Neuroscience Week 8: Anti-psychotic drugs Flashcards
(102 cards)
1
Q
Title
A
2
Q
Objectives
A
3
Q
Antipsychotics Prototype agents
A
4
Q
Typical Antipsychotics
3 listed
A
- Haloperidol
- Perphenazine
- Chlorpromazine
5
Q
Atypical Antipsychotics
5 listed
A
- Clozapine
- Risperidone
- Olanzepine
- Ziprasidone
- Aripiprazole
6
Q
Haloperidol related agents
A
Pimozide
7
Q
Perphenazine related agents
2 listed
A
- Fluphenazine
- Trifluoperazine
8
Q
Chlorpromazine related agents
A
Thioridazine
9
Q
Risperidone related agents
A
- Paliperidone
- Iloperidone
10
Q
Olanzapine related agents
2 listed
A
- Quetiapine
- Asenapine
11
Q
Ziprasidone
A
Lurasidone
12
Q
Aripiprazole related agents
A
Brexiprazole
13
Q
Long-acting Depot preps
4 listed
A
- fluphenazine
- haloperidol
- risperidone
- olanzepine
14
Q
Group II mGluR agonists & Glycine transporter 1 inhibitors
A
adjunct agents for cognitive enhancement
SOON?
15
Q
Major tranquilizers
A
Major tranquilizers do not cure schizophrenia but merely suppress its symptoms, and they are usually prescribed on a long-term basis.
The basic types are the phenothiazines, thioxanthines, butyrophenones, clozapine, and rauwolfia alkaloids.
16
Q
Neuroleptics AKA
A
Antipsychotics
17
Q
Antipsychotic?
A
- 1st gen vs 2nd gen
- Typical vs atypical
18
Q
Therapeutic potency - high vs low
A
refers to dose effective for treating positive symptoms
19
Q
Common pharmacokinetic properties of antipsychotics
6 listed
A
20
Q
Treating the components of Schizophrenia
4 listed
A
21
Q
typical positive symptoms of schizophrenia
A
22
Q
typical negative symptoms of schizophrenia
4 listed
A
23
Q
typical mood symptoms of schizophrenia
A
24
Q
typical cognitive deficit symptoms of schizophrenia
4 listed
A
25
Dopamine in Schizophrenia
5 listed
26
Drugs that deplete dopamine have some?
efficacy as antipsychotics
27
Chronic amphetamine abuse can produce
some symptoms of paranoia
28
Centrally acting dopamine receptor agonist common side effect
Hallucinations
29
Postmortem and PET studies suggest increased ____________ in schizophrenics
Dopamine D2 receptor binding
30
Almost all antipsychotics have ______________ antagonist properties
Dopamine D2 receptor antagonist
31
For treating positive symptoms of schizophrenia D2 binding
32
Haloperidol D2 antagonism
Very high
33
Perphenazine D2 antagonism
High
34
Chlorpromazine D2 antagonism
Medium
35
Clozapine D2 antagonism
medium but major selectivity to D4
36
Olanzapine D2 antagonism
medium
37
Risperidone D2 antagonism
medium
38
Ziprasidone D2 antagonism
medium
39
Ariprazole D2 antagonism
Low
because it is a partial D2 agonist
40
Aripiprazole MOA
D2 receptor partial agonist
41
What are the advantages of a partial agonist
reduce overall stimulation?
42
Antipsychotics MOA in addition to D2 antagonism
4 listed
43
Drugs acting on other neurotransmitter systems besides D2 produce symptoms of psychosis such as?
* Serotonin - LSD/5HT2A agonists produce hallucinations
* Glutamate: Phencyclidine - animal model of psychosis
44
Many antipsychotic agents can act on various combinations of other neurotransmitter systems besides dopamine, such as?
4 listed
* serotonergic
* cholinergic
* Noradrenergic
* Histaminergic
45
Haloperidol 5HT2A antagonism
None
46
Perphenazine 5HT2A antagonism
Low
47
Chlorpromazine 5HT2A antagonism
medium
48
Clozapine 5HT2A antagonism
medium
49
Olanzapine 5HT2A antagonism
medium
50
Risperidone 5HT2A antagonism
High
51
Ziprasidone 5HT2A antagonism
medium
52
Aripiprazole 5HT2A antagonism
High
53
Antipsychotics efficacy on positive symptoms
similar efficacies
54
Antipsychotics efficacy on negative symptoms
Atypical \> Typical
55
5HT2A receptor antagonism correlates better with efficacy for treating?
the negative symptoms of schizophrenia
56
Those agents with some balance of both D2 and 5HT2A receptor antagonism appear?
more efficacious overall for schizophrenia for the positive and negative symptoms
57
Treating depressive symptoms of schizophrenia
Antidepressants
58
Treatment of cognitive dysfunction of schizophrenia
* Antipsychotic agents have variable efficacy
* Adjunct agents/cognition enhancers
59
Cognition enhancers general strategy
Agents that enhance acetylcholine and/or glutamate influence
(clozapine, risperidone, olanzapine ↑ ACh release)
60
Cognitive enhancers: Agents that prolong transmitter effect in the synapse
Cholinesterase inhibitors (Tacrine)
61
Cognitive enhancers: agents acting as agonists or positive allosteric modulators
3 listed
* AMPAkines
* Glycine modulators of the NMDA receptor
* Group I mGlu agonists
62
Cognitive enhancers: agents that enhance transmitter release from nerve terminals (ACh/Glutamate)
* Subtype-selective nNCR agonists
* 5HT4 / 5HT6 / H3 receptor antagonists or inverse agonists
63
Cognitive enhancers overview
64
Dopamine pathways in the brain
4 listed
65
Neurologic side effects of D2 receptor antagonists
More frequently observed with haloperidol-like agents
66
Basis Neurologic side effects of D2 receptor antagonists?
↓ DA/ACh balance in the basal ganglia
67
Neurologic side effects of D2 receptor antagonists acute symptom management
Acute symptoms can be managed with MCR antagonists or switching to atypicals
68
Endocrinologic side effects of D2 receptor antagonists
more frequent with haloperidol-like drugs
69
Endocrinologic side effects of D2 receptor antagonists: Side effects lessened with?
Switch to atypical antipsychotics
70
Basis of atypicals on Endocrinologic side effects of D2 receptor antagonists
lesser impact on hypothalamic DA/5HT regulatory balance influencing pituitary hormone secretion
71
Antipsychotic side effects related to antagonism of other receptors: Organ systems
3 listed
* CNS
* ANS
* Metabolic
72
Antipsychotic side effects related to antagonism of other receptors: CNS receptors
* MCR
* α1
* H1
73
Antipsychotic side effects related to antagonism of other receptors: CNS symptoms
* Sedation
* Cognitive impairments
* ↓ seizure threshold (Clozapine, 2-5%)
* ↑ appetite - weight gain
74
Antipsychotic side effects related to antagonism of other receptors: ANS receptors
* MCR
* α1
75
Antipsychotic side effects related to antagonism of other receptors: ANS symptoms
4 system effects listed
* hypotension, tachycardia
* Dry mouth, constipation
* Urinary retention, nasal stuffiness
* Sexual dysfunction
76
Antipsychotic side effects related to antagonism of other receptors: Metabolic receptors
* α1
* H1
77
Antipsychotic side effects related to antagonism of other receptors: Metabolic symptoms
* Hyperlipidemia
* Impaired glucose tolerance → Diabetes
* Metabolic syndrome: ↑ risk of CAD, hypertension, stroke
78
Typicals and atypicals structures
79
Serious complications of antipsychotic treatments
4 listed
* Tardive Dyskinesia
* Neuroleptic Malignant Syndrome
* Severe Agranulocytosis
* Seizures - (Clozapine most notable; lower incidence with chlorpromazine-like agents)
80
Tardive Dyskinesia Description
"Late-occurring" stereotypic oral-facial movements
81
Tardive Dyskinesia Risk Factors
* Age
* gender
* Renal/CV disease
* length of treatment (3% per year on haloperidol)
* D2 receptor antagonist \>\> MCR antagonist profile
82
Tardive Dyskinesia Treatment options
reduce dosage OR switch to other atypical antipsychotics (clozapine)
83
Neuroleptic Malignant Syndrome description
5 listed
* Severe muscle ridgidity
* ANS-CV instability
* Sweating
* Hyperrexia
* Myoglobinuria
84
Neuroleptic Malignant Syndrome Treatment options
3 listed
* Muscle relaxants
* D2 receptor agonists (bromocriptine)
* Switch to atypical antipsychotics
85
Severe Agranulocytosis common causative agent
clozapine
86
Severe Agranulocytosis prevalence
occurs in 1% to 2% of patients
87
Severe Agranulocytosis monitoring
requires weekly blood counts first 6 months/every 3rd week thereafter
88
Seizures antipsychpotics common causative agents)
Clozapine; to a lesser degree chlorpromazine-like agents)
89
Seizures prevalence antipsychpotics
2% to 5% of patients
90
Treatment considerations I
7 listed
91
Patterns of psychotic episodes
92
Impact of multiple schizophrenic relapses
93
Treatment considerations II
6 listed
94
Treatment considerations III
3 listed
95
Other uses of antipsychotic agents
3 listed
96
Antipsychotic antiemetic
DA receptor blockade in the chemoreceptor trigger zone (CTZ)
97
Antipsychotic Neuroleptic analgesia
* combination of a haloperidol-like agent and a fast-acting opioid analgesic (such as fentanyl)
98
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