Title: Analysis of Pharmacotherapy by patients with diagnosis of arterial hypertension Student: Vasiliki Kontou Tutor: Prof. RNDr. Jiri Vlcek, CSs Department of Social and Clinical Pharmacy, Charles University of Prague, Faculty of Pharmacy in Hradec Kralove Introduction: Arterial Hypertension (AH) is characterized by elevated blood pressure, which often leads to increased morbidity and mortality. AH divided into primary and secondary. Aim: In the theoretical part the aim is to analyse the etiopathogenesis, methods of diagnosis and the treatment strategies of arterial hypertension in the recent literature. In the experimental part the aim is to analyse the provisions of the above diagnosis of arterial hypertension. Method: During a six month period were collected 58 prescriptions with the diagnosis of arterial hypertension from a pharmacy that provided pharmaceutical care in the Greek village, Mytikas. Only one prescription for one patient was analysed. In the prescriptions were collected data on drugs, patients and physicians. Results: The pilot study included 58 prescriptions. Most patients were elderly, over 65 years old and 30% were in age 71 - 80 years. General practitioners prescribed 65% of the medical prescriptions. Most frequently prescribed ARBs with hydrochlorothiazide drugs (27%) and...

Cocaine use disorder is a serious public health issue for which no approved pharmacotherapies exist. The development of a pharmacotherapy for cocaine use disorder is a priority for the National Institute on Drug Abuse. Amphetamine maintenance has been shown to be effective to reduce cocaine use in double-blind placebo controlled clinical trials, but has not been approved due to concerns over safety and abuse liability. Development of new pharmacotherapies is facilitated by preclinical testing for effectiveness and identification of new targets for medication development. The first part of this dissertation develops a novel non-human primate cocaine self-administration choice procedure that is modeled after a human laboratory cocaine self-administration choice procedure to improve translational research and facilitate medication development. The second part of this dissertation is devoted to examining the mechanisms of amphetamine maintenance-induced decreases in cocaine use. In the novel non-human primate choice procedure, monkeys chose between injections of cocaine or food pellets (0, 1, 3 or 10) in a 9-choice discrete trials procedure. The reinforcers were available on concurrent independent progressive-ratio schedules. Monkeys chose between cocaine and food in a dose- and magnitude-dependent manner. Maintenance on 7 days of lisdexamfetamine and amphetamine decreased cocaine choices without decreasing food responding, providing evidence that this model may be able to predict drugs that will have clinical efficacy to decrease cocaine use. The next set of experiments examined the effects of amphetamine maintenance on the abuse-related behavioral (intracranial self-stimulation, ICSS) and neurochemical [nucleus accumbens dopamine (DA) and serotonin (5-HT)] effects of cocaine, methylenedioxypyrovalerone, and methamphetamine in rats. Amphetamine maintenance produced sustained increases in ICSS baseline responding and nucleus accumbens DA levels without affecting 5-HT levels. Amphetamine maintenance also attenuated the behavioral and neurochemical abuse-related effects of cocaine but not those of methamphetamine, and with MDPV, amphetamine maintenance decreased the abuse-related neurochemical effect of MDPV, but not the abuse-related behavioral effect. This suggests that amphetamine would likely be most effective against cocaine, least effective against methamphetamine and between the two for MDPV. These data suggest targets that selectively release DA will be the most effective against cocaine use disorder.

Opioid dependence is a chronic relapsing condition resulting in significant individual and community harms, for which the most effective treatment is long term opioid pharmacotherapy (OP). In contrast to other Australian states and territories, in Victoria, 80-85 % of OP prescribing is undertaken by GPs, and while demand for this treatment is difficult to estimate, all evidence indicates that the current and future GP workforce is inadequate to meet projected need. / GPs have shown a reluctance to become actively involved in the treatment of patients with drug dependence, especially where illicit drugs are involved. In order to prescribe OP, Australian medical practitioners are required to complete a specific training program. Little is known of the reasons why GPs decline to undertake this training, and why the majority who complete training, subsequently prescribe to very few or no patients. / Using in-depth interviews and an analysis of existing data from the Victorian Department of Human Services, this thesis not only explores why GPs are unwilling to complete OP training, and why many subsequently fail to prescribe, but also identifies both barriers and facilitators which influence GPs in their decisions regarding these issues. The results have not only provided new information on the reasons GPs decline the offer of training but also supported existing research.

<p>Established quantitative relationships between dose, plasma concentrations and response [pharmacokinetic-pharmacodynamic (PKPD) models] have a high potential in improving therapeutic indices of anticancer drug therapy and in increasing drug development efficiency. PKPD modelling is a helpful tool for characterising and understanding schedule dependence. The aim of this thesis was to develop PKPD models of anticancer drugs for tumour effects and haematological toxicity, which is the most frequent dose-limiting toxicity.</p><p>PK and haematological toxicity after several schedules were studied in rats and semi-physiological PKPD models for the whole time course of myelosuppression were developed from animal and patient data. The possibility to implant hollow fibres filled with tumour cells in immunocompetent rats was investigated for simultaneous assessment of PK, tumour response and haematological toxicity. Population data analyses were performed using the software NONMEM. </p><p>When all injections were administered within eight hours, fractionated schedules of 5-fluorouracil and epirubicin produced similar haematological toxicity in rats as a single dose, when the non-linear PK of 5-fluorouracil was accounted for. When the time interval was extended to two days for 5-fluorouracil, the fractionated regimens were more toxic. </p><p>The developed semi-physiological PKPD models included transit compartments that mimic maturation stages in bone marrow and explain the time lag. Feedback mechanisms characterised the rebound. The models successfully described myelosuppression in patients (DMDC) and rats (5-fluorouracil), after different administration schedules. Further developments made it possible to characterise the time course of myelosuppression after administration of each one of six different drugs, with parameters related to the haematopoietic system consistent across drugs. </p><p>The developed hollow fibre model in immunocompetent rats was successfully applied to monitor PK, toxicity and the time course of antitumour effects. PKPD modelling illustrated that the schedule dependence of the anticancer agent CHS 828 is partly due to dose-dependent bioavailability and partly due to a schedule-dependent PD effect.</p>

<p>Acid related diseases like GERD, duodenal-and gastric ulcers and H. Pylori-positive peptic ulcer disease are primarily managed by reducing gastric acidity. Irreversible proton pump inhibitors (PPIs) inhibit gastric acid secretion effectively throughout the day by irreversibly inhibiting the gastric proton pump, H+, K+-ATPase, in the parietal cells. Reversible gastric proton pump inhibitors are under development, but have not yet reached clinical use.</p><p>The pharmacokinetic/pharmacodynamic (PK/PD) relationships of these compounds are nonlinear, with a delay in the effect-time profile compared to the plasma concentration-time course. PK/PD-modelling was used to characterize and quantify the pharmacological effect with regard to onset, intensity and duration of effect. Models based on functional data, that discriminate between drug-and system-specific parameters, were developed. </p><p>In general, the plasma concentration-time course for each individual was approximated by linear interpolation between time-points and served as input into the pharmacodynamic models. A turnover model of irreversible inhibition of gastric acid secretion by omeprazole in the dog described the data well. The model was challenged and found to be robust under different experimental conditions. This model could predict the effect following different exposure of omeprazole and following different histamine provocation. Different fitting approaches (naïve pooling, standard two-stage and nonlinear mixed effects modelling) were compared and resulted in similar parameter estimates. For the reversible inhibitors, a kinetic binding model was finally selected. With a binding model the delay in the effect-time profile is explained by prolonged binding to the enzyme. </p><p>Use of these results in drug development can be helpful with regard to selection of drugs for further development and to predict the first clinical dose.</p>

Established quantitative relationships between dose, plasma concentrations and response [pharmacokinetic-pharmacodynamic (PKPD) models] have a high potential in improving therapeutic indices of anticancer drug therapy and in increasing drug development efficiency. PKPD modelling is a helpful tool for characterising and understanding schedule dependence. The aim of this thesis was to develop PKPD models of anticancer drugs for tumour effects and haematological toxicity, which is the most frequent dose-limiting toxicity. PK and haematological toxicity after several schedules were studied in rats and semi-physiological PKPD models for the whole time course of myelosuppression were developed from animal and patient data. The possibility to implant hollow fibres filled with tumour cells in immunocompetent rats was investigated for simultaneous assessment of PK, tumour response and haematological toxicity. Population data analyses were performed using the software NONMEM. When all injections were administered within eight hours, fractionated schedules of 5-fluorouracil and epirubicin produced similar haematological toxicity in rats as a single dose, when the non-linear PK of 5-fluorouracil was accounted for. When the time interval was extended to two days for 5-fluorouracil, the fractionated regimens were more toxic. The developed semi-physiological PKPD models included transit compartments that mimic maturation stages in bone marrow and explain the time lag. Feedback mechanisms characterised the rebound. The models successfully described myelosuppression in patients (DMDC) and rats (5-fluorouracil), after different administration schedules. Further developments made it possible to characterise the time course of myelosuppression after administration of each one of six different drugs, with parameters related to the haematopoietic system consistent across drugs. The developed hollow fibre model in immunocompetent rats was successfully applied to monitor PK, toxicity and the time course of antitumour effects. PKPD modelling illustrated that the schedule dependence of the anticancer agent CHS 828 is partly due to dose-dependent bioavailability and partly due to a schedule-dependent PD effect.

Acid related diseases like GERD, duodenal-and gastric ulcers and H. Pylori-positive peptic ulcer disease are primarily managed by reducing gastric acidity. Irreversible proton pump inhibitors (PPIs) inhibit gastric acid secretion effectively throughout the day by irreversibly inhibiting the gastric proton pump, H+, K+-ATPase, in the parietal cells. Reversible gastric proton pump inhibitors are under development, but have not yet reached clinical use. The pharmacokinetic/pharmacodynamic (PK/PD) relationships of these compounds are nonlinear, with a delay in the effect-time profile compared to the plasma concentration-time course. PK/PD-modelling was used to characterize and quantify the pharmacological effect with regard to onset, intensity and duration of effect. Models based on functional data, that discriminate between drug-and system-specific parameters, were developed. In general, the plasma concentration-time course for each individual was approximated by linear interpolation between time-points and served as input into the pharmacodynamic models. A turnover model of irreversible inhibition of gastric acid secretion by omeprazole in the dog described the data well. The model was challenged and found to be robust under different experimental conditions. This model could predict the effect following different exposure of omeprazole and following different histamine provocation. Different fitting approaches (naïve pooling, standard two-stage and nonlinear mixed effects modelling) were compared and resulted in similar parameter estimates. For the reversible inhibitors, a kinetic binding model was finally selected. With a binding model the delay in the effect-time profile is explained by prolonged binding to the enzyme. Use of these results in drug development can be helpful with regard to selection of drugs for further development and to predict the first clinical dose.

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Made available in DSpace on 2014-06-11T19:27:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2006Bitstream added on 2014-06-13T18:31:19Z : No. of bitstreams: 1 guarido_cf_me_botfm.pdf: 383179 bytes, checksum: c08b432bb0b458a9426c62884b0bb43d (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os adenomas hipofisários são lesões relativamente comuns, representando 10 a 15% de todos os tumores intracranianos. Dentre os tumores secretores, os produtores de prolactina (prolactinoma), são os mais freqüentes. O tratamento de escolha é o medicamentoso, que ocorre de modo prolongado e, geralmente múltiplo, elevando, portanto, os riscos de interações medicamentosas (IM), reações adversas a medicamentos (RAM) e outros problemas relacionados com medicamentos (PRM). O objetivo desse estudo foi aplicar a Atenção Farmacêutica no tratamento de pacientes portadores de prolactinomas, para investigar e descrever as possíveis IM, RAM e PRM e auxiliar na orientação farmacoterapêutica e melhorar a qualidade de vida do paciente. Utilizamos a metodologia Dáder para o seguimento farmacoterapêutico e a metodologia de Minessota para a classificação dos PRM. Foram utilizadas as técnicas da análise de variância não-paramétrica para o modelo de medidas repetidas em dois grupos independentes e o teste do qui-quadrado de Mc Neman e Mann-Whitney para comparações dos resultados, com nível de significância de 5%. Observamos diminuição dos custos dos medicamentos, dos níveis séricos de prolactina dos pacientes e da automedicação; houve detecção e resolução de RAM, PRM e IM. Concluímos que o seguimento farmacoterapêutico mediante a aplicação da AF foi útil para o tratamento de portadores de prolactinoma. / Pituitary adenomas are relatively common disorders, representing 10 to 15% of all intracranious tumors. Among the secreting tumors, prolactinomas, which secrete prolactina, are the most frequent ones. The treatment of choice of prolactinoma is clinical and generally involves multiple and long-term pharmacotherapy which may predispose to drug-related problems (DRP) such as drug interactions (DI) or adverse drug reactions (ADR). The objective of this study was to apply Pharmaceutical Care in the pharmacotherapy follow-up of patients with prolactinoma in order to investigate and describe possible DI, ADR and other DRP that could modify the success and insurance of treatment and assist on the pharmacoterapy orientation. We used Dader s methodology to apply Pharmaceutical Care and methodology of Minessota to classify the DRP. For statistical analysis we used non-parametric analysis of variance for repeated measurements in two independent groups and the test of chi-square of Mc Neman and Mann-Whitney for comparisons of the results, with level of significance of 5%. We detected and/or resolved the majority of ADR, DRP and DI and reduced medical-costs, prolactinemia levels and frequency of self-medication practice. We conclude that pharmaceutical care is an important approach to the pharmacotherapy follow-up of patients with prolactinoma.

Class of 2015 Abstract / Objectives: Pharmacists’ level of training and experience in psychiatric pharmacy were compared for: 1) self-perceived preparedness to provide pharmacotherapy services; and 2) perceived barriers to providing services to individuals with psychiatric disorders. Methods: This study used data from an internet-based questionnaire. Respondents were divided into 2 groups: 1) completed the Arizona Pharmacy Association’s Psychiatric Certificate Program, and/or Board Certified in Psychiatric Pharmacy, and/or College of Psychiatric and Neurologic Pharmacists member, and/or completed a PGY2 psychiatric pharmacy residency; and 2) no specialized training/experience in psychiatric pharmacy. A Mann-Whitney U analysis was used to compare the scaled responses for each group. A Bonferroni alpha correction was use in the case of multiple tests. Results: Compared to pharmacists without training/experience in psychiatry (N = 235), respondents with specialized training/experience in psychiatry pharmacy (N = 38) reported more frequent interactions with psychiatric patients and provided more counseling/drug information, monitoring for adverse drug reactions, recommending non-pharmacological treatments, screening for treatment issues, and making therapeutic recommendations (p < 0.05). Trained pharmacists in psychiatry reported being more prepared to provide all pharmacotherapy services (p = 0.003), except in addressing non-adherence, utilizing online resources, and providing pharmacotherapy services to patients with attention deficit-hyperactivity disorder. They reported fewer barriers (α = 0.005) except for time to provide services, having a private consultation area, and reimbursement for patient care activities. Conclusions: This study found that responding pharmacists without psychiatric training/experience may need additional education/training post-graduation and that they perceive more barriers in providing services to this population.