Psychosis

Question 1

Psychosis positive (type 1) symptoms caused by mesolimbic pathway hyperactivity

Answer 1

Delusions
Auditory hallucinations
Thought broadcasting

Question 2

Psychosis negative (type 2) symptoms caused by mesocortical hypoactivity

Answer 2

Lack of drive
Social withdrawal
Motor disturbance (catatonia)

Question 3

Schizophrenia causes

Answer 3

Genetic increases susceptibility, not definitive
Viral in some cases
Developmental disorder (gestational perhaps)

Question 4

Receptors affected in schizophrenia

Answer 4

D2 like dopamine receptors (D2,3,4)

Question 5

Schizophrenia working hypothesis

Answer 5

Poor dopamine levels in prefrontal cortex correlated with schizophrenia, as a result mesolithic pathway disinhibited and there’s hyperactivity

Question 6

Chlorpromazine SE

Answer 6

alpha-1, H1, mACh antagonist
Very sedative
Moderate EPSs and anticholinergic

Question 7

Typical neuroleptics

Answer 7

Phenothiazines (chlorpromazine, thioridazine or trifluoperazine/fluphenazine as depot administration)
Thioxanthines (e.g. flupenthixol)
Butyrphenones (e.g. haloperidol)

Question 8

Typical neuroleptics MOA

Answer 8

Antagonise D2 receptors

Question 9

Thioridazine SE

Answer 9

strong mACh antagonist
moderately sedative
not many EPSs

Question 10

Fluphenazine/trifluoperazine SE

Answer 10

Not very sedative
Not many mACh effects
Pronounced EPSs

Question 11

Neuroleptics SE

Answer 11

EPS (parkinsonian like, tardive dyskinesia, involuntary motor restlessness)
Hyperprolactinaemia
Sedation (H1 block)
Autonomic effects (alpha-1 and mACh block)
Aplastic anaemia (chlorpromazine)

Question 12

Effect of typical neuroleptics on psychosis symptoms

Answer 12

DA antagonists reduce positive symptoms, don’t reduce negative

Question 13

Clozapine advantages over typicals

Answer 13

Fewer EPS
Positive and negative symptom relief
Less tardive dyskinesia
Higher efficacy despite lower affinity

Question 14

Atypical neuroleptics

Answer 14

Dibenzapine derivatives (clozapine, olanzapine, quetiapine)
Benzisoxazole derivatives (risperidone and its primary active metabolite paliperidone, ziprasidone)

Question 15

Atypical MOA

Answer 15

Clozapine/risperidone etc antagonise D2 and 5HT2a (causes hallucinations like in LSD which acts on it)

Question 16

Atypicals SE

Answer 16

Reduced EPS and no mACh effects
Hyperprolactinaemia
Orthostatic hypotension
ECG QT interval prolongation
Metabolic effects (weight gain especially olanzapine, hypercholesterolaemia, type 2 diabetes)
Dribbling
Agranulocytosis (1%)/leukopenia

Question 17

Aripiprazole MOA

Answer 17

D2 partial agonist, 5HT1A partial agonist (helps depression/anxiety effects) and 5HT2A weak antagonist (hasn’t got 5HT2A SE)

Question 18

Aripiprazole advantages

Answer 18

Few EPS (no diff from placebo)
Little weight gain/few CV abnormalities
Apparently safe in OD

Question 19

Aripiprazole disadvantages

Answer 19

Hyperprolactinaemia
Hypercholesterolaemia
Akathisia (restlessness)

Question 20

First line drugs for psychosis

Answer 20

Atypicals e.g. clozapine