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Psychiatry > Neurobiology of Psychosis > Flashcards

Neurobiology of Psychosis Flashcards

1
Q

Brain changes in schizophrenia?

A

Reduced frontal lobe volume
Reduced frontal lobe grey matter
Enlarged lateral ventricle volume

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2
Q

Dopamine hypothesis of schizophrenia?

A

Excess D2

THEREFORE dopamine receptor agonists are used to treat symptoms of schizophrenia

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3
Q

Action of D1 receptor family?

A

Stimulates cAMP

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4
Q

Action of D2 receptor family?

A

Inhibits adenylyl cyclase
Inhibits voltage-activated Ca2+ channels
Opens K+ channels

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5
Q

Where are D1 receptors found?

A

Neostriatum; cerebral cortex. olfactory tubercle, nucleus accumbens

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6
Q

Where are D2 receptors found?

A

Neostriatum; olfactory tubercle; nucleus accumbens

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7
Q

Where are D3 receptors found?

A

Nucleus accumbens; island of Calleja

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8
Q

Where are D4 receptors found?

A

Midbrain; amygdala

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9
Q

Where are D5 receptors found?

A

Hippocampus

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10
Q

D2 antagonists?

A

Haloperidol

Atypical antipsychotics

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11
Q

D4 antagonists?

A

Clozapine

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12
Q

Dopamine relationship to psychosis?

A

Subcortical dopamine hyperactivity

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13
Q

Dopamine relationship to negative and cognitive symptoms in schizophrenia?

A

Mesocortical dopamine hypoactivity

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14
Q

What other nTs aparat from dopamine are involved in schizophrenia?

A

Glutamatergic; altered NMDA receptors

5-HT

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15
Q

What genes are dysregulated in schizophrenia?

A

Neuregulin (growth and development of brain)
Dysbindin (neuronal plasticity)
DISC-1 (neurite growth)

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16
Q

Examples of typical antipsychotics?

A

Haloperidol

Chlorpromazine

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17
Q

Action of typical antipsychotics?

A

D2 antagonism - block post synaptic receptor

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18
Q

Are antipsychotics dose dependent?

A

Strong correlation between the average dose required to improve clinical symptoms and D2 receptor binding activity

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19
Q

What are atypical antipsychotics?

A

Less likely to induce EPS
High 5-HT2a to D2 ratio
Better efficacy against negative symptoms

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20
Q

What are the atypical antipsychotics?

A 
Olanzapine
Risperidone
Quetiapine
Clozapine
Aripiprazole
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21
Q

Why do antipsychotics result in parkinsonism?

A

Block D2 receptors in niostriatum

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22
Q

What is acute dystonic reaction?

A

Muscle spasms

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23
Q

How are acute dystonic reactions treated?

A

Prochlorperazine
Procyclidine
ACh antagonists

24
Q

What is akathisia?

A

Internal restlessness; feeling need to constantly move, fidgeting, wriggling or pacin

25
Q

What is tardive dyskinesia?

A

Repetitive involuntary purposeless movements; gramicing, sticking tongue out, lip smacking, pursing lips, blinking

26
Q

Hyperprolactinemia?

A 
Sexual dysfunction 
Galactorrhoea 
Gynaecomastia
Amenorrhoea
Infertility
Lower oestrogen and testerone = osteoporosis
27
Q

What does 5HT-2 blockade via atypical antipsychotics result in?

A

Metabolic syndrome

28
Q

What does antagonism of histamine via atypical antipsychotics result in?

A

Sedation
Increased appetite
Can reduce nausea and vomiting

29
Q

What does the antagonism of alpha-1 adrenergic activity via atypical antipsychotics result in?

A

Hypotension

Interrupts the baroreflex; dizziness, lightheadedness, fainting

30
Q

Consequences of muscarinic blockade?

A 
Blurred vision 
Dry mouth
Constipation 
Urinary retention 
Sedation and confusion
31
Q

Which antipsychotics are daily dosing?

A

Olanzapine

Quetiapine

32
Q

Which antipsychotics will be used in those already with parkinson’s?

A

Clozapine (weekly FBC for 18 weeks then fortnightly)

Quetiapine

33
Q

Which antipsychotics are most likely to cause metabolic syndrome?

A 
OLANZAPINE
CLOZAPINE
Risperidone 
Quetiapine
Aripiprazole
These are ordered from worst to least
34
Q

Which antipsychotics are most likely to cause falls?

A

Those with alpha adrenergic blockage (clozapine, quetiapine, risperidone)
Those with histamine blockade (Quetiapine, clozapine, olanzapine)

35
Q

Which antipsychotics are most likely to cause sedation?

A

Those with histamine blockage; quetiapine, clozapine, olanzapine

36
Q

Which antipsychotic is least likely to cause a recurrence of parkinsonism?

A

Clozapine

Quetipapine

37
Q

What is the side effect caused by haloperidol antagonisms in the pituitary gland?

A

Sexual dysfunction

38
Q

When is clozapine prescribed in schizophrenia?

A

After 2 adequate trials of other antipsychotics

39
Q

Why is clozapine a scary drug to prescribe?

A 
Agranulocytosis 
Myocarditis; non specific ST changes 
Weight gain - up to 20kgs
Hyper salivation - treat with hyoscine 
Cardiomyopathy
Pulmonary embolism
40
Q

Monitoring with clozapine?

A 
Weekly FBC for the first 6 months
Fortnightly for next 6 months
Every 4 weeks thereafter
One month after cessation of clozapine 
ECG
BP
HR
41
Q

What is the pathogenesis behind myocarditis induced by clozapine?

A

IgE reaction; cytokine release of hypercatecholaminaemia

42
Q

What does blockage of the D2 receptors in the mesolimbic system result in?

A

Reduction in positive symptoms such as delusions and hallucinations

43
Q

What does blockage of the D2 receptors in the mesocortical system (already underactive in schizophrenia) result in?

A

Worsening of negative symptoms; diminished energy, restriction in emotional and verbal engagement

44
Q

What does blockage of the D2 receptors in the nigrostriatal system result in?

A

Extrapyramidal symptoms
Tardive dyskinesia
Parkinsonian symptoms; tremor, muscle rigidity, bradykinesia

45
Q

What does blockage of the D2 receptors in the tuberoinfundibular system result in?

A

Increase in blood prolactin levels; amenorrhoea, gynaecomastia, sexual dysfunction

46
Q

Low-potency typical antipsychotic?

A

Chlopromazine

47
Q

High-potency typical antipsychotic?

A

Haloperidol

48
Q

Which atypical antipsychotic has the strongest affinity for D2 receptors?

A

Risperidone; highest potential for EPS and hyperprolactinemia

49
Q

Main receptors acted on by risperidone?

A

5-HT2A

50
Q

Main receptor acted on by olanzapine?

A

5-HT2A

51
Q

Main receptor acted on by aripiprazole?

A

5-HT5A

52
Q

What are the 2 main receptors acted on by quetiapine?

A

H1

Alpha

53
Q

Treatment of acute dystonic reaction?

A

Acetylcholine antagonists

Procyclidine, prochlorperazine, orhphenadrine

54
Q

Areas of the brain involved in the mesolimbic dopamine system?

A 
Ventral tegmental area 
Amygdala
Hippocampus 
Nucleus accumbens
Frontal cortex
55
Q

Antagonism of which receptor can help with the negative symptoms seen in schizophrenia?

A

Serotonin

Psychiatry (35 decks)

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