Research around food-derived compounds possessing pharmacological effects and potentially also affecting health status beneficially has during the recent years increased. At the same time, new regulations have been put in place to direct the use of different claims on food products. Distinction between food and drugs needs to be clear and consumers and patients cannot be misled. One of the focus areas in research has been products affecting cardiovascular function. The aim of this licentiate thesis was to find out if already developed high blood pressure can be decreased and endothelial dysfunction improved by bioactive milk-derived tripeptides isoleucine-prolineproline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) and plant sterols in an experimental animal model (spontaneously hypertensive rats, SHR). In addition, one of the aims was to investigate if combining tripeptides and plant sterols could have positive, synergistic effects on the development of hypertension and endothelial dysfunction. As pre-clinical studies precede extensive clinical studies in humans also during the drug development process, some comparison between food-derived substances and blood pressure-lowering drugs was made and interfaces between functional foods and drugs was discussed. This licentiate thesis showed that long-term treatment with fermented milk enriched with tripeptides and plant sterols decreased systolic blood pressure, improved endothelial dysfunction and affected signaling pathways related to inflammatory responses in SHR with already established hypertension. Long-term treatment with plant sterols had only a slight but not significant effect for the development of hypertension. Plant sterols did not provide any beneficial effects on endothelial function in hypertensive rats; however, treatment with both plant sterols and tripeptides showed mild anti-inflammatory effects. To get a better picture of the magnitude of the effect of the studied food-derived substances on blood pressure and vascular function, further studies (either with animals or humans) would benefit from including both food-derived substances and drugs as different treatment arms in the same study. Taken together, there are some similarities between functional foods and drugs what comes to product approval processes or claims made on the products, research and effects on blood pressure, for example, but studying food-derived substances brings several challenges compared to drugs what comes to study set-up and interpretation of the results. However, reflecting on the results of the present studies and available literature, food-derived substances such as tripeptides from milk could be a good alternative for subjects with increased blood pressure who do not yet implicitly need drug treatment and can still try to improve their health status with lifestyle changes, such as nutrition.

This study was conducted in a local context within Lahti City Hospital, Päijät-Häme Central Hospital and Päijät-Häme Joint Authority for Health and Wellbeing. In 2010, the development of clinical pharmacy services was started in the Lahti City Hospital Pharmacy, which merged with Päijät-Häme Central Hospital Pharmacy in 2017, forming Päijät-Häme Joint Authority for Health and Wellbeing Hospital Pharmacy, which continues the development work. This licentiate thesis in hospital pharmacy speicialization describes long-term local service development responding to national health and social services reform, and implementing national policies concerning medicines management services for older people. The aim of this study was to develop the medication management process and related practices to foster rational and safe pharmacotherapy on geriatric wards in the hospital and in home care. Two service development projects in medication reconciliation and review of geriatric patients’ medications on hospital admission (Study I) and utilization of health and functional capacity measures in the monitoring of rational pharmacotherapy in home care (Study II) have been described in detail. The objective of Study I was to develop a procedure and a tool for medication reconciliation and review of geriatric patients’ medications on hospital admission. Action research, with a literature review, and the ward care team as a development team, was employed in the collaborative development process that first identified problems in the then current admission process and, secondly, developed a procedure and a tool. The participants of the study, two physicians, three nurses and two clinical pharmacists, on two geriatric wards in primary care in Lahti were concordant regarding the problems experienced, such as a lack of an up-to-date home medication list in the then current medication process in 2012. To solve these problems, the care team recommended that clinical pharmacists should reconcile and review patients’ medications. The developed and piloted medication reconciliation and review procedure and tool guided the pharmacist to interview the patient, take the medication history, reconcile and review the medication, and make recommendations for possible medication changes. In 2013, the paper-based procedure, the tool and instructions for their use were partly converted to electronic format. Later, a new page was created for the pharmacists’ notes in the electronic medical record. The objective of Study II was to explore, which health and functional capacity measures were used, how the patient-specific information obtained was utilized in the monitoring of pharmacotherapy in older home care clients, and how the use of this information could be enhanced. The study was conducted in home care in two medium-sized cities in southern Finland in 2017. The perceptions of home care physicians (city A: n=3, response rate 60%; city B: n=3, response rate could not be calculated) and nurses (city A: n=50, response rate 21%; city B: n=65, response rate 53%) were investigated by an electronic survey. The perceptions of home care management personnel (city A: n=3 and city B: n=2) by telephone interviews were studied. Of the responding nurses, 70% were practical nurses. The physicians reported that they utilized health status measures at varying degrees to assess the effects of pharmacotherapy in older home care clients. According to the physicians, they regularly used glomerular filtration rate (GFR) measurements, blood pressure, blood glucose and INR measurements. The responding nurses recognized and utilized the Mini-Mental State Exam (MMSE), Mini Nutritional Assessment (MNA), and Body Mass Index (BMI). Of the responding nurses, many performed RAI (Resident Assessment Instrument) or RAVA (Rajala-Vaissi) functional capacity assessments, however, the physicians reported that they used these results seldom. The nurses experienced RAI assessments as quite time consuming but they considered them important in sharing information with the physicians and agreeing on a client’s health condition. According to the interviewed home care managers, RAI assessments were utilized in setting goals for care and rehabilitation plans of home care clients and for monitoring their functional capacity. The home care managers thought RAI assessments were a good way to follow up a client’s condition. In home care, a wide range of measurements are made to assess health status and functional capacity, the use of which could be enhanced in the planning and monitoring of pharmacotherapy. This use of the patient data could be extended to pharmacist-conducted collaborative medication reviews. The long-term local development of hospital pharmacy services in Päijät-Häme demonstrates that hospital pharmacies and pharmacists are increasingly needed in the future to participate collaboratively in managing, coordinating, and developing the medication management process within evolving social and health services.

The number and proportion of elderly people in the population have increased sharply since the late 1900s and the growth will continue. Elderly home care clients have many illnesses and they use many drugs. In order for an older client to be able to live safely at home, the pharmacotherapy process amongst others must work well. This licentiate thesis aimed at evaluating the functionality of the pharmacotherapy services from the point of view of elderly home care clients and their family caregivers. The functionality of the services was evaluated through two main research objectives. The first was to study the equivalence of the medication list in electronic medication records (EMRs) with the medicines actually used by the elderly home care clients. The second was to study what kind of experiences elderly home care clients and their family care givers who managed the medications for their family members have on pharmacotherapy services. The aim of the study was to identify whether the functionality of the services differs depending on who is responsible for managing the medications. Either the client her/himself, the family caregiver or the home care providers can be responsible for managing the medications. According to the literature, these differences between the groups have not been studied previously. This work consisted of both a literature review and an empirical part. According to 26 studies found, medication management process of elderly home care clients involves many safety-impairing factors, such as uncontrolled polypharmacy and problems with the information flow. In addition, discrepancies between recorded drug lists and actual drug use could be found amongst 53- 94 % of home care clients. Different kind of interventions and tools have been developed to improve the safety of pharmacotherapy of elderly home care clients. The empirical part of the work was carried out in the home care of City of Turku. The participants were home care clients aged 65 years or more living in central, suburban or rural areas. Altogether, 17 elderly home care clients and 6 informal caregivers participated in the study, comprising an in-home survey and theme interview. The average age of the clients was 83 years (67-97 v) and they represented three different ways of taking the responsibility for managing the medications: the client her/himself, the family caregiver or the home care providers was responsible for managing the medications. Elderly home care clients and their family caregivers were very satisfied with the home care pharmacotherapy services regardless of the group. The services were considered sufficient for the current functional status. However, safety-impairing factors were also observed in the home care drug management process. The customers used many drugs and the medication lists were not always up to date. Discrepancies were more common among the caregiver –group. However, the differences between the groups were small. With respect to the ability to manage the medication use, the groups showed great variation. In addition, the study revealed that adverse drug reactions were not systematically observed and acted upon in home care. The clients and family care givers had not, in their opinion, received support in the medication management from health care professionals. Family caregivers hoped for more coco-operation with home care. The study showed the need for actions to ensure accurate information on currently used medication. Attention should be paid to the monitoring of adverse drug reactions and optimizing the medications in the home care and further training should be offered for nurses. Elderly home care clients are a very heterogeneous group for physical and cognitive function and, therefore, pharmacotherapy services and drug information for elderly home care clients should be tailored individually listening their opinion and, if needed their relatives.

This thesis describes current and past n-in-one methods and presents three early experimental studies using mass spectrometry and the triple quadrupole instrument on the application of n-in-one in drug discovery. N-in-one strategy pools and mix samples in drug discovery prior to measurement or analysis. This allows the most promising compounds to be rapidly identified and then analysed. Nowadays properties of drugs are characterised earlier and in parallel with pharmacological efficacy. Studies presented here use in vitro methods as caco-2 cells and immobilized artificial membrane chromatography for drug absorption and lipophilicity measurements. The high sensitivity and selectivity of liquid chromatography mass spectrometry are especially important for new analytical methods using n-in-one. In the first study, the fragmentation patterns of ten nitrophenoxy benzoate compounds, serial homology, were characterised and the presence of the compounds was determined in a combinatorial library. The influence of one or two nitro substituents and the alkyl chain length of methyl to pentyl on collision-induced fragmentation was studied, and interesting structurefragmentation relationships were detected. Two nitro group compounds increased fragmentation compared to one nitro group, whereas less fragmentation was noted in molecules with a longer alkyl chain. The most abundant product ions were nitrophenoxy ions, which were also tested in the precursor ion screening of the combinatorial library. In the second study, the immobilized artificial membrane chromatographic method was transferred from ultraviolet detection to mass spectrometric analysis and a new method was developed. Mass spectra were scanned and the chromatographic retention of compounds was analysed using extract ion chromatograms. When changing detectors and buffers and including n-in-one in the method, the results showed good correlation. Finally, the results demonstrated that mass spectrometric detection with gradient elution can provide a rapid and convenient n-in-one method for ranking the lipophilic properties of several structurally diverse compounds simultaneously. In the final study, a new method was developed for caco-2 samples. Compounds were separated by liquid chromatography and quantified by selected reaction monitoring using mass spectrometry. This method was used for caco-2 samples, where absorption of ten chemically and physiologically different compounds was screened using both single and nin- one approaches. These three studies used mass spectrometry for compound identification, method transfer and quantitation in the area of mixture analysis. Different mass spectrometric scanning modes for the triple quadrupole instrument were used in each method. Early drug discovery with n-in-one is area where mass spectrometric analysis, its possibilities and proper use, is especially important.