Antipsychotic Drugs

  • sometimes called neuroleptics or major tranquilizers

    • neurolept means affects the brain

  • are not curative

  • schizophrenia

    • chronic psychosis

    • characteristics

      • delusions

      • hallucinations

    • several different forms

  • 1st generation

    • block dopamine D2 receptors

      • receptors part of the reward system

    • side effects include movement disorders (extrapyramidal symptoms)

    • no one drug is more effective than another

  • 2nd generation

    • lower risk of EPS

    • higher risk of metabolic side effects

      • diabetes

      • hypercholesterolemia

    • act on serotonin and dopamine recepotrs

    • drug selection

      • control with minimal side effects

      • refractory patients

  • MOA

    • block D2 receptors

    • block serotonin receptors

      • most 2nd generation

      • block 5-HT2A

    • chlorpromazine

      • blocks all

  • Actions

    • antipsychotic effects

      • D2 blockade: mesolimbic (reward center)

        • positive effects

          • reduction in hallucinations

          • reduction in delusions

        • negative effects (more prominent in 1st generation)

          • blunted affect

          • apathy

          • impaired attention

          • cognitive impairment

    • extrapyramidal effects

      • dystonias

      • tardive dyskinesia

      • better in 2nd generations

    • antiemetic effects

      • mainly anti-parasympathetic effects

    • alpha-adrenergic receptor blockade

      • hypotension

    • other effects

      • thermoregulation issues

      • increased prolactin

        • general contentment

      • sedation

  • Therapeutic uses

    • schizophrenia

    • prevention of ausea/vomiting

    • other uses

      • tranquilizers

      • motor tics with Tourette’s

      • bipolar disorder

      • adjuncts to antidepressants

  • Kinetics

    • oral administration

    • large Vd

    • metabolized by CYP450

  • Adverse effects

    • significant side effects occur in 80% of patients

      • low TI

      • sometimes permanent

    • extrapyramidal

    • tardive dyskinesia

      • permanent

    • neuroleptic malignant syndrome

    • others

      • may lower seizure threshold

      • may worsen mood

    • urinary retention

    • weight gain

    • seizure

    • sedation

    • extrapyramidal

    • postural hypotension

    • sexual dysfunction

    • arrhythmias and sudden cardiac death

    • dry mouth