Lecture 17 - Antipsychotics Flashcards
What is dementia praecox?
Cognitive problems associated with aging
What name was given to replace dementia praecox?
Schizophrenia
What are particular disorder a constellation of?
Number of signs and symptoms
What is schizophrenia?
A psychotic disorder characterised by loss of contact with the environment - deterioration in level of functioning in everyday life - disintegration of personality
Schizophrenia
Disorder of feeling, thought, perception and behaviour
What are the positive symptoms?
Any change in behaviour or thoughts (hallucinations or delusions) Hallucination Disorganised speech Disorganised or catatonic behaviour
What are negative symptoms?
Withdrawal or lack of function; emotionless and flat Anhedonia Lack of motivation
What symptoms are more responsive to therapeutic drugs?
Positive symptoms
What symptom is more difficult to treat?
Negative symptoms
What mode is hallucination found in?
Auditory - form of voices being heard in head, thinking their thoughts are being broadcast
What are the characteristics of positive symptoms?
Disorganised speech and behaviour
What behaviour do some individuals display that appear to make them withdrawn from society
Catatonic
What is anhedonia
When an individual doesn’t experience pleasure in anything
What are key symptoms of depression?
Anhedonia and lack of motivation
Why does DSM-V exist?
Attempt to distinguish certain pattern of symptoms to aid treatment options that are available
Why is there an increase in ventricular size after disease develops?
Loss of brain tissue (grey matter)
What does the loss of gray matter anywhere in brain result in?
Increase in ventricular size
What brain regions are associated with grey matter loss?
Cortical areas and Hippocampus
What are developed to understand schizophrenia?
Animal models
What destroys certain neuronal pathways?
Infusion of ibotenic acid
What does the animal model suggest?
There is damage in the form of a lesion to the hippocampus soon after birth
Following hippocampal lesions what are some deficits observed?
Deficit in social interaction Aggressive behaviour Deficits in grooming
Going from puberty to young adulthood what developmental plaice like symptoms are observed?
Locomotor hypersensitivity to amphetamine Hyperresponsiveness to stress Enhanced sensitivity to NMDA antagonist Deficit in sensorimotor gating and ppi
In the model what are some cognitive like symptoms observed?
Deficit in working memory Deficit in spatial learning and memory Deficit is in place learning
What did Carlson and Lindqvist hypothesise?
Dopaminergic transmission is altered in schizophrenia ‘the original dopamine hypothesis’
What is the original dopamine hypothesis ?
There is an increase in dopamine within CNS in the brain that gives signs and symptoms that are related to schizophrenia
What drug was initially developed to be used for anaesthesia
Largactil - now known as chlorpromazine
What effect did chlorpromazine produce in schizophrenic individuals?
Calming effects and allow schizophrenic to live a normal life
What is chlorpromazine in terms of receptor ?
Dopamine receptor antagonist
Chlorpromazine is an example of what type of drug?
Phenothiazine
What is the structure of chlorpromazine ?
3 rings with 2 functional groups
What is schizophrenia due to?
Overactivity if dopamine at D2 receptors
How many dopaminergic pathways are there in the brain!
3
A9 substantial nigra pathway
Project from substantial nigra into striatum (caudate, putamen and Globus Pallidus) Coordination of movement
A10 ventral tegmental area pathway
Mesoaccumbens pathways Tied to more basic functions I.e experience of pleasure (pleasure centre activator) Associated with pleasurable effects associated with drug abuse
A10 ventral tegmental area
Mesocortical pathway Tied up with more cortical and cognitive functions
In all three pathways what is there an increase of ?
Dopamine
What is dopaminergic hypofunction?
Drop in levels of dopamine
What did Davis propose
Damage to to the dopaminergic pathway that projects to the cortex (mesocortical pathway) hence reduction in dopamine
What does reduced inhibitory effect cause?
Increase develops of dopamine
Where is there an increase in dopamine?
Mesolimbic pathway
Where is there a decrease in dopamine?
Mesocortical pathway
What are negative symptoms associated with?
Hypofrontality (reduced dopamine in the frontal cortex)
What are positive symptoms due to?
Overactivity in the mesolimbic system
If the A9 pathway is blocked what symptoms are mimicked?
Parkinson’s disease
What does the antagonist action at 5HT2A receptors do?
Directly or indirectly increase cortical dopamine
What is the pre pulse inhibition of startle ?
Expose experimental animal/ human to startling noise they will hum and have some sort of response
What does accelerometer measure?
Changes in force
What does amphetamine have an effect upon?
Dopaminergic system
What effect does ketamine have?
Glutamatergic systems
Where is the neurochemical lesion located?
Neonatal ventricular hippocampal region
