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Antipsychotics I

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This PPT is part 1 of 2 lectures given to second year pharmacy students in a pharmacology & toxicology class.

Antipsychotics I

  1. 1. Antipsychotics IBrian J. Piper, Ph.D., M.S. piperbj@husson.edu February 4, 2013
  2. 2. Goals• Pharmacy students should: – be familiar with the symptoms & health consequences of schizophrenia – be able to describe the mechanism(s) of action and adverse effects of first- generation antipsychotics
  3. 3. SchizophreniaThe Greek translation is schizein “split” and phren“mind” which refers to a split from reality. A groupof severe disorders characterized by atypical: 1. Cognition 2. Behavior 3. Emotions NOT Multiple Personality Disorder
  4. 4. Symptoms of SchizophreniaPositive symptoms: the presence of inappropriatebehaviors delusions: thoughts hallucinations: auditory >>> visual > other disorganized talking: “word salad” movementsNegative symptoms: the absence of appropriatebehaviors flat affect: joy, anger, disgust anhedonia catatonia: waxy flexibility
  5. 5. Example PatientDelusions of grandeurinappropriate beliefs aboutone’s self-worth or specialpowersGerald (upto 2:30): http://www.youtube.com/watch?v=gGnl8dqEoPQ
  6. 6. Epidemiology of Schizophrenia Frequency: 0.7% Sex: Males > Females (1.4:1) in # and severity Low SES (downward drift) Rule of thirds Comorbidity with depression & smokingSources: Anna K. Kring
  7. 7. History of Antipsychotics• 1953: an antihistamine agent (cholpromazine) is found to improve psychosis in schizophrenics• 1960-1970: identification of D2 blockade as the key mechanism, development of these first-generation of antipsychotic agents
  8. 8. Dopamine System I• nigrostriatal: substania nigra (soma) to striatum (axons)Stahl, S. (2008). Essential Psychopharmacology, p. 330.
  9. 9. Antipsychotics & Tardive Dyskinesia Chronic blockade of D2 receptors leads This may cause involuntary movements. them to up-regulate. tardive: slow or belated onset dyskinesia: presence of involuntary movements, tongue thrusts, lip smacking, eye blinking Potentially permanent!Example: 4:20 to 5:50: http://www.youtube.com/watch?v=QYYx1mZDpPw
  10. 10. TD = Extrapyramidal Symptoms (Long-Term)Brodal (2010). The central nervous system. p. 83.
  11. 11. Extrapyramidal Symptoms (Short-term) • Pseudo-Parkinsonism: – tremor – rigidity – bradykinesia • dystonia: involuntary muscle spasms – torticollis: abnormal head or neck position • akathisia: severe sensation of restlessness, strong desire to moveExcellent Examples (0:30- 4:50-9:15): http://www.youtube.com/watch?v=WAg2iLEWVh0
  12. 12. Dopamine Inhibits AcetylcholineStahl, S. (2008). Essential Psychopharmacology, p. 338.
  13. 13. D2 Inhibition & Increased AChStahl, S. (2008). Essential Psychopharmacology, p. 339.
  14. 14. Solution: Anti-cholinergicsStahl, S. (2008). Essential Psychopharmacology, p. 339.
  15. 15. Dopamine Inhibits Prolactin Consequences amenorrhea galactorhea ↓ sex interest gynecomastiaStahl, S. (2008). Essential Psychopharmacology, p. 334.
  16. 16. Dopamine & Mood• Dopamine projections to nucleus accumbens• Increasing dopamine increases reward• anti-psychotics block this pathway
  17. 17. Non-Selectivity of FGAStahl, S. (2008). Essential Psychopharmacology, p. 338, 340.
  18. 18. Haloperidol• MOA: D2 antagonist, α1 antagonist• Indications: acute psychosis/schizophrenia• Adverse Effects: extrapyramidal symptoms (EPS), hypotension
  19. 19. Summary: Pros & Cons • FGAs have strong efficacy against + symptoms. • FGAs either do not help – symptoms or exacerbate them. • The primary concern with FGAs is long-term development of tardive dyskinesia although acute EPS impair the quality of life of schizophrenics.Stahl, S. (2008). Essential Psychopharmacology, p. 369.
  20. 20. Terminology• Neuroleptic = major tranquilizer = antipsychotic• First Generation Antipsychotic = Typical = Conventional
  21. 21. Reduced Lifespan (N = 5,036,662) Male Male Female Female Life Expectancy Years Life Years Lost Lost ExpectancyAll (Psychiatric 76.5 NA 80.9 NAHistory - )Schizophrenia 57.8 18.7 64.6 16.3Bipolar 62.9 13.6 68.8 12.1 Contributing Factors suicide, accident, homicides, self-care (diet/smoking), metabolic (?) Laursen (2011). Schizophrenia Research, 131, 101-104.

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