3.1 Psychosis: Basic Sciences Flashcards Preview

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Flashcards in 3.1 Psychosis: Basic Sciences Deck (18)
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1
Q

What brain morphology is associated with poorer outcomes in schizophrenia?

A
  • Reduced frontal lobe volume and frontal lobe grey matter
  • Enlarged lateral ventricle volume
  • Reduced temporal cortex volume- superior temporal gyrus
  • Reduced temporal cortex and median temporal lobe volumes
2
Q

What is the dopamine hypothesis of schizophrenia?

A
  • Dopamine releasing drugs (amphetamines) or D2 receptor agonists produce psychotic state
  • dopamine receptor antagonists treat symptoms of schizophrenia
  • schizophrenia due to overactivity of dopamine pathways
3
Q

What do the dopamine receptor subtypes do in the brain?

A

D1/F5: stimulate cAMP

D2/3/4: inhibit adenylyl cyclase, inhibit voltage activated Ca2+ channels and open K+ channels (makes cell more -)

4
Q

What is the distribution of D1 receptors? D2 receptors?

A

D1: neostriatum, cerebral cortex, olfactory tubercle, nucleus accumbens
D2: neostriatum, olfactory tubercle, nucleus accumbens

5
Q

What is an agonist and antagonist of dopamine D2 receptor?

A

Agonist: bromocriptine (can tx parkinsons, pit tumour, hyperprolactinemia)
Antagonist: raclopride, haloperidol

6
Q

What receptor does clozapine block?

A

Clozapine is a D4 antagonist

7
Q

What is the reformulated Dopamine hypothesis?

A

Psychosis: due to subcortical dopamine hyperactivity
Negative/cognitive symptoms: due to mesocortical dopamine hypoactivity.

Failure to activate ventral striatum during rewarding cues associated with stronger negative symptoms

8
Q

What is the glutamatergic hypothesis of schizophrenia?

A

Due to altered NMDA receptor subunit expression

Evidence: ketamine can cause psychotic symptoms

9
Q

What is the Serotonergic hypothesis of schizophrenia?

A

Due to abnormal serotonin NA binding potential in frontal cortex
Evidence: this binding potential is smaller in pts with schizophrenia

10
Q

What genes are implicated in schizophrenia brain pathology?

A

neuregulin- role in growth and development of organs
dysbindin- essential for neural plasticity
DISC-1- neurite outgrowth and cortical development role

11
Q

Name some typical antipsychotics, and the definition

A

drugs without atypical properties

  • chlorpormazine
  • thioridazine
  • fluphenazine
  • haloperidol
  • zuclopentixol
12
Q

What is the definition of atypical antipsychotic? What are some examples?

A
  1. Less likely to cause extrapyramidal side effects
  2. High 5HT-2A to D2 blockade ratio
  3. Better efficacy vs. negative symptoms
  4. Effective in pts not responsive to typical drugs
    - olanzapine
    - risperidone
    - quetiapine
    - clozapine
    - aripiprazole
    - amisulpride
13
Q

What do extrapyramidal effects mean?

A

Akathesia
Acute dystonia
Parkinsonism
(Tardive dyskinesia- the presentation of these effects after several months)

Do not occur with clozapine
Less prominent with atypical antipsychotics
-Result from D2 blockade in the nigrostriatal pathways

14
Q

What is the principle SE of 5HT-2 blockade in antipsychotics?

A

Metabolic syndrome
-related to antagonism/inverse agonist activity at 5HT2C receptors

  • weight gain
  • hypertension
  • hyperglycaemia
  • hypercholesterolaemia
15
Q

What is the principle SE of histamine blockade in antipsychotics?

A

Sedation

Increased appetite

16
Q

What is the principle SE of alpha-1 adrenergic blockade in antipsychotics?

A

Postural hypotension
Problems ejaculating
Nasal stuffiness

Due to lack of sympathetic stimulation that should cause increased HR and BP.

17
Q

What are the principle SE of muscarinic blockade in antipsychotics?

A
Dry eyes/mouth
Constipation 
Blurred vision
Increased ocular pressure
Trouble micturating

CNS muscarinic blockade may also cause confusion

18
Q

Which is the best drug for treatment resistant psychosis/schizphrenia? What is it’s major side effect?

A

Clozapine

  • Drowsiness (high H1, M1 and 5HT blocking effect, low S2 effect)
  • agranulocytosis - do FBC q1/52 x 6/12, then q2/52 x 6/12, then q1/12 x duration of therapy + 1/12
  • myocarditis