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Used Drugs (used + drug)
Selected AbstractsA survey on two years of medication regulation in horse races in IranEQUINE VETERINARY JOURNAL, Issue 2 2010S. LOTFOLLAHZADEH Summary Reasons for performing study: The present survey evaluated the use of prohibited substances cases in the first 2 years of medication regulation in horseracing in Iran so that the impact of these regulations on the level of positive cases over the period could be assessed. Objectives: To determine the prevalence of positive tests for prohibited substances in horse races during 2 years of a drugs testing programme in Iran. Methods: A total of 656 horses that were winners or second in races were tested during the 2 year study. In the first year 354 horses (209 males and 145 females) and in the second year 302 horses (155 males and 147 females) were tested. In the 2 years, 306 were found to be positive. Urine samples were taken from candidate horses and sent to the Central Doping Laboratory. Blood samples were taken from those horses where a urine sample could not be taken within one hour. Detection and measurement of prohibited substances were carried out by ELISA, GC and HPLC using standard methods. Results: Thirty-two percent of males were positive for prohibited substances, which was not significantly different from the percentage of females (25.5%). In the second year, of the 302 horses tested for prohibited substances, 33.5% of males were positive, again similar to females (33.3%). Almost 83% of horses tested positive for prohibited substances once in the first year, 15% tested positive twice and 2% tested positive 3 times. In the second year 78% tested positive once, 15% tested positive twice and 7% tested positive 3 times. Morphine was the most used prohibited substance and was detected 42 times during the survey, followed by caffeine and phenylbutazone. Morphine was also the most used drug in combination with other drugs in both years. Conclusions: Morphine and caffeine were the most popular prohibited substances found in the measurements. As these substances were found in the environment and food stuffs, their presence in the samples may be due to unintentional feeding of contaminated materials (bread, hay and chocolate). [source] Areca nut-abuse liability, dependence and public healthADDICTION BIOLOGY, Issue 1 2002A. Winstock It may, however, stigmatize substance use, especially when western diagnostic criteria are applied to essentially culture-bound substances. However, when the pattern of use of a substance results in significant personal harm, then whether dependence exists or not is less important than developing an appropriate response, if its use is associated with significant morbidity and mortality. Such is the case with areca nut, the fourth most commonly used drug in the world after tobacco, alcohol and caffeine. In this paper I will explore its use and properties with respect to its abuse and dependence liability and consider the associated implications for public health. [source] Antidiabetic Drug Therapy of African-American and White Community-Dwelling Elderly Over a 10-Year PeriodJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2003Catherine I. Lindblad PharmD Objectives: To determine the prevalence and predictors of antidiabetic medication use over a 10-year period in a general population of African-American and white community-dwelling elderly. Design: Survey. Setting: Five adjacent counties (one urban and four rural) in the Piedmont area of North Carolina. Participants: Those aged 65 and older present at the baseline (n=4,136), second (n=3,234), third (n=2,508), and fourth (n=1,633) in-person waves of the Duke Established Populations for Epidemiologic Studies of the Elderly. Measurements: The use of six discrete categories of antidiabetic medications (insulin, first-generation oral sulfonylureas, second-generation oral sulfonylureas, metformin, oral combination therapy, and insulin combination therapy) was determined. Multivariate analyses, using weighted data adjusted for sampling design, were conducted to assess the association between antidiabetic medication use and race and other sociodemographic, health-status, and access-to-healthcare factors at baseline and 10 years later. Results: Antidiabetic medications were taken by 21.4% of the population at baseline; this increased to 28.1% at the 10-year follow-up (P<.001). Insulin was the most commonly used drug at baseline (7.9%). The use of second-generation sulfonylureas increased, and use of first-generation sulfonylureas decreased over the 10-year time period. Combination antidiabetic therapy and metformin use was infrequent throughout the study. Multivariate analyses revealed that, at baseline, African Americans were nearly twice as likely (adjusted odds ratio (AOR)=1.93, 95% confidence interval (CI)=1.46,2.54) to receive any antidiabetic medication as their white counterparts. Other significant (P<.05) factors were hypertension (AOR=1.38, 95% CI=1.03,1.84), stroke (AOR=1.98, 95% CI=1.43,2.73), one or more mobility difficulties (AOR=1.29, 95% CI=1.01,1.66), continuity of care (AOR=1.74, 95% CI=1.20,2.54), and multiple doctor visits (1,4 visits, AOR=1.69, 95% CI=1.08,2.65; ,5 visits, AOR=3.15, 95% CI=1.95,5.07). Being underweight (AOR=0.45, 95% CI=0.30,0.67) and being cognitively impaired (AOR=0.60, 95% CI=0.41,0.87) were factors significantly (P<.05) associated with a decreased risk of antidiabetic medication use. At the 10-year follow-up, similar trends were seen associating these sociodemographic, health-status, and access-to-healthcare factors with antidiabetic medication use. Conclusion: Antidiabetic medication use is common and increases over time for community-dwelling elderly. Race is significantly associated with antidiabetic medication use, even after controlling for other sociodemographic, health-status, and access-to-healthcare variables. [source] Chronic lithium administration to FTDP-17 tau and GSK-3, overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre-formed neurofibrillary tangles do not revertJOURNAL OF NEUROCHEMISTRY, Issue 6 2006Tobias Engel Abstract Glycogen synthase kinase-3 (GSK-3) has been proposed as the main kinase able to aberrantly phosphorylate tau in Alzheimer's disease (AD) and related tauopathies, raising the possibility of designing novel therapeutic interventions for AD based on GSK-3 inhibition. Lithium, a widely used drug for affective disorders, inhibits GSK-3 at therapeutically relevant concentrations. Therefore, it was of great interest to test the possible protective effects of lithium in an AD animal model based on GSK-3 overexpression. We had previously generated a double transgenic model, overexpressing GSK-3, in a conditional manner, using the Tet-off system and tau protein carrying a triple FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) mutation. This transgenic line shows tau hyperphosphorylation in hippocampal neurones accompanied by neurofibrillary tangles (NFTs). We used this transgenic model to address two issues: first, whether chronic lithium treatment is able to prevent the formation of aberrant tau aggregates that result from the overexpression of FTDP-17 tau and GSK-3,; second, whether lithium is able to change back already formed NFTs in aged animals. Our data suggest that progression of the tauopathy can be prevented by administration of lithium when the first signs of neuropathology appear. Furthermore, it is still possible to partially reverse tau pathology in advanced stages of the disease, although NFT-like structures cannot be changed. The same results were obtained after shut-down of GSK-3, overexpression, supporting the possibility that GSK-3 inhibition is not sufficient to reverse NFT-like aggregates. [source] Analysis of 5-fluorouracil in saliva using surface-enhanced Raman spectroscopyJOURNAL OF RAMAN SPECTROSCOPY, Issue 3 2005Stuart Farquharson Abstract The ability of surface-enhanced Raman spectroscopy (SERS) to measure the chemotherapy drug 5-fluorouracil in saliva is presented. A silver-doped sol,gel provided SERS and also some chemical selectivity. 5-Fluorouracil and physiological thiocyanate produced SERS, whereas large biochemicals, such as enzymes and proteins, did not, supporting the expectation that the larger molecules do not diffuse through the sol,gel to any appreciable extent. In addition, 5-fluorouracil samples of 2 µg ml,1 were easily measured, and an estimated limit of detection of 150 ng ml,1 in 5 min should provide sufficient sensitivity to perform pharmacokinetic studies and to monitor and regulate patient dosage. This would fill a critical need for this highly used drug, since genetic-based variations in its metabolism can range by as much as five-fold from one patient to another. Copyright © 2004 John Wiley & Sons, Ltd. [source] Clonidine in paediatric anaesthesia: review of the literature and comparison with benzodiazepines for premedicationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2006H. Bergendahl Background:, Children undergoing anaesthesia and surgery can experience significant anxiety and distress during the peri-operative period, but whether routine premedication is necessary is currently debated. Benzodiazepines are the most frequently used drugs as premedication in paediatric anaesthesia. In the US, 50% of young children undergoing surgery receive premedication and midazolam is the most frequently used drug in this context (1). Nishina and coworkers (2) concluded in a review article in 1999 that clonidine, administered via an oral, rectal, or caudal route, is a promising adjunct to anaesthetics and analgesics to enhance quality of peri-operative management in infants and children. Later publications also support the use of clonidine for premedication (3,6). The aim of this communication is to review the use of clonidine in paediatric anaesthesia and to propose clonidine as a promising alternative to midazolam. Clonidine is associated with a number of beneficial effects in the context ofanaesthesia both in adults and children. Why clonidine is not routinely use in clinical practice despite the massive publication list is to a large extent due to the lack of marketing efforts from the pharmaceutical industry since multiplegeneric preparations are now readily available on most markets. Midazolam is also associated with a number of beneficial effects, but is far from an ideal premedicant in children, especially with regards to the amnesia, confusion and long term behavioural disturbances. Clonidine has contrary to midazolam no effect on respiration. We believe that clonidine is a good alternative to midazolam as premedication in infants and children. [source] The novel 2Fe,2S outer mitochondrial protein mitoNEET displays conformational flexibility in its N-terminal cytoplasmic tethering domainACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 7 2009Andrea R. Conlan A primary role for mitochondrial dysfunction is indicated in the pathogenesis of insulin resistance. A widely used drug for the treatment of type 2 diabetes is pioglitazone, a member of the thiazolidinedione class of molecules. MitoNEET, a 2Fe,2S outer mitochondrial membrane protein, binds pioglitazone [Colca et al. (2004), Am. J. Physiol. Endocrinol. Metab.286, E252,E260]. The soluble domain of the human mitoNEET protein has been expressed C-terminal to the superfolder green fluorescent protein and the mitoNEET protein has been isolated. Comparison of the crystal structure of mitoNEET isolated from cleavage of the fusion protein (1.4,Å resolution, R factor = 20.2%) with other solved structures shows that the CDGSH domains are superimposable, indicating proper assembly of mitoNEET. Furthermore, there is considerable flexibility in the position of the cytoplasmic tethering arms, resulting in two different conformations in the crystal structure. This flexibility affords multiple orientations on the outer mitochondrial membrane. [source] Risk of diarrhoea in a long-term cohort of renal transplant patients given mycophenolate mofetil: the significant role of the UGT1A8*2 variant alleleBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2010Jean-Baptiste Woillard WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Mycophenolate mofetil (MMF), the most widely used drug in allograft transplantation, is subject to hepatic and intestinal glucuronidation and entero-hepatic cycling. , Diarrhoea is its most frequent adverse event leading to non-compliance, treatment interruption and ultimately to an increased rate of acute rejection. , Cyclosporin reduces the biliary excretion of mycophenolate metabolites, presumably by inhibiting the efflux transporter MRP2. , When combined with MMF, cyclosporin reduces the incidence of diarrhoea, suggesting the role played by biliary excretion of mycophenolate glucuronides in this adverse event. WHAT THIS STUDY ADDS , In a long-term cohort of renal transplant patients on MMF, the two factors significantly associated with a reduced incidence of diarrhoea were the co-medication with cyclosporin (as opposed to tacrolimus or sirolimus) and the *2 variant allele of the intestinal UGT1A8. , Polymorphisms in the other UDP-glucuronosyl-transferases and MRP2 were not significant. AIM In renal transplant patients given mycophenolate mofetil (MMF), we investigated the relationship between the digestive adverse events and polymorphisms in the UGT genes involved in mycophenolic acid (MPA) intestinal metabolism and biliary excretion of its phase II metabolites. METHODS Clinical data and DNA from 256 patients transplanted between 1996 and 2006 and given MMF with cyclosporin (CsA, n = 185), tacrolimus (TAC, n = 49) or sirolimus (SIR, n = 22), were retrospectively analysed. The relationships between diarrhoea and polymorphisms in UGT1A8 (*2; 518C>G, *3; 830G>A), UGT1A7 (622C>T), UGT1A9 (,275T>A), UGT2B7 (,840G>A) and ABCC2 (,24C>T, 3972C>T) or the co-administered immunosuppressant were investigated using the Cox proportional hazard model. RESULTS Multivariate analysis showed that patients on TAC or SIR had a 2.8 higher risk of diarrhoea than patients on CsA (HR = 2.809; 95%CI (1.730, 4.545); P < 0.0001) and that non-carriers of the UGT1A8*2 allele (CC518 genotype) had a higher risk of diarrhoea than carriers (C518G and 518GG genotypes) (HR = 1.876; 95%CI (1.109, 3.175); P = 0.0192). When patients were divided according to the immunosuppressive co-treatment, a significant effect of UGT1A8*2 was found in those co-treated with CsA (HR = 2.414; 95%CI (1.089, 5.354); P = 0.0301) but not TAC or SIR (P = 0.4331). CONCLUSION These results suggest that a possible inhibition of biliary excretion of MPA metabolites by CsA and a decreased intestinal production of these metabolites in UGT1A8*2 carriers may be protective factors against MMF-induced diarrhoea. [source] Hypersensitivity to local anaesthetics , update and proposal of evaluation algorithmCONTACT DERMATITIS, Issue 2 2008Jacob Pontoppidan Thyssen Local anaesthetics (LA) are widely used drugs. Adverse reactions are rare but may be caused by delayed-type hypersensitivity reactions and probably also immediate-type reactions. As it is not always easy to clinically differ between these subtypes, allergy skin testing should be considered. Although numerous test protocols have been published, how patients with hypersensitivity reactions to LA are ideally evaluated remains a topic of discussion. This review attempts to generate a comprehensive update on allergic reactions to LA and to present an algorithm that can be used for the evaluation of patients suspected with immediate- and delayed-type immune reactions. Literature was examined using PubMed-Medline, EMBASE, Biosis and Science Citation Index. Based on the literature, the proposed algorithm may safely and rapidly distinguish between immediate-type and delayed-type allergic immune reactions. [source] Current treatment of non-alcoholic fatty liver diseaseDIABETES OBESITY & METABOLISM, Issue 3 2009Mohamed H. Ahmed Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in Western World and frequently associated with insulin resistance and overweight and occurs often with type 2 diabetes. Interestingly, NAFLD is not only regarded as a hepatic component of the metabolic syndrome but also as an independent risk factor and a marker for increase in cardiovascular disease (CVD). Significantly, NAFLD is associated with an increased risk of all-cause mortality and predicts future CVD events independent of age, sex, LDL-cholesterol and features of metabolic syndrome. Although there was initial concern about drug toxicity with NAFLD, increasing evidence suggests that commonly used drugs such as metformin and statins do not cause harm and the thiazolidinediones (TZDs) may even confer a therapeutic benefit in NAFLD. Interestingly, medical and surgical treatments of obesity show potential benefit in treating NAFLD. In this review, we have focused on the safety and therapeutic impact of TZDs, statins, metformins and obesity medications in NAFLD. The potential benefit of bariatric surgery and the role of weight loss per se in treating NAFLD are also discussed. [source] Long-term use of acid-suppressive therapy after the endoscopic diagnosis of reflux esophagitisDISEASES OF THE ESOPHAGUS, Issue 4 2000H. D. Boom A study was carried out in a group of patients in whom reflux esophagitis was diagnosed 4.5,7.5 years previously in order to assess current complaints and use of medication. A questionnaire was mailed to all patients in whom reflux esophagitis was diagnosed. Patients were asked about the presence of reflux complaints. Use of medication was assessed (continuous, intermittent, or on demand). In the 3-year period, reflux esophagitis was diagnosed in 312 patients (195 men, 117 women, mean age 59.6 years, range 17,96 years). The questionnaire was mailed to 246 patients, of whom 172 (70%) responded. Of these, 146 (85%) used acid-suppressive therapy. One hundred and eight (74%) used drugs on a daily basis, 31 on demand and 19 prophylactically in order to prevent the occurrence of reflux complaints. Despite the use of medication, patients suffered significantly more often from reflux complaints than did individuals who did not use any medication. It is concluded that the majority of patients (85%) still use acid-suppressive therapy and, in 74% of cases, on a daily basis. Maintenance therapy cannot prevent clinical relapse. [source] Global use of alcohol, drugs and tobaccoDRUG AND ALCOHOL REVIEW, Issue 6 2006PETER ANDERSON Abstract Humans have always used drugs, probably as part of their evolutionary and nutritional heritage. However, this previous biological adaptation is unlikely to be so in the modern world, in which 2 billion adults (48% of the adult population) are current users of alcohol, 1.1 billion adults (29% of the adult population) are current smokers of cigarettes and 185 million adults (4.5% of the adult population) are current users of illicit drugs. The use of drugs is determined largely by market forces, with increases in affordability and availability increasing use. People with socio-economic deprivation, however measured, are at increased risk of harmful drug use, as are those with a disadvantaged family environment, and those who live in a community with higher levels of substance use. Substance use is on the increase in low-income countries which, in the coming decades, will bear a disproportionate burden of substance-related disability and premature death. [source] Motives for substance use among young people seeking mental health treatmentEARLY INTERVENTION IN PSYCHIATRY, Issue 3 2008Leanne Hides Abstract Aims: To explore substance use motives among young people seeking mental health treatment. Methods: Participants consisted of 103 young people seeking mental health treatment, who had used drugs or alcohol in the past year. The young people completed a 42-item substance use motives measure based on the Drinking Motives Measure for their most frequently used substance in the past year. Results: Exploratory factor analysis of the substance use motives scale indicated the young people reported using substances for positive and negative drug effects, to socialize with their peers, and to cope with a negative affect. They did not report using substances for enhancement or conformity motives. Coping motives predicted the presence of a current substance use disorder. Conclusions: The findings support the need for integrated treatment approaches within mental health settings, particularly targeted at young people with co-occurring mental health and substance use problems. [source] Prevalence and socio-demographic correlates of drug use among adolescents: results from the Mexican Adolescent Mental Health SurveyADDICTION, Issue 8 2007Corina Benjet ABSTRACT Aims To estimate the life-time and 12-month prevalence of illicit drug use among Mexican adolescents, the age of onset of first drug use and the socio-demographic correlates. Method A multi-stage probability survey of adolescents aged 12,17 years residing in the Mexico City Metropolitan Area was carried out in 2005. Adolescents were administered the computer-assisted adolescent version of the World Mental Health Composite International Diagnostic Interview by trained lay interviewers in their homes. The response rate was 71% (n = 3005). Descriptive and logistic regression analyses were performed considering the multi-stage and weighted sample design of the survey. Findings Of the adolescents, 5.2% have ever tried illicit drugs, 2.9% in the last 12 months. The most frequently used drugs are marijuana, followed by tranquilizers/stimulants. The median age of first use is 14 years. Correlates of life-time drug use are older age, having dropped out of school, parental drug problems, low religiosity and low parental monitoring. Conclusions While drug use among Mexican adolescents is lower than among adolescents from other developed countries, its increasing prevalence with age and the narrowing male/female ratio calls for firm public health actions, particularly prevention strategies. [source] Drug use among female sex workers in Hanoi, VietnamADDICTION, Issue 5 2005Trung Nam Tran ABSTRACT Aims To describe the drug use practices among female sex workers (FSWs) in Hanoi and to identify factors associated with their drug injecting. Design, setting and particicipants A two-stage cluster survey of 400 FSWs was conducted from June to September, 2002. Participating FSWs were both establishment- (160) and street-based (240), who were practising in seven urban and one suburban districts of Hanoi. Measurements Subjects were interviewed face to face using a structured questionnaire. Findings Among the middle-class FSWs, 27% used drugs, of whom 79% injected. Among low-class FSWs, 46% used drugs and 85% injected. Among drug-using FSWs, 86% had started using drugs within the past 6 years. Among drug-injecting FSWs, 81% had started injecting within the past 4 years. Cleaning of injecting equipment was not common among those who shared. Having drug-injecting ,love mates', drug-using clients, longer residence in Hanoi, more clients and not currently cohabiting were found to be independently associated with drug injecting among FSWs. Conclusions The high prevalence of injecting drug use among FSWs makes them susceptible to HIV infection, and is a threat to their clients. There is a strong relationship between drug-using FSWs and male drug-using clients and non-client partners. Intervention to prevent drug use initiation among non-drug-using FSWs and harm reduction among drug-using FSWs are urgently needed. [source] Dealing with the offer of drugs: the experiences of a sample of pre-teenage schoolchildrenADDICTION, Issue 7 2003James McIntosh ABSTRACT Aims To investigate the ways in which pre-teenage children anticipate and deal with the offer of drugs. Design A qualitative study based on semi-structured interviews with 10,12-year-old schoolchildren. Setting The cities of Glasgow (Scotland) and Newcastle (England), UK. Participants A sample of 216 pre-teenage children. Forty-three had used drugs on at least one occasion, 42 had been offered but had not used drugs and 131 had neither used drugs nor been offered them. Most of the results reported in the paper relate to the experiences of the 42 children who had declined the offer of drugs. Findings While children who had not been exposed to drug offers expressed a high degree of confidence in their ability to deal with them, those who had actually had to cope with such offers experienced a variety of difficulties. The ease with which an offer could be declined appeared to depend upon two main factors: who was making the offer and the context in which it was being made. According to the children, offers from people with whom they had a close relationship and those in which pressure or encouragement were involved were particularly difficult to deal with. Conclusions The paper concludes that there is a need to equip young people better with the interpersonal tools they require to deal with the various situations they are likely to encounter in which drugs may be offered. It is suggested that a broadly based life skills approach to drug education may provide the best way of helping young people to deal with these situations. [source] Variable expression of CYP and Pgp genes in the human small intestineEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2003M. Lindell Abstract Background ,The small intestine is receiving increased attention for its importance in drug metabolism. However, knowledge of the intervariability and regulation of the enzymes involved, cytochrome P450 and P-Glycoproteins (CYP and Pgp), is poor when compared with the corresponding hepatic enzymes. Methods ,The expression of eight different CYP genes and the Pgp were determined by reverse transcription polymerase chain reaction (RT-PCR) in 51 human duodenum biopsies. And the variability and correlation of expression was analyzed. Results ,Extensive interindividual variability was found in the expression of most of the genes. Only CYP2C9, CYP3A4 and Pgp were found in all samples. CYP1A2, CYP2A6 and CYP2E1 exhibited the highest interindividual variability. No strong correlation of expression existed between the genes. But a highly significant correlation was found between CYP2D6/1A2, 2D6/2E1, 1A2/2E1 and 2B6/2C9. Acetylsalicylic acid and omeprazole significantly increased the expression of CYPs 2A6, 2E1 and 3A4, respectively. Conclusions ,Extensive interindividual variability is characteristic for the expression of drug-metabolizing CYP and Pgp genes in human duodenum, and external factors such as drugs may further increase the variability. It is possible that the large interindividual variability may lead to variable bioavailability of orally used drugs and hence complicate optimal drug therapy, especially for drugs with a small therapeutic window. Elucidation of factors contributing to clinically important variances warrants further investigation. [source] Overview of adverse reactions to nefopam: an analysis of the French Pharmacovigilance databaseFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2007G. Durrieu Abstract Nefopam is widely used for the relief of moderate acute pain. Its safety profile remains to be specified. The objective of the study was to review adverse reactions to nefopam spontaneously reported to the French Pharmacovigilance system. All cases of adverse drug reactions (ADRs) associated with nefopam, registered in the French Pharmacovigilance database from January 1, 1995 to December 31, 2004, were reviewed. For each reported ADR, information about patient (age, gender, medical history), drug exposure (suspected and concomitantly used drugs), characteristics of ADRs (imputability score, time of onset, seriousness, outcome) were collected. A total of 114 ADRs with an imputability rated from ,plausible' (I2) to ,likely' (I3) and ,very likely' (I4) was analysed. The most frequent ADRs included ,expected' ADRs such as sweating, nausea, tachycardia, malaise or vomiting; 61 ADRs were ,unexpected. No overdose was reported; 26 ADRs (23%) were considered as ,serious'. Most of them were ,unexpected', including neuropsychiatric (hallucinations, convulsions) or cutaneous (pruritus, erythema, urticaria) ADRs. Six cases of anaphylactic ADRs (two angioedema and four anaphylactic shocks) were reported, all occurring shortly after use of nefopam during the post-operative period. Physicians should be aware of the possible occurrence of some serious ADRs when using nefopam such as convulsions and anaphylactic shocks, especially when the drug is used in special medical conditions, like post-operative periods. [source] Chronic neuropathic pain: mechanisms, drug targets and measurementFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2007Nanna B. Finnerup Abstract Neuropathic pain is common in many diseases or injuries of the peripheral or central nervous system, and has a substantial impact on quality of life and mood. Lesions of the nervous system may lead to potentially irreversible changes and imbalance between excitatory and inhibitory systems. Preclinical research provides several promising targets for treatment such as sodium and calcium channels, glutamate receptors, monoamines and neurotrophic factors; however, treatment is often insufficient. A mechanism-based treatment approach is suggested to improve treatment. Valid and reliable tools to assess various symptoms and signs in neuropathic pain and knowledge of drug mechanisms are prerequisites for pursuing this approach. The present review summarizes mechanisms of neuropathic pain, targets of currently used drugs, and measures used in neuropathic pain trials. [source] The therapeutic potential of NO-NSAIDsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2003John L. Wallace Abstract NSAIDs, including those that are selective for cyclooxygenase-2, are among the most widely used drugs. However, these drugs produce significant side effects in the gastrointestinal and cardiorenal systems, which greatly limit their utility. In recent years, a new type of anti-inflammatory agent has been developed that appears to offer significant advantages over conventional and Cox-2-selective NSAIDs. No-NSAIDs are derivatives of conventional NSAIDs, which are able to release nitric oxide over prolonged periods of time. The combination of balanced inhibition of the two main isoforms of COX with controlled release of nitric oxide yields a series of drugs that exert anti-inflammatory and analgesic activities in a wide range of settings, and have markedly reduced gastrointestinal and cardiorenal toxicity. Recent clinical trials of NO-NSAIDs have provided a ,proof of concept' that is completely consistent with pre-clinical characterization of these compounds. [source] Influence of therapy on the antioxidant status in patients with melanomaJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2008V. Gadjeva DSc Summary Background and objective:, Some anticancer drugs can result in increased production of reactive oxygen species (ROS). Alkylating agents are the most frequently used drugs in chemotherapeutic regimens for the treatment of malignant melanoma. It is known that triazenes exhibit in vivo activity by alkylation of nucleic acids and proteins, but there is no data about ROS formation during oxidative metabolism. Single agents of most interest for treatment of malignant melanomas include 5-(3,3-dimethyltriazene-1-yl)-imidazole-4-carboxamide (DTIC) and nitrosoureas such as 1-(2-chloroethyl) -3-cyclohexyl-1-nitrosourea (CCNU), but complete response to these drugs is rare. The present study aimed to determine whether an oxidative stress occurs during the clinical course of melanoma and the influence of therapy on the antioxidant status of patients with melanoma. For this purpose, we investigated plasma concentrations of MDA as indices of the levels of lipid peroxidation products. In addition, we studied the activities of the antioxidant enzymes superoxide dismutases (SOD) and catalase (CAT) in patients with melanoma before any treatment, after surgical removal of melanoma, and after chemotherapy with DTIC or in combination with CCNU of the operated patients. Methods:, Twenty one patients with melanoma were studied. Patients were operated prior to chemotherapy. After recovery for 10,20 days postoperatively, they were studied again for MDA, SOD and CAT activity. The patients were divided into two groups according to the chemotherapy (3,7 treatment cycles): with DTIC , given orally daily for 5 days, every 3 weeks as a single 2200 mg/kg dose and with the combination , DTIC (the same dose) + CCNU , administered orally at a dosage of 120 mg/m2 once every 40 days in accordance with protocols, approved by the Bulgarian Ministry of Health. The total amount of lipid peroxidation products in plasma was assayed. Results and discussion:, Plasma levels of MDA and CAT activity were significantly higher, and erythrocyte SOD activity significantly lower, in patients with melanoma, than in control healthy volunteers (P < 0·0001). Ten to twenty days after surgery, oxidative stress decreased but levels of MDA increased as a result of therapy. Important sources of increased ROS production may be the monocytes, phagocytosis of tumour cells and the cancer tissues. Plasma MDA in patients treated with DTIC + CCNU were significantly higher (P < 0·001), but erythrocyte SOD statistically lower (P < 0·00001), compared with patients treated with DTIC only. However, a combination of DTIC + CCNU did not attenuate oxidative stress, or reduced antioxidant status. Patients treated with this combination are at bigger risk of oxidative injury. Therefore, this disturbance might be due to augmented generation of toxic ROS, possibly from the metabolism of CCNU. Conclusion:, Increased oxidative stress follows an imbalance in antioxidant defence in non-treated patients with melanoma. The impaired antioxidant system favours accumulation of ROS, which may promote the cancer process. After complete removal of melanoma tissues, oxidative stress decreased. The antioxidant status of melanoma patients operated on was influenced by the different chemotherapeutic regimens used and may play an important role in the response. Patients on DTIC + CCNU are at higher risk of oxidative injury. This drug combination probably exerts its toxic activity by ROS, which could be products of the metabolism of CCNU. [source] Clonidine in paediatric anaesthesia: review of the literature and comparison with benzodiazepines for premedicationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2006H. Bergendahl Background:, Children undergoing anaesthesia and surgery can experience significant anxiety and distress during the peri-operative period, but whether routine premedication is necessary is currently debated. Benzodiazepines are the most frequently used drugs as premedication in paediatric anaesthesia. In the US, 50% of young children undergoing surgery receive premedication and midazolam is the most frequently used drug in this context (1). Nishina and coworkers (2) concluded in a review article in 1999 that clonidine, administered via an oral, rectal, or caudal route, is a promising adjunct to anaesthetics and analgesics to enhance quality of peri-operative management in infants and children. Later publications also support the use of clonidine for premedication (3,6). The aim of this communication is to review the use of clonidine in paediatric anaesthesia and to propose clonidine as a promising alternative to midazolam. Clonidine is associated with a number of beneficial effects in the context ofanaesthesia both in adults and children. Why clonidine is not routinely use in clinical practice despite the massive publication list is to a large extent due to the lack of marketing efforts from the pharmaceutical industry since multiplegeneric preparations are now readily available on most markets. Midazolam is also associated with a number of beneficial effects, but is far from an ideal premedicant in children, especially with regards to the amnesia, confusion and long term behavioural disturbances. Clonidine has contrary to midazolam no effect on respiration. We believe that clonidine is a good alternative to midazolam as premedication in infants and children. [source] Recent advances in antimalarial drug developmentMEDICINAL RESEARCH REVIEWS, Issue 1 2007Suryanaryana Vangapandu Abstract Malaria caused by protozoa of the genus Plasmodium, because of its prevalence, virulence, and drug resistance, is the most serious and widespread parasitic disease encountered by mankind. The inadequate armory of drugs in widespread use for the treatment of malaria, development of strains resistant to commonly used drugs such as chloroquine, and the lack of affordable new drugs are the limiting factors in the fight against malaria. These factors underscore the continuing need of research for new classes of antimalarial agents, and a re-examination of the existing antimalarial drugs that may be effective against resistant strains. This review provides an in-depth look at the most significant progress made during the past 10 years in antimalarial drug development. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 1, 65,107, 2007 [source] A practice survey on vasopressor and inotropic drug therapy in Scandinavian intensive care unitsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2003A. Oldner Background: This practice survey was performed to analyse the indications for use of vasopressor/inotropic drugs, preferred drugs and doses as well as concomitant monitoring and desired haemodynamic target values in Scandinavian ICUs. An internet-based reporting system was implemented. Methods: A total of 223 ICUs were identified in the Scandinavian countries and invited to participate in a one-day point-prevalence study. An internet-based database was constructed and a practice survey protocol designed to identify haemodynamic monitoring, indications for vasopressor/inotropic drug-therapy, fluids used for volume loading, pretreatment circulatory state, actual and targeted haemodynamic variables. Patients were eligible for the study if on vasopressor/inotropic drug-therapy for more than 4 h. Results: A total of 114 ICUs participated. A total of 114 adult patients matched the inclusion criteria. Sixty-seven per cent of the patients had received vasopressor/inotropic drug-treatment for >24 h and 32% received more than one drug. Arterial hypotension (92%) and oliguria (50%) were most common indications. Fluid loading prior to therapy was reported in 87% of patients. Dopamine (47%) and noradrenaline (44%) were the most commonly used drugs followed by dobutamine (24%). No other drug exceeded 6%. Non-catecholamine drugs were rarely used even in cardiac failure patients. Invasive arterial pressure was monitored in 95% of patients, pulmonary artery catheters were used in 19%. Other cardiac output monitoring techniques were used in 8.5% of the patients. Conclusion: Dopamine and noradrenaline seem to be the most commonly used inotropic/vasopressor drugs in Scandinavia. Traditional indications for inotropic/vasopressor support as hypotension and oliguria seem to be most common. Invasive monitoring was used in almost all patients, whereas a limited use of pulmonary artery catheters was noted. The internet-based reporting system proved to be an efficient tool for data collection. [source] Initial testing of cisplatin by the pediatric preclinical testing program,PEDIATRIC BLOOD & CANCER, Issue 5 2008Mimi Tajbakhsh BS Abstract Background Cisplatin is one of the most widely used drugs for the treatment of solid tumors in adults and children. Here, we report the activity of cisplatin against the PPTP panels of childhood cancer xenografts. Procedures Cisplatin was evaluated against 23 cell lines, and 40 xenografts representing brain tumors, neuroblastoma, rhabdoid tumors, sarcoma, Wilms tumor, and acute lymphoblastic leukemia (ALL). The IC50 concentration in vitro was determined for 96 hr exposure. Solid tumors were grown subcutaneously in immune-deficient mice, and tumor dimensions measured weekly. ALL xenografts were inoculated intravenously and the percent human CD45+ cells in the peripheral blood determined weekly. The antitumor activity of cisplatin (7 mg/kg administered intraperitoneally on Days 0 and 21) was evaluated using time to event (EFS T/C), tumor growth delay (tumor volume T/C), and objective response measures. Results The median IC50 concentration in vitro was 0.87 µM (0.24,4.29 µM), and cisplatin exhibited broad range activity. Cisplatin induced significant differences in EFS distributions compared to controls in 20/28 solid tumors and 4/8 ALL models. Objective responses were observed in 7/28 solid tumor models (25%): partial responses in three rhabdomyosarcomas and one Ewing's sarcoma; complete responses in one rhabdoid tumor and the medulloblastoma; and a maintained complete response in one Wilms tumor. No objective responses were observed in the ALL panel. Conclusions Cisplatin exhibits significant antitumor activity against a broad range of solid tumor xenograft models and limited activity against ALL xenografts. This preclinical pattern of activity is generally consistent with cisplatin's clinical activity. Pediatr Blood Cancer 2008;50:992,1000. © 2007 Wiley-Liss, Inc. [source] Nerve growth factor mediates steroid-resistant inflammation in respiratory syncytial virus infection,,PEDIATRIC PULMONOLOGY, Issue 6 2007Lida Mohtasham MD Abstract Neurotrophic factors and receptors are upregulated in the respiratory tract of humans and rodents infected by the respiratory syncytial virus, leading to airway inflammation and hyperreactivity. The contribution of neurotrophic pathways to the recruitment of immuno-inflammatory cells and their response to anti-inflammatory therapy remains unclear. We sought to determine whether selective nerve growth factor inhibition prevents the immuno-inflammatory response against infection, and explored the effect of inhaled corticosteroids on virus-induced neurotrophic upregulation and the consequent recruitment of immuno-inflammatory cells into the airways. We tried to inhibit the recruitment of lymphocytes and monocytes into the airways of infected weanling rats using immunologic inhibition of nerve growth factor with a specific blocking antibody, or chemical inhibition of receptor tyrosine kinase with K252a. The anti-inflammatory activity of inhaled corticosteroids was studied in infected rats treated with budesonide, fluticasone, or vehicle. Immunological or chemical inhibition of nerve growth factor or its high-affinity receptor tyrosine kinase pathway inhibited the recruitment of inflammatory cells triggered by nociceptive irritation of infected rat airways, thereby reducing local and systemic immuno-inflammatory responses against the virus. Neurotrophic upregulation in infected airways was not affected by inhaled corticosteroids. As a logical consequence, these commonly used drugs were also unable to stop the recruitment of immune and inflammatory effector cells into infected airways. Overexpression of neurotrophic factors and receptors in airways infected by respiratory syncytial virus is critical for the development of airway inflammation and hyperreactivity, which is resistant to the anti-inflammatory effect of inhaled corticosteroids. Pediatr Pulmonol. 2007; 42:496,504. © 2007 Wiley-Liss, Inc. [source] Perspectives on Health Among Adult Users of Illicit Stimulant Drugs in Rural OhioTHE JOURNAL OF RURAL HEALTH, Issue 2 2006Harvey A. Siegal PhD ABSTRACT:,Context: Although the nonmedical use of stimulant drugs such as cocaine and methamphetamine is increasingly common in many rural areas of the United States, little is known about the health beliefs of people who use these drugs. Purpose: This research describes illicit stimulant drug users' views on health and health-related concepts that may affect their utilization of health care services. Methods: A respondent-driven sampling plan was used to recruit 249 not-in-treatment, nonmedical stimulant drug users who were residing in 3 rural counties in west central Ohio. A structured questionnaire administered by trained interviewers was used to collect information on a range of topics, including current drug use, self-reported health status, perceived need for substance abuse treatment, and beliefs about health and health services. Findings: Participants reported using a wide variety of drugs nonmedically, some by injection. Alcohol and marijuana were the most commonly used drugs in the 30 days prior to the interview. Powder cocaine was used by 72.3% of the sample, crack by 68.3%, and methamphetamine by 29.7%. Fair or poor health status was reported by 41.3% of the participants. Only 20.9% of the sample felt they needed drug abuse treatment. Less than one third of the sample reported that they would feel comfortable talking to a physician about their drug use, and 65.1% said they preferred taking care of their problems without getting professional help. Conclusions: Stimulant drug users in rural Ohio are involved with a range of substances and hold health beliefs that may impede health services utilization. [source] Evolving Paradigms That Determine the Fate of an AllograftAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010J. S. Bromberg Despite the many advances in both immunological knowledge and the practical application of clinical immunosuppression, the holy grail of indefinite graft survival with immune tolerance in clinical solid organ transplantation remains a distant dream. The tremendous progress made in understanding the molecular and cellular basis of allograft rejection has not been translated into durable modalities that have advanced clinical care and outcomes. Indeed, currently used drugs and treatment protocols, largely directed at inhibiting alloreactive T cells, have not optimally improved allograft survival or function. A shift in emphasis, focusing on under appreciated immune pathways must now be considered to make further improvement. We highlight three areas of recent interest, complement, NK cells and lymphatics, which reinforce the concept that the transplant community must direct attention on how the immune system as a whole responds to a transplant. The current challenge is to integrate molecular, cellular and anatomic concepts to achieve the equivalent of a unified field theory of the immune response to organ transplants. [source] Promoting effect and recovery activity from physical stress of the fruit of Morus albaBIOFACTORS, Issue 1-4 2004Keum Hee Hwang Abstract We examined the effects of the fruit of M. alba extracts on the changes of the monoamine oxidase (MAO) activities during and after the physical exercise in rat. Each activity was measured by used serotonin(5-HT) and benzylamine as substrate. Lactate dehydrogenase(LDH) activity and the concentrations of lactate in blood which were clinical indexes of physical exercise were also determined to compare with the relation of MAO activities. Those activities during and after the physical exercise have different tendency in each other enzyme. MAO-A activity was sharply decreased with stress by physical activities compared to the normal group, whereas MAO-B activity was increased for 60 minutes after exercise. All of these indexes were recovered to normal state by oral administration of extract of M. alba. These results of this study suggested M. alba may modulate the MAO activities during exercise and promote the capability of physical activities and show anti-stress effect. In general, MAO inhibitors have been used drugs for the purpose of treatment Parkinson's disease, dementia, deprression. These results can apply to produce the health and functional foods that have modulating effects for these diseases. [source] Perceived adverse drug reactions among non-institutionalized children and adolescents in GermanyBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2010Hildtraud Knopf WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Drug safety in paediatric medication is a public health concern. According to previous studies, the incidence of adverse drug reactions (ADRs) varies greatly from 0.7% to 2.7% among paediatric outpatients and from 2.6% to 18.1% among paediatric inpatients. Little has been reported on the risks of drug use in the general child population. WHAT THIS STUDY ADDS Our study showed that the prevalence of perceived ADRs in Germany was 0.9% among non-institutionalized children in general and 1.7% among children who had used at least one medicine within the 7 days before the medical interview. Perceived ADRs in the general child population were clustered with gastrointestinal disorders and subcutaneous tissue disorders. They appeared to be mild and at the lower limits of the range reported in other studies. Health surveys covering the use of a diverse range of drugs might be suitable for computing ADR prevalence and for identifying risk factors among non-institutionalized children. They should be taken into account together with other pharmacovigilance systems. AIMS Little has been reported on the risks of drug use in the general child population. This study investigated perceived adverse drug reactions (ADRs) among non-institutionalized children in Germany. METHODS All medicines used in the last 7 days before the medical interview were recorded among the 17 450 children aged 0,17 years who participated in the 2003,06 German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Perceived ADRs were reported by the children's parents and confirmed by trained medical professionals during the medical interview. RESULTS One hundred and fifty-seven medicines were involved in the occurrence of 198 perceived ADRs in 153 patients. This corresponded to 1.1% of total used drugs, 0.9% (95% confidence intervals 0.7, 1.1%) of all children, and 1.7% (1.4, 2.1%) of children treated with medications. About 40% of all perceived ADRs involved gastrointestinal disorders and 16% involved skin tissue disorders. Perceived ADRs were most frequently reported in relation to drugs acting on the nervous system (25.8%), followed by systemic anti-infectives (18.7%) and drugs acting on the respiratory system (16.2%). Risk factors for perceived ADRs included older age groups, polypharmacy (,2) and a poor health status. CONCLUSION Perceived ADRs in the general child population were clustered with gastrointestinal disorders and subcutaneous tissue disorders. They appeared to be mild and at the lower limits of the range reported in other studies. Health surveys covering the use of a diverse range of drugs might be suitable for computing ADR prevalence and identifying risk factors among non-institutionalized children. They should be taken into account together with other pharmacovigilance systems. [source] | |||||||||||||||||||||||||||||||