Class of 2009 Abstract / OBJECTIVES: The objectives of this study were 1) to review the University of Arizona College of Pharmacy’s curriculum to assess if courses cover pertinent topics in the use of prescription and over-the-counter (OTC) medications by pregnant and lactating women based on The American Association of Colleges of Pharmacy (AACP) Gender and Sex-Related Health Care Pharmacy Curriculum Guide and 2) to assess pharmacy students’ knowledge and abilities to counsel women during pregnancy and breastfeeding. METHODS: The curriculum review was a retrospective, descriptive analysis to assess how well the required curriculum addressed eight pertinent topics in the use of prescription and OTC medications by pregnant and lactating women. The self-assessment questionnaire was a cross-sectional, descriptive analysis that measured student pharmacists’ comfort level with counseling pregnant and lactating women, their perception of how well pharmacy school has prepared them for this role, and their familiarity with and use of available resources. RESULTS: The College of Pharmacy was not in compliance with AACP’s Pharmacy Curriculum Guide. This was reinforced by the questionnaire, which showed that the majority of students, regardless of year in school, did not feel they had been adequately prepared to counsel or to make recommendations to this population. CONCLUSIONS: It is recommended that the curriculum be amended by adding a lecture on teratogenicity. A list of gender and sex- related topics should be provided as well as a handout with available resources. In addition, case studies in each course should be revised to include critical decision-making, recommendations, and counseling if the patient were pregnant or breastfeeding.

Class of 2009 / OBJECTIVES: To compare the attitudes of community pharmacy managers who did and did not contract with Mirixa to provide Medicare Part D medication therapy management (MTM) services in 2006. METHODS: Design: Cross-sectional descriptive study. Setting: United States in 2006. Participants: 100 pharmacy managers contracted to provide MTM services in 2006 and 100 pharmacy managers not contracted to provide MTM services in 2006. Intervention: Telephone-administered survey of independent community pharmacy managers. Main outcome measures: Pharmacist knowledge of and attitudes toward Medicare Part D MTM services. RESULTS: 200 pharmacy managers completed the study (n = 100 for each group). Pharmacists who contracted with Mirixa to provide MTM services in 2006 were more familiar with Medicare Part D MTM (80% vs. 59%, P = 0.001). Significantly more pharmacists contracted with Mirixa to provide MTM services agreed that they were qualified to provide MTM services (96% vs. 88%, P = 0.01) and strongly agreed that an annual personal medication review would benefit patient outcomes (59% vs. 45%, P = 0.04). No significant difference was found between groups with regard to other variables addressed in the survey. CONCLUSIONS: Results of this study suggest that familiarity with Medicare Part D MTM services was a key factor in whether pharmacists chose to contract to provide MTM in 2006. Additionally, significantly more pharmacists who contracted felt strongly that personal medication reviews would improve patient outcomes.

Antiretroviral therapy has given hope and expectations for a better life to HIV positive individuals, however, HIV medication cannot be effective without HIV positive individuals’ compliance to it. This study investigated the ways in which living with HIV and taking medication is located within the psychological, social and cultural context of everyday life and relationships in Greece. It also examined gender and identity issues, which make compliance/non-compliance understandable from the HIV positive peoples’ perspective. In addition, emphasis was given to locating compliance to medical regimes in which the perspectives of HIV positive persons were prioritised and understood in relation to relationships with health care professionals. A mixed methods approach was undertaken to provide understanding of compliance and non-compliance factors to HIV medication in a holistic way. A self-completed questionnaire was used to examine the psychosocial factors underpinning compliance to medication. Face-to-face semi-structured interviews were used to explore issues of identity, gender, relationship between doctors and patients and social understandings of HIV. Finally, self-completed weekly diaries were used to document compliance actions, thoughts and feelings in order to reveal the ways medical regimes fit into everyday life. The study was conducted in three Public Hospitals, one Governmental Hospice and one Non-governmental Organization. Eighty (63 males and 17 females) Greek HIV positive patients completed the questionnaire. Interview sample consisted of 7 and 3 males and females respectively. Finally, 6 Greek HIV positive males and 3 females completed the diaries of the research. The questionnaire data was analysed using descriptive statistics via SPSS 11. In addition, a range of non-parametric tests (Mann Whitney and Kruskal Wallis) were used in order to check if ordinal variables influence compliance with HIV medication. Finally linear regression analysis was used in order to establish the influence of factors on compliance with HIV medication. Interviews and the diaries data were analysed though thematic analysis, focusing on identification of patterns and behaviours which were then interpreted in terms of themes. The findings of the study indicated that, when support was given from life partners compliance with HV medication was increased. However, when support was given from family members, compliance with HIV medication was decreased. According to the findings, family dynamics have changed in several cultures over recent decades, partner roles have changed especially in the west and in Mediterranean societies. In regards to 6 medicalization in everyday life, the study showed that when individuals were experiencing side effects, or had fears of future side effects, religious issues (punishment for homosexuality), loss of one’s freedom due to medication, non-compliant behaviours could occur. Finally, the study indicated that some HIV positive individuals perceived their health levels as good and believed that not taking medication once or twice a week was a compliant behaviour. Hence, false perceptions regarding health levels and compliance issues could lead to non-compliant behaviours. A further examination on the communication patterns of the family system and its impact on HIV positive individuals is recommended as it is clearly not very helpful any more. Further exploration of the general socio-cultural positioning of Greece is recommended as certain HIV positive individuals coped with HIV diagnosis and taking medication, by rejecting it. Finally, the need for psychological support is recommended as it is very rarely provided within the Greek health care system.

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disability diagnosed in an increasing number of children. ASD has few effective treatment options. This study describes ASD prevalence and use of psychotropic medications among children and youth in Manitoba. Methodology: Administrative data from the Repository at the Manitoba Centre for Health Policy (MCHP) were used to create a cohort of children born in Manitoba. Diagnoses of ASD were based on medical claim records, hospital abstracts, or special education funding data. Results: Between 2010 and 2014, 3079 Manitoba children aged 0-14 had an ASD diagnosis (1.2% prevalence). Child demographic, health and education, and family environmental characteristics were compared between children with ASD and children in the general population; children with ASD with and without psychotropic medications; and among all children with psychotropic medications. Children with ASD were more likely to have a psychotropic medication than children in the general population. Children with ASD were more likely to receive a psychotropic medication if they were older than age 4, were diagnosed with ASD later than age 4, received special education funding, had participated in behavioural programming, had a co-occurring psychiatric condition, had a sibling diagnosed with ASD or had ever been in the care of child welfare. This study demonstrated that children with ASD received a greater number and intensity of psychotropic medications than children in the general population with similar demographic and psychiatric conditions. Conclusions: In Manitoba, the prevalence of ASD is increasing and differences exist between children with ASD and children in the general population. Future research and treatment planning for children with mental disorders and developmental disabilities should consider the appropriateness of the patterns of medication use and equity of treatment interventions found in this study. / October 2016

Class of 2007 Abstract / Objectives: A prescription claims database from COPE Behavioral Services in Tucson, Arizona was used to retrospectively assess the differences between patients receiving <4 and those receiving > 4 psychotropic medications over a 12-month period in adult patients with schizophrenia. Methods: Medication groups (i.e., < 4 versus > 4 concomitant psychotropic agents) were compared for differences in gender, age, duplication of antipsychotic therapy, adherence rates, court order treatment status, psychiatric hospitalization rates and length of stay, cost of services provided, and concomitant psychotropic medications. Results: A total of 506 adult patients with schizophrenia (F=214 and M=292) met the inclusion criteria for receiving psychotropic medications during the 12-month study. Of those, 388 patients (76.7%) were found to have an average of < 4 medications, while 118 patients (23.3%) were found to have > 4 medications. Duplication of antipsychotic therapy was more common in the > 4 group (29.7%) compared to the < 4 group (3.1%), p < 0.001. Psychotropic adherence rates were significantly higher in the > 4 group based on month’s supply of prescriptions. Demographic differences between groups included: increased age, more women, fewer court order status, and higher cost of care in the > 4 compared to the < 4 medication group. No differences in hospitalizations, length of stay, and hospital costs were found between groups. Conclusions: Our findings suggest that patients with schizophrenia with increased rates of polypharmacy have higher adherence rates, more duplication of antipsychotics, and a higher cost of care (i.e., case management, laboratory, other services, total prescription costs) compared to patients receiving < 4 psychotropic medications.

Student Number : 9803027N - MA research report - School of Psychology - Faculty of Humanities / The recent introduction of antiretroviral treatment (ART) to the public health sector has meant that for millions of Human Immunodeficiency Virus (HIV)-positive patients this deadly disease has been transformed into a chronic condition. There has been much research done internationally on adherence to ART but in South Africa there has been little investigation in this area. This study aimed to bridge this gap by exploring expert and patient opinions and recommendatio ns regarding adherence to antiretroviral medication. To attain this, four experts and seven patients were interviewed using a semistructured interview schedule. The experts had worked within the HIV field for at least two years while the patients had been chosen from public antiretroviral roll-out programmes and had been on ART for at least six months. These interviews were audio recorded and transcribed. The transcriptions were then explored for themes using thematic content analysis. These themes were categorised and discussed under four broad categories: patients’ perceptions of barriers to adherence, patients’ recommendations for improving adherence, experts’ perceptions of barriers to adherence and experts’ recommendations for improving adherence.

O conhecimento do paciente sobre os seus medicamentos é fundamental para que os use de forma a ser beneficiado por seus efeitos terapêuticos. A Organização Mundial de Saúde (OMS) recomenda a prescrição de medicamentos como um parâmetro para conhecermos as características do uso de medicamentos nas populações. O presente estudo, uma investigação de corte transversal, teve o objetivo de analisar as características das prescrições médicas, utilizando por referência indicadores selecionados de prescrição da OMS, bem como avaliar o conhecimento sobre medicamentos prescritos a idosos cadastrados nos Núcleos de Saúde da Família ligados à Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Os indicadores de prescrição foram verificados nas receitas médicas e o conhecimento foi verificado através da aplicação de um questionário contendo perguntas relativas à indicação terapêutica do medicamento, nome, dosagem, quantidade de forma farmacêutica a ser administrada a cada vez e freqüência de administração. As respostas foram comparadas com a receita médica. O número médio de medicamentos prescritos por paciente foi de 2,76. Foram dispensados 89,49% dos medicamentos prescritos, 91,30% foram prescritos pelo nome genérico e 90,94% foram prescritos de acordo com a lista padronizada de medicamentos. Foram prescritos 0,36% de antibióticos e 0,72% de medicamentos injetáveis. Do total de 100 entrevistados, 44% obtiveram um bom conhecimento sobre os medicamentos utilizados. No que se refere à dosagem, à quantidade de forma farmacêutica a ser administrada a cada vez e à freqüência de administração, 39%, 87% e 85% das respostas, respectivamente, estavam de acordo com a prescrição médica. Em 87% dos casos, indicação terapêutica foi declarada corretamente e, em 45%, o nome do medicamento estava correto. Os resultados sugerem que o Programa de Saúde da Família tem boa resolutividade no que se refere ao uso de medicamentos por idosos, mas que poderia melhorar em alguns aspectos através da atenção farmacêutica. / The patients’ knowledge on their medication is crucial to use them properly. The World Health Organization (WHO) recommends the prescription to be used as a parameter (criteria) to characterize medications use among the population. This cross-sectional study had the objectives of identifying the features of medical prescriptions using the WHO indicators as reference, and, to assess the knowledge of elderly patients who were enrolled in the Family Healthcare Units of the Medical School of Ribeirão Preto – University of São Paulo. The prescription indicators were verified in the medical prescriptions and the knowledge was verified through the administration of a questionnaire to 100 elderly patients. The questionnaire included questions on the therapeutic indication, name, of the drugs dosis, and the quantity of pharmaceutical form to be taken, and the frequency of administration. The answers were compared to the prescriptions. The mean of the prescribed medications for patient was 2,76. 89,49% of prescribed medications were dispensed, and 91,39% were prescribed by generic name and 90,94% prescribed according to the standard list of medications. It has been prescribed 0,36% of antibiotics and 0,72% of injectable medications. Out of one hundred interviewee, of whom 44% showed a good knowledge about their medicaments. Regarding to dosis (39%), amount of pharmaceutical form taken (87%) and the frequency of administration (85%) of answers were in accordance with the medical prescription. In 87% of cases the patients answered correctly to the therapeutical indication and 45% of the cases they correctly answered the name of medication. The results suggest that the Family Healthcare has a good performance regarding the use of medicaments by old-aged patients, there is some room for improvement through pharmaceutical care.

目的：抗精神病藥物是多功能的藥物。鼻腔給藥可提供高效的藥物遞送，但關於鼻腔遞送抗精神病藥物的研究仍十分有限。此外，有關鼻腔給藥後生成的活性代謝物於全身及中樞神經系統的分佈的報導亦很少。本研究的主要目的在於：1）篩選出適合鼻腔給藥的抗精神病藥物，以及2）研究被選定抗精神病藥物在鼻腔給藥後於中樞神經系統的藥代動力學和藥效學特徵，尤其關注藥物代謝在藥代動力學和藥效學中的作用。 / 方法：本研究系統地採用了in silico 評估及體外透過模型，篩選出具有較高鼻腔給藥發展潛力的抗精神病藥物。通過不同的鼻腔給藥動物體內模型，研究所選藥物全身及中樞神經系統的藥代動力學和藥效學特徵，並與口服和靜脈注射進行比較。 / 結果：第一階段的in silico篩選包括了二十二種抗精神病藥物。其中氯丙嗪、氟奮乃靜、丙氯拉嗪及洛沙平具有鼻腔給藥所需的良好的理化性質和臨床特點，因此被挑選到第二階段篩選。第二階段篩選採用體外Calu-3單層細胞模型研究藥物經鼻腔吸收的能力。Calu-3細胞模型的實驗結果表明，抗精神病藥物的表觀滲透係數與藥物的親脂性和總回收率呈負相關，其中洛沙平具有最高的透過性，並被選擇作進一步的體內研究。 / 我們建立了一種全新的可以同時測定大鼠腦內和血漿中洛沙平及其體內代謝產物（包括7-羥基-洛沙平）的液質聯用方法，並比較了在大鼠清醒及麻醉狀態下洛沙平鼻腔給藥後的藥代動力學。結果表明無論在大鼠清醒還是麻醉狀態下，鼻腔給藥均具有較高的絶對生物利用度（清醒狀態：~50%；麻醉狀態：~100%）。另外，研究發現麻醉和鼻腔手術對洛沙平及其代謝產物的體內處置具有很大影響，且這些影響依賴於給藥途徑。 / 本研究亦考察了洛沙平在鼻腔及口服給藥後，於大鼠中樞神經系統的藥代動力學和藥效學特徵。鼻腔給藥後，洛沙平迅速被吸收入血，隨即進入腦部，且15分鐘內在所有腦部區域達至最高藥物濃度。與之相反，口服給藥後僅有極少量的洛沙平吸收入血及腦部。但是，在鼻腔與口服給藥後，主要代謝產物7-羥基-洛沙平在腦內的濃度水平相當，且兩種給藥途徑對腦部紋狀體中多巴胺、5-羥色胺、和它們的代謝物水平的影響亦無差異。由於錐體外系癥狀乃抗精神病藥物常見的運動障礙性副作用，我們採用了大鼠僵直模型對大鼠在服用洛沙平後的運動障礙反應進行了評價。研究表明相比鼻腔給藥而言，口服洛沙平後誘發了大鼠更強的僵直反應。另外，當分別靜脈注射洛沙平及7-羥基-洛沙平後，7-羥基-洛沙平誘發的僵直反應比洛沙平更強；但同時注射洛沙平及7-羥基-洛沙平則降低了由7-羥基-洛沙平誘發的僵直反應。 / 結論：洛沙平有望進一步開發成為一種鼻腔遞藥，用於治療精神分裂症及其他中樞神經系統疾病。服用洛沙平後，錐體外系癥狀副作用很大程度上是由體內代謝產物7-羥基-洛沙平引起，而非洛沙平本身。藥物代謝對抗精神病藥物及鼻腔遞藥的臨床作用能產生很大的影響。 / Purpose: Antipsychotics are versatile drugs. Intranasal route could provide efficient delivery for certain therapeutic agents; however, studies on intranasal antipsychotics are limited. Moreover, the systemic and central nervous system (CNS) dispositions of active metabolites after intranasal drug administration are seldom investigated. The current project aims to 1) identify the antipsychotics that are more suitable to be developed into intranasal medications; and 2) characterize the CNS pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the selected antipsychotic delivered by intranasal route, with a special attention to the role of drug metabolism in PK and PD outcomes. / Methods: To select an antipsychotic with greater potential for intranasal delivery, a systematic approach was adopted to screen antipsychotic candidates with in silico evaluations and then in vitro permeability assays. The systemic and CNS PK and PD profiles of the selected antipsychotic would be investigated in different intranasal delivery models and compared to that after oral and intravenous (IV) administrations. / Results: Twenty two antipsychotics were included in the primary in silico screening. Chlorpromazine, fluphenazine, prochlorperazine, and loxapine, which possessed more favorable physicochemical and clinical properties required for intranasal delivery, were selected. Secondary screening in the Calu-3 cell monolayer model demonstrated that the apparent permeability coefficients (P[subscript app]) correlated inversely to the antipsychoitc’s lipophilicity and total recovery. Loxapine, which demonstrated the highest permeability, was selected for further in vivo investigations. / A novel LCMS/MS assay method was first developed for quantification of loxapine and its metabolites including 7-hydroxy-loxapine (7-OH-loxapine) in rat brain and plasma. The systemic PKs of loxapine in conscious and anesthetized rat models of intranasal delivery were then studied and compared. While intranasal loxapine achieved satisfactory absolute bioavailabilities in both conscious (~50%) and anesthetized (~100%) models, anesthesia and nasal surgery were found to exert profound effects on the systemic disposition of loxapine and its metabolites, and such effects were dependent on the administration route. / The CNS PK and PD outcomes after intranasal and oral loxapine administrations were characterized. Intranasally administered loxapine was efficiently absorbed into systemic circulation followed by entering brain, with a t[subscript max] less than 15 min in all the studied brain regions. In contrast, oral route delivered minimal amounts of loxapine to plasma and brain. Intranasal and oral loxapine achieved similar brain levels of 7-OH-loxapine, the major metabolite, and these two routes induced similar changes in the striatal levels of dopamine, serotonin, and their metabolites. Extrapyramidal symptoms (EPS), the motor side effects frequently associated with antipsychotics, were evaluated by the catalepsy models. The severity and incidence of catalepsy were consistently higher after oral than after intranasal loxapine administration. Individual IV injections of loxapine and 7-OH-loxapine to rats revealed that 7-OH-loxapine was even more cataleptogenic than the loxapine, while co-injection of loxapine tended to lower the catalepsy induced by 7-OH-loxapine. / Conclusion: Loxapine seems to be a promising antipsychotic for further development into intranasal medication. 7-OH-loxapine, rather than the parent loxapine, could be the culprit in EPS associated with loxapine treatment. Drug metabolism could have considerable contribution to the clinical effects of antipsychotics and intranasal drugs. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Wong, Yin Cheong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 259-296). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese. / Table of contents --- p.I / Acknowledgements --- p.VII / Publications --- p.IX / Abstract --- p.XI / 摘要 --- p.XIII / List of Tables --- p.XV / List of Figures --- p.XVII / List of Abbreviations --- p.XX / Chapter Chapter One. --- Introduction --- p.1 / Chapter 1.1 --- Overview of antipsychotics --- p.1 / Chapter 1.1.1 --- Pharmacology --- p.1 / Chapter 1.1.2 --- Therapeutic applications --- p.7 / Chapter 1.1.2.1 --- Schizophrenic and other mental disorders --- p.7 / Chapter 1.1.2.2 --- Pain management --- p.9 / Chapter 1.1.3 --- Antipsychotic-induced extrapyramidal symptoms (EPS) --- p.11 / Chapter 1.1.3.1 --- Clinical manifestations --- p.11 / Chapter 1.1.3.2 --- Preclinical evaluation of EPS by catalepsy tests --- p.13 / Chapter 1.1.3.3 --- Role of active metabolites in EPS --- p.16 / Chapter 1.2 --- Overview of intranasal drug delivery --- p.20 / Chapter 1.2.1 --- Absorption of drug in nasal cavity --- p.21 / Chapter 1.2.1.1 --- Nasal anatomy --- p.21 / Chapter 1.2.1.2 --- Pathways from the nasal passages to the central nervous system --- p.25 / Chapter 1.2.2 --- Metabolite formation after intranasal drug application --- p.26 / Chapter 1.2.2.1 --- Nasal metabolisms --- p.27 / Chapter 1.2.2.2 --- Contribution of gastrointestinal absorption and metabolism --- p.27 / Chapter 1.3 --- Potentials of delivering antipsychotics via intranasal route --- p.33 / Chapter 1.3.1 --- Advantages and limitations of intranasal drug delivery --- p.33 / Chapter 1.3.2 --- Advantages of intranasal antipsychotics --- p.37 / Chapter 1.4 --- Research questions and hypotheses of current study --- p.40 / Chapter 1.5 --- Objectives and thesis outline --- p.42 / Chapter 1.6 --- Significance of the current study --- p.46 / Chapter Chapter Two. --- In silico screening of antipsychotic candidates for their intranasal delivery potential --- p.47 / Chapter 2.1 --- Introduction --- p.47 / Chapter 2.2 --- Methods --- p.49 / Chapter 2.2.1 --- Antipsychotic candidates included in the in silico screening --- p.49 / Chapter 2.2.2 --- Evaluation of physicochemical properties of the candidates --- p.49 / Chapter 2.2.3 --- Clinical development potential of the candidates --- p.51 / Chapter 2.2.3.1 --- Therapeutic uses in conditions other than chronic schizophrenia --- p.51 / Chapter 2.2.3.2 --- Previous reports on intranasal delivery of antipsychotics --- p.52 / Chapter 2.2.4 --- Set up of selection criteria for further in vitro investigations --- p.53 / Chapter 2.3 --- Results and discussions --- p.54 / Chapter 2.3.1 --- Selection based on physicochemical characteristics --- p.54 / Chapter 2.3.2 --- Selection based on therapeutic usage --- p.58 / Chapter 2.3.3 --- Antipsychotic candidates selected for further in vitro investigations --- p.61 / Chapter 2.4 --- Conclusion --- p.66 / Chapter Chapter Three. --- In vitro permeation studies of selected antipsychotic candidates using Calu-3 cell line model --- p.67 / Chapter 3.1 --- Introduction --- p.67 / Chapter 3.2 --- Materials --- p.70 / Chapter 3.2.1 --- Chemicals --- p.70 / Chapter 3.2.2 --- Materials for cell culture --- p.70 / Chapter 3.2.3 --- Instruments --- p.71 / Chapter 3.3 --- Methods --- p.71 / Chapter 3.3.1 --- Cell culture --- p.71 / Chapter 3.3.2 --- Cytotoxicities of the drug candidates on Calu-3 cells by MTS/PES assay --- p.72 / Chapter 3.3.3 --- Stabilities of the drug candidates in loading solutions --- p.74 / Chapter 3.3.4 --- Permeation studies of drug candidates using Calu-3 cell line model --- p.75 / Chapter 3.3.5 --- HPLC/UV assay development and validation for the drug candidates --- p.77 / Chapter 3.3.6 --- Data analysis --- p.79 / Chapter 3.4 --- Results and discussions --- p.80 / Chapter 3.4.1 --- HPLC/UV methods for the drug candidates --- p.80 / Chapter 3.4.2 --- Cytotoxicities of the drug candidates on Calu-3 cells by MTS/PES assay --- p.82 / Chapter 3.4.3 --- Stabilities of the drug candidates in loading solutions --- p.85 / Chapter 3.4.4 --- Permeation studies of drug candidates using Calu-3 cell line model . --- p.86 / Chapter 3.4.4.1 --- Permeability across Calu-3 cell monolayer --- p.86 / Chapter 3.4.4.2 --- Relationship between lipophilicity and permeability and cellular uptake of the antipsychotic candidates --- p.89 / Chapter 3.5 --- Conclusion --- p.93 / Chapter Chapter Four. --- LCMS/MS assay development for quantification of loxapine, amoxapine and their hydroxylated metabolites in rat brain tissues, plasma and CSF --- p.94 / Chapter 4.1 --- Introduction --- p.94 / Chapter 4.2 --- Materials and chemicals --- p.100 / Chapter 4.3 --- Methods --- p.100 / Chapter 4.3.1 --- Preparation of stock solutions, calibration standards and quality control (QC) samples --- p.100 / Chapter 4.3.2 --- Sample extraction procedure --- p.102 / Chapter 4.3.2.1 --- Plasma --- p.102 / Chapter 4.3.2.2 --- Brain tissue --- p.103 / Chapter 4.3.2.3 --- CSF --- p.103 / Chapter 4.3.3 --- LCMS/MS conditions --- p.104 / Chapter 4.3.4 --- Method validation --- p.106 / Chapter 4.3.4.1 --- Linearity and range --- p.106 / Chapter 4.3.4.2 --- Accuracy and precision --- p.106 / Chapter 4.3.4.3 --- Recovery and stability --- p.107 / Chapter 4.3.4.4 --- Assay selectivity and matrix effects --- p.107 / Chapter 4.3.5 --- Application to pharmacokinetic study of orally administered loxapine in rats --- p.108 / Chapter 4.4 --- Results and discussions --- p.110 / Chapter 4.4.1 --- Optimization of LC and MS conditions --- p.110 / Chapter 4.4.2 --- Extraction of loxapine and metabolites from biological matrices --- p.114 / Chapter 4.4.2.1 --- Plasma --- p.114 / Chapter 4.4.2.2 --- Brain tissue --- p.115 / Chapter 4.4.2.3 --- Sample cleanup by SPE --- p.115 / Chapter 4.4.3 --- Method validation --- p.119 / Chapter 4.4.3.1 --- Linearity and range --- p.119 / Chapter 4.4.3.2 --- Accuracy and precision --- p.120 / Chapter 4.4.3.3 --- Recovery and stability --- p.120 / Chapter 4.4.3.4 --- Assay selectivity and matrix effects --- p.121 / Chapter 4.4.4 --- Application to pharmacokinetic study of orally administered loxapine in rats --- p.124 / Chapter 4.4.4.1 --- Plasma pharmacokinetic profiles --- p.124 / Chapter 4.4.4.2 --- Brain distribution study --- p.126 / Chapter 4.4.4.3 --- CSF disposition --- p.128 / Chapter 4.4.5 --- Implications on the further investigations of low-dose loxapine --- p.128 / Chapter 4.5 --- Conclusion --- p.131 / Chapter Chapter Five. --- Pharmacokinetic profiles of loxapine and its metabolites after intranasal loxapine administration: comparison of conscious and anesthetized rat models --- p.132 / Chapter 5.1 --- Introduction --- p.132 / Chapter 5.2 --- Materials and chemicals --- p.135 / Chapter 5.3 --- Methods --- p.135 / Chapter 5.3.1 --- Animal surgery --- p.135 / Chapter 5.3.1.1 --- Conscious rat model --- p.135 / Chapter 5.3.1.2 --- Anesthetized rat model --- p.136 / Chapter 5.3.2 --- Loxapine administration through intranasal, oral and IV routes --- p.138 / Chapter 5.3.2.1 --- Preparation of drug solutions --- p.138 / Chapter 5.3.2.2 --- Drug administration in conscious rat model --- p.138 / Chapter 5.3.2.3 --- Drug administration in anesthetized rat model --- p.139 / Chapter 5.3.3 --- Blood and brain samplings --- p.139 / Chapter 5.3.4 --- Pharmacokinetic and statistical analyses --- p.142 / Chapter 5.4 --- Results and discussions --- p.143 / Chapter 5.4.1 --- Pharmacokinetics of loxapine and its metabolites in conscious model --- p.149 / Chapter 5.4.1.1 --- Plasma concentration versus time profiles --- p.149 / Chapter 5.4.1.2 --- Brain dispositions of loxapine and its metabolites --- p.150 / Chapter 5.4.2 --- Pharmacokinetics of loxapine and its metabolites in anesthetized model --- p.151 / Chapter 5.4.2.1 --- Plasma concentration versus time profiles --- p.151 / Chapter 5.4.2.2 --- Brain dispositions of loxapine and its metabolites --- p.153 / Chapter 5.4.3 --- Effects of anesthesia and nasal surgery on the pharmacokinetics of loxapine and its metabolites --- p.155 / Chapter 5.4.3.1 --- Effects of anesthesia and nasal surgery on loxapine absorption --- p.158 / Chapter 5.4.3.2 --- Effects of anesthesia and nasal surgery on distribution of loxapine and its metabolites --- p.161 / Chapter 5.4.3.3 --- Effects of anesthesia and nasal surgery on loxapine metabolism --- p.164 / Chapter 5.4.3.4 --- Effects of anesthesia and nasal surgery on elimination of loxapine and its metabolites --- p.167 / Chapter 5.4.3.5 --- Overall effects of anesthesia and nasal surgery on the pharmacokinetics of loxapine and its metabolites --- p.168 / Chapter 5.5 --- Conclusion --- p.172 / Chapter Chapter Six. --- CNS pharmacokinetics of loxapine and its metabolites and pharmacodynamic effects on catalepsy and neurotransmission after intranasal loxapine administration --- p.173 / Chapter 6.1 --- Introduction --- p.173 / Chapter 6.2 --- Materials and chemicals --- p.178 / Chapter 6.3 --- Methods --- p.178 / Chapter 6.3.1 --- LCMS/MS assay development for quantification of neurotransmitters and their metabolites in rat brain tissue --- p.178 / Chapter 6.3.1.1 --- Preparation of stock solutions, calibration standards and quality control samples --- p.178 / Chapter 6.3.1.2 --- Sample extraction procedure --- p.179 / Chapter 6.3.1.3 --- LCMS/MS conditions --- p.180 / Chapter 6.3.1.4 --- Method validation --- p.180 / Chapter 6.3.2 --- Experimental procedures --- p.182 / Chapter 6.3.2.1 --- Drug administration through nasal and oral routes --- p.183 / Chapter 6.3.2.2 --- Catalepsy tests --- p.184 / Chapter 6.3.2.3 --- Drug and neurotransmitter analyses --- p.185 / Chapter 6.3.3 --- Data analysis --- p.185 / Chapter 6.4 --- Results and discussions --- p.187 / Chapter 6.4.1 --- LCMS/MS assay for quantification of neurotransmitters and their metabolites in rat brain tissue --- p.187 / Chapter 6.4.2 --- Pharmacokinetics of loxapine and its metabolites --- p.192 / Chapter 6.4.2.1 --- Pharmacokinetic profiles of loxapine and its metabolites in brain --- p.192 / Chapter 6.4.2.2 --- Pharmacokinetic profiles of loxapine and its metabolites in plasma --- p.197 / Chapter 6.4.3 --- Effects of nasal and oral loxapine administrations on catalepsy --- p.202 / Chapter 6.4.4 --- Effects of nasal and oral loxapine administrations on neurotransmitter levels --- p.208 / Chapter 6.4.5 --- Comparison of the present study on intranasal loxapine with previous studies on intranasal delivery of CNS drugs --- p.215 / Chapter 6.4.5.1 --- Intranasal delivery of antipsychotic --- p.215 / Chapter 6.4.5.2 --- Metabolite disposition in brain after intranasal administration of CNS drugs --- p.218 / Chapter 6.4.6 --- Clinical significance of the present study --- p.221 / Chapter 6.5 --- Conclusion --- p.225 / Chapter Chapter Seven. --- Cataleptogenic effects of loxapine and its metabolites --- p..226 / Chapter 7.1 --- Introduction --- p.226 / Chapter 7.2 --- Methods --- p.229 / Chapter 7.2.1 --- Literature study on the cataleptogenicity of loxapine and its metabolites --- p.229 / Chapter 7.2.2 --- Cataleptogenic effects of loxapine and its metabolites given by IV route --- p.229 / Chapter 7.2.2.1 --- Cataleptogenic effect of individual compounds --- p.229 / Chapter 7.2.2.2 --- Effect of addition of loxapine on the cataleptogenic effect of 7-OH-loxapine --- p.230 / Chapter 7.2.3 --- Data analysis --- p.230 / Chapter 7.3 --- Results and discussions --- p.231 / Chapter 7.3.1 --- Literature study on the cataleptogenicity of loxapine and its metabolites --- p.231 / Chapter 7.3.2 --- Cataleptogenic effects of loxapine and its metabolites given by IV route --- p.236 / Chapter 7.3.2.1 --- Cataleptogenic effect of individual compounds --- p.236 / Chapter 7.3.2.2 --- Effect of addition of loxapine on the cataleptogenic effect of 7-OH-loxapine --- p.240 / Chapter 7.3.3 --- Clinical significance of the present study --- p.245 / Chapter 7.4 --- Conclusion --- p.252 / Chapter Chapter Eight. --- Overall Conclusion --- p.253 / References --- p.259

O conhecimento do paciente sobre os seus medicamentos é fundamental para que os use de forma a ser beneficiado por seus efeitos terapêuticos. A Organização Mundial de Saúde (OMS) recomenda a prescrição de medicamentos como um parâmetro para conhecermos as características do uso de medicamentos nas populações. O presente estudo, uma investigação de corte transversal, teve o objetivo de analisar as características das prescrições médicas, utilizando por referência indicadores selecionados de prescrição da OMS, bem como avaliar o conhecimento sobre medicamentos prescritos a idosos cadastrados nos Núcleos de Saúde da Família ligados à Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Os indicadores de prescrição foram verificados nas receitas médicas e o conhecimento foi verificado através da aplicação de um questionário contendo perguntas relativas à indicação terapêutica do medicamento, nome, dosagem, quantidade de forma farmacêutica a ser administrada a cada vez e freqüência de administração. As respostas foram comparadas com a receita médica. O número médio de medicamentos prescritos por paciente foi de 2,76. Foram dispensados 89,49% dos medicamentos prescritos, 91,30% foram prescritos pelo nome genérico e 90,94% foram prescritos de acordo com a lista padronizada de medicamentos. Foram prescritos 0,36% de antibióticos e 0,72% de medicamentos injetáveis. Do total de 100 entrevistados, 44% obtiveram um bom conhecimento sobre os medicamentos utilizados. No que se refere à dosagem, à quantidade de forma farmacêutica a ser administrada a cada vez e à freqüência de administração, 39%, 87% e 85% das respostas, respectivamente, estavam de acordo com a prescrição médica. Em 87% dos casos, indicação terapêutica foi declarada corretamente e, em 45%, o nome do medicamento estava correto. Os resultados sugerem que o Programa de Saúde da Família tem boa resolutividade no que se refere ao uso de medicamentos por idosos, mas que poderia melhorar em alguns aspectos através da atenção farmacêutica. / The patients’ knowledge on their medication is crucial to use them properly. The World Health Organization (WHO) recommends the prescription to be used as a parameter (criteria) to characterize medications use among the population. This cross-sectional study had the objectives of identifying the features of medical prescriptions using the WHO indicators as reference, and, to assess the knowledge of elderly patients who were enrolled in the Family Healthcare Units of the Medical School of Ribeirão Preto – University of São Paulo. The prescription indicators were verified in the medical prescriptions and the knowledge was verified through the administration of a questionnaire to 100 elderly patients. The questionnaire included questions on the therapeutic indication, name, of the drugs dosis, and the quantity of pharmaceutical form to be taken, and the frequency of administration. The answers were compared to the prescriptions. The mean of the prescribed medications for patient was 2,76. 89,49% of prescribed medications were dispensed, and 91,39% were prescribed by generic name and 90,94% prescribed according to the standard list of medications. It has been prescribed 0,36% of antibiotics and 0,72% of injectable medications. Out of one hundred interviewee, of whom 44% showed a good knowledge about their medicaments. Regarding to dosis (39%), amount of pharmaceutical form taken (87%) and the frequency of administration (85%) of answers were in accordance with the medical prescription. In 87% of cases the patients answered correctly to the therapeutical indication and 45% of the cases they correctly answered the name of medication. The results suggest that the Family Healthcare has a good performance regarding the use of medicaments by old-aged patients, there is some room for improvement through pharmaceutical care.

Addiction is a national problem in the United States that impacts public health and social and economic welfare. The purpose of this case study was to identify barriers that impede treatment and hinder the success of client recovery from addiction. The research question focused on social work clinicians' perceptions of barriers to effective treatment with substance abuse clients in Coastal South Mississippi. The theoretical framework for this research was the reasoned action theory. Data was collected from a focus group, personal interviews, and the review of literature. Purposeful sampling was used to select 13 social workers for interviews and for a focus group. The social workers needed to have obtained a bachelor or higher degree and a minimum of one year professional experience working with substance abuse clients. Data analysis was conducted by evaluating transcripts of audio recordings from the focus group. The results were then further developed using common words and phrases among the participants to assist in the development of themes. Three themes emerged from this research study: the counselor attitudes/perceptions to treatment, client identified barriers to successful treatment, and the identification of environmental barriers to treatment. The findings of this study might bring about social change by helping social workers to identify factors that influence substance abuse treatment delivery and adapt successful treatment approaches to serve clients by providing social workers with the knowledge and awareness of practitioners' perceptions on treating substance abuse clients. This should lead to enhanced clinical practices by empowering treatment outcomes for the benefit of substance abuse clients.