Antipsychotic drugs
Define antipsychotic drugs
o
Antipsychotic drugs, neuroleptic or anti-schizophrenic
drugs are used mainly to manage psychosis (including delusions
or hallucinations and disordered thought) particularly in schizophrenia and bipolar depression.
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__________________________ Define schizophrenia
__________________________ Define schizophrenia
o
Chronic disabling disorder which affects people during
late adolescence or early adulthood.
o
Schizophrenia has a strong genetic component and is
probably due to biochemical abnormality (dysfunction of dopaminergic neurons).
o
There is some evidence for involvement of 5-HT.
o
Patients with schizophrenia have problems with seeing
things, hearing voices, imagining things, having terrifying thoughts (positive symptoms), Apathy, blunted
emotions, anhedonia and reduced ability to react with people 'social
withdrawal' (Negative symptoms).
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The nature of schizophrenia?
o
Psychotic illness
characterized by hallucinations, delusions and thought disorder (positive
symptoms); together
with social withdrawal and flattening of emotional responses (negative
symptoms).
o
Acute episodes (mainly positive symptoms) frequently
recur and develop into chronic schizophrenia, with predominantly negative
symptoms.
o
Incidence is about 1% of population, with a strong,
but not invariable, hereditary component.
o
Pharmacological evidence is generally consistent with
dopamine over activity hypothesis.
o
Increase in dopamine receptors in limbic system
(especially in left hemisphere) is consistently found.
o
There is some evidence for involvement of 5-HT, and
possibly other mediators, such as glutamate.
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Summary of schizophrenic symptoms:
1- Positive Symptoms:
o
Hallucinations.
o
Delusions (bizarre, persecutory).
o
Disorganized Thought.
o
Perception disturbances.
o
Inappropriate emotions.
2- Negative Symptoms:
o
Blunted emotions.
o
Anhedonia.
o
Lack of feeling.
3- Mood Symptoms:
o
Loss of motivation.
o
Social withdrawal.
o
Insight.
o
Demoralization.
o
Suicide.
4- Cognition:
o
New Learning.
o
Memory.
___________________________________________________ Hypothesis of schizophrenia:
1- Dopamine hypothesis:
o
The clinical features of schizophrenia are related to
over activity of dopaminergic function within the brain.
2- Serotonin Hypothesis:
o
Some antipsychotic drugs also act at 5-HT receptors
(antagonists of 5-HT2).
o
5-HT has a modulatory effect on dopaminergic neurons.
3- Glutamate Hypothesis:
o
Preclinical as well as clinical studies provide
evidence of hypofunction of NMDA receptors as a primary, or at least, a
contributory process in the pathophysiology of schizophrenia.
___________________________________________________Classification of antipsychotic drugs:
Antipsychotics are broadly divided into two groups:
1- Typical = 1st generation antipsychotics.
2- Atypical = 2nd generation antipsychotics.
Atypical drugs are preferred as a first line treatment
because:
o
They have fewer side effects.
o They have additional benefits for the –ve symptoms
of schizophrenia.
Mechanism of Action:
o
All antipsychotic drugs block D2 receptors in the
brain & periphery.
o
Atypical antipsychotics exert part of their action
through blocking of 5-HT2A receptors.
o
Antipsychotics take days or weeks to work, suggesting
that secondary effects (e.g. increase in number of D2-receptors in limbic
structure) may be more important than direct effect of D2-receptor block.
o
Many antipsychotics block other receptors e.g.
acetylcholine (M), noradrenaline (α) and histamine (H1) receptors.
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