Antipsychotics Flashcards
What are the 5 symptom domains of schizophrenia?
- positive symptoms
- negative symptoms
- anxiety/depression
- aggressive symptoms
- cognitive symptoms
What are some examples of positive symptoms?
Delusions (paranoia)
Hallucinations (voices)
Thought disorder: thoughts controlled by external agency
Abnormal behaviours
*Lack of insight/self-awareness of abnormal behaviour
Which type of symptoms are more disturbing to patients and why?
Negative symptoms: something is missing
withdrawal from social contacts, flattening of emotional responses
When do negative symptoms occur?
Primary deficit of illness
Secondary to: depression, extrapyramidal symptoms, environmental deprivation, positive symptoms
What is cognitive dysfunction?
Impairment of selective attention
Impairment of working memory
Why is cognitive dysfunction a good predictor of treatment outcome?
Predicts level of social and vocational functioning more than positive symptoms
What are the causes of schizophrenia?
- Genetic: partially hereditary, candidate genes (DISC1, neuregulin-1, dysbindin-1, and catechol-O-methyltransferase(COMT))
- > not universal mutations of susceptibility genes - Environment: (during pregnancy) maternal viral infections or complications
- Neurodevelopmental disorder: enlarged ventricles, abnormalities in laminar organization of cortical cells
List the 4 dopamine pathways of the brain
- Nigrostriatal: substantial nigra to dorsal striatum
- Mesocortal: ventral tegmental area to prefrontal cortex
- Mesolimbic: VTA to limbic (emotional) brain
- Tuberoinfundibular: hypothalamus to anterior pituitary
Which dopamine pathways are most relevant to schizophrenia?
Mesocortal: reward & emotion
Mesolimbic: cognition & attention
Which 2 dopamine pathways are off-target for antipsychotics?
Nigrostriatal: voluntary movement/extrapyramidal motor system (EPS symptoms = parkinsonian)
Tuberoinfundibular: regulate prolactin secretion to activate milk production
How do the 3 theories of positive symptoms work?
Produce smx similar to acute schizophrenia: Dopamine agonist (amphetamine) Serotonin agonist (LSD 5-HT2) Glutamate antagonist (PCP, ketamine NMDA antagonist)
What is the main difference between typical and atypical antipsychotics?
Typical: EPS (extrapyramidal side effects in basal ganglia + nigrostriatal pathway) e.g. acute dystonia, tardive dyskinesia & akathisia
Atypical: less EPS
Why do EPS occur?
Acute dystonia: D2 antagonism in nigrostriatal pathway, reversible if drug stopped
Tardive dyskinesia & akathisia: upregulation or supersensitivity of dopamine receptors in nigrostriatal system, usually irreversible
Akathisia: correlates with duration on medication
List 4 typical antipsychotics
Haloperidol
Chlorpromazine
Fluphenazine
Trifluoroperazine
What are the ADRs associated with typical antipsychotics?
Antimuscarinic: dry mouth, constipation, blurred vision
1st gen antihistamine: sedation, weight gain
A-adrenergic receptor block: (vasodilation) postural hypotension, dizziness
Why is haloperidol the only frequently used typical antipsychotic now?
Less EPS
No antimuscarinic and sedative side effects due to single selective mechanism
List 4 atypical antipsychotics
Amisulpride
Aripiprazole
Clozapine/olanzapine
Risperidone
Which receptors do all atypical antipsychotics act on?
Antagonism of 5HT2 & D2 receptors
Why was olanzapine developed?
Clozapine had agranulocytosis (lack of granulocyte WBC) which was rare but could be fatal
-> Needed regular blood count monitoring
Olanzapine is related to clozapine but has no agranulocytosis adverse effect
Which atypical antipsychotics have the typical antipsychotic ADRs?
Clozapine & olanzapine: antimuscarinic & antihistamine (sedation)
Risperidone: (a1-adrenoceptor antagonism) postural hypotension & reflex tachycardia
Amisulpride has an atypical receptor affinity pattern for atypical antipsychotics because ___.
It has no serotonin affinity and no affinity for a-adrenoceptor, muscarinic or histamine antagonism.
It is a selective D2/D3 antagonist
How does amisulpride exert an effect on mammary glands and tissues?
Block dopamine receptors in anterior pituitary gland in tuberoinfundibular pathway -> increase prolactin secretion
Which drug causes gynaecomastia?
Amisulpride
Female: breast swelling, pain, lactation
Male: gynaecomastia
What is the mechanism of action of aripiprazole?
Partial agonist that displaces dopamine -> decrease effect of dopamine (antagonist effect)
