Schizophrenia + antipsychotic drugs Flashcards
What is schizophrenia?
Chronic mental disorder characterised by a triad of symptoms:
positive
negative
cognitive
What are positive, negative + cognitive symptoms?
Positive: hallucinations, delusion, agitation, disorganised thinking
Negative: introversion, apathy, low self-esteem, personal neglect
Cognitive: poor memory (working/short term memory particularly affected), attention deficit, executive function
How is schizophrenia diagnosed?
At least 2 of the following symptoms: - delusions - hallucinations - disorganised speech (at least one of these is required) - disorganised or catatonic behaviour - negative symptoms Signs of disturbance must be continuous for at least 6 months -> pt must experience at leat 1 month of active symptoms, with social/occupational deterioration prblems
Which genes have been associated with schizophrenia?
BDNF
COMT
DAOA
Neuregulin 1 - involved in synaptic plasticity and myelination** important
Dysbindin: may affect dopamine D2 receptor level sand glutamate + GABA transmission
DISC 1
What structural differences in the brain are seen in someone with schizophrenia?
Larger ventricles + smaller medial temporal lobe
Grey matter loss is widespread
- significant progressive loss of parietal, motor, supplementary motor, and superior frontal cortices
- severe loss in the temporal cortex + superior temporal gyrus
What functional differences in the brain are seen in someone with schizophrenia?
Hypofrontality: fMRI shows reduced frontal lobe activation in schizophrenia during a cognitive task
What is the association between schizophrenia and inflammation?
Prenatal infection increased levels of cytokines during pregnancy increases the risk of schizophrenia in offspring
proinflammatory cytokines are increased in the PFC of SCH pts –> display greater signs of immune cell migration into the brain
Why is oligodendrocyte density reduced in SCH?
may be due to inflammation and immune activation leading to oligodendrocyte damage
How are the mesolimbic and mesocortical pathways affected in SCH?
Hyperactivity in the mesolimbic pathway
Hypoactivity in the mesocortical pathway
Part of the dual dopaminergic imbalance
Give examples of typical antipsychotics.
Chlorpromazine Thioridazine Fluphenazine Haloperidol Flupenthixol
Give examples of atypical antipsychotics.
Risperidone Olanzapine Clozapine Quetiapine Paliperidone Aripiprazole
Which receptors do atypical antipsychotics affect?
They antagonise 5-HT2 receptors
Which receptors does clozapine block?
D4 receptors
Which receptors does aripiprazole act on?
Partial agonist of presynaptic D2 receptors
Antagonist of postsynaptic D2 receptors
What are the adverse effects of antipsychotics?
- Extrapyramidal effects = acute dystonia, parkinsonism, tardive dyskinesia
- Rise in prolactin = weight gain, dyslipidaemia, T2D
- General = allergies + toxic reactions
- Anticholinergic effects (clozapine + haloperidol)
- Postural hypotension
Compare atypical and typical antipsychotics.
Atypical:
- Less EPS
- Less cardiac toxicity (QT segment prolongatin)
- Less hyperprolactinaemia
- Weight gain
- hyperglycaemia, diabetes
- insulin resistance
- dyslipidaemia
- cardiovascular disease
Typical:
- EPS
- Tardive dyskinesias
- weight gain
- Qt segment prolongation
- sudden death
- hyperprolactinaemia
What is neuroleptic malignant syndrome? How is it treated?
Potentially lethal reaction to antipsychotic drugs S+S: - hyperpyrexia - muscle rigidity - tremor - confusion - autonomic instability
Can be treated with:
- Amantadine
- Bromocriptine
- Dantrolene
What is tardive dyskinesia?
IRREVERSIBLE complication of taking antipsychotics
Involuntary movements of the lips, jaw, face, also cause grimacing and constant chewing
*mostly associated with typical antipsychotics which have been taken for >few months/years
How many patients are resistant to drug treatment? Which drug is used in antipsychotic drug resistance? What is the risk with taking this drug?
30% of patients
Clozapine
Can cause agranulocytosis = weaken the immune system
What non-pharmacological methods of treatment are there for SCH?
CBT
Family therapy
**non-pharmacological does not replace pharmacological
What are the risk factors for schizophrenia?
- complication during pregnancy/at birth
- older father
- immune system activation
- excessive use of cannabinoids
