[Pharmacology of non-opioid analgesics]. / Pharmakologie der Nichtopioidanalgetika.

Due to high prescription rates as well as the frequent use as over the counter drugs, it is of interest to consider non-opioid analgesics when evaluating the quality and appropriateness of a given overall medication. This article sums up the basic pharmacology and main adverse effects of these analgesics. Non-opioids can be further classified according to their additional mechanisms of action besides analgesia. High-dose acetylsalicylic acid, traditional nonsteroidal anti-inflammatory drugs, and coxibs exhibit antipyretic and anti-inflammatory properties. Acetaminophen and metamizole (dipyrone) are analgesics and antipyretic agents, while metamizole exhibits also spasmolytic effects. Capsaicin and intrathecal ziconotide are pure analgesics.

European guidelines on lifestyle changes for management of hypertension : Awareness and implementation of recommendations among German and European physicians.

BACKGROUND: In the 2013 European Society of Hypertension (ESH) and European Society of Cardiology (ESC) guidelines for the management of arterial hypertension, six lifestyle changes for treatment are recommended for the first time with class I, level of evidence A. We initiated a survey among physicians to explore their awareness and consideration of lifestyle changes in hypertension management. METHODS: The survey included questions regarding demographics as well as awareness and implementation of the recommended lifestyle changes. It was conducted at two German and two European scientific meetings in 2015. RESULTS: In all, 1064 (37.4% female) physicians participated (806 at the European and 258 at the German meetings). Of the six recommended lifestyle changes, self-reported awareness was highest for regular exercise (85.8%) followed by reduction of weight (66.2%). The least frequently self-reported lifestyle changes were the advice to quit smoking (47.3%) and moderation of alcohol consumption (36.3%). Similar frequencies were observed for the lifestyle changes implemented by physicians in their care of patients. CONCLUSION: A close correlation between awareness of guideline recommendations and their implementation into clinical management was observed. European physicians place a stronger emphasis on regular exercise and weight reduction than on the other recommended lifestyle changes. Moderation of alcohol consumption is the least emphasized lifestyle change.

Effect of UMOD genotype on long-term graft survival after kidney transplantation in patients treated with cyclosporine-based therapy.

The genetic rs12917707-G>T variant in uromodulin (UMOD) has been associated with renal function, chronic kidney disease and hypertension with the minor T-allele showing a protective effect. Hypertension and nephrotoxicity are adverse effects of chronic cyclosporine treatment. We tested whether UMOD rs12917707-T in donor kidneys associates with long-term graft survival in 393 Caucasian patients with stable graft function for more than 10 weeks after kidney transplantation treated with a cyclosporine-based maintenance therapy (mean graft survival 9 years). Presence of the donor T-allele had no effect on blood pressure, serum creatinine 1 year after transplantation, and on number of acute graft rejections during the first year. No significant effect on overall graft survival was observed in Kaplan-Meier analysis (P=0.65). In death-censored adjusted multivariate analysis, presence of donor T-allele associated with a significant lower hazard ratio of 0.67 (95% confidence interval: 0.46-0.97, P=0.05) for graft loss. This protective effect of the donor T-allele on graft loss observed in multivariate adjusted analysis justifies further investigations including patients treated with similar or other immunosuppressive regimens.

Antipsychotic drugs predominate in pharmacotherapy of nursing home residents with dementia.

INTRODUCTION: The aim of this study was to investigate the frequency of benzodiazepines, antidementia and antipsychotic drug prescriptions in nursing home residents (NHR).Data of a German health insurance company were retrospectively analyzed for the year 2008. METHODS: The study cohort comprised 13,042 NHR (82% women, mean age 83.6 ± 7 years). Following analgetics, antipsychotic drugs were the second most frequently prescribed drug group with 13.3% of all prescriptions. Dementia was diagnosed in 8 017 (61.5%) NHR. Thereof 51.6% received an antipsychotic, 17.3% a benzodiazepine and 15.2% an antidementia pharmaceutical, respectively. 18.1% of NHR with dementia and antipsychotic drug prescriptions were in combined treatment with antidementia pharmaceuticals. The rate of antipsychotic drug prescribing was significantly doubled in NHR with dementia compared to those without this diagnosis (p<0.01); the most frequently prescribed antipsychotics were melperone, risperidone and pipamperone. DISCUSSION: This study demonstrates the wide-spread use of psychotropic drugs in NHR. Moreover, dementia in NHR was associated with antipsychotic drug prescribing in every second patient. This highlights the need for further studies analyzing alternative treatments for dementia-related symptoms.

[Prescribing of antihypertensive drugs to elderly residents of nursing homes in Germany]. / Verordnung von Antihypertensiva bei geriatrischen Pflegeheimbewohnern in Deutschland.

OBJECTIVE: To analyse and evaluate the use of antihypertensive medication in elderly patients of nursing homes in Germany. METHODS: Data from a large German health insurance company were collected in a cross sectional study. Included were all insured persons aged 65 years or older, who were residents of a nursing home between 1 April and 30 June 2007 throughout Germany. Antihypertensive drugs were those classified according to the current guidelines published by the German Hypertension Society. RESULTS: The study comprised 8,685 residents of nursing homes, 84 % women. The mean age was 84 years (range 65 - 106 years). Antihypertensive drug prescriptions accounted for 17 % of all drug prescriptions and about 70 % of all residents received at least one prescription for antihypertensive drugs. The most frequently prescribed antihypertensive drugs were diuretics, of which 70 % were loop diuretics. Potentially inappropriate combinations of antihypertensive drugs were noted in 5.2 % of patients receiving these drugs. CONCLUSION: Antihypertensive drugs account for a notable part (17 %) of all drug prescriptions in elderly residents of nursing homes throughout Germany. These results indicate that only a minority of all residents were treated with potentially inappropriate or potentially harmful drug combinations. However, the relatively high rate of prescriptions for loop diuretics is a matter of potential concern in this vulnerable group of patients.

[Antihypertensive drug treatment and renal function in geriatric emergency patients]. / Antihypertensive Pharmakotherapie und Nierenfunktion bei geriatrischen Notfallpatienten.

OBJECTIVE: The aim of this study was to assess drug prescriptions and renal function in a cohort of geriatric emergency patients with a focus on antihypertensive drug treatment. PATIENTS AND METHODS: The one-year observational study was conducted among patients from nursing and retirement homes or outpatient care who were treated by the emergency medical service. Overall, 109 patients (85 women, mean age 85+/-8 years) were studied. Glomerular filtration rate was estimated (eGFR) on the basis of creatinine and cystatin C serum concentrations. RESULTS: The most common emergency admission diagnosis was syncope (n = 23), while the most common clinical diagnoses were dementia (n = 61) and hypertension (n = 60). Overall, 603 drugs were prescribed (mean 5.5 +/- 3, range 0 - 13), with 65 patients (60 %) receiving >/= 5 drugs per day. Of 60 patients with the known diagnosis of hypertension 55 (92 %) were being treated, while 71 % received at least 2 antihypertensive drugs. ACE-inhibitors (n = 33), loop diuretics (n = 28), beta-blockers (n = 22) and hydrochlorothiazide (n = 15) were the most frequently prescribed drugs. Mean creatinine (1.33 +/- 0.66 mg/dl) and cystatin C (1.78 +/- 0.83 mg/l) concentrations were elevated. Overall, up to two thirds of patients had eGFR values of < 60 ml/min/1.73 m (2). In up to 31 % of patients dosages were too high in relation to renal dysfunction. CONCLUSIONS: The prescription of antihypertensive drugs contributes significantly to polypharmacy in geriatric emergency patients. About two thirds of these patients had clinically relevant impairment of renal function. The latter, together with the high number of prescribed drugs, may expose geriatric patients to an increased risk of adverse drug reactions requiring emergency treatment.

Comparative expression analysis of the renin-angiotensin system components between white and brown perivascular adipose tissue.

Recent studies have demonstrated that the rat adipose tissue expresses some of the components necessary for the production of angiotensin II (Ang II) and the receptors mediating its actions. The aim of this work is to characterize the expression of the renin-angiotensin system (RAS) components in perivascular adipose tissue and to assess differences in the expression pattern depending on the vascular bed and type of adipose tissue. We analyzed Ang I and Ang II levels as well as mRNA levels of RAS components by a quantitative RT-PCR method in periaortic (PAT) and mesenteric adipose tissue (MAT) of 3-month-old male Wistar-Kyoto rats. PAT was identified as brown adipose tissue expressing uncoupling protein-1 (UCP-1). It had smaller adipocytes than those from MAT, which was identified as white adipose tissue. All RAS components, except renin, were detected in both PAT and MAT. Levels of expression of angiotensinogen, Ang-converting enzyme (ACE), and ACE2 were similar between PAT and MAT. Renin receptor expression was five times higher, whereas expression of chymase, AT(1a), and AT(2) receptors were significantly lower in PAT compared with MAT respectively. In addition, three isoforms of the AT(1a) receptor were found in perivascular adipose tissue. The AT(1b) receptor was found at very a low expression level. Ang II levels were higher in MAT with no differences between tissues in Ang I. The results show that the RAS is differentially expressed in white and brown perivascular adipose tissues implicating a different role for the system depending on the vascular bed and the type of adipose tissue.

CYP3A5 genotype is associated with longer patient survival after kidney transplantation and long-term treatment with cyclosporine.

The CYP3A5*1 allele has been linked to high expression of CYP3A5 and metabolism of cyclosporine. We evaluated the role of CYP3A5*1 for long-term survival in renal transplant patients in a cohort of 399 patients who underwent cadaveric or living donor kidney allograft transplantation. All patients were treated with a similar cyclosporine-based immunosuppressive maintenance therapy protocol. The mean duration of follow-up was 8.6+/-3.7 years. In univariate survival analysis, the presence of the CYP3A5*1 allele in recipients significantly increased patient survival P=0.028 (log-rank), resulting in a hazard ratio (HR) of 0.52 (95% CI=0.29-0.94). When the presence of the CYP3A5*1 allele was included in multivariate Cox regression analyses accounting for major risk factors for patient death, CYP3A5*1 still conferred a protective effect. Further, haplotype analysis at the CYP3A5 locus confirmed that CYP3A5*1 might indeed be responsible for this survival benefit.

Characterization of the c-specific promoter of the gene encoding human endothelin-converting enzyme-1 (ECE-1).

Human ECE-1 is expressed in four isoforms with different tissue distribution and its mRNA and protein levels are altered under certain pathophysiological conditions. To investigate the transcriptional regulation of ECE-1, we studied the regulatory region of ECE-1c, the major ECE-1 isoform. A genomic clone comprising the complete human ECE-1 gene including the putative ECE-1c-specific promoter was obtained. Up to 968 bp upstream of the putative c-specific translation initiation start codon and several serial deletion mutants were subcloned into a reporter vector and transfected into endothelial (BAEC, EA.hy926, ECV304) and epithelial (MDA MB435S, MCF7) cells, showing very strong promoter activity in comparison to the SV40 promoter and to the previously described ECE-1a and 1b promoters. Transfection of serial deletion mutants indicated two positive regulatory regions within the promoter (-142/-240 and -240/490) likely involved in binding GATA and ETS transcription factors. RNase protection assay (RPA) and 5'-RACE revealed multiple transcriptional start sites located at about -110, -140 and -350 bp. Site-directed mutagenesis demonstrated a crucial role for the E2F cis-element for basal ECE-1c promoter activity. Additionally, we found a correlation between isoform-specific ECE-1 mRNA levels and corresponding ECE-1a, 1b, 1c promoter activities.