Wk 28 - Schizophrenia Flashcards
Define schizophrenia
Psychotic disorder involving disturbance of thought, emotion and behaviour
In which gender is schizophrenia most prevalent?
Males (1.4:1)
When is the usual onset of schizophrenia?
- Late adolescence + early adulthood
- Males: 16-25
- Females: 25-34
Outline the percentages for genetic factors
- Relative: 2.9% inc risk
- 17% concordance dizygotic twins
- 50% concordance monozygotic twins
Give examples of biological environmental factors that inc the risk of developing schizophrenia
- Age >45
- Maternal infection
- Maternal malnutrition
- Pregnancy + birth complications - gestational diabetes, hypoxia, low birth weight, premature birth
- Season of birth
- Cannabis use
Give examples of psychosocial environmental factors that inc the risk of developing schizophrenia
- Urban birth + upbringing
- Migration
- Social disadvantage
- Exposure to negative life events
Outline the dopamine hypothesis
- Schizo results from dysregulation of dopaminergic system in brain
- +ve symptoms = overactivity in mesolimbic dopaminergic pathway
- -ve symptoms = dec activity in mesocortical dopaminergic pathway
Outline the glutamate hypothesis
- 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
Outline the neurodevelopmental model
Schizo results from structural + functional brain abnormality during early utero/pre-adolescence
The main symptoms can be grouped into what 3 major clusters?
- Positive symptoms
- Negative symptoms
- Cognitive impairment
Give examples of positive symptoms
- Hallucinations
- Delusions
- Speech + thought disorder
- Disorganised motor behaviour
Give examples of negative symptoms
- 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
In cognitive impairment, where are disturbances found?
- Memory
- Attention
- Sensory info processing
- Fluency of speech
What is used to diagnose schizophrenia?
Clinical features:
- The international statistical classification of diseases (ICD 10)
- The diagnostic + statistical manual of mental disorders (DSN-IV/DSM-V)
Outline what ONE must be present most of the time during a 1 month period using the ICD 10 criteria?
- Withdrawal
- Delusions of control (body parts, actions or sensations)
- Delusional perception
- Hallucinatory voices (running commentary or discussing patient)
- Persistent bizarre or culturally inappropriate delusions
Outline what TWO must be present most of the time during a 1 month period using the ICD 10 criteria?
- Persistent daily hallucinations w/ delusions
- Incoherent speech
- Catatonic behaviour
- Negative symptoms
What is the criteria for the DSM-V?
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
What are the 2 broad classes of antipsychotics?
- 1st gen (FGA/typical): 1950-70 (chlorpromazine + haloperidol)
- 2nd gen (SGA/atypical): 1980s (clozapine + olanzapine)
What are the classes of 1st generation antipsychotics?
- Phenothiazines
- Butyrophenones
- Thioxanthenes
- Substituted benzamides
Give an example of a phenothiazines
Chlorpromazine
Give an example of a butyrophenone
Haloperidol
Give an examples of a thioxanthenes
Flupentixol
Give an example of a substituted benzamides
Sulpiride
What is the main mechanism of action of antipsychotics?
- Block dopamine D2 receptors in mesolimbic pathway
- Clinical potency correlate w/ D2 receptor affinity
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
What happens when a-adrenoreceptors are blocked?
- Postural hypotension
- Sexual dysfunction
What happens when Histamine H1 receptors are blocked?
- Sedation
- Weight gain
What happens when muscarinic receptors are blocked?
- Dry mouth
- Blurred vision
- Constipation
- Urinary retention
- Memory deficit
Outline the different on target adverse effects
- Acute extrapyramidal side effect
- Tardive dyskinesia
- Hyperprolactinemia + sexual dysfunction
- Neuroleptic malignant syndrome
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)
Outline tardive dyskinesia
- Late onset movement disorder
- Due to prolonged use
- Rhythmic + involuntary movements
- Worsens w/ w/drawal
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
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
What is mesolimbic + how does antipsychotic drugs affect it?
- Emotion + sensation of pleasure
- Hyperactivity = psychosis
- Red +ve symptom
What is mesocortical + how does antipsychotic drugs affect it?
- Cognitive function
- Hypoactivity = -ve + cognitive symptom
- Worsens -ve + cognitive symptoms
What is Nigrostriatal + how does antipsychotic drugs affect it?
- Controls movement
- Extrapyramidal symptoms, akathisia, dystonia + tardive dyskinesia
What is tuberoinfundibular + how does antipsychotic drugs affect it?
- Controls prolactin release
- Hyperprolactinemia + sexual dysfunction
Give examples of second generation antipsychotic drugs
- Clozapine
- Risperidone
- Olanzapine
- Quetiapine
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)
Serotonin dopamine antagonist
- High selectivity for 5HT2a + D2 receptors
- Risperidone + paliperidone
Multi-acting receptor-targeted antipsychotics
- Affinity for 5HT2a + D2 receptors + other systems
- Clozapine, olanzapine, quetiapine
Combined D2/D3 dopamine receptor antagonist
- Block D2 + D3 subtypes of D2 like receptors
- Amisulpride
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
What needs to be taken into account when choosing antipsychotic?
- Metabolic (weight gain)
- Extrapyramidal (dystonia, dyskinesia)
- Cardiovascular (QT prolongation)
- Hormonal (inc prolactin)
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
When should a person w/ psychosis be offered an ECG?
- Specified in summary of product. characteristic
- Identified specific CV risk
- History of CVD
- Inpatient
How is antipsychotic medication started?
Carry out for 4-6 wks
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
Depot or long-acting antipsychotic formulation
- Slow release
- Deep IM injection every 1-4 wks
- Maintain treatment (symptom control + relapse prevention)
Give examples of FGA LAIs
- Haloperidol
- Flupenthixol
- Fluphenazine
- Zuclopenthixol
Give examples of SGA LAIs
- Olanzapine
- Risperidone
- Paliperidone
- Aripiprazole
What are the advantages of LAIs?
- Consistent bioavailability
- Lower dose
- Red adverse effects
- Enhanced med adherence
- Red overdose
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
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
When should clozapine be offered?
Illness not responded adequately to treatment despite sequential use of adequate dose of at least 2 diff. drugs
What are the adverse effects of clozapine?
- Agranulocytosis
- Neutropenia
- Myocarditis: full physical + MHx before initiation
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
When should you stop taking clozapine + refer to haematologist?
Leukocyte below 3x10^9/L or absolute neutrophil count below 1.5x10^9/L
