Drugs Used to Treat Schizophrenia

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Drugs Used to TreatSchizophrenia

• Chapter 17

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Positive symptoms of schizophrenia

• Delusions
• Hallucinations
• Bizarre behaviors
• Dissociated or fragmented thoughts
• Incoherence
• illogicality

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Negative symptoms of schizophrenia

• Blunted affect
• Impaired emotional responsiveness
• Apathy
• Loss of motivation interest
• Social withdrawal

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Why are these symptoms important in drug therapy?

• Classic agents affect primarily positive
  symptoms, while the atypical antipsychotics
  relieve both positive and negative symptoms

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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
  interactiondrug-induced serotonin blockade
  functions to limit glutamate release

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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
  effectsa neuroleptic state.
• Atypical antipsychotics can produce effects at
  doses that do not produce motor side effects and
  do not produce a neuroleptic state.

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Primary clinical differences between traditional
and atypical antipsychotics

• Separation of side effects and antipsychotic
  effects
• Traditional block dopamineeffective for positive
  symptoms Atypical block dopamine plus action on
  serotonin glutamateeffective for negative and
  symptoms and cognitive deficits as well

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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

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Mechanisms of action of traditional antipsychotics

• Block dopamine D2 receptors

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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

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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

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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

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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.

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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.

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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.

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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.

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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.

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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.