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.

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  • 1. Antipsychotics IBrian J. Piper, Ph.D., M.S. piperbj@husson.eduFebruary 4, 2013

2. Goals Pharmacy studentsshould: be familiar with thesymptoms & healthconsequences ofschizophrenia be able to describe themechanism(s) of actionand adverse effects of first-generation antipsychotics 3. SchizophreniaThe Greek translation is schizein split and phrenmind which refers to a split from reality. A groupof severe disorders characterized by atypical:1. Cognition2. Behavior3. EmotionsNOT Multiple Personality Disorder 4. Symptoms of SchizophreniaPositive symptoms: the presence of inappropriatebehaviorsdelusions: thoughtshallucinations: auditory >>> visual > otherdisorganized talking: word saladmovementsNegative symptoms: the absence of appropriatebehaviorsflat affect: joy, anger, disgustanhedoniacatatonia: waxy flexibility 5. Example PatientDelusions of grandeurinappropriate beliefs aboutones self-worth or specialpowersGerald (upto 2:30): http://www.youtube.com/watch?v=gGnl8dqEoPQ 6. Epidemiology ofSchizophrenia 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. History of Antipsychotics 1953: an antihistamine agent (cholpromazine) is found toimprove psychosis in schizophrenics 1960-1970: identification of D2 blockade as the keymechanism, development of these first-generation ofantipsychotic agents 8. Dopamine System I nigrostriatal: substania nigra (soma) to striatum (axons)Stahl, S. (2008). Essential Psychopharmacology, p. 330. 9. Antipsychotics & Tardive Dyskinesia Chronic blockade of D2 receptors leadsThis may cause involuntary movements. them to up-regulate.tardive: slow or belated onsetdyskinesia: presence of involuntary movements, tongue thrusts, lip smacking, eye blinkingPotentially permanent!Example: 4:20 to 5:50: http://www.youtube.com/watch?v=QYYx1mZDpPw 10. TD = Extrapyramidal Symptoms (Long-Term)Brodal (2010). The central nervous system. p. 83. 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. Dopamine Inhibits AcetylcholineStahl, S. (2008). Essential Psychopharmacology, p. 338. 13. D2 Inhibition & Increased AChStahl, S. (2008). Essential Psychopharmacology, p. 339. 14. Solution: Anti-cholinergicsStahl, S. (2008). Essential Psychopharmacology, p. 339. 15. Dopamine Inhibits ProlactinConsequencesamenorrheagalactorhea sex interestgynecomastiaStahl, S. (2008). Essential Psychopharmacology, p. 334. 16. Dopamine & Mood Dopamine projections to nucleus accumbens Increasing dopamine increases reward anti-psychotics block this pathway 17. Non-Selectivity of FGAStahl, S. (2008). Essential Psychopharmacology, p. 338, 340. 18. Haloperidol MOA: D2 antagonist, 1 antagonist Indications: acute psychosis/schizophrenia Adverse Effects: extrapyramidal symptoms(EPS), hypotension 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 oftardive dyskinesia although acute EPS impair the quality oflife of schizophrenics.Stahl, S. (2008). Essential Psychopharmacology, p. 369. 20. Terminology Neuroleptic = major tranquilizer =antipsychotic First Generation Antipsychotic = Typical =Conventional 21. Reduced Lifespan (N = 5,036,662) MaleMale FemaleFemale Life Expectancy YearsLifeYears Lost Lost ExpectancyAll (Psychiatric 76.5NA 80.9NAHistory - )Schizophrenia57.818.7 64.616.3Bipolar62.913.6 68.812.1 Contributing Factors suicide, accident, homicides, self-care (diet/smoking), metabolic (?)Laursen (2011). Schizophrenia Research, 131, 101-104.