Acute Kidney Injury and Electrolyte Imbalances Caused by Dapagliflozin Short-Term Use.

Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), has shown demonstrated benefits for renal and cardiovascular outcomes in large clinical trials. However, short-term concerns regarding its impact on renal function and electrolyte balance exist. This study aimed to evaluate the short-term effects of dapagliflozin on renal function and electrolyte balance in patients newly prescribed the medication. A retrospective analysis of 246 patients who initiated dapagliflozin therapy was conducted. Serum creatinine, sodium, and potassium levels were measured at baseline (before dapagliflozin) and 5-8 days after initiation (endpoint). A Wilcoxon signed-rank test, Pearson's chi-square test, and Fischer's exact test were used for the data analysis. Glycemia and sodium levels were significantly higher at the baseline compared to the endpoint (p < 0.001). Conversely, creatinine and potassium levels were significantly higher at the endpoint than at the baseline (p < 0.001). The prevalence of hyponatremia and hyperkalemia were increased at the endpoint (17.5% vs. 10.2% and 16.7% vs. 8.9%, respectively). Although not statistically significant, a trend towards increased hyponatremia with the co-administration of furosemide was observed (p = 0.089). No significant association was found between potassium-sparing medications (p > 0.05) and hyperkalemia, except for angiotensin receptor blockers (p = 0.017). The combination of dapagliflozin and furosemide significantly increased the risk of acute kidney injury (AKI) at the endpoint (p = 0.006). Age, gender, and chronic kidney disease status did not significantly influence the occurrence of AKI, hyponatremia, or hyperkalemia (p > 0.05). These findings emphasize the importance of the close monitoring of renal function and electrolyte balance, particularly in the early stages of dapagliflozin therapy, especially in patients receiving diuretics or renin-angiotensin-aldosterone system inhibitors.

Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle.

Vascular smooth muscle tone is controlled by a balance between the cellular signaling pathways that mediate the generation of force (vasoconstriction) and release of force (vasodilation). The initiation of force is associated with increases in intracellular calcium concentrations, activation of myosin light-chain kinase, increases in the phosphorylation of the regulatory myosin light chains, and actin-myosin crossbridge cycling. There are, however, several signaling pathways modulating Ca(2+) mobilization and Ca(2+) sensitivity of the contractile machinery that secondarily regulate the contractile response of vascular smooth muscle to receptor agonists. Among these regulatory mechanisms involved in the physiological regulation of vascular tone are the cyclic nucleotides (cAMP and cGMP), which are considered the main messengers that mediate vasodilation under physiological conditions. At least four distinct mechanisms are currently thought to be involved in the vasodilator effect of cyclic nucleotides and their dependent protein kinases: (1) the decrease in cytosolic calcium concentration ([Ca(2+)]c), (2) the hyperpolarization of the smooth muscle cell membrane potential, (3) the reduction in the sensitivity of the contractile machinery by decreasing the [Ca(2+)]c sensitivity of myosin light-chain phosphorylation, and (4) the reduction in the sensitivity of the contractile machinery by uncoupling contraction from myosin light-chain phosphorylation. This review focuses on each of these mechanisms involved in cyclic nucleotide-dependent relaxation of vascular smooth muscle under physiological conditions.

Clinical and Pharmacotherapeutic Profile of Patients with Type 2 Diabetes Mellitus Admitted to a Hospital Emergency Department.

Type 2 diabetes mellitus (T2DM) is closely associated with other pathologies, which may require complex therapeutic approaches. We aim to characterize the clinical and pharmacological profile of T2DM patients admitted to an emergency department. Patients aged ≥65 years and who were already using at least one antidiabetic drug were included in this analysis. Blood glycemia, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hemoglobin were analyzed for each patient, as well as personal pathological history, diagnosis(s) at admission, and antidiabetic drugs used before. Outcome variables were analyzed using Pearson's Chi-Square, Fisher's exact test, and linear regression test. In total, 420 patients were randomly selected (48.6% male and 51.4% female). Patients with family support showed a lower incidence of high glycemia at admission (p = 0.016). Higher blood creatinine levels were associated with higher blood glycemia (p = 0.005), and hyperuricemia (HU) (p = 0.001), as well as HU, was associated with a higher incidence of acute cardiovascular diseases (ACD) (p = 0.007). Hemoglobin levels are lower with age (p = 0.0001), creatinine (p = 0.009), and female gender (p = 0.03). The lower the AST/ALT ratio, the higher the glycemia at admission (p < 0.0001). Obese patients with (p = 0.021) or without (p = 0.027) concomitant dyslipidemia had a higher incidence of ACD. Insulin (p = 0.003) and glucagon-like peptide-1 agonists (GLP1 RA) (p = 0.023) were associated with a higher incidence of decompensated heart failure, while sulfonylureas (p = 0.009), metformin-associated with dipeptidyl peptidase-4 inhibitors (DPP4i) (p = 0.029) or to a sulfonylurea (p = 0.003) with a lower incidence. Metformin, in monotherapy or associated with DPP4i, was associated with a lower incidence of acute kidney injury (p = 0.017) or acute chronic kidney injury (p = 0.014). SGLT2i monotherapy (p = 0.0003), associated with metformin (p = 0.026) or with DPP4i (p = 0.007), as well as insulin and sulfonylurea association (p = 0.026), were associated with hydroelectrolytic disorders, unlike GLP1 RA (p = 0.017), DPP4i associated with insulin (p = 0.034) or with a GLP1 RA (p = 0.003). Insulin was mainly used by autonomous and institutionalized patients (p = 0.0008), while metformin (p = 0.003) and GLP1 RA (p < 0.0001) were used by autonomous patients. Sulfonylureas were mostly used by male patients (p = 0.027), while SGLT2 (p = 0.0004) and GLP1 RA (p < 0.0001) were mostly used by patients within the age group 65-85 years. Sulfonylureas (p = 0.008), insulin associated with metformin (p = 0.040) or with a sulfonylurea (p = 0.048), as well as DPP4i and sulfonylurea association (p = 0.031), were associated with higher blood glycemia. T2DM patients are characterized by great heterogeneity from a clinical point of view presenting with several associated comorbidities, so the pharmacotherapeutic approach must consider all aspects that may affect disease progression.

Peripheral Neuropathy Potentially Associated to Poly (ADP-Ribose) Polymerase Inhibitors: An Analysis of the Eudravigilance Database.

Poly (ADP-Ribose) polymerase inhibitors (PARPi) have emerged as a targeted therapy in cancer treatment with promising results in various types of cancer. This work aims to investigate the profile of adverse drug reactions (ADRs) associated with PARPi through the reports provided by the Eudravigilance (EV) database. We also intend to analyze the potential association of peripheral neuropathy to PARPi. Data on individual case safety reports (ICSRs) were obtained by accessing the European spontaneous reporting system via the EV website. A total of 12,762 ICSRs were collected from the EV database. Serious cases of nervous system disorders were analyzed providing strong evidence that peripheral neuropathy was reported in a higher frequency in patients treated with niraparib. Most cases reported a not recovered/not resolved outcome and involved drug withdrawal. However, several studies suggest that PARPi attenuate chemotherapy-induced painful neuropathy. Unexpected ADRs such as peripheral neuropathy may also occur, mostly in patients taking niraparib. Further pharmacovigilance studies should be conducted in this area to clarify with more precision the toxicity profile of these drugs.

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database.

BACKGROUND: Semaglutide is a Glucagon-like peptide-1 receptor agonist used in the second-line treatment of poorly controlled type 2 diabetes and can be used in monotherapy or associated with other oral antidiabetics or even insulin, increasing the effectiveness of the treatment. This work aims to analyze the profile of adverse drug reactions reported for semaglutide in Eudravigilance. RESEARCH DESIGN AND METHODS: Data on Individual Cases Safety Reports were obtained from the database of the centralized European spontaneous reporting system Eudravigilance by accessing www.adrreports.eu. (1 December 2021). RESULTS: It is possible to observe a high prevalence of gastrointestinal disorders (N = 3502, 53.2%). The most severe reported cases were primarily gastrointestinal disorders, metabolic, and nutritional disorders, eye disorders, renal and urinary disorders and cardiac disorders, with an evident higher prevalence of adverse gastrointestinal events both in oral and injectable dosage form (N = 133, 50.0% vs N = 588, 47.2%, respectively). Through a comparative analysis, semaglutide had a greater number of reported gastrointestinal adverse events compared to sitagliptin and empaglifozin (p < 0.00001). CONCLUSIONS: Semaglutide has a good safety profile, however the definition of subgroups within the type 2 diabetes population who are particularly prone to develop serious adverse event when treated with GLP-1 RAs is crucial.

Hematological Events Potentially Associated with CDK4/6 Inhibitors: An Analysis from the European Spontaneous Adverse Event Reporting System.

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are a recent targeted therapy approved for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. Abemaciclib, palbociclib and ribociclib demonstrated great efficacy and safety during clinical studies. However, differences in their adverse-event profiles have been observed. This work aims to describe the suspected adverse drug reactions (ADRs), such as leukopenia and thrombocytopenia, reported for each CDK4/6 inhibitor in the EudraVigilance (EV) database. Data on individual case safety reports (ICSRs) were obtained by accessing the European spontaneous reporting system via the EV website. Information on concomitant drug therapy, including fulvestrant, letrozole, anastrozole and exemestane, was also analyzed. A total of 1611 ICSRs were collected from the EV database. Most reports of palbociclib and ribociclib were classified as serious cases for both suspected leukopenia and thrombocytopenia ADRs. However, most patients had their leukopenia and thrombocytopenia recovered/resolved. On the contrary, reports of abemaciclib were mostly characterized as non-serious cases. Abemaciclib and palbociclib were often combined with fulvestrant, while ribociclib was generally associated with letrozole. Pharmacovigilance studies are crucial for the early identification of potential ADRs and to better differentiate the toxicity profile of the different CDK4/6 inhibitors, particularly in a real-world setting.

Active Pharmacovigilance Study: A Follow-Up Model of Oral Anti-Cancer Drugs under Additional Monitoring.

Adverse drug reactions (ADRs) are responsible for almost 5% of hospital admissions, making it necessary to implement different pharmacovigilance strategies. The additional monitoring (AM) concept has been highlighted and intended to increase the number of suspected ADRs reported, namely in medicines with limited safety data. A prospective, descriptive study of active pharmacovigilance (AP) was conducted between 2019 and 2021 in the Local Health Unit of Matosinhos (LHUM) (Porto, Portugal). A model of AP for medicines under AM, namely oral antineoplastic agents, was designed. Follow-up consultations were performed, and adverse events (AEs) data were collected. The overall response to the treatment was evaluated through the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. A total of 52 patients were included in the study, and 14 antineoplastic drugs under AM were analyzed. Of the total number of patients included, only 29 developed at least one type of toxicity. Hematological disorders were the most reported suspected ADR. However, only four patients interrupted their treatment due to toxicity. After 12 months of treatment, most patients had disease progression, which was the main reason for therapy discontinuation. This AP model played an important role in the early detection of AEs and, consequently, contributed to better management of them. Increasing the number of suspected ADR reports is crucial for drugs with limited safety data.

PARP inhibitors: clinical relevance and the role of multidisciplinary cancer teams on drug safety.

INTRODUCTION: Cancer is considered one of the most devastating causes of death for humanity. Innovative and targeted therapies have become urgent in the treatment of this large subset of diseases. Over the last decade, the development of PARP (poly (ADP-Ribose) polymerase) inhibitors has emerged as a new target in cancer therapy. AREAS COVERED: The authors conducted a review focusing on the clinic relevance and adverse effects of the four drugs already approved by drug regulatory agencies, namely: olaparib, rucaparib, niraparib and talazoparib. Despite the targeted action of this drug class, the adverse effects should be carefully monitored for the adequate safety of cancer patients taking them. The role of multidisciplinary cancer teams is crucial to help more and more patients to benefit from these revolutionary agents. EXPERT OPINION: PARP (poly (ADP-Ribose) polymerase) inhibitors are drugs with great potential in the treatment of several types of cancer. However, their toxicity profiles often lead to treatment interruption or early discontinuation. The daily monitoring of these cancer patients by multidisciplinary cancer teams is essential for the success of therapy and for the promotion of a better quality of life.

Trends and Geographic Variabilities in Benzodiazepines Prescription in Primary Care to Older Adults: A 3-Year Population-Based Ecological Study in Portugal.

(1) Background: According to the World Health Organization (WHO), benzodiazepines (BZD) are considered essential medicines for the treatment of several mental disorders in older adults over 65 years old. However, the long-term use of BZD could present a harmful impact on this population, leading to cognitive deficits, drug dependence, falls, and fractures. This study aims to analyze trends of BZD prescription to Portuguese older adults in the primary care setting, and to analyze the change in the prescription rate of BZD over time, assessing the geographical variability in mainland Portugal. (2) Methods: A nationwide, retrospective ecological study was performed between January 2019 and December 2021 for BZD prescribing data reported in a national public database for all persons aged 65 and older in mainland Portugal (about 2.4 million). Trends of BZD by defined daily doses (DDD) and per 1000 older adults' inhabitants per day (DID) were analyzed. (3) Results: A total of 19 BZD were included in this study and more than 1 million BZD prescriptions were recorded in each year of this study period. BZD prescriptions were three times higher in females than in males. Alprazolam, lorazepam, diazepam, ethyl loflazepate, and bromazepam were the most prescribed BZD over the years, presenting the higher DDD and DID values. (4) Conclusions: Despite the DID value growth of several BZD, Portugal is now showing stable BZD prescriptions in older adults, between the years 2019 to 2021. More studies are needed to access if these results are a consequence of successful health programs or just a consequence of the pandemic context that we are facing, which limited older adults' clinical appointments.

Behavioral Sciences in the Optimization of Pharmacological and Non-Pharmacological Therapy for Type 2 Diabetes.

Type 2 diabetes mellitus is one of the main chronic diseases worldwide, with a significant impact on public health. Behavioral changes are an important step in disease prevention and management, so the way in which individuals adapt their lifestyle to new circumstances will undoubtedly be a predictor of the success of the treatments instituted, contributing to a reduction in the morbidity and mortality that may be associated with them. It is essential to prepare and educate all diabetic patients on the importance of changing behavioral patterns in relation to the disease, with health professionals assuming an extremely important role in this area, both from a pharmacological and non-pharmacological point of view, and also ensuring the monitoring of the progress of these measures. Diabetes is a chronic disease that requires a high self-management capacity on the part of patients in order to achieve success in treating the disease, and non-adherence to therapy or non-compliance with the previously defined plan, together with an erratic lifestyle, will contribute to failure in controlling the disease. The lower adherence to pharmacological and non-pharmacological treatment in diabetes is mainly correlated to socio-economic aspects, lower health literacy, the side effects associated with the use of antidiabetic therapy or even the concomitant use of several drugs. This article consists of a narrative review that aims to synthesize the findings published in the literature, retrieved by searching databases, manuals, previously published scientific articles and official texts, following the methodology of the Scale for Assessment of Narrative Review Articles (SANRA). We aim to address the importance of behavioral sciences in the treatment of diabetes, in order to assess behavior factors and barriers for behavior changes that have an impact on the therapeutic and non-therapeutic optimization in patients with type 2 diabetes mellitus control.

Acceptance of Pharmaceutical Services by Home-Dwelling Older Patients: A Case Study in a Portuguese Community Pharmacy.

BACKGROUND: Aging-related comorbidities predispose older adults to polypharmacy and consequently an increased risk of adverse drug reactions and poor compliance. Pharmacists' interventions can have a beneficial impact on the improvement of clinical outcomes. Thus, this work aimed to assess the acceptance of Portuguese home-dwelling older adults regarding a pharmaceutical service paid by patients for medication management and pharmacotherapy follow-up. We also intended to analyze medication, characterize the medication consumption profile, and identify the main difficulties of our sample during their daily medication management. METHODS: A questionnaire on adherence and medication therapy management was applied to polymedicated patients ≥65 years old, in a community pharmacy. RESULTS: Of the 88 participants, 92.2% would be willing to pay for a pharmacotherapy management service, and 75.6% answered that they would be willing to pay for an individual medication preparation service. In addition, 45.7% of the participants were categorized as lower adherents to a medication therapeutic regimen. Our sample reported that during their daily lives, they felt difficulty: to remember to take their pills (17%), to manage so many medicines (15.9%), and to swallow the pills (9.1%). CONCLUSIONS: Polymedicated older adults are willing to pay for a service to improve the management of their medicines, suggesting that they recognize the role of pharmacists in medication management. This study provides useful information for the conceptualization of a pharmacotherapy management service that includes medication review and a pharmacotherapy follow-up.

Allergic rhinitis characterization in community pharmacy customers: a cross-sectional study.

Background Allergic rhinitis represents a public health problem that is significantly prevalent in the global population and has been associated with asthma, a strong desire to sleep and a low quality of life. Objective This study aims to evaluate the prevalence, symptoms, control strategies and treatment, as well as the control of this condition and its impact on the quality of life of customers of community pharmacies with allergic rhinitis. Setting A questionnaire survey was carried out in nine community pharmacies in the city of Guarda, Portugal. Method In this cross-sectional study, data was collected by an interview between May 2014 and December 2014. The control of the illness and the impact of allergic rhinitis on the quality of life were assessed through a CARAT10 test and a WHOQOL-BREF instrument, respectively. Main outcome measure The impact of allergic rhinitis on the patient's quality of life. Results The estimated prevalence of allergic rhinitis was between 10.8% and 15.4%, from which 63 and 42 individuals were medically and symptomatically diagnosed, respectively, from a study population of 804 respondents. The majority of participants (57.1%) suffered from the symptoms more than twice a year. The symptoms, such as difficulty in falling asleep, repeated and continuous sneezing and bilateral nasal obstruction, were severe. There were patients with uncontrolled allergic rhinitis symptoms after the CARAT10 test, even when the individual's perception of the quality of life was good according to the WHOQOL-BREF score, with gender differences in the psychological domain. It should also be emphasized that there was a significant association between higher education levels with better control of the illness/quality of life. Additionally, most participants used pharmacological treatment (not alternative therapies) and the adoption of self-management measures to relieve their symptoms. Conclusions The findings of this study showed that the estimated prevalence of allergic rhinitis seems to be apparently lower in Guarda than that found in the general Portuguese population. From the data, some patients showed uncontrolled allergic rhinitis symptoms, strengthening the importance of the role of intervention by a health professional.

Blood pressure control and antihypertensive pharmacotherapy patterns in a hypertensive population of Eastern Central Region of Portugal.

BACKGROUND: Interventions to improve blood pressure control in hypertension have had limited success in clinical practice despite evidence of cardiovascular disease prevention in randomised controlled trials.The objectives of this study were to evaluate blood pressure control and antihypertensive pharmacotherapy patterns in a population of Eastern Central Region of Portugal, attending a hospital outpatient clinic (ambulatory setting) for routine follow-up. METHODS: Medical data of all patients that attended at least two medical appointments of hypertension/dyslipidemia in a university hospital over a one and a half year period (from January 2008 to June 2009) were retrospectively analysed. Demographic variables, clinical data and blood pressure values of hypertensive patients included in the study, as well as prescribing metrics were examined on a descriptive basis and expressed as the mean ± SD, frequency and percentages. Student's test and Mann-Whitney rank sum test were used to compare continuous variables and χ2 test and Fisher exact probability test were used to test for differences between categorical variables. RESULTS: In all, 37% of hypertensive patients (n = 76) had their blood pressure controlled according to international guidelines. About 45.5% of patients with a target blood pressure <140/90 mmHg (n = 156) were controlled, whereas in patients with diabetes or chronic kidney disease (n = 49) the corresponding figure was only 10.2% (P < 0.001). Among patients initiating hypertension/dyslipidemia consultation within the study period 32.1% had stage 2 hypertension in the first appointment, but this figure decreased to 3.6% in the last consultation (P = 0.012). Thiazide-type diuretics were the most prescribed antihypertensive drugs (67%) followed by angiotensin receptor blockers (60%) and beta-blockers (43%). About 95.9% patients with comorbid diabetes were treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. CONCLUSIONS: Clinically important blood pressure decreases can be achieved soon after hypertension medical appointment initiation. However, many hypertensive patients prescribed with antihypertensive therapy fail to achieve blood pressure control in clinical practice, this control being worse among patients with diabetes or chronic kidney disease. As pharmacotherapy patterns seem to coincide with international guidelines, further research is needed to identify the causes of poor blood pressure control.

Management of the Adverse Effects of Immune Checkpoint Inhibitors.

By increasing the activity of the immune system, immune checkpoint inhibitors (ICPI) can have adverse inflammatory effects, which are referred to as immune-related adverse effects (irAEs). In this review, we present the recommendations for the appropriate identification and treatment of irAEs associated with ICPI to increase the safety and effectiveness of therapy with these immuno-oncological drugs. Several guidelines to manage irAEs adopted by different American and European societies in the field of oncology were identified. A narrative review of the several strategies adopted to manage irAEs was performed. With close clinical surveillance, ICPI can be used even in patients who have mild irAEs. Moderate to severe events require early detection and appropriate treatment, particularly in patients with a history of transplantation or pre-existing autoimmune disease. In most cases, adverse reactions can be treated with the interruption of treatment and/or supportive therapy, which includes, in serious adverse reactions, the administration of immunosuppressants. The identification and treatment of irAEs in the early stages may allow patients to resume therapy with ICPI. This review is an instrument to support healthcare professionals involved in the treatment and monitoring of patients who are administered ICPI, contributing to the timely identification and management of irAEs.

Drug-related Problems in Home-dwelling Older Adults: A Systematic Review.

PURPOSE: The complex combination of medicines associated with age-related physiological alterations leads older adults to experience drug-related problems (DRPs). The goal of this study was to review the frequency and type of DRPs and DRP risk factors in home-dwelling older adults. METHODS: A MEDLINE PubMed and EMBASE scientific databases search was performed. Articles published from January 2000 through December 2018 reporting DRPs in home-dwelling older adults were included. FINDINGS: From 668 articles screened, 13 met the inclusion criteria and were included in this study. Overall, the studies included 8935 home-dwelling patients. The mean number of DRPs per patient observed was 4.16 (1.37-10). The main causes of DRPs were "drug selection" (51.41%), "dose selection" (11.62%), and "patient related" (10.70%) problems. The drug classes more frequently associated with DRPs were "cardiovascular system," "alimentary tract and metabolism," and "nervous system," and they represented 32.1%, 29.4%, and 16.5% of all drug selection problems, respectively. Respiratory system medicines accounted for 6.65% of all DRPs, of which "patient related" problems accounted for 97.28%. IMPLICATIONS: Despite the heterogeneity of methodology of the included studies and the heterogeneity of tools used to identify DRPs, this analysis clearly shows the high prevalence of DRPs in home-dwelling older adults and highlights the need for interventions to improve medicine use in this population. This work also provides useful information for the development of strategies to improve medication use in home-dwelling older adults.

Clinical pharmacists´ interventions in the management of type 2 diabetes mellitus: a systematic review.

BACKGROUND: Type 2 diabetes mellitus is a chronic disease that is reaching epidemic proportions worldwide. It is imperative to adopt an integrated strategy, which involves a close collaboration between the patient and a multidisciplinary team of which pharmacists should be integral elements. OBJECTIVE: This work aims to identify and summarize the main effects of interventions carried out by clinical pharmacists in the management of patients with type 2 diabetes, considering clinical, humanistic and economic outcomes. METHODS: PubMed and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials assessing the effectiveness of such interventions compared with usual care that took place in hospitals or outpatient facilities. RESULTS: This review included 39 studies, involving a total of 5,474 participants. Beneficial effects were observed on various clinical outcomes such as glycemia, blood pressure, lipid profile, body mass index and coronary heart disease risk. For the following parameters, the range for the difference in change from baseline to final follow-up between the intervention and control groups was: HbA1c, -0.05% to -2.1%; systolic blood pressure, +3.45 mmHg to -10.6 mmHg; total cholesterol, +10.06 mg/dL to -32.48 mg/dL; body mass index, +0.6 kg/m2 to -1.94 kg/m2; and coronary heart disease risk, -3.0% and -12.0% (among the studies that used Framinghan prediction method). The effect on medication adherence and health-related quality of life was also positive. In the studies that performed an economic evaluation, the interventions proved to be economically viable. CONCLUSIONS: These findings support and encourage the integration of clinical pharmacists into multidisciplinary teams, underlining their role in improving the management of type 2 diabetes.

Daily Medication Management and Adherence in the Polymedicated Elderly: A Cross-Sectional Study in Portugal.

The presence of age-related comorbidities prone elderly patients to the phenomenon of polypharmacy and consequently to a higher risk of nonadherence. Thus, this paper aims to characterize the medication consumption profile and explore the relationship of beliefs and daily medication management on medication adherence by home-dwelling polymedicated elderly people. A questionnaire on adherence, managing, and beliefs of medicines was applied to polymedicated patients with ≥65 years old, in primary care centers of the central region of Portugal. Of the 1089 participants, 47.7% were considered nonadherent. Forgetfulness (38.8%), difficulties in managing medication (14.3%), concerns with side effects (10.7%), and the price of medication (9.2%) were pointed as relevant medication nonadherence-related factors. It was observed that patients who had difficulties managing medicines, common forgetfulness, concerns with side effects, doubting the need for the medication, considered prices expensive, and had a lack of trust for some medicines had a higher risk of being nonadherent. This study provides relevant information concerning the daily routine and management of medicines that can be useful to the development of educational strategies to promote health literacy and improve medication adherence in polymedicated home-dwelling elderly.

PDE4 and PDE5 regulate cyclic nucleotides relaxing effects in human umbilical arteries.

Cyclic nucleotides (cAMP and cGMP) are the main second messengers linked to vasodilatation. They are synthesized by cyclases and degraded by different types of phosphodiesterases (PDE). The effect of PDE inhibition and cyclases stimulation on 5-hydroxytryptamine (5-HT; 1 microM) and histamine (10 microM) contracted arteries was analysed. Stimulation of guanylate cyclase or adenylate cyclase relaxed the histamine- and 5-HT-induced contractions indicating that intracellular increase of cyclic nucleotides leads to vasodilatation of the human umbilical artery. We investigated the role of different PDE families in the regulation of this effect. The presence of the different PDE types in human umbilical artery smooth muscle was analysed by RT-PCR and the expression of PDE1B, PDE3A, PDE3B, PDE4C, PDE4D and PDE5A was detected. The unspecific PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX; 50 microM) relaxed histamine-contracted human umbilical artery on 47.4+/-7.2%. This effect seems to be due to PDE4 and PDE5 inhibition because among the selective PDE inhibitors used only the PDE4 inhibitor (rolipram; 1 microM) and the PDE5 inhibitors (dipyridamole and T0156; 3 microM and 1 microM respectively) induced significant relaxation (39.0+/-8.7, 30.4+/-6.0 and 36.3+/-2.8 respectively). IBMX, dipyridamole and T0156 produced similar relaxation on 5-HT-induced contraction. After forskolin, the addition of IBMX or rolipram increased the effect of the adenylate cyclase stimulator and almost completely relaxed the human umbilical artery contracted by histamine (92.5+/-4.9 and 90.9+/-4.7 respectively), suggesting a main role of PDE4. The data obtained with 5-HT contracted arteries confirmed this, because only rolipram and IBMX significantly increased the forskolin vasodilator effect. The administration of dipyridamole and T0156 after sodium nitroprusside (SNP) induced a significant increase of the SNP relaxant effect on histamine-contracted arteries, but PDE1 and PDE3 inhibition did not increase the effect of the guanylate cyclase stimulator. Similar effects were obtained in 5-HT contracted arteries, the SNP induced relaxation was increased by the PDE5 inhibition, but not by PDE1 or PDE3 inhibition. In summary, our results demonstrate that: 1) the increase of cAMP and/or cGMP levels induces relaxation of the human umbilical vascular smooth muscle; 2) four families of PDE are expressed in this smooth muscle: PDE1, PDE3, PDE4 and PDE5; 3) between these families, PDE4 and PDE5 are the key enzymes involved in the regulation of the relaxation associated to cAMP and cGMP, respectively.

Arbutus unedo L.: From traditional medicine to potential uses in modern pharmacotherapy.

ETHNOPHARMACOLOGICAL RELEVANCE: Arbutus unedo L., the strawberry tree (Ericaceae family) is of increasing interest because of its common traditional, industrial, chemical and pharmaceutical uses. The plant is a typical evergreen plant of the Mediterranean basin, as well as of other regions with hot summers and mild rainy winters. This review covers the studies relevant to Arbutus unedo L. utilization in the current pharmacological therapy. MATERIALS AND METHODS: The available information on traditional uses, phytochemistry and biological activities of Arbutus unedo L. was collected from scientific databases through a search using the keywords 'Arbutus unedo L.' and/or 'strawberry tree' in 'Google Scholar', 'Pubmed', 'Sciencedirect', 'SpringerLink', 'Web of Science - Clarivate Analytics' and 'Wiley'. Unpublished Ph.D. and M.Sc. dissertations were also consulted for chemical composition, biological activities and traditional uses of Arbutus unedo L. and for manual search of additional references. RESULTS: The fruits of the plant have been traditionally used as antiseptics, diuretics and laxatives in folk medicine, while the leaves have been used due to their diuretic, urinary antiseptic, antidiarrheal, astringent, depurative and antihypertensive properties. According to the scientific literature survey, different extracts obtained from Arbutus unedo L. have demonstrated a high pharmacological potential due to their in vitro and preclinical antibiotic, antifungal, antiparasitic, antiaggregant, antidiabetic, antihypertensive, anti-inflammatory, antitumoral, antioxidant, and spasmolytic properties. CONCLUSION: This review suggests that A. unedo is a promising source of phytopharmaceutical products. The potential advantages of Arbutus unedo are related with the presence of polyphenolic compounds in its composition. However, further studies are needed to ascertain some profitable effects in humans. The beneficial effects associated with this shrub suggest that Arbutus unedo can be used for the development of new drugs to treat diseases such diabetes, hypertension, among others. Nonetheless, the safety of the Arbutus unedo compounds should also be examined.