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PHA333 > Wk 28 - Schizophrenia > Flashcards

Wk 28 - Schizophrenia Flashcards

1
Q

Define schizophrenia

A

Psychotic disorder involving disturbance of thought, emotion and behaviour

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2
Q

In which gender is schizophrenia most prevalent?

A

Males (1.4:1)

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3
Q

When is the usual onset of schizophrenia?

A
  • Late adolescence + early adulthood
  • Males: 16-25
  • Females: 25-34
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4
Q

Outline the percentages for genetic factors

A
  • Relative: 2.9% inc risk
  • 17% concordance dizygotic twins
  • 50% concordance monozygotic twins
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5
Q

Give examples of biological environmental factors that inc the risk of developing schizophrenia

A
  • Age >45
  • Maternal infection
  • Maternal malnutrition
  • Pregnancy + birth complications - gestational diabetes, hypoxia, low birth weight, premature birth
  • Season of birth
  • Cannabis use
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6
Q

Give examples of psychosocial environmental factors that inc the risk of developing schizophrenia

A
  • Urban birth + upbringing
  • Migration
  • Social disadvantage
  • Exposure to negative life events
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7
Q

Outline the dopamine hypothesis

A
  • Schizo results from dysregulation of dopaminergic system in brain
  • +ve symptoms = overactivity in mesolimbic dopaminergic pathway
  • -ve symptoms = dec activity in mesocortical dopaminergic pathway
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8
Q

Outline the glutamate hypothesis

A
  • Schizo results from hypofunction of NMDA receptor in brain
  • Dec stim of GABA interneurons = disinhibition + hyperactivity of mesolimbic dopamine pathway (+ve symptom)
  • Dec stim + hypoactivity of mesocortical dopamine pathway = -ve + cognitive symptom
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9
Q

Outline the neurodevelopmental model

A

Schizo results from structural + functional brain abnormality during early utero/pre-adolescence

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10
Q

The main symptoms can be grouped into what 3 major clusters?

A
  • Positive symptoms
  • Negative symptoms
  • Cognitive impairment
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11
Q

Give examples of positive symptoms

A
  • Hallucinations
  • Delusions
  • Speech + thought disorder
  • Disorganised motor behaviour
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12
Q

Give examples of negative symptoms

A
  • Social withdrawal
  • Anhedonia - inability to experience pleasure
  • Flattening of emotional responses
  • Avolition - Loss of motivation + reluctance to perform everyday task
  • Alogia - Impoverished speech + mental creativity
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13
Q

In cognitive impairment, where are disturbances found?

A
  • Memory
  • Attention
  • Sensory info processing
  • Fluency of speech
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14
Q

What is used to diagnose schizophrenia?

A

Clinical features:

  • The international statistical classification of diseases (ICD 10)
  • The diagnostic + statistical manual of mental disorders (DSN-IV/DSM-V)
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15
Q

Outline what ONE must be present most of the time during a 1 month period using the ICD 10 criteria?

A
  • Withdrawal
  • Delusions of control (body parts, actions or sensations)
  • Delusional perception
  • Hallucinatory voices (running commentary or discussing patient)
  • Persistent bizarre or culturally inappropriate delusions
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16
Q

Outline what TWO must be present most of the time during a 1 month period using the ICD 10 criteria?

A
  • Persistent daily hallucinations w/ delusions
  • Incoherent speech
  • Catatonic behaviour
  • Negative symptoms
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17
Q

What is the criteria for the DSM-V?

A

Two or more symptoms each present for sig portion of time during 1 month (at least 1 of first 3 symptoms)

  • Delusions
  • Hallucinations
  • Disorganised speech
  • Catatonic behaviour
  • Negative symptom
  • Social/occupational decline
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18
Q

What are the 2 broad classes of antipsychotics?

A
  • 1st gen (FGA/typical): 1950-70 (chlorpromazine + haloperidol)
  • 2nd gen (SGA/atypical): 1980s (clozapine + olanzapine)
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19
Q

What are the classes of 1st generation antipsychotics?

A
  • Phenothiazines
  • Butyrophenones
  • Thioxanthenes
  • Substituted benzamides
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20
Q

Give an example of a phenothiazines

A

Chlorpromazine

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21
Q

Give an example of a butyrophenone

A

Haloperidol

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22
Q

Give an examples of a thioxanthenes

A

Flupentixol

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23
Q

Give an example of a substituted benzamides

A

Sulpiride

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24
Q

What is the main mechanism of action of antipsychotics?

A
  • Block dopamine D2 receptors in mesolimbic pathway

- Clinical potency correlate w/ D2 receptor affinity

25
Give examples of the adverse effects that can occur when blocking D2 receptors in other CNS pathways?
- Basal ganglia: acute extrapyramidal symptom = movement disorder - Hypothalamus-pituitary gland - inc prolactin secretion = endocrine effects
26
What happens when a-adrenoreceptors are blocked?
- Postural hypotension | - Sexual dysfunction
27
What happens when Histamine H1 receptors are blocked?
- Sedation | - Weight gain
28
What happens when muscarinic receptors are blocked?
- Dry mouth - Blurred vision - Constipation - Urinary retention - Memory deficit
29
Outline the different on target adverse effects
- Acute extrapyramidal side effect - Tardive dyskinesia - Hyperprolactinemia + sexual dysfunction - Neuroleptic malignant syndrome
30
Outline acute extrapyramidal side effects
- D2 blockade in basal ganglia - Early onset - Akathisia: repetitive purposeless actions, pacing (red dose) - Dystonic reactions: abnormal movement of face + bod (procyclidine) - Pseudoparkinsonism: tremor, bradykinesia + rigidity (gradual onset over weeks)
31
Outline tardive dyskinesia
- Late onset movement disorder - Due to prolonged use - Rhythmic + involuntary movements - Worsens w/ w/drawal
32
Outline hyperprolactinemia + sexual dysfunction
- D2 blockade in pituitary gland - Inc prolactin + red gonadotropin release - Male: gynaecomastia, ejaculation failure, dec libido, impotence - Female: Galactorrhoea, anovulation, amenorrhoea, dec libido, infertility
33
Outline neuroleptic malignant syndrome
- Rare but life threatening - 90% occur w/in 10 days - Associated w/ highly potent agents - Catatonia, rigidity, stupor, fever + autonomic instability - Myoglobinuria + death in 10% cases - Due to D2 blockade in corpus striatum + hypothalamus
34
What is mesolimbic + how does antipsychotic drugs affect it?
- Emotion + sensation of pleasure - Hyperactivity = psychosis - Red +ve symptom
35
What is mesocortical + how does antipsychotic drugs affect it?
- Cognitive function - Hypoactivity = -ve + cognitive symptom - Worsens -ve + cognitive symptoms
36
What is Nigrostriatal + how does antipsychotic drugs affect it?
- Controls movement | - Extrapyramidal symptoms, akathisia, dystonia + tardive dyskinesia
37
What is tuberoinfundibular + how does antipsychotic drugs affect it?
- Controls prolactin release | - Hyperprolactinemia + sexual dysfunction
38
Give examples of second generation antipsychotic drugs
- Clozapine - Risperidone - Olanzapine - Quetiapine
39
What are the pharmacodynamic classifications of 2nd generation antipsychotics?
- Serotonin dopamine antagonist - Multi-acting receptor-targeted antipsychotics - Combined D2/D3 dopamine receptor antagonist - Partial dopamine receptor antagonist (aripiprazole)
40
Serotonin dopamine antagonist
- High selectivity for 5HT2a + D2 receptors | - Risperidone + paliperidone
41
Multi-acting receptor-targeted antipsychotics
- Affinity for 5HT2a + D2 receptors + other systems | - Clozapine, olanzapine, quetiapine
42
Combined D2/D3 dopamine receptor antagonist
- Block D2 + D3 subtypes of D2 like receptors | - Amisulpride
43
Outline the clinical effects of 2nd gen antipsychotics
- Block D2 receptors - antipsychotic effect - Low affinity for binding/rapid dissociation from D2 receptor in basal ganglia: milder extrapyramidal symptoms - Better adverse effect profile + patient compliance
44
What needs to be taken into account when choosing antipsychotic?
- Metabolic (weight gain) - Extrapyramidal (dystonia, dyskinesia) - Cardiovascular (QT prolongation) - Hormonal (inc prolactin)
45
What needs to be investigated before starting antipsychotic medication?
- Weight (plotted on a chart) - Waist circumference - Pulse + bp - Fasting blood glucose, HbA1c, lipid + prolactin - Movement disorders • Nutritional status, diet + level of physical activity
46
When should a person w/ psychosis be offered an ECG?
- Specified in summary of product. characteristic - Identified specific CV risk - History of CVD - Inpatient
47
How is antipsychotic medication started?
Carry out for 4-6 wks
48
What should be monitored during treatment?
- Responses to treatment - S/e - Weight: 1st 6 wks, 12 wks, 1 year + annually - Waist: annually - Pulse + BP: 12 wks, 1 year + annually - Fasting blood glucose, lipid: 12wks, 1 yr + annually - Adherence
49
Depot or long-acting antipsychotic formulation
- Slow release - Deep IM injection every 1-4 wks - Maintain treatment (symptom control + relapse prevention)
50
Give examples of FGA LAIs
- Haloperidol - Flupenthixol - Fluphenazine - Zuclopenthixol
51
Give examples of SGA LAIs
- Olanzapine - Risperidone - Paliperidone - Aripiprazole
52
What are the advantages of LAIs?
- Consistent bioavailability - Lower dose - Red adverse effects - Enhanced med adherence - Red overdose
53
What are the disadvantages of LAIs?
- Inc risk relapse following dose red - Long elimination HL - Lack flexibility in dealing w/ emergent s/e - Uncomfortable local reaction at injection site
54
What are the important practice guideline points?
- Avoid high dose except after adequate sequential trial of >2 agents - Avoid combination except short period - When switching, consider gradual cross tapering - Regularly monitor
55
When should clozapine be offered?
Illness not responded adequately to treatment despite sequential use of adequate dose of at least 2 diff. drugs
56
What are the adverse effects of clozapine?
- Agranulocytosis - Neutropenia - Myocarditis: full physical + MHx before initiation
57
What are the monitoring requirements for clozapine?
- Same brand - Report signs of infection - Leukocyte + diff. blood count normal before starting: every wk 18 wks, after year every 4 wks + 4 wks after discontinuation
58
When should you stop taking clozapine + refer to haematologist?
Leukocyte below 3x10^9/L or absolute neutrophil count below 1.5x10^9/L

PHA333 (35 decks)

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