Transcript Drugs Used to Treat Schizophrenia

Drugs Used to Treat
Schizophrenia
Chapter 17
Positive symptoms of
schizophrenia
Delusions
 Hallucinations
 Bizarre behaviors
 Dissociated or fragmented thoughts
 Incoherence
 illogicality

Negative symptoms of
schizophrenia
Blunted affect
 Impaired emotional responsiveness
 Apathy
 Loss of motivation & interest
 Social withdrawal

Why are these symptoms
important in drug therapy?
Classic agents affect primarily positive
symptoms, while the atypical
antipsychotics relieve both positive and
negative symptoms
Neurotransmitters involved in the
pathogenesis of schizophrenia

Dopamine: antipsychotics work by being
antagonists of dopamine
 Glutamate: a glutamate-NMDA receptor
deficiency may explain negative symptoms &
cognitive dysfunction
 Serotonin: serotoninergic activity may be a
complementary action to dopaminergic
blockade; also may be a serotonin-glutamate
interaction—drug-induced serotonin blockade
functions to limit glutamate release
Are all antipsychotics
neuroleptics?
Neuroleptic means “to take control of the
neuron”.
Traditional antipsychotics were previously
viewed to be inseparable from extrapyramidal
side effects. The neuroleptic dose was
gradually increased to the level that produced
these effects—a neuroleptic state.
Atypical antipsychotics can produce effects at
doses that do not produce motor side effects
and do not produce a neuroleptic state.
Primary clinical differences
between traditional and atypical
antipsychotics
Separation of side effects and
antipsychotic effects
 Traditional block dopamine—effective
for positive symptoms; Atypical block
dopamine plus action on serotonin &
glutamate—effective for negative and
symptoms and cognitive deficits as well

What is a tranquilizer?

Tranquilizers are typically thought of as
agents that induce a peaceful, tranquil, calm,
or pleasant state
 It is important to distinguish between two
types
– Minor: (benzodiazapines) reduce anxiety, produce
calm, pleasant state
– Major: (antipsychotics) psychological effects
produced are seldom pleasant or euphoric;
especially unpleasant & dysphoric with
nonpsychotic persons
Mechanisms of action of
traditional antipsychotics
Block dopamine D2 receptors
Mechanisms of Atypical
Antipsychotics

Clozapine: blocks serotonin 5-HT2 receptors;
weak blocker of dopamine
 Olanzapine: blocks dopamine D2 and
serotonin 5-HT receptors
 Sertindole: effects a variety of dopamine and
serotonin receptors
 Quetiapine & ziprasidone: antagonists at
neurotransmitter receptors including 5-HT1A,
5-HT2, D1, D2, histamine, and adrenergic
Side Effects of Phenothiazines
Altered pigmentation of the skin
 Pigment deposits in the retina
 Permanently impaired vision
 Decreased pituitary function
 Menstrual dysfunction
 Allergic reactions, which include liver
dysfunction and blood disorders

Clozapine

It is the only antipsychotic drug that is
effective in treating treatment-resistant
schizophrenics.
 It is clinically superior to traditional
antipsychotics
 It relieves many of the negative
symptomatology of schizophrenia, and lacks
many of the extrapyramidal side effects of
standard neuroleptics
Chlorpromazine
Chlorpromazine was first used to allay
fears and anxieties in surgery patients
the night before surgery.
 It was found to be remarkably effective
in alleviating the clinical manifestations
of the psychotic process.

Olanzapine

Olanzapine has been shown to be produce
improvements in positive and negative
symptoms of schizophrenia.
 Extrapyramidal side effects are only rarely
observed.
 Results suggest olanzapine may be more
effective and better tolerated than traditional
antipsychotics in less severely impaired
patients.
Atypical Antipsychotic Drugs
Molindone, loxapine, clozapine,
risperidone, pimozide, olanzapine,
sertindole, quetiapine, and ziprazadone
 They are all alternatives to
phenothiazines, and the all are unique
in action.

Amisulpride

This drug has a unique neurochemical
and psychopharmacological profile: it
has high selectivity for blocking
dopamine D2 & D3 receptor subtypes in
the limbic system, but not the basal
ganglia, and it blocks functional
responses mediated by those receptors.
Amisulpride

As a dopamine blocker, one would predict
that it would exert actions similar to those of
the traditional antipsychotics, however,
amisulpride is twice as selective for D3
receptors than for D2 receptors; at low doses
it blocks presynaptic dopamine autoreceptors
while postsynaptic dopamine receptor D2
antagonism becomes apparent at higher
doses.
Amisulpride

This dual action results in increased
dopamine activity in the mesolimbic
system at low doses and an
antipsychotic action at higher doses,
with a low incidence of extrapyramidal
side effects.