Psychosis Flashcards
Psychosis positive (type 1) symptoms caused by mesolimbic pathway hyperactivity
Delusions
Auditory hallucinations
Thought broadcasting
Psychosis negative (type 2) symptoms caused by mesocortical hypoactivity
Lack of drive
Social withdrawal
Motor disturbance (catatonia)
Schizophrenia causes
Genetic increases susceptibility, not definitive Viral in some cases Developmental disorder (gestational perhaps)
Receptors affected in schizophrenia
D2 like dopamine receptors (D2,3,4)
Schizophrenia working hypothesis
Poor dopamine levels in prefrontal cortex correlated with schizophrenia, as a result mesolithic pathway disinhibited and there’s hyperactivity
Chlorpromazine SE
alpha-1, H1, mACh antagonist
Very sedative
Moderate EPSs and anticholinergic
Typical neuroleptics
Phenothiazines (chlorpromazine, thioridazine or trifluoperazine/fluphenazine as depot administration)
Thioxanthines (e.g. flupenthixol)
Butyrphenones (e.g. haloperidol)
Typical neuroleptics MOA
Antagonise D2 receptors
Thioridazine SE
strong mACh antagonist
moderately sedative
not many EPSs
Fluphenazine/trifluoperazine SE
Not very sedative
Not many mACh effects
Pronounced EPSs
Neuroleptics SE
EPS (parkinsonian like, tardive dyskinesia, involuntary motor restlessness)
Hyperprolactinaemia
Sedation (H1 block)
Autonomic effects (alpha-1 and mACh block)
Aplastic anaemia (chlorpromazine)
Effect of typical neuroleptics on psychosis symptoms
DA antagonists reduce positive symptoms, don’t reduce negative
Clozapine advantages over typicals
Fewer EPS
Positive and negative symptom relief
Less tardive dyskinesia
Higher efficacy despite lower affinity
Atypical neuroleptics
Dibenzapine derivatives (clozapine, olanzapine, quetiapine) Benzisoxazole derivatives (risperidone and its primary active metabolite paliperidone, ziprasidone)
Atypical MOA
Clozapine/risperidone etc antagonise D2 and 5HT2a (causes hallucinations like in LSD which acts on it)
Atypicals SE
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
Aripiprazole MOA
D2 partial agonist, 5HT1A partial agonist (helps depression/anxiety effects) and 5HT2A weak antagonist (hasn’t got 5HT2A SE)
Aripiprazole advantages
Few EPS (no diff from placebo)
Little weight gain/few CV abnormalities
Apparently safe in OD
Aripiprazole disadvantages
Hyperprolactinaemia
Hypercholesterolaemia
Akathisia (restlessness)
First line drugs for psychosis
Atypicals e.g. clozapine
