L20: Schizophrenia And Antipsychotic Drugs Flashcards
What does schizophrenia mean
Divided mind
What are the clinical features of patients with schizophrenia
- Diagnosis in adolescence/ early adulthood
- You can see repeated episodes and then a recovery before another break happens
Or
Chronic with a progressive decline
What can the symptoms of schizophrenia be divided into
Positive (type 1) and negative (type2) symptoms
What are positive symptoms
Presence of abnormal thought and behaviour on top of normal behaviour hence it is positive (extra)
What are the positive symptoms according to DSM 5
- delusions
- auditory hallucinations
- disorganised speech
- grossly disorganised or catatonic behaviour
What are negative symptoms
The absence of behaviour or responses
What are the negative symptoms according to the DSM 5
- Reduced expression of emotion
- social withdrawal
Which symptom makes it harder to notice and diagnose schizophrenia
Negative symptoms
What happens to the risk of schizophrenia when there is a first degree relative with schizophrenia
Increases
What other factors increases the risk of schizophrenia
The environment:
- slow viral infection
- autoimmune process
- poor maternal nutrition
- developmental abnormality
What is the hypothesis called that suggests an explanation to schizophrenia
Dopamine hypothesis
What does the dopamine hypothesis state
That the dopaminergic hyperactivity underlies schizophrenia
What evidence has led to the dopamine hypothesis
Evidence from drugs
What are the 3 drugs that have led to the dopamine hypothesis
- amphetamine
- D2 receptor agonist
- L-dopa
How does amphetamine work
Releases dopamine in the brain
When there is too much amphetamine what does this lead to
Toxic psyhosis:
Paranoid delusions
Visual or auditory hallucinations
Compulsive behaviour
What are the toxic psychosis symptoms called
Type 1 like symptoms in non schizophrenia
What can happen to the positive symptoms if someone with schizophrenia takes amphetamine
Exacerbate positive symptoms
What type of symptoms do D2 receptor agonist increase
Type 1 like symptoms
Overall what does the dopamine hypothesis suggest
Increase in dopamine transmission can exacerbate type 1 symptoms
What was the first drug discovered as an anti-psychotic drug
Chlorpromazine
What symptoms does chlorpromazine reduce
Positive symptoms
What is another effect of chlorpromazine
Sedation i.e decreased irritability
What group of drug is chlorpromazine part of
Typical neuroleptics
What is neuroleptics the same as
Anti-schizophrenic
Anti-psychotic
Major tranquilliser
(All mean the same as neuroleptic)
What are the main 3 classes of typical neuroleptics
Phenothiazine
Butyrophenones
Thiozanthines
Name an example of a phenothiazine
Chlorpromazine
Name an example of butyrophenones
Haloperidol
Name an example of thioxanthines
Flupenthixol
What are typical neuroleptics known as
Dirty drugs
What is the mechanism of action of typical neuroleptics
Receptor antagonists of:
- d1 and d2 for dopamine
- ach mucarinic receptors
- histamine receptors
- noradrenaline alpha receptors
- 5HT receptors
Which symptoms are typical neuroleptics are good at treating
Positive symptoms
What are atypical neuroleptics
Receptor antagonist that are more selective i.e not dirty drugs
Show fewer motor side effects
What are atypical neuroleptics good at treating
Negative symptoms
Treatment resistant schizophrenia i.e when treatment doesn’t work
Which atypical neuroleptic drugs are good at targeting D2 receptors
Sulpiride
Amisulpride
What are the classes of atypical neuroleptics
Selective d2 receptor antagonist
Multi acting receptor targeted agents
Serotonin dopamine antagonist
Novel type
Name example of drugs that are multi acting receptor targeted agents
Clozapine
Alanzapine
Name examples of drugs that are serotonin-dopamine antagonists
Reperidone
Zotepine
Sertindole
Name example of drugs that are novel type
Quetiadipine
Which pathway in the brain results in positive symptoms
Mesolimbic pathway due to hyper function
Which pathway in the brain results in negative symptoms
Mesocortical pathway due to hypo function
What are the 2 main reasons for getting side effects of anti-psychotic drugs
- Blocking dopamine receptors
- Blocking other receptors
What are the 3 broad side effects due to targeting dopamine receptors
1) anti-emetic
2) increased prolactin release
3) extrapyramidal motor symptoms
What do we get an anti-emetic effect
Due to D2 receptor block in the chemoreceptor trigger zone and histamine receptor block
What does anti-emetic mean
Decrease in nausea and vomiting
Why do we get an increased prolactin release
1) In normal circumstances dopamine inhibits prolactin release from the pituitary gland
2) when we block the dopamine receptors (D2) on the pituitary gland this causes the release of prolactin
What does increased prolactin release cause as a side effect
Breast swelling
Pain
Lactation
What are the 2 types of extra-pyramidal motor symptoms that can occur
Acute: dystonias
Chronic: tardive dyskinesia
Why do we get extra-pyramidal motor symptoms
Due to blockade of nigra-striata pathway involved for normal movement
Striatum that has dopamine receptors become blocked in the basal ganglia
What are dystonias
- Involuntary movement of the face, neck and tongue
- Parkinsonian: tremor at rest, muscle rigidity, decreased mobility
What is tardive dyskinesia
Involuntary movement of the face, tongue, limbs and trunk
It is slowly developing with long term use
What are the 3 main broad side effects caused by blocking other receptors with neuroleptic drugs
- anti muscarinic effect: dry mouth, constipation, visual disturbance
- postural hypertension due to alpha adrenoceptor block
- sedation due to histamine receptor block
What is the problem with the dopamine hypothesis
- Neuroleptic drugs takes weeks to be effective which suggests the treatment is giving secondary effects to be effective
- typical drugs are not good for negative symptoms, hypothesis is too simple and there is evidence that under activity of dopaminergic signalling from the mesocortical pathway leads to negative symptoms. Whereas the dopamine hypothesis suggests an over activity of dopaminergic pathway.
