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Antipsychotics Flashcards

1
Q

When were antipychotics introduced?

A

1950s

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2
Q

Antipsychotics do not only treat the symptoms but also the cause
True or false?

A

False

Treat only the symptoms

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3
Q

Name the two major classes of antipsychotics

A

Dopamine receptor antagonists (typical)

Serotonin-dopamine antagonists (atypical)

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4
Q

How do dopamine antipsychotics work?

A

Blocks the D2 receptor -> improves positive symptoms

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5
Q

Which dopamine pathways are most important for therapeutic effects?

A

Mesolimbic

Mesocortical

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6
Q

Which transmitters are involved in dopamine antipsychotics?

A

5HT
NE
GABA
Glutamate

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7
Q

How is the mesolimbic pathway related to psychosis?

A

Dopamine agonist hyperactivity -> psychotic symptoms

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8
Q

How is the mesocortical pathway related to psychosis?

A

Dopamine agonist deficit -> negative and cognitive psychotic symptms

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9
Q

Give causes of decreased dopamine agonists in the mesocortical pathway

A

Excito-toxicity of glutamate system
Secondary to inhibition by excess serotonin
D2 block by antipsychotics

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10
Q

Which degenerative process could explain the worsening of negative psychotic symptoms over time?

A

Deficit of dopamine agonists in the mesocortical pathway

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11
Q

Which nervous system is the nigrostriatal pathway part of?

A

Extrapyramidal nervous system

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12
Q

What is the function of the nigrostriatal pathway?

A

Controls motor movements

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13
Q

What is the effect of a dopamine agonist deficit in the nigrostriatal pathway?

A

Movement disorders

Extrapyramidal side effects (EPSE)

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14
Q

What is the function of the tuberoinfinidbular pathway?

A

Controls prolactin secretion

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15
Q

What is the effect of dopamine antagonists on the tuberoinfindibular pathway?

A

Inhibits prolactin

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16
Q

What are indications for antipsychotics?

A 
Psychotic disorders
Dementia 
MDD augmentation
OCD augmentation
Tic disorders
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17
Q

What element of dementia do antipsychotics assist with?

A

Behavioural symptoms

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18
Q

Discuss the acute management of psychosis

A

Lorazepam 2-4mg imi w/
IM
- Haloperidol 5 – 10mg/2-4h (max 40mg/d)
• Olanzapine (not with BZ) 10mg 2-4h (max 30mg/d)
• Ziprasidone 10 – 20mg/4h (max40mg/d)
• Zuclopenthixol-acetate 50 – 100mg/ 72h (max
400mg over 2 weeks)

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19
Q

Give another name for typical antipsychotics

A

1st generation antipsychotics

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20
Q

Give another name for atypical antipsychotics

A

2nd generation antipsychotics

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21
Q

Antagonism of which receptors is performed by 1st generation antipsychotics?

A

D2
M1
H1
Alpha-1

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22
Q

Antagonism of which receptors is performed by 2nd generation antipsychotics?

A 
5HT2A
M1
H1
2HT2c
Alpha-1
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23
Q

Agonism of which receptor is performed by 2nd generation antipsychotics?

A

5HT1A

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24
Q

Give common examples of 1st generation antipsychotics

A

Haloperidol

Chlorpromazine

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25
Q

Give common examples of 2nd generation antipsychotics

A

Clozapine
Risperidone
Olanzapine

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26
Q

Name the drug classes of 1st generation antipsychotics

A 
Butyrophenone
Phenothiazines
Diphenylbutylpiperidine
Benzamide
Thioxanthines
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27
Q

Give examples of butyophenone

A

Haloperidol

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28
Q

Give examples of phenothiazines

A

Chlorpromazine
Trifluperazine
Fluphenazine

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29
Q

Give examples of diphenylbutylpiperidine

A

Pimozide

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30
Q

Give examples of benzamide

A

Sulpiride

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31
Q

Give examples of thioxanthenes

A

Flupenthixol

Zuclopenthixol

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32
Q

What are the differences and similarities between 1st generation antipsychotics

A

Differ in molecular structure
Differ in potency
Differ in side effect profiles
Equal positive symptom efficacy

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33
Q

What is the dosage range for chlorpromazine?

A

200-800mg

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34
Q

What is the dosage range for haloperidol?

A

0.5-15mg

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35
Q

What is the dosage range for trifluoperazine?

A

2-15mg

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36
Q

What is the dosage range for pimozide?

A

1-12mg

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37
Q

When is the peak oral concentration of 1st generation antipsychotics?

A

1-4hrs

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38
Q

When is the peak parenteral concentration of 1st generation antipsychotics?

A

30-60min

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39
Q

How quickly does the antipsychotic effect take place with 1st generation antipsychotics?

A

D2 receptor block = immediate

But effects takes weeks

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40
Q

What are the side effects of high potency 1st generation antipsychotics?

A

Increased EPSE
Decreased anti-Ach
Decreased anti-epileptic

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41
Q

What are the side effects of the D2 receptor block dueto 1st generation antipsychotics?

A 
Antipsychotic effect
Worse negative symptoms
Movement disorders
ESPE
Hyperprolactinaemia
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42
Q

What are the side effects of the muscarinic cholinergic block due to 1st generation antipsychotics

A

Mitigates D2 block effects -> less ESPE

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43
Q

Name 2nd generation antipsychotics

A 
Clozapine
Risperidone
Olanzapine
Quetiapine
Aripriazole
Ziprasidone
Palperidone
Amisulpiride
Sulpiride
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44
Q

Give the trade name for clozapine

A

Leponex

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45
Q

Give the trade name for risperidone

A

Risperdal

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46
Q

Give the trade name for olanzapine

A

Zyprexa

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47
Q

Give the trade name for quetiapine

A

Seroquel

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48
Q

Give the trade name for ariprizaole

49
Q

Give the trade name for ziprasidone

50
Q

Give the trade name for palperidone

51
Q

Give the trade name for amisulpiride

52
Q

Give the trade name for sulpiride

53
Q

What kind of antagonist is amisulpiride?

A

Selective D2/3 antagonist

54
Q

What is the effect of 5HT1A agonism by 2nd generation antipsychotics?

A

Increased dopamine agonist release in prefrontal cortex -> decreased glutamate release

55
Q

Which 2nd generation antipsychotics commonly cause 5HT1A agonism?

A

Ziprasidone
Quetiapine
Clozapine

56
Q

What is the dosage range for olanzepine?

57
Q

What is the dosage range for clozapine?

58
Q

What is the dosage range for risperidone?

59
Q

What is the dosage range for paliperidone?

60
Q

What is the dosage range for quetiapine?

61
Q

What is the dosage range for amisulpiride?

62
Q

Give indications for 2nd generation antipsychotics`

A 
Severe EPSE
Tardive dyskinesia
1st episode in young person
Better for - symptoms
Treatment-resistance
NMS rechallenge
Unacceptable prolactin levels
Mood symptoms 
Increased suicide risk
Behavioural symptoms in elderly
63
Q

Which 2nd generation antipsychotic is preferred in treatment resistance?

64
Q

What are side effects of 2nd generation antipsychotics?

A

Metabolic disturbances

65
Q

What options are there when patient is experiencing side effects?

A

Reduce dose
Switch medications
Treat side effect

66
Q

Name advantages of 1st generation antipsychotics

A

Effective

Affordable

67
Q

Name disadvantages of 1st generation antipsychotics

A 
EPSE
Tardive dyskinesia
Limited - symptom effectiveness
Neurocognitive symptoms
20% no treatment response
68
Q

Name advantages of 2nd generation antipsychotics

A

Fewer EPSE
Effective with - symptoms
Effective with neurocognitive deficits
Mood problems assoc w/ schizophrenia

69
Q

Name disadvantages of 2nd generation antipsychotics

A

Cardiac conduction abnormalities
Metabolic syndrome
High cost
Limited availability

70
Q

What are metabolic side effects of 2nd generation antipsychotics?

A 
Dyslipidaemias
Hyperglycemia
Insulin resistance
Obesity
Hypertension
Pro-inflammatory state
Pro-thrombotic state
71
Q

Name risk factors for acute dystonia in antipsychotic treatment

A

Young
Males
High potency

72
Q

What abnormal movements are seen in acute dystonia?

A 
Torticollis
Trismus
Tongue protrusion
Dysphagia
Laryngopharyngeal spasm
Oculogyric crisis
73
Q

What is the treatment for acute dystonia in antipsychotic treatment

A

Biperidine 5mg IVI/IMI

74
Q

What is the cause of EPSE in antipsychotic treatment?

A

Dopamine agonist receptor blocked -> increased acetylcholine

75
Q

What is the treatment for parkinsonism in antipsychotic treatment?

A 
Anticholinergics
- orphenadrine 50mg po 1-3x/d
- biperidine 2mg 1-3x/d 
Lower dose
Replace with serotonin dopamine agonist (SDA)
76
Q

What is akathisia?

A

Akathisia is a movement disorder characterized by a feeling of inner restlessness and inability to stay still.

77
Q

What is the treatment for akathisia in antipsychotic treatment?

A 
Propanolol 10-30mg tds
BZDs
Lower dosage
Change to low potency typical
Change to SDA
78
Q

What drug class does propanolol belong to?

A

Beta blocker

79
Q

Tardive dyskinesia due to antipsychotic treatment is reversible/irreversible

A

Irreversible

80
Q

Name risk factors for tardive dyskinesia in antipsychotic treatment

A

Female
Elderly
Increased dosage

81
Q

What is the cause of tardive dyskinesia in antipsychotic treatment?

A

Upregulation of D2 receptors in the nigrostriatal pathway

82
Q

How can you treat tardive dyskinesia in antipsychotic treatment?

A

Reduce dose
Stop anticholinergics
Try clozapine
Try SDA

83
Q

What are the features of neuroleptic malignant syndrome

A

Advanced parkinsonism

Catatonia

84
Q

Which neurotransmitters are blocked in neuroleptic malignant syndrome?

A

GAMA
NE
5HT
Ach

85
Q

Neuroleptic malignant syndrome is potentially lethal

True or false?

86
Q

Name features of neuroleptic malignant syndrome

A 
Diaphoresis
Autonomic instability
Tremor
Dysphagia
Mutism
Incontinence
Leukocytosis
Delirium
Increased CK
87
Q

What is the management of neuroleptic malignant syndrome?

A
  1. Stop all antipsychotics
  2. Admit to medical ward/high care
  3. Exclude other serious conditions
  4. Supportive measures
    - cool pt off
    - hydration
    - monitor vitals
    - NG tube
  5. Diazepam/lorazepam
  6. DVT prophylaxis
  7. Beware renal failure
  8. Dantrolene/bromocriptine
  9. ECT if no response
  10. Rechallenge with low dose atypical + ECT
88
Q

Why should you avoid anticholinergics in neuroleptic malignant syndrome?

A

DVT prophylaxis

89
Q

Name anticholinergic side effects in neuroleptic malignancy syndrome

A 
Dry mouth
Blurred vision -> dry eyes
Constipation
Urinary retention
Cognitive dysfunction
90
Q

What are the anticholinergic side effects in neuroleptic malignancy syndrome due to?

A

Muscarinic antagonism

91
Q

What are the cardiovascular side effects in neuroleptic malignancy syndrome due to?

A

Alpha-1 antagonism

Muscarinic antagonism

92
Q

Name the cardiovascular side effects in neuroleptic malignancy syndrome

A 
Postural hypotension
Tachycardia
ECG changes - prolonged QT interval
Arrythmias
Cardiomyopathy
93
Q

What side effect can clozapine have on the heart?

A

Cardiomyopathy

94
Q

Name the neurological side effects in neuroleptic malignancy syndrome

A

Lowers the seizure threshold

95
Q

What are the neurological side effects in neuroleptic malignancy syndrome due to?

A

D2 antagonism

96
Q

Name the cognitive side effects in neuroleptic malignancy syndrome

A

Sedation
Headaches
Decreased concentration
Depression

97
Q

What are the cognitive side effects in neuroleptic malignancy syndrome due to?

A

Histaminergic antagonism

98
Q

Name the sexual side effects in neuroleptic malignancy syndrome

A

Decreased libido
Anorgasmio
Erectile dysfunction
Ejaculation inhibition

99
Q

What are the sexual side effects in neuroleptic malignancy syndrome due to?

A

D2 antagonism
Alpha-1 antagonism
Muscarinic antagonism

100
Q

Name the endocrine side effects in neuroleptic malignancy syndrome

A 
Sexual dysfunction
Galactorrhoea
Increased weight
SIAHD
Incr/decr glucose
101
Q

What does SIAHD stand for?

A

Syndrome of inappropriate antidiuretic hormone secretion

102
Q

What are the endocrine side effects in neuroleptic malignancy syndrome due to?

A

Increased prolactin

103
Q

Name the hypersensitivity side effects in neuroleptic malignancy syndrome

A

Photosensitivity
Skin reactions
Aganulocytosis

104
Q

Name the ocular side effects in neuroleptic malignancy syndrome

A

Retinitis pigmentosa

105
Q

Name the gastrointestinal side effects in neuroleptic malignancy syndrome

A

Weight gain
Metabolic syndrome
Constipation
Sialorrhoea

106
Q

What are the gastrointestinal side effects in neuroleptic malignancy syndrome due to?

A

5HT2c antagonism

H1 antagonism

107
Q

Name indications for clozapine

A

Treatment resistant schizophrenia
Introlerable EPS
Tardive dyskinesia

108
Q

Why should you monitor WBC when taking clozapine?

A

Aganulocytosis risk

109
Q

What is agranulocytosis?

A

An acute condition involving a severe and dangerous leukopenia, most commonly of neutrophils.

110
Q

What are the dangers of clozapine?

A

Myocarditis
Toxic megacolon
Seizures (high doses)
Metabolic syndrome

111
Q

Name common side effects of clozapine

A

Hypersalivation
Constipation
Weight gain
Sedation

112
Q

Until when should depot preparations not be used in antipsychotic treatment?

A

Until response to oral medication demonstrated

113
Q

Name the depot preparations of antipsychotic treatment

A
  • Flupentixol decanoate 10 - 60mg 2-4 weekly
  • Fluphenazine decanoate 6.25 - 50mg 2-4
    weekly
  • Zuclopenthixol decanoate 100 - 400mg 2-
    4weekly
  • Risperidone 25-50mg 2 weekly
  • Paliperidone
114
Q

What should be taken into consideration when prescribing antipsychotic treatment?

A 
Prominent current symptoms
Comorbid conditions
Past therapeutic response
Adverse effects
Patient choice
Patient expectations
Gradual dose increased
Lowest effective dose
Sufficient time (4-6w)
Prolonged use of prophylactic treatment
115
Q

How can you give antipsychotic medication in a patient who is non-compliant?

A

Long acting depot injections

116
Q

Why is zuclopenthixol-acetate best in the chronic psychosis management?

A

Late action

Long duration

117
Q

Explain oculogyric crisis

A

A dystonic reaction to certain drugs or medical conditions characterized by a prolonged involuntary upward deviation of the eyes.

118
Q

How can temporal lobe epilepsy resemble schizophrenia?

A

Presents with psychotic aggression and hallucinations

Pharmacology (32 decks)

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