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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
Q

Give examples of the adverse effects that can occur when blocking D2 receptors in other CNS pathways?

A
  • Basal ganglia: acute extrapyramidal symptom = movement disorder
  • Hypothalamus-pituitary gland - inc prolactin secretion = endocrine effects
26
Q

What happens when a-adrenoreceptors are blocked?

A
  • Postural hypotension

- Sexual dysfunction

27
Q

What happens when Histamine H1 receptors are blocked?

A
  • Sedation

- Weight gain

28
Q

What happens when muscarinic receptors are blocked?

A
  • Dry mouth
  • Blurred vision
  • Constipation
  • Urinary retention
  • Memory deficit
29
Q

Outline the different on target adverse effects

A
  • Acute extrapyramidal side effect
  • Tardive dyskinesia
  • Hyperprolactinemia + sexual dysfunction
  • Neuroleptic malignant syndrome
30
Q

Outline acute extrapyramidal side effects

A
  • 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
Q

Outline tardive dyskinesia

A
  • Late onset movement disorder
  • Due to prolonged use
  • Rhythmic + involuntary movements
  • Worsens w/ w/drawal
32
Q

Outline hyperprolactinemia + sexual dysfunction

A
  • 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
Q

Outline neuroleptic malignant syndrome

A
  • 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
Q

What is mesolimbic + how does antipsychotic drugs affect it?

A
  • Emotion + sensation of pleasure
  • Hyperactivity = psychosis
  • Red +ve symptom
35
Q

What is mesocortical + how does antipsychotic drugs affect it?

A
  • Cognitive function
  • Hypoactivity = -ve + cognitive symptom
  • Worsens -ve + cognitive symptoms
36
Q

What is Nigrostriatal + how does antipsychotic drugs affect it?

A
  • Controls movement

- Extrapyramidal symptoms, akathisia, dystonia + tardive dyskinesia

37
Q

What is tuberoinfundibular + how does antipsychotic drugs affect it?

A
  • Controls prolactin release

- Hyperprolactinemia + sexual dysfunction

38
Q

Give examples of second generation antipsychotic drugs

A
  • Clozapine
  • Risperidone
  • Olanzapine
  • Quetiapine
39
Q

What are the pharmacodynamic classifications of 2nd generation antipsychotics?

A
  • Serotonin dopamine antagonist
  • Multi-acting receptor-targeted antipsychotics
  • Combined D2/D3 dopamine receptor antagonist
  • Partial dopamine receptor antagonist (aripiprazole)
40
Q

Serotonin dopamine antagonist

A
  • High selectivity for 5HT2a + D2 receptors

- Risperidone + paliperidone

41
Q

Multi-acting receptor-targeted antipsychotics

A
  • Affinity for 5HT2a + D2 receptors + other systems

- Clozapine, olanzapine, quetiapine

42
Q

Combined D2/D3 dopamine receptor antagonist

A
  • Block D2 + D3 subtypes of D2 like receptors

- Amisulpride

43
Q

Outline the clinical effects of 2nd gen antipsychotics

A
  • 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
Q

What needs to be taken into account when choosing antipsychotic?

A
  • Metabolic (weight gain)
  • Extrapyramidal (dystonia, dyskinesia)
  • Cardiovascular (QT prolongation)
  • Hormonal (inc prolactin)
45
Q

What needs to be investigated before starting antipsychotic medication?

A
  • 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
Q

When should a person w/ psychosis be offered an ECG?

A
  • Specified in summary of product. characteristic
  • Identified specific CV risk
  • History of CVD
  • Inpatient
47
Q

How is antipsychotic medication started?

A

Carry out for 4-6 wks

48
Q

What should be monitored during treatment?

A
  • 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
Q

Depot or long-acting antipsychotic formulation

A
  • Slow release
  • Deep IM injection every 1-4 wks
  • Maintain treatment (symptom control + relapse prevention)
50
Q

Give examples of FGA LAIs

A
  • Haloperidol
  • Flupenthixol
  • Fluphenazine
  • Zuclopenthixol
51
Q

Give examples of SGA LAIs

A
  • Olanzapine
  • Risperidone
  • Paliperidone
  • Aripiprazole
52
Q

What are the advantages of LAIs?

A
  • Consistent bioavailability
  • Lower dose
  • Red adverse effects
  • Enhanced med adherence
  • Red overdose
53
Q

What are the disadvantages of LAIs?

A
  • Inc risk relapse following dose red
  • Long elimination HL
  • Lack flexibility in dealing w/ emergent s/e
  • Uncomfortable local reaction at injection site
54
Q

What are the important practice guideline points?

A
  • 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
Q

When should clozapine be offered?

A

Illness not responded adequately to treatment despite sequential use of adequate dose of at least 2 diff. drugs

56
Q

What are the adverse effects of clozapine?

A
  • Agranulocytosis
  • Neutropenia
  • Myocarditis: full physical + MHx before initiation
57
Q

What are the monitoring requirements for clozapine?

A
  • 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
Q

When should you stop taking clozapine + refer to haematologist?

A

Leukocyte below 3x10^9/L or absolute neutrophil count below 1.5x10^9/L

PHA333 (35 decks)

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