Download Schizophrenia - Beauchamp College

Schizophrenia
The Unwell Brain
Disturbance in the
Neurochemistry
 The first discovery in the mid 1950s was that
chronic usage of large daily doses of
Amphetamines could produce a psychosis that
was virtually indistinguishable from schizophrenia.
 The second discovery was that Chlorpromazine
could improve symptoms for schizophrenia.
 The effects of Amphetamines and
Chlorpromazine on the neurochemistry of the
brain were unknown.
Further Discoveries
 It was found that Amphetamine could enhance
neurotransmission of Dopamine, Norepinephrine
and (to a lesser extent) Serotonin Synapses.
 It was also discovered that Chlorpromazine could
prevent Dopamine from activating it’s D2
receptor subtype.
 The knowledge that Chlorpromazine improves
symptoms of schizophrenia while blocking D2
receptors for Dopamine has led to the
development of drugs that have similar
pharmacological properties to chlorpromazine.
Neuroleptics & Atypicals
 The Neuroleptics (older generation) are identified
in two categories: Phenothiazines &
Butyrophenones.
 Chlorpromazine (Thorazine) is the original
phenothiazine anti-schizophrenic drug.
 Haloperidol (Haldol) is the most familiar and
widely used butyrophenone.
 What do these drugs have in common and what
are their effectiveness with treating schizophrenic
symptoms?
Positive symptoms
 The symptoms that are the most responsive to these
types of drugs came to be called the ‘positive
symptoms’ because they showed a positive
response to neuroleptic drug therapy.
 These positive symptoms included: delusions,
hallucinations, disorganised speech and bizarre
behaviour.
 The negative symptoms included: flattened
emotional response, impoverished speech,
diminished initiative and motivation, social
withdrawal, lack of feeling pleasure (anhedonia)
and intellectual impairment.
“Problem Schizophrenics”
 Newer generation antipsychotics (Atypicals) can
be effective in these normally unresponsive
schizophrenics. They also lack some of the
debilitating side effects of the older neuroleptics.
 These newer generation antipsychotics appear
to block multiple subtypes of dopamine
receptors (including D1 D2 D3 D4 D5); they are
also reported to alter serotonin neurotransmission
and to effect several other neurotransmitters,
including, acetylcholine, norepinephrine, and
histamine.
Clozapine (Clozaril)
 Clozapine is effective in some schizophrenics
whose symptoms do not improve on haloperidol.
A patient maintained on clozapine is less likely to
show side effects related to involuntary
movements (tardive dyskinesia). It tends not to
block the receptors for dopamine in the striatum
(could explain it’s lack of motor side effects).
However it has been observed to have sever
negative effects on the immune system
 Haloperidol tends to block D2 receptors in the
caudate and putamen areas of the brain
whereas clozapine blocks D1, D2, D3, D4 and D5
receptors as well as multiple subtypes of
serotonin receptors.