Schizophrenia and neuroleptics

Question 1

Psychosis

Answer 1

Affective disorders (mood disorders)
Organic psychosis is caused by trauma, alcoholism.
Schizophrenia has positive and negative symptoms.

Question 2

Schizophrenia

Answer 2

Affects about 1% of the population
Often begins in adolescence/young adults
Relapses and remission or chronic and progressive
Genetic and environmental factors
Possibly a neurodevelopmental disorder caused by maternal viral infection.

Question 3

Positive symptoms

Answer 3

Delusions
Hallucinations- both auditory and visual
Thought disorder
Neuroleptic drugs are effective here

Question 4

Negative symptoms

Answer 4

Withdrawal from society
Flattening of emotional responses
Dementia
Neuroleptic drugs less effective here.

Question 5

Anti-schizophrenic drugs

Answer 5

Antipsychotic drugs
Neuroleptic drugs
Major tranquilizers

Question 6

Dopamine hypothesis

Answer 6

All anti-psychotic drugs are dopamine antagonists.
Chronic amphetamine use can lead to psychosis (increased DA in the brain)
Chronic L-dopa can also lead to psychosis.
There is overactivity of DA neurones to the limbic region and prefrontal cortex.
In the schizophrenic brain post-mortem there is increased dopamine receptor number and increased dopamine concentration in the l.amygdala.
D4 receptors are increased 6-fold but D4 antagonists are ineffective.
Is increased D receptor number due to schizophrenia or treatment?

Question 7

5-HT hypothesis

Answer 7

LSD is a 5-HT analogue, it causes hallucinations and delusions.
Dimethyltryptamine (5-HT metabolite) causes hallucinations and occurs in the urine of patients with schizophrenia.
Some newer antipsychotics are 5-HT2a antagonists.

Question 8

Classes of anti-psychotics

Answer 8

1. Typical (“classical”) antipsychotics - chlorpromazine,haloperidol,thioridazine.
2. Atypical antipsychotics - clozapine, risperidone, sulpiridine,olanzapine.

Question 9

Typical neuroleptics (pre-1980)

Answer 9

Prromethazine (not Neuroleptic) given to reduce stress during surgery, marked calming effect.
Chlorpromazine is good at controlling positive schizophrenic symptoms.
All have similar properties.
Extra pyramidal side effects (EPS).
Little action on negative symptoms.
Phenothiazines also block histamine, catecholamine, ACh and 5-HT receptors causing further side effects.

Question 10

Extrapyramidal side effects

Answer 10

From D2 receptor block -
Acute dystonias - involuntary movements, decline over time, reversible when drug therapy is stopped. Consistent with block of the nigrostriatal pathway.
Tardive dyskinesia - involuntary movements of the face, tongue, trunk and limbs. Can last for months or years, resistant to drug therapy, worsens when drug therapy is stopped initially, often irreversible.

Question 11

Other side effects

Answer 11

H1 block - sedation, anti-emetic
Muscarinic block - blurred vision, dry mouth/eyes, urinary retention, constipation.
Alpha-adrenoceptor block - hypotension
Also jaundice, leukopenia, agranulocytosis.

Question 12

Atypical neuroleptics

Answer 12

Newer compounds, more varied effects.
Effective in treatment-resistant patients and negative symptoms.
More selective for mesolimbic/mesocortical pathway.
Clozapine lacks EPS, only affects ventral tegmental neurones (D4>D2)
Weight gain a major problem due to 5HT block.
Leukopenia/agranulocytosis May be fatal.

Question 13

Dopamine system stabilisers (DSS)

Answer 13

Partial agonists at DA receptors, very little side effects (aripiprazole) facilitates low level of receptor activation while blocking higher levels. Possible drugs from the future.
Glutamate receptor agonists also possibility for future.

Question 14

Disc-1 gene

Answer 14

Increased chance of developing schizophrenia.

Acts as regulator for PDE4BETA gene

Question 15

PDE4beta gene

Answer 15

Damage to this increases chance of developing mental illness, role in brain in Thinking and memory building.