antipsychotics/schizo

• Anti-psychotic agents


  A chemically diverse group of compounds used for a diverse spectrum of psychotic disorders
• Psychotic disorders treated by anti-psychotic agents

  • Schizophrenia
  • Delusional disorders
  • Bipolar disorder
  • Depressive psychosis
  • Drug induced psychosis
• Other uses of anti-psychotic agents

  • Suppress emesis
  • Treat Tourette syndrome
  • Treat Huntington chorea
• Anti-psychotics should not be used to treat dementia-related psychosis in older adults due to risk for increased mortality
• Groups of anti-psychotic agents

  • First generation (FGAs)
  • Second generation (SGAs)
• First generation anti-psychotics (FGAs)


  Also known as conventional anti-psychotics, produce a strong blockade of receptors for dopamine in the central nervous system, can cause serious movement disorders known as extra pyramidal symptoms (EPS)
• Second generation anti-psychotics (SGAs)

  Produce only moderate blockade of dopamine receptors and a stronger blockade of serotonin receptors, less risk for EPSs than FGAs
• Schizophrenia


  A chronic psychotic illness characterized by disordered thinking and reduced ability to comprehend reality
• Symptoms of schizophrenia


  • Positive symptoms (exaggeration or distortion of normal function)
  • Negative symptoms (loss or diminution of normal function)
  • Cognitive symptoms (disordered thinking, reduced ability to focus attention, prominent learning and memory difficulties)
• Positive symptoms of schizophrenia


  • Hallucinations
  • Delusions
  • Agitation
  • Tension
  • Paranoia
• Negative symptoms of schizophrenia

  • Lack of motivation
  • Poverty of speech
  • Blunted affect
  • Poor self-care
  • Social withdrawal
• Positive, negative, and cognitive symptoms of schizophrenia respond equally to FGAs and SGAs
• Delusions


  Fixed false beliefs
• Hallucinations


  Auditory hallucinations may consist of voices arguing or commenting on one's behavior
• Disordered thinking and loose association may render rational conversation impossible during an acute schizophrenic episode
• After florid symptoms of an acute episode, less vivid symptoms may remain including suspiciousness, poor anxiety management, and diminished judgement, insight, motivation, and capacity for self-care
• Patients with schizophrenia have difficulty with relationships, employment and functioning independently in society
• Long-term course of schizophrenia

  Episodic acute exacerbations separated by intervals of partial remission
• Possible primary defects in schizophrenia

  • Excessive activation of CNS receptors for dopamine
  • Insufficient activation of CNS receptors for glutamate
• First-generation anti-psychotics (FGAs)


  Also known as neuroleptics, cause extrapyramidal symptoms (EPSs) as a major concern

  classified by potency or chemical structure

  classified as high, medium, or low potency
• Chemical categories of FGAs

  • Phenothiazines
  • Thioxanthene
  • Butyrophenone
  • Dibenzoxazepine
• FGAs block a variety of receptors within and outside the central nervous system including receptors for dopamine, acetylcholine, histamine, and norepinephrine</b>
• The blockade of these receptors is responsible for the major adverse effects of FGAs
• Dominant theory for therapeutic effects of FGAs

  They suppress symptoms of psychosis by blocking dopamine 2 receptors in the mesolimbic area of the brain
• FGAs do not alter the underlying pathology of schizophrenia
• Adverse effects of FGAs

  • Extrapyramidal symptoms (EPSs) especially tardive dyskinesia
  • Acute dystonia - severe spasms of face, tongue, neck, or back
  • Oculogyric crisis
  • joint dislocation from muscle spasms
  • Laryngeal dystonia - impair respiration
• Neonates exposed to antipsychotic drugs during the 3rd trimester of pregnancy may experience EPSs and signs of withdrawal
• Development of physical and psychological dependence on antipsychotic drugs is rare
• Drugs that can interact with antipsychotics

  • Drugs with anticholinergic properties - intensify FGA anticholinergic effects
  • Antihistamines and OTC sleep meds - avoid due to CNS depression
  • Alcohol
  • Benzodiazepines
  • Barbiturates
  • Levodopa - counteract antipsychotic effects
• Overdose of FGAs produces hypotension, CNS depression, and EPS
• All FGAs are equally effective in alleviating symptoms of schizophrenia, differences relate primarily to side effects
• High potency FGAs


  Cause more early EPSs but less sedation, orthostatic hypotension, and anticholinergic effects compared to low potency FGAs
• Haloperidol


  A member of the butyrophenone family, prototype drug for FGAs, principal indications are schizophrenia and acute psychosis
• Levodopa may counteract


  The antipsychotic effects of these drugs
• FGAs


  • Very safe
  • Overdose is extremely rare
• Treatment for FGA overdose

  1. Antiparkinsonism drugs for EPSs

  2. Fluids and alpha adrenergic agonists for hypotension

  3. Gastric lavage to remove any excess drug
• Emetics are not effective because neuroleptics block the antiemetic action
• All of the FGAs are equally effective in alleviating symptoms of schizophrenia
• Differences between FGAs


  • Relate primarily to side effects
  • High potency agents produce fewer side effects than the low potency agents
• Compared with low-potency FGAs, the high potency FGAs cause more early EPSs but cause less sedation, orthostatic hypotension, and anticholinergic effects