Home About us Contact
|
Home About us Contact | ||
|
|
||
Drug Classes (drug + class)
Selected AbstractsFactor and item-response analysis DSM-IV criteria for abuse of and dependence on cannabis, cocaine, hallucinogens, sedatives, stimulants and opioidsADDICTION, Issue 6 2007Nathan A. Gillespie ABSTRACT Aims This paper explored, in a population-based sample of males, the factorial structure of criteria for substance abuse and dependence, and compared qualitatively the performance of these criteria across drug categories using item,response theory (IRT). Design Marginal maximum likelihood was used to explore the factor structure of criteria within drug classes, and a two-parameter IRT model was used to determine how the difficulty and discrimination of individual criteria differ across drug classes. Participants A total of 4234 males born from 1940 to 1974 from the population-based Virginia Twin Registry were approached to participate. Measurements DSM-IV drug use, abuse and dependence criteria for cannabis, sedatives, stimulants, cocaine and opiates. Findings For each drug class, the pattern of endorsement of individual criteria for abuse and dependence, conditioned on initiation and use, could be best explained by a single factor. There were large differences in individual item performance across substances in terms of item difficulty and discrimination. Cocaine users were more likely to have encountered legal, social, physical and psychological consequences. Conclusions The DSM-IV abuse and dependence criteria, within each drug class, are not distinct but best described in terms of a single underlying continuum of risk. Because individual criteria performed very differently across substances in IRT analyses, the assumption that these items are measuring equivalent levels of severity or liability with the same discrimination across different substances is unsustainable. Compared to other drugs, cocaine usage is associated with more detrimental effects and negative consequences, whereas the effects of cannabis and hallucinogens appear to be less harmful. Implications for other drug classes are discussed. [source] The Effect of Three-Tier Formulary Adoption on Medication Continuation and Spending among Elderly RetireesHEALTH SERVICES RESEARCH, Issue 5 2007Haiden A. Huskamp Objective. To assess the effect of three-tier formulary adoption on medication continuation and spending among elderly members of retiree health plans. Data Sources. Pharmacy claims and enrollment data on elderly members of four retiree plans that adopted a three-tier formulary over the period July 1999 through December 2002 and two comparison plans that maintained a two-tier formulary during this period. Study Design. We used a quasi-experimental design to compare the experience of enrollees in intervention and comparison plans. We used propensity score methods to match intervention and comparison users of each drug class and plan. We estimated repeated measures regression models for each class/plan combination for medication continuation and monthly plan, enrollee, and total spending. We estimated logit models of the probability of nonpersistent use, medication discontinuation, and medication changes. Data Collection/Extraction Methods. We used pharmacy claims to create person-level drug utilization and spending files for the year before and year after three-tier adoption. Principal Findings. Three-tier formulary adoption resulted in shifting of costs from plan to enrollee, with relatively small effects on medication continuation. Although implementation had little effect on continuation on average, a small minority of patients were more likely to have gaps in use and discontinue use relative to comparison patients. Conclusions. Moderate cost sharing increases from three-tier formulary adoption had little effect on medication continuation among elderly enrolled in retiree health plans with relatively generous drug coverage. [source] Management of hypertension and stroke prevention: results of the Italian cardiologist surveyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2009G. Tocci Summary Objective: To provide an overview of current habits, priorities, perceptions and knowledge of cardiologists with regard to hypertension and stroke prevention in outpatient practice. Methods: A sample of 203 cardiologists operating in outpatient clinics and randomly selected amongst members of the largest Italian Outpatient Cardiologist Association were interviewed by e-mail, in April,May 2007. Results: The interviewed cardiologists reported that hypertensive outpatients represent a large percentage of their practice population, in which the clinical priority was blood pressure (BP) reduction. Stroke was identified as the most important event to prevent and it was also perceived as the most preventable hypertension-related cardiovascular event. A remarkably high rate of achieved BP control was reported, to a degree that it is inconsistent with current epidemiological reports and with the relatively low percentage use of combination therapies declared by cardiologists. Additional risk factors, organ damage, diabetes mellitus and atrial fibrillation were consistently reported in hypertensive patients. Among antihypertensive drug classes, a preference for angiotensin-converting enzyme inhibitors has been expressed by the majority of physicians; this choice was generally justified by evidence derived from international trials or by the antihypertensive efficacy of this drug class. Conclusions: The results confirm the presence of weaknesses in the current services for patients with hypertension, even when being managed by cardiologists. Discrepancies between perceptions and reality, or clinical practice and guideline recommendations are also highlighted. An analysis of these aspects may help to identify current areas of potential improvement for stroke prevention in the clinical management of hypertension in cardiology practice. [source] The Role of Benzodiazepines in the Treatment of InsomniaJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2001Meta-Analysis of Benzodiazepine Use in the Treatment of Insomnia PURPOSE: To obtain a precise estimate of the efficacy and common adverse effects of benzodiazepines for the treatment of insomnia compared with those of placebo and other treatments. BACKGROUND: Insomnia, also referred to as disorder of initiating or maintaining sleep, is a common problem and its prevalence among older people is estimated to be 23% to 34%.1 The total direct cost in the United States for insomnia in 1995 was estimated to be $13.9 billion.2 The complaint of insomnia in older people is associated with chronic medical conditions; psychiatric problems, mainly depression, chronic pain, and poor perceived general condition;1,3,4 and use of sleep medications.5 Thus in most cases, insomnia is due to some other underlying problem and is not just a consequence of aging.6 Accordingly, the management of insomnia should focus on addressing the primary problem and not just short-term treatment of the insomnia. Benzodiazepines belong to the drug class of choice for the symptomatic treatment of primary insomnia.7 This abstract will appraise a meta-analysis that compared the effect of benzodiazepines for short-term treatment of primary insomnia with placebo or other treatment. DATA SOURCES: Data sources included articles listed in Medline from 1966 to December 1998 and the Cochrane Controlled Trials Registry. The medical subject heading (MeSH) search terms used were "benzodiazepine" (exploded) or "benzodiazepine tranquillizers" (exploded) or "clonazepam,""drug therapy,""randomized controlled trial" or "random allocation" or "all random,""human," and "English language." In addition, bibliographies of retrieved articles were scanned for additional articles and manufacturers of brand-name benzodiazepines were asked for reports of early trials not published in the literature. STUDY SELECTION CRITERIA: Reports of randomized controlled trials of benzodiazepine therapy for primary insomnia were considered for the meta-analysis if they compared a benzodiazepine with a placebo or an alternative active drug. DATA EXTRACTION: Data were abstracted from 45 randomized controlled trials representing 2,672 patients, 47% of whom were women. Fifteen studies included patients age 65 and older and four studies involved exclusively older patients. Twenty-five studies were based in the community and nine involved inpatients. The duration of the studies ranged from 1 day to 6 weeks, with a mean of 12.2 days and median of 7.5 days. The primary outcome measures analyzed were sleep latency and total sleep duration after a sleep study, subjects' estimates of sleep latency and sleep duration, and subjects' report of adverse effects. Interrater reliability was checked through duplicate, independent abstraction of the first 21 articles. Overall agreement was between 95% and 98% (kappa value of 0.90 and 0.95 accordingly) for classification of the studies and validity of therapy, and 76% (kappa value of 0.51) for study of harmful effects. A scale of 0 to 5 was used to rate the individual reports, taking into account the quality of randomization, blinding, follow-up, and control for baseline differences between groups. Tests for homogeneity were applied across the individual studies and, when studies were found to be heterogeneous, subgroup analysis according to a predefined group was performed. MAIN RESULTS: The drugs used in the meta-analysis included triazolam in 16 studies; flurazepam in 14 studies; temazepam in 13 studies; midazolam in five studies; nitrazepam in four studies; and estazolam, lorazepam, and diazepam in two studies each. Alternative drug therapies included zopiclone in 13 studies and diphenhydramine, glutethimide, and promethazine in one study each. Only one article reported on a nonpharmacological treatment (behavioral therapy). The mean age of patients was reported in 33 of the 45 studies and ranged between 29 and 82. SLEEP LATENCY: In four studies involving 159 subjects, there was sleep-record latency (time to fall asleep) data for analysis. The pooled difference indicated that the latency to sleep for patients receiving a benzodiazepine was 4.2 minutes (95% CI = (,0.7) (,9.2)) shorter than for those receiving placebo. Patient's estimates of sleep latency examined in eight studies showed a difference of 14.3 minutes (95% CI = 10.6,18.0) in favor of benzodiazepines over placebo. TOTAL SLEEP DURATION: Analysis of two studies involving 35 patients in which total sleep duration using sleep-record results was compared indicated that patients in the benzodiazepine groups slept for an average of 61.8 minutes (95% CI = 37.4,86.2) longer than those in the placebo groups. Patient's estimates of sleep duration from eight studies (566 points) showed total sleep duration to be 48.4 minutes (95% CI = 39.6,57.1) longer for patients taking benzodiazepines than for those on placebo. ADVERSE EFFECTS: Analysis of eight studies (889 subjects) showed that those in the benzodiazepine groups were more likely than those in the placebo groups to complain of daytime drowsiness (odds ratio (OR) 2.4, 95% confidence interval (CI) = 1.8,3.4). Analysis of four studies (326 subjects) also showed that subjects in the benzodiazepine groups were more likely to complain of dizziness or lightheadedness than the placebo groups. (OR 2.6, 95% CI = 0.7,10.3). Despite the increased reported side effects in the benzodiazepine groups, drop-out rates were similar in the benzodiazepine and placebo groups. For patient reported outcome, there was no strong correlation found for sleep latency data, (r = 0.4, 95% CI = (,0.3) (,0.9)) or for sleep duration (r = 0.2, 95% CI = ,0.8,0.4) between benzodiazepine dose and outcome. COMPARISON WITH OTHER DRUGS AND TREATMENTS: In three trials with 96 subjects, meta-analysis of the results comparing benzodiazepines with zopiclone, did not show significant difference in sleep latency in the benzodiazepine and placebo groups, but the benzodiazepine groups had increased total sleep duration (23.1 min. 95% CI = 5.6,40.6). In four trials with 252 subjects, the side effect profile did not show a statistically significant difference (OR 1.5, CI 0.8,2.9). There was only one study comparing the effect of behavioral therapy with triazolam. The result showed that triazolam was more effective than behavioral therapy in decreasing sleep latency, but its efficacy declined by the second week of treatment. Behavioral therapy remained effective throughout the 9-week follow-up period. There were four small trials that involved older patients exclusively, with three of the studies having less than 2 weeks of follow-up. The results were mixed regarding benefits and adverse effects were poorly reported. CONCLUSION: The result of the meta-analysis shows that the use of benzodiazepines results in a decrease in sleep latency and a significant increase in total sleep time as compared with placebo. There was also a report of significantly increased side effects, but this did not result in increased discontinuation rate. There was no dose-response relationship for beneficial effect seen with the use of benzodiazepines, although the data are scant. Zopiclone was the only alternative pharmacological therapy that could be studied with any precision. There was no significant difference in the outcome when benzodiazepines were compared with zopiclone. There was only one study that compared the effect of benzodiazepines with nonpharmacological therapy; thus available data are insufficient to comment. [source] The pharmacological properties of anisodamine,JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2007Jay M. Poupko Abstract Anisodamine is a naturally occurring atropine derivative that has been isolated, synthesized and characterized by scientists in the People's Republic of China. Like atropine and scopolamine, anisodamine is a non-specific cholinergic antagonist exhibiting the usual spectrum of pharmacological effects of this drug class. It appears to be less potent and less toxic than atropine and displays less CNS toxicity than scopolamine. Anisodamine has been shown to interact with and disrupt liposome structure which may reflect its effects on cellular membranes. Experimental evidence implicates anisodamine as an anti-oxidant that may protect against free radical-induced cellular damage. Its cardiovascular properties include depression of cardiac conduction and the ability to protect against arrhythmia induced by various agents. Anisodamine is a relatively weak ,1 adrenergic antagonist which may explain its vasodilating activity. Its anti-thrombotic activity may be a result of inhibition of thromboxane synthesis. The T1/2 of anisodamine in humans is about 2,3 h. Numerous therapeutic uses of anisodamine have been proposed including treatment of septic shock, various circulatory disorders, organophosphorus (OP) poisoning, migraine, gastric ulcers, gastrointestinal colic, acute glomerular nephritis, eclampsia, respiratory diseases, rheumatoid arthritis, obstructive jaundice, opiate addiction, snake bite and radiation damage protection. The primary therapeutic use of anisodamine has been for the treatment of septic shock. Several mechanisms have been proposed to explain its beneficial effect though most mechanisms are based upon the assumption that anisodamine ultimately acts by an improvement of blood flow in the microcirculation. Preliminary studies suggest another important therapeutic use of anisodamine is for the treatment of OP poisoning. Additional research is needed to delineate further the clinical usefulness of anisodamine relative to other anti-muscarinic drugs such as atropine and scopolamine. Copyright © 2006 John Wiley & Sons, Ltd. [source] Pharmacologic and Therapeutic Considerations in Hypertension Therapy With Calcium Channel Blockers: Focus on VerapamilJOURNAL OF CLINICAL HYPERTENSION, Issue 2 2007Domenic A. Sica MD In the past 2 decades, calcium channel blockers have emerged as important and useful agents for treating hypertension. The safety of this drug class has been vigorously debated for some time, and it has only been in the past few years that such debate has been quieted by favorable outcomes data with these compounds. Calcium channel blockers are a heterogeneous group of compounds as alike as they are dissimilar. Calcium channel blockers can be separated into dihydropyridine and nondihydropyridine subclasses, with representatives of the latter being verapamil and diltiazem. A lengthy treatment experience exists for verapamil, a compound that has progressed from an immediate-release to a sustained-release and, more recently, a delayed/sustained-release formulation designated for administration at bedtime. This latter formulation synchronizes drug delivery with the early morning rise in blood pressure, which is a particularly attractive feature when viewed in the context of the distinctive pharmacokinetic and pharmacodynamic features of verapamil. [source] Pharmacotherapy Review: Calcium Channel BlockersJOURNAL OF CLINICAL HYPERTENSION, Issue 1 2006Domenic A. Sica MD As a drug class, calcium channel blockers encompass a heterogeneous group of compounds with distinctive structures and pharmacologic characteristics. These agents are widely used in the treatment of hypertension, chronic coronary ischemia, and/or supraventricular arrhythmias. Much of the early debate alluding to increased cardiovascular risk associated with calcium channel blocker use has been silenced by an array of outcomes trials that show these drugs to be both safe and effective in reducing hard cardiovascular end points. The most common side effects associated with calcium channel blockers are vasodilatory in nature and include a non-volume-dependent form of peripheral edema, flushing, and headache. Despite the sometimes discomforting side effects seen with calcium channel blocker therapy, their robust blood pressure-lowering effect makes them an important component of most multidrug regimens used for blood pressure control. [source] Radioiodinated clioquinol as a biomarker for ,-amyloid: Zn2+ complexes in Alzheimer's diseaseAGING CELL, Issue 1 2006Carlos Opazo Summary Neocortical ,-amyloid (A,) aggregates in Alzheimer's disease (AD) are enriched in transition metals that mediate assembly. Clioquinol (CQ) targets metal interaction with A, and inhibits amyloid pathology in transgenic mice. Here, we investigated the binding properties of radioiodinated CQ ([125I]CQ) to different in vitro and in vivo Alzheimer models. We observed saturable binding of [125I]CQ to synthetic A, precipitated by Zn2+ (Kd = 0.45 and 1.40 nm for A,1-42 and A,1-40, respectively), which was fully displaced by free Zn2+, Cu2+, the chelator DTPA (diethylene triamine pentaacetic acid) and partially by Congo red. Sucrose density gradient of post-mortem AD brain indicated that [125I]CQ concentrated in a fraction enriched for both A, and Zn, which was modulated by exogenous addition of Zn2+ or DTPA. APP transgenic (Tg2576) mice injected with [125I]CQ exhibited higher brain retention of tracer compared to non-Tg mice. Autoradiography of brain sections of these animals confirmed selective [125I]CQ enrichment in the neocortex. Histologically, both thioflavine-S (ThS)-positive and negative structures were labeled by [125I]CQ. A pilot SPECT study of [123I]CQ showed limited uptake of the tracer into the brain, which did however, appear to be more rapid in AD patients compared to age-matched controls. These data support metallated A, species as the neuropharmacological target of CQ and indicate that this drug class may have potential as in vivo imaging agents for Alzheimer neuropathology. [source] Cardioprotection with beta-blockers: myths, facts and Pascal's wagerJOURNAL OF INTERNAL MEDICINE, Issue 3 2009F. H. Messerli Abstract. Beta-blockers were documented to reduce reinfarction rate more than 3 decades ago and subsequently touted as being cardioprotective for a broad spectrum of cardiovascular indications such as hypertension, diabetes, angina, atrial fibrillation as well as perioperatively in patients undergoing surgery. However, despite lowering blood pressure, beta-blockers have never shown to reduce morbidity and mortality in uncomplicated hypertension. Also, beta-blockers do not prevent heart failure in hypertension any better than any other antihypertensive drug class. Beta-blockers have been shown to increase the risk on new onset diabetes. When compared with nondiuretic antihypertensive drugs, beta-blockers increase all-cause mortality by 8% and stroke by 30% in patients with new onset diabetes. Beta-blockers are useful for rate control in patients with chronic atrial fibrillation but do not help restore sinus rhythm or have antifibrillatory effects in the atria. Beta-blockers provide symptomatic relief in patients with chronic stable angina but do not reduce the risk of myocardial infarction. Adverse effects of beta-blockers are common including fatigue, dizziness, depression and sexual dysfunction. However, beta-blockers remain a cornerstone in the management of patients having suffered a myocardial infarction and for patients with heart failure. Thus, recent evidence argues against universal cardioprotective properties of beta-blockers but attest to their usefulness for specific cardiovascular indications. [source] Analysis of the diversity of the HIV-1 pol gene and drug resistance associated changes among drug-naïve patients in Burkina FasoJOURNAL OF MEDICAL VIROLOGY, Issue 10 2009Denis M. Tebit Abstract A cross-sectional study was undertaken among drug-naïve HIV patients at the University Hospital in Ouagadougou shortly before and after the introduction of large-scale antiretroviral therapy (ART) in Burkina Faso. Baseline clinical and virological data as well as protease (PR) and 5, reverse transcriptase (RT) sequences from 104 HIV infected patients were analyzed. Genotypic classification revealed the following subtypes and recombinant forms: CRF06_cpx, n,=,46 (44.2%); CRF02_AG, n,=,39 (37.5%); subtype A, n,=,4 (3.8%); CRF09_cpx, n,=,2 (1.9%); and unclassified, n,=,13 (12.5%). Bootstrap analysis of CRF02_AG and CRF06_cpx viruses showed that >80% had a similar structure to their respective prototypes. The prevalence of primary drug resistance mutations was 12.5%, all mutations arising in the RT sequences in accordance with the dominance of this drug class in Burkina Faso. The mutations were distributed as follows: NRTI (10.6%): M41L (n,=,2), D67N (n,=,2), K70K/E (n,=,2), L210W (n,=,1), T215S/Y (n,=,2), and K219K/Q (n,=,2); NNRTI (6.1%): K103K/N (n,=,2), Y181C (n,=,2), G190G/A (n,=,1), and P236P/L (n,=,1). Subtype specific secondary polymorphisms such as K20I and M36I in the PR were observed in almost all patients. Drug resistance mutations occurred at similar frequencies (12.8% and 10.8%, respectively) among patients infected with CRF02_AG and CRF06_cpx. Some subtype specific polymorphisms were observed within important HLA epitopes, including B35, B7, and A2 in the RT, and A*6802 in the PR sequences. The observed resistance mutations are most likely to have been transmitted based on the timing of the study but prior undocumented use of ART cannot be excluded. J. Med. Virol. 81:1691,1701, 2009. © 2009 Wiley-Liss, Inc. [source] Prediction of human pharmacokinetics , improving microsome-based predictions of hepatic metabolic clearanceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2007Urban Fagerholm Physiologically based methods generally perform poorly in predicting in-vivo hepatic CL (CLH) from intrinsic clearance (CLint) in microsomes in-vitro and unbound fraction in blood (fu,bl). Various strategies to improve the predictability have been developed, and inclusion of an empirical scaling factor (SF) seems to give the best results. This investigation was undertaken to evaluate this methodology and to find ways to improve it further. The work was based on a diverse data set taken from Ito and Houston (2005). Another objective was to evaluate whether rationalization of CLH predictions can be made by replacing blood/plasma-concentration ratio (Cbl/Cpl) measurements with SFs. There were apparently no or weak correlations between prediction errors and lipophilicity, permeability (compounds with low permeability missing in the data set) and main metabolizing CYP450s. The use of CLint class (high/low) and drug class (acid/base/neutral) SFs (the CD-SF method) gives improved and reasonable predictions: 1.3-fold median error (an accurate prediction has a 1-fold error), 76% within 2-fold-error, and a median absolute rank ordering error of 2 for CLH (n = 29). This approach is better than the method with a single SF. Mean (P < 0.05) and median errors, fraction within certain error ranges, higher percentage with most accurate predictions, and ranking were all better, and 76% of predictions were more accurate with this new method. Results are particularly good for bases, which generally have higher CLH and the potential to be incorrectly selected/rejected as candidate drugs. Reasonable predictions of fu,bl can be made from plasma fu (fu,pl) and empirical blood cell binding SFs (B-SFs; 1 for low fu,pl acids; 0.62 for other substances). Mean and median fu,bl prediction errors are negligible. The use of the CD-SF method with predicted fu,bl (the BCD-SF method) also gives improved and reasonable results (1.4-fold median error; 66% within 2-fold-error; median absolute rank ordering error = 1). This new empirical approach seems sufficiently good for use during the early screening; it gives reasonable estimates of CLH and good ranking, which allows replacement of Cbl/Cpl measurements by a simple equation. [source] RT08 Population PK and PK/PD investigations and Monte Carlo simulations for a rational dosage regimenJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2006P. L. TOUTAIN Objective There are several means whereby dosage schedules for clinical use may be set, some more appropriate and scientific than others! The challenge of the 21st century must be for colleagues in the pharmaceutical industry, those serving registration bodies and academic colleagues to pool their expertise with the objective of designing dosage schedules for clinical use, which are based on the application of sound scientific principles appropriate for each drug class. In this Roundtable Session colleagues of international standing will review (a) pharmacological and other sources of variability in the responses to drugs; (b) the advantages and limitations of pre-clinical studies for dose selection; (c) the roles of population PK and population PK/PD together with Monte Carlo simulations in dosage regimen selection; (d) Bayesian approaches to dosage selection and (e) regulatory guidelines on the type and extent of studies required for selecting dosages. There is no unanimity amongst stakeholders on either the principles or the methods underlying dosage schedule design. Dose titration studies have long been the principal means of fixing doses but PK-PD and population PK-PD studies are now challenging more traditional approaches. The papers and discussion in this Roundtable Session will provide a critical basis for future advances in this crucial area of therapeutic drug usage. Getting the doses right means that the patient will receive maximum benefit, in terms of optimal efficacy with minimal toxicity, and hence correct dosing will contribute enormously to animal welfare. [source] RT09 Bayesian approaches in dosage selectionJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2006D. CONCORDET Objective There are several means whereby dosage schedules for clinical use may be set, some more appropriate and scientific than others! The challenge of the 21st century must be for colleagues in the pharmaceutical industry, those serving registration bodies and academic colleagues to pool their expertise with the objective of designing dosage schedules for clinical use, which are based on the application of sound scientific principles appropriate for each drug class. In this Roundtable Session colleagues of international standing will review (a) pharmacological and other sources of variability in the responses to drugs; (b) the advantages and limitations of pre-clinical studies for dose selection; (c) the roles of population PK and population PK/PD together with Monte Carlo simulations in dosage regimen selection; (d) Bayesian approaches to dosage selection and (e) regulatory guidelines on the type and extent of studies required for selecting dosages. There is no unanimity amongst stakeholders on either the principles or the methods underlying dosage schedule design. Dose titration studies have long been the principal means of fixing doses but PK-PD and population PK-PD studies are now challenging more traditional approaches. The papers and discussion in this Roundtable Session will provide a critical basis for future advances in this crucial area of therapeutic drug usage. Getting the doses right means that the patient will receive maximum benefit, in terms of optimal efficacy with minimal toxicity, and hence correct dosing will contribute enormously to animal welfare. [source] A Critical Appraisal of COX-2 Selective Inhibition and Analgesia: How Good So Far?PAIN PRACTICE, Issue 3 2003Pedro F. Bejarano MD Abstract: The development of COX-2 selective inhibitors has opened a new era of clinical investigation in NSAIDs. Discussion of the established concepts of inflammation and therapeutical uses of these drugs has changed the rationale for its clinical use and therapeutic labeling of these drugs. A comprehensive discussion across basic science and clinical areas involved in each of these concepts is presented. This led to a remarkable re-evaluation of our insights on their traditionally proposed mechanisms of analgesia, their side-effects, and the clinical indication of NSAIDs as "over the counter" pain killers. This may shift physicians toward a more rational use of this drug class. [source] Adverse drug reactions in medical intensive care unit of a tertiary care hospital,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2009Lisha Joshua MBBS Abstract Purpose Patients in the intensive care unit (ICU) have multiorgan dysfunction as well as altered pharmacokinetic parameters. Hence they are susceptible to adverse drug reactions (ADRs). The objective of the study is to assess the characteristics of ADRs among inpatients in the medical ICU and to compare the same with patients who have not experienced ADRs. Methods Prospective, observational study for a period of 1 year in medical ICU of a tertiary care hospital. Relevant data of patients with ADRS were analysed. Characteristics of patients with and without ADRs were compared. Results Of 728 patients admitted in medical ICU, 222 (28.4%) had ADRs. Multiple ADRs (38.7%) implicated by the same drug and serious ADRs (37%) were noticed. Renal/electrolyte system (21%) was most commonly involved. Clinical spectrum included acute renal failure (ARF, 11.4%), hepatic injuries (5.4%), haematological dysfunction (4.2%), seizures (3.3%), upper gastrointestinal bleed (3.3%) and cutaneous ADRs (3.3%). Antimicrobials (27%) were the commonly implicated drug class. The most commonly implicated drug was furosemide (6.8%). Infrequently reported ADRs included azithromycin-induced erythema multiforme, leflunamide-induced erythema multiforme and vasculitis, ceftazidime-induced seizures and ceftriaxone-induced hepatitis. Co-morbidity, polypharmacy and duration of stay were significantly higher in patients with ADRs compared to those who have not experienced ADRs. Three patients died. Conclusion High incidence of serious and multiple ADRs noticed. A wide clinical spectrum of ADRs and infrequently reported ADRs to newer drugs were also observed. Copyright © 2009 John Wiley & Sons, Ltd. [source] Latest news and product developmentsPRESCRIBER, Issue 5 2007Article first published online: 16 MAY 200 OFT wants PPRS reform The Office of Fair Trading (www.oft.gov.uk) says reform of the Pharmaceutical Price Regulatory Scheme (PPRS) would allow the NHS to re- invest £500 million in drugs it needs. Its investigation of the 50- year-old PPRS concludes that the scheme does not reflect the therapeutic value of drugs and, while providing a financial safety net for the industry, it mitigates against innovation. The OFT believes drugs should be priced according to their therapeutic value based on their cost effectiveness. Analyses would be fast- tracked for new drugs or, if there are insufficient data, a risk-sharing scheme should be adopted. The ABPI insists that its medicines offer the NHS value for money and believes the OFT's proposal for drug- by-drug pricing would delay access to new medicines. Switching saves money and is problem free Switching to cheaper alternatives within a drug class does not affect the quality of care and offers substantial savings, say UK researchers (Int J Clin Pract 2007;61:15-23). They switched selected patients from atorvastatin (Lipitor) to simvastatin and from losartan (Cozaar) to candesartan (Amias). Exclusion criteria included previous unsuccessful use, poor control of lipids or blood pressure, contraindications and potential drug interactions. In 70 patients switched to simvastatin, there was no change in mean total cholesterol after four months; one patient reverted to atorvastatin due to adverse effects. Of 115 switched to candesartan, seven reverted to losartan; in the remainder, blood pressure was slightly reduced after four months. The switch was not associated with adverse effects. Savings for the year 2005/06 were estimated at £12 716 for statins and £13 374 for antihypertensive drugs. Scotland gets donepezil for mild to moderate AD The Scottish Medicines Consortium (www.scottish medicines.org.uk) has approved the use of orodispersible donepezil (Aricept Evess) for the treatment of mild to moderate Alzheimer's disease in NHS Scotland. The decision conflicts with NICE advice that the drug is not appropriate for patients with mild disease. The SMC has not approved rimonabant (Acomplia) as adjunctive treatment for obese patients. Adherence threatens anticoagulation Patients find it difficult to adhere to anticoagulant treatment ,significantly impairing the quality of anticoagulation, US investigators have shown (Arch Intern Med 2007;167:229-35). Using electronic containers to monitor dose adherence over 32 weeks in 136 patients, they found that 92 per cent opened the container at least once too often or too little and one-third missed 20 per cent of scheduled openings. Patients with less than 20 per cent adherence were twice as likely to be undercoagulated compared with adherent patients. Those with overadherence were overcoagulated. Hypo risk greatest with glibenclamide Glibenclamide is associated with a significantly greater risk of hypoglycaemic events than other secretagogues, a new systematic review has concluded (Diabetes Care 2007;30:389-94). The review of 21 randomised trials found that the risk of experiencing at least one hypoglycaemic event was 52 per cent greater with glibenclamide compared with other secretagogues and 83 per cent greater than with other sulphonylureas. In three comparative trials with insulin, there was no significant difference in the risk of hypoglycaemia (though this could not be excluded) but only insulin was associated with weight gain. Glibenclamide was not associated with significantly increased risks of cardiovascular events, weight gain or death. Few major hypoglycaemic events were reported in these trials. Drug groups implicated in ADR admissions Four classes of drugs account for half of hospital admissions for adverse reactions, according to a new systematic review (Br J Clin Pharmacol 2007;63:136-47). Antiplatelet agents (16 per cent of admissions), diuretics (16 per cent), NSAIDs (11 per cent) and anticoagulants (8 per cent) were implicated in drug- related admissions according to a review of nine studies. Analysis of five studies also showed that adherence problems were associated with one-third of drug-related admissions. The authors suggest that focussing resources in these areas could substantially reduce admissions. Value of pharmacist MUR questioned Pharmacist medicines use review (MUR) for older patients does not reduce hospital readmission and is not cost effective by current standards, according to a study from Norfolk (Pharmacoeconomics 2007;25:171-80). A total of 872 patients aged over 80 who had been admitted as an emergency and discharged taking two or more drugs were randomised to MUR by a pharmacist or usual care. The pharmacist visited twice, providing education, removing out-of-date drugs and checking for adverse effects, interactions and the need for compliance aids. After six months, the admissions rate was not reduced among patients who received MUR and quality of life was not significantly improved. The estimated cost per QALY gained was £54 454 , above the conventional threshold for cost effectiveness of £30 000. MHRA review of LABAs The MHRA has clarified which aspects of long-acting beta-agonists (LABAs) are being addressed in its current review. This full review of salmeterol (Serevent) and formoterol, following advice issued in December last year, will consider recent research, whether the two agents differ significantly, dose-response relationships, the effect of concurrent treatment with inhaled steroid and how they are used in practice. Manufacturers have been asked to provide data by the end of March. Interventions for weight gain in schizophrenia There is not enough evidence to support the use of drugs to reduce weight gain associated with schizophrenia, a new Cochrane review has found (Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD005148. DOI: 10.1002/14651858. CD005148.pub2). Noting a lack of adequate trials, the review found that cognitive/behavioural interventions effectively prevented weight gain by a mean of 3.4kg and reduced established weight gain by a mean of 1.7kg. Drugs prevented weight gain by about 1.2kg. Switching anti-TNFs An analysis of a UK rheumatoid arthritis (RA) registry has shown that patients who stop treatment with their first anti-TNF agent should be switched to a second (Arthr Rheum 2007;56:13-20). Every UK patient with RA who receives an anti-TNF agent is included in the British Society for Rheumatology Biologics Register. Analysis of this database identified 6739 patients who started treatment, of whom 841 stopped within 15 months due to lack of efficacy and 1023 due to toxicity. Of these, 503 and 353 respectively were switched to another anti- TNF agent. Overall, 73 per cent of patients remained on their second drug by the end of follow-up, but patients were two to three times more likely to stop their second treatment for the same reason they discontinued their first. Copyright © 2007 Wiley Interface Ltd [source] Antidepressants in the Treatment of Neuropathic PainBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2005Søren H. Sindrup Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2,3 patients with peripheral neuropathic pain, serotonin noradrenaline reuptake inhibitors one in every 4,5 and selective serotonin reuptake inhibitors one in every 7 patients. Thus, based on efficacy measures such as numbers needed to treat, tricyclic antidepressants tend to work better than the anticonvulsant gabapentin and treatment options such as tramadol and oxycodone, whereas the serotonin noradrenaline reuptake inhibitor venlafaxine appears to be equally effective with these drugs and selective serotonin reuptake inhibitors apparently have lower efficacy. Head-to-head comparisons between antidepressants and the other analgesics are lacking. Contraindications towards the use of tricyclic antidepressants and low tolerability in general of this drug class , may among the antidepressants , favour the use of the serotonin noradrenaline reuptake inhibitors. A recent study on bupropion, which is a noradrenaline and dopamine uptake inhibitor, indicated a surprisingly high efficacy of this drug in peripheral neuropathic pain. In conclusion, antidepressants represent useful tools in neuropathic pain treatment and must still be considered as first line treatments of neuropathic pain. However, without head-to-head comparisons between antidepressants and other analgesics, it is not possible to provide real evidence-based treatment algorithms for neuropathic pain. [source] Perception of risk of adverse drug reactions by medical students: influence of a 1 year pharmacological courseBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2007G. Durrieu What is already known about this subject ,,Previous studies have pointed out the question of effective training and information for health professionals on adverse drug reactions (ADRs). ,,This lack of training is known to induce inadequate use of drugs and noncompliance of patients. What this study adds ,,Our study was the first to evaluate the perceived risk of ADRs among young medical students and to investigate the impact of university pharmacology courses on their perception of this risk. ,,The aim of our study was not to assess a definite level of perception of risk for the different drug classes but to determine whether the perceived risk of ADRs differs after attending pharmacology courses. ,,Our results show that the pharmacological training allows young medical students to be aware of potentially serious ADRs, especially related to drugs considered as relatively safe, such as NSAIDs and aspirin. Aims To investigate how adverse drug reactions (ADRs) to several classes of drugs are perceived by young medical students before and after a 1 year pharmacology course. Methods The whole cohort of 92 medical students (63 females and 29 males) was questioned during their third year. A visual analogue scale was used to define a score (ranging from 0 to 10) of perceived risk of ADRs associated with each drug class before and at the end of the pharmacological training period. Results Before the pharmacology course, hypnotics were ranked as the most dangerous drugs by the medical students, followed by antidepressants and anticoagulants. Contraceptive pills were listed in the last position. After pharmacological training, antidepressants moved into the first position, followed by anticoagulants and hypnotics. When all different drug classes were taken as a whole, the mean (±SD) of median scores of the perceived risk were 4.8 (±1.3) before and 5.8 (±1.5) at the end of the pharmacology course (P < 0.0001). Except for antidiabetics, antihypertensive drugs, tranquillizers, corticosteroids and hypnotics, the perceived risk significantly increased after the pharmacology course for the other drugs. The highest increases were observed for contraceptive pills (+104%, P < 0.01), NSAIDs (+86%, P < 0.01) and aspirin (+56%, P < 0.01). Conclusions Pharmacological training allows young medical students to be aware of potentially serious ADRs associated with drugs, in particular with drugs considered relatively safe (such as NSAIDs and aspirin) by nonhealth professionals. [source] Strategies to improve efficacy and safety of a novel class of antiviral hyper-activation-limiting therapeutic agents: the VS411 model HIV/AIDSBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2010D De Forni BACKGROUND AND PURPOSE Antiviral hyper-activation-limiting therapeutic agents (AV-HALTs) are a novel experimental drug class designed to both decrease viral replication and down-regulate excessive immune system activation for the treatment of chronic infections, including human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. VS411, a first-in-class AV-HALT, is a single-dosage form combining didanosine (ddI, 400 mg), an antiviral (AV), and hydroxyurea (HU, 600 mg), a cytostatic agent, designed to provide a slow release of ddI to reduce its maximal plasma concentration (Cmax) to potentially reduce toxicity while maintaining total daily exposure (AUC) and the AV activity. EXPERIMENTAL APPROACH This was a pilot phase I, open-label, randomized, single-dose, four-way crossover trial to investigate the fasted and non-fasted residual variance of AUC, Cmax and the oral bioavailability of ddI and HU, co-formulated as VS411, and administered as two different fixed-dose combination formulations compared to commercially available ddI (Videx EC) and HU (Hydrea) when given simultaneously. KEY RESULTS Formulation VS411-2 had a favourable safety profile, displayed a clear trend for lower ddI Cmax (P= 0.0603) compared to Videx EC, and the 90% confidence intervals around the least square means ratio of Cmax did not include 100%. ddI AUC, was not significantly decreased compared to Videx EC. HU pharmacokinetic parameters were essentially identical to Hydrea, although there was a decrease in HU exposure under fed versus fasted conditions. CONCLUSIONS AND IMPLICATIONS A phase IIa trial utilizing VS411-2 formulation has been fielded to identify the optimal doses of HU plus ddI as an AV-HALT for the treatment of HIV disease. [source] The abuse of diuretics as performance-enhancing drugs and masking agents in sport doping: pharmacology, toxicology and analysisBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2010Amy B Cadwallader Diuretics are drugs that increase the rate of urine flow and sodium excretion to adjust the volume and composition of body fluids. There are several major categories of this drug class and the compounds vary greatly in structure, physicochemical properties, effects on urinary composition and renal haemodynamics, and site and mechanism of action. Diuretics are often abused by athletes to excrete water for rapid weight loss and to mask the presence of other banned substances. Because of their abuse by athletes, diuretics have been included on The World Anti-Doping Agency's (WADA) list of prohibited substances; the use of diuretics is banned both in competition and out of competition and diuretics are routinely screened for by anti-doping laboratories. This review provides an overview of the pharmacology and toxicology of diuretics and discusses their application in sports. The most common analytical strategies currently followed by the anti-doping laboratories accredited by the WADA are discussed along with the challenges laboratories face for the analysis of this diverse class of drugs. [source] ThiaZolidineDiones and the Influence of Media Adverse Reporting on Prescribing Attitudes in PraCTice (TZD-IMPACT) StudyCARDIOVASCULAR THERAPEUTICS, Issue 2 2009Jacob George Prescribing behavior may be linked to media influence rather than to scientific evidence. Recently, the oral diabetic drug class of thiazolidinedione has been under the spotlight because of concerns over their cardiovascular safety. We have therefore conducted an electronic questionnaire survey among prescribing physicians in Tayside, Scotland to evaluate the prescribing attitudes and knowledge of the available evidence regarding the cardiovascular safety of thiazolidinedione use. Nationally representative prescribing data thoughout Scotland and Tayside from the IMS Health RSA dataset were also examined. Prescriptions for rosiglitazone alone or in combination with metformin have steadily decreased since the publication of a meta-analysis suggesting harm from rosiglitazone. This was mirrored by a gradual increase in prescriptions of pioglitazone. However, when questioned, the majority of doctors rate the level of information received regarding drug safety information on thiazolidinediones to be low with 68% of respondents scoring 5 or less (scale 1,10) on the level of information received. The source of information regarding drug safety warning was highly varied ranging from journals (21%), scientific meetings (19%) and the news media (15%). The findings of this study clearly show a need to disseminate reliable drug safety information more effectively to prescribers. [source] Pharmacological profile of the new antihistaminesCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 1 2005J.-P. Tillement Summary The second-generation H1 antihistamines are a highly efficacious drug class in the treatment of allergic rhinitis (AR) and dermatitis, and distinct from the first-generation H1 antihistamines, predominantly because of their non-sedating nature at recommended dosages. Despite a marked chemical heterogeneity, the non-sedating H1 antihistamines have many similarities, in particular, high affinity for H1 receptors, high efficacy, anti-inflammatory effects, which may be independent of direct H1 -receptor function, and lack of central nervous system side-effects. Some studies have suggested that differences in the chemical structures of these compounds generally lead to differences in the pharmacokinetic properties, which determine their overall clinical usefulness. In particular, it has been demonstrated that there are differences in selectivity for H1 receptors, the apparent volume of distribution, metabolism and elimination and interaction with other drugs. A comparison of levocetirizine, fexofenadine, desloratadine and mizolastine (some of the most commonly prescribed drugs in the treatment of AR and dermatitis) has demonstrated that, unlike levocetirizine and fexofenadine, desloratadine and mizolastine can bind to muscarinic receptors and cardiac K+ channels, and therefore have both lower selectivity and the potential to induce muscarinic and serious cardiac side-effects. However, this is noted at higher than recommended doses. Similarly, desloratadine and mizolastine undergo extensive metabolism and, together with fexofenadine, have the potential to interact with other drugs, in turn increasing the potential for severe toxic effects. In contrast, levocetirizine is not metabolized, is eliminated rapidly from the body, does not demonstrate any significant drug interactions and has the lowest volume of distribution. These findings suggest that levocetirizine is likely to be a safer drug than fexofenadine, desloratadine and mizolastine. [source] Positron emission tomography and its use to image the occupancy of drug binding sitesDRUG DEVELOPMENT RESEARCH, Issue 2 2003S. John Gatley Abstract The development of positron emission tomography (PET) and the ability to synthesize compounds labeled with the short-lived positron emitters 11C and 18F has made possible the imaging and quantification of drug binding sites in the human body. By conducting PET studies with an appropriate radioligand before and after treatment with a drug, the fraction of the total number of binding sites that is occupied by the drug (the "occupancy" of the site) can often be determined. To the extent that occupancy is a good indicator of pharmacological activity, such PET experiments can aid the development of drug dosage regimens. Some of the general issues involved in PET studies of drug occupancy are discussed. There have been many such studies involving antipsychotic drugs and dopamine D2 receptor radioligands. Since neuroleptics have been extensively reviewed elsewhere, only the major findings are discussed here. Other binding sites (and drug classes) in the dopamine system to which this methodology has been applied include: the dopamine transporter (stimulant drugs) and monoamine oxidase A and B (antidepressant drugs). Occupancy studies are also possible for many drug targets beyond the dopamine system. Drug Dev. Res. 59:194,207, 2003. © 2003 Wiley-Liss, Inc. [source] Out-of-hospital Care of Critical Drug Overdoses Involving Cardiac ArrestACADEMIC EMERGENCY MEDICINE, Issue 1 2004Valentine L. Paredes MD Objectives: Death from acute drug poisoning, also termed drug overdose, is a substantial public health problem. Little is known regarding the role of emergency medical services (EMS) in critical drug poisonings. This study investigates the involvement and potential mortality benefit of EMS for critical drug poisonings, characterized by cardiovascular collapse requiring cardiopulmonary resuscitation (CPR). Methods: The study population was composed of death events caused by acute drug poisoning, defined as poisoning deaths and deaths averted (persons successfully resuscitated from out-of-hospital cardiac arrest by EMS) in King County, Washington, during the year 2000. Results: Eleven persons were successfully resuscitated and 234 persons died from cardiac arrest caused by acute drug poisoning, for a total of 245 cardiac events. The EMS responded to 79.6% (195/245), attempted resuscitation in 34.7% (85/245), and successfully resuscitated 4.5% (11/245) of all events. Among the 85 persons for whom EMS attempted resuscitation, opioids, cocaine, and alcohol were the predominant drugs involved, although over half involved multiple drug classes. Among the 11 persons successfully resuscitated, return of circulation was achieved in six following EMS cardiopulmonary resuscitation alone, in one following CPR and defibrillation, and in the remaining four after additional advanced life support. Conclusions: In this community, EMS was involved in the majority of acute drug poisonings characterized by cardiovascular collapse and may potentially lower total mortality by approximately 4.5%. The results show that, in some survivors, return of spontaneous circulation may be achieved with CPR alone, suggesting a different pathophysiology in drug poisoning compared with cardiac arrest due to heart disease. [source] Factor and item-response analysis DSM-IV criteria for abuse of and dependence on cannabis, cocaine, hallucinogens, sedatives, stimulants and opioidsADDICTION, Issue 6 2007Nathan A. Gillespie ABSTRACT Aims This paper explored, in a population-based sample of males, the factorial structure of criteria for substance abuse and dependence, and compared qualitatively the performance of these criteria across drug categories using item,response theory (IRT). Design Marginal maximum likelihood was used to explore the factor structure of criteria within drug classes, and a two-parameter IRT model was used to determine how the difficulty and discrimination of individual criteria differ across drug classes. Participants A total of 4234 males born from 1940 to 1974 from the population-based Virginia Twin Registry were approached to participate. Measurements DSM-IV drug use, abuse and dependence criteria for cannabis, sedatives, stimulants, cocaine and opiates. Findings For each drug class, the pattern of endorsement of individual criteria for abuse and dependence, conditioned on initiation and use, could be best explained by a single factor. There were large differences in individual item performance across substances in terms of item difficulty and discrimination. Cocaine users were more likely to have encountered legal, social, physical and psychological consequences. Conclusions The DSM-IV abuse and dependence criteria, within each drug class, are not distinct but best described in terms of a single underlying continuum of risk. Because individual criteria performed very differently across substances in IRT analyses, the assumption that these items are measuring equivalent levels of severity or liability with the same discrimination across different substances is unsustainable. Compared to other drugs, cocaine usage is associated with more detrimental effects and negative consequences, whereas the effects of cannabis and hallucinogens appear to be less harmful. Implications for other drug classes are discussed. [source] Cocaine Rapid Efficacy Screening Trial (CREST): a paradigm for the controlled evaluation of candidate medications for cocaine dependenceADDICTION, Issue 2005Deborah B. Leiderman ABSTRACT Aim Development of effective medications for the treatment of cocaine dependence remains a major priority for the National Institute on Drug Abuse (NIDA) at the National Institutes of Health. The Cocaine Rapid Efficacy Screening Trial (CREST) paradigm was developed by the Division of Treatment Research and Development (DT R&D) at NIDA with the goal of enhancing pilot clinical trial validity when systematically assessing a range of medications and drug classes for potential utility in treatment of cocaine dependence. Design CREST utilizes a randomized, controlled, parallel group, blinded methodology for comparing one or more marketed medications against a standard, pharmaceutical grade placebo. The trial design is comprised of a flexible 2,4-week screening/baseline period followed by randomization to an 8-week treatment period. Measures Standard measures of outcomes for the CREST included urinary benzoylecgonine (primary metabolite of cocaine), retention, cocaine craving, depression, clinical global impression and HIV-risk behaviors. In order to facilitate comparisons of data from the CREST studies across sites, drug classes and time, standardized procedures, measures and psychosocial counseling were used. Results A total of 19 medications were evaluated in out-patient treatment research clinics in Boston, Cincinnati, Los Angeles, New York and Philadelphia. Conclusions Findings supported decisions to move forward three medications (cabergoline, reserpine, tiagabine) using full-scale, adequately powered, randomized placebo-controlled trial designs. Lessons learned from the CREST experience continue to shape cocaine pharmacotherapy trial design and execution. [source] An update on cyathostomins: Anthelmintic resistance and worm controlEQUINE VETERINARY EDUCATION, Issue 10 2008J. B. Matthews Summary Intestinal nematodes are an important cause of equine disease. Of these parasites, the Cyathostominae are the most important group, both in terms of their prevalence and their pathogenicity. Cyathostomin infections are complex and control is further complicated by ever-increasing levels of resistance to some of the commonly used anthelmintics. There are no new equine anthelmintics under development, so it is imperative that the efficacy of any currently-effective drug classes be maintained for as long as possible. It is believed that the proportion of refugia (i.e. the percentage of parasites not exposed to a drug at each treatment) is one of the most crucial factors in determining the rate at which anthelmintic resistance develops. It is important, therefore, that levels of refugia be taken into account when designing nematode control programmes for horses. This can be assisted by knowledge of the local epidemiology of the infection, supplemented by faecal egg count analysis to identify those animals that are making the major contribution to pasture contamination. This type of rational nematode control requires equine veterinary surgeons to get involved in designing and implementing deworming programmes. The advice given must be based on a combination of knowledge of cyathostomin biology and epidemiology as well as an awareness of the parasite population's current drug sensitivity and a sound history of husbandry at the establishment. As anthelmintic resistance will be the major constraint on the future control of cyathostomins, researchers are now actively investigating this area. Studies are underway to develop tests that will enable earlier detection of anthelmintic resistance and an assay that will help identify those horses that require anthelmintic treatments targeted at intestinal wall larvae. [source] Synthesis of "Trioxaquantel"® Derivatives as Potential New Antischistosomal DrugsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 5 2008Sophie A.-L. Abstract Over the past 20 years, praziquantel, a pyrazinoisoquinoline derivative, has become the mainstay for morbidity control of human and animal schistosomiasis. From early in their lives in vertebrate hosts, schistosomes ingest hemoglobin and aggregate the released heme as a dark pigment very similar to the hemozoin produced by Plasmodium in malaria infection. The antimalarial artemisinin derivatives have real, though low, schistosomicide activity. Because of the complementarity of the two drug classes , praziquantel and artemisinin derivatives , we designed new molecules, named trioxaquantels®, that combine the 1,2,4-trioxane unit responsible for the activity of artemisinin, and the pyrazinoisoquinoline moiety of praziquantel within a single drug. The synthesis of these new drugs and their preliminary evaluation in mice infected with Schistosoma mansoni is reported here.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Drug effect on EEG connectivity assessed by linear and nonlinear couplingsHUMAN BRAIN MAPPING, Issue 3 2010Joan F. Alonso Abstract Quantitative analysis of human electroencephalogram (EEG) is a valuable method for evaluating psychopharmacological agents. Although the effects of different drug classes on EEG spectra are already known, interactions between brain locations remain unclear. In this work, cross mutual information function and appropriate surrogate data were applied to assess linear and nonlinear couplings between EEG signals. The main goal was to evaluate the pharmacological effects of alprazolam on brain connectivity during wakefulness in healthy volunteers using a cross-over, placebo-controlled design. Eighty-five pairs of EEG leads were selected for the analysis, and connectivity was evaluated inside anterior, central, and posterior zones of the scalp. Connectivity between these zones and interhemispheric connectivity were also measured. Results showed that alprazolam induced significant changes in EEG connectivity in terms of information transfer in comparison with placebo. Trends were opposite depending on the statistical characteristics: decreases in linear connectivity and increases in nonlinear couplings. These effects were generally spread over the entire scalp. Linear changes were negatively correlated, and nonlinear changes were positively correlated with drug plasma concentrations; the latter showed higher correlation coefficients. The use of both linear and nonlinear approaches revealed the importance of assessing changes in EEG connectivity as this can provide interesting information about psychopharmacological effects. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc. [source] Management of hypertension and stroke prevention: results of the Italian cardiologist surveyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2009G. Tocci Summary Objective: To provide an overview of current habits, priorities, perceptions and knowledge of cardiologists with regard to hypertension and stroke prevention in outpatient practice. Methods: A sample of 203 cardiologists operating in outpatient clinics and randomly selected amongst members of the largest Italian Outpatient Cardiologist Association were interviewed by e-mail, in April,May 2007. Results: The interviewed cardiologists reported that hypertensive outpatients represent a large percentage of their practice population, in which the clinical priority was blood pressure (BP) reduction. Stroke was identified as the most important event to prevent and it was also perceived as the most preventable hypertension-related cardiovascular event. A remarkably high rate of achieved BP control was reported, to a degree that it is inconsistent with current epidemiological reports and with the relatively low percentage use of combination therapies declared by cardiologists. Additional risk factors, organ damage, diabetes mellitus and atrial fibrillation were consistently reported in hypertensive patients. Among antihypertensive drug classes, a preference for angiotensin-converting enzyme inhibitors has been expressed by the majority of physicians; this choice was generally justified by evidence derived from international trials or by the antihypertensive efficacy of this drug class. Conclusions: The results confirm the presence of weaknesses in the current services for patients with hypertension, even when being managed by cardiologists. Discrepancies between perceptions and reality, or clinical practice and guideline recommendations are also highlighted. An analysis of these aspects may help to identify current areas of potential improvement for stroke prevention in the clinical management of hypertension in cardiology practice. [source] | |||||||||||||||||||||||||||||||