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Neuroscience > Neuroscience Week 8: Anti-psychotic drugs > Flashcards

Neuroscience Week 8: Anti-psychotic drugs Flashcards

1
Q

Title

A
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2
Q

Objectives

A
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3
Q

Antipsychotics Prototype agents

A
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4
Q

Typical Antipsychotics

3 listed

A
  • Haloperidol
  • Perphenazine
  • Chlorpromazine
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5
Q

Atypical Antipsychotics

5 listed

A
  • Clozapine
  • Risperidone
  • Olanzepine
  • Ziprasidone
  • Aripiprazole
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6
Q

Haloperidol related agents

A

Pimozide

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7
Q

Perphenazine related agents

2 listed

A
  • Fluphenazine
  • Trifluoperazine
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8
Q

Chlorpromazine related agents

A

Thioridazine

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9
Q

Risperidone related agents

A
  • Paliperidone
  • Iloperidone
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10
Q

Olanzapine related agents

2 listed

A
  • Quetiapine
  • Asenapine
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11
Q

Ziprasidone

A

Lurasidone

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12
Q

Aripiprazole related agents

A

Brexiprazole

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13
Q

Long-acting Depot preps

4 listed

A
  • fluphenazine
  • haloperidol
  • risperidone
  • olanzepine
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14
Q

Group II mGluR agonists & Glycine transporter 1 inhibitors

A

adjunct agents for cognitive enhancement

SOON?

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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.

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16
Q

Neuroleptics AKA

A

Antipsychotics

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17
Q

Antipsychotic?

A
  • 1st gen vs 2nd gen
  • Typical vs atypical
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18
Q

Therapeutic potency - high vs low

A

refers to dose effective for treating positive symptoms

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19
Q

Common pharmacokinetic properties of antipsychotics

6 listed

A
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20
Q

Treating the components of Schizophrenia

4 listed

A
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21
Q

typical positive symptoms of schizophrenia

A
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22
Q

typical negative symptoms of schizophrenia

4 listed

A
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23
Q

typical mood symptoms of schizophrenia

A
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24
Q

typical cognitive deficit symptoms of schizophrenia

4 listed

A
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25
Q

Dopamine in Schizophrenia

5 listed

A
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26
Q

Drugs that deplete dopamine have some?

A

efficacy as antipsychotics

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27
Q

Chronic amphetamine abuse can produce

A

some symptoms of paranoia

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28
Q

Centrally acting dopamine receptor agonist common side effect

A

Hallucinations

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29
Q

Postmortem and PET studies suggest increased ____________ in schizophrenics

A

Dopamine D2 receptor binding

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30
Q

Almost all antipsychotics have ______________ antagonist properties

A

Dopamine D2 receptor antagonist

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31
Q

For treating positive symptoms of schizophrenia D2 binding

A
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32
Q

Haloperidol D2 antagonism

A

Very high

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33
Q

Perphenazine D2 antagonism

A

High

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34
Q

Chlorpromazine D2 antagonism

A

Medium

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35
Q

Clozapine D2 antagonism

A

medium but major selectivity to D4

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36
Q

Olanzapine D2 antagonism

A

medium

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37
Q

Risperidone D2 antagonism

A

medium

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38
Q

Ziprasidone D2 antagonism

A

medium

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39
Q

Ariprazole D2 antagonism

A

Low

because it is a partial D2 agonist

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40
Q

Aripiprazole MOA

A

D2 receptor partial agonist

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41
Q

What are the advantages of a partial agonist

A

reduce overall stimulation?

42
Q

Antipsychotics MOA in addition to D2 antagonism

4 listed

43
Q

Drugs acting on other neurotransmitter systems besides D2 produce symptoms of psychosis such as?

A
  • Serotonin - LSD/5HT2A agonists produce hallucinations
  • Glutamate: Phencyclidine - animal model of psychosis
44
Q

Many antipsychotic agents can act on various combinations of other neurotransmitter systems besides dopamine, such as?

4 listed

A
  • serotonergic
  • cholinergic
  • Noradrenergic
  • Histaminergic
45
Q

Haloperidol 5HT2A antagonism

46
Q

Perphenazine 5HT2A​ antagonism

47
Q

Chlorpromazine 5HT2A​ antagonism

48
Q

Clozapine 5HT2A​ antagonism

49
Q

Olanzapine 5HT2A antagonism

50
Q

Risperidone 5HT2A​ antagonism

51
Q

Ziprasidone 5HT2A​ antagonism

52
Q

Aripiprazole 5HT2A​ antagonism

53
Q

Antipsychotics efficacy on positive symptoms

A

similar efficacies

54
Q

Antipsychotics efficacy on negative symptoms

A

Atypical > Typical

55
Q

5HT2A receptor antagonism correlates better with efficacy for treating?

A

the negative symptoms of schizophrenia

56
Q

Those agents with some balance of both D2 and 5HT2A receptor antagonism appear?

A

more efficacious overall for schizophrenia for the positive and negative symptoms

57
Q

Treating depressive symptoms of schizophrenia

A

Antidepressants

58
Q

Treatment of cognitive dysfunction of schizophrenia

A
  • Antipsychotic agents have variable efficacy
  • Adjunct agents/cognition enhancers
59
Q

Cognition enhancers general strategy

A

Agents that enhance acetylcholine and/or glutamate influence

(clozapine, risperidone, olanzapine ↑ ACh release)

60
Q

Cognitive enhancers: Agents that prolong transmitter effect in the synapse

A

Cholinesterase inhibitors (Tacrine)

61
Q

Cognitive enhancers: agents acting as agonists or positive allosteric modulators

3 listed

A
  • AMPAkines
  • Glycine modulators of the NMDA receptor
  • Group I mGlu agonists
62
Q

Cognitive enhancers: agents that enhance transmitter release from nerve terminals (ACh/Glutamate)

A
  • Subtype-selective nNCR agonists
  • 5HT4 / 5HT6 / H3 receptor antagonists or inverse agonists
63
Q

Cognitive enhancers overview

64
Q

Dopamine pathways in the brain

4 listed

65
Q

Neurologic side effects of D2 receptor antagonists

A

More frequently observed with haloperidol-like agents

66
Q

Basis Neurologic side effects of D2 receptor antagonists?

A

↓ DA/ACh balance in the basal ganglia

67
Q

Neurologic side effects of D2 receptor antagonists acute symptom management

A

Acute symptoms can be managed with MCR antagonists or switching to atypicals

68
Q

Endocrinologic side effects of D2 receptor antagonists

A

more frequent with haloperidol-like drugs

69
Q

Endocrinologic side effects of D2 receptor antagonists: Side effects lessened with?

A

Switch to atypical antipsychotics

70
Q

Basis of atypicals on Endocrinologic side effects of D2 receptor antagonists

A

lesser impact on hypothalamic DA/5HT regulatory balance influencing pituitary hormone secretion

71
Q

Antipsychotic side effects related to antagonism of other receptors: Organ systems

3 listed

A
  • CNS
  • ANS
  • Metabolic
72
Q

Antipsychotic side effects related to antagonism of other receptors: CNS receptors

A
  • MCR
  • α1
  • H1
73
Q

Antipsychotic side effects related to antagonism of other receptors: CNS symptoms

A
  • Sedation
  • Cognitive impairments
  • ↓ seizure threshold (Clozapine, 2-5%)
  • ↑ appetite - weight gain
74
Q

Antipsychotic side effects related to antagonism of other receptors: ANS receptors

75
Q

Antipsychotic side effects related to antagonism of other receptors: ANS symptoms

4 system effects listed

A
  • hypotension, tachycardia
  • Dry mouth, constipation
  • Urinary retention, nasal stuffiness
  • Sexual dysfunction
76
Q

Antipsychotic side effects related to antagonism of other receptors: Metabolic receptors

77
Q

Antipsychotic side effects related to antagonism of other receptors: Metabolic symptoms

A
  • Hyperlipidemia
  • Impaired glucose tolerance → Diabetes
  • Metabolic syndrome: ↑ risk of CAD, hypertension, stroke
78
Q

Typicals and atypicals structures

79
Q

Serious complications of antipsychotic treatments

4 listed

A
  • Tardive Dyskinesia
  • Neuroleptic Malignant Syndrome
  • Severe Agranulocytosis
  • Seizures - (Clozapine most notable; lower incidence with chlorpromazine-like agents)
80
Q

Tardive Dyskinesia Description

A

“Late-occurring” stereotypic oral-facial movements

81
Q

Tardive Dyskinesia Risk Factors

A
  • Age
  • gender
  • Renal/CV disease
  • length of treatment (3% per year on haloperidol)
  • D2 receptor antagonist >> MCR antagonist profile
82
Q

Tardive Dyskinesia Treatment options

A

reduce dosage OR switch to other atypical antipsychotics (clozapine)

83
Q

Neuroleptic Malignant Syndrome description

5 listed

A
  • Severe muscle ridgidity
  • ANS-CV instability
  • Sweating
  • Hyperrexia
  • Myoglobinuria
84
Q

Neuroleptic Malignant Syndrome Treatment options

3 listed

A
  • Muscle relaxants
  • D2 receptor agonists (bromocriptine)
  • Switch to atypical antipsychotics
85
Q

Severe Agranulocytosis common causative agent

86
Q

Severe Agranulocytosis prevalence

A

occurs in 1% to 2% of patients

87
Q

Severe Agranulocytosis monitoring

A

requires weekly blood counts first 6 months/every 3rd week thereafter

88
Q

Seizures antipsychpotics common causative agents)

A

Clozapine; to a lesser degree chlorpromazine-like agents)

89
Q

Seizures prevalence antipsychpotics

A

2% to 5% of patients

90
Q

Treatment considerations I

7 listed

91
Q

Patterns of psychotic episodes

92
Q

Impact of multiple schizophrenic relapses

93
Q

Treatment considerations II

6 listed

94
Q

Treatment considerations III

3 listed

95
Q

Other uses of antipsychotic agents

3 listed

96
Q

Antipsychotic antiemetic

A

DA receptor blockade in the chemoreceptor trigger zone (CTZ)

97
Q

Antipsychotic Neuroleptic analgesia

A
  • combination of a haloperidol-like agent and a fast-acting opioid analgesic (such as fentanyl)
98
Q

Question

99
Q

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100
Q

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101
Q

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102
Q

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