Background: The increased use of medicines in recent decades has affected the environmentand led to negative consequences. Environmental risk for a drug can be classified by using PBTindex and PEC / PNEC-ratio. Environmental risk information can be found on the knowledgesupport websites "medicines and the environment" at Janusinfo.se and in environmentalinformation at Fass.se. The Drug- and Therapeutics Committees (DTCs) ensure that medicinesare used in a correct and cost-effective manner and recommend medicines in annually updatedguidelines. Method: A survey was created and pilot-tested by 10 persons experienced from DTCs. Thequestionnaire consisted of four parts, general questions, questions about the use of theknowledge support "medicines and the environment" on janusinfo, questions about the use ofenvironmental information from Fass.se and other questions about environmental aspects. Result: In total, 9 out of 10 people who were included in the pilot study answered. Threerespondents had only positive feedback on the questionnaires. Some respondents thought thatthere were some questions and answers’ options that were not easy to understand and that somequestions could be answered only by people familiar with the subject.Conclusions: The conclusion is that the pilot study has led to many improvements in surveyquestions and approaches. In the future, further research is needed for knowledge about drugeffects in the environment.

Background:  Generic substitution has resulted in large economical savings for prescription drugs, but there is concern about potential negative consequences such as double medication, altered effect and poor compliance. Such problems would be worst among the elderly since they use many drugs, some have impaired cognitive function and a higher risk of serious consequences. Objective: The purpose of this study is to assess if there are any negative consequences of genetic changes in the elderly. Method: The study was a systematic review where data from scientific articles were collected from the PubMed database. A search strategy was developed using MeSH terms and keywords. The work was carried out according to the PRISMA guidelines for systematic review. A total of 232 papers were screened and 5 papers remained fulfilling inclusion and exclusion critera. Results: Two studies show that generic substitution has no effect on patient compliance. One study on antiepiletics showdes that patients experienced different effects and new side effects after switching to generic drugs. However there was no association between switching and seizure related hospital visits. In another study, the results showed no association between hospitalization and generic substitution Conclusion: There are few studies on the consequences of generic substitution in elderly. Current studies indicate that generic substitution has no effect on the patient's compliance, it may  cause some confusion and anxiety in certain groups, but no increase in hospital admissions been found.

No description available.

Lorcaserin represents a new serotonergic medication used as an adjunct to a reduced-calorie diet and increased physical activity treatment plan for chronic weight management in adult patients with an initial body mass index ≥ 30 kg/m 2 or in adult patients with an initial body mass index ≥ 27 kg/m 2 who have ≥ 1 comorbid condition associated with weight (eg, hypertension, dyslipidemia, or type 2 diabetes mellitus). In 2012, lorcaserin became the first obesity treatment medication to gain US Food and Drug Administration (FDA) approval since 1999. Lorcaserin is a centrally acting, selective serotonin C (5-HT2C) receptor full agonist that is associated with increased satiety and decreased food consumption in patients. The selectivity of lorcaserin for 5-HT2C receptors should reduce patient risk for the serious adverse complications that are associated with nonselective 5-HT agonist therapies, such as cardiac valvulopathy and pulmonary hypertension. The safety and efficacy of lorcaserin (10 mg twice daily) for ≥ 52 weeks has been evaluated in 3 separate Phase 3 trials. The primary outcome of patient weight loss in the 3 trials satisfied the FDA categorical benchmark but patient outcomes in the trials failed to achieve the FDA mean benchmark of patient weight loss. Secondary patient outcomes after lorcaserin therapy were favorable. Lorcaserin appears to be well tolerated in patients and the most common adverse events reported did not include serious complications. The incidence of FDA-defined valvulopathy in patients after 1 year of treatment was low and nonsignificant, but the statistical analysis of this safety endpoint was limited due to the small size of the study populations and high patient dropout rates. Continued post-marketing surveillance of patients taking lorcaserin is warranted.

In human rehabilitation medicine, dexamethasone-phosphate is theoretically iontophoresed to localized subcutaneous tissue where conversion to dexamethasone occurs. This delivery system has recently been introduced into veterinary medicine for the same purpose. However, the pharmacokinetic justification for parenteral delivery of this prodrug remains undocumented. Utilizing iontophoretic methods that are relevant to both human and veterinary clinical practice, the present investigation compared injection and iontophoresis of dexamethasone-phosphate into the equine tibiotarsal joint, also known as the tarsocrual joint. The tibiotarsal joints of seven horses were injected with 4 mL of 6 mg/mL dexamethasone-phosphate. With a similar drug concentration and over the same application site, six different horses underwent simultaneous cathodic iontophoresis (4 mA, 40 min) or passive application (0 mA, 40 min) on contralateral limbs. Following all applications, tibiotarsal joint synovium was collected. Local venous blood samples were also collected from the iontophoretic and passive application sites for analysis of plasma drug concentrations. Because of the potential for conversion of dexamethasone-phosphate to dexamethasone, an extraction and analysis protocol was developed for both chemicals. The technique demonstrated a linear range of detection (0.39-12 μg/mL) and a capability for measuring both chemicals in plasma and synovium. Conversion of dexamethasone-phosphate to dexamethasone occurred during synovial incubation (37 °C) and following freeze-thaw cycles. In contrast to the measurable synovial concentrations of dexamethasone-phosphate (2.3±0.96 mg/mL) and dexamethasone (0.27±0.07 mg/mL) following injection, neither drug was detected in the synovium or the local venous blood following iontophoretic or passive applications. In conclusion, these results do not confirm iontophoretic or passive delivery of measurable dexamethasone-phosphate into the tibiotarsal joint using current clinical methods.

Lorcaserin represents a new serotonergic medication used as an adjunct to a reduced-calorie diet and increased physical activity treatment plan for chronic weight management in adult patients with an initial body mass index ≥ 30 kg/m 2 or in adult patients with an initial body mass index ≥ 27 kg/m 2 who have ≥ 1 comorbid condition associated with weight (eg, hypertension, dyslipidemia, or type 2 diabetes mellitus). In 2012, lorcaserin became the first obesity treatment medication to gain US Food and Drug Administration (FDA) approval since 1999. Lorcaserin is a centrally acting, selective serotonin C (5-HT2C) receptor full agonist that is associated with increased satiety and decreased food consumption in patients. The selectivity of lorcaserin for 5-HT2C receptors should reduce patient risk for the serious adverse complications that are associated with nonselective 5-HT agonist therapies, such as cardiac valvulopathy and pulmonary hypertension. The safety and efficacy of lorcaserin (10 mg twice daily) for ≥ 52 weeks has been evaluated in 3 separate Phase 3 trials. The primary outcome of patient weight loss in the 3 trials satisfied the FDA categorical benchmark but patient outcomes in the trials failed to achieve the FDA mean benchmark of patient weight loss. Secondary patient outcomes after lorcaserin therapy were favorable. Lorcaserin appears to be well tolerated in patients and the most common adverse events reported did not include serious complications. The incidence of FDA-defined valvulopathy in patients after 1 year of treatment was low and nonsignificant, but the statistical analysis of this safety endpoint was limited due to the small size of the study populations and high patient dropout rates. Continued post-marketing surveillance of patients taking lorcaserin is warranted.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are assembled into two categories; cyclooxygenase (COX-1) sparing inhibitors of COX-2 and non-selective NSAIDs. Diclofenac (DICLO) is a non-selective NSAID that has been linked to serious side effects including gastric ulcers and renal injury. In this study, we examine the effect of poly(lactic-co-glycolic) acid nanoformulation on DICLO-associated adverse events and pharmacokinetics using a nanoparticle (NP) formulation previously developed in our laboratory.MATERIALS AND METHODS: Rats were administered a single dose of methylcellulose (VEH), blank NP, DICLO (10 mg/kg), or a DICLO-NP suspension equivalent to the DICLO dose. Urinary and blood parameters were measured at baseline and following treatment. Duodenal and gastric prostaglandin E2 (PGE2) and duodenal myeloperoxidase (MPO) were collected to assess inflammation at 24 hrs post-treatment.RESULTS: The mean percent change from baseline in sodium excretion rate (µmol/min/100 g body weight) differed significantly from VEH in the NP (p < 0.0001), DICLO (p < 0.0001), and DICLO-NP (p = 0.0001) groups. The differences among groups did not reach significance for plasma sodium or potassium concentrations, potassium excretion rate, gastric PGE2, or intestinal biomarker concentrations. Regarding renal histopathology, DICLO produced considerably more necrosis compared to VEH; while DICLO-NP did not elicit notable differences from VEH.CONCLUSIONS: Our results suggest that over the duration and dosage examined, DICLO-NP may reduce renal necrosis without influencing other side effects or drug characteristics.

Pain management in the pediatric population is complex for many reasons. Mild pain is usually managed quite well with oral acetaminophen or ibuprofen. Situations involving more severe pain often require the use of an opioid, which may be administered by many different routes, depending on clinical necessity. Acute and chronic disease states, as well as the constantly changing maturational process, produce unique challenges at every level of pediatrics in dosing and management of all medications, especially with regard to high-risk opioids. Although there has been significant progress in the understanding of opioid pharmacokinetics and pharmacodynamics in neonates, infants, children, and adolescents, somewhat limited data exist from which necessary information, concerning the safe and effective use of these agents, may be drawn. The evidence here provided is intended to be helpful in directing the practitioner to patient-specific reasons for preferring one opioid over another. As our knowledge of opioids and their effects has grown, it has become clear that older medications like codeine and meperidine (pethidine) have very limited use in pediatrics. This review provides pharmacokinetic and pharmacodynamic evidence on the currently available opioids: morphine, fentanyl (and derivatives), codeine, meperidine, oxycodone, hydrocodone, hydromorphone, methadone, buprenorphine, butorphanol, nalbuphine, pentazocin, ketobemidone, tramadol, piritramide, naloxone and naltrexone. Morphine, being the most studied opioid analgesic, is the standard against which all others are compared. Pharmacokinetic parameters of morphine that have been found in neonates, i.e., higher volume of distribution, immature metabolic processes that develop at various rates, elimination that is variable based on age and weight, as well as treated and untreated disease processes, are an example of all opioids in the population discussed in this review. Outside the premature and neonatal population, the use of opioids in infants, children, and adolescents quickly begins to resemble the established values found in adults. As such, the concerns (risks) of these medications become comparable to those seen in adults.

No description available.

Breast cancer is a leading cancer among women and is a major cause of death worldwide. While not just one disease, breast cancer encompasses many biologically different subtypes with distinct pathologies and clinical ramifications. In the case of estrogen receptor (ER) positive breast cancer, estrogens stimulate mammary epithelial cell proliferation and contribute to the development and progression of the disease. To treat ER-positive breast cancer patients, endocrine targeted therapies such as tamoxifen are commonly used. However, 40–50% of these patients do not respond or develop resistance to these therapies, and therefore additional treatment options are needed. In the case of triple negative breast cancer (TNBC), there is a lack of expression of the ER, progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) and this subtype has the poorest prognosis. There are currently very limited therapies available for TNBC, and due to the receptor status, endocrine therapies are ineffective. This leaves TNBC patients with chemotherapy and radiation as the only options, and therefore additional treatments are urgently needed. CAPER is a coactivator of activating protein-1 (AP-1) (interacting specifically with the c-Jun component) and the ER and is known to be involved in human breast cancer pathogenesis. Not only has CAPER shown a role in ER-positive breast cancer but recent data has also demonstrated a role for CAPER in TNBC. In normal breast tissue, CAPER is not detectable or expressed at low levels. However, in both ER-positive and TNBC, CAPER exhibits a significantly higher level of expression. Additionally, it has been shown that when CAPER expression is reduced via knockdown cell proliferation is decreased in both in vitro and in vivo settings. Due to CAPER’s role in both ER-positive and TNBC, disrupting the interaction of CAPER with the ER and/ or c-Jun could be a novel approach to treat breast cancer patients. The work described herein will review the development and in vitro testing of CAPER peptides to inhibit the coactivator activity of CAPER with c-Jun and/or the ER.