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Antipsychotics Part II

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

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Antipsychotics Part II

  1. 1. Anti-psychotics IIBrian J. Piper, Ph.D., M.S. piperbj@husson.edu February 4, 2013
  2. 2. Goals• Pharmacy students should be able to: – describe the MOA and adverse effects of second generation antipsychotics – evaluate the relative pros and cons (acute and long-term) of first and second generation antipsychotics
  3. 3. DSM5 Diagnosis of Schizophrenia• Two or more of the following, including 1, 2, or 3 1. Delusions 2. Hallucinations 3. Disorganized speech 4. Grossly abnormal psychomotor behavior 5. Negative symptoms• Duration: 1 month during last 6• Social/occupational dysfunction• Exclusion: medical condition or drug
  4. 4. Atypical (Second Generation) • Mechanism of Action – Dissociate more rapidly from the D2 receptorStahl, S. (2008). Essential Psychopharmacology, p. 369-370.
  5. 5. MOA of Atypical Antipsychotics • Dissociate more rapidly from the D2 receptor – ↓ acute EPS, ↓ hyperprolactinemiaStahl, S. (2008). Essential Psychopharmacology, p. 371.
  6. 6. MOA of Atypicals • Atypicals – Dissociate more rapidly from the D2 receptor – Block the 5-HT2A (and so many other!) receptorsStahl, S. (2008). Essential Psychopharmacology, p. 384.
  7. 7. 5-HT2A • Hallucinogens = 5-HT2A agonists • Receptor Distribution: cortex [11C]MDL100,907Meyer et al. (2010). Neuroimage, 50(3), 984-993.
  8. 8. Brain Morphology & Schizophrenia Some schizophrenia patients exhibit morphological changes in the brain like enlargement of fluid-filled ventricles.
  9. 9. Adverse Effect of Atypicals I: Weight Gain
  10. 10. Weight Gain & Olanzapine Weight Gain % of Patients Relative to Baseline (1.6 yrs) > 7% 64% > 15% 32% > 25% 12%Citrome et al. (2011). Journal of Clinical Investigation, 31(7), 455-482.
  11. 11. Risks with long-term Atypicals Mechanism: 5-HT2C Mechanism: X $515 Million
  12. 12. Concern • Adult monkeys received FGA (haloperidol) or * SGA (olanzapine) * antipsychotics for 2 years at doses similar to schizophrenics. • Gray matter in parietal cortex was examined.Konopaske et al. (2007). Neuropsychopharmacology, 32, 1216-1223.
  13. 13. Do antipsychotics cause neurostructural changes? Repeated MRI of schizophrenics Ventricular volume change (slope) by antipsychotic treatment – most (+.39) – intermediate (+.36) – least (+.16)Beng-Choon et al. (2011). Archives of General Psychiatry, 68(2), 128-137.
  14. 14. Do antipsychotics cause neurostructural changes? Repeated MRI of schizophrenics White matter change (slope) by antipsychotic treatment – most (-.64) – intermediate (-.51) – least (+1.30)Beng-Choon et al. (2011). Archives of General Psychiatry, 68(2), 128-137.
  15. 15. Practice Makes Perfect• FGA: http://www.howjsay.com/index.php?word=perphenazine&submit=Submit• SGA: – http://www.howjsay.com/index.php?word=ziprasidone&submit=Submit – http://www.howjsay.com/index.php?word=quetiapine&submit=Submit – http://www.howjsay.com/index.php?word=risperidone&submit=Submit
  16. 16. Clinical Antipsychotic Trials for Intervention Effectiveness) CATIE • 18-month randomized, double-blind trial of FGA & SGAs in real-world (N=1,432) funded by non-industry (NIMH) Perphenazine Olanzapine Risperidone Ziprasidone Quetiapine Discontinuation Rate 75% 64% 74% 79% 82% Weight Change (lbs/month) -0.2 +2.0 +0.4 -0.3 +0.5 Change in Cholesterol +1.5 +9.4 -1.3 -8.2 +6.6 Change in Prolactin = = ↑ = =Lieberman et al. (2005). New England Journal of Medicine, 353(12), 1209-1223.
  17. 17. CATIE Findings • FGAs & SGAs showed similar efficacy with a slight advantage for olanzapine. • Olanzapine showed a higher metabolic risk relative to both FGA and other SGAs.Black Box For All SGAs
  18. 18. Cognitive Behavioral Therapy • Antipsychotics show limited efficacy for negative symptoms & many patients continue to exhibit hallucinations & delusions • Cognitive Behavioral Therapy is a short-term, empirically based psychotherapy developed by Aaron “Tim” Beck (left) that is used with antipsychotics. 1921 -Rector & Beck (2012). J Nervous & Mental Disease, 200(10), 832-839.
  19. 19. Onset Age• Males: early 20s• Females: late 20s
  20. 20. Schizophrenia in Children • More frequently recognized • Example (0 to 3 min): http://www.youtube.com/watch?v=UTU Mt05_nCI:
  21. 21. Summary• SGAs produce less acute EPS than FGA but also cause diabetes.• No clear consensus exists in the choice between FGA and SGA.• Using agents at above recommended doses or combining drugs are common clinically but are not well studied.
  22. 22. Receptor/Adverse Effect X: diabetes M1: sedation H1: sedation, appetite α1: sedation 5-HT2C: appetiteStahl, S. (2008). Essential Psychopharmacology, p. 384.
  23. 23. Self-Test #1 • _________ were the top selling drugs in 2009. – A) antipsychotics – B) oncology agents – C) antidiabetics – D) respiratory agents – E) HIV antiviralshttp://www.nytimes.com/2010/10/03/business/03psych.html?_r=4&hp=&pagewanted=all&http://survivingantidepressants.org/index.php?/topic/2963-the-top-prescription-drugs-of-2011/
  24. 24. Self-Test #2• If a family member were diagnosed with schizophrenia, what agent would you prefer they receive and why? Would this differ based on age or health?

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