Schizophrenia Flashcards
What is the definition of schizophrenia?
- ‘divided mind’, severe psychiatric disorder, distortion of thoughts and perception, also mood
- loss of touch with reality
When in the most common onset?
during adolescence
What are the two types of presentation of schizophrenia?
- repeated episodes or
progressive chronic decline
What are the Type I and Type II symptoms of schizophrenia?
Type 1 (postive symptoms) = presence of abnormal thoughts or behaviours
- delusions
- hallucinations (auditory)
- disorganised speech
- grossly disorganised or catatonic behaviour
Type 2 (negative symptoms) = absence of normal behaviours
- decreased expression of emotion
- social withdrawal (avolition)
Where can you find the diagnostic criteria for schizophrenia?
DSM 5 = diagnostic and statistical manual of mental disorders
What is the aetiology of schizophrenia?
strong but not invariable hereditary component
- suggests environment has an impact
other suggested factors include:
- slow viral infection
- associated autoimmune process
- poor maternal nutrition
- developmental abnormality (arising from the above)
genetic predisposition with environmental trigger
What is the dopamine hypothesis of schizophrenia?
Where does the evidence for this come from?
- states that dopaminergic hyperactive underlies schizophrenia
- evidence comes from the effect of a number of dopaminergic agents
What drug effects back up the dopamine hypothesis?
Amphetamine is a dopamine releasing drug
- can lead to toxic psychosis manifesting as type 1 like symptoms
- exacerbates the symptoms of schizophrenics
Dopamine receptor D2 receptor agonists e.g apomorphine, bromocriptine)
L-DOPA –> type 1 symptoms in XS
What was the first antipsychotic to be developed?
What drug group is it a part of?
Cholorpromazine:
- originally developed as an antihistamine
- attenuates positive symptoms without excessive sedation
- not depressant - preserves intellectual functions
- put of the typical neuroleptics
What are typical neuroleptics?
Give some examples
What is their mechanism of action?
- receptor antagonists
- phenothiazines e.g. chlorpromazine, fluphenazine
- butyrophenones e.g. haloperidol, droperidol =]
- thioxanthines e.g. flupenthixol, clopenthixol
- -> block a variety of receptor sites: dopamine (D1 and D2 receptor families), ACh (muscarinic), histamine (H1), noradrenaline (alpha), 5-HT
- -> antipsychotic activity through dopamine receptor block
How to atypical neuroleptics differ from typical neuroleptics?
- pharmacological profile - increased domaines receptor selectivity
- fewer extrapyramidal side effects
- more effected against negative symptoms
- treated resistant group efficacy
Give some examples of the different atypical neuroleptics
Selective dopamine receptor antagonists - sulpiride, amisulpride Multi Acting Receptor Targeted Agents (MARTAs) - clozapine, olanzapine Serotonin Dopamine Antagonists - risperidone, zotepine, sertindole Novel type - quetiapine D2 receptor partial agonist - aripiprazole
What are the characteristics of therapy with typical vs atypical antipsychotic drugs?
Typical - control positive symptoms - negative symptoms not so well treated - side effects problematic Atypical - better for negative symptoms - side effect less marked - some efficacy in treatment resistant group
What determines the efficacy of a neuroleptic drug?
- no difference between typical and atypical
- higher D2 receptor binding affinity, lower conc needed, higher efficacy
What are the two main dopamine pathways thought to be involved in schizophrenia and what are their functions?
Mesocortical pathway hypofunction –> responsible for negative symptoms
Mesolimbic pathway, hyper function –> responsible for positive symptoms
What are the dopamine block side effects of neuroleptics?
- antiemetic: chemoreceptor trigger zone, dopamine receptors block in chemoreceptor trigger
- increased prolactin release: pituitary gland, release normally inhibited by dopamine, neuroleptics block inhibition, breast swelling, pain, lactation
What are the short terms and long term motor disturbances of neuroleptics?
Short term
= parkinsonian, tremor at rest, muscle rigidity, decreased mobility
= acute dystonias, involuntary movements (face, tongue,
Long term
= tardive dyskinesia, severely disliking motor disturbance, involuntary movements, of face, limbs, trunk, slow developing, chronic treatment, generally irreversible
What are the non-dopamingeric side effects of neuroleptic drugs?
Drug mouth, constipation, visual disturbances, etc --> antimuscarinic effect Postural hypotension --> alpha adrenoreceptor block Sedation --> H1 receptor block
What are the differences between atypical and typical neuroleptics in terms of side effects?
better side effect profiles, mainly due to greater selectivity
lower incidence of motor disturbances
increased likelihood of compliance
What are the nondopaminergic effects of neuroleptics
- many neuroleptics blocks 5-HT2A with similar affinities as D2
- MARTAs block D2, D4, 5-HT, ACh muscarinic
- more effect for treatment of negative symptoms
- action at many receptors probably accounts for antipsychotic activity
Why do they not just give clozipine to everyone?
serious side effects
agrunolcytosis and myocarditis
What are the problems with the dopamine hypothesis?
- neuroleptics take weeks to work , secondary effects important, adaptive changes
- less effective on negative symptoms, two simplistic
- dysfunction of dopaminergic systems may not be primary cause
