased ___ and ___ with Olanzapine (Zyprexa) than other atypical antipsychotics or placebo
Glucose; lipids
164
What should be monitored for those taking Olanzapine (Zyprexa)?
-Glucose
-Weight
-Lipids
165
Abnormal or borderline glucose at baseline is a risk factor for further glucose ______ when taking Olanzapine (Zyprexa)
Increase
166
The FDA mandated changes in labeling for all atypical antipsychotics to include warnings for ____ and ____
Hyperglycemia and diabetes
167
There have been numerous reports of hyperglycemia and diabetes with ___ and ___, but fewer reports with Risperidone and Quetiapine
Clozapine, Olanzapine
168
The Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes stated that Aripiprazole and Ziprasidone have ____ metabolic side effects like weight gain, DM, and dyslipidemia
Less
169
The American Diabetes Association Monitoring Recommendations for those on antipsychotics include...
-Personal/family Hx: Baseline, annually
-Weight (BMI): Baseline, 4 weeks, 8 weeks, 12 weeks, quarterly
-Waist circumference: baseline, annually
-Blood pressure: baseline, 12 weeks, annually
-Fasting plasma glucose: baseline, 12 weeks, annually
-Fasting lipid profile: baseline, 12 weeks, generally every 5 years
170
Quetiapine (Seroquel) causes no clinically significant ___ ___ or alterations in cardiac intervals
Cardiac arrhythmias
171
Quetiapine (Seroquel) causes limited weight gain (about ____ pounds), mainly during the early weeks of treatment
5
172
There are ____ changes in patients who are on Quetiapine (Seroquel) long-term; they should have ophthalmological exams every 6 months
Lens
173
Quetiapine (Seroquel) is not indicated for ____
Sleep
174
What are some common side effects of Quetiapine (Seroquel)?
-Headache
-Agitation
-Somnolence
-Dizziness
-Dry mouth
-Weight gain
175
Ziprasidone (Geodon) is structurally similar to ____
Risperidone
176
Ziprasidone (Geodon) blocks ____ and ____, similar to other atypical antipsychotics
5HT2 (Serotonin) and dopamine
177
Ziprasidone (Geodon) has unique receptor actions that include...
-Agonist at 5HT1A receptor (a "buspirone-like" action)
-Moderately blocks 5-HT (serotonin) and norepinephrine reuptake
178
Ziprasidone (Geodone) improves ___ and ____ symptoms
Depressive and negative
179
Side effects of Ziprasidone (Geodone):
-Extrapyramidal symptoms
-Somnolence
-Nausea
-Constipation
-Dyspepsia
-Dizziness
180
Ziprasidone (Geodone) has more ____ properties than other atypical antipsychotics
Proarrhythmic
181
There is an absence of significant ____ ____ with Ziprasidone (Geodon)
Weight gain
182
Ziprasidone (Geodone) can be injected _____, but injections for more than 3 consecutive days has not been studied
Intramuscularly
183
For long-term therapy with Ziprasidone (Geodon), patients should switch to an ____ dosage form
Oral
184
Co-administration of ____ and ____ doses of Ziprasidone (Geodon) is not recommended
IM and oral
185
Ziprasidone (Geodone) injection has less side effects and is more effective at reducing acute symptoms than IM ____
Haloperidol
186
Lurasidone (Latuda) is a 2nd generation atypical much like ____
Ziprasidone (Geodone)
187
Mechanism of Lurasidone (Latuda):
-D2, 5HT2a, 5HT7 antagonist
-5HT1A partial agonist
-Minimal alpha 1
-No M1 or H1
188
Lurasidone (Latuda) is metabolized by what CYP450 enzyme?
CYP3A4
189
What are some adverse effects of Lurasidone (Latuda)?
-Insomnia
-Akathisia
-Nausea
-Parkinsonism
-Agitation
-Metabolic syndrome
190
What are the dosage forms of Aripiprazole (Abilify)?
-Oral solution
-Tablet
-Discmelt (disintegrating tablet)
-IM injection
191
Benefits of Aripiprazole (Abilify):
-Minimal weight gain or sedation
-Low incidence of extrapyramidal symptoms, even at high doses
-No prolactin elevation or QT prolongation
192
Common side effects of Aripiprazole (Abilify) include...
-Headache
-Nausea
-Insomnia
193
Overall, first-generation antipsychotics cause what side effects?
-Extrapyramidal symptoms
-Tardive dynskinesia
194
Second-generation antipsychotics generally have ____ side effects
Metabolic
