Hempfling, W.; Dilger, K.; Beuers, U.
BACKGROUND: Ursodeoxycholic acid is increasingly being used for the treatment of chronic cholestatic liver diseases. It appears to be generally well tolerated, but a systematic review on drug safety is lacking. AIM: As experimental data suggest a role of bile acids in the regulation of hepatic drug
Werb, Dan; Rowell, Greg; Guyatt, Gordon; Kerr, Thomas; Montaner, Julio; Wood, Evan
Violence is amongst the primary concerns of communities around the world and research has demonstrated links between violence and the illicit drug trade, particularly in urban settings. Given the growing emphasis on evidence-based policy-making, and the ongoing severe drug market violence in Mexico and other settings, we conducted a systematic review to examine the impacts of drug law enforcement on drug market violence. We conducted a systematic review using Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Specifically, we undertook a search of English language electronic databases (Academic Search Complete, PubMed, PsycINFO, EMBASE, Web of Science, Sociological Abstracts, Social Service Abstracts, PAIS International and Lexis-Nexis), the Internet (Google, Google Scholar), and article reference lists, from database inception to January 24, 2011. Overall, 15 studies were identified that evaluated the impact of drug law enforcement on drug market violence, including 11 (73%) longitudinal analyses using linear regression, 2 (13%) mathematical drug market models, and 2 (13%) qualitative studies. Fourteen (93%) studies reported an adverse impact of drug law enforcement on levels of violence. Ten of the 11 (91%) studies employing longitudinal qualitative analyses found a significant association between drug law enforcement and drug market violence. Our findings suggest that increasing drug law enforcement is unlikely to reduce drug market violence. Instead, the existing evidence base suggests that gun violence and high homicide rates may be an inevitable consequence of drug prohibition and that disrupting drug markets can paradoxically increase violence. In this context, and since drug prohibition has not meaningfully reduced drug supply, alternative regulatory models will be required if drug supply and drug market violence are to be meaningfully reduced. Copyright © 2011 Elsevier B.V. All rights reserved.
To ensure proper radioactive drug use (such as quality, diagnostic improvement, and minimal radioactive exposure), the Food and Drug Administration evaluates new drugs with respect to safety, effectiveness, and accuracy and adequacy of the labeling. The IND or NDA process is used for this purpose. A brief description of the process, including the Chemical Classification System and the therapeutic potential classification, is presented as it applies to radiopharmaceuticals. Also, the status of the IND or NDA review of radiopharmaceuticals is given
tests (LFTs) to monitor hepatotoxicity (liver [hepatic] damage) is uncommon in many resource-poor ... cholesterol ester storage disease. ... The problem with many patients is that they are taking several drugs often ... Urine, saliva and other body fluids may be coloured orange-red: this can be very alarming to patients.
Title: The Drug Effect: Health, Crime and Society Editors: Suzanne Fraser and David Moore Publisher: Cambridge University Press Price: R500.00 (incl. VAT and postage) Pages: 260. Availability: Published. Available through all academic bookstores. ISBN: 978-0-521-15605-9 ...
Frohmader, Karla S; Pitchers, Kyle K; Balfour, Margaret E; Coolen, Lique M
Drugs of abuse act on the brain circuits mediating motivation and reward associated with natural behaviors. There is ample evidence that drugs of abuse impact male and female sexual behavior. First, the current review discusses the effect of drugs of abuse on sexual motivation and performance in male and female humans. In particular, we discuss the effects of commonly abused drugs including psychostimulants, opiates, marijuana/THC, and alcohol. In general, drug use affects sexual motivation, arousal, and performance and is commonly associated with increased sexual risk behaviors. Second, studies on effects of systemic administration of drugs of abuse on sexual behavior in animals are reviewed. These studies analyze the effects on sexual performance and motivation but do not investigate the effects of drugs on risk-taking behavior, creating a disconnect between human and animal studies. For this reason, we discuss two studies that focus on the effects of alcohol and methamphetamine on inhibition of maladaptive sex-seeking behaviors in rodents. Third, this review discusses potential brain areas where drugs of abuse may be exerting their effect on sexual behavior with a focus on the mesolimbic system as the site of action. Finally, we discuss recent studies that have brought to light that sexual experience in turn can affect drug responsiveness, including a sensitized locomotor response to amphetamine in female and male rodents as well as enhanced drug reward in male rats. Copyright 2009 Elsevier Inc. All rights reserved.
Klungel, Olaf H|info:eu-repo/dai/nl/181447649; Martens, Edwin P|info:eu-repo/dai/nl/088859010; Psaty, Bruce M; Grobbee, Diederik E; Sullivan, Sean D; Stricker, Bruno H Ch; Leufkens, Hubert G M|info:eu-repo/dai/nl/075255049; de Boer, A|info:eu-repo/dai/nl/075097346
BACKGROUND AND OBJECTIVE: To review methods that seek to adjust for confounding in observational studies when assessing intended drug effects. METHODS: We reviewed the statistical, economical and medical literature on the development, comparison and use of methods adjusting for confounding. RESULTS:
Selvaggi, Gennaro; Spagnolo, Antonio G; Elander, Anna
Limited information is present in literature regarding detection of illicit drug users visiting physicians when planning elective surgery; also, there is no update manuscript that is illustrating the effects of illicit drugs use that require reconstructive surgery interventions. Aims of this manuscript are: 1) to summarize existing knowledge, and give surgeons information how to detect patients who might possible use illicit drugs; 2) to review the effects of illicit drug use that specifically require reconstructive surgery interventions; 3) to assess on existing policies on asymptomatic illicit drug users when planning elective surgery. Studies were identified by searching systematically in the electronic databases PubMed, Medline, The Cochrane Library and SveMed+. Because of the nature of research questions to be investigated (drug policy and surgery), a "systematic review" was not possible. In spite of some existing policies to detect illicit drug use in specific situations such as workplaces or acute trauma patients, there is a lack of data and lack of information, and subsequently no policy has ever been made, for detection and management of illicit drug use asymptomatic patients requesting or referred for plastic surgery interventions. This manuscript poses questions for further ethical evaluations and future policy. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
Blanco-Gandía, Maria C; Mateos-García, Ana; García-Pardo, Maria P; Montagud-Romero, Sandra; Rodríguez-Arias, Marta; Miñarro, José; Aguilar, María A
Social behaviour is disturbed in many substance abuse and psychiatric disorders. Given the consensus that social behaviours of lower mammals may help to understand some human emotional reactions, the aim of the present work was to provide an up-to-date review of studies on the changes in social behaviour induced by drugs of abuse. Various animal models have been used to study the relationship between drugs of abuse and social behaviour. Herein, we describe the effects of different substances of abuse on the three most commonly used animal models of social behaviour: the social play test, the social interaction test and the resident-intruder paradigm. The first is the most widely used test to assess adolescent behaviour in rodents, the second is generally used to evaluate a wide repertoire of behaviours in adulthood and the latter is specific to aggressive behaviour. Throughout the review we will explore the most relevant studies carried out to date to evaluate the effects of alcohol, cocaine, opioids, 3,4-methylenedioxymethamphetamine (MDMA), cannabinoids, nicotine and other drugs of abuse on these three paradigms, taking into account the influence of different variables, such as social history, age and type of exposure. Drugs of diverse pharmacological classes induce alterations in social behaviour, although they can be contrasting depending on several factors (drug, individual differences and environmental conditions). Ethanol and nicotine increase social interaction at low doses but reduce it at high doses. Psychostimulants, MDMA and cannabinoids reduce social interaction, whereas opiates increase it. Ethanol and psychostimulants enhance aggression, whereas MDMA, opiates, cannabinoids and nicotine reduce it. Prenatal drug exposure alters social behaviour, whereas drug withdrawal decreases sociability and enhances aggression. As a whole, this evidence has improved our understanding of the social dimension of drug addiction.
Rosi-Marshall, E J; Snow, D; Bartelt-Hunt, S L; Paspalof, A; Tank, J L
Although illicit drugs are detected in surface waters throughout the world, their environmental fate and ecological effects are not well understood. Many illicit drugs and their breakdown products have been detected in surface waters and temporal and spatial variability in use translates into "hot spots and hot moments" of occurrence. Illicit drug occurrence in regions of production and use and areas with insufficient wastewater treatment are not well studied and should be targeted for further study. Evidence suggests that illicit drugs may not be persistent, as their half-lives are relatively short, but may exhibit "pseudo-persistence" wherein continual use results in persistent occurrence. We reviewed the literature on the ecological effects of these compounds on aquatic organisms and although research is limited, a wide array of aquatic organisms, including bacteria, algae, invertebrates, and fishes, have receptors that make them potentially sensitive to these compounds. In summary, illicit drugs occur in surface waters and aquatic organisms may be affected by these compounds; research is needed that focuses on concentrations of illicit drugs in areas of production and high use, environmental fate of these compounds, and effects of these compounds on aquatic ecosystems at the concentrations that typically occur in the environment. Copyright © 2014 Elsevier B.V. All rights reserved.
Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint
Purpose: This review evaluates the evidence of the effects of multidimensional family therapy (MDFT) on drug use reduction in young people for the treatment of nonopioid drug use. Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials. Meta-analytic methods were used to…
Jacob, Nilan T
Over the years, the pharmaceutical industry has been at the forefront of research and innovation in drug discovery and development. The process of drug discovery extending from preclinical studies to multicentric clinical trials and postmarketing phase is a costly affair running into billions of dollars. On the flip side, not all investigational molecules clear the trial phases and get approved, which puts pressure on the manufacturers to maximize the profit from approved drugs. It is in this key area that the practice of drug promotion plays its role. The World Health Organization defines drug promotion as "all informational and persuasive activities by manufacturers and distributors, the effect of which is to influence the prescription, supply, purchase or use of medicinal drugs". With its humble intent of creating awareness among healthcare professionals and updating their knowledge on recent advances in treatment options, drug promotion has been an important tool, but gradually it has evolved to embrace aggressive marketing strategies and sometimes unethical business and scientific practices where the need for profit-making eclipses commitment to patient care and scientific exploration. In this review, we discuss the evolution of drug promotion practices, the various types, its merits and demerits, the influence of drug promotion on physician prescribing behaviour, the role of regulatory bodies, unethical promotional practices and finally summarize with future directions. © 2018 The British Pharmacological Society.
Baker, Danial E
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433. The September 2017 monograph topics are brigatinib, durvalumab, edaravone, midostaurin, and sarilumab. The MUE is on sarilumab.
Baker, Danial E
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service , contact Wolters Kluwer customer service at 866-397-3433.
Ali, Zaynah K; Baker, Danial E
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service , contact Wolters Kluwer customer service at 866-397-3433.
Baker, Danial E
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service , contact Wolters Kluwer customer service at 866-397-3433. The November 2017 monograph topics are Ertugliflozin, Glecaprevir / pibrentasvir, Neratinib, Sofosbuvir, velpatasvir, voxilaprevir and SQ C1 esterase inhibitor. The MUE is on glecaprevir, pibrentasvir.
Ali, Zaynah K; Baker, Danial E
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service , contact Wolters Kluwer customer service at 866-397-3433.
Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma
Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...
Kesselheim, Aaron S
With the development of transformative drugs at a low point, numerous commentators have recommended new legislation that uses supplementary market exclusivity as an incentive to promote innovation in the pharmaceutical market. This report provides an historical perspective on proposals for encouraging drug research. Four legislative programs have been primarily designed to offer market exclusivity to promote public health goals in the pharmaceutical or biomedical sciences: the Bayh-Dole Act of 1980, the Orphan Drug Act of 1983, the Hatch-Waxman Act of 1984, and the pediatric exclusivity provisions of the FDA Modernization Act of 1997. I reviewed quantitative and qualitative studies that reported on the outcomes from these programs and evaluated the quality of evidence generated. All four legislative programs generally have been regarded as successful, although such conclusions are largely based on straightforward descriptive reports rather than on more rigorous comparative data or analyses that sufficiently account for confounding. Overall, solid data demonstrate that market exclusivity incentives can attract interest from parties involved in drug development. However, using market exclusivity to promote innovation in the pharmaceutical market can be prone to misuse, leading to improper gains. In addition, important collateral effects have emerged with substantial negative public health implications. Using market exclusivity to promote pharmaceutical innovation can lead to positive outcomes, but the practice is also characterized by waste and collateral effects. Certain practices, such as mechanisms for reevaluation and closer ties of incentives programs to public health outcomes, can help address these problems. © 2011 Milbank Memorial Fund. Published by Wiley Periodicals Inc.
Viana, Karolline A; Daher, Anelise; Maia, Lucianne C; Costa, Paulo S; Martins, Carolina C; Paiva, Saul M; Costa, Luciane R
Some sedatives used in children and adolescents can affect memory function. Memory impairment of traumatic experience can minimize the chance of future psychological trauma. Knowledge about the potential of different sedatives to produce amnesia can help in the decision-making process of choosing a sedative regimen. The aim of this systematic review is to evaluate the effect of different sedatives on memory of perioperative events in children and adolescents. Electronic databases and other sources, such as trial registers, gray literature, and conference abstracts will be searched. Randomized controlled trials will be included that assess memory of perioperative events in children and adolescents 2-19 years old receiving sedative drugs as premedication or as agents for procedural sedation in a medical or dental settings. The outcomes will be loss of memory after and before sedative administration (anterograde and retrograde amnesia). Two independent reviewers will perform screening, study selection, and data extraction. Disagreement at all levels will be resolved by consensus or by involving a third reviewer. Assessment of the risk of bias of included studies will be performed according to "Cochrane Collaboration's Tool for Assessing Risk of Bias in Randomized Trials." Clinical and methodological heterogeneity across studies will be evaluated to determine if it is possible to combine or not combine study results in a meta-analysis. To the best of our knowledge, there is no systematic review that specifically addresses this question. Findings from the review will be useful in the decision-making process about the best sedative for minimizing recall of the medical/dental event and possible psychological trauma. PROSPERO CRD42015017559.
Wilby, J; Kainth, A; Hawkins, N; Epstein, D; McIntosh, H; McDaid, C; Mason, A; Golder, S; O'Meara, S; Sculpher, M; Drummond, M; Forbes, C
To examine the clinical effectiveness, tolerability and cost-effectiveness of gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), tiagabine (TGB), topiramate (TPM) and vigabatrin (VGB) for epilepsy in adults. Electronic databases. Internet resources. Pharmaceutical company submissions. Selected studies were screened and quality assessed. Separate analyses assessed clinical effectiveness, serious, rare and long-term adverse events and cost-effectiveness. An integrated economic analysis incorporating information on costs and effects of newer and older antiepileptic drugs (AEDs) was performed to give direct comparisons of long-term costs and benefits. A total of 212 studies were included in the review. All included systematic reviews were Cochrane reviews and of good quality. The quality of randomised controlled trials (RCTs) was variable. Assessment was hampered by poor reporting of methods of randomisation, allocation concealment and blinding. Few of the non-randomised studies were of good quality. The main weakness of the economic evaluations was inappropriate use of the cost-minimisation design. The included systematic reviews reported that newer AEDs were effective as adjunctive therapy compared to placebo. For newer versus older drugs, data were available for all three monotherapy AEDs, although data for OXC and TPM were limited. There was limited, poor-quality evidence of a significant improvement in cognitive function with LTG and OXC compared with older AEDs. However, there were no consistent statistically significant differences in other clinical outcomes, including proportion of seizure-free patients. No studies assessed effectiveness of AEDs in people with intellectual disabilities or in pregnant women. There was very little evidence to assess the effectiveness of AEDs in the elderly; no significant differences were found between LTG and carbamazepine monotherapy. Sixty-seven RCTs compared adjunctive therapy with placebo, older
Fadlallah, Racha; El-Jardali, Fadi; Annan, Farah; Azzam, Hayat; Akl, Elie A
A recent systematic review suggested that drug registrations and onsite quality inspections may be effective in reducing the prevalence of counterfeit and substandard drugs. However, simply replicating the most effective interventions is problematic, as it denotes implementing the intervention without further adaptation. The aim was to systematically review the evidence beyond effectiveness for systems-level interventions to combat or prevent drug counterfeiting. We conducted an extensive search, including an electronic search of 14 databases. We included studies examining the efficiency, feasibility, reliability, and economic outcomes of the interventions, as well as barriers and facilitators to their implementation. Two reviewers selected eligible studies and abstracted data in duplicate and independently. We synthesized the results narratively, stratified by type of intervention. Of 10,220 captured citations, 19 met our inclusion criteria. The findings suggest that the following may strengthen regulatory measures (e.g., registration): minimizing drug diversion, enhancing lines of communications, ensuring feedback on drug quality, and promoting strict licensing criteria. There is evidence that onsite quality surveillance and inspection systems may be efficient and cost-effective for preliminary testing of large samples of drugs. Laws and legislation need to be specific to counterfeit drugs, include firm penalties, address online purchasing of drugs, and be complemented by education of judges and lawyers. Public awareness and education should rely on multiple platforms and comprehensive and dedicated content. While product authentication technologies may be efficient and reliable in detecting counterfeit drugs in the supply chain, they require a strong information system infrastructure. As for pharmacovigilance systems, it is critical to tackle the issue of underreporting, to enhance their chances of success. Several factors are critical to the successful design
van Veenendaal, Tamar M; IJff, Dominique M; Aldenkamp, Albert P; Hofman, Paul A M; Vlooswijk, Marielle C G; Rouhl, Rob P W; de Louw, Anton J; Backes, Walter H; Jansen, Jacobus F A
As a large number of patients with epilepsy do not respond favorably to antiepileptic drugs (AEDs), a better understanding of treatment failure and the cause of adverse side effects is required. The working mechanisms of AEDs also alter neurotransmitter concentrations and brain activity, which can be measured using MR spectroscopy and functional MR imaging, respectively. This review presents an overview of clinical research of MR spectroscopy and functional MR imaging studies to the effects of AEDs on the brain. Despite the scarcity of studies associating MR findings to the effectiveness of AEDs, the current research shows clear potential regarding this matter. Several GABAergic AEDs have been shown to increase the GABA concentration, which was related to seizure reductions, while language problems due to topiramate have been associated with altered activation patterns measured with functional MR imaging. MR spectroscopy and functional MR imaging provide biomarkers that may predict individual treatment outcomes, and enable the assessment of mechanisms of treatment failure and cognitive side effects. Copyright © 2015 Elsevier Ltd. All rights reserved.
Jun Goo Kang
Full Text Available The current recommendations for the treatment of obese people include increased physical activity and reduced calories intake. When the behavioral approach is not sufficient, a pharmacologic treatment is recommended. In past years, numerous drugs have been approved for the treatment of obesity; however, most of them have been withdrawn from the market because of their adverse effects. In fact, amphetamine, rimonabant and sibutramine licenses have been withdrawn due to an increased risk of psychiatric disorders and non-fatal myocardial infarction or stroke. Even if orlistat is not as effective as other drugs in reducing body weight, orlistat is presently the only available choice for the treatment of obesity because of its safety for cardiovascular events and positive effects on diabetic control. Hopefully, more effective and better tolerated anti-obesity drugs will be developed through an improved understanding of the multiple mechanisms and complex physiological systems targeting appetite.
disease. The :most dangerous but least co:m:mon for:m of drug allergy is .... immune response, and allergic reaction occur in only ... mental sensitisation by milk and aerosol.11,19 ... requires cross-linking of the high-affinity specific IgE Fc.
Full Text Available Abstract Background Studies have shown that residents in nursing homes often are exposed to inappropriate medication. Particular concern has been raised about the consumption of psychoactive drugs, which are commonly prescribed for nursing home residents suffering from dementia. This review is an update of a Norwegian systematic review commissioned by the Norwegian Directorate of Health. The purpose of the review was to identify and summarise the effect of interventions aimed at reducing potentially inappropriate use or prescribing of drugs in nursing homes. Methods We searched for systematic reviews and randomised controlled trials in the Cochrane Library, MEDLINE, EMBASE, ISI Web of Knowledge, DARE and HTA, with the last update in April 2010. Two of the authors independently screened titles and abstracts for inclusion or exclusion. Data on interventions, participants, comparison intervention, and outcomes were extracted from the included studies. Risk of bias and quality of evidence were assessed using the Cochrane Risk of Bias Table and GRADE, respectively. Outcomes assessed were use of or prescribing of drugs (primary and the health-related outcomes falls, physical limitation, hospitalisation and mortality (secondary. Results Due to heterogeneity in interventions and outcomes, we employed a narrative approach. Twenty randomised controlled trials were included from 1631 evaluated references. Ten studies tested different kinds of educational interventions while seven studies tested medication reviews by pharmacists. Only one study was found for each of the interventions geriatric care teams, early psychiatric intervening or activities for the residents combined with education of health care personnel. Several reviews were identified, but these either concerned elderly in general or did not satisfy all the requirements for systematic reviews. Conclusions Interventions using educational outreach, on-site education given alone or as part of an
de Groot, Maartje H.; van Campen, Jos P. C. M.; Moek, Marije A.; Tulner, Linda R.; Beijnen, Jos H.; Lamoth, Claudine J. C.
Meta-analyses showed that psychotropic drugs (antidepressants, neuroleptics, benzodiazepines, antiepileptic drugs) and some cardiac drugs (digoxin, type IA anti-arrhythmics, diuretics) are associated with increased fall risk. Because balance and gait disorders are the most consistent predictors of
Nathan W Kopper
Full Text Available Nathan W Kopper, Jennifer Gudeman, Daniel J ThompsonKV Pharmaceutical, St. Louis, MO, USAAbstract: Vasomotor symptoms (VMS associated with menopause can cause significant discomfort and decrease the quality of life for women in the peri-menopausal and post-menopausal stages of life. Hormone therapy (HT is the mainstay of treatment for menopausal symptoms and is currently the only therapy proven effective for VMS. Numerous HT options are available to treat VMS, including estrogen-only and estrogen-progestogen combination products to meet the needs of both hysterectomized and nonhysterectomized women. In addition to selecting an appropriate estrogen or estrogen-progestogen combination, consideration should be given to the route of administration to best suit the needs of the patient. Delivery systems for hormone therapy include oral tablets, transdermal patches, transdermal topical (nonpatch products, and intravaginal preparations. Oral is currently the most commonly utilized route of administration in the United States. However, evidence suggests that oral delivery may lead to some undesirable physiologic effects caused by significant gut and hepatic metabolism. Transdermal drug delivery may mitigate some of these effects by avoiding gut and hepatic first-pass metabolism. Advantages of transdermal delivery include the ability to administer unmetabolized estradiol directly to the blood stream, administration of lower doses compared to oral products, and minimal stimulation of hepatic protein production. Several estradiol transdermal delivery technologies are available, including various types of patches, topical gels, and a transdermal spray.Keywords: estradiol, hormone therapy, menopause, transdermal drug delivery, vasomotor symptoms
Winocur, Ephraim; Gavish, Anat; Voikovitch, Michal; Emodi-Perlman, Alona; Eli, Ilana
Bruxism associated with drugs can be destructive, resulting in severe consequences to health that include destruction of tooth structure, irreversible harm to the temporomandibular joint, severe myofascial pain, and muscle contraction headache. However, reports concerning a possible association between bruxism and various pharmacologic drugs are scarce and mostly anecdotal. The purpose of this article was to review the existing literature concerning the exacerbating or ameliorating effect of drugs on bruxism in humans. A search of the MEDLINE, EMBASE, and PsicINFO databases from 1982 to 2001 was conducted, and the term bruxism and one of the following terms were used: drugs, medicine(s), pharmaceutical, movement disorders, akathisia, dyskinesia, dystonia, central or autonomic nervous system, dopamine, serotonin, and GABA. Furthermore, a search using the term bruxism was carried out on the weekly journal Reactions, which deals with side effects of drugs. Several chemical terms were searched separately (e.g., caffeine, nicotine). Relevant information was also derived from reference lists of the retrieved publications. The search yielded complex information referring to the association between bruxism and dopamine-related drugs, antidepressant drugs, sedative and anxiolytic drugs, and drugs of abuse. There is insufficient evidence-based data to draw definite conclusions concerning the effects of various drugs on bruxism. Although certain substances related to the dopaminergic, serotonergic, and adrenergic systems suppress or exacerbate bruxist activity in humans and animals, the literature is still controversial, and based mostly on anecdotal case reports. More controlled, evidence-based research on this under-explored subject is needed.
Full Text Available Gabrielle H Kingsley, David L Scott Rheumatology Unit, Kings College London, London, UK Background: Psoriatic arthritis is an inflammatory arthritis the primary manifestations of which are locomotor and skin disease. Although a number of guidelines have been published citing strategies for reducing disease progression, the evidence base for disease-modifying agents is unclear. This forms the focus of this systematic review. Methods: The systematic review was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 checklist. We selected randomized controlled trials (RCTs that looked at the impact of interventions with disease-modifying agents, either synthetic drugs or biologics on musculoskeletal outcomes, notably American College of Rheumatology 20 percent responders. Results were analyzed using Review Manager 5.1.6 (Cochrane Collaboration, Oxford, UK. Whilst our primary focus was on published trials, we also looked at new trials presented in abstract form in 2013–2014 that were not yet published to avoid omitting important and up-to-date information on developing treatments. Results: Our in-depth analysis included 28 trials overall enrolling 5,177 patients published between the 1980s and now as well as limited analysis of some studies in abstract form as described earlier. The most frequently available locomotor outcome measure was the American College of Rheumatology 20 percent responders. The risk ratio for achieving an American College of Rheumatology 20 percent responders response was positive in favor of treatment (risk ratio 2.30; 95% confidence interval 1.78–2.96; however, there was evidence of considerable heterogeneity between trials. Overall randomized controlled trials of established synthetic disease-modifying agents were largely negative (methotrexate, ciclosporin and sulfasalazine though leflunomide showed a small positive effect. A new synthetic agent, apremilast, did show a
Full Text Available Abstract Background Drug utilization review (DUR programs are being conducted in Canadian hospitals with the aim of improving the appropriateness of prescriptions. However, there is little evidence of their effectiveness. The objective of this study was to assess the impact of both a retrospective and a concurrent DUR programs on the quality of in-hospital prescribing. Methods We conducted an interrupted time series quasi-experimental study. Using explicit criteria for quality of prescribing, the natural history of cisapride prescription was established retrospectively in three university-affiliated hospitals. A retrospective DUR was implemented in one of the hospitals, a concurrent DUR in another, whereas the third hospital served as a control. An archivist abstracted records of all patients who were prescribed cisapride during the observation period. The effect of DURs relative to the control hospital was determined by comparing estimated regression coefficients from the time series models and by testing the statistical significance using a 2-tailed Student's t test. Results The concurrent DUR program significantly improved the appropriateness of prescriptions for the indication for use whereas the retrospective DUR brought about no significant effect on the quality of prescribing. Conclusion Results suggest a retrospective DUR approach may not be sufficient to improve the quality of prescribing. However, a concurrent DUR strategy, with direct feedback to prescribers seems effective and should be tested in other settings with other drugs.
Salomé, F; Boyer, P; Fayol, M
The aim of this survey is to present an overview of research into psychopharmacology as regards the effects of different psychoactive drugs and neuroleptics (NL) on language in normal subjects and schizophrenic patients. Eighteen studies that have investigated the effects of different drugs (alcohol, amphetamines, secobarbital, L-dopa, psilocybin, ketamine, fenfluramine) and neuroleptics (conventional and atypical) on language are reviewed. There are no studies concerning the effects of neuroleptics on language in healthy subjects. The results of the effects of other molecules indicate that language production can be increased (alcohol, amphetamine, secobarbital), rendered more complex (d-amphetamine), more focused (L-dopa) or more unfocused (psilocybin) and clearly impaired (ketamine). For schizophrenic patients, most studies show that conventional neuroleptic treatments, at a therapeutic dosage and in acute or chronic mode, reduce language disorders at all levels (clinic, linguistic, psycholinguistic). In conjunction with other molecules, the classical NL, when administered at a moderate dosage and in chronic mode, modify language in schizophrenia, either by improving the verbal flow and reducing pauses and positive thought disorder (NL + amphetamine) or by inducing an impairment in the language measurements (NL + fenfluramine). Clinical, methodological and theoretical considerations of results are debated in the framework of schizophrenic language disorders.
Smit, E.; Verdurmen, J.E.E.; Engels, R.C.M.E.
In order to quantify the effectiveness of family interventions in preventing and reducing adolescent illicit drug use, we conducted a systematic review and meta-analysis of randomized controlled trials. We searched the Cochrane Database of Systematic Reviews, Educational Research Information Centre
Full Text Available Nanotechnology has finally and firmly entered the realm of drug delivery. Performances of intelligent drug delivery systems are continuously improved with the purpose to maximize therapeutic activity and to minimize undesirable side-effects. This review describes the advanced drug delivery systems based on micelles, polymeric nanoparticles, and dendrimers. Polymeric carbon nanotubes and many others demonstrate a broad variety of useful properties. This review emphasizes the main requirements for developing new nanotech-nology-based drug delivery systems.
Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh
Today, the advanced drug delivery systems have been focused on targeted drug delivery fields. The novel drug delivery is involved with the improvement of the capacity of drug loading in drug carriers, cellular uptake of drug carriers, and the sustained release of drugs within target cells. In this review, six groups of therapeutic drug carriers including biomimetic hydrogels, biomimetic micelles, biomimetic liposomes, biomimetic dendrimers, biomimetic polymeric carriers and biomimetic nanostructures, are studied. The subject takes advantage of the biomimetic methods of productions or the biomimetic techniques for the surface modifications, similar to what accrues in natural cells. Moreover, the effects of these biomimetic approaches for promoting the drug efficiency in targeted drug delivery are visible. The study demonstrates that the fabrication of biomimetic nanocomposite drug carriers could noticeably promote the efficiency of drugs in targeted drug delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.
Nunes, Amanda A; Dos Santos, Rafael G; Osório, Flávia L; Sanches, Rafael F; Crippa, José Alexandre S; Hallak, Jaime E C
Recently, the anti-addictive potential of ayahuasca, a dimethyltryptamine(DMT)- and β-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of the Northwest Amazon and currently by syncretic churches worldwide, has received increased attention. To better evaluate this topic, we performed a systematic literature review using the PubMed database to find quantitative studies (using statistical analysis) that assessed the effects of ayahuasca or its components in drug-related symptoms or disorders. We found five animal studies (using harmaline, harmine, or ayahuasca) and five observational studies of regular ayahuasca consumers. All animal studies showed improvement of biochemical or behavioral parameters related to drug-induced disorders. Of the five human studies, four reported significant reductions of dependence symptoms or substance use, while one did not report significant results. The mechanisms responsible for the anti-addictive properties of ayahuasca and its alkaloids are not clarified, apparently involving both peripheral MAO-A inhibition by the β-carbolines and central agonism of DMT at 5-HT2A receptors expressed in brain regions related to the regulation of mood and emotions. Although results are promising, controlled studies are needed to replicate these preliminary findings.
McCrackin, M A; Helke, Kristi L; Galloway, Ashley M; Poole, Ann Z; Salgado, Cassandra D; Marriott, Bernadette P
Controversy continues concerning antimicrobial use in food animals and its relationship to drug-resistant infections in humans. We systematically reviewed published literature for evidence of a relationship between antimicrobial use in agricultural animals and drug-resistant foodborne campylobacteriosis in humans. Based on publications from the United States (U.S.), Canada and Denmark from 2010 to July 2014, 195 articles were retained for abstract review, 50 met study criteria for full article review with 36 retained for which data are presented. Two publications reported increase in macrolide resistance of Campylobacter coli isolated from feces of swine receiving macrolides in feed, and one of these described similar findings for tetracyclines and fluoroquinolones. A study in growing turkeys demonstrated increased macrolide resistance associated with therapeutic dosing with Tylan® in drinking water. One publication linked tetracycline-resistant C. jejuni clone SA in raw cow's milk to a foodborne outbreak in humans. No studies that identified farm antimicrobial use also traced antimicrobial-resistant Campylobacter from farm to fork. Recent literature confirms that on farm antibiotic selection pressure can increase colonization of animals with drug-resistant Campylobacter spp. but is inadequately detailed to establish a causal relationship between use of antimicrobials in agricultural animals and prevalence of drug-resistant foodborne campylobacteriosis in humans.
Stander, Valerie A; Reed, Cheryl; Olson, Cheryl B; Johnson, Judy; Merrill, Lex L; Clapp, John; Elder, John; Lawson, Gary; Mangual, George; Lowe, Nate
.... Some of the common components were information on the consequences of drug use, decision-making skill training, public pledges not to use drugs, values clarification, goal setting, stress management...
Feng, Ye; Yang, Huixia
Metformin has been gradually used in the management of gestational diabetes mellitus (GDM). In order to prove the safety and efficacy of metformin used in pregnancy, we searched several databases for the reports of randomized trials comparing insulin and metformin used in GDM and conducted a meta-analysis. Data showed the rates of neonatal large for gestational age, cesarean section, neonatal respiratory distress and preterm birth were similar in both groups. Maternal glycated hemoglobin-% at gestational week 36-37 was significantly lower in metformin group, indicating good glycemic control of metformin. Maternal weight gain since enrollment to gestational week 36-37 was also lower in metformin group, making metformin worth using even when metformin is insufficient and supplementary insulin is needed. Data also showed that metformin significantly reduced the gestational hypertension complications in GDM patients, probably by reducing the endothelial activation and maternal inflammatory response of insulin resistance. Although metformin can cross the placenta, it is less likely to cause severe neonatal hypoglycemia compared with insulin since it neither stimulates pancreatic insulin release nor increases circulating insulin levels. According to most maternal and neonatal outcomes, metformin is an effective and safe alternative to insulin for GDM patients.
Yu, Jingjing; Ritchie, Tasha K; Mulgaonkar, Aditi; Ragueneau-Majlessi, Isabelle
The aim of the present work was to perform a systematic review of drug metabolism, transport, pharmacokinetics, and DDI data available in the NDAs approved by the FDA in 2013, using the University of Washington Drug Interaction Database, and to highlight significant findings. Among 27 NMEs approved, 22 (81%) were well characterized with regard to drug metabolism, transport, or organ impairment, in accordance with the FDA drug interaction guidance (2012) and were fully analyzed in this review. In vitro, a majority of the NMEs were found to be substrates or inhibitors/inducers of at least one drug metabolizing enzyme or transporter. However, in vivo, only half (n = 11) showed clinically relevant drug interactions, with most related to the NMEs as victim drugs and CYP3A being the most affected enzyme. As perpetrators, the overall effects for NMEs were much less pronounced, compared with when they served as victims. In addition, the pharmacokinetic evaluation in patients with hepatic or renal impairment provided useful information for further understanding of the drugs' disposition. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.
Full Text Available BACKGROUND: The present systematic review aimed to express the clinical anti-lipid effects of different types of herbs, as well as described studied interactions between herbal remedies and prescribed drugs for hyperlipidemic patients which were based on in vitro experiments, animal studies, and empirical clinical experiences. METHODS: For this systematic review, we explored 2183 published papers about herbal drugs interactions from November 1967 to August 2014, fulfilling eligibility criteria by searching in some databases such as Web of Science, Medline, Scopus, Embase, Cinahl, and the Cochrane database. The main keywords used for searching included: herbal medicine, herbs, statin, lipid, and herb-drug interaction. RESULTS: Among published articles about herb-drug interactions, 185 papers met the initial search criteria and among them, 92 papers were potentially retrievable including a description of 17 herbs and medicinal plants. In first step and by reviewing all published manuscripts on beneficial effects of herbs on serum lipids level, 17 herbs were described to be effective on lipid profile as lowering serum triglyceride, total cholesterol, low-density lipoprotein cholesterol as well as increasing serum high-density lipoprotein level. Some herbs such as celery could even affect the hepatic triglyceride concentrations. The herbal reaction toward different types of statins is varied so that grapefruit or pomegranate was interacted with only some types of statins, but not with all statin types. In this context, administration of herbal materials can lead to decreased absorption of statins or decreased the plasma concentration of these drugs. CONCLUSION: Various types of herbs can potentially reduce serum lipid profile with the different pathways; however, the herb-drug interactions may decrease pharmacological therapeutic effects of anti-hyperlipidemic drugs that should be considered when approved herbs are prescribed.
Bowker, James D.; Gaikowski, Mark P.
Only eight active pharmaceutical ingredients available in 18 drug products have been approved by the U.S. Food and Drug Administration for use in aquaculture. The approval process can be lengthy and expensive, but several new drugs and label claims are under review. Progress has been made on approvals for Halamid (chloramine-T), Aquaflor (florfenicol) and 35% PeroxAid (hydrogen peroxide) as therapeutic drugs. Data are also being generated for AQUI-S 20E, a fish sedative.
Full Text Available Electrospinning is a fast emerging technique for producing ultrafine fibers by utilizing electrostatic repulsive forces. The technique has gathered much attention due to the emergence of nanotechnology that sparked worldwide research interest in nanomaterials for their preparation and application in biomedicine and drug delivery. Electrospinning is a simple, adaptable, cost-effective, and versatile technique for producing nanofibers. For effective and efficient use of the technique, several processing parameters need to be optimized for fabricating polymeric nanofibers. The nanofiber morphology, size, porosity, surface area, and topography can be refined by varying these parameters. Such flexibility and diversity in nanofiber fabrication by electrospinning has broadened the horizons for widespread application of nanofibers in the areas of drug and gene delivery, wound dressing, and tissue engineering. Drug-loaded electrospun nanofibers have been used in implants, transdermal systems, wound dressings, and as devices for aiding the prevention of postsurgical abdominal adhesions and infection. They show great promise for use in drug delivery provided that one can confidently control the processing variables during fabrication. This paper provides a concise incursion into the application of electrospun nanofibers in drug delivery and cites pertinent processing parameters that may influence the performance of the nanofibers when applied to drug delivery.
Pillay, V.; Dott, C.; Choonara, Y.E.; Tyagi, Ch.; Tomar, L.; Kumar, P.; Toit, L.C.D.; Ndesendo, V.M.K.
Electro spinning is a fast emerging technique for producing ultrafine fibers by utilizing electrostatic repulsive forces. The technique has gathered much attention due to the emergence of nano technology that sparked worldwide research interest in nano materials for their preparation and application in biomedicine and drug delivery. Electro spinning is a simple, adaptable, cost-effective, and versatile technique for producing nano fibers. For effective and efficient use of the technique, several processing parameters need to be optimized for fabricating polymeric nano fibers. The nano fiber morphology, size, porosity, surface area, and topography can be refined by varying these parameters. Such flexibility and diversity in nano fiber fabrication by electro spinning has broadened the horizons for widespread application of nano fibers in the areas of drug and gene delivery, wound dressing, and tissue engineering. Drug-loaded electro spun nano fibers have been used in implants, transdermal systems, wound dressings, and as devices for aiding the prevention of post surgical abdominal adhesions and infection. They show great promise for use in drug delivery provided that one can confidently control the processing variables during fabrication. This paper provides a concise incursion into the application of electro spun nano fibers in drug delivery and cites pertinent processing parameters that may influence the performance of the nano fibers when applied to drug delivery.
Turanli, Beste; Grøtli, Morten; Boren, Jan; Nielsen, Jens; Uhlen, Mathias; Arga, Kazim Y; Mardinoglu, Adil
Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-κB inhibition, Wnt/β-Catenin pathway inhibition, DNMT1 inhibition, and GSK-3β inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.
Kleinstreuer, Clement; Feng, Yu; Childress, Emily
Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume that the drug-particles are already at the target site or at least in its direct vicinity. In this review, drug-delivery methodologies, drug types and drug-delivery devices are discussed with examples in two major application areas: (1) inhaled drug-aerosol delivery into human lung-airways; and (2) intravascular drug-delivery for solid tumor targeting. The major problem addressed is how to deliver efficiently the drug-particles from the entry/infusion point to the target site. So far, most experimental results are based on animal studies. Concerning pulmonary drug delivery, the focus is on the pros and cons of three inhaler types, i.e., pressurized metered dose inhaler, dry powder inhaler and nebulizer, in addition to drug-aerosol formulations. Computational fluid-particle dynamics techniques and the underlying methodology for a smart inhaler system are discussed as well. Concerning intravascular drug-delivery for solid tumor targeting, passive and active targeting are reviewed as well as direct drug-targeting, using optimal delivery of radioactive microspheres to liver tumors as an example. The review concludes with suggestions for future work, considereing both pulmonary drug targeting and direct drug delivery to solid tumors in the vascular system. PMID:25516850
Harnish Patel; Upendra Patel; Hiren Kadikar; Bhavin Bhimani; Dhiren Daslaniya; Ghanshyam Patel
Conventional oral drug delivery systems supply an instantaneous release of drug, which cannot control the release of the drug and effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the process of osmosis. Osmotic devices are the most promising strategy based systems for controlled drug delivery. They are the most reliable con...
intent to deceptively represent its origin authenticity or effectiveness. A counterfeit drug ... version of medication. The business of fake drugs is a lucrative crime that is .... management of target or most vulnerable groups of patients with high risk ...
Birkenhäger-Gillesse, Elizabeth G; Kollen, Boudewijn J; Achterberg, Wilco P; Boersma, Froukje; Jongman, Lydia; Zuidema, Sytse U
Dementia is often accompanied by neuropsychiatric symptoms. Psychotropic drugs for the treatment of neuropsychiatric symptoms are frequently used to manage these problems, but they are of limited effectiveness and can have serious side effects. Psychosocial interventions are advocated as first line treatment and may help to reduce psychotropic drug use. To assess the effect of multidisciplinary psychosocial interventions in nursing homes on the psychotropic drug prescription rate. Literature obtained from searches in 9 electronic databases was systematically reviewed. In addition, the pooled effects of specific psychosocial interventions in homogenous subgroups were analyzed (meta-analysis). Eleven randomized controlled studies that investigated multiple psychotropic drugs interventions (psychotropic drugs in 3, antipsychotics in 9, and antidepressants in 5 studies) as well as different types of psychosocial interventions were included. We separately analyzed interventions directed at the care staff level (educational programs in 3, in-reach services or consultation in 1, cultural or process change in 6 studies) and the individual resident level in 1 study. In 7 out of 9 studies reporting on antipsychotic drug use, the physician was actively involved. Nine studies in which antipsychotic drug use was specified reported a significant decrease in prescription rate as a result of psychosocial interventions [relative risk (RR) 0.71, 95% confidence interval (CI) 0.59-0.88], whereas meta-analysis of 5 studies investigating antidepressant drug use failed to show a significant effect (RR 0.82, 95% CI 0.64-1.02). Pooled effect sizes of 6 studies investigating cultural change, showed a significant decrease in antipsychotic drug use (RR 0.65, 95% CI 0.57-0.73). Effect sizes of 2 studies on educational programs on antipsychotic use were nonsignificant (RR 1.50, 95% CI 0.49-4.64). Sensitivity analysis of 7 studies reporting on antipsychotic drug use involving prescribing
... Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search ... who aren't yet born. Drug use can hurt the body and the brain, sometimes forever. Drug use can also lead to addiction, a long-lasting brain disease in which people ...
Full Text Available BACKGROUND: Anti-obesity drugs are widely used to prevent the complications of obesity, however, the effects of anti-obesity drugs on cardiovascular risk factors are unclear at the present time. We carried out a comprehensively systematic review and meta-analysis to assess the effects of anti-obesity drugs on cardiovascular risk factors. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles and proceedings of major meetings for relevant literatures. We included randomized placebo-controlled trials that reported the effects of anti-obesity drugs on cardiovascular risk factors compared to placebo. Overall, orlistat produced a reduction of 2.39 kg (95%CI-3.34 to -1.45 for weight, a reduction of 0.27 mmol/L (95%CI: -0.36 to -0.17 for total cholesterol, a reduction of 0.21 mmol/L (95%CI: -0.30 to -0.12 for LDL, a reduction of 0.12 mmol/L (95%CI: -0.20 to -0.04 for fasting glucose, 1.85 mmHg reduction (95%CI: -3.30 to -0.40 for SBP, and a reduction of 1.49 mmHg (95%CI: -2.39 to -0.58 for DBP. Sibutramine only showed effects on weight loss and triglycerides reduction with statistical significances. Rimonabant was associated with statistically significant effects on weight loss, SBP reduction and DBP reduction. No other significantly different effects were identified between anti-obesity therapy and placebo. CONCLUSION/SIGNIFICANCE: We identified that anti-obesity therapy was associated with a decrease of weight regardless of the type of the drug. Orlistat and rimonabant could lead to an improvement on cardiovascular risk factors. However, Sibutramine may have a direct effect on cardiovascular risk factors.
Zheng, Sean Lee; Chan, Fiona T; Nabeebaccus, Adam A; Shah, Ajay M; McDonagh, Theresa; Okonko, Darlington O; Ayis, Salma
Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO 2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo. The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Zheng, Sean Lee; Chan, Fiona T; Nabeebaccus, Adam A; Shah, Ajay M; McDonagh, Theresa; Okonko, Darlington O; Ayis, Salma
Background Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. Methods We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. Results We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo. Conclusion The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group. PMID:28780577
Schumacher, Justin D.; Guo, Grace L.
Drug-induced steatohepatitis is a rare form of liver injury known to be caused by only a handful of compounds. These compounds stimulate the development of steatohepatitis through their toxicity to hepatocyte mitochondria; inhibition of beta-oxidation, mitochondrial respiration, and/or oxidative phosphorylation. Other mechanisms discussed include the disruption of phospholipid metabolism in lysosomes, prevention of lipid egress from hepatocytes, targeting mitochondrial DNA and topoisomerase, decreasing intestinal barrier function, activation of the adenosine pathway, increasing fatty acid synthesis, and sequestration of coenzyme A. It has been found that the majority of compounds that induce steatohepatitis have cationic amphiphilic structures; a lipophilic ring structure with a side chain containing a cationic secondary or tertiary amine. Within the last decade, the ability of many chemotherapeutics to cause steatohepatitis has become more evident coining the term chemotherapy-associated steatohepatitis (CASH). The mechanisms behind drug-induced steatohepatitis are discussed with a focus on cationic amphiphilic drugs and chemotherapeutic agents. - Highlights: • Reviewed the mechanisms underlying drug-induced steatohepatitis for many compounds • Mitochondrial dysfunction is critical in the development of drug-induced steatohepatitis. • Majority of drugs that induce steatohepatitis are cationic amphiphilic drugs. • Chemotherapeutics that induce CASH are cationic amphiphilic drugs. • Majority of drugs that induce steatohepatitis are carnitine palmitoyltransferase-I inhibitors.
Schumacher, Justin D., E-mail: Justin.firstname.lastname@example.org; Guo, Grace L.
Drug-induced steatohepatitis is a rare form of liver injury known to be caused by only a handful of compounds. These compounds stimulate the development of steatohepatitis through their toxicity to hepatocyte mitochondria; inhibition of beta-oxidation, mitochondrial respiration, and/or oxidative phosphorylation. Other mechanisms discussed include the disruption of phospholipid metabolism in lysosomes, prevention of lipid egress from hepatocytes, targeting mitochondrial DNA and topoisomerase, decreasing intestinal barrier function, activation of the adenosine pathway, increasing fatty acid synthesis, and sequestration of coenzyme A. It has been found that the majority of compounds that induce steatohepatitis have cationic amphiphilic structures; a lipophilic ring structure with a side chain containing a cationic secondary or tertiary amine. Within the last decade, the ability of many chemotherapeutics to cause steatohepatitis has become more evident coining the term chemotherapy-associated steatohepatitis (CASH). The mechanisms behind drug-induced steatohepatitis are discussed with a focus on cationic amphiphilic drugs and chemotherapeutic agents. - Highlights: • Reviewed the mechanisms underlying drug-induced steatohepatitis for many compounds • Mitochondrial dysfunction is critical in the development of drug-induced steatohepatitis. • Majority of drugs that induce steatohepatitis are cationic amphiphilic drugs. • Chemotherapeutics that induce CASH are cationic amphiphilic drugs. • Majority of drugs that induce steatohepatitis are carnitine palmitoyltransferase-I inhibitors.
Full Text Available Introduction: Psychotropic drugs are often implicated in cutaneous adverse drug reactions. While most of these reactions have a benign character, it is still important, however, to consider its role in the increasing stigma and treatment adherence. A small number of the cutaneous adverse drug reactions can develop into serious and potentially fatal conditions. Objectives: This article aims to review the most common cutaneous adverse drug reactions in patients taking psychotropic drugs. Methods: In this study, a search was carried out in the MEDLINE database for English language articles published , from 1999 to 2014, using as keywords: psychiatric, psychotropic, cutaneous, adverse reaction, antidepressive agents, antipsychotics, benzodiazepines, mood stabilizers, anticonvulsant, dementia. Information available from the Portuguese regulatory and supervising agency (Infarmed was also included.Results: 121 articles were found with reference to cutaneous adverse drug reactions associated with psychotropic drugs. The drugs most frequently reported as associated with such adverse effects were anticonvulsants used as mood stabilizers, followed by the antipsychotics . The antidementia drugs were rarely associated with serious cutaneous adverse reactions. Discussion and Conclusion: Cutaneous drug adverse reactions are common in psychiatric clinical practice and typically are minor in severity. The most severe reactions are most often associated with the use of mood stabilizing medications. Some of these side effects can be solved with reduction or drug discontinuation. More severe cases should be referred to a specialist in dermatology.
Link R. Swanson
Full Text Available How do psychedelic drugs produce their characteristic range of acute effects in perception, emotion, cognition, and sense of self? How do these effects relate to the clinical efficacy of psychedelic-assisted therapies? Efforts to understand psychedelic phenomena date back more than a century in Western science. In this article I review theories of psychedelic drug effects and highlight key concepts which have endured over the last 125 years of psychedelic science. First, I describe the subjective phenomenology of acute psychedelic effects using the best available data. Next, I review late 19th-century and early 20th-century theories—model psychoses theory, filtration theory, and psychoanalytic theory—and highlight their shared features. I then briefly review recent findings on the neuropharmacology and neurophysiology of psychedelic drugs in humans. Finally, I describe recent theories of psychedelic drug effects which leverage 21st-century cognitive neuroscience frameworks—entropic brain theory, integrated information theory, and predictive processing—and point out key shared features that link back to earlier theories. I identify an abstract principle which cuts across many theories past and present: psychedelic drugs perturb universal brain processes that normally serve to constrain neural systems central to perception, emotion, cognition, and sense of self. I conclude that making an explicit effort to investigate the principles and mechanisms of psychedelic drug effects is a uniquely powerful way to iteratively develop and test unifying theories of brain function.
Swanson, Link R.
How do psychedelic drugs produce their characteristic range of acute effects in perception, emotion, cognition, and sense of self? How do these effects relate to the clinical efficacy of psychedelic-assisted therapies? Efforts to understand psychedelic phenomena date back more than a century in Western science. In this article I review theories of psychedelic drug effects and highlight key concepts which have endured over the last 125 years of psychedelic science. First, I describe the subjective phenomenology of acute psychedelic effects using the best available data. Next, I review late 19th-century and early 20th-century theories—model psychoses theory, filtration theory, and psychoanalytic theory—and highlight their shared features. I then briefly review recent findings on the neuropharmacology and neurophysiology of psychedelic drugs in humans. Finally, I describe recent theories of psychedelic drug effects which leverage 21st-century cognitive neuroscience frameworks—entropic brain theory, integrated information theory, and predictive processing—and point out key shared features that link back to earlier theories. I identify an abstract principle which cuts across many theories past and present: psychedelic drugs perturb universal brain processes that normally serve to constrain neural systems central to perception, emotion, cognition, and sense of self. I conclude that making an explicit effort to investigate the principles and mechanisms of psychedelic drug effects is a uniquely powerful way to iteratively develop and test unifying theories of brain function. PMID:29568270
Kellogg, Marissa; Meador, Kimford J
Increasing evidence suggests that exposure to certain antiepileptic drugs (AEDs) during critical periods of development may induce transient or long-lasting neurodevelopmental deficits across cognitive, motor and behavioral domains. The developing nervous system may endure prolonged chronic exposure to AEDs during pregnancy (in utero) or during childhood, which can lead to neurodevelopmental defects such as congenital neural tube defects, lower IQ, language deficits, autism and ADHD. To date, valproate is the most widely recognized AED to significantly negatively affect neurodevelopment, and demonstrates greater adverse effects than any other AEDs that have been assessed. Although some AEDs appear to have low risk (i.e., lamotrigine, levetiracetam), other AEDs have been implicated in a variety of studies detailed below, and many AEDs have not been adequately assessed. The purpose of this review article is to summarize our current understanding of the neurodevelopmental effects of AEDs.
Kazantsev, S. O.; Korovin, M. S.
Application of antitumor chemotherapeutic drugs is hindered by a number of barriers, multidrug resistance that makes effective drug deposition inside cancer cells difficult is among them. Recent research shows that potential efficiency of anticancer drugs can be increased with nanoparticles. This review is devoted to the application of nanoparticles for cancer treatment. Various types of nanoparticles currently used in medicine are reviewed. The nanoparticles that have been used for cancer therapy and targeted drug delivery to damaged sites of organism are described. Also, the possibility of nanoparticles application for cancer diagnosis that could help early detection of tumors is discussed. Our investigations of antitumor activity of low-dimensional nanostructures based on aluminum oxides and hydroxides are briefly reviewed.
Tan, Mei Lan; Lim, Lin Ee
Andrographis paniculata (Burm.f.) Nees is a popular medicinal plant and its components are used in various traditional product preparations. However, its herb-drug interactions risks remain unclear. This review specifically discusses the various published studies carried out to evaluate the effects of Andrographis paniculata (Burm.f.) Nees plant extracts and diterpenoids on the CYP450 metabolic enzyme and if the plant components pose a possible herb-drug interaction risk. Unfortunately, the current data are insufficient to indicate if the extracts or diterpenoids can be labeled as in vitro CYP1A2, CYP2C9 or CYP3A4 inhibitors. A complete CYP inhibition assay utilizing human liver microsomes and the derivation of relevant parameters to predict herb-drug interaction risks may be necessary for these isoforms. However, based on the current studies, none of the extracts and diterpenoids exhibited CYP450 induction activity in human hepatocytes or human-derived cell lines. It is crucial that a well-defined experimental design is needed to make a meaningful herb-drug interaction prediction.
Wekesah, Frederick M; Mbada, Chidozie E; Muula, Adamson S; Kabiru, Caroline W; Muthuri, Stella K; Izugbara, Chimaraoke O
Many interventions have been implemented to improve maternal health outcomes in sub-Saharan Africa (SSA). Currently, however, systematic information on the effectiveness of these interventions remains scarce. We conducted a systematic review of published evidence on non-drug interventions that reported effectiveness in improving outcomes and quality of care in maternal health in SSA. African Journals Online, Bioline, MEDLINE, Ovid, Science Direct, and Scopus databases were searched for studies published in English between 2000 and 2015 and reporting on the effectiveness of interventions to improve quality and outcomes of maternal health care in SSA. Articles focusing on interventions that involved drug treatments, medications, or therapies were excluded. We present a narrative synthesis of the reported impact of these interventions on maternal morbidity and mortality outcomes as well as on other dimensions of the quality of maternal health care (as defined by the Institute of Medicine 2001 to comprise safety, effectiveness, efficiency, timeliness, patient centeredness, and equitability). Seventy-three studies were included in this review. Non-drug interventions that directly or indirectly improved quality of maternal health and morbidity and mortality outcomes in SSA assumed a variety of forms including mobile and electronic health, financial incentives on the demand and supply side, facility-based clinical audits and maternal death reviews, health systems strengthening interventions, community mobilization and/or peer-based programs, home-based visits, counseling and health educational and promotional programs conducted by health care providers, transportation and/or communication and referrals for emergency obstetric care, prevention of mother-to-child transmission of HIV, and task shifting interventions. There was a preponderance of single facility and community-based studies whose effectiveness was difficult to assess. Many non-drug interventions have been
Amanda E. Perry
Full Text Available Background: The numbers of incarcerated people suffering from drug dependence has steadily risen since the 1980s and only a small proportion of these receive appropriate treatment. A systematic review to evaluate the effectiveness and economic evidence of non-pharmacological interventions for drug using offenders was conducted. Methods: Cochrane Collaboration criteria were used to identify trials across 14 databases between 2004 and 2014. A series of meta-analyses and an economic appraisal were conducted. Results: 43 trials were identified showing to have limited effect in reducing re-arrests RR 0.97 (95% CI 0.89–1.07 and drug use RR 0.90 (95% CI 0.80–1.00 but were found to significantly reduce re-incarceration RR 0.70 (95% CI 0.57–0.85. Therapeutic community programs were found to significantly reduce the number of re-arrests RR 0.70 (95% CI 0.56–0.87. 10 papers contained economic information. One paper presented a cost-benefit analysis and two reported on the cost and cost effectiveness of the intervention. Conclusions: We suggest that therapeutic community interventions have some benefit in reducing subsequent re-arrest. We recommend that economic evaluations should form part of standard trial protocols.
Full Text Available Nowadays, polymer nanofibers have gained attention due to remarkable characteristics such as high porosity and large surface area to volume ratio. Among their fabrication methods, electrospinning technique has been attracted as a simple and reproducible approach. It is a versatile, simple and cost-effective technique for the production of continuous nanofibers with acceptable characteristics such as high porosity, high surface area to volume ratio, high loading capacity and encapsulation efficiency, delivery of multiple drugs, and enhancement of drug solubility. Due to these properties electrospun nanofibers have been extensively used for different biomedical applications including wound dressing, tissue engineering, enzyme immobilization, artificial organs, and drug delivery. Different synthetic and natural polymers have been successfully electrospun into ultrafine fibers. Using electrospun nanofibers as vehicles for oral drug delivery has been investigated in different release manners- fast, biphasic or sustained release. This article presents a review on application of electrospinning technique in oral drug delivery.
Tao, Da; Wang, Tieyan; Wang, Tieshan; Qu, Xingda
A drug's physical characteristics, such as colour, could be factors influencing its therapeutic effects. It is not well understood whether people's expectations on drug effects and efficacy are affected by colour, especially among Chinese population. This study was conducted to examine people's expectations on drug effects and efficacy on the basis of drug colour, and to reveal possible gender differences in colour-related drug expectations. Participants (n = 224) were asked to classify seven single-coloured and six two-coloured capsules into one of four categories of drug effects, and to indicate the strength of drug efficacy. It is found that all the coloured capsules yielded non-chance distributions in classifications of drug effects, with six single-coloured and four two-coloured capsules associated with specific drug effects. Colour also conveyed differential strengths of drug efficacy in general and in relation to specific drug effects. There were gender differences in drug expectations for some colours and colour combinations. Practitioner Summary: Drug colour was found to have impacts on perceived drug effects and efficacy. The findings from the present study can be used by ergonomics practitioners to design appropriate drug colours in support of drug differentiation, therapeutic effects and medication adherence.
Santos-Oliveira, Ralph; Smith, Sheila W.; Carneiro-Leao, Ana Maria A.
Radiopharmaceuticals play a critical role in modern medicine primarily for diagnostic purposes, but also for monitoring disease progression and response to treatment. As the use of image has been increased, so has the use of prescription medications. These trends increase the risk of interactions between medications and radiopharmaceuticals. These interactions which have an impact on image by competing with the radiopharmaceutical for binding sites for example can lead to false negative results. Drugs that accelerate the metabolism of the radiopharmaceutical can have a positive impact (i.e. speeding its clearance) or, if repeating image is needed, a negative impact. In some cases, for example in cardiac image among patients taking doxirubacin, these interactions may have a therapeutic benefit. The incidence of drug-radiopharmaceuticals adverse reactions is unknown, since they may not be reported or even recognized. Here, we compiled the medical literature, using the criteria of a systematic review established by the Cochrane Collaboration, on pharmaceutical-drug interactions to provide a summary of documented interactions by organ system and radiopharmaceuticals. The purpose is to provide a reference on drug interactions that could inform the nuclear medicine staff in their daily routine. Efforts to increase adverse event reporting, and ideally consolidate reports worldwide, can provide a critically needed resource for prevention of drug-radiopharmaceuticals interactions. (author)
Full Text Available Kylie Thaler1, Divya V Chandiramani2, Richard A Hansen2, Gerald Gartlehner11Department for Evidence-based Medicine and Clinical Epidemiology, Danube University Krems, Krems, Austria; 2UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAObjective: To systematically review the general and comparative efficacy and safety of anakinra for rheumatoid arthritis.Methods: We searched MEDLINE®, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 to April 2009. We manually searched reference lists of pertinent review articles and explored the Center for Drug Evaluation and Research database. For efficacy we included randomized controlled trials (RCTs comparing anakinra with placebo or other biologics. For safety both experimental and observational studies were eligible. Two persons independently reviewed abstracts and full text articles and extracted relevant data.Results: We included data from 3 RCTs comparing anakinra with placebo for rheumatoid arthritis (RA. The pooled relative risk (RR of an ACR50 (American College of Rheumatology response for anakinra compared with placebo is 2.28 (95% CI 1.41 to 3.67. Adjusted indirect comparisons of ACR50 response rates of anakinra and anti-TNF agents showed a RR of 0.67 (95% CI 0.38 to 1.17 favoring the anti-TNF drugs. This result did not reach statistical significance. For safety, we included 9 experimental and observational studies of 24 weeks to 3 years duration. Up to 30% of patients withdrew from the studies due to adverse events. 67.2% (95% CI 38.7 to 95.7 of patients experienced an injection site reaction.Conclusions: Anakinra is an effective drug for treating RA. Indirect comparisons with adalimumab, etanercept and infliximab, however, showed a trend towards greater efficacy for the anti-TNF drugs. Anakinra also seems to be associated with comparably high rates of injection site reactions. These results should be taken into
Mitra, Amitava; Kesisoglou, Filippos
Published reports have clearly shown that weakly basic drugs which have low solubility at high pH could have impaired absorption in patients with high gastric pH thus leading to reduced and variable bioavailability. Since such reduction in exposure can lead to significant loss of efficacy, it is imperative to (1) understand the behavior of the compound as a function of stomach pH to inform of any risk of bioavailability loss in clinical studies and (2) develop a robust formulation which can provide adequate exposure in achlorhydric patients. In this review paper, we provide an overview of the factors that can cause high gastric pH in human, discuss clinical and preclinical pharmacokinetic data for weak bases under conditions of normal and high gastric pH, and give examples of formulation strategies to minimize or mitigate the reduced absorption of weakly basic drugs under high gastric pH conditions. It should be noted that the ability to overcome pH sensitivity issues is highly compound dependent and there are no obvious and general solutions to overcome such effect. Further, we discuss, along with several examples, the use of biopharmaceutical tools such as in vitro dissolution, absorption modeling, and gastric pH modified animal models to assess absorption risk of weak bases in high gastric pH and also the use of these tools to enable development of formulations to mitigate such effects.
Full Text Available The emergence and spread of drug resistant malaria represents a considerable challenge to controlling malaria. To date, malaria control has relied heavily on a comparatively small number of chemically related drugs, belonging to either the quinoline or the antifolate groups. Only recently have the artemisinin derivatives been used but mostly in south east Asia. Experience has shown that resistance eventually curtails the life-span of antimalarial drugs. Controlling resistance is key to ensuring that the investment put into developing new antimalarial drugs is not wasted. Current efforts focus on research into new compounds with novel mechanisms of action, and on measures to prevent or delay resistance when drugs are introduced. Drug discovery and development are long, risky and costly ventures. Antimalarial drug development has traditionally been slow but now various private and public institutions are at work to discover and develop new compounds. Today, the antimalarial development pipeline is looking reasonably healthy. Most development relies on the quinoline, antifolate and artemisinin compounds. There is a pressing need to have effective, easy to use, affordable drugs that will last a long time. Drug combinations that have independent modes of action are seen as a way of enhancing efficacy while ensuring mutual protection against resistance. Most research work has focused on the use of artesunate combined with currently used standard drugs, namely, mefloquine, amodiaquine, sulfadoxine/pyrimethamine, and chloroquine. There is clear evidence that combinations improve efficacy without increasing toxicity. However, the absolute cure rates that are achieved by combinations vary widely and depend on the level of resistance of the standard drug. From these studies, further work is underway to produce fixed dose combinations that will be packaged in blister packs. This review will summarise current antimalarial drug developments and outline recent
Levien, Terri L; Baker, Danial E
This article reviews the use of several valuation methods as they relate to drug abuse and places them within the context of U.S. policy. First, cost-of-illness (COI) studies are reviewed and their limitations discussed. Second, three additional economic methods of valuing drug abuse are reviewed, including cost-effectiveness analysis (CEA),…
Full Text Available Mikkel Z Ankarfeldt,1,2 Erpur Adalsteinsson,1 Rolf HH Groenwold,2,3 M Sanni Ali,2,3,4 Olaf H Klungel,2,3 On behalf of GetReal Work Package 2 1Novo Nordisk A/S, 2Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, the Netherlands; 4Nuffield Department of Orthopaedics, Rheumatology, Musculoskeletal Sciences, University of Oxford, Oxford, UK Aim: To identify a potential efficacy–effectiveness gap and possible explanations (drivers of effectiveness for differences between results of randomized controlled trials (RCTs and observational studies investigating glucose-lowering drugs. Methods: A systematic literature review was conducted in English language articles published between 1 January, 2000 and 31 January, 2015 describing either RCTs or observational studies comparing glucagon-like peptide-1 analogs (GLP-1 with insulin or comparing dipeptidyl peptidase-4 inhibitors (DPP-4i with sulfonylurea, all with change in glycated hemoglobin (HbA1c as outcome. Medline, Embase, Current Content, and Biosis were searched. Information on effect estimates, baseline characteristics of the study population, publication year, study duration, and number of patients, and for observational studies, characteristics related to confounding adjustment and selection- and information bias were extracted. Results: From 312 hits, 11 RCTs and 7 observational studies comparing GLP-1 with insulin, and from 474 hits, 16 RCTs and 4 observational studies comparing DPP-4i with sulfonylurea were finally included. No differences were observed in baseline characteristics of the study populations (age, sex, body mass index, time since diagnosis of type 2 diabetes mellitus, and HbA1c or effect sizes across study designs. Mean effect sizes ranged from −0.43 to 0.91 and from −0.80 to 1.13 in RCTs and
Full Text Available BACKGROUND: Second-generation antihistamines (AHs have, in general, fewer sedative effects than the first-generation. However, important inter-drug differences remain in the degree of cognitive and/or psychomotor impairment. The extent to which a particular compound causes disruption can be conveniently compared, to all other AHs, using the Proportional Impairment Ratio (PIR. Although the PIR can differentiate the relative impairment caused by individual drugs, there is no indication of the reliability of the ratios obtained. OBJECTIVE: To calculate the PIRs -together with 95% confidence intervals (CIs, as an index of reliability- and compare AHs currently, or soon to be, available in Japan, with respect to their intrinsic capacity to cause impairment. METHODS: Results from studies of cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, mequitazine, and olopatadine were included in the PIR calculations. All data utilised came from crossover studies in healthy volunteers which were randomised and placebo and positive-internal controlled. Existing databases from studies reporting the sedative effects of AHs on objective (speed, accuracy, memory and subjective (feeling psychometrics were augmented, via results from suitable studies published after the previous reviews. The null value for a PIR was one. RESULTS: A total of 45 studies were finally included for this review. Of the AHs assessed, fexofenadine, ebastine, and levocetirizine showed a PIR for objective tests of 0. However, only fexofenadine (PIR = 0.49 had an upper limit of the 95% CI of less than 1. Fexofenadine, levocetirizine, desloratadine, olopatadine, loratadine, and mequitazine all had a PIR for subjective ratings of 0, but the upper limits of the 95% CIs were all in excess of 1, although fexofenadine (PIR = 2.57 was the lowest. CONCLUSIONS: The results show that there are differences between second-generation AHs in the extent of sedation produced
Full Text Available A new phenomenon in the drug market has appeared in recent years: there has been an increase in the number and types of designer drugs. A massive influx of these structural and/or functional analogs of controlled substances has resulted in an increase in their marketing and abuse. At present, these drugs are significantly more widely available compared to previous years because they are relatively inexpensive and marketed as being safer than classic drugs of abuse. The most important factor in the spread of designer drugs is that the majority of these substances are undetectable as drugs or illegal drugs in standard drug testing procedures. The biological effects of these substances are largely unknown to both users and medical scientists. However, most known cases of abuse have shown serious and dangerous physical and psychological reactions in users. The manufacturing and marketing of designer drugs presents a major challenge for specialist sectors, especially laboratories that have to test these substances. This highlights the important role of drugcontrol institutions and regulatory and legislative bodies to determine the legal status of these drugs, which are designed and marketed - mostly through the internet - as being legal. All of these factors make it incumbent upon these sectors to form a unified goal and strategy to control these substances and prevent their spread. This review provides fundamental information about designer drugs. This will provide an accurate overview of their status, and will aid future work to develop a regulatory and legislative strategy to combat their manufacture, marketing, and use.
Tran, Stephanie; DeGiovanni, Peter-Joseph; Piel, Brandon; Rai, Prakash
Cancer continues to be one of the most difficult global healthcare problems. Although there is a large library of drugs that can be used in cancer treatment, the problem is selectively killing all the cancer cells while reducing collateral toxicity to healthy cells. There are several biological barriers to effective drug delivery in cancer such as renal, hepatic, or immune clearance. Nanoparticles loaded with drugs can be designed to overcome these biological barriers to improve efficacy while reducing morbidity. Nanomedicine has ushered in a new era for drug delivery by improving the therapeutic indices of the active pharmaceutical ingredients engineered within nanoparticles. First generation nanomedicines have received widespread clinical approval over the past two decades, from Doxil ® (liposomal doxorubicin) in 1995 to Onivyde ® (liposomal irinotecan) in 2015. This review highlights the biological barriers to effective drug delivery in cancer, emphasizing the need for nanoparticles for improving therapeutic outcomes. A summary of different nanoparticles used for drug delivery applications in cancer are presented. The review summarizes recent successes in cancer nanomedicine in the clinic. The clinical trials of Onivyde leading to its approval in 2015 by the Food and Drug Adminstration are highlighted as a case study in the recent clinical success of nanomedicine against cancer. Next generation nanomedicines need to be better targeted to specifically destroy cancerous tissue, but face several obstacles in their clinical development, including identification of appropriate biomarkers to target, scale-up of synthesis, and reproducible characterization. These hurdles need to be overcome through multidisciplinary collaborations across academia, pharmaceutical industry, and regulatory agencies in order to achieve the goal of eradicating cancer. This review discusses the current use of clinically approved nanomedicines, the investigation of nanomedicines in clinical
Sulochana, Suresh P; Syed, Muzeeb; Chandrasekar, Devaraj V; Mullangi, Ramesh; Srinivas, Nuggehally R
Sucralfate, a complex of aluminium hydroxide with sulfated sucrose, forms a strong gastrointestinal tract (GIT) mucosal barrier with excellent anti-ulcer property. Because sucralfate does not undergo any significant oral absorption, sucralfate resides in the GIT for a considerable length of time. The unabsorbed sucralfate may alter the pharmacokinetics of the oral drugs by impeding its absorption and reducing the oral bioavailability. Because of the increased use of sucralfate, it was important to provide a reappraisal of the published clinical drug-drug interaction studies of sucralfate with scores of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along with study design, objectives and key remarks. While the loss of oral bioavailability was significant for the fluoroquinolone class, it generally varied for other classes of drugs, suggesting that impact of the co-administration of sucralfate is manageable in clinical situations. Given the technology advancement in formulation development, it may be in order feasible to develop appropriate formulation strategies to either avoid or minimize the absorption-related issues when co-administered with sucralfate. It is recommended that consideration of both in vitro and preclinical studies may be in order to gauge the level of interaction of a drug with sucralfate. Such data may aid in the development of appropriate strategies to navigate the co-administration of sucralfate with other drugs in this age of polypharmacy.
Full Text Available Although psychostimulants have been used for the treatment of attention deficit hyperactivity disorder for approximately 70 years, little is known about the long term effects of these drugs on developing brain. The observable effects of psychostimulants are influenced by the timing of exposure, the age of examination after drug exposure and sex. Preclinical studies point out that chronic psychostimulant exposure before adolescence cause reverse sensitization or tolerance and this leads to reduction in stimulant effectiveness in adolesecence and adulthood. Preclinical studies show the potential long term effects of psychostimulants. But it is necessary to investigate the relationship between preclinical effects and clinical practice. A developmental approach is needed to understand the impact of pediatric medications on the brain that includes assessment at multiple ages to completely characterize the long term effects of these medications. The aim of this paper is to review the effects of psychostimulants on developing brain.
Esmay, J B; Wertheimer, A I
The authors review the extent of the use of nonprescription drugs as well as possible variables influencing such consumption. Various studies indicate that age, sex, personality characteristics, perceptions of health status, socioeconomic factors, parental example, and pharmacists all play parts in determining over-the-counter (OTC) drug utilization. Several sources express concern about the inaccessibility of accurate OTC drug information to the consumer. Indeed, even the FDA has occasional difficulty obtaining reliable facts on both the numbers and formulae of such products. Several studies indicate that consumers acquire information about their home remedies through advertising, friends and relatives, physicians, pharmacists, and product labels. By far the most influential of these is advertising, and much concern has been voiced over consumers' unquestioning faith in drug ads. Examples are cited of deceptive, inaccurate, and unfair advertising practices used by some OTC drug manufacturers. The pros and cons of the "drug-oriented society" theory are discussed, including an analysis of its underlying origins. Testing of the safety and efficacy of nonrescription remedies has proved to be controversial, especially when considering the ramifications of the placebo effect. Different surveys report widespread misuse of OTC's by consumers through overuse, taking several drugs concurrently, and using home remedies to treat potentially serious diseases.
Andersen, Susan L; Navalta, Carryl P
Our aim is to present a working model that may serve as a valuable heuristic to predict enduring effects of drugs when administered during development. Our primary tenet is that a greater understanding of neurodevelopment can lead to improved treatment that intervenes early in the progression of a given disorder and prevents symptoms from manifesting. The immature brain undergoes significant changes during the transitions between childhood, adolescence, and adulthood. Such changes in innervation, neurotransmitter levels, and their respective signaling mechanisms have profound and observable changes on typical behavior, but also increase vulnerability to psychiatric disorders when the maturational process goes awry. Given the remarkable plasticity of the immature brain to adapt to its external milieu, preventive interventions may be possible. We intend for this review to initiate a discussion of how currently used psychotropic agents can influence brain development. Drug exposure during sensitive periods may have beneficial long-term effects, but harmful delayed consequences may be possible as well. Regardless of the outcome, this information needs to be used to improve or develop alternative approaches for the treatment of childhood disorders. With this framework in mind, we present what is known about the effects of stimulants, antidepressants, and antipsychotics on brain maturation (including animal studies that use more clinically-relevant dosing paradigms or relevant animal models). We endeavor to provocatively set the stage for altering treatment approaches for improving mental health in non-adult populations. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.
van Galen, Katy A.; Nellen, Jeannine F.; Nieuwkerk, Pythia T.
Administering drugs as fixed-dose combinations (FDCs) versus the same active drugs administered as separate pills is assumed to enhance treatment adherence. We synthesized evidence from randomized controlled trials (RCTs) about the effect of FDCs versus separate pills on adherence. We searched
Khoshnood, Saeed; Heidary, Mohsen; Mirnejad, Reza; Bahramian, Aghil; Sedighi, Mansour; Mirzaei, Habibollah
Urinary tract infection(UTI) caused by Gram-negative bacteria is the second most common infectious presentation in community medical practice. Approximately 150 million people are diagnosed with UTI each year worldwide. Drug resistance in Gram-negative uropathogens is a major global concern which can lead to poor clinical outcomes including treatment failure, development of bacteremia, requirement for intravenous therapy, hospitalization, and extended length of hospital stay. The mechanisms of drug resistance in these bacteria are important due to they are often not identified by routine susceptibility tests and have an exceptional potential for outbreaks. Treatment of UTIs depends on the access to effective drugs, which is now threatened by antibiotic resistant Gram-negative uropathogens. Although several effective antibiotics with activity against highly resistant Gram-negatives are available, there is not a unique antibiotic with activity against the high variety of resistance. Therefore, antimicrobial susceptibility tests, correlation between clinicians and laboratories, development of more rapid diagnostic methods, and continuous monitoring of drug resistance are urgent priorities. In this review, we will discuss about the current global status of drug-resistant Gram-negative uropathogens and their mechanisms of drug resistance to provide new insights into their treatment options. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Full Text Available Drug-induced cutaneous eruptions are named among the most common side effects of many medications. Thus, cutaneous drug eruptions are a common cause of morbidity and mortality, especially in hospital settings. The present article reviews different presentations of drug-induced cutaneous eruptions, with a focus on eruptions reported secondary to the use of interferon and ribavirin. Presentations include injection site reactions, psoriasis, eczematous drug reactions, alopecia, sarcoidosis, lupus, fixed drug eruptions, pigmentary changes and lichenoid eruptions. Also reviewed are findings regarding life-threatening systemic drug reactions.
Chary, Aarthi; Nguyen, Nancy N; Maiton, Kimberly; Holodniy, Mark
The number of older HIV-infected people is growing due to increasing life expectancies resulting from the use of antiretroviral therapy (ART). Both HIV and aging increase the risk of other comorbidities, such as cardiovascular disease, osteoporosis, and some malignancies, leading to greater challenges in managing HIV with other conditions. This results in complex medication regimens with the potential for significant drug-drug interactions and increased morbidity and mortality. Area covered: We review the metabolic pathways of ART and other medications used to treat medical co-morbidities, highlight potential areas of concern for drug-drug interactions, and where feasible, suggest alternative approaches for treating these conditions as suggested from national guidelines or articles published in the English language. Expert commentary: There is limited evidence-based data on ART drug interactions, pharmacokinetics and pharmacodynamics in the older HIV-infected population. Choosing and maintaining effective ART regimens for older adults requires consideration of side effect profile, individual comorbidities, interactions with concurrent prescriptions and non-prescription medications and supplements, dietary patterns with respect to dosing, pill burden and ease of dosing, cost and affordability, patient preferences, social situation, and ART resistance history. Practitioners must remain vigilant for potential drug interactions and intervene when there is a potential for harm.
Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint
trials. Meta-analytic methods were used to quantitatively synthesize study results. Results: The search yielded five studies that met inclusion criteria. MDFT was found to be more effective than other treatments on drug abuse problem severity and drug use frequency in the short run but not in the long...... run and demonstrated positive effects on treatment retention compared to control conditions. Discussion: While additional research is needed, the review offers support for MDFT as a treatment to young nonopioid drug abusers. The number of studies included in this review was limited, however......Purpose: This review evaluates the evidence of the effects of multidimensional family therapy (MDFT) on drug use reduction in young people for the treatment of nonopioid drug use. Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized...
Full Text Available Barbara Kneidl,1,2 Michael Peller,3 Gerhard Winter,2 Lars H Lindner,1 Martin Hossann11Department of Internal Medicine III, University Hospital Munich, 2Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, 3Institute for Clinical Radiology, University Hospital Munich, Ludwig-Maximilians University, Munich, GermanyAbstract: Thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local hyperthermia or high intensity focused ultrasound. In vivo results have demonstrated strong evidence that external targeting is superior over passive targeting achieved by highly stable long-circulating drug formulations like PEGylated liposomal doxorubicin. Up to March 2014, the Web of Science listed 371 original papers in this field, with 45 in 2013 alone. Several formulations have been developed since 1978, with lysolipid-containing, low temperature-sensitive liposomes currently under clinical investigation. This review summarizes the historical development and effects of particular phospholipids and surfactants on the biophysical properties and in vivo efficacy of thermosensitive liposome formulations. Further, treatment strategies for solid tumors are discussed. Here we focus on temperature-triggered intravascular and interstitial drug release. Drug delivery guided by magnetic resonance imaging further adds the possibility of performing online monitoring of a heating focus to calculate locally released drug concentrations and to externally control drug release by steering the heating volume and power. The combination of external targeting with thermosensitive liposomes and magnetic resonance-guided drug delivery will be the unique characteristic of this nanotechnology approach in medicine.Keywords: thermosensitive liposomes, phosphatidyloligoglycerol, hyperthermia, high intensity focused ultrasound, drug delivery, drug targeting
Full Text Available Colloidal drug delivery systems have been extensively investigated as drug carriers for the application of different drugs via different routes of administration. Systems, such as solid lipid nanoparticles, polymeric nanoparticles and liposomes, have been investigated for a long time for the treatment of various lung diseases. The pulmonary route, owing to a noninvasive method of drug administration, for both local and systemic delivery of an active pharmaceutical ingredient (API forms an ideal environment for APIs acting on pulmonary diseases and disorders. Additionally, this route offers many advantages, such as a high surface area with rapid absorption due to high vascularization and circumvention of the first pass effect. Aerosolization or inhalation of colloidal systems is currently being extensively studied and has huge potential for targeted drug delivery in the treatment of various diseases. Furthermore, the surfactant-associated proteins present at the interface enhance the effect of these formulations by decreasing the surface tension and allowing the maximum effect. The most challenging part of developing a colloidal system for nebulization is to maintain the critical physicochemical parameters for successful inhalation. The following review focuses on the current status of different colloidal systems available for the treatment of various lung disorders along with their characterization. Additionally, different in vitro, ex vivo and in vivo cell models developed for the testing of these systems with studies involving cell culture analysis are also discussed.
Dubald, Marion; Bourgeois, Sandrine; Andrieu, Véronique; Fessi, Hatem
The last fifty years, ophthalmic drug delivery research has made much progress, challenging scientists about the advantages and limitations of this drug delivery approach. Topical eye drops are the most commonly used formulation in ocular drug delivery. Despite the good tolerance for patients, this topical administration is only focus on the anterior ocular diseases and had a high precorneal loss of drugs due to the tears production and ocular barriers. Antibiotics are popularly used in solution or in ointment for the ophthalmic route. However, their local bioavailability needs to be improved in order to decrease the frequency of administrations and the side effects and to increase their therapeutic efficiency. For this purpose, sustained release forms for ophthalmic delivery of antibiotics were developed. This review briefly describes the ocular administration with the ocular barriers and the currently topical forms. It focuses on experimental results to bypass the limitations of ocular antibiotic delivery with new ocular technology as colloidal and in situ gelling systems or with the improvement of existing forms as implants and contact lenses. Nanotechnology is presently a promising drug delivery way to provide protection of antibiotics and improve pathway through ocular barriers and deliver drugs to specific target sites. PMID:29342879
Semet, M; Paci, M; Saïas-Magnan, J; Metzler-Guillemain, C; Boissier, R; Lejeune, H; Perrin, J
Beside cytotoxic drugs, other drugs can impact men's fertility through various mechanisms. Via the modification of the hypothalamic-pituitary-gonadal axis hormones or by non-hormonal mechanisms, drugs may directly and indirectly induce sexual dysfunction and spermatogenesis impairment and alteration of epididymal maturation. This systematic literature review summarizes existing data about the negative impact and associations of pharmacological treatments on male fertility (excluding cytotoxic drugs), with a view to making these data more readily available for medical staff. In most cases, these effects on spermatogenesis/sperm maturation/sexual function are reversible after the discontinuation of the drug. When a reprotoxic treatment cannot be stopped and/or when the impact on semen parameters/sperm DNA is potentially irreversible (Sulfasalazine Azathioprine, Mycophenolate mofetil and Methotrexate), the cryopreservation of spermatozoa before treatment must be proposed. Deleterious impacts on fertility of drugs with very good or good level of evidence (Testosterone, Sulfasalazine, Anabolic steroids, Cyproterone acetate, Opioids, Tramadol, GhRH analogues and Sartan) are developed. © 2017 American Society of Andrology and European Academy of Andrology.
Full Text Available The last fifty years, ophthalmic drug delivery research has made much progress, challenging scientists about the advantages and limitations of this drug delivery approach. Topical eye drops are the most commonly used formulation in ocular drug delivery. Despite the good tolerance for patients, this topical administration is only focus on the anterior ocular diseases and had a high precorneal loss of drugs due to the tears production and ocular barriers. Antibiotics are popularly used in solution or in ointment for the ophthalmic route. However, their local bioavailability needs to be improved in order to decrease the frequency of administrations and the side effects and to increase their therapeutic efficiency. For this purpose, sustained release forms for ophthalmic delivery of antibiotics were developed. This review briefly describes the ocular administration with the ocular barriers and the currently topical forms. It focuses on experimental results to bypass the limitations of ocular antibiotic delivery with new ocular technology as colloidal and in situ gelling systems or with the improvement of existing forms as implants and contact lenses. Nanotechnology is presently a promising drug delivery way to provide protection of antibiotics and improve pathway through ocular barriers and deliver drugs to specific target sites.
Helena Prior Filipe
Full Text Available ABSTRACT Topically applied therapy is the most common way to treat ocular diseases, however given the anatomical and physiological constraints of the eye, frequent dosing is required with possible repercussions in terms of patient compliance. Beyond refractive error correction, contact lenses (CLs have, in the last few decades emerged as a potential ophthalmic drug controlled release system (DCRS. Extensive research is underway to understand how to best modify CLs to increase residence time and bioavailability of drugs within therapeutic levels on the ocular surface.These devices may simultaneously correct ametropia and have a role in managing ophthalmic disorders that can hinder CL wear such as dry eye, glaucoma, ocular allergy and cornea infection and injury. In this narrative review the authors explain how the ocular surface structures determine drug diffusion in the eye and summarize the strategies to enhance drug residence time and bioavailability. They synthesize findings and clinical applications of drug soaked CLs as DCRS combined with delivery diffusion barriers, incorporation of functional monomers, ion related controlled release, molecular imprinting, nanoparticles and layering. The authors draw conclusions about the impact of these novel ophthalmic agents delivery systems in improving drug transport in the target tissue and patient compliance, in reducing systemic absorption and undesired side effects, and discuss future perspectives.
Sklar, Lindsay R; Burnett, Christopher T; Waibel, Jill S; Moy, Ronald L; Ozog, David M
Topically applied drugs have a relatively low cutaneous bioavailability. This article reviews the existing applications of laser assisted drug delivery, a means by which the permeation of topically applied agents can be enhanced into the skin. The existing literature suggests that lasers are a safe and effective means of enhancing the delivery of topically applied agents through the skin. The types of lasers most commonly studied in regards to drug delivery are the carbon dioxide (CO2 ) and erbium:yttrium-aluminum-garnet (Er:YAG) lasers. Both conventional ablative and fractional ablative modalities have been utilized and are summarized herein. The majority of the existing studies on laser assisted drug delivery have been performed on animal models and additional human studies are needed. Laser assisted drug delivery is an evolving technology with potentially broad clinical applications. Multiple studies demonstrate that laser pretreatment of the skin can increase the permeability and depth of penetration of topically applied drug molecules for both local cutaneous and systemic applications. © 2014 Wiley Periodicals, Inc.
van Galen, Katy A; Nellen, Jeannine F; Nieuwkerk, Pythia T
Administering drugs as fixed-dose combinations (FDCs) versus the same active drugs administered as separate pills is assumed to enhance treatment adherence. We synthesized evidence from randomized controlled trials (RCTs) about the effect of FDCs versus separate pills on adherence. We searched PubMed for RCTs comparing a FDC with the same active drugs administered as separate pills, including a quantitative estimate of treatment adherence, without restriction to medical condition. The odds ratio (OR) of optimal adherence with FDCs versus separate pills was used as common effect size and aggregated into a pooled effect estimate using a random effect model with inverse variance weights. Out of 1258 articles screened, only six studies fulfilled inclusion criteria. Across medical conditions, administering drugs as FDC significantly increased the likelihood of optimal adherence (OR 1.33 (95% CI, 1.03-1.71)). Within subgroups of specific medical conditions, the favourable effect of FDCs on adherence was of borderline statistical significance for HIV infection only (OR 1.46 (95% CI, 1.00-2.13)). We observed a remarkable paucity of RCTs comparing the effect on adherence of administering drugs as FDC versus as separate pills. Administering drugs as FDC improved medication adherence. However, this conclusion is based on a limited number of RCTs only.
Full Text Available Propafenone HCI (p, is a relatively new Class IC antiarrhythmic agent. It has been reported to be superior to conventional antiarrhythmics in the control of supraventricular, ventricular and WPW associated tachyarrhythmias. It has been also shown to be well tolerated. In our study protocol, which extends over 2~ years period , we used (p in 87 patients for management of various types of cardiac arrhythmias (most of whom were resistant to conventmonal antiarrhythmics . Intravenously administered, (P was effective in 85% of patients with paroxysmal reentrant supraventricular tachycardia (PRSVT, 75% of those with paroxysmal atrial fibrillation (PAF , 50% and 42% of those with refractory premature ventricular contractions (PVC and ventricular tachycardia (V. Tach, respectively. Orally administered, (P was effective in 73% of those with resistant PVCs and nonsustained ventricular tachycardia (NSV Tach, and 75% of those with resistant sustained ventricular tachycardia (RSVT •
Injecting drug use is a growing problem in Africa and a growing risk factor for contracting HIV in the region. It is imperative that HIV research includes injecting drug users so that they too are able to benefit from safe and effective behavioural interventions and biomedical HIV prevention and treatment products. This article relates a critical review of the findings of a desk review of previously published literature. The article examines injecting drug use in relation to HIV-related risk and research in Kenya, Mauritius, Nigeria, South Africa and Tanzania. The ethical challenges of including people who inject drugs in HIV research in Africa are also presented. The review found injecting drug use to be on the increase in all the countries reviewed. HIV-risk behaviour among people who inject drugs, such as needle-sharing and higher-risk sexual behaviour, was also found to be widespread. Furthermore, criminalisation of drug use and strict anti-drug laws are common in the countries reviewed, while harm-reduction programmes for people who inject drugs were found to be limited. The review identified a number of ethical challenges to the involvement of people who inject drugs in HIV research in Africa. This includes the illegal status and stigma surrounding injecting drug use, which may complicate participant recruitment, enrolment and retention. In addition, a lack of funding for supportive programmes to help injecting drug users may hinder the provision of appropriate standards of prevention and care and treatment for those who seroconvert.
Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint
Objectives: This review evaluates the evidence on the effects of functional family therapy (FFT) on drug abuse reduction for young people in treatment for nonopioid drug use. Data and Analysis: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials. Results: The search yielded two…
Krishnan Vengadaragava Chary
Full Text Available Objective: The objective of this study is to assess the postmarketing status: Efficacy and safety drugs and biologics related with cancer approved under expedited review. Methods: This observational, analytical study was carried between January and April 2016 by the Department of Pharmacology and Medical Oncology, Saveetha Medical College. Drugs approved under expedited review, fast-track status and its association with anti-cancer effects, postmarketing efficacy and safety, propensity to induce the second tumor was noted. Drug approval status and average time of review process were obtained from the United States-Food and Drug Administration (FDA, Center for Drugs and Biologics Center (Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research. Postmarketing adverse events and safety issues were collected FDA adverse effects reporting system. Further, evidence efficacy and safety of drugs were taken from various meta-analysis, reports on BioMed journals, and Cochrane systematic reviews. Results: In the last 5 years, 166 products were approved by expedited review. Out of 166, 48 (28.9% drugs/biologics are anticancer drugs and drugs used in precancerous conditions. The average time of review varies from19 months to 8.2 months. Out of these 48 molecules, 37 (77% molecules received serious adverse event alert. Positive correlation is seen between average time of review and number of adverse events reported. Seven (14.5% drugs were proven to induce second tumor among receivers. Conclusion: Although expedited review facilitates faster approval of drugs; selection and assessment criteria should be stringent to prevent clinical failure, serious adverse effects of such drugs exposed to many individuals. Focus should be given developing chemosensitizing molecule and evaluation of metronomic regimen which is being more optimistic in current cancer therapeutics.
Full Text Available Radiopharmaceuticals play a critical role in modern medicine primarily for diagnostic purposes, but also for monitoring disease progression and response to treatment. As the use of image has been increased, so has the use of prescription medications. These trends increase the risk of interactions between medications and radiopharmaceuticals. These interactions which have an impact on image by competing with the radiopharmaceutical for binding sites for example can lead to false negative results. Drugs that accelerate the metabolism of the radiopharmaceutical can have a positive impact (i.e. speeding its clearance or, if repeating image is needed, a negative impact. In some cases, for example in cardiac image among patients taking doxirubacin, these interactions may have a therapeutic benefit. The incidence of drug-radiopharmaceuticals adverse reactions is unknown, since they may not be reported or even recognized. Here,we compiled the medical literature, using the criteria of a systematic review established by the Cochrane Collaboration, on pharmaceutical-drug interactions to provide a summary of documented interactions by organ system and radiopharmaceuticals. The purpose is to provide a reference on drug interactions that could inform the nuclear medicine staff in their daily routine. Efforts to increase adverse event reporting, and ideally consolidate reports worldwide, can provide a critically needed resource for prevention of drug-radiopharmaceuticals interactions.Os radiofármacos desempenham função crítica na medicina moderna, primariamente para fins diagnósticos, mas também no monitoramento da progressão de doenças assim como na avaliação de respostas ao tratamento. O uso da tecnologia por imagem tem crescido e conseqüentemente as prescrições de medicamentos (radiofármacos em especial com esse propósito. Este fato, aumenta o risco de interações entre medicamentos e radiofármacos. Interações que podem ter um impacto na
Martelli, Laura; Olivera, Pablo; Roblin, Xavier; Attar, Alain; Peyrin-Biroulet, Laurent
Therapeutic drug monitoring (TDM) of anti-TNF is increasingly used to manage inflammatory bowel diseases (IBD) and rheumatoid arthritis (RA). The cost-effectiveness of this strategy is debated. All studies comparing the cost-effectiveness of a TDM-based strategy and an empirical dose management of anti-TNF in IBD or RA were screened. Studies were identified through the MEDLINE electronic database (up to July 2016), and annual international meeting abstracts were also manually reviewed. Seven studies were included: two randomized controlled trials (RCTs) enrolling 332 patients [247 Crohn's disease (CD) and 85 ulcerative colitis (UC)] and five modeling approaches. Four studies included only CD patients, one included both CD and UC patients, and two included only RA patients. Three studies compared the cost-effectiveness of the two strategies in patients with secondary infliximab (IFX) failure (dose-escalation strategy), one in patients in remission on optimized IFX (de-escalation strategy), one in patients starting adalimumab, and two in patients with clinical response to maintenance anti-TNF therapy. The two RCTs demonstrated that a TDM strategy led to major cost savings, ranging from 28 to 34 %. The three modeling approaches with regard to CD patients demonstrated cost savings ranging from $5396 over a 1-year period to €13,130 per patient at 5 years of follow-up. A TDM strategy also led to major cost savings in the two modeling approaches in RA patients. Available evidence indicates that a TDM strategy leads to major cost savings related to anti-TNF therapy in both IBD and RA patients, with no negative impact on efficacy.
Kopp, S W; Bang, H K
As pharmaceutical companies began to advertise prescription drugs directly to consumers as well as to physicians, understanding the impact of benefit and risk information in drug advertising on physicians and consumers has become more critical. This paper reviews previous empirical studies that examined the content of benefit and risk information in drug advertising and its potential effects on physicians' subsequent prescribing behaviors. It also reviews studies that investigated how consumers process information on a drug's efficacy and side effects. Based on the findings of these studies, implications are discussed for effective marketing information development as well as for government regulation.
Vignon Zomahoun, H.T.; de Bruin, M.; Guillaumie, L.; Moisan, J.; Grégoire, J.P.; Pérez, N.; Vézina-Im, L.A.; Guénette, L.
Objectives To estimate the pooled effect size of oral antidiabetic drug (OAD) adherence-enhancing interventions and to explore which of the behavior change techniques (BCTs) applied in the intervention groups modified this pooled intervention effect size. Methods We searched relevant studies
Full Text Available Pharmacokinetic drug–drug interactions (in particular at metabolism may result in fatal adverse effects in some cases. This basic information, therefore, is needed for drug therapy even in veterinary medicine, as multidrug therapy is not rare in canines and felines. The aim of this review was focused on possible drug–drug interactions in dogs and cats. The interaction includes enzyme induction by phenobarbital, enzyme inhibition by ketoconazole and fluoroquinolones, and down-regulation of enzymes by dexamethasone. A final conclusion based upon the available literatures and author’s experience is given at the end of the review.
Chambers, James D; Thorat, Teja; Wilkinson, Colby L; Neumann, Peter J
We investigated whether drugs approved by the Food and Drug Administration (FDA) through expedited review have offered larger health gains, compared to drugs approved through conventional review processes. We identified published estimates of additional health gains (measured in quality-adjusted life-years, or QALYs) associated with drugs approved in the period 1999-2012 through expedited (seventy-six drugs) versus conventional (fifty-nine) review processes. We found that drugs in at least one expedited review program offered greater gains than drugs reviewed through conventional processes (0.182 versus 0.003 QALYs). We also found that, compared to drugs not included in the same program, greater gains were provided by drugs in the priority review (0.175 versus 0.007 QALYs), accelerated approval (0.370 versus 0.031 QALYs), and fast track (0.254 versus 0.014 QALYs) programs. Our analysis suggests that the FDA has prioritized drugs that offer the largest health gains. Project HOPE—The People-to-People Health Foundation, Inc.
Dvortsin, Evgeni; Gout-Zwart, Judith; Eijssen, Ernst-Lodewijk Marie; van Brussel, Jan; Postma, Maarten J.
Background Many oncological drugs that are being used in the adjuvant setting were first submitted for reimbursement in the metastatic stage, with differences in incremental cost-effectiveness ratios (ICERs) in both settings having potential implications for reimbursement and pricing. The aim of
Andersen, Susan L.; Navalta, Carryl P.
Our aim is to present a working model that may serve as a valuable heuristic to predict enduring effects of drugs when administered during development. Our primary tenet is that a greater understanding of neurodevelopment can lead to improved treatment that intervenes early in the progression of a given disorder and prevents symptoms from…
La Gerche, André; Brosnan, Maria J
Exercise and competitive sports should be associated with a wide range of health benefits with the potential to inspire a positive community health legacy. However, the reputation of sports is being threatened by an ever-expanding armamentarium of agents with real or perceived benefits in performance enhancement. In addition to the injustice of unfair advantage for dishonest athletes, significant potential health risks are associated with performance-enhancing drugs. Performance-enhancing drugs may have an effect on the cardiovascular system by means of directly altering the myocardium, vasculature, and metabolism. However, less frequently considered is the potential for indirect effects caused through enabling athletes to push beyond normal physiological limits with the potential consequence of exercise-induced arrhythmias. This review will summarize the known health effects of PEDs but will also focus on the potentially greater health threat posed by the covert search for performance-enhancing agents that have yet to be recognized by the World Anti-Doping Agency. History has taught us that athletes are subjected to unmonitored trials with experimental drugs that have little or no established efficacy or safety data. One approach to decrease drug abuse in sports would be to accept that there is a delay from when athletes start experimenting with novel agents to the time when authorities become aware of these drugs. This provides a window of opportunity for athletes to exploit with relative immunity. It could be argued that all off-label use of any agent should be deemed illegal. © 2016 American Heart Association, Inc.
Full Text Available Illicit drug problem is one of the most worrying issues of the presenet century in all countries and anti-drug addiction programs are included in the agenda of all governments and international community. Drug abuse/addiction in Iran has been one of the most important social and economical problems for several years and the number and percentage of drug users/addicts are growing. Campaign against this phenomenon needs in-depth recognition of all aspects (economic, social and political of this problem. So, such programs will be successful in fighting against illicit drugs and drug addiction if they are developed and implemented through a realistic recognition. One can not hope the success of anti-drug programs if they are not planned on the basis of researches. Therefore, reviewing the economical aspect of illicit drugs via usrers’ viewpoints will help to undrestand illicit drug addiction phenomenon. In this article, the behaviour of drug usres is studied on the basis of micro-economic traditional assumptions. The relation between deman and prices of illicit drugs, the relation between tendency to drug consumption and the amount of drug consumption and the relaion between drug consumption and criminal acts are among the discussed issues of this article. Finally, a summary of the situation of illicit drug consumption is presented.
Rodríguez Salgado, Beatriz; Gómez-Arnau Ramírez, Jorge; Sánchez Mateos, Daniel; Dolengevich Segal, Helen
There is growing interest in plants with psychoactive effects among consumers with different levels of experience. This has generated a need for updated knowledge among medical professionals and other health workers. These plants, which may be used in shamanic healing ceremonies or rituals or just for traditional purposes, have emerged in the Western world as new psychoactive drugs; largely thanks to the ease of purchase, sale, cultivation and exchange of information that the Internet offers. This review summarizes the current knowledge about the most important psychoactive plants, either by their mention in Internet forums or harm-reduction portals or by their allusion in scientific texts.
Pal, Raktim; Megharaj, Mallavarapu; Kirkbride, K Paul; Naidu, Ravi
Illicit drugs and their metabolites are the latest group of emerging pollutants. Determination of their concentration in environment (such as water bodies, soil, sediment, air) is an indirect tool to estimate the community level consumption of illicit drug and to evaluate potential ecotoxicological impacts from chronic low level exposure. They enter the wastewater network as unaltered drugs and/or their active metabolites by human excretion after illegal consumption or by accidental or deliberate disposal from clandestine drug laboratories. This article critically reviews the occurrence and concentration levels of illicit drugs and their metabolites in different environmental compartments (e.g., wastewater, surface waters, groundwater, drinking water, and ambient air) and their potential impact on the ecosystem. There is limited published information available on the presence of illicit drugs in the environment, reports are available mainly from European countries, UK, USA, and Canada but there is a lack of information from the remainder of the world. Although the environmental concentrations are not very high, they can potentially impact the human health and ecosystem functioning. Cocaine, morphine, amphetamine, and MDMA have potent pharmacological activities and their presence as complex mixtures in water may cause adverse effect on aquatic organisms and human health. However, there is no current regulation demanding the determination of occurrence of these emerging pollutants in treated wastewater, surface water, drinking water, or atmosphere. Thus, critical investigation on distribution pattern of this new group of emerging contaminant and their potential harmful impact on our environment needs immediate attention. Copyright © 2012. Published by Elsevier B.V.
Lauve Rachel Tchokouaha Yamthe
Full Text Available Leishmaniasis is a vector-borne neglected tropical disease caused by protozoan parasites of the Leishmania genus and transmitted by the female Phlebotomus and Lutzomyia sand flies. The currently prescribed therapies still rely on pentavalent antimonials, pentamidine, paromomycin, liposomal amphotericin B, and miltefosine. However, their low efficacy, long-course treatment regimen, high toxicity, adverse side effects, induction of parasite resistance and high cost require the need for better drugs given that antileishmanial vaccines may not be available in the near future. Although most drugs are still derived from terrestrial sources, the interest in marine organisms as a potential source of promising novel bioactive natural agents has increased in recent years. About 28,000 compounds of marine origin have been isolated with hundreds of new chemical entities. Recent trends in drug research from natural resources indicated the high interest of aquatic eukaryotic photosynthetic organisms, marine algae in the search for new chemical entities given their broad spectrum and high bioactivities including antileishmanial potential. This current review describes prepared extracts and compounds from marine macroalgae along with their antileishmanial activity and provides prospective insights for antileishmanial drug discovery.
T.A. Kanters (Tim A.); C. de Sonneville (Caroline); W.K. Redekop (Ken); L. van Hakkaart-van Roijen (Leona)
markdownabstract__Abstract__ __Background__: Attention for Evidence Based Medicine (EBM) is growing, but evidence for orphan drugs is argued to be limited and inferior. This study systematically reviews the available evidence on clinical effectiveness, costeffectiveness and budget impact for
McCarthy, Carol A; Ahern, Robert J; Dontireddy, Rakesh; Ryan, Katie B; Crean, Abina M
Silica materials, in particular mesoporous silicas, have demonstrated excellent properties to enhance the oral bioavailability of poorly water-soluble drugs. Current research in this area is focused on investigating the kinetic profile of drug release from these carriers and manufacturing approaches to scale-up production for commercial manufacture. This review provides an overview of different methods utilized to load drugs onto mesoporous silica carriers. The influence of silica properties and silica pore architecture on drug loading and release are discussed. The kinetics of drug release from mesoporous silica systems is examined and the manufacturability and stability of these formulations are reviewed. Finally, the future prospects of mesoporous silica drug delivery systems are considered. Substantial progress has been made in the characterization and development of mesoporous drug delivery systems for drug dissolution enhancement. However, more research is required to fully understand the drug release kinetic profile from mesoporous silica materials. Incomplete drug release from the carrier and the possibility of drug re-adsorption onto the silica surface need to be investigated. Issues to be addressed include the manufacturability and regulation status of formulation approaches employing mesoporous silica to enhance drug dissolution. While more research is needed to support the move of this technology from the bench to a commercial medicinal product, it is a realistic prospect for the near future.
Howard, Jennifer N; Harris, Ilene; Frank, Gavriella; Kiptanui, Zippora; Qian, Jingjing; Hansen, Richard
With an increase in prescription drug spending and rising drug costs there is a need to encourage the use of generic prescription drugs. However, maximizing generic drug use is not possible without the public's positive perception and meeting their informational needs about generic drugs. Thus, improving the public's confidence in, and knowledge of generic drugs on the market is critical. The objective of this systematic review is to examine and evaluate the studies focusing on the nature and extent of key factors influencing generic drug use in the United States in order to help guide policy, education and practice interventions. Using multiple search engines and key word screening criteria, empirical studies published in English between January 1, 2005 and December 31, 2015 were identified. A qualitative synthesis of the evidence identified domains of key factors that influenced generic drug use across studies. Over 3000 citations met the key word screening criteria; 67 of these met inclusion criteria for the systematic review. Seven domains of factors that influence generic drug utilization were identified: 1) patient-related factors, 2) formulary management or cost containment, 3) healthcare policies, 4) promotional activities, 5) educational initiatives, 6) technology, and 7) physician-related factors. Patients, physicians, pharmacists, formulary managers, and policymakers play an important role in generic drug use. Understanding the factors influencing generic drug use can help guide future policy, education, and practice interventions to increase generic drug use. Copyright © 2017 Elsevier Inc. All rights reserved.
Romagnoli, Katrina M; Nelson, Scott D; Hines, Lisa; Empey, Philip; Boyce, Richard D; Hochheiser, Harry
Drug information compendia and drug-drug interaction information databases are critical resources for clinicians and pharmacists working to avoid adverse events due to exposure to potential drug-drug interactions (PDDIs). Our goal is to develop information models, annotated data, and search tools that will facilitate the interpretation of PDDI information. To better understand the information needs and work practices of specialists who search and synthesize PDDI evidence for drug information resources, we conducted an inquiry that combined a thematic analysis of published literature with unstructured interviews. Starting from an initial set of relevant articles, we developed search terms and conducted a literature search. Two reviewers conducted a thematic analysis of included articles. Unstructured interviews with drug information experts were conducted and similarly coded. Information needs, work processes, and indicators of potential strengths and weaknesses of information systems were identified. Review of 92 papers and 10 interviews identified 56 categories of information needs related to the interpretation of PDDI information including drug and interaction information; study design; evidence including clinical details, quality and content of reports, and consequences; and potential recommendations. We also identified strengths/weaknesses of PDDI information systems. We identified the kinds of information that might be most effective for summarizing PDDIs. The drug information experts we interviewed had differing goals, suggesting a need for detailed information models and flexible presentations. Several information needs not discussed in previous work were identified, including temporal overlaps in drug administration, biological plausibility of interactions, and assessment of the quality and content of reports. Richly structured depictions of PDDI information may help drug information experts more effectively interpret data and develop recommendations
Chole, Revant H; Gondivkar, Shailesh M; Gadbail, Amol R; Balsaraf, Swati; Chaudhary, Sudesh; Dhore, Snehal V; Ghonmode, Sumeet; Balwani, Satish; Mankar, Mugdha; Tiwari, Manish; Parikh, Rima V
This study undertook a review of the literature on drug treatment of oral submucous fibrosis. An electronic search was carried out for articles published between January 1960 to November 2011. Studies with high level of evidence were included. The levels of evidence of the articles were classified after the guidelines of the Oxford Centre for Evidence-Based Medicine. The main outcome measures used were improvement in oral ulceration, burning sensation, blanching and trismus. Only 13 publications showed a high level of evidence (3 randomized controlled trials and 10 clinical trials/controlled clinical trials), with a total of 1157 patients. Drugs like steroids, hyaluronidase, human placenta extracts, chymotrypsin and collagenase, pentoxifylline, nylidrin hydrochloride, iron and multivitamin supplements including lycopene, have been used. Only systemic agents were associated with few adverse effects like gastritis, gastric irritation and peripheral flushing with pentoxifylline, and flushingly warm skin with nylidrin hydrochloride; all other side-effects were mild and mainly local. Few studies with high levels of evidence were found. The drug treatment that is currently available for oral submucous fibrosis is clearly inadequate. There is a need for high-quality randomized controlled trials with carefully selected and standardized outcome measures. Copyright © 2011 Elsevier Ltd. All rights reserved.
Drug treatment can have a detrimental effect on nutritional status and drugs ... non-prescription medication dispensed due to chronic diseases such ... and cytochrome P450 in the liver, lungs and small intestine and ... Alcoholic beverages.
Application of an adapted PRECIS-2 instrument to assess efficacy- and effectiveness-study designs in a systematic review of intervention studies of the hepatitis C virus-care continuum among people who use drugs
Full Text Available Ashly E Jordan,1,2 David C Perlman,2,3 Daniel J Smith,1 Holly Hagan1,2 1New York University, Rory Meyers College of Nursing, New York, NY, USA; 2Center for Drug Use and HIV Research, 3Icahn School of Medicine, Mount Sinai Beth Israel, New York, NY, USA Introduction: Systematic reviews and meta-analyses examining intervention studies may need to categorize studies by the degree to which they reflect efficacy or effectiveness study-design elements when reporting systematic reviews and meta-analysis results.Materials and methods: We identified reports presenting data from intervention studies eligible for evaluation with an adapted PRECIS-II instrument as part of a larger systematic review of the hepatitis C virus (HCV-care continuum among people who used drugs. We applied the instrument to score reports examining any of the HCV-care-continuum steps of testing, linkage to care, and treatment on an efficacy–effectiveness spectrum. Composite scores are presented in tabular format and in stacked dot plots.Results: The adapted PRECIS-II instrument was applied to 37 unique reports that presented data on 51 HCV-care-continuum outcomes of testing (n=16, linkage to care (n=12, and treatment (n=23. Totals of 28, six, and three reports had been produced on one, two, or all three outcomes, respectively. Ten and eight studies described themselves as having efficacy or effectiveness designs, respectively; 33 did not specify. PRECIS-II composite scores for reports produced on testing, linkage to care, and treatment ranged widely: 1.22–5. Composite scores for reports examining HCV treatment indicated study designs that tended toward effectiveness (3.35, but those examining testing (3.85 or linkage (3.8 had more effectiveness-study designs (P=0.003, P=0.013, respectively.Conclusion: Reviewed reports varied widely in their use of efficacy/effectiveness-study designs, suggesting that systematic reviews and meta-analyses need to consider heterogeneity in efficacy/effectiveness
Hao, Jinsong; Ghosh, Priyanka; Li, S. Kevin; Newman, Bryan; Kasting, Gerald B.; Raney, Sam G.
Introduction Exposure to heat can impact the clinical efficacy and/or safety of transdermal and topical drug products. Understanding these heat effects and designing meaningful in vitro and in vivo methods to study them are of significant value to the development and evaluation of drug products dosed to the skin. Areas covered This review provides an overview of the underlying mechanisms and the observed effects of heat on the skin and on transdermal/topical drug delivery, thermoregulation and heat tolerability. The designs of several in vitro and in vivo heat effect studies and their results are reviewed. Expert opinion There is substantial evidence that elevated temperature can increase transdermal/topical drug delivery. However, in vitro and in vivo methods reported in the literature to study heat effects of transdermal/topical drug products have utilized inconsistent study conditions, and in vitro models require better characterization. Appropriate study designs and controls remain to be identified, and further research is warranted to evaluate in vitro-in vivo correlations and the ability of in vitro models to predict in vivo effects. The physicochemical and pharmacological properties of the drug(s) and the drug product, as well as dermal clearance and heat gradients may require careful consideration. PMID:26808472
Gluud, Lise L; Christensen, Kurt; Christensen, Erik
Vasoconstrictor drugs may improve renal function in hepatorenal syndrome (HRS), but the effect on mortality has not been established. We therefore performed a systematic review of randomized trials on vasoconstrictor drugs for type 1 or type 2 HRS. Mortality was the primary outcome measure...
Tamargo, Juan; Rosano, G.; Thomas, W
. A better understanding of these sex-related differences is fundamental to improve the safety and efficacy of cardiovascular drugs and for developing proper individualized cardiovascular therapeutic strategies both in men and women. This review briefly summarize gender differences in the pharmacokinetics......Although sex-specific differences in cardiovascular medicine are well-known, the exact influences of sex on the effect of cardiovascular drugs remain unclear. Women and men differ in body composition and physiology (hormonal influences during the menstrual cycle, menopause and pregnancy...... and pharmacodynamics of cardiovascular drugs and provides recommendations to close the gaps in our understanding of sex-specific differences in drug efficacy and safety....
Roth, Megan E; Cosgrove, Kelly P; Carroll, Marilyn E
Clinical and preclinical findings indicate that males and females differ on several aspects of drug reinforcement. Females are more vulnerable than males during transition periods of drug use that are characteristic of drug addiction and relapse. Females are also more sensitive than males to the reinforcing effects of stimulants. It has been suggested that ovarian hormones contribute to the mechanisms of action underlying these sex differences. This review examines the preclinical literature on sex differences and ovarian hormonal influences on drug self-administration in animals. It summarizes the findings on the effects of these variables during different phases of drug addiction. Possible differences in the mechanisms of action of drugs of abuse due to interactions with sex differences or ovarian hormonal factors are considered. The animal literature on sex differences in drug abuse treatment effectiveness is also discussed.
Dalwadi, Chintan; Patel, Gayatri
Nanohydrogel combines the advantages of hydrogel and nano particulate systems. Similar to the hydrogel and macrogel, nanohydrogel can protect the drug and control drug release by stimuli responsive conformation or biodegradable bond into the polymer networks. Nanohydrogel has drawn huge interest due to their potential applications, such as carrier in target-specific controlled drug delivery, absorbents, chemical/biological sensors, and bio-mimetic materials. Similar to the nanoparticles, stimuli responsive nanohydrogel can easily be delivered in the liquid form for parenteral drug delivery application. This review highlights the methods to prepare nanohydrogel based on natural and synthetic polymers for diverse applications in drug delivery. It also encompasses the drug loading and drug release mechanism of the nanohydrogel formulation and patents related to the composition and chemical methods for preparation of nanohydrogel formulation with current status in clinical trials.
Ströhle, Andreas; Schmidt, Dietlinde K; Schultz, Florian; Fricke, Nina; Staden, Theresa; Hellweg, Rainer; Priller, Josef; Rapp, Michael A; Rieckmann, Nina
Demographic changes are increasing the pressure to improve therapeutic strategies against cognitive decline in Alzheimer disease (AD) and mild cognitive impairment (MCI). Besides drug treatment, physical activity seems to be a promising intervention target as epidemiological and clinical studies suggest beneficial effects of exercise training on cognition. Using comparable inclusion and exclusion criteria, we analyzed the efficacy of drug therapy (cholinesterase inhibitors, memantine, and Ginkgo biloba) and exercise interventions for improving cognition in AD and MCI populations. We searched The Cochrane Library, EBSCO, OVID, Web of Science, and U.S Food and Drug Administration data from inception through October 30, 2013. Randomized controlled trials in which at least one treatment arm consisted of an exercise or a pharmacological intervention for AD or MCI patients, and which had either a non-exposed control condition or a control condition that received another intervention. Treatment discontinuation rates and Standardized Mean Change score using Raw score standardization (SMCR) of cognitive performance were calculated. Discontinuation rates varied substantially and ranged between 0% and 49% with a median of 18%. Significantly increased discontinuation rates were found for galantamine and rivastigmine as compared to placebo in AD studies. Drug treatments resulted in a small pooled effect on cognition (SMCR: 0.23, 95% CI: 0.20 to 0.25) in AD studies (N = 45, 18,434 patients) and no effect in any of the MCI studies (N = 5, 3,693 patients; SMCR: 0.03, 95% CI: 0.00 to 0.005). Exercise interventions had a moderate to strong pooled effect size (SMCR: 0.83, 95% CI: 0.59 to 1.07) in AD studies (N = 4, 119 patients), and a small effect size (SMCR: 0.20, 95% CI: 0.11 to 0.28) in MCI (N = 6, 443 patients). Drug treatments have a small but significant impact on cognitive functioning in AD and exercise has the potential to improve cognition in AD and MCI. Head
Full Text Available Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS/drug-induced hypersensitivity syndrome (DIHS, or Stevens–Johnson syndrome (SJS/toxic epidermal necrolysis (TEN. Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs. The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity.
Abe, Riichiro; Pan, Ren-You; Wang, Chuang-Wei
Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria) to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), or Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR) molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity. PMID:29651444
Stender, Stefan; Tybjærg-Hansen, Anne
PURPOSE OF REVIEW: 'Genetic proxies' are increasingly being used to predict the effects of drugs. We present an up-to-date overview of the use of human genetics to predict effects and adverse effects of lipid-targeting drugs. RECENT FINDINGS: LDL cholesterol lowering variants in HMG-Coenzyme A re...
Full Text Available Lower urinary tract symptoms (LUTS due to benign prostatic hyperplasia (BPH are common in elder men and a number of drugs alone or combined are clinically used for this disorder. But available studies investigating the comparative effects of different drug therapies are limited. This study was aimed to compare the efficacy of different drug therapies for LUTS/BPH with network meta-analysis.An electronic search of PubMed, Cochrane Library and Embase was performed to identify randomized controlled trials (RCTs comparing different drug therapies for LUTS/BPH within 24 weeks. Comparative effects were calculated using Aggregate Data Drug Information System. Consistency models of network meta-analysis were created and cumulative probability was used to rank different therapies.A total 66 RCTs covering seven different therapies with 29384 participants were included. We found that α-blockers (ABs plus phosphodiesterase 5 inhibitors (PDE5-Is ranked highest in the test of IPSS total score, storage subscore and voiding subscore. The combination therapy of ABs plus 5α-reductase inhibitors was the best for increasing maximum urinary flow rate (Qmax with a mean difference (MD of 1.98 (95% CI, 1.12 to 2.86 as compared to placebo. ABs plus muscarinic receptor antagonists (MRAs ranked secondly on the reduction of IPSS storage subscore, although monotherapies including MRAs showed no effect on this aspect. Additionally, PDE5-Is alone showed great effectiveness for LUTS/BPH except Qmax.Based on our novel findings, combination therapy, especially ABs plus PDE5-Is, is recommended for short-term treatment for LUTS/BPH. There was also evidence that PDE5-Is used alone was efficacious except on Qmax. Additionally, it should be cautious when using MRAs. However, further clinical studies are required for longer duration which considers more treatment outcomes such as disease progression, as well as basic research investigating mechanisms involving PDE5-Is and other
Planès, Sara; Villier, Céline; Mallaret, Michel
While the placebo effect has been studied for a long time, much less is known about its negative counterpart, named the nocebo effect. However, it may be of particular importance because of its impact on the treatment outcomes and public health. We conducted a review on the nocebo effect using PubMed and other databases up to July 2014. The nocebo effect refers by definition to the induction or the worsening of symptoms induced by sham or active therapies. Examples are numerous and concerns both clinical trials and daily practice. The underlying mechanisms are, on one hand, psychological (conditioning and negative expectations) and, on the other hand, neurobiological (role of cholecystokinin, endogenous opioids and dopamine). Nocebo effects can modulate the outcome of a given therapy in a negative way, as do placebo effects in a positive way. The verbal and nonverbal communications of physicians contain numerous unintentional negative suggestions that may trigger a nocebo response. This raises the important issue of how physicians can at the same time obtain informed consent and minimize nocebo-related risks. Every physician has to deal with this apparent contradiction between primum non nocere and to deliver truthful information about risks. Meticulous identification of patients at risk, information techniques such as positive framing, contextualized informed consent, and even noninformation, is valuable.
Jones, Woodrow, Jr.
This study examined the interaction effect of students, drugs, and alienation in a large university, i.e., the linkages of both social and political alienation with drug behavior. The interaction terms which composed these forms of alienation were evaluated as to their comparative ability to produce drug behavior. (Author)
Presents information on psychotropic drugs for individuals who are not specialists in pharmacology. Discusses: alcohol and barbituates; dependence and withdrawal; central nervous system depressors (anaesthetics, narcotic analgesics, sedatives and hypnotic drugs, tranquilizers), central nervous stimulants (amphetamines, cocaine, tobacco, caffeine),…
Fríguls, Bibiana; Joya, Xavier; García-Algar, Oscar; Pallás, C R; Vall, Oriol; Pichini, Simona
Most of the licit and illicit drugs consumed by the breastfeeding woman pass into the milk and can modify the production, volume and composition of the milk, as well as hypothetically have short- and long-term harmful effects on the infant. There is much confusion in the scientific community regarding this issue: should a woman breastfeed her baby while continuing to use prescription drugs and/or drugs of abuse? There are many case reports of clinically significant toxicity in breast-fed infants from some substances used by mothers (such as irritability, vomiting, sedation, respiratory depression, shock), but there are too few data on studies conducted in breastfeeding women and their infants to make a realistic risk assessment. The objective measurement of a drug and/or metabolites in maternal milk is the first step when investigating the amount of drug excreted in milk and subsequently calculating the daily dose administered to the breast-fed infant. The present review reports the analytical methods developed to detect different drugs in the breast milk, listing the principal characteristics and validation parameters, advantages and disadvantages. Furthermore, the mechanisms of drug transfer into breast milk are discussed, the correlation between the concentration of the drug in breast milk and potential adverse outcomes on the infant are described for each drug, and suggested harm minimization strategies and approved breastfeeding recommendations are indicated.
Bahar, Muh Akbar; Setiawan, Didik; Hak, Eelko; Wilffert, Bob
Currently, most guidelines on drug-drug interaction (DDI) neither consider the potential effect of genetic polymorphism in the strength of the interaction nor do they account for the complex interaction caused by the combination of DDI and drug-gene interaction (DGI) where there are multiple biotransformation pathways, which is referred to as drug-drug-gene interaction (DDGI). In this systematic review, we report the impact of pharmacogenetics on DDI and DDGI in which three major drug-metabolizing enzymes - CYP2C9, CYP2C19 and CYP2D6 - are central. We observed that several DDI and DDGI are highly gene-dependent, leading to a different magnitude of interaction. Precision drug therapy should take pharmacogenetics into account when drug interactions in clinical practice are expected.
Max Joseph Herman
Full Text Available Drug is one of the essential elements in healthcare that should be effectively and efficiently managed. Following thedecentralization in 2001 in Indonesia, drug management has changed in district drug management units and also in District General Hospitals. Certainly this condition influences the sustainability of drug access in primary health care such as in Community Health Center and District General Hospital, especially in drug financing policy. A cross sectional descriptive study to obtain information on drug management in public healthcare in district had been carried out between July and December 2006 in 10 District Public Drug Management Units from 10 district health offices and 9 district general hospitals as samples. Data were collected by interviewing heads of Drug Section in District Health Offices and heads of Hospital Pharmacies using structured questionnaires and observing drug storage in District Drug Management Units, Community Health Centers, and Hospital Pharmacies. Results of the study show that drug planning in District Health Offices and General Hospitals did not meet the basic real need in some districts nor District Hospitals. The minimum health service standards had no been achieved yet. Furthermore, drug procurement, storage and recording as well as reporting was not good enough either, such as shown by the existence of expired drugs. Lead time for drug delivery to community health centers in some districts was longer than the average of lead time in the past 3 years.
Rodrigues, Maria Cristina Soares; Oliveira, Cesar de
to identify and summarize studies examining both drug-drug interactions (DDI) and adverse drug reactions (ADR) in older adults polymedicated. an integrative review of studies published from January 2008 to December 2013, according to inclusion and exclusion criteria, in MEDLINE and EMBASE electronic databases were performed. forty-seven full-text studies including 14,624,492 older adults (≥ 60 years) were analyzed: 24 (51.1%) concerning ADR, 14 (29.8%) DDI, and 9 studies (19.1%) investigating both DDI and ADR. We found a variety of methodological designs. The reviewed studies reinforced that polypharmacy is a multifactorial process, and predictors and inappropriate prescribing are associated with negative health outcomes, as increasing the frequency and types of ADRs and DDIs involving different drug classes, moreover, some studies show the most successful interventions to optimize prescribing. DDI and ADR among older adults continue to be a significant issue in the worldwide. The findings from the studies included in this integrative review, added to the previous reviews, can contribute to the improvement of advanced practices in geriatric nursing, to promote the safety of older patients in polypharmacy. However, more research is needed to elucidate gaps. identificar e sintetizar estudos que examinam as interações medicamentosas (IM) e reações adversas a medicamentos (RAM) em idosos polimedicados. revisão integrativa de estudos publicados de janeiro de 2008 a dezembro de 2013, de acordo com critérios de inclusão e exclusão, nas bases de dados eletrônicas MEDLINE e EMBASE. foram analisados 47 estudos de texto completo, incluindo 14,624,492 idosos (≥ 60 anos): 24 (51,1%) sobre RAM, 14 (29,8%) sobre IM e 9 estudos (19,1%) que investigaram tanto IM como RAM. Encontramos uma variedade de desenhos metodológicos. Os estudos revisados reforçaram que a polifarmácia é um processo multifatorial, e os preditores e a prescrição inadequada estão associados a
Pathan, Shadab A; Iqbal, Zeenat; Sahani, Jasjeet K; Talegaonkar, Sushma; Khar, Roop K; Ahmad, Farhan J
Peroral administration of drugs, although most preferred by both clinicians and patients has several disadvantages such as hepatic first pass metabolism and enzymatic degradation within the GI tract, that prohibit oral administration of certain classes of drugs especially peptides and proteins. Consequently, other absorptive mucosae are considered as potential sites for administration of these drugs. Among the various transmucosal routes studied the buccal mucosa offers several advantages for controlled drug delivery for extended period of time. The mucosa is well supplied with both vascular and lymphatic drainage and first-pass metabolism in the liver and pre-systemic elimination in the gastrointestinal tract is avoided. The area is well suited for a retentive device and appears to be acceptable to the patient. With the right dosage form, design and formulation, the permeability and the local environment of the mucosa can be controlled and manipulated in order to accommodate drug permeation. Buccal drug delivery is thus a promising area for continued research with the aim of systemic and local delivery of orally inefficient drugs as well as feasible and attractive alternative for non-invasive delivery of potent protein and peptide drug molecules. Extensive review pertaining specifically to the patents relating to buccal drug delivery is currently available. However, many patents e.g. US patents 6, 585,997; US20030059376A1 etc. have been mentioned in few articles. It is the objective of this article to extensively review buccal drug delivery by discussing the recent patents available. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based delivery systems.
Nosten, François; McGready, Rose; d'Alessandro, Umberto; Bonell, Ana; Verhoeff, Francine; Menendez, Clara; Mutabingwa, Thenonest; Brabin, Bernard
In this review we examine the available information on the safety of antimalarials in pregnancy, from both animal and human studies. The antimalarials that can be used in pregnancy include (1) chloroquine, (2) amodiaquine, (3) quinine, (4) azithromycin, (5) sulfadoxine-pyrimethamine, (6) mefloquine,
Schlienger, R G
Adverse drug reactions (ADRs) are still considered one of the main problems of drug therapy. ADRs are associated with considerable morbidity, mortality, decreased compliance and therapeutic success as well as high direct and indirect medical costs. Several considerations have to come into play when managing a potential ADR. It is critical to establish an accurate clinical diagnosis of the adverse event. Combining information about drug exposure together with considering other possible causes of the reaction is crucial to establish a causal relationship between the reaction and the suspected drug. Identification of the underlying pathogenesis of an ADR together with the severity of the reaction will have profound implications on continuation of drug therapy after an ADR. Since spontaneous reports about ADRs are a key stone of a functioning post-marketing surveillance system and therefore play a key role in improving drug safety, health care professionals are highly encouraged to report ADRs to a local or national organization. However, because the majority of ADRs is dose-dependent and therefore preventable, individualization of pharmacotherapy may have a major impact on reducing such events.
Verhoef, Talitha I; Morris, Stephen
Growing resistance to antibacterial agents has increased the need for the development of new drugs to treat bacterial infections. Given increasing pressure on limited health budgets, it is important to study the cost-effectiveness of these drugs, as well as their safety and efficacy, to find out whether or not they provide value for money and should be reimbursed. In this article, we systematically reviewed 38 cost-effectiveness analyses of new antibacterial agents. Most studies showed the new antibacterial drugs were cost-effective compared to older generation drugs. Drug pricing is a complicated process, involving different stakeholders, and has a large influence on cost-effectiveness. Value-based pricing is a method to determine the price of a drug at which it can be cost-effective. It is currently unclear what the influence of value-based pricing will be on the prices of new antibacterial agents, but an important factor will be the definition of 'value', which as well as the impact of the drug on patient health might also include other factors such as wider social impact and the health impact of disease. © 2015 The Authors. Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.
de Witte, Wilhelmus E A; Wong, Yin Cheong; Nederpelt, Indira; Heitman, Laura H; Danhof, Meindert; van der Graaf, Piet H; Gilissen, Ron A H J; de Lange, Elizabeth C M
Drug-target binding kinetics are major determinants of the time course of drug action for several drugs, as clearly described for the irreversible binders omeprazole and aspirin. This supports the increasing interest to incorporate newly developed high-throughput assays for drug-target binding kinetics in drug discovery. A meaningful application of in vitro drug-target binding kinetics in drug discovery requires insight into the relation between in vivo drug effect and in vitro measured drug-target binding kinetics. In this review, the authors discuss both the relation between in vitro and in vivo measured binding kinetics and the relation between in vivo binding kinetics, target occupancy and effect profiles. More scientific evidence is required for the rational selection and development of drug-candidates on the basis of in vitro estimates of drug-target binding kinetics. To elucidate the value of in vitro binding kinetics measurements, it is necessary to obtain information on system-specific properties which influence the kinetics of target occupancy and drug effect. Mathematical integration of this information enables the identification of drug-specific properties which lead to optimal target occupancy and drug effect in patients.
Objective To review existing regulations and policies utilised by countries to enable patient access to orphan drugs. Methods A review of the literature (1998 to 2014) was performed to identify relevant, peer-reviewed articles. Using content analysis, we synthesised regulations and policies for access to orphan drugs by type and by country. Results Fifty seven articles and 35 countries were included in this review. Six broad categories of regulation and policy instruments were identified: national orphan drug policies, orphan drug designation, marketing authorization, incentives, marketing exclusivity, and pricing and reimbursement. The availability of orphan drugs depends on individual country’s legislation and regulations including national orphan drug policies, orphan drug designation, marketing authorization, marketing exclusivity and incentives such as tax credits to ensure research, development and marketing. The majority of countries (27/35) had in place orphan drug legislation. Access to orphan drugs depends on individual country’s pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access. Conclusions Overall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented. Importantly, China and India, two of the largest countries by population size, both lack national legislation for orphan medicines and rare diseases, which could have substantial negative impacts on their patient populations with rare diseases. PMID:26451948
Gammie, Todd; Lu, Christine Y; Babar, Zaheer Ud-Din
To review existing regulations and policies utilised by countries to enable patient access to orphan drugs. A review of the literature (1998 to 2014) was performed to identify relevant, peer-reviewed articles. Using content analysis, we synthesised regulations and policies for access to orphan drugs by type and by country. Fifty seven articles and 35 countries were included in this review. Six broad categories of regulation and policy instruments were identified: national orphan drug policies, orphan drug designation, marketing authorization, incentives, marketing exclusivity, and pricing and reimbursement. The availability of orphan drugs depends on individual country's legislation and regulations including national orphan drug policies, orphan drug designation, marketing authorization, marketing exclusivity and incentives such as tax credits to ensure research, development and marketing. The majority of countries (27/35) had in place orphan drug legislation. Access to orphan drugs depends on individual country's pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access. Overall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented. Importantly, China and India, two of the largest countries by population size, both lack national legislation for orphan medicines and rare diseases, which could have substantial negative impacts on their patient populations with rare diseases.
Full Text Available To review existing regulations and policies utilised by countries to enable patient access to orphan drugs.A review of the literature (1998 to 2014 was performed to identify relevant, peer-reviewed articles. Using content analysis, we synthesised regulations and policies for access to orphan drugs by type and by country.Fifty seven articles and 35 countries were included in this review. Six broad categories of regulation and policy instruments were identified: national orphan drug policies, orphan drug designation, marketing authorization, incentives, marketing exclusivity, and pricing and reimbursement. The availability of orphan drugs depends on individual country's legislation and regulations including national orphan drug policies, orphan drug designation, marketing authorization, marketing exclusivity and incentives such as tax credits to ensure research, development and marketing. The majority of countries (27/35 had in place orphan drug legislation. Access to orphan drugs depends on individual country's pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access.Overall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented. Importantly, China and India, two of the largest countries by population size, both lack national legislation for orphan medicines and rare diseases, which could have substantial negative impacts on their patient populations with rare diseases.
Hussain, Fahmida; Frare, Robert W; Py Berrios, Karen L
Properly identifying patients with a history of drug abuse is the first step in providing effective dental care. Dental professionals need to be fully aware of the challenges associated with treating this population. In the current study, the authors analyzed the physical and oral manifestations of illicit drug abuse to aid in the identification of patients who abuse drugs and the pain management strategies needed to treat them. The authors also present a clinical case of a patient with unique skin lesions and discuss the typical clinical findings of drug abuse based on a literature review.
Subcutaneous drug infusion using a portable syringe driver has had a significant impact on patient comfort in palliative care. It permits the continuous delivery of a range of drug therapies, so bypassing problems of dysphagia, weakness and the inability of many patients in the terminal phase to take oral medication. The devices are not problem-free, however. Mechanical problems, reactions at the infusion site and difficulties with the mixing of drugs in the syringe are all widely recognized. This article reviews some general issues with the operation of portable syringe drivers, and discusses a range of potential problems and their solutions.
Musselman, Megan E; Hampton, Jeremy P
Synthetic, or "designer" drugs, are created by manipulating the chemical structures of other psychoactive drugs so that the resulting product is structurally similar but not identical to illegal psychoactive drugs. Originally developed in the 1960s as a way to evade existing drug laws, the use of designer drugs has increased dramatically over the past few years. These drugs are deceptively packaged as "research chemicals," "incense," "bath salts," or "plant food," among other names, with labels that may contain warnings such as "not for human consumption" or "not for sale to minors." The clinical effects of most new designer drugs can be described as either hallucinogenic, stimulant, or opioid-like. They may also have a combination of these effects due to designer side-chain substitutions. The easy accessibility and rapid emergence of new designer drugs have created challenges for health care providers when treating patients presenting with acute toxicity from these substances, many of which can produce significant and/or life-threatening adverse effects. Moreover, the health care provider has no way to verify the contents and/or potency of the agent ingested because it can vary between packages and distributors. Therefore, a thorough knowledge of the available designer drugs, common signs and symptoms of toxicity associated with these agents, and potential effective treatment modalities are essential to appropriately manage these patients. © 2014 Pharmacotherapy Publications, Inc.
Full Text Available Magnetic microspheres hold great promise for reaching the goal of controlled and site specific drug delivery. Magnetic microspheres as an alternative to traditional radiation methods which uses highly penetrating radiations that is absorbed throughout the body. Its use is limited by toxicity and side effects. Now days, several targeted treatment systems including magnetic field, electric field, ultrasound, temperature, UV light and mechanical force are being used in many disease treatments (e.g. cancer, nerve damage, heart and artery, anti-diabetic, eye and other medical treatments. Among them, the magnetic targeted drug delivery system is one of the most attractive and promising strategy for delivering the drug to the specified site. Magnetically controlled drug targeting is one of the various possible ways of drug targeting. This technology is based on binding establish anticancer drug with ferrofluid that concentrate the drug in the area of interest (tumor site by means of magnetic fields. There has been keen interest in the development of a magnetically target drug delivery system. These drug delivery systems aim to deliver the drug at a rate directed by the needs of the body during the period of treatment, and target the activity entity to the site of action. Magnetic microspheres were developed to overcome two major problems encountered in drug targeting namely: RES clearance and target site specificity.
Midford, Richard; Munro, Geoffrey; McBride, Nyanda; Snow, Pamela; Ladzinski, Ursula
This study identifies the conceptual underpinnings of effective school-based drug education practice in light of contemporary research evidence and the practical experience of a broad range of drug education stakeholders. The research involved a review of the literature, a national survey of 210 Australian teachers and others involved in drug education, and structured interviews with 22 key Australian drug education policy stakeholders. The findings from this research have been distilled and presented as a list of 16 principles that underpin effective drug education. In broad terms, drug education should be evidence-based, developmentally appropriate, sequential, and contextual. Programs should be initiated before drug use commences. Strategies should be linked to goals and should incorporate harm minimization. Teaching should be interactive and use peer leaders. The role of the classroom teacher is central. Certain program content is important, as is social and resistance skills training. Community values, the social context of use, and the nature of drug harm have to be addressed. Coverage needs to be adequate and supported by follow-up. It is envisaged that these principles will provide all those involved in the drug education field with a set of up-to-date, research-based guidelines against which to reference decisions on program design, selection, implementation, and evaluation.
Bernardo-Filho, Mario; Santos-Filho, Sebastiao David; Moura, Egberto Gaspar de; Maiworm, Adalgisa Ieda; Bernardo, Luciana Camargo; Brito, Lavinia de Carvalho; Orlando, Margarida Maria de Camoes; Penas, Maria Exposito; Cardoso, Valbert Nascimento
Clinical images are worthwhile in Health Sciences and their analysis and correct interpretation aid the professionals,such as physicians, physiotherapists and occupational therapists, to make decisions and take subsequent therapeutic and/or rehabilitation measures. Other factors, besides the state of the disease, may interfere and affect the bioavailability of the radiopharmaceuticals (radiobiocomplexes) and the quality of the SPECT and PET images. Furthermore, the labeling of some of these radiobiocomplexes, such as plasma proteins, white blood cells and red blood cells, with 99m T, can also be modified. These factors include drugs (synthetic and natural) and dietary conditions, as well as some medical procedures (invasive or non-invasive), such as radiation therapy, surgical procedures, prostheses, cardioversion, intubation, chemo perfusion, external massage, immunotherapy, blood transfusion and hemodialysis. In conclusion, the knowledge about these factors capable of interfering with the bioavailability of the radiobiocomplexes is worthwhile for secure diagnosis. Moreover, the development of biological models to study these phenomena is highly relevant and desirable.(author)
Rodriguez, Daniel M; Teesson, Maree; Newton, Nicola C
Serious educational games (SEG) have been shown to be effective in educating young people about a range of topics, including languages and maths. This paper identifies the use of computerised SEGs in education about alcohol and other drugs and reviews their impact on the prevention of alcohol and drug use. The Cochrane Library, EMBASE, MEDLINE, ERIC, Scopus, psychINFO, pubMED and DRUG databases were searched in February 2013. Additional publications were obtained from the reference lists of the relevant papers. Studies were included if they described an evaluation of a computerised SEG that targeted alcohol and/or other drugs and had been trialled with adolescents. Eight SEGs were identified targeting tobacco, alcohol, cannabis, methamphetamine, ecstasy, inhalants, cocaine and opioids. Six reported positive outcomes in terms of increased content knowledge and two reported increased negative attitudes towards the targeted drugs. Only one reported a decrease in the frequency of drug use. This is the first review of the efficacy of computerised SEGs for alcohol and other drugs for adolescents. Results suggest that SEGs can increase content knowledge of alcohol and other drugs. Evidence concerning impacts on negative attitudes and alcohol and drug use is limited, with few studies examining these outcomes. © 2013 Australasian Professional Society on Alcohol and other Drugs.
Crista Laslo; Beatrice G. Ioan; Ovidiu G. Bratu; Bogdan Socea; Camelia Diaconu
Illicit drugs use is a real public health issue, especially among young people. The totality of the drugs harmful effects on the body is difficult to quantify, especially because of poor epidemiological data and ethical concerns about the inclusion of consumers in clinical trials. However, health professionals need to be alert to identify, report and fight drug-related pathology. This article aims to draw attention to the lung pathology induced by the consumption of some of the most commonly ...
The majority of psychotropic drugs entail sexual side effects. The sexual side effects may reduce quality of life and may give rise to non-compliance. For example, 30-60 per cent of patients treated with antidepressants are known to develop a sexual dysfunction. However, some psychotropic drugs...... with no or very few sexual side effects have begun to emerge. The treatment of sexual side effects induced by psychotropic drugs may consist of: modified sexual habits, reduction in dosage, switching to another medication, possibly in combination with different psychotropic agents, other varieties...
Full Text Available Clinical images are worthwhile in Health Sciences and their analysis and correct interpretation aid the professionals,such as physicians, physiotherapists and occupational therapists, to make decisions and take subsequent therapeutic and/or rehabilitation measures. Other factors, besides the state of the disease, may interfere and affect the bioavailability of the radiopharmaceuticals (radiobiocomplexes and the quality of the SPECT and PET images. Furthermore, the labeling of some of these radiobiocomplexes, such as plasma proteins, white blood cells and red blood cells, with 99mT, can also be modified. These factors include drugs (synthetic and natural and dietary conditions, as well as some medical procedures (invasive or non-invasive, such as radiation therapy, surgical procedures, prostheses, cardioversion, intubation, chemoperfusion, external massage, immunotherapy, blood transfusion and hemodialysis. In conclusion, the knowledge about these factors capable of interfering with the bioavailability of the radiobiocomplexes is worthwhile for secure diagnosis. Moreover, the development of biological models to study these phenomena is highly relevant and desirable.Imagens clínicas são valiosas em Ciências da Saúde e a análise e a interpretação correta das mesmas auxiliam os profissionais, como médico, fisioterapeuta, terapeuta ocupacional, na tomada de decisões e subseqüentes ações terapêuticas e/ou de reabilitação. Além das doenças outros fatores podem interferir e afetar a biodisponibilidade dos radiofármacos (radiobiocomplexos e a qualidade das imagens (SPECT e PET. Além disso, a marcação de alguns desses radiobiocomplexos com Tc-99m, como proteínas plasmáticas, leucócitos e hemácias, também pode ser modificada. Entre esses fatores, estão drogas (sintéticas e naturais e condições alimentares, assim como alguns procedimentos médicos (invasivos e não invasivos, como a radioterapia, processos cirúrgicos, pr
Besag, Frank; Ettinger, Alan B.; Mula, Marco; Gobbi, Gabriella; Comai, Stefano; Aldenkamp, Albert P.; Steinhoff, Bernhard J.
Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, and we present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases. PMID:27255267
Cardoso, G.P.; Faria, A.C.S. de; Carvalho, M.C. de; Guimaraes, M.M.; Cordeiro, J.G.H.; Santa Casa do Rio de Janeiro
The effects of drugs in the results of thyroid function tests, which could lead to misinterpretation of the real clinical state of the patients, are reviewed. The aspects of the metabolism of the thyreoidean hormones which could be related to these alterations are presented. (Author) [pt
and steam aided granulation. In these techniques carrier plays an important role in improving solubility and dissolution rate. Polymers, superdisintegrants, surfactants are extensively studied in recent years for dissolution enhancement in drugs. This part of this review discusses technological overview and effect of polymers,
Full Text Available Illicit drugs use is a real public health issue, especially among young people. The totality of the drugs harmful effects on the body is difficult to quantify, especially because of poor epidemiological data and ethical concerns about the inclusion of consumers in clinical trials. However, health professionals need to be alert to identify, report and fight drug-related pathology. This article aims to draw attention to the lung pathology induced by the consumption of some of the most commonly used illicit drugs: cocaine, heroin and cannabis.
Among the various routes of drug delivery, the vaginal route offers many advantages due to its large permeation area, rich vascularization, avoidance of first pass metabolism and relatively low enzymatic activity. Several studies have shown that the vaginal cavity is an effective route for drug administration intended mainly ...
J Gordon Millichap
Full Text Available Clinical trial and postmarketing surveillance data for drugs used in treatment of attention deficit hyperactivity disorder were analyzed to determine the frequency of hallucinations and other psychotic side effects, in a study at the US Food and Drug Administration, and Department of Health and Human Services, Maryland.
Peltzer, Karl; Ramlagan, Shandir; Johnson, Bruce D; Phaswana-Mafuya, Nancy
This review synthesizes available epidemiological data on current drug use and substance user treatment admissions in South Africa since 1994, and how changes in the political, economic, and social structures within South Africa, both before and after Apartheid, has made the country more vulnerable to drug use. Based on national surveys, current use of cannabis ranged among adolescents from 2% to 9% and among adults it was 2%, cocaine/crack (0.3%), mandrax/sedatives (0.3%), club drugs/amphetamine-type stimulants (0.2%), opiates (0.1%), and hallucinogens (0.1%). The use of primary illicit substance at admission to South African drug user treatment centers was cannabis 16.9%, methamphetamine (tik) 12.8%, crack/cocaine 9.6%, cannabis and mandrax 3.4%, heroin/opiates 9.2%, and prescription and OTC drugs 2.6%. An increase in substance user treatment admissions has increased. While the prevalence of illicit drug use in South Africa is relatively low compared to the United States and Australia, prevention and intervention policies need to be designed to reduce these levels by targeting the more risky subpopulations identified from this review.
Sun, Wei-Lun; Quizon, Pamela M; Zhu, Jun
Addiction to psychostimulants has been considered as a chronic psychiatric disorder characterized by craving and compulsive drug seeking and use. Over the past two decades, accumulating evidence has demonstrated that repeated drug exposure causes long-lasting neurochemical and cellular changes that result in enduring neuroadaptation in brain circuitry and underlie compulsive drug consumption and relapse. Through intercellular signaling cascades, drugs of abuse induce remodeling in the rewarding circuitry that contributes to the neuroplasticity of learning and memory associated with addiction. Here, we review the role of the extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase, and its related intracellular signaling pathways in drug-induced neuroadaptive changes that are associated with drug-mediated psychomotor activity, rewarding properties and relapse of drug seeking behaviors. We also discuss the neurobiological and behavioral effects of pharmacological and genetic interferences with ERK-associated molecular cascades in response to abused substances. Understanding the dynamic modulation of ERK signaling in response to drugs may provide novel molecular targets for therapeutic strategies to drug addiction. Copyright © 2016. Published by Elsevier Inc.
Kroon, Féline P. B.; van der Burg, Lennart R. A.; Ramiro, Sofia; Landewé, Robert B. M.; Buchbinder, Rachelle; Falzon, Louise; van der Heijde, Désirée
To determine the benefits and harms of nonsteroidal antiinflammatory drugs (NSAID) in axial spondyloarthritis (axSpA). Systematic review using Cochrane Collaboration methodology. randomized controlled trials (RCT) and quasi-RCT (to June 2014), investigating NSAID versus any control for axSpA, and
Rodrigues, Maria Cristina Soares; de Oliveira, Cesar
ABSTRACT Objective: to identify and summarize studies examining both drug-drug interactions (DDI) and adverse drug reactions (ADR) in older adults polymedicated. Methods: an integrative review of studies published from January 2008 to December 2013, according to inclusion and exclusion criteria, in MEDLINE and EMBASE electronic databases were performed. Results: forty-seven full-text studies including 14,624,492 older adults (≥ 60 years) were analyzed: 24 (51.1%) concerning ADR, 14 (29.8%) DDI, and 9 studies (19.1%) investigating both DDI and ADR. We found a variety of methodological designs. The reviewed studies reinforced that polypharmacy is a multifactorial process, and predictors and inappropriate prescribing are associated with negative health outcomes, as increasing the frequency and types of ADRs and DDIs involving different drug classes, moreover, some studies show the most successful interventions to optimize prescribing. Conclusions: DDI and ADR among older adults continue to be a significant issue in the worldwide. The findings from the studies included in this integrative review, added to the previous reviews, can contribute to the improvement of advanced practices in geriatric nursing, to promote the safety of older patients in polypharmacy. However, more research is needed to elucidate gaps. PMID:27598380
Aghabegi Moghanjoughi, Arezou; Khoshnevis, Dorna; Zarrabi, Ali
Design and synthesis of efficient drug delivery systems are of critical importance in health care management. Innovations in materials chemistry especially in polymer field allows introduction of advanced drug delivery systems since polymers could provide controlled release of drugs in predetermined doses over long periods, cyclic and tunable dosages. To this end, researchers have taken advantages of smart polymers since they can undergo large reversible, chemical, or physical fluctuations as responses to small changes in environmental conditions, for instance, in pH, temperature, light, and phase transition. The present review aims to highlight various kinds of smart polymers, which are used in controlled drug delivery systems as well as mechanisms of action and their applications.
Wadhwa, Sheetu; Paliwal, Rishi; Paliwal, Shivani Rai; Vyas, S P
Controlled drug delivery to eye is one of the most challenging fields of pharmaceutical research. Low drug-contact time and poor ocular bioavailability due to drainage of solution, tear turnover and its dilution or lacrimation are the problems associated with conventional systems. In addition, anatomical barriers and physiological conditions of eye are also important parameters which control designing of drug delivery systems. Nanosized carriers like micro/nano-suspensions, liposome, niosome, dendrimer, nanoparticles, ocular inserts, implants, hydrogels and prodrug approaches have been developed for this purpose. These novel systems offer manifold advantages over conventional systems as they increase the efficiency of drug delivery by improving the release profile and also reduce drug toxicity. Conventional delivery systems get diluted with tear, washed away through the lacrimal gland and usually require administering at regular time intervals whereas nanocarriers release drug at constant rate for a prolonged period of time and thus enhance its absorption and site specific delivery. This review presents an overview of the various aspects of the ocular drug delivery, with special emphasis on nanocarrier based strategies, including structure of eye, its barriers, delivery routes and the challenges/limitations associated with development of novel nanocarriers. The recent progresses in therapy of ocular disease like gene therapy have also been included so that future options should also be considered from the delivery point of view. Recent progress in the delivery of proteins and peptides via ocular route has also been incorporated for reader benefit.
Full Text Available The Drug Supply Chain Security Act (DSCSA signed into law in November 27, 2013 by president Obama creates a uniform national standard for tracing drug products through the supply chain. The goal of DQSA is to enhance FDA’s ability to help protect consumers by detecting and removing potential dangerous products from the pharmaceutics distribution supply chain. A new electronic, interoperable system will identify and trace only prescription drugs in the finished form for human use while distributed in the United States. The purpose of this review was to shed light on a complex and complicated process that it will require cooperation between FDA and drug manufactures, wholesale drug distributors, repackagers and dispensers. The implementation of the DSCSA is based on several law requirements and FDA has developed a schedule with time frames for each of them to be executed over a 10-year period. From this review, FDA recommendations are provided through the FDA Guidance on Identifying Suspect Product document to help trading partners and provide information about the risk of suspect drugs entering the supply chain. Moreover, FDA organized on April 5-6, 2016 in Silver Spring, MD a public workshop to gather valuable feedback from stakeholders who shared their input about the implementation of the new electronic system and its requirements. By the end of 2023, a unified system will provide easier data exchange and less errors, and will increase the safety and security of the pharmaceutical distribution supply chain. Type: Student Project
Zhang, Jiefeng [Division of Environmental and Water Resources, School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Chang, Victor W.C., E-mail: email@example.com [Division of Environmental and Water Resources, School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Giannis, Apostolos [Residues and Resource Reclamation Centre (R3C), Nanyang Environment and Water Research Institute, Nanyang Technological University, 1 Cleantech Loop, CleanTech One, Singapore 637141 (Singapore); Wang, Jing-Yuan [Division of Environmental and Water Resources, School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Residues and Resource Reclamation Centre (R3C), Nanyang Environment and Water Research Institute, Nanyang Technological University, 1 Cleantech Loop, CleanTech One, Singapore 637141 (Singapore)
Cytostatic drugs have been widely used for chemotherapy for decades. However, many of them have been categorized as carcinogenic, mutagenic and teratogenic compounds, triggering widespread concerns about their occupational exposure and ecotoxicological risks to the environment. This review focuses on trace presence, fate and ecotoxicity of various cytostatic compounds in the environment, with an emphasis on the major sources contributing to their environmental concentrations. Past records have documented findings mainly on hospital effluents though little effort has been directed to household discharges. There is also a lack in physico-chemical data for forecasting the chemodynamics of cytostatics in natural waters along with its human metabolites and environmental transformation products. In this light, obtaining comprehensive ecotoxicity data is becoming pressingly crucial to determine their actual impacts on the ecosystem. Literature review also reveals urinary excretion as a major contributor to various cytostatic residues appeared in the water cycle. As such, engaging urine source-separation as a part of control strategy holds a rosy prospect of addressing the “emerging” contamination issue. State-of-the-art treatment technologies should be incorporated to further remove cytostatic residues from the source-separating urine stream. The benefits, limitations and trends of development in this domain are covered for membrane bio-reactor, reverse/forward osmosis and advanced oxidation processes. Despite the respective seeming advantages of source separation and treatment technology, a combined strategy may cost-effectively prevent the cytostatic residues from seeping into the environment. However, the combination calls for further evaluation on the associated technological, social-economic and administrative issues at hand. Highlights: ► We review the environmental occurrence, fate and ecotoxicity of cytostatic drugs. ► Four major sources contributing to
In the current economic environment, health care systems are constantly struggling to contain rapidly rising costs. Drug costs are targeted by a wide variety of measures. Many jurisdictions have implemented reference drug programs (RDPs) or similar therapeutic substitution programs. This paper summarizes the mechanism and rationale of RDPs and presents evidence of their economic effectiveness and clinical safety. RDPs for pharmaceutical reimbursement are based on the assumption that drugs within specified medication groups are therapeutically equivalent and clinically interchangeable and that a common reimbursement level can thus be established. If the evidence documents that a higher price for a given drug does not buy greater effectiveness or reduced toxicity, then under RDP such extra costs are not covered. RDPs or therapeutic substitutions based on therapeutic equivalence are seen as logical extensions of generic substitution that is based on bioequivalence of drugs. If the goal is to achieve full drug coverage for as many patients as possible in the most efficient manner, then RDPs in combination with prior authorization programs are safer and more effective than simplistic fiscal drug policies, including fixed co-payments, co-insurances, or deductibles. RDPs will reduce spending in the less innovative but largest market, while fully covering all patients. Prior authorization will ensure that patients with a specified indication will benefit from the most innovative therapies with full coverage. In practice, however, not all patients and drugs will fit exactly into one of the two categories. Therefore, a process of medically indicated exemptions that will consider full coverage should accompany an RDP. In the current economic environment, health care systems are constantly struggling to contain rapidly rising costs. Drug costs are targeted by a wide variety of measures. Many jurisdictions have implemented reference drug programs, and others are considering
Full Text Available Abstract Background Blood pressure lowering drugs are usually evaluated in short term trials determining the absolute blood pressure reduction during trough and the duration of the antihypertensive effect after single or multiple dosing. A lack of persistence with treatment has however been shown to be linked to a worse cardiovascular prognosis. This review explores the blood pressure reduction and persistence with treatment of antihypertensive drugs and the cost consequences of poor persistence with pharmaceutical interventions in arterial hypertension. Methods We have searched the literature for data on blood pressure lowering effects of different antihypertensive drug classes and agents, on persistence with treatment, and on related costs. Persistence was measured as patients' medication possession rate. Results are presented in the form of a systematic review. Results Angiotensin II receptor blocker (ARBs have a competitive blood pressure lowering efficacy compared with ACE-inhibitors (ACEi and calcium channel blockers (CCBs, beta-blockers (BBs and diuretics. 8 studies describing the persistence with treatment were identified. Patients were more persistent on ARBs than on ACEi and CCBs, BBs and diuretics. Thus the product of blood pressure lowering and persistence was higher on ARBs than on any other drug class. Although the price per tablet of more recently developed drugs (ACEi, ARBs is higher than that of older ones (diuretics and BBs, the newer drugs result in a more favourable cost to effect ratio when direct drug costs and indirect costs are also considered. Conclusion To evaluate drugs for the treatment of hypertension several key variables including the blood pressure lowering effect, side effects, compliance/persistence with treatment, as well as drug costs and direct and indirect costs of medical care have to be considered. ARBs, while nominally more expensive when drug costs are considered only, provide substantial cost savings
Radha, G V; Rani, T Sudha; Sarvani, B
Proniosomes are dry formulation of water soluble carrier particles that are coated with surfactant. They are rehydrated to form niosomal dispersion immediately before use on agitation in hot aqueous media within minutes. Proniosomes are physically stable during the storage and transport. Drug encapsulated in the vesicular structure of proniosomes prolong the existence of drug in the systematic circulation and enhances the penetration into target tissue and reduce toxicity. From a technical point of view, niosomes are promising drug carriers as they possess greater chemical stability and lack of many disadvantages associated with liposomes, such as high- cost and variable purity problems of phospholipids. The present review emphasizes on overall methods of preparation characterization and applicability of proniosomes in targeted drug action.
Full Text Available Azuana Ramli,1,3 Syed Mohamed Aljunid,1,2 Saperi Sulong,2 Faridah Aryani Md Yusof31United Nations University International Institute for Global Health (UNU-IIGH, Kuala Lumpur, Malaysia; 2International Centre for Casemix and Clinical Coding (ITCC, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia; 3Pharmaceutical Services Division, Ministry of Health, Petaling Jaya, MalaysiaPurpose: HMG-CoA reductase inhibitors (statins are extensively used in treating hypercholesterolemia. The statins available in Malaysia include atorvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin, and fluvastatin. Over the years, they have accumulated in the National Drug Formulary; hence, the need for review. Effective selection of the best drugs to remain in the formulary can become complex due to the multiple drug attributes involved, and is made worse by the limited time and resources available. The multiattribute scoring tool (MAST systematizes the evaluation of the drug attributes to facilitate the drug selection process. In this study, a MAST framework was developed to rank the statins based on their utilities or benefits.Methods: Published literature on multicriteria decision analysis (MCDA were studied and five sessions of expert group discussions were conducted to build the MAST framework and to review the evidence. The attributes identified and selected for analysis were efficacy (clinical efficacy, clinical endpoints, safety (drug interactions, serious side effects and documentation, drug applicability (drug strength/formulation, indications, dose frequency, side effects, food–drug interactions, and dose adjustments, and cost. The average weights assigned by the members for efficacy, safety, drug applicability and cost were 32.6%, 26.2%, 24.1%, and 17.1%, respectively. The utility values of the attributes were scored based on the published evidence or/and agreements during the group discussions. The attribute scores were added up
Barkla, Xanthe M; McArdle, Paul A; Newbury-Birch, Dorothy
Among young people up to 18 years of age, approximately 5% have attention deficit hyperactivity disorder (ADHD), many of whom have symptoms persisting into adulthood. ADHD is associated with increased risk of co-morbid psychiatric disorders, including substance misuse. Many will be prescribed medication, namely methylphenidate, atomoxetine, dexamphetamine and lisdexamfetamine. If so, it is important to know if interactions exist and if they are potentially toxic. Three databases (Medline, EMBASE and PsychINFO) from a 22 year period (1992 - June 2014) were searched systematically. Key search terms included alcohol, substance related disorders, methylphenidate, atomoxetine, dexamphetamine, lisdexamfetamine, and death, which identified 493 citations (344 after removal of duplicates). The eligibility of each study was assessed jointly by two investigators, leaving 20 relevant articles. We identified only a minimal increase in side-effects when ADHD medication (therapeutic doses) was taken with alcohol. None of the reviewed studies showed severe sequelae among those who had overdosed on ADHD medication and other coingestants, including alcohol. The numbers across all the papers studied remain too low to exclude uncommon effects. Also, studies of combined effects with novel psychoactive substances have not yet appeared in the literature. Nevertheless, no serious sequelae were identified from combining ADHD medication with alcohol/illicit substances from the pre-novel psychoactive substance era.
Claudius, C; Garvey, L H; Viby-Mogensen, J
Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor...... in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect...... of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking...
Hampel, Silke; Spizzirri, Umile Gianfranco; Parisi, Ortensia Ilaria; Picci, Nevio; Iemma, Francesca
The use of biologics, polymers, silicon materials, carbon materials, and metals has been proposed for the preparation of innovative drug delivery devices. One of the most promising materials in this field are the carbon-nanotubes composites and hybrid materials coupling the advantages of polymers (biocompatibility and biodegradability) with those of carbon nanotubes (cellular uptake, stability, electromagnatic, and magnetic behavior). The applicability of polymer-carbon nanotubes composites in drug delivery, with particular attention to the controlled release by composites hydrogel, is being extensively investigated in the present review. PMID:24587993
Systematic review of the cost effectiveness of prophylactic treatments in the prevention of gastropathy in patients with rheumatoid arthritis or osteoarthritis taking non-steroidal anti-inflammatory drugs.
van Dieten, H E; Korthals-de Bos, I B; van Tulder, M W; Lems, W F; Dijkmans, B A; Boers, M
A systematic review on the cost effectiveness of prophylactic treatments of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy in patients with osteoarthritis or rheumatoid arthritis was conducted. Two reviewers conducted the literature search and the review. Both full and partial economic evaluations published in English, Dutch, or German were included. The criteria list published in the textbook of Drummond was used to determine the quality of the economic evaluations. The methodological quality of three randomised controlled trials (RCTs) in which the economic evaluations obtained probability estimates of NSAID induced gastropathy and adverse events was assessed by a list of internal validity criteria. The conclusions were based on a rating system consisting of four levels of evidence. Ten economic evaluations were included; three were based on RCTs. All evaluations studied misoprostol as prophylactic treatment: in one evaluation misoprostol was studied as a fixed component in a combination with diclofenac (Arthrotec). All economic evaluations comprised analytical studies containing a decision tree. The three trials were of high methodological quality. Nine economic evaluations were considered high quality and one economic evaluation was considered of low methodological quality. There is strong evidence (level "A") that the use of misoprostol for the prevention of NSAID induced gastropathy is cost effective, and limited evidence (level "C") that the use of Arthrotec is cost effective. Although the levels of evidence used in this review are arbitrary, it is believed that a qualitative analysis is useful: quantitative analyses in this field are hampered by the heterogeneity of economic evaluations. Existing criteria to evaluate the methodological quality of economic evaluations may need refinement for use in systematic reviews.
Systematic review of the cost effectiveness of prophylactic treatments in the prevention of gastropathy in patients with rheumatoid arthritis or osteoarthritis taking non-steroidal anti-inflammatory drugs
van Dieten, H. E M; Bos, I.; van Tulder, M. W; Lems, W.; Dijkmans, B.; Boers, M.
A systematic review on the cost effectiveness of prophylactic treatments of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy in patients with osteoarthritis or rheumatoid arthritis was conducted. Two reviewers conducted the literature search and the review. Both full and partial economic evaluations published in English, Dutch, or German were included. The criteria list published in the textbook of Drummond was used to determine the quality of the economic evaluations. The methodological quality of three randomised controlled trials (RCTs) in which the economic evaluations obtained probability estimates of NSAID induced gastropathy and adverse events was assessed by a list of internal validity criteria. The conclusions were based on a rating system consisting of four levels of evidence. Ten economic evaluations were included; three were based on RCTs. All evaluations studied misoprostol as prophylactic treatment: in one evaluation misoprostol was studied as a fixed component in a combination with diclofenac (Arthrotec). All economic evaluations comprised analytical studies containing a decision tree. The three trials were of high methodological quality. Nine economic evaluations were considered high quality and one economic evaluation was considered of low methodological quality. There is strong evidence (level "A") that the use of misoprostol for the prevention of NSAID induced gastropathy is cost effective, and limited evidence (level "C") that the use of Arthrotec is cost effective. Although the levels of evidence used in this review are arbitrary, it is believed that a qualitative analysis is useful: quantitative analyses in this field are hampered by the heterogeneity of economic evaluations. Existing criteria to evaluate the methodological quality of economic evaluations may need refinement for use in systematic reviews. PMID:11005773
Sanz, Roser; Calpena, Ana C; Mallandrich, Mireia; Clares, Beatriz
Topical administration is an appealing method for drug delivery due to its non-invasiveness, self-controlled application, avoidance of first-pass metabolism in the liver and reduction of systemic side effects compared to other conventional routes such as oral and parenteral. However, topical administration must overcome the permeable barriers that skin and mucosa represent for the drug to achieve its desired therapeutic effect. Penetration of drugs through human skin is mainly impaired by the stratum corneum- the uppermost keratinized skin layer. In contrast, the stratified squamous epithelium (a nonkeratinized tissue) represents the major physical barrier for transbuccal drug administration in humans. Different technologies have been studied to enhance the bioavailability or local effects of drugs administered through skin and buccal mucosa. Those technologies involve the use of physical or chemical enhancers and new dosage forms such as vesicles, cyclodextrins, nanoparticles and other complex systems. Combinations of these technologies may further increase drug delivery in some cases. As analgesia is one of the main therapeutic effects sought through topical administration, this paper focuses on the review of drug delivery systems to improve the topical and transdermal/transbuccal drug delivery of substances with known analgesic action. A discussion of their possibilities and limitations is also included.
Kuhn, Michael; Campillos, Monica; Letunic, Ivica
The molecular understanding of phenotypes caused by drugs in humans is essential for elucidating mechanisms of action and for developing personalized medicines. Side effects of drugs (also known as adverse drug reactions) are an important source of human phenotypic information, but so far research...
Full Text Available Drug nanocrystals are a versatile option for drug delivery purposes, and while the number of poorly soluble drug materials is all the time increasing, more research in this area is performed. Drug nanocrystals have a simple structure—a solid drug core is surrounded by a layer of stabilizing agent. However, despite the considerably simple structure, the selection of an appropriate stabilizer for a certain drug can be challenging. Mostly, the stabilizer selection is based purely on the requirement of physical stability, e.g., maintaining the nanosized particle size as long as possible after the formation of drug nanocrystals. However, it is also worth taking into account that stabilizer can affect the bioavailability in the final formulation via interactions with cells and cell layers. In addition, formation of nanocrystals is only one process step, and for the final formulation, more excipients are often added to the composition. The role of the stabilizers in the final formulation can be more than only stabilizing the nanocrystal particle size. A good example is the stabilizer’s role as cryoprotectant during freeze drying. In this review, the stabilizing effect, role of stabilizers in final nanocrystalline formulations, challenges in reaching in vitro–in vivo correlation with nanocrystalline products, and stabilizers’ effect on higher bioavailability are discussed.
Melo, Jason S; Mittal, Maria Luisa; Horyniak, Danielle; Strathdee, Steffanie A; Werb, Dan
Dual epidemics of injection drug use and blood-borne disease, characterized as "syndemics," are present in a range of settings. Behaviors that drive such syndemics are particularly prevalent among mobile drug-using populations, for whom cross-border migration may pose additional risks. This narrative review aims to characterize the risk factors for injection drug use initiation associated with migration, employing a risk environment framework and focusing on the San Diego-Tijuana border region as the most dynamic example of these phenomena. Based on previous literature, we divide migration streams into three classes: intra-urban, internal, and international. We synthesized existing literature on migration and drug use to characterize how mobility and migration drive the initiation of injection drug use, as well as the transmission of hepatitis and HIV, and to delineate how these might be addressed through public health intervention. Population mixing between migrants and receiving communities and the consequent transmission of social norms about injection drug use create risk environments for injection drug use initiation. These risk environments have been characterized as a result of local policy environments, injection drug use norms in receiving communities, migration-related stressors, social dislocation, and infringement on the rights of undocumented migrants. Policies that exacerbate risk environments for migrants may inadvertently contribute to the expansion of epidemics of injection-driven blood-borne disease. Successful interventions that address emerging syndemics in border regions may therefore need to be tailored to migrant populations and distinguish between the vulnerabilities experienced by different migration classes and border settings.
Bolhuis, Mathieu S; Panday, Prashant N; Pranger, Arianna D; Kosterink, Jos G W; Alffenaar, Jan-Willem C
Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug interactions. These drug interactions are a major concern in clinical practice as they may have an effect on efficacy and toxicity. This article provides an overview of all published pharmacokinetic studies on drug
Kouprianova, I.; Ek, D.; Showalter, R.; Bergman, M.
As part of the on-going DOE/Russian MPC and A activities at the Institute of Physics and Power Engineering (IPPE) and in order to provide a basis for planning MPC and A enhancements, an expedient method to review the effectiveness of the MPC and A system has been adopted. These reviews involve the identification of appropriate and cost-effective enhancements of facilities at IPPE. This effort requires a process that is thorough but far less intensive than a traditional vulnerability assessment. The SER results in a quick assessment of current and needed enhancements. The process requires preparation and coordination between US and Russian analysts before, during, and after information gathering at the facilities in order that the analysis is accurate, effective, and mutually agreeable. The goal of this paper is to discuss the SER process, including the objectives, time scale, and lessons learned at IPPE
Malik, Nisar Ahmad
In this review, bile salt, bile salt-surfactant, and bile salt-drug interactions and their solubilization studies are mainly focused. Usefulness of bile salts in digestion, absorption, and excretion of various compounds and their rare properties in ordering the shape and size of the micelles owing to the presence of hydrophobic and hydrophilic faces are taken into consideration while compiling this review. Bile salts as potential bio-surfactants to solubilize drugs of interest are also highlighted. This review will give an insight into the selection of drugs in different applications as their properties get modified by interaction with bile salts, thus influencing their solution behavior which, in turn, modifies the phase-forming behavior, microemulsion, and clouding phenomenon, besides solubilization. Finally, their future perspectives are taken into consideration to assess their possible uses as bio-surfactants without side effects to human beings.
Windiarti, Sri Endang; Indriati, Indriati; Surachmi, Fajar
The purpose of this study was to determine the effect of therapy stop thinking negatively against drug addiction in Rehabilitation Orphanage Rumah Damai Gunung Pati Semarang. This research is quasy experiment with pretest - posttes without the control group design. Thirty respondents were taken to the reseach sujects. Stop thinking negative therapy before and after thebehavior of drug addiction there are differences (t = 0.00), so it can be stated that the therapy stop thinking negatively inf...
Sjöberg, Christina; Wallerstedt, Susanna M
To investigate whether medication reviews increase treatment with fracture-preventing drugs and decrease treatment with fall-risk-increasing drugs. Randomized controlled trial (1:1). Departments of orthopedics, geriatrics, and medicine at Sahlgrenska University Hospital, Gothenburg, Sweden. One hundred ninety-nine consecutive individuals with hip fracture aged 65 and older. Medication reviews, based on assessments of risks of falls and fractures, regarding fracture-preventing and fall-risk-increasing drugs, performed by a physician, conveyed orally and in written form to hospital physicians during the hospital stay, and to general practitioners after discharge. Primary outcomes were changes in treatment with fracture-preventing and fall-risk-increasing drugs 12 months after discharge. Secondary outcomes were falls, fractures, deaths, and physicians' attitudes toward the intervention. At admission, 26% of intervention and 29% of control participants were taking fracture-preventing drugs, and 12% and 11%, respectively, were taking bone-active drugs, predominantly bisphosphonates. After 12 months, 77% of intervention and 58% of control participants were taking fracture-preventing drugs (P = .01), and 29% and 15%, respectively, were taking bone-active drugs (P = .04). Mean number of fall-risk-increasing drugs per participants was 3.1 (intervention) and 3.1 (control) at admission and 2.9 (intervention) and 3.1 (control) at 12 months (P = .62). No significant differences in hard endpoints were found. The responding physicians (n = 65) appreciated the intervention; on a scale from 1 (very bad) to 6 (very good), the median rating was 5 (interquartile range (IQR) 4-6) for the oral part and 5 (IQR 4-5.5) for the text part. Medication reviews performed and conveyed by a physician increased treatment with fracture-preventing drugs but did not significantly decrease treatment with fall-risk-increasing drugs in older adults with hip fracture. Prescribing physicians appreciated
Schjødt-Eriksen, Jens; Clausen, Jens
We give a review of pharmaceutical R&D and mathematical simulation and optimization methods used to support decision making within the pharmaceutical development process. The complex nature of drug development is pointed out through a description of the various phases of the pharmaceutical develo...... development process. A part of the paper is dedicated to the use of simulation techniques to support clinical trials. The paper ends with a section describing portfolio modelling methods in the context of the pharmaceutical industry....
Deckers, C.L.P.; Czuczwar, S.J.; Hekster, Y.A.; Keyser, A.J.M.; Kubova, H.; Meinardi, H.; Patsalos, P.N.; Renier, W.O.; Rijn, C.M. van
Purpose: When monotherapy with antiepileptic drugs (AEDs) fails, combination therapy is tried so as to improve effectiveness, by improving either efficacy, or tolerability, or both. We have reviewed the available studies (both animal and human) on AED polytherapy to determine whether AEDs can be
Full Text Available Objective. Herbal medicine has been widely used to treat drug resistant epilepsy. Shihogyejitang (SGT has been commonly used to treat epilepsy. We investigated the effect and safety of SGT in children with drug resistant epilepsy. Design. We reviewed medical records of 54 patients with epilepsy, who failed to respond to at least two antiepileptic drugs and have been treated with SGT between April 2006 and June 2014 at the Department of Pediatric Neurology, I-Tomato Hospital, Korea. Effect was measured by the response rate, seizure-free rate, and retention rate at six months. We also checked adverse events, change in antiepileptic drugs use, and the variables related to the outcome. Results. Intent-to-treat analysis showed that, after six months, 44.4% showed a >50% seizure reduction, 24.1% including seizure-free, respectively, and 53.7% remained on SGT. Two adverse events were reported, mild skin rash and fever. Focal seizure type presented significantly more positive responses when compared with other seizure types at six months (p=0.0284, Fisher’s exact test. Conclusion. SGT is an effective treatment with excellent tolerability for drug resistant epilepsy patients. Our data provide evidence that SGT may be used as alternative treatment option when antiepileptic drug does not work in epilepsy children.
Csermely, Peter; Korcsmáros, Tamás; Kiss, Huba J.M.; London, Gábor; Nussinov, Ruth
Despite considerable progress in genome- and proteome-based high-throughput screening methods and in rational drug design, the increase in approved drugs in the past decade did not match the increase of drug development costs. Network description and analysis not only gives a systems-level understanding of drug action and disease complexity, but can also help to improve the efficiency of drug design. We give a comprehensive assessment of the analytical tools of network topology and dynamics. The state-of-the-art use of chemical similarity, protein structure, protein-protein interaction, signaling, genetic interaction and metabolic networks in the discovery of drug targets is summarized. We propose that network targeting follows two basic strategies. The “central hit strategy” selectively targets central node/edges of the flexible networks of infectious agents or cancer cells to kill them. The “network influence strategy” works against other diseases, where an efficient reconfiguration of rigid networks needs to be achieved. It is shown how network techniques can help in the identification of single-target, edgetic, multi-target and allo-network drug target candidates. We review the recent boom in network methods helping hit identification, lead selection optimizing drug efficacy, as well as minimizing side-effects and drug toxicity. Successful network-based drug development strategies are shown through the examples of infections, cancer, metabolic diseases, neurodegenerative diseases and aging. Summarizing >1200 references we suggest an optimized protocol of network-aided drug development, and provide a list of systems-level hallmarks of drug quality. Finally, we highlight network-related drug development trends helping to achieve these hallmarks by a cohesive, global approach. PMID:23384594
Full Text Available The cost of pharmaceuticals, as a percentage of total healthcare spending, has been rising worldwide. This has resulted in strained national budgets and a high proportion of people without access to essential medications. Though India has become a global hub of generic drug manufacturing, the expected benefits of cheaper drugs are not translating into savings for ordinary people. This is in part due to the rise of branded generics, which are marketed at a price point close to the innovator brands. Unbranded generic medicines are not finding their way into prescriptions due to issues of confidence and perception, though they are proven to be much cheaper and comparable in efficacy to branded medicines. The drug inventory of unbranded generic manufacturers fares reasonably when reviewed using the World Health Organization-Health Action International (WHO-HAI tool for analysing drug availability. Also, unbranded generic medicines are much cheaper when compared to the most selling brands and they can bring down the treatment costs in primary care and family practice. We share our experience in running a community pharmacy for an urban health center in the Pathanamthitta district of Kerala State, which is run solely on generic medicines. The drug availability at the community pharmacy was 73.3% when analyzed using WHO-HAI tool and the savings for the final consumers were up to 93.1%, when compared with most-selling brand of the same formulation.
Allan, G Michael; Lexchin, Joel; Wiebe, Natasha
Pharmaceutical costs are the fastest-growing health-care expense in most developed countries. Higher drug costs have been shown to negatively impact patient outcomes. Studies suggest that doctors have a poor understanding of pharmaceutical costs, but the data are variable and there is no consistent pattern in awareness. We designed this systematic review to investigate doctors' knowledge of the relative and absolute costs of medications and to determine the factors that influence awareness. Our search strategy included The Cochrane Library, EconoLit, EMBASE, and MEDLINE as well as reference lists and contact with authors who had published two or more articles on the topic or who had published within 10 y of the commencement of our review. Studies were included if: either doctors, trainees (interns or residents), or medical students were surveyed; there were more than ten survey respondents; cost of pharmaceuticals was estimated; results were expressed quantitatively; there was a clear description of how authors defined "accurate estimates"; and there was a description of how the true cost was determined. Two authors reviewed each article for eligibility and extracted data independently. Cost accuracy outcomes were summarized, but data were not combined in meta-analysis because of extensive heterogeneity. Qualitative data related to physicians and drug costs were also extracted. The final analysis included 24 articles. Cost accuracy was low; 31% of estimates were within 20% or 25% of the true cost, and fewer than 50% were accurate by any definition of cost accuracy. Methodological weaknesses were common, and studies of low methodological quality showed better cost awareness. The most important factor influencing the pattern and accuracy of estimation was the true cost of therapy. High-cost drugs were estimated more accurately than inexpensive ones (74% versus 31%, Chi-square p price of expensive drugs and overestimate the price of inexpensive ones, demonstrate a
Furlanello, Francesco; Bentivegna, Stefano; Cappato, Riccardo; De Ambroggi, Luigi
Cardiac arrhythmias are among the most important causes of non-eligibility to sports activities, and may be due to different causes (cardiomyopathies, myocarditis, coronary abnormalities, valvular diseases, primary electrical disorders, abuse of illicit drugs). The list of illicit drugs banned by the International Olympic Committee and yearly updated by the World Anti-Doping Agency includes the following classes: stimulants, narcotics, anabolic agents (androgenic steroids and others such as beta-2 stimulants), peptide hormones, mimetics and analogues, diuretics, agents with an antiestrogenic activity, masking agents. Almost all illicit drugs may cause, through a direct or indirect arrhythmogenic effect, in the short, medium or long term, a wide range of cardiac arrhythmias (focal or reentry type, supraventricular and/or ventricular), lethal or not, even in healthy subjects with no previous history of cardiac diseases. Therefore, given the widespread abuse of illicit drugs among athletes, in the management of arrhythmic athletes the cardiologist should always take into consideration the possibility that the arrhythmias be due to the assumption of illicit drugs (sometimes more than one type), especially if no signs of cardiac diseases are present. On the other hand, in the presence of latent underlying arrhythmogenic heart disease including some inherited cardiomyopathies at risk of sudden cardiac death, illicit drugs could induce severe cardiac arrhythmic effects.
Morean, Meghan E.; de Wit, Harriet; King, Andrea C.; Sofuoglu, Mehmet; Rueger, Sandra Y.; O’Malley, Stephanie S.
Rationale The Drug Effects Questionnaire (DEQ) is widely used in studies of acute subjective response (SR) to a variety of substances, but the format of the DEQ varies widely across studies, and details of its psychometric properties are lacking. Thus, the field would benefit from demonstrating the reliability and validity of the DEQ for use across multiple substances. Objective The current study evaluated the psychometric properties of several variations of DEQ items, which assessed the extent to which participants (1) feel any substance effect(s), (2) feel high, (3) like the effects, (4) dislike the effects, and (5) want more of the substance using 100mm Visual Analog Scales. Methods DEQ data from three placebo-controlled studies were analyzed to examine SR to amphetamine, nicotine, and alcohol. We evaluated the internal structure of the DEQ for use with each substance as well as relationships between scale items, measures of similar constructs, and substance-related behaviors. Results Results provided preliminary psychometric support for items assessing each DEQ construct (FEEL, HIGH, DISLIKE, LIKE, and MORE). Conclusions Based on the study results, we identify several common limitations of extant variants of the DEQ and recommend an improved version of the measure. The simplicity and brevity of the DEQ combined with its promising psychometric properties support its use in future SR research across a variety of substances. PMID:23271193
Full Text Available Abstract Background The objective of this systematic review was to examine the benefits, harms and pharmacokinetic interactions arising from the co-administration of commonly used dietary supplements with cardiovascular drugs. Many patients on cardiovascular drugs take dietary supplements for presumed benefits and may be at risk for adverse supplement-drug interactions. Methods The Allied and Complementary Medicine Database, the Cochrane Library, EMBASE, International Bibliographic Information on Dietary Supplements and MEDLINE were searched from the inception of the review to October 2011. Grey literature was also reviewed. Two reviewers independently screened records to identify studies comparing a supplement plus cardiovascular drug(s with the drug(s alone. Reviewers extracted data using standardized forms, assessed the study risk of bias, graded the strength of evidence and reported applicability. Results Evidence was obtained from 65 randomized clinical trials, 2 controlled clinical trials and 1 observational study. With only a few small studies available per supplement, evidence was insufficient for all predefined gradable clinical efficacy and harms outcomes, such as mortality and serious adverse events. One long-term pragmatic trial showed no benefit from co-administering vitamin E with aspirin on a composite cardiovascular outcome. Evidence for most intermediate outcomes was insufficient or of low strength, suggesting no effect. Incremental benefits were noted for triglyceridemia with omega-3 fatty acid added to statins; and there was an improvement in levels of high-density lipoprotein cholesterol with garlic supplementation when people also consumed nitrates Conclusions Evidence of low-strength indicates benefits of omega-3 fatty acids (plus statin, or calcium channel blockers and antiplatelets and garlic (plus nitrates or warfarin on triglycerides and HDL-C, respectively. Safety concerns, however, persist.
Full Text Available Chitosan obtained by alkaline deacetylation of chitin is a non-toxic, biocompatible, and biodegradable natural polymer. Chitosan-based hydrogel polymeric beads have been extensively studied as micro- or nano-particulate carriers in the pharmaceutical and medical fields, where they have shown promise for drug delivery as a result of their controlled and sustained release properties, as well as biocompatibility with tissue and cells. To introduce desired properties and enlarge the scope of the potential applications of chitosan, graft copolymerization with natural or synthetic polymers on it has been carried out, and also, various chitosan derivatives have been utilized to form beads. The desired kinetics, duration, and rate of drug release up to therapeutical level from polymeric beads are limited by specific conditions such as beads material and their composition, bead preparation method, amount of drug loading, drug solubility, and drug polymer interaction. The present review summarizes most of the available reports about compositional and structural effects of chitosan-based hydrogel polymeric beads on swelling, drug loading, and releasing properties. From the studies reviewed it is concluded that chitosan-based hydrogel polymeric beads are promising drug delivery systems.
Rozas-Moreno, Pedro; Reyes-García, Rebeca; Jódar-Gimeno, Esteban; Varsavsky, Mariela; Luque-Fernández, Inés; Cortés-Berdonces, María; Muñoz-Torres, Manuel
To provide recommendations on the effect of antidiabetic drugs on bone fragility to help select the most adequate antidiabetic treatment, especially in diabetic patients with high risk of fracture. Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. The GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) was used to establish both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each antidiabetic drug: AND "osteoporosis", "fractures", "bone mineral density", "bone markers", "calciotropic hormones". Papers in English with publication date before 30 April 2016 were reviewed. Recommendations were jointly discussed by the Working Group. The document summaries the data on the potential effects of antidiabetic drugs on bone metabolism and fracture risk. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.
Ayala, María Elena
Serotonin, a biogenic amine, is present in significant amounts in many structures of the CNS. It is involved in regulation of a wide variety of physiological functions, such as sensory and motor functions, memory, mood, and secretion of hormones including reproductive hormones. It has also been implicated in the etiology of a range of psychiatric disorders such as anxiety, depression, and eating disorders, along with other conditions such as obesity and migraine. While some drugs that affect serotonin, such as fenfluramine and fluoxetine, have been successfully used in treatment of a range of psychiatric diseases, others, such as the amphetamine analogues MDMA and METH, are potent psychostimulant drugs of abuse. Alterations in serotonergic neurons caused by many of these drugs are well characterized; however, little is known about the reproductive consequences of such alterations. This review evaluates the effects of drugs such as MDMA, pCA, fenfluramine, and fluoxetine on serotonergic transmission in the brain, examines the relationships of these drug effects with the neuroendocrine mechanisms modulating reproductive events such as gonadotropin secretion, ovulation, spermatogenesis, and sexual behavior in animal models, and discusses possible reproductive implications of these drugs in humans.
Drug packaging plays an important role in protecting and providing information to patients. The packaging examined by Prescrire in 2012, on the whole, still fails to perform all of these functions effectively. Two issues are especially worrisome. First, packaging too often poses a danger to children. In addition, too many patient leaflets provide incomplete information about adverse effects, thus failing to properly protect the most vulnerable patients. Yet, the method Prescrire used to analyse drug packaging shows that it is not difficult to detect and anticipate risks. It is up to healthcare professionals to take advantage of the method, to protect patients from, and report, dangerous packaging.
Amjad, Waseem; Qureshi, Waqas; Farooq, Ali; Sohail, Umair; Khatoon, Salma; Pervaiz, Sarah; Narra, Pratyusha; Hasan, Syeda M; Ali, Farman; Ullah, Aman; Guttmann, Steven
Antiarrhythmic drugs are commonly prescribed cardiac drugs. Due to their receptor mimicry with several of the gastrointestinal tract receptors, they can frequently lead to gastrointestinal side effects. These side effects are the most common reasons for discontinuation of these drugs by the patients. Knowledge of these side effects is important for clinicians that manage antiarrhythmic drugs. This review focuses on the gastrointestinal side effects of these drugs and provides a detailed up-to-date literature review of the side effects of these drugs. The review provides case reports reported in the literature as well as possible mechanisms that lead to gastrointestinal side effects.
Zhang, Jingya; Gou, Haimei; Hu, Xuejiao; Hu, Xin; Shang, Mengqiao; Zhou, Juan; Zhou, Yi; Ye, Yuanxin; Song, Xingbo; Lu, Xiaojun; Chen, Xuerong; Ying, Binwu; Wang, Lanlan
We conducted a systematic review and meta-analysis on drug-resistant tuberculosis in China to provide useful data for tuberculosis (TB) surveillance and treatment. Several databases, including PubMed, Embase, and the Chinese Biological Medical Database, were systematically searched between January 1, 1999, and August 31, 2015, using strict inclusion and exclusion criteria. The corresponding drug-resistant TB prevalence between the new and previously treated cases was significantly different in almost all of the economic regions. The Eastern coastal region is the most developed economic region with the lowest total drug-resistant TB prevalence (any drug resistance: 28%; 95% confidence interval [CI], 25%-32%; multidrug resistance: 9%; 95% CI, 8%-12%) and the lowest number of new cases (any drug resistance: 21%; 95% CI, 19%-23%; multidrug resistance: 4%; 95% CI, 3%-5%). The Northwest is the least developed area with the lowest drug-resistant TB prevalence for previously treated cases (any drug resistance: 45%; 95% CI, 36%-55%; multidrug resistance: 17%; 95% CI, 11%-26%). The prevalence (multidrug and first-line drug resistance) exhibited a downward trend from 1996-2014. The extensively drug-resistant prevalence in China was 3% (95% CI, 2%-5%) in this review. Overall, the status of drug-resistant tuberculosis in China is notably grim and exhibits regional epidemiologic characteristics. We are in urgent need of several comprehensive and effective control efforts to reverse this situation. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
Full Text Available This study develops an effective method for sentiment analysis of user-generated content on drug review websites, which has not been investigated extensively compared to other general domains, such as product reviews. A clause-level sentiment analysis algorithm is developed since each sentence can contain multiple clauses discussing multiple aspects of a drug. The method adopts a pure linguistic approach of computing the sentiment orientation (positive, negative, or neutral of a clause from the prior sentiment scores assigned to words, taking into consideration the grammatical relations and semantic annotation (such as disorder terms of words in the clause. Experiment results with 2,700 clauses show the effectiveness of the proposed approach, and it performed significantly better than the baseline approaches using a machine learning approach. Various challenging issues were identified and discussed through error analysis. The application of the proposed sentiment analysis approach will be useful not only for patients, but also for drug makers and clinicians to obtain valuable summaries of public opinion. Since sentiment analysis is domain specific, domain knowledge in drug reviews is incorporated into the sentiment analysis algorithm to provide more accurate analysis. In particular, MetaMap is used to map various health and medical terms (such as disease and drug names to semantic types in the Unified Medical Language System (UMLS Semantic Network.
Anderson, Beth M.; Rizzo, Matthew; Block, Robert I.; Pearlson, Godfrey D.; O'Leary, Daniel S.
Despite the knowledge that many drugs affect men and women differently, few studies exploring the effects of marijuana use on cognition have included women. Findings from both animal and human studies suggest marijuana may have more marked effects in women. This study examined sex differences in the acute effects of marijuana on cognition in 70 (n= 35 male, 35 female) occasional users of marijuana. Tasks were chosen to tap a wide variety of cognitive domains affected by sex and/or marijuana i...
Solimini, Renata; Rotolo, Maria C; Pellegrini, Manuela; Minutillo, Adele; Pacifici, Roberta; Busardò, Francesco P; Zaami, Simona
Powdery drugs such as cocaine and heroin are frequently adulterated or diluted predominantly to obtain more doses and to increase the drug dealer's profits, but also to enhance, to modify or to oppose drug effects. The aim of this report is to provide an overview of the recent scientific literature on medicines as well as on new psychoactive substances, used as cutting agents (i.e. pharmacologically active adulterants) and on the related adverse health effects on consumers, possibly due to the synergistic effect of the adulterants laced with substances of abuse. A literature search up to January 2017 was performed on MEDLINE, Scopus and Web of Science and reports and documents of international agencies or institutions were also searched. Pharmacologically active substances such as: paracetamol, caffeine, dextromethorphan, clenbuterol for heroin; levamisole, phenacetine, lidocaine, hydroxyzine and diltiazem for cocaine; caffeine and phentermine for amphetamine, have been identified over the years. Furthermore, since cocaine and morphine (this latter as a precursor of heroin) are both extracted from natural products, some impurities and minor alkaloids can be present in the final preparation. In this context, it is worth considering that new psychoactive substances are also used as cutting agents. The wide availability of illicit psychotropic drugs is the most serious hazard threatening consumers. Indeed emergency departments are often responsible in evaluating damages caused not only by the base substance, but also by other eventual compounds added to mimic or antagonize drug effects or simply dilute the drug amount, with a possible harmful synergic toxic action. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Magnetic microsphere is newer approach in pharmaceutical field. Magnetic microspheres as an alternative to traditional radiation methods which use highly penetrating radiation that is absorbed throughout the body. Its use is limited by toxicity and side effects. The aim of the specific targeting is to enhance the efficiency of drug delivery & at the same time to reduce the toxicity & side effects. This kind of delivery system is very much important which localises the drug to the disease site. In this larger amount of freely circulating drug can be replaced by smaller amount of magnetically targeted drug. Magnetic carriers receive magnetic responses to a magnetic field from incorporated materials that are used for magnetic microspheres are chitosan, dextran etc. magnetic microspheres can be prepared from a variety of carrier material. One of the most utilized is serum albumin from human or other appropriate species. Drug release from albumin microspheres can be sustained or controlled by various stabilization procedures generally involving heat or chemical cross-linking of the protein carrier matrix.
Bajaj, Vijay Kumar; Gupta, Radhey S
Male contraceptive development in the present scenario is most viable aspect of research due to uncontrolled population growth in the world. In this respect investigators are busy to find out a safe male contraceptive drug. Researchers have started their finding for a suitable drug from natural sources because these are safe and easily acceptable for common man, most of natural sources are plants and their products. In this review 137 plants and their effects on reproduction and reproductive physiology are summarized. Some of them have intense effect on male reproductive system and do not produce any side effects. Reproductive toxicological studies are also important aspects of these kinds of researches, so it is important that drugs are safe and widely acceptable. An ideal male contraceptive can influence semen, testes, hormone level, accessory reproductive organs and general physiology of animals and produced some alterations. Many plants in this review are showing antifertility as well as antispermatogenic effects, so these may be used for further study for contraceptives development but it is important to find out the mechanism of reaction and further laboratory and clinical research on some plants are needed for final male contraceptive drug development. In conclusion this review will help for finding suitable plant products for male contraceptive clinical and laboratory studies.
Connor, Thomas H.; Lawson, Christina C.; Polovich, Martha; McDiarmid, Melissa A.
Objectives Antineoplastic drugs are known reproductive and developmental toxicants. Our objective was to review the existing literature of reproductive health risks to workers who handle antineoplastic drugs. Methods A structured literature review of 18 peer-reviewed, English language publications of occupational exposure and reproductive outcomes was performed. Results While effect sizes varied with study size and population, occupational exposure to antineoplastic drugs appears to raise the risk of both congenital malformations and miscarriage. Studies of infertility and time-to-pregnancy also suggested an increased risk for sub-fertility. Conclusions Antineoplastic drugs are highly toxic in patients receiving treatment and adverse reproductive effects have been well documented in these patients. Healthcare workers with chronic, low level occupational exposure to these drugs also appear to have an increased risk of adverse reproductive outcomes. Additional precautions to prevent exposure should be considered. PMID:25153300
Karavolos, Stamatios; Reynolds, Michael; Panagiotopoulou, Nikoletta; McEleny, Kevin; Scally, Michael; Quinton, Richard
Androgen- or anabolic steroid-induced hypogonadism (ASIH) is no longer confined to professional athletes; its prevalence amongst young men and teenagers using androgens and/or anabolic steroids (AASs) is rising fast, and those affected can experience significant symptoms. Clinicians are increasingly encountering demanding, well-informed men affected by ASIH, yet lacking authoritative information on the subject may struggle to project a credible message. In this article, we overview the methods and drugs that men use in an attempt to counteract ASIH (with a view to either preventing its onset, or reversing it once it has developed) and summarize the scientific evidence underpinning these. The main channel for obtaining these drugs is the Internet, where they can be readily sourced without a valid prescription. An Internet search using relevant terms revealed a huge number of websites providing advice on how to buy and use products to counteract ASIH. Drugs arising repeatedly in our search included human chorionic gonadotrophin (hCG), selective oestrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). The quality and accuracy of the online information was variable, but review of medical literature also highlighted a lack of scientific data to guide clinical practice. It is important for clinicians to be aware of the AAS user's self-treatment strategies with regard to ASIH side-effect mitigation. By ensuring that they are well-informed, clinicians are more likely to retain the credibility and trust of AAS users, who will in turn likely be more open to engage with appropriate management. © 2014 John Wiley & Sons Ltd.
in 1994 by the FAA revealed that an estimated 14 000 US pilots flew while using prohibited medications or illegal substances or flew with significant unreported medical conditions.1. Greater understanding of the effects of medication in humans, and advances in drug development have now made possible the use of various ...
examiners, pilots, cabin crew and air traffic services personnel) to consider the effects that medicine or drugs may have on performance. Studies confirm that some pilots, and other crew members while on duty, used prohibited medications or illegal substances or performed duties while suffering significant unreported
Singh, T; Natu, M V
Attitudes of 40 interns towards rational drug use (RDU) were assessed, using a standardized Likert type scale. The assessment was repeated after 4 months to evaluate the effect of usual working conditions of the hospital. After this period, the attitudes had slided towards negative side (p attitudes of test group returned towards positive side (p attitudes.
Full Text Available Glaucoma is a progressive optic neuropathy and medical therapy is the initial option for the treatment of this potentially blinding condition. Topical instillation of eye drops from the bottle is the most common glaucoma drug delivery form. Due to limited permeability of anterior ocular surface, natural clearance and drainage, eye drops contain large amounts of inactive ingredients. Effective penetration enhancers are known as irritants causing ocular discomfort. Although drug efficacy is determined by active ingredients, inactive agents can affect tolerance and can result in conjunctival irritation and hyperemia and influence patients’ adherence and quality of life.
Goenka, Luxitaa; George, Melvin; Sen, Maitrayee
Endometriosis is a gynaecological disease that is characterised by the presence of endometrium like tissue-epithelium and stroma that develops outside the uterine cavity, which is responsible for pelvic pain and infertility. Even though several medical therapies exist for the treatment of endometriosis, each of the drug class has its own limitations such as cost of treatment, side-effects and its short-term effect on the symptoms of endometriosis. In this review, we have attempted to summarize the current status and challenges of drug development for endometriosis. A systematic review was done and all the RCTs were selected from the identified hits. We included studies that explored the usage of therapeutic drugs on endometriosis patients from inception till November 2016. The search term used was 'Endometriosis' using PubMed and Clinicaltrials.gov. For the final analysis, 60 articles were analyzed and we identified the newly emerging drug therapies for endometriosis treatment and have briefed their current status and challenges in drug development for endometriosis. The quality of the selected studies was assessed based on the degree of bias. The current classes of drugs that have shown promising therapeutic results include Gonadotropin- releasing hormone (GnRH) antagonists, aromatase inhibitors (AI), and selective progesterone and estrogen receptor modulators, dopamine receptor-2-agonists and statins. The drugs that failed midway during development include tanezumab, rosiglitazone, infliximab, pentoxifylline, telapristone acetate, asoprisnil and raloxifene. From the literature review, it appears that the most promising molecules for the treatment of endometriosis in the near future include elagolix, mifepristone, TAK-385, KLH-2109 and ASP1707 and cabergoline. It remains to be seen if these molecules would succeed large phase 3 clinical trials and overcome the regulatory hurdles to become an essential tool in the gynaecologist's armamentarium against endometriosis
Thamyris Alexandre Salles
Full Text Available A systematic review was conducted with the objective of identifying scientific evidence of strategies for prevention or reduction of drug use among adolescents. Searches were conducted in databases LILACS, CINAHL, MEDLINE, Scopus and Cochrane Library, with descriptors Ensino, Educação em Saúde, Transtornos relacionados ao uso de substâncias, Adolescentes and Enfermagem Psiquiátrica. Twenty-seven articles were chosen. Results pointed to a variety of software, projects and interventions that are used as strategies for prevention or reduction of drug use among adolescents. Among the studies, 74.1% (n=20 reached satisfactory results and 25.9% (n=7 reached partially satisfactory results. Only Narconon Project and Brief Intervention were widely effective in reducing use of a variety of drugs among adolescents, since the other studies were focused on specific drugs or were limited to use prevention among non-using adolescents.
Rigon, Roberta Balansin; Oyafuso, Márcia Helena; Fujimura, Andressa Terumi; Gonçalez, Maíra Lima; do Prado, Alice Haddad; Gremião, Maria Palmira Daflon; Chorilli, Marlus
Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy.
Alwardt, Cory M; Redford, Daniel; Larson, Douglas F
General anesthesia is defined as complete anesthesia affecting the entire body with loss of consciousness, analgesia, amnesia, and muscle relaxation. There is a wide spectrum of agents able to partially or completely induce general anesthesia. Presently, there is not a single universally accepted technique for anesthetic management during cardiac surgery. Instead, the drugs and combinations of drugs used are derived from the pathophysiologic state of the patient and individual preference and experience of the anesthesiologist. According to the definition of general anesthesia, current practices consist of four main components: hypnosis, analgesia, amnesia, and muscle relaxation. Although many of the agents highlighted in this review are capable of producing more than one of these effects, it is logical that drugs producing these effects are given in combination to achieve the most beneficial effect. This review features a discussion of currently used anesthetic drugs and clinical practices of general anesthesia during cardiac surgery. The information in this particular review is derived from textbooks, current literature, and personal experience, and is designed as a general overview of anesthesia during cardiac surgery.
Fattore, Liana; Altea, Silvia; Fratta, Walter
Addiction research has historically neglected research on women, and most studies have been conducted on men only, with the concluding results generalized to the female population. The role of sex differences in vulnerability to drug abuse, their repercussions on prevention and treatment strategies all require detailed studies, as does the progression from recreational drug use to dependence. This review synthesizes evidence of gender differences in drug addiction, with particular emphasis on women's health and implications. We first reviewed behavioral studies showing sex differences in the preference for and self-administration of licit (i.e., alcohol and nicotine) and illicit (i.e., cocaine, amphetamine, heroin and cannabis) substances as revealed by animal models of addiction. Clinical studies demonstrating differences between men and women in craving, drug use, abstinence and relapse will then be examined. For both animal and human studies, the effects of hormones and estrous/menstrual cycle will be reviewed. Finally, neurobiological factors underlying gender differences in vulnerability to drug addiction (i.e., brain morphology and neurotransmission) and need for gender-specific detoxification treatments will be discussed.
Kazemi, Donna M; Borsari, Brian; Levine, Maureen J; Dooley, Beau
The use of social media (SM) as a surveillance tool of global illicit drug use is limited. To address this limitation, a systematic review of literature focused on the ability of SM to better recognize illicit drug use trends was addressed. A search was conducted in databases: PubMed, CINAHL via Ebsco, PsychINFO via Ebsco, Medline via Ebsco, ERIC, Cochrane Library, Science Direct, ABI/INFORM Complete and Communication and Mass Media Complete. Included studies were original research published in peer-reviewed journals between January 2005 and June 2015 that primarily focused on collecting data from SM platforms to track trends in illicit drug use. Excluded were studies focused on purchasing prescription drugs from illicit online pharmacies. Selected studies used a range of SM tools/applications, including message boards, Twitter and blog/forums/platform discussions. Limitations included relevance, a lack of standardized surveillance systems and a lack of efficient algorithms to isolate relevant items. Illicit drug use is a worldwide problem, and the rise of global social networking sites has led to the evolution of a readily accessible surveillance tool. Systematic approaches need to be developed to efficiently extract and analyze illicit drug content from social networks to supplement effective prevention programs. © The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: email@example.com
Beloate, Lauren N; Coolen, Lique M
Different factors influence the development of drug addiction in humans, including social reward experiences. In animals, experience with social rewards, such as sexual behavior, pair bonding, social and environmental enrichment, can be protective. However, loss or lack of social rewards can lead to a vulnerability to drug-seeking behavior. The effects of social reward experience on drug-seeking behavior are associated with changes in the neural pathways that control drug-related behavior. This review will provide an introduction and overview of the mesolimbic pathway and the influence of social reward experience on drug-seeking behavior in rodents. Moreover, the research from our laboratory on effects of sexual experience and loss of sex reward on psychostimulant and opiate reward will be reviewed. Finally, we will review current knowledge of the neural mechanisms that underlie these interactions. Investigations of the neural underpinnings by which social and drug rewards interact contribute to improved understanding of the neural basis of vulnerability for drug addiction and reward-related behaviors in general. Copyright © 2017 Elsevier Ltd. All rights reserved.
A. S. Kotov
Full Text Available Impaired cognitive function is a common problem in epileptic patients. The exact cause of cognitive impairment in case of epilepsy has not been explored fully, but there is no doubt that a role in this is played by three factors: the disease underlying epilepsy; epileptic seizures proper; and negative side effects of antiepileptic drugs. Their cognitive effects are one of the major problems affecting the tolerance of therapy. The review considers the effects of phenobarbital, phenytoin, carbamazepine, valproates, oxcarbazepine, topiramate, lamotrigine, and levetiracetam in terms of their action on the cognitive function of healthy volunteers and epileptic patients.
de Vries, Max; Seppala, Lotta J; Daams, Joost G; van de Glind, Esther M M; Masud, Tahir; van der Velde, Nathalie
Use of certain medications is recognized as a major and modifiable risk factor for falls. Although the literature on psychotropic drugs is compelling, the literature on cardiovascular drugs as potential fall-risk-increasing drugs is conflicting. The aim of this systematic review and meta-analysis is to provide a comprehensive overview of the associations between cardiovascular medications and fall risk in older adults. Design: A systematic review and meta-analysis. Medline, Embase, and PsycINFO. Key search concepts were "fall," "aged," "causality," and "medication." Studies that investigated cardiovascular medications as risk factors for falls in participants ≥60 years old or participants with a mean age of 70 or older were included. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratios (ORs) separately. In total, 131 studies were included in the qualitative synthesis. Meta-analysis using adjusted ORs showed significant results (pooled OR [95% confidence interval]) for loop diuretics, OR 1.36 (1.17, 1.57), and beta-blocking agents, OR 0.88 (0.80, 0.97). Meta-analysis using unadjusted ORs showed significant results for digitalis, OR 1.60 (1.08, 2.36); digoxin, OR 2.06 (1.56, 2.74); and statins, OR 0.80 (0.65, 0.98). Most of the meta-analyses resulted in substantial heterogeneity that mostly did not disappear after stratification for population and setting. In a descriptive synthesis, consistent associations were not observed. Loop diuretics were significantly associated with increased fall risk, whereas beta-blockers were significantly associated with decreased fall risk. Digitalis and digoxin may increase the risk of falling, and statins may reduce it. For the majority of cardiovascular medication groups, outcomes were inconsistent. Furthermore, recent studies indicate that specific drug properties, such as selectivity of beta-blockers, may affect fall risk, and drug-disease interaction also may play
Roman Aleksandrovich Bekker
Full Text Available Purpose. To study and summarize the existing evidence base for the use of melatonin as a mean to counteract or diminish the side effects of various psychotropic drugs and electroconvulsive therapy, and to provide the reader with relevant conclusions. Methodology. The authors have searched for the scientific literature regarding the use of melatonin as a mean to counteract or diminish the side effects of various psychotropic drugs and electroconvulsive therapy, using the PubMed and Google Scholar as a search tool. Then the authors thoroughly reviewed the data they found. The resulting review is presented in this article. Results. The data we have obtained from this review of the literature indicate that melatonin can be effectively used both in monotherapy and in combination with other therapeutic means in order to reduce several different side effects of psychotropic drugs and electroconvulsive therapy. Melatonin also deserves further study in this regard. The evidence base for its use in this manner is very variable in quality for different side effects. For now, the greatest evidence base exists regarding the potential effectiveness of melatonin in the prevention and treatment of drug-induced insomnia, memory and cognitive impairment, akathisia, tardive dyskinesias, and metabolic syndrome. Practical implications. The results we have obtained can be widely applied in psychiatry, neurology and addiction medicine, as well as in all those areas of general medicine, which make use of psychotropic drugs.
Bernabeu-Martínez, Mari A; Ramos Merino, Mateo; Santos Gago, Juan M; Álvarez Sabucedo, Luis M; Wanden-Berghe, Carmina; Sanz-Valero, Javier
To review the scientific literature related to the safe handling of hazardous drugs (HDs). Critical analysis of works retrieved from MEDLINE, the Cochrane Library, Scopus, CINHAL, Web of Science and LILACS using the terms "Hazardous Substances", "Antineoplastic Agents" and "Cytostatic Agents", applying "Humans" and "Guidelines" as filters. Date of search: January 2017. In total, 1100 references were retrieved, and from those, 61 documents were selected based on the inclusion and exclusion criteria: 24 (39.3%) documents related to recommendations about HDs; 27 (44.3%) about antineoplastic agents, and 10 (33.3%) about other types of substances (monoclonal antibodies, gene medicine and other chemical and biological agents). In 14 (23.3%) guides, all the stages in the manipulation process involving a risk due to exposure were considered. Only one guide addressed all stages of the handling process of HDs (including stages with and without the risk of exposure). The most described stages were drug preparation (41 guides, 67.2%), staff training and/or patient education (38 guides, 62.3%), and administration (37 guides, 60.7%). No standardized informatics system was found that ensured quality management, traceability and minimization of the risks associated with these drugs. Most of the analysed guidelines limit their recommendations to the manipulation of antineoplastics. The most frequently described activities were preparation, training, and administration. It would be convenient to apply ICTs (Information and Communications Technologies) to manage processes involving HDs in a more complete and simpler fashion.
Jahangirian, Hossein; Lemraski, Ensieh Ghasemian; Webster, Thomas J; Rafiee-Moghaddam, Roshanak; Abdollahi, Yadollah
This review discusses the impact of green and environmentally safe chemistry on the field of nanotechnology-driven drug delivery in a new field termed "green nanomedicine". Studies have shown that among many examples of green nanotechnology-driven drug delivery systems, those receiving the greatest amount of attention include nanometal particles, polymers, and biological materials. Furthermore, green nanodrug delivery systems based on environmentally safe chemical reactions or using natural biomaterials (such as plant extracts and microorganisms) are now producing innovative materials revolutionizing the field. In this review, the use of green chemistry design, synthesis, and application principles and eco-friendly synthesis techniques with low side effects are discussed. The review ends with a description of key future efforts that must ensue for this field to continue to grow.
Fog, Amura Francesca; Kvalvaag, Gunnar; Engedal, Knut; Straand, Jørund
We describe the drug-related problems (DRPs) identified during medication reviews (MRs) and the changes in drug utilization after MRs at nursing homes in Oslo, Norway. We explored predictors for the observed changes. Observational before-after study. Forty-one nursing homes. MRs performed by multidisciplinary teams during November 2011 to February 2014. In all, 2465 long-term care patients. DRPs identified by explicit criteria (STOPP/START and NORGEP) and drug-drug interaction database; interventions to resolve DRPs; drug use changes after MR. A total of 6158 DRPs were identified, an average of 2.6 DRPs/patient, 2.0 for regular and 0.6 for pro re nata (prn) drugs. Of these patients, 17.3% had no DRPs. The remaining 82.7% of the patients had on average 3.0 DRPs/patient. Use of unnecessary drugs (43.5%), excess dosing (12.5%) and lack of monitoring of the drug use (11%) were the most frequent DRPs. Opioids and psychotropic drugs were involved in 34.4% of all DRPs. The mean number of drugs decreased after the MR from 6.8 to 6.3 for regular drugs and from 3.0 to 2.6 for prn drugs. Patients with DRPs experienced a decrease of 1.1 drugs after MR (0.5 for regular and 0.6 for prn drugs). The reduction was most pronounced for the regular use of antipsychotics, antidepressants, hypnotics/sedatives, diuretics, antithrombotic agents, antacid drugs; and for prn use of anxiolytics, opioids, hypnotics/sedatives, metoclopramide and NSAIDs. The medication review resulted in less drug use, especially opioids and psychotropic drugs.
Tetteh, Ebenezer; Morris, Stephen
The acquisition costs of biologic drugs are often considered to be relatively high compared with those of nonbiologics. However, the total costs of delivering these drugs also depend on the cost of administration. Ignoring drug administration costs may distort resource allocation decisions because these affect cost effectiveness. The objectives of this systematic review were to develop a framework of drug administration costs that considers both the costs of physical administration and the associated proximal costs; and, as a case example, to use this framework to evaluate administration costs for biologics within the UK National Health Service (NHS). We reviewed literature that reported estimates of administration costs for biologics within the UK NHS to identify how these costs were quantified and to examine how differences in dosage forms and regimens influenced administration costs. The literature reviewed were identified by searching the Centre for Review and Dissemination Databases (DARE, NHS EED and HTA); EMBASE (The Excerpta Medica Database); MEDLINE (using the OVID interface); Econlit (EBSCO); Tufts Medical Center Cost Effectiveness Analysis (CEA) Registry; and Google Scholar. We identified 4,344 potentially relevant studies, of which 43 studies were selected for this systematic review. We extracted estimates of the administration costs of biologics from these studies. We found evidence of variation in the way that administration costs were measured, and that this affected the magnitude of costs reported, which could then influence cost effectiveness. Our findings suggested that manufacturers of biologic medicines should pay attention to formulation issues and their impact on administration costs, because these affect the total costs of healthcare delivery and cost effectiveness.
Gorman, Dennis M
This paper critically reviews the published evidence pertaining to Project Towards No Drug Abuse (Project TND). Publications from seven evaluation studies of Project TND are reviewed, and the results from these are discussed as related to the following outcomes: main effects on the use of cigarettes, alcohol and marijuana; main effects on the use of "hard drugs," defined in the evaluations as cocaine, hallucinogens, stimulants, inhalants, ecstasy and other drugs (e.g., depressants, PCP, steroids and heroin); subgroup and interaction analyses of drug use; and violence-related behaviors. Very few main effects have been found for cigarette, alcohol and marijuana use in the Project TND evaluations. While studies do report main effects for hard drug use, these findings are subject to numerous threats to validity and may be attributable to the data analyses employed. Similarly, while isolated subgroup and interaction effects were found for alcohol use among baseline nonusers and some violence-related behaviors in the early Project TND evaluations, these findings have not been replicated in more recent studies and may result from multiple comparisons between study conditions. In conclusion, there is little evidence to support the assertion that Project TND is an effective drug or violence prevention program. The broader implications of these findings for prevention science are discussed and suggestions are made as to how the quality of research in the field might be improved.
Full Text Available Orthodontic treatment is based on the premise that when force is delivered to a tooth and thereby transmitted to the adjacent investing tissues, certain mechanical, chemical, and cellular events take place within these tissues, which allow for structural alterations and contribute to the movement of that tooth. Molecules present in drugs and nutrients consumed regularly by patients can reach the mechanically stressed paradental tissues through the circulation and interact with local target cells. The combined effect of mechanical forces and one or more of these agents may be inhibitory, additive, or synergistic. Current orthodontic research aims to develop methods of increasing the tissue concentration of molecules promoting tooth movement, while simultaneously decreasing the concentration of unwanted elements which can produce harmful side effects. This article discusses in detail the various possible drugs that can bring about alterations in the desired orthodontic tooth movement.
Torkhovskaia, T I; Ipatova, O M; Medvedeva, N V; Ivanov, V S; Ivanova, L I
The extensive development of nanotechnologies in the last two decades has brought about new understanding of plasma lipoproteins (LP) as natural drug nanocarriers that escape interaction with immune and reticuloendothelial systems. Drugs bound to LP (especially LDL) can more actively penetrate into cells of many cancer and inflammation tissues with enhanced expression or/and dysregulation of B,E receptors or possibly scavenger SR-BI receptors. Relevant studies are focused on the development of new dosage forms by conjugating lipophilic drugs either with isolated plasma LP or with their model formulations, such as nanoemulsions, mimetics, lipid nanospheres, etc. Some authors include in these particles serum or recombinant apoproteins, peptides, and modified polymer products. As shown recently, protein-free lipid nanoemulsions in plasma take up free apoA and apoE. Complexes with various LP also form after direct administration of lypophilic drugs into blood especially those enclosed in phospholipid formulations, e.g. liposomes. Results of evaluation of some lipophilic dugs (mainly cytostatics, amphotericin B, cyclosporine A, etc.) are discussed. Original data are presented on the influence of phospholipid formulations on the distribution of doxorubicin and indomethacin between LP classes after in vitro incubation in plasma. On the whole, the review illustrates the importance of research on LP and phospholi pid forms as drug nanocarriers to be used to enhance effect of therapy.
Van Esdonk, Michiel J.; Van Zutphen, Eline J. M.; Roelfsema, Ferdinand; Pereira, Alberto M.; Van Der Graaf, Piet H.; Biermasz, Nienke R.; Stevens, Jasper; Burggraaf, Jacobus
Objective. In rare disease research, most randomized prospective clinical trials can only use limited number of patients and are comprised of highly heterogeneous populations. Therefore, it is crucial to report the results in such a manner that it allows for comparison of treatment effectiveness and
Kuribayashi, Ryosuke; Appleton, Scott
Generic drugs are assuming an increasingly important role in sustaining modern healthcare systems, as the cost of healthcare, including drug usage, is gradually expanding around the world. To date, published articles comparing generic drug reviews between different countries are scarce. The objective of this study was to examine generic drug reviews in Japan and Canada. We surveyed generic drug reviews from Japan and Canada and compared the following points: general matter (application types, type of partial change or Supplement to an Abbreviated New Drug Submission, application and approval numbers, review period, application format, review report, responsibility for review), bioequivalence studies for solid oral dosage forms, and bioequivalence guidelines, guidance, or basic principles regarding various dosage forms. This survey described the many similarities and differences in generic drug reviews between the two countries and points that should be improved to promote better generic drug reviews. In particular, regulations for the definition of the same or different active pharmaceutical ingredients (APIs) are similar for both authorities. The results clarified the future challenges of generic drug reviews, and the differences highlighted by this survey will be important considerations for the future. This is the first article to present and discuss the details of generic drug reviews between Japan and Canada.
Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K
From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.
Le Grand, A; Van Hogerzeil, H; Haaijer-Ruskamp, FM; LeGrand, A.
Many studies have been done to document drug use patterns, and indicate that overprescribing, multi-drug prescribing, misuse of drugs, use of unnecessary expensive drugs and overuse of antibiotics and injections are the most common problems of irrational drug use by prescribers as well as consumers.
Rowell, P.; Garner, A.
The release of neurotransmitter is routinely studied in a superfusion system in which serial samples are collected and the effects of drugs or other treatments on the amount of material in the superfusate is determined. With frequent sampling interval, this procedure provides a mechanism for dynamically characterizing the release process itself. Using automated data collection in conjunction with polyexponential computer analysis, the equation which describes the release process in each experiment is determined. Analysis of the data during the nontreated phase of the experiment allows an internal control to be used for accurately assessing any changes in neurotransmitter release which may occur during a subsequent treatment phase. The use of internal controls greatly improves the signal to noise ratio and allows determinations of very low concentrations of drugs on small amounts of tissue to be made. In this presentation, the effects of 10 μM nicotine on 3 H-dopamine release in rat nucleus accumbens is described. The time course, potency and efficacy of the drug treatment is characterized using this system. Determinations of the exponential order of the release as well as the rate constants allow one to study the mechanism of the release process. A description of 3 H-dopamine release in normal as well as Ca ++ -free medium is presented
Full Text Available Dermatological drugs, mostly corticosteroids and isotretinoin, cause different psychiatric adverse effects. During steroid therapy, a wide range of psychiatric conditions, from minor clinical symptoms like insomnia and anxiety to serious psychiatric syndromes like psychosis and delirium might be seen. In medical literature, a causal connection is usually suggested between “isotretinoin”, which is used for treatment of acne vulgaris and depression and suicide attempts. However, there are no statistically significant double-blind randomized studies that support this connection. Clinicians must know patient’s psychiatric history before using any dermatological treatment known as causing psychiatric adverse effects, and psychiatric consultation should be established whenever necessary.
Cohen, Bruce M Z; Butler, Rachael
BZP-party pills are yet another 'designer drug' which mimics the stimulant qualities of amphetamines and MDMA/Ecstasy. As legal markets for the substance have developed in the last decade (especially amongst young people) so has public and governmental concern. This article provides a summary of the available international research on benzylpiperazine (BZP) and its popular use in the compound form known as 'party pills'. Through performing an analysis of the available medical and social scientific literature, the review outlines current knowledge on the compound, the prevalence of usage of BZP-party pills, as well as the associated harms, risks and rationales for use of the drug. Despite moves towards legislative control of BZP-party pills, the evidence presented suggests limited social and health harms associated with the drug, although research on long term effects is a significant gap in the literature. It also remains inconclusive as to whether BZP-party pills act as a 'gateway' to illegal drugs or, conversely, play a role in harm reduction with illegal drug users turning to legal alternatives; there is some evidence for both positions. With increasing controls of BZP-party pills, and with the increasing numbers of 'legal highs' and new designer drugs on the market, we conclude that new legal alternatives will continue to surface to replace the drug in the future. Considering a harm reduction approach to drug taking, it is suggested that policy makers consider the creation of a legal holding category which restricts and regulates the market in legal highs whilst the social and health harms associated with each drug can be thoroughly investigated. Copyright © 2011 Elsevier B.V. All rights reserved.
Siti Sarah Aulia Amrullah
Full Text Available Orthodontic tooth movement is basically a biological response to mechanical forces given to the teeth in orthodontic treatment, which involving the periodontal tissue and alveolar bone, resulting in the release of numerous substances from the dental tissues and surrounding structure. Remodeling changes in periodontal tissues are considered to be essential in effecting orthodontic tooth movement which is the base of orthodontic correction. Molecules produced in various diseased tissues or drugs and nutrients consumed regularly by patients, can influence mechanically stressed periodontal tissue through the circulation and interact with target cell combination of which may be inhibitory, additive or synergize. Medications might have an important influence on the rate of tooth movement, and information on their consumption is essential to adequately discuss treatment planning with patients. Therefore it is imperative to the practitioners being in medical profession, must pay close attention to the drug consumption history of every patient before and during the course of treatment.
Pisano, Umberto; Deosaran, Jordanna; Leslie, Stephen J; Rushworth, Gordon F; Stewart, Derek; Ford, Ian; Watson, Angus J M
Nicorandil is a popular anti-anginal drug in Europe and Japan. Apart from some common adverse drug reactions (ADR), its safety is satisfactory. Several reports have suggested a link between nicorandil, gastrointestinal (GI) ulceration and fistulas. The review aims to critically appraise, synthesize and present the available evidence of all known GI ADR per anatomical location. The study complied with the PRISMA statement. Literature and pharmacovigilance databases were used to provide rate and/or calculate parameters (median age, median dose, history of symptoms, length of therapy and healing time after withdrawal of the drug). Differences in distribution of quantitative variables were analyzed via Mann-Whitney test. Correlation between quantitative variables was assessed with a Spearman's correlation coefficient. A p value <0.05 was significant. Oral ulcerations occur in 0.2% of the subjects, anal ulcerations are present between 0.07% and 0.37% of patients. Oral and distal GI involvements are the most common ADR (28-29% and 27-31% of all GI ADR, respectively). The hepatobiliary system, the pancreas and salivary glands are not affected by nicorandil exposure. The time to develop oral ulcerations is 74 weeks among people on <30 mg/day compared to only 7.5 weeks in individuals on higher regimens (p = 0.47). There is a significant correlation between dose and ulcer healing time (Spearman's 0.525, p < 0.001). Ulcerative disease is a very commonly reported GI ADR. A delayed ulcerative tendency supports the hypothesis of an ulcerogenic metabolite. Nicorandil seems to act as a cause of the ulcerations, but appears to also work in synergy with other promoting factors. Whether the action of the metabolites relies on a specific mechanism or a simple chemical ulceration is still to be established.
Oliveira, Marlange A; Guimarães, Adriana G; Araújo, Adriano A S; Quintans-Júnior, Lucindo J; Quintans, Jullyana S S
Fibromyalgia (FM) is a musculoskeletal condition characterized by chronic widespread pain, tenderness and often accompanied by other comorbid conditions such as depression, anxiety, chronic fatigue, among others. Now, we aimed to survey the recent patents describing new drugs or alternative therapy for FM. Areas covered: This review covers the therapeutic patents published between 2010 and 2017 from specialized search databases (WIPO, DERWENT, INPI, ESPANET and USPTO) that report the discovery of new drugs or pharmacologic alternative for the treatment of FM. Expert opinion: New therapeutic substances have been proposed in the last seven years. At least as it has been found in our survey, most are still in the pre-clinical phase of the study, and its clinical applicability is unclear. However, other therapeutic approaches were found in patents such as well-established drugs in the market in combination or drug repositioning that combines the 'new analgesic' effects with the old side effects. Hence, it is a safe approach for pharmaceutical market, but poorer to patients who need a radical innovation. So, there is the emerging need for further studies on the safety and efficacy of such therapeutic measures and the search for improvement of side effects, as well as the development of new drugs that are unorthodox for different FM symptoms.
Pawluk, Shane Ashley; Roels, Craig Allan; Wilby, Kyle John; Ensom, Mary H H
Medications indicated for helminthes and other parasitic infections are frequently being used in mass populations in endemic areas. Currently, there is a lack of guidance for clinicians on how to appropriately manage drug interactions when faced with patients requiring short-term anthelmintic therapy with albendazole or mebendazole while concurrently taking other agents. The objective of this review was to systematically summarize and evaluate published literature on the pharmacokinetics of albendazole or mebendazole when taken with other interacting medications. A search of MEDLINE (1946 to October 2014), EMBASE (1974 to October 2014), International Pharmaceutical Abstracts (1970 to October 2014), Google, and Google Scholar was conducted for articles describing the pharmacokinetics of albendazole or mebendazole when given with other medications (and supplemented by a bibliographic review of all relevant articles). Altogether, 17 articles were included in the review. Studies reported data on pharmacokinetic parameters for albendazole or mebendazole when taken with cimetidine, dexamethasone, ritonavir, phenytoin, carbamazepine, phenobarbital, ivermectin, praziquantel, diethylcarbamazine, azithromycin, and levamisole. Cimetidine increased the elimination half-life of albendazole and maximum concentration (Cmax) of mebendazole; dexamethasone increased the area under the plasma concentration-time curve (AUC) of albendazole; levamisole decreased the Cmax of albendazole; anticonvulsants (phenytoin, phenobarbital, carbamazepine) decreased the AUC of albendazole; praziquantel increased the AUC of albendazole; and ritonavir decreased the AUC of both albendazole and mebendazole. No major interactions were found with ivermectin, azithromycin, or diethylcarbamazine. Future research is required to clarify the clinical relevance of the interactions observed.
Mamen, Anette Vik; Håkonsen, Helle; Kjome, Reidun L S; Gustavsen-Krabbesund, Bjørn; Toverud, Else-Lydia
Medication use review (MUR) is a community pharmacy service in several countries. Knowledge about what patients want from such a service is limited. The aim of this study was therefore to investigate Norwegian elderly patients' need for drug information and their attitudes towards MURs. In Norway's two largest cities, 162 patients (72% women; mean age: 78.9 years) who used at least one prescription drug were recruited from 18 senior centres. They were interviewed personally with a structured questionnaire (29 closed and 4 open-ended questions). The average number of prescription drugs used was 4.4. Seventy per cent also used over-the-counter drugs. The main source of drug information was the general practitioner (GP) followed by package inserts and pharmacy staff. For drug-related problems, 62% would contact the GP compared with 24% who preferred the pharmacist. Fifty per cent remembered no information when collecting prescriptions. However, 56% wanted to know more about their medication and 55% were interested in a MUR. The main topics they wished to address were effect/side effects and interactions. Lack of privacy was reported to be a major obstacle in the current situation. This study shows that community pharmacies in Norway play a minor role regarding drug information to elderly polypharmacy patients. The GP is both their main information source and whom they contact for drug-related problems. However, half of the patients would like to know more about their medication. More than half were positive towards taking part in a MUR. © 2015 Royal Pharmaceutical Society.
Yokota, M; Kusama, M; Matsuki, N; Ono, S
External experts play an important role in shaping regulatory decisions in the new drug review process in the United States, Europe and Japan. No rigorous study has been performed addressing how and to what extent external experts, in contrast to internal reviewers in the agency, influence the regulatory decisions during new drug reviews. We examined their contributions in Japanese regulatory reviews in contrast to the internal reviewers, focusing on the labelling decision on therapeutic indications. With the data set of 219 new molecular entities (NMEs) approved in Japan from 2000 to 2009, we observed how proposed indications in labelling were modified in a stepwise manner during the review process and conducted multinomial logistic analysis to examine the possible mechanism behind. We found that interim assessment of indications by the internal reviewers was modified substantially by the influence of the external experts in about 20% of the 219 NMEs. Our analysis suggested that internal reviewers provided their opinion mainly based on strict review discipline, whereas external experts added flexibility and reality to their reviews. Our analysis revealed different evaluations between internal reviewers and external experts during regulatory discussions in new drug reviews and how the external panel contributes to changing internal decisions. This study provides a new and quantitative approach to better label setting by emphasizing the contributions of each stakeholder in new drug reviews, which would improve the efficiency, quality and transparency of new drug reviews to enhance public health. © 2013 John Wiley & Sons Ltd.
Sophie A. Montandon
Full Text Available Gut microbiota forms a catalog of about 1000 bacterial species; which mainly belong to the Firmicutes and Bacteroidetes phyla. Microbial genes are essential for key metabolic processes; such as the biosynthesis of short-chain fatty acids (SCFA; amino acids; bile acids or vitamins. It is becoming clear that gut microbiota is playing a prevalent role in pathologies such as metabolic syndrome; type 2 diabetes (T2D; inflammatory and bowel diseases. Obesity and related diseases; notably type 2 diabetes, induce gut dysbiosis. In this review; we aim to cover the current knowledge about the effects of antidiabetic drugs on gut microbiota diversity and composition as well as the potential beneficial effects mediated by specific taxa. Metformin is the first-line treatment against T2D. In addition to its glucose-lowering and insulin sensitizing effects, metformin promotes SCFA-producing and mucin-degrading bacteria. Other antidiabetic drugs discussed in this review show positive effects on dysbiosis; but without any consensus specifically regarding the Firmicutes to Bacteroidetes ratio. Thus, beneficial effects might be mediated by specific taxa.
Dranove, David; Olsen, Chris
Immediately prior to the passage of the 1962 Food and Drug Administration Amendments, there were a number of drugs recalled from markets worldwide. Announcements about the dangerous side effects of these drugs were associated with lower-share prices for their manufacturers and the industry as a whole. We perform several analyses to sort out alternative explanations for the observed declines. We find that dangerous drug announcements had no effect on the sales of other drugs and didn't affect ...
Zilverstand, Anna; Huang, Anna S; Alia-Klein, Nelly; Goldstein, Rita Z
The impaired response inhibition and salience attribution (iRISA) model proposes that impaired response inhibition and salience attribution underlie drug seeking and taking. To update this model, we systematically reviewed 105 task-related neuroimaging studies (n > 15/group) published since 2010. Results demonstrate specific impairments within six large-scale brain networks (reward, habit, salience, executive, memory, and self-directed networks) during drug cue exposure, decision making, inhibitory control, and social-emotional processing. Addicted individuals demonstrated increased recruitment of these networks during drug-related processing but a blunted response during non-drug-related processing, with the same networks also being implicated during resting state. Associations with real-life drug use, relapse, therapeutic interventions, and the relevance to initiation of drug use during adolescence support the clinical relevance of the results. Whereas the salience and executive networks showed impairments throughout the addiction cycle, the reward network was dysregulated at later stages of abuse. Effects were similar in alcohol, cannabis, and stimulant addiction. Copyright © 2018 Elsevier Inc. All rights reserved.
Ardal, Christine; Alstadsæter, Annette; Røttingen, John-Arne
Innovation through an open source model has proven to be successful for software development. This success has led many to speculate if open source can be applied to other industries with similar success. We attempt to provide an understanding of open source software development characteristics for researchers, business leaders and government officials who may be interested in utilizing open source innovation in other contexts and with an emphasis on drug discovery. A systematic review was performed by searching relevant, multidisciplinary databases to extract empirical research regarding the common characteristics and barriers of initiating and maintaining an open source software development project. Common characteristics to open source software development pertinent to open source drug discovery were extracted. The characteristics were then grouped into the areas of participant attraction, management of volunteers, control mechanisms, legal framework and physical constraints. Lastly, their applicability to drug discovery was examined. We believe that the open source model is viable for drug discovery, although it is unlikely that it will exactly follow the form used in software development. Hybrids will likely develop that suit the unique characteristics of drug discovery. We suggest potential motivations for organizations to join an open source drug discovery project. We also examine specific differences between software and medicines, specifically how the need for laboratories and physical goods will impact the model as well as the effect of patents.
Mosińska, Paula; Salaga, Maciej; Fichna, Jakub
Constipation-predominant irritable bowel syndrome (IBS-C) is a functional gastrointestinal (GI) disorder with an unknown etiology. A number of the drugs tested for IBS-C have also been applied to chronic constipation and chronic idiopathic constipation. Unfortunately, due to severe adverse effects, many drugs envisioned for IBS-C had been withdrawn from the market. Nevertheless, a number of potential new agents for this indication are now under development. The following review describes the most recently developed agents in preclinical as well as Phase 1 and Phase 2 clinical studies. Information was obtained from published literature, abstracts and the latest results found in Clinicaltrial.gov database. The authors put a special interest on glucagon-like peptide 1 analogue, bile acid modulators, serotonergic agents, guanylate cyclase C and cannabinoid antagonists. To enter the market, a newly-developed drug has to meet several criteria, such as good bioavailability or the absence of drug-related adverse events. Taking into account constipation and abdominal pain as the main symptoms in IBS-C, a novel successful drug is usually able to improve both at the same time. Four out of fifteen investigational drugs described in this paper belong to the serotonergic family and have a good prognosis to reach the market; still, more long-term clinical studies are warranted.
Dasan, K Priya; Rekha, C
The use of polymers and their microspheres in drug delivery is well known for they are being widely used in the field of drug delivery. The polymer entraps a drug which is to be released in a predesigned manner in the body through biodegradation. The blending of polymers is one way of modifying and enhancing the properties of polymer- based products which is also a cost effective procedure rather than developing a new product. The molecular weight of the polymer, the composition of the blend, the sphere porosity and size, and drug distribution are found to be controllable factors on which drug delivery depends. Polymer blends are obtained by allowing two polymers to combine as one material which has the advantage of two or more polymers. Polymer microspheres are small spherical particles with diameters in the micrometer range between 1μm to 1000μm which are manufactured from various natural and synthetic materials. Microspheres are used to administer medication in a rate- controlled manner and sometimes in a targeted manner. This review presents various polymer blend- combinations in different ratios, the different processing techniques adopted and the details of their characterization through examples found in a literature survey. The characterization of the different polymer blends or microspheres showed changes in structure, increase in drug loading, encapsulation efficiency, biocompatibility and low cytotoxicity.
Review of Theoretical Prediction Models for Organic Extract Metabolites, Effect of Drying Temperature on Smooth Muscle Relaxing Activity Induced by Organic Extracts Specially Cecropia Obtusifolia Portal and Web Server Predictors of Drug-Protein Interaction.
Aguirre-Crespo, Francisco; García-Mera, Xerardo; Guillén-Poot, Mónica Anahi; May-Díaz, Héctor Fernado; Tun-Suárez, Adrián; Aguirre-Crespo, A; Hernández-Rodríguez, J; Vergara-Galicia, Jorge; Rodríguez-López, V; Prado-Prado, Francisco J
Cecropia obtusifolia bertol is medicinal specie used in the treatment of diabetes mellitus and hypertension and it has scientific studies that support the traditional use. However, it is required to understand the influence of drying temperature on the yield and pharmacological activity. Drying rate, extraction efficiency, changes in the UV-Vis spectrum and estimating chlorophylls were stimulated with the increasing temperature. Finally, relaxant activity of vascular smooth muscle is increased by 70ºC and reducing ability by the method of CARF increases with temperature. Analytical studies are required to identify changes in the metabolic content and those that ensure the safety and efficacy for human consumption. In this sense, bioinformatic studies may be helpful. Studies such as QSAR can help us to study these metabolites derived from natural products. MIND-BETS model and NL MIND-BETS model to predict DPIs was introduced using MARCH-INSIDE (MI) software to calculate structural parameters for drugs and enzymes respectively. We firstly revised the state-of-art on the design with review of previous works with hypertension activity based on theoretical studies. A study, evaluating the effect of drying temperature of leaves of C. obtusifolia on the relaxing of vascular smooth muscle, antioxidant activity and the presence of chlorophylls, with a focus on Cecropia metabolites. Last, we carried out QSAR studies using MIND-BEST and NL MIND-BEST web servers in order to understand the essential metabolites structural requirement for binding with receptors for FDA proteins.
Full Text Available Daniel J Pilowsky1, Li-Tzy Wu21Departments of Epidemiology and Psychiatry, Columbia University, and the New York State Psychiatric Institute, New York City, NY, 2Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University Medical Center, Durham, NC, USABackground: The Patient Protection and Affordable Care Act of 2010 supports integration of substance abuse interventions and treatments into the mainstream health care system. Thus, effective screening and intervention for substance use disorders in health care settings is a priority.Objective: This paper reviews the prevalence of alcohol and drug use disorders (abuse or dependence in primary care settings and emergency departments, as well as current screening tools and brief interventions.Methods: MEDLINE was searched using the following keywords: alcohol use, alcohol use disorder, drug use, drug use disorder, screening, primary care, and emergency departments. Using the related-articles link, additional articles were screened for inclusion. This review focuses on alcohol and drug use and related disorders among adults in primary care settings.Conclusion: Screening, brief intervention, and referral for treatment are feasible and effective in primary care settings, provided that funding for screening is available, along with brief interventions and treatment facilities to which patients can be referred and treated promptly.Keywords: brief intervention, emergency departments
E. V. Moroz
Full Text Available Prevention of gastrointestinal tract (GIT complications is the most important element for the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs and low-dose aspirin (LDA. Proton pump inhibitors (PPIs have long been the only medication to prevent these complications. However, PPIs are only effective in preventing and treating upper GIT diseases (NSAID gastropathy rather than small intestinal injury (NSAID enteropathy. Rebamipide has emerged as a novel agent to protect the gastrointestinal mucosa today. The effect of the drug differs from that of PPIs: it is a typical gastroand enteroprotector that enhances the synthesis of endogenous prostaglandins and possesses a significant anti-inflammatory potential. Rebamipide has long been widely used by doctors inJapan,South Korea, andChinaas an effective and safe agent for the treatment of many diseases of the digestive system. There is a strong evidence base for the efficacy of rebamipide in preventing and treating NSAID gastropathy and NSAID enteropathy (including LDA-induced injuries. Controlled studies have found that the drug is not inferior to the classic gastroprotective agent misoprostol, significantly outperforming the latter in its tolerability. This review describes the mechanism of action of rebamipide and main clinical trials of its therapeutic effect in NSAID gastropathy and NSAID enteropathy.
Araújo, F; Cordeiro, I; Teixeira, F; Gonçalves, J; Fonseca, J E
To review current evidence concerning pharmacology of biosimilar candidates to be used in rheumatology. A PubMed search up to August 2013 was performed using relevant search terms to include all studies assessing pharmacological properties of biosimilar candidates to be used in rheumatology. Data on study characteristics, type of intervention, pharmacokinetics (PK), pharmacodynamics (PD) and bioequivalence ratios was extracted. Of 280 articles screened, 5 fulfilled our inclusion criteria. Two trials, PLANETAS and PLANETRA, compared CT-P13 and infliximab in patients with active ankylosing spondylitis and rheumatoid arthritis, respectively. PK bioequivalence was demonstrated in the phase 1 PLANETAS trial by highly comparable area under the curve (AUC) and maximum drug concentrations (Cmax), whose geometric mean ratios fell between the accepted bioequivalence range of 80-125%. Equivalence in efficacy and safety was demonstrated in the phase 3 PLANETRA trial. Two phase 1 trials comparing etanercept biosimilar candidates TuNEX and HD203 in healthy volunteers showed a high degree of similarity in AUC and Cmax, with respective geometric mean ratios between PK bioequivalence range. The last included trial referred to GP2013, a rituximab biosimilar candidate, which demonstrated PK and PD bioequivalence to reference product in three different dosing regimens in cynomolgus monkeys. Infliximab, etanercept and rituximab biosimilar candidates have demonstrated PK bioequivalence in the trials included in this review. CT-P13 has recently been approved for use in the European market and the remaining biosimilar candidates are currently being tested in patients with rheumatoid arthritis.
Synthetic or semi synthetic chemical drugs were used for treatment of Theileria species. These drugs include antimalarial, trypanocides and antibiotics, antiviral, etc. The aim of this study was to over-view chemical drugs tested for treatment of theileriosis. Keywords: Theileria, treatment, chemical drug ...
Merla, Anna; Schulz, Peter J; Gelatti, Umberto
Background Online pharmacies are companies that sell pharmaceutical preparations, including prescription-only drugs, on the Internet. Very little is known about this phenomenon because many online pharmacies operate from remote countries, where legal bases and business practices are largely inaccessible to international research. Objective The aim of the study was to perform an up-to-date and comprehensive review of the scientific literature focusing on the broader picture of online pharmacies by scanning several scientific and institutional databases, with no publication time limits. Methods We searched 4 electronic databases up to January 2011 and the gray literature on the Internet using the Google search engine and its tool Google Scholar. We also investigated the official websites of institutional agencies (World Health Organization, and US and European centers for disease control and drug regulation authorities). We focused specifically on online pharmacies offering prescription-only drugs. We decided to analyze and report only articles with original data, in order to review all the available data regarding online pharmacies and their usage. Results We selected 193 relevant articles: 76 articles with original data, and 117 articles without original data (editorials, regulation articles, or the like) including 5 reviews. The articles with original data cover samples of online pharmacies in 47 cases, online drug purchases in 13, consumer characteristics in 15, and case reports on adverse effects of online drugs in 12. The studies show that random samples with no specific limits to prescription requirements found that at least some websites sold drugs without a prescription and that an online questionnaire was a frequent tool to replace prescription. Data about geographical characteristics show that this information can be concealed in many websites. The analysis of drug offer showed that online a consumer can get virtually everything. Regarding quality of drugs
Orizio, Grazia; Merla, Anna; Schulz, Peter J; Gelatti, Umberto
Online pharmacies are companies that sell pharmaceutical preparations, including prescription-only drugs, on the Internet. Very little is known about this phenomenon because many online pharmacies operate from remote countries, where legal bases and business practices are largely inaccessible to international research. The aim of the study was to perform an up-to-date and comprehensive review of the scientific literature focusing on the broader picture of online pharmacies by scanning several scientific and institutional databases, with no publication time limits. We searched 4 electronic databases up to January 2011 and the gray literature on the Internet using the Google search engine and its tool Google Scholar. We also investigated the official websites of institutional agencies (World Health Organization, and US and European centers for disease control and drug regulation authorities). We focused specifically on online pharmacies offering prescription-only drugs. We decided to analyze and report only articles with original data, in order to review all the available data regarding online pharmacies and their usage. We selected 193 relevant articles: 76 articles with original data, and 117 articles without original data (editorials, regulation articles, or the like) including 5 reviews. The articles with original data cover samples of online pharmacies in 47 cases, online drug purchases in 13, consumer characteristics in 15, and case reports on adverse effects of online drugs in 12. The studies show that random samples with no specific limits to prescription requirements found that at least some websites sold drugs without a prescription and that an online questionnaire was a frequent tool to replace prescription. Data about geographical characteristics show that this information can be concealed in many websites. The analysis of drug offer showed that online a consumer can get virtually everything. Regarding quality of drugs, researchers very often found
Personalized medicine and orphan drugs share many characteristics-both target small patient populations, have uncertainties regarding efficacy and safety at payer submission, and frequently have high prices. Given personalized medicine's rising importance, this review summarizes international coverage and pricing strategies for personalized medicine and orphan drugs as well as their impact on therapy development incentives, payer budgets, and therapy access and utilization. PubMed, Health Policy Reference Center, EconLit, Google Scholar, and references were searched through February 2017 for articles presenting primary data. Sixty-nine articles summarizing 42 countries' strategies were included. Therapy evaluation criteria varied between countries, as did patient cost-share. Payers primarily valued clinical effectiveness; cost was only considered by some. These differences result in inequities in orphan drug access, particularly in smaller and lower-income countries. The uncertain reimbursement process hinders diagnostic testing. Payer surveys identified lack of comparative effectiveness evidence as a chief complaint, while manufacturers sought more clarity on payer evidence requirements. Despite lack of strong evidence, orphan drugs largely receive positive coverage decisions, while personalized medicine diagnostics do not. As more personalized medicine and orphan drugs enter the market, registries can provide better quality evidence on their efficacy and safety. Payers need systematic assessment strategies that are communicated with more transparency. Further studies are necessary to compare the implications of different payer approaches. Copyright © 2017 Elsevier B.V. All rights reserved.
Stafford, Andrew C; Tenni, Peter C; Peterson, Gregory M
OBJECTIVE: In Australia, accredited pharmacists perform medication reviews for patients to identify and resolve drug-related problems. We analysed the drug-related problems identified in reviews for both home-dwelling and residential care-facility patients. The objective of this study was to exam......OBJECTIVE: In Australia, accredited pharmacists perform medication reviews for patients to identify and resolve drug-related problems. We analysed the drug-related problems identified in reviews for both home-dwelling and residential care-facility patients. The objective of this study....... These reviews had been self-selected by pharmacists and submitted as part of the reaccreditation process to the primary body responsible for accrediting Australian pharmacists to perform medication reviews. The drug-related problems identified in each review were classified by type and drugs involved. MAIN...... OUTCOME MEASURE: The number and nature of drug-related problems identified in pharmacist-conducted medication reviews. RESULTS: There were 1,038 drug-related problems identified in 234 medication reviews (mean 4.6 (+/-2.2) problems per review). The number of problems was higher (4.9 +/- 2.0 vs. 3.9 +/- 2...
Campillos, Monica; Kuhn, Michael; Gavin, Anne-Claude
Targets for drugs have so far been predicted on the basis of molecular or cellular features, for example, by exploiting similarity in chemical structure or in activity across cell lines. We used phenotypic side-effect similarities to infer whether two drugs share a target. Applied to 746 marketed...... drugs, a network of 1018 side effect-driven drug-drug relations became apparent, 261 of which are formed by chemically dissimilar drugs from different therapeutic indications. We experimentally tested 20 of these unexpected drug-drug relations and validated 13 implied drug-target relations by in vitro...... binding assays, of which 11 reveal inhibition constants equal to less than 10 micromolar. Nine of these were tested and confirmed in cell assays, documenting the feasibility of using phenotypic information to infer molecular interactions and hinting at new uses of marketed drugs....
Full Text Available Non-steroidal anti-inflammatory drugs like ibuprofen or indomethacin are commonly prescribed drugs to induce pharmacologic closure of a patent ductus arteriosus in preterm neonates. Based on a recently published Cochrane meta-analysis, both drugs are equally effective to induce closure. Drug choice can therefore be based on differences in side effects or pharmaco-economic arguments. The current review quantifies the negative impact of either ibuprofen or indomethacin on renal function, including diuresis, glomerular filtration rate and renal tubular function. Both ibuprofen and indomethacin have a quantifiable impact on renal function. However, compared to ibuprofen, the negative impact of indomethacin is more pronounced.
Systematic review and cost-effectiveness evaluation of 'pill-in-the-pocket' strategy for paroxysmal atrial fibrillation compared to episodic in-hospital treatment or continuous antiarrhythmic drug therapy.
Saborido, C Martin; Hockenhull, J; Bagust, A; Boland, A; Dickson, R; Todd, D
Atrial fibrillation (AF) is a tachyarrhythmia characterised by uncoordinated atrial activation with consequent deterioration of impairment of atrial function and a rapid, irregular heartbeat. The annual incidence rate of paroxysmal AF (PAF) has been estimated at 1.0 per 1000 person-years (95% confidence interval 0.9 to 1.1), and reported prevalence rates show wide variations depending on age and country. Conventional treatment strategies for PAF focus on the suppression of paroxysms of AF and return to normal sinus rhythm. To summarise the results of the rapid reviews of the clinical effectiveness and cost-effectiveness literature describing the pill-in-the-pocket (PiP) approach for the treatment of patients with PAF; and to develop an economic model to assess the cost-effectiveness of PiP compared with in-hospital treatment (IHT) or continuous antiarrhythmic drugs (AADs) for the treatment of patients with PAF. Ovid MEDLINE and Ovid OLDMEDLINE 1950 to present with Daily Update were searched. The following electronic databases were searched for ongoing trials: Health Services Research Projects in Progress, ClinicalTrials.gov, metaRegister of Current Controlled Trials, BioMed Central, World Health Organization International Clinical Trials Registry Platform, ClinicalStudyResults.org and the National Library of Medicine Gateway. Inclusion criteria, which included patients suffering from PAF, were independently applied to all identified references by two reviewers (JH and CMS). Electronic searches were conducted to identify clinical effectiveness and cost-effectiveness evidence describing the use of a PiP strategy for the treatment of PAF, published since the release of the Royal College of Physicians' national guidelines on AF in June 2006. A Markov model was constructed to examine differences between three PAF strategies (PiP, AAD and IHT) in terms of cost per quality-adjusted life-year (QALY). A Markov model structure was chosen because it is assumed that PAF is a
Palleria, Caterina; Cozza, Giuseppe; Khengar, Rajeshree; Libri, Vincenzo; De Sarro, Giovambattista
Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice. However, the main cause of treatment failure is still poor patient compliance due to the occurrence of adverse drug reactions (ADRs) that lead to treatment withdrawal in about 25% of cases before achieving maximal efficacy, and is associated with increasing health care costs. In this Review, we conducted an online database search using Medline, PubMed, Embase, and the Cochrane Online Library to review the available studies highlighting the clinical relevance of side effects, pharmacological interactions, safety and tolerability of the newest AEDs: Brivaracetam (BRV), Cannabidiol (CBD), Eslicarbazepine acetate (ESL), Lacosamide (LCM), and Perampanel (PER). The principal benefit of the newest AEDs, in addition to reduced frequency and seizure severity, is the low number and severity of ADRs reported compared to more historic drugs. Early detection of ADRs could lead to an improvement in patients' quality of life, therefore it is important to monitor ADRs and to adequately perform post marketing surveillance in the clinical practice setting. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Belleudi, Valeria; Trotta, Francesco; Vecchi, Simona; Amato, Laura; Addis, Antonio; Davoli, Marina
Several drugs share the same therapeutic indication, including those undergoing patent expiration. Concerns on the interchangeability are frequent in clinical practice, challenging the evaluation of switchability through observational research. To conduct a scoping review of observational studies on drug switchability to identify methodological strategies adopted to deal with bias and confounding. We searched PubMed, EMBASE, and Web of Science (updated 1/31/2017) to identify studies evaluating switchability in terms of effectiveness/safety outcomes or compliance. Three reviewers independently screened studies extracting all characteristics. Strategies to address confounding, particularly, previous drug use and switching reasons were considered. All findings were summarized in descriptive analyses. Thirty-two studies, published in the last 10 years, met the inclusion criteria. Epilepsy, cardiovascular and rheumatology were the most frequently represented clinical areas. 75% of the studies reported data on effectiveness/safety outcomes. The most frequent study design was cohort (65.6%) followed by case-control (21.9%) and self-controlled (12.5%). Case-control and case-crossover studies showed homogeneous methodological strategies to deal with bias and confounding. Among cohort studies, the confounding associated with previous drug use was addressed introducing variables in multivariate model (47.3%) or selecting only adherent patients (14.3%). Around 30% of cohort studies did not report reasons for switching. In the remaining 70%, clinical parameters or previous occurrence of outcomes were measured to identify switching connected with lack of effectiveness or adverse events. This study represents a starting point for researchers and administrators who are approaching the investigation and assessment of issues related to interchangeability of drugs. Copyright © 2018. Published by Elsevier Inc.
Full Text Available Hossein Jahangirian,1 Ensieh Ghasemian Lemraski,2 Thomas J Webster,1 Roshanak Rafiee-Moghaddam,3 Yadollah Abdollahi4 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2Department of Chemistry, Faculty of Science, Ilam University, Ilam, Iran; 3School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Selangor, 4Department of Electrical Engineering, Faculty of Engineering, University of Malaysia, Kuala Lumpur, Malaysia Abstract: This review discusses the impact of green and environmentally safe chemistry on the field of nanotechnology-driven drug delivery in a new field termed “green nanomedicine”. Studies have shown that among many examples of green nanotechnology-driven drug delivery systems, those receiving the greatest amount of attention include nanometal particles, polymers, and biological materials. Furthermore, green nanodrug delivery systems based on environmentally safe chemical reactions or using natural biomaterials (such as plant extracts and microorganisms are now producing innovative materials revolutionizing the field. In this review, the use of green chemistry design, synthesis, and application principles and eco-friendly synthesis techniques with low side effects are discussed. The review ends with a description of key future efforts that must ensue for this field to continue to grow. Keywords: green chemistry, cancer, drug delivery, nanoparticle
Mauskopf, Josephine; Earnshaw, Stephanie
A budget-impact analysis is required by many jurisdictions when adding a new drug to the formulary. However, previous reviews have indicated that adherence to methodological guidelines is variable. In this methodological review, we assess the extent to which US budget-impact analyses for new drugs use recommended practices. We describe recommended practice for seven key elements in the design of a budget-impact analysis. Targeted literature searches for US studies reporting estimates of the budget impact of a new drug were performed and we prepared a summary of how each study addressed the seven key elements. The primary finding from this review is that recommended practice is not followed in many budget-impact analyses. For example, we found that growth in the treated population size and/or changes in disease-related costs expected during the model time horizon for more effective treatments was not included in several analyses for chronic conditions. In addition, all drug-related costs were not captured in the majority of the models. Finally, for most studies, one-way sensitivity and scenario analyses were very limited, and the ranges used in one-way sensitivity analyses were frequently arbitrary percentages rather than being data driven. The conclusions from our review are that changes in population size, disease severity mix, and/or disease-related costs should be properly accounted for to avoid over- or underestimating the budget impact. Since each budget holder might have different perspectives and different values for many of the input parameters, it is also critical for published budget-impact analyses to include extensive sensitivity and scenario analyses based on realistic input values.
Adusumalli, Swarnaseetha; Lee, HueyTyng; Hoi, Qiangze; Koo, Si-Lin; Tan, Iain Beehuat
Background Some health websites provide a public forum for consumers to post ratings and reviews on drugs. Drug reviews are easily accessible and comprehensible, unlike clinical trials and published literature. Because the public increasingly uses the Internet as a source of medical information, it is important to know whether such information is reliable. Objective We aim to examine whether Web-based consumer drug ratings and reviews can be used as a resource to compare drug performance. Methods We analyzed 103,411 consumer-generated reviews on 615 drugs used to treat 249 disease conditions from the health website WebMD. Statistical analysis identified 427 drug pairs from 24 conditions for which two drugs treating the same condition had significantly and substantially different satisfaction ratings (with at least a half-point difference between Web-based ratings and Paddictive properties were rated higher than their counterparts in Web-based reviews, and (3) second-line or alternative drugs were rated higher. In addition, Web-based ratings indicated drug delivery problems. If FDA black box warning labels are used to resolve disagreements between publications and online trends, the concordance rate increases to 71% (55/77) (Pmanufacturers to assess the performance of a drug. However, one should be cautious to rely solely on consumer reviews as ratings can be strongly influenced by the consumer experience. PMID:26319108
Guzman-Aranguez, Ana; Fonseca, Begoña; Carracedo, Gonzalo; Martin-Gil, Alba; Martinez-Aguila, Alejandro; Pintor, Jesús
Dry eye disease affects a substantial segment of the word population with increasing frequency. It is a multifactorial disease of the ocular surface and tear film, which causes ocular discomfort, visual disturbances, and tear instability with potential damage to the cornea and conjunctiva. Because of its multifactorial etiology, the use of different pharmacological treatment for dry eye treatment has been proposed, which include anti-inflammatory molecules, lubricants or comfort agents, and secretagogues. However, in some cases these pharmacological approaches only relieve symptoms temporarily, and consequently, eye care professionals continue to have difficulties managing dry eye. To improve pharmacological therapy that allows a more efficient and long-term action, effective ocular drug delivery of the currently available drugs for dry eye treatment is required. Contact lenses are emerging as alternative ophthalmic drugs delivery systems that provide an increased residence time of the drug at the eye, thus leading to enhanced bioavailability and more convenient and efficacious therapy. In this article, we reviewed the different techniques used to prepare contact lens-based drug delivery systems and focused on articles that describe the delivery of compounds for dry eye treatment through contact lenses.
Drug resistance is a serious limitation to the effective treatment of a number of common malignancies. Thirty years of laboratory and clinical research have greatly defined the molecular alterations underlying many drug resistance processes in cancer. Based on this knowledge, strategies to overcome the impact of resistance and increase the efficacy of cancer treatment have been translated from laboratory models to clinical trials. This article reviews laboratory and, in particular, clinical attempts at drug resistance circumvention from early forays in the inhibition of cellular efflux pump-mediated drug resistance through to more selective circumvention agent strategies and into inhibition of the other important mechanisms which can allow cancer cells to survive therapy, such as apoptosis resistance. Despite some promising results to date, resistance inhibition strategies have largely failed due to poor understanding of the pharmacology, dynamics and complexity of the resistance phenotype. With the realisation that new molecularly-targeted agents can also be rendered ineffectual by the actions of resistance mechanisms, a major focus is once again emerging on identifying new strategies/pharmaceuticals which can augment the activity of the arsenal of more conventional cytotoxics and newer targeted anti-cancer drugs. Future tactical directions where old and new resistance strategies may merge to overcome this challenge are discussed.
Effect of Nonsteroidal Anti-inflammatory Drug as an Oral Premedication on the Anesthetic Success of Inferior Alveolar Nerve Block in Treatment of Irreversible Pulpitis: A Systematic Review with Meta-analysis and Trial Sequential Analysis.
Nagendrababu, Venkateshbabu; Pulikkotil, Shaju Jacob; Veettil, Sajesh K; Teerawattanapong, Nattawat; Setzer, Frank C
Successful anesthesia with an inferior alveolar nerve block (IANB) is imperative for treating patients with irreversible pulpitis in mandibular teeth. This systematic review assessed the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) as oral premedications on the success of IANBs in irreversible pulpitis. Three databases were searched to identify randomized clinical trials (RCTs) published up until September 2017. Retrieved RCTs were evaluated using the revised Cochrane Risk of Bias Tool. The primary efficacy outcome of interest was the success rate of IANB anesthesia. Meta-analytic estimates (risk ratio [RR] with 95% confidence intervals [CIs]) performed using a random effects model and publication bias determined using funnel plot analysis were assessed. Random errors were evaluated with trial sequential analyses, and the quality of evidence was appraised using a Grading of Recommendations, Assessment, Development and Evaluation approach. Thirteen RCTs (N = 1034) were included. Eight studies had low risk of bias. Statistical analysis of good-quality RCTs showed a significant beneficial effect of any NSAID in increasing the anesthetic success of IANBs compared with placebo (RR = 1.92; 95% CI, 1.55-2.38). Subgroup analyses showed a similar beneficial effect for ibuprofen, diclofenac, and ketorolac (RR = 1.83 [95% CI, 1.43-2.35], RR = 2.56 [95% CI, 1.46-4.50], and RR = 2.07 [95% CI, 1.47-2.90], respectively). Dose-dependent ibuprofen >400 mg/d (RR = 1.85; 95% CI, 1.39-2.45) was shown to be effective; however, ibuprofen ≤400 mg/d showed no association (RR = 1.78; 95% CI, 0.90-3.55). TSA confirmed conclusive evidence for a beneficial effect of NSAIDs for IANB premedication. The Grading of Recommendations, Assessment, Development and Evaluation approach did not reveal any concerns regarding the quality of the results. Oral premedication with NSAIDs and ibuprofen (>400 mg/d) increased the anesthetic success of IANBs in patients with irreversible
Amit Chandna; Deepa Batra; Satinder Kakar; Ramandeep Singh
Novel drug delivery system aims to deliver the drug at a rate directed by the needs of the body during the period of treatment, and target the active entity to the site of action. A number of novel drug delivery systems have emerged encompassing various routes of administration, to achieve controlled and targeted drug delivery, magnetic micro carriers being one of them. Magnetic microsphere is newer approach in pharmaceutical field. Magnetic microspheres as an alternative to traditional ra...
Effect of Contemporary Social Environment, Drug Abuse and Cultism on the Health of ... This health situation comes as results of substance abuse which these ... the patent medicine stores, from hard drugs like (marijuana, cannabis) or others ...
... another test, performed by the gas chromatography/mass spectrometry method (GC/MS). This procedure is... 10 Energy 4 2010-01-01 2010-01-01 false Medical review of results of tests for illegal drug use... Procedures § 707.13 Medical review of results of tests for illegal drug use. (a) All test results shall be...
Andresen, Thomas Lars; Thompson, David H.; Kaasgaard, Thomas
-based strategies are particularly interesting as they require no prior knowledge of the tumour localization. The basis of this review is an evaluation of the current status of drug delivery strategies focused on triggered drug release by disease-associated enzymes. We limit ourselves to reviewing the liposome...
Mumoli, Laura; Ciriaco, Miriam; Gambardella, Antonio; Bombardiere, Giuseppe Nicodemo; Valentino, Paola; Palleria, Caterina; Labate, Angelo; Russo, Emilio
β-Interferon therapy is known to be a potential trigger of suicidal behavior, but this effect has not been previously reported for other multiple sclerosis (MS) treatments, such as, natalizumab. Here we report the case history of a 32-year-old woman affected by relapsing-remitting MS, who attempted suicide during natalizumab treatment. This case suggests that a suicidal ideation might be a rare side effect of natalizumab. Nevertheless, this case represents the first evidence of the new adverse drug reaction related to natalizumab treatment. We should alert clinicians to be aware of the possibility of paradoxical activation of suicidality during its therapeutic use. The main purpose of the present article is to use this case to review the possible relationship between suicidal behavior and drugs.
Prescrire's analyses showed that the quality of drug packaging in 2010 still left much to be desired. Potentially dangerous packaging remains a significant problem: unclear labelling is source of medication errors; dosing devices for some psychotropic drugs create a risk of overdose; child-proof caps are often lacking; and too many patient information leaflets are misleading or difficult to understand. Everything that is needed for safe drug packaging is available; it is now up to regulatory agencies and drug companies to act responsibly. In the meantime, health professionals can help their patients by learning to identify the pitfalls of drug packaging and providing safe information to help prevent medication errors.
Chen Xiaojing; Jin Yizun
Hypoxia is a feature that exists in most solid tumors. Bio-reductive drugs are pro-drugs that can selectively target the hypoxia cells in tumors. In reductive environment, they are reductively metabolized to generate toxic species. There are 3 main classes of bio-reductive drugs: the nitro-aromatics, N-oxides and quinones. Recently, bio-reductive drugs were combined with GDEPT for the treatment of cancer, in addition to radiation and the chemotherapeutic agents. Bio-reductive drugs will play a significant role in future cancer therapy
Dhaval A. Pate; M. R. Pate; K. R. Pate; N. M. Pate
Within the oral mucosal cavity, the buccal region offers an attractive route of administration for systemic drug delivery. The mucosa has a rich blood supply and it is relatively permeable. It is the objective of this article to review buccal drug delivery by discussing the structure and environment of the oral mucosa and the experimental methods used in assessing buccal drug permeation/absorption. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based deliv...
Shojaei, A H
Within the oral mucosal cavity, the buccal region offers an attractive route of administration for systemic drug delivery. The mucosa has a rich blood supply and it is relatively permeable. It is the objective of this article to review buccal drug delivery by discussing the structure and environment of the oral mucosa and the experimental methods used in assessing buccal drug permeation/absorption. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based delivery systems
Full Text Available The range of osteoporosis treatments is increasingly large and, like any disease, the pharmacological management of patients should involve a risk/benefit evaluation to attain the greatest reduction in risk of fracture with the lowest incidence of adverse events. The aim of this review is to critically appraise the literature about the safety issues of the main pharmacological treatments of osteoporosis. This document is the result of a consensus of experts based on a systematic review of regulatory documents, randomized controlled trials, metaanalyses, pharmacovigilance surveys and case series related to possible adverse drug reactions to osteoporosis treatment with calcium and vitamin D supplements, bisphosphonates, strontium ranelate, selective estrogen receptor modulators, denosumab, and teriparatide. As expected, randomized controlled trials showed only the most common adverse events due to the samples size and the short observation time. Case series and observational studies are able to provide data about uncommon side effects, but in some cases a sure cause-effect relationship needs still to be confirmed. Consistently with methodological limitations, the newer drugs have a tolerance profile that has not been fully explored yet. Osteoporosis treatments showed an overall good tolerance profile with rare serious adverse events that, however, must be well known by the clinician who prescribes these drugs. The concern about possible adverse events should be weighed against the reduction of morbidity and mortality associated with a significant fracture risk reduction.
Thevis, Mario; Kuuranne, Tiia; Walpurgis, Katja; Geyer, Hans; Schänzer, Wilhelm
The aim of improving anti-doping efforts is predicated on several different pillars, including, amongst others, optimized analytical methods. These commonly result from exploiting most recent developments in analytical instrumentation as well as research data on elite athletes' physiology in general, and pharmacology, metabolism, elimination, and downstream effects of prohibited substances and methods of doping, in particular. The need for frequent and adequate adaptations of sports drug testing procedures has been incessant, largely due to the uninterrupted emergence of new chemical entities but also due to the apparent use of established or even obsolete drugs for reasons other than therapeutic means, such as assumed beneficial effects on endurance, strength, and regeneration capacities. Continuing the series of annual banned-substance reviews, literature concerning human sports drug testing published between October 2014 and September 2015 is summarized and reviewed in reference to the content of the 2015 Prohibited List as issued by the World Anti-Doping Agency (WADA), with particular emphasis on analytical approaches and their contribution to enhanced doping controls. Copyright © 2016 John Wiley & Sons, Ltd.
Zuleta-Alarcón, Alix; Coffman, John C; Soghomonyan, Suren; Papadimos, Thomas J; Bergese, Sergio D; Moran, Kenneth R
The objective of this narrative review is to provide an overview of the problem of non-opioid anesthetic drug abuse among anesthesia care providers (ACPs) and to describe current approaches to screening, therapy, and rehabilitation of ACPs suffering from non-opioid anesthetic drug abuse. We first performed a search of all literature available on PubMed prior to April 11, 2016. The search was limited to articles published in Spanish and English, and the following key words were used: anesthesiology, anesthesia personnel, AND substance-related disorders. We also searched Ovid MEDLINE ® databases from 1946-April 11, 2016 using the following search terms: anesthesiology OR anesthesia, OR nurse anesthetist OR anesthesia care provider OR perioperative nursing AND substance-related disorders. Despite an increased awareness of drug abuse among ACPs and improvements in preventive measures, the problem of non-opioid anesthetic drug abuse remains significant. While opioids are the most commonly abused anesthesia medications among ACPs, the abuse of non-opioid anesthetics is a significant cause of morbidity, mortality, and professional demise. Early detection, effective therapy, and long-term follow-up help ACPs cope more effectively with the problem and, when possible, resume their professional activities. There is insufficient evidence to determine the ability of ACPs to return safely to anesthesia practice after rehabilitation, though awareness of the issue and ongoing treatment are necessary to minimize patient risk from potentially related clinical errors.
Kuhn, Michael; Al Banchaabouchi, Mumna; Campillos, Monica
Side effect similarities of drugs have recently been employed to predict new drug targets, and networks of side effects and targets have been used to better understand the mechanism of action of drugs. Here, we report a large-scale analysis to systematically predict and characterize proteins...... that cause drug side effects. We integrated phenotypic data obtained during clinical trials with known drug-target relations to identify overrepresented protein-side effect combinations. Using independent data, we confirm that most of these overrepresentations point to proteins which, when perturbed, cause......) is responsible for hyperesthesia in mice, which, in turn, can be prevented by a drug that selectively inhibits HTR7. Taken together, we show that a large fraction of complex drug side effects are mediated by individual proteins and create a reference for such relations....
Setlow, Barry; Mendez, Ian A; Mitchell, Marci R; Simon, Nicholas W
Drug-addicted individuals show high levels of impulsive choice, characterized by preference for small immediate over larger but delayed rewards. Although the causal relationship between chronic drug use and elevated impulsive choice in humans has been unclear, a small but growing body of literature over the past decade has shown that chronic drug administration in animal models can cause increases in impulsive choice, suggesting that a similar causal relationship may exist in human drug users. This article reviews this literature, with a particular focus on the effects of chronic cocaine administration, which have been most thoroughly characterized. The potential mechanisms of these effects are described in terms of drug-induced neural alterations in ventral striatal and prefrontal cortical brain systems. Some implications of this research for pharmacological treatment of drug-induced increases in impulsive choice are discussed, along with suggestions for future research in this area.
Maher, Chris G; Ferreira, Manuela L; Ferreira, Paulo H; Hancock, Mark; Oliveira, Vinicius C; McLachlan, Andrew J; Koes, Bart
Objective To investigate the efficacy and tolerability of analgesic and adjuvant pain drugs typically administered in primary care for the management of patients with sciatica. Design Systematic review. Data source International Pharmaceutical Abstracts, PsycINFO, Medline, Embase, Cochrane Central Register of Clinical Trials (CENTRAL), CINAHL, and LILACS. Study selection Randomised controlled trials assessing the efficacy and tolerability of drugs versus placebo or other treatment for sciatica. Data extraction Two independent reviewers extracted data and assessed methodological quality using the PEDro scale. Pain and disability outcomes were converted to a common 0 to 100 scale. Data were pooled with a random effects model, and the GRADE approach was used in summary conclusions. Results Twenty three published reports met the inclusion criteria. The evidence to judge the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antidepressants, anticonvulsants, muscle relaxants, and opioid analgesics ranged from moderate to low quality. Most of the pooled estimates did not favour the active treatment over placebo. The pooled results of two trials of corticosteroids (mean difference in overall and leg pain −12.2, 95% confidence interval −20.9 to −3.4) and a single trial of the anticonvulsant gabapentin for chronic sciatica (mean difference in overall pain relief −26.6, −38.3 to −14.9) showed some benefits but only in the short term. The median rate of adverse events was 17% (interquartile range 10-30%) for the active drugs and 11% (3-23%) for placebo. Trial limitations included failure to use validated outcome measures, lack of long term follow-up, and small sample size. Conclusions As the existing evidence from clinical trials is of low quality, the efficacy and tolerability of drugs commonly prescribed for the management of sciatica in primary care is unclear. PMID:22331277
Wang, Xiujuan; Thijssen, Bram; Yu, Haiyuan
Author Summary The ultimate goal of medical research is to develop effective treatments for disease with minimal side effects. Currently, about 20% of drug candidates failed at clinical trial phases II and III due to safety issues. Therefore, understanding the determining factors of drug side effects is of paramount importance to human health and the pharmaceutical industry. Here, we present the first systematic study to uncover key factors leading to drug side effects within the framework of...
Full Text Available The primary task of the lungs is to maintain oxygenation of the blood and eliminate carbon dioxide through the network of capillaries alongside alveoli. This is maintained by utilising ventilatory reserve capacity and by changes in lung mechanics. Induction of anaesthesia impairs pulmonary functions by the loss of consciousness, depression of reflexes, changes in rib cage and haemodynamics. All drugs used during anaesthesia, including inhalational agents, affect pulmonary functions directly by acting on respiratory system or indirectly through their actions on other systems. Volatile anaesthetic agents have more pronounced effects on pulmonary functions compared to intravenous induction agents, leading to hypercarbia and hypoxia. The posture of the patient also leads to major changes in pulmonary functions. Anticholinergics and neuromuscular blocking agents have little effect. Analgesics and sedatives in combination with volatile anaesthetics and induction agents may exacerbate their effects. Since multiple agents are used during anaesthesia, ultimate effect may be different from when used in isolation. Literature search was done using MeSH key words 'anesthesia', 'pulmonary function', 'respiratory system' and 'anesthesia drugs and lungs' in combination in PubMed, Science Direct and Google Scholar filtered by review and research articles sorted by relevance.
Full Text Available Cachexia is a weight-loss process caused by an underlying chronic disease such as cancer, chronic heart failure, chronic obstructive pulmonary disease, or rheumatoid arthritis. It leads to changes in body structure and function that may influence the pharmacokinetics of drugs. Changes in gut function and decreased subcutaneous tissue may influence the absorption of orally and transdermally applied drugs. Altered body composition and plasma protein concentration may affect drug distribution. Changes in the expression and function of metabolic enzymes could influence the metabolism of drugs, and their renal excretion could be affected by possible reduction in kidney function. Because no general guidelines exist for drug dose adjustments in cachectic patients, we conducted a systematic search to identify articles that investigated the pharmacokinetics of drugs in cachectic patients.
Kharat, Rekha; Bathe, Ritesh Suresh
Transdermal drug delivery system was introduced to overcome the difficulties of drug delivery through oral route. Despite their relatively higher costs, transdermal delivery systems have proved advantageous for delivery of selected drugs, such as estrogens, testosterone, clonidine and nitro-glycerine. Transdermal delivery provides a leading edge over injectable and oral routes by increasing patient compliance and avoiding first pass metabolism respectively. Topical administration of therap...
Ismael Laurindo Costa Junior; Universidade Tecnológica Federal do Paraná; Adelmo L. Pletsch; Universidade Tecnológica Federal do Paraná; Yohandra R. Torres; Universidade Estadual do Centro Oeste
Lately, the identification of emerging pollutants in environmental matrices has become frequent. Among these pollutants, the presence of drugs is highly relevant, because these categories of contaminants comprised thousands of active substances highly consumed worldwide. In the last decades, there has been a significant increase in the prescription and consumption of neuroactive drugs, such as antidepressants, and due to their direct action on the nervous system, neuroactive drugs are cited a...
Rinky Maurya; Dr. Pramod Kumar Sharma; Rishabha Malviya
Spansules are a dosage form which was considered as one of the Advanced Drug Delivery System. Multidrug preparations can be delivered easily by spansules or granules in capsule technology. This type of delivery system designed to release a drug or a medicament at two or more different rates or in different span of time. A quick/slow release system provides an initial release of drug followed by a constant rate of drug release over a extended period or a defined period of time and in slow/quic...
Blackstone, Erwin A; Fuhr, Joseph P; Pociask, Steve
Counterfeit drugs comprise an increasing percentage of the US drug market and even a larger percentage in less developed countries. Counterfeit drugs involve both lifesaving and lifestyle drugs. To review the health and economic consequences of counterfeit drugs on the US public and on the healthcare system as a whole. This comprehensive review of the literature encompassed a search of MEDLINE/PubMed, Google Scholar, and ProQuest using the keywords "counterfeit drugs," "counterfeit medicines," "fake drugs," and "fake medicines." A search of the various FiercePharma daily newsletter series on the healthcare market was also conducted. In addition, the US Food and Drug Administration and the World Health Organization websites were reviewed for additional information. The issue of counterfeit drugs has been growing in importance in the United States, with the supply of these counterfeit drugs coming from all over the world. Innovation is important to economic growth and US competitiveness in the global marketplace, and intellectual property protections provide the ability for society to prosper from innovation. Especially important in terms of innovation in healthcare are the pharmaceutical and biopharmaceutical industries. In addition to taking income from consumers and drug companies, counterfeit drugs also pose health hazards to patients, including death. The case of bevacizumab (Avastin) is presented as one recent example. Internet pharmacies, which are often the source of counterfeit drugs, often falsely portray themselves as Canadian, to enhance their consumer acceptance. Adding to the problems are drug shortages, which facilitate access for counterfeits. A long and convoluted supply chain also facilitates counterfeits. In addition, the wholesale market involving numerous firms is a convenient target for counterfeit drugs. Trafficking in counterfeits can be extremely profitable; detection of counterfeits is difficult, and the penalties are modest. Counterfeit
Obesity has been a main risk for the development of diabetes mellitus, cardiovascular diseases and many other chronic problems worldwide. Lifestyle modification is the best way to lose weight but very hard to implement, thus pharmacotherapy is regarded as a good add-on to dietary and lifestyle therapies. This review provides an overview of the olistat, a drug for obesity approved by FDA, about its mechanism of action, efficacy for obesity and some other diseases including cardiovascular disease, type 2 diabetes and some cancers, as well as its safety and adverse effects.
The in vivo effect of co-administration of the NSAIDs (acetyl salicylic acid (ASA), piroxicam, indomethacin and paracetamol) with ciprofloxacin against Staphylococcus aureus in Swiss mice, rendered neutropenic by pre-treatment with cyclophosphamide, was evaluated using animal model. Using the murine thigh model, ...
Diniz, Tâmara Coimbra; Pinto, Tiago Coimbra Costa; Menezes, Paula Dos Passos; Silva, Juliane Cabral; Teles, Roxana Braga de Andrade; Ximenes, Rosana Christine Cavalcanti; Guimarães, Adriana Gibara; Serafini, Mairim Russo; Araújo, Adriano Antunes de Souza; Quintans Júnior, Lucindo José; Almeida, Jackson Roberto Guedes da Silva
Depression is a serious mood disorder and is one of the most common mental illnesses. Despite the availability of several classes of antidepressants, a substantial percentage of patients are unresponsive to these drugs, which have a slow onset of action in addition to producing undesirable side effects. Some scientific evidence suggests that cyclodextrins (CDs) can improve the physicochemical and pharmacological profile of antidepressant drugs (ADDs). The purpose of this paper is to disclose current data technology prospects involving antidepressant drugs and cyclodextrins. Areas covered: We conducted a patent review to evaluate the antidepressive activity of the compounds complexed in CDs, and we analyzed whether these complexes improved their physicochemical properties and pharmacological action. The present review used 8 specialized patent databases for patent research, using the term 'cyclodextrin' combined with 'antidepressive agents' and its related terms. We found 608 patents. In the end, considering the inclusion criteria, 27 patents reporting the benefits of complexation of ADDs with CDs were included. Expert opinion: The use of CDs can be considered an important tool for the optimization of physicochemical and pharmacological properties of ADDs, such as stability, solubility and bioavailability.
Full Text Available The molecular mechanisms that translate drug treatment into beneficial and unwanted effects are largely unknown. We present here a novel approach to detect gene-drug and gene-side effect associations based on the phenotypic similarity of drugs and single gene perturbations in mice that account for the polypharmacological property of drugs. We scored the phenotypic similarity of human side effect profiles of 1,667 small molecules and biologicals to profiles of phenotypic traits of 5,384 mouse genes. The benchmarking with known relationships revealed a strong enrichment of physical and indirect drug-target connections, causative drug target-side effect links as well as gene-drug links involved in pharmacogenetic associations among phenotypically similar gene-drug pairs. The validation by in vitro assays and the experimental verification of an unknown connection between oxandrolone and prokineticin receptor 2 reinforces the ability of this method to provide new molecular insights underlying drug treatment. Thus, this approach may aid in the proposal of novel and personalized treatments.
McCall, Ann-Kathrin; Bade, Richard; Kinyua, Juliet; Lai, Foon Yin; Thai, Phong K; Covaci, Adrian; Bijlsma, Lubertus; van Nuijs, Alexander L N; Ort, Christoph
Wastewater-based epidemiology (WBE) applies advanced analytical methods to quantify drug residues in wastewater with the aim to estimate illicit drug use at the population level. Transformation processes during transport in sewers (chemical and biological reactors) and storage of wastewater samples before analysis are expected to change concentrations of different drugs to varying degrees. Ignoring transformation for drugs with low to medium stability will lead to an unknown degree of systematic under- or overestimation of drug use, which should be avoided. This review aims to summarize the current knowledge related to the stability of commonly investigated drugs and, furthermore, suggest a more effective approach to future experiments. From over 100 WBE studies, around 50 mentioned the importance of stability and 24 included tests in wastewater. Most focused on in-sample stability (i.e., sample preparation, preservation and storage) and some extrapolated to in-sewer stability (i.e., during transport in real sewers). While consistent results were reported for rather stable compounds (e.g., MDMA and methamphetamine), a varying range of stability under different or similar conditions was observed for other compounds (e.g., cocaine, amphetamine and morphine). Wastewater composition can vary considerably over time, and different conditions prevail in different sewer systems. In summary, this indicates that more systematic studies are needed to: i) cover the range of possible conditions in sewers and ii) compare results more objectively. To facilitate the latter, we propose a set of parameters that should be reported for in-sewer stability experiments. Finally, a best practice of sample collection, preservation, and preparation before analysis is suggested in order to minimize transformation during these steps. Copyright © 2015 Elsevier Ltd. All rights reserved.
Marcum, Zachary A; Vande Griend, Joseph P; Linnebur, Sunny A
The US Food and Drug Administration (FDA) has new regulatory authorities intended to enhance drug safety monitoring in the postmarketing period. This has resulted in an increase in communication from the FDA in recent years about the safety profile of certain drugs. It is important to stay abreast of the current literature on drug risks to effectively communicate these risks to patients, other health care providers, and the general public. To summarize 4 new FDA drug safety communications by describing the evidence supporting the risks and the clinical implications for older adults. The FDA Web site was reviewed for new drug safety communications from May 2011 to April 2012 that would be relevant to older adults. Approved labeling for each drug or class was obtained from the manufacturer, and PubMed was searched for primary literature that supported the drug safety concern. FDA drug safety communications for 4 drugs were chosen because of the potential clinical importance in older adults. A warning for citalopram was made because of potential problems with QT prolongation in patients taking less than 40 mg per day. The evidence suggests minor changes in QT interval. Given the flat dose-response curve in treating depression with citalopram, the new 20-mg/d maximum dose in older adults is sensible. Another warning was made for proton pump inhibitors (PPIs) and an increased risk of Clostridium difficile infection. A dose-response relationship was found for this drug risk. With C. difficile infections on the rise in older adults, along with other safety risks of PPI therapy, PPIs should only be used in older adults indicated for therapy for the shortest duration possible. In addition, a warning about dabigatran was made. There is strong evidence from a large clinical trial, as well as case reports, of increased bleeding risk in older adults taking dabigatran, especially in older adults with decreased renal function. This medication should be used with caution in older
Vilar, Santiago; Hripcsak, George
Explosion of the availability of big data sources along with the development in computational methods provides a useful framework to study drugs' actions, such as interactions with pharmacological targets and off-targets. Databases related to protein interactions, adverse effects and genomic profiles are available to be used for the construction of computational models. In this article, we focus on the description of biological profiles for drugs that can be used as a system to compare similarity and create methods to predict and analyze drugs' actions. We highlight profiles constructed with different biological data, such as target-protein interactions, gene expression measurements, adverse effects and disease profiles. We focus on the discovery of new targets or pathways for drugs already in the pharmaceutical market, also called drug repurposing, in the interaction with off-targets responsible for adverse reactions and in drug-drug interaction analysis. The current and future applications, strengths and challenges facing all these methods are also discussed. Biological profiles or signatures are an important source of data generation to deeply analyze biological actions with important implications in drug-related studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: email@example.com.
Azmi, Asfar S.; Bao, Bin; Sarkar, Fazlul H.
Trafficking of biological material across membranes is an evolutionary conserved mechanism and is part of any normal cell homeostasis. Such transport is comprised of active, passive, export through microparticles and vesicular transport (exosomes) that collectively maintain proper compartmentalization of important micro and macromolecules. In pathological states, such as cancer, aberrant activity of export machinery results in expulsion of a number of key proteins and microRNAs resulting in their misexpression. Exosome mediated expulsion of intracellular drugs could be another barrier in the proper action of most of the commonly used therapeutics, targeted agents and their intracellular metabolites. Over the last decade, a number of studies have revealed that exosomes cross-talk and/or influence major tumor related pathways such as hypoxia driven EMT, cancer stemness, angiogenesis and metastasis involving many cell types within the tumor microenvironment. Emerging evidence suggest that exosome secreted proteins can also propel fibroblast growth, resulting in Desmoplastic reaction (DR); a major barrier in effective cancer drug delivery. This comprehensive review highlights the advancements in the understanding of the biology of exosomes secretions and the consequence on cancer drug resistance. We propose that the successful combination of cancer treatments to tackle exosome mediated drug resistance requires an interdisciplinary understanding of these cellular exclusion mechanisms, and how secreted biomolecules are involved in cellular cross-talk within the tumor microenvironment. PMID:23709120
Economic evaluations of health technologies typically assume constant real drug prices and model only the cohort of patients currently eligible for treatment. It has recently been suggested that, in the UK, we should assume that real drug prices decrease at 4% per annum and, in New Zealand, that real drug prices decrease at 2% per annum and at patent expiry the drug price falls. It has also recently been suggested that we should model multiple future incident cohorts. In this article, the cost effectiveness of drugs is modelled based on these ideas. Algebraic expressions are developed to capture all costs and benefits over the entire life cycle of a new drug. The lifetime of a new drug in the UK, a key model parameter, is estimated as 33 years, based on the historical lifetime of drugs in England over the last 27 years. Under the proposed methodology, cost effectiveness is calculated for seven new drugs recently appraised in the UK. Cost effectiveness as assessed in the future is also estimated. Whilst the article is framed in mathematics, the findings and recommendations are also explained in non-mathematical language. The 'life-cycle correction factor' is introduced, which is used to convert estimates of cost effectiveness as traditionally calculated into estimates under the proposed methodology. Under the proposed methodology, all seven drugs appear far more cost effective in the UK than published. For example, the incremental cost-effectiveness ratio decreases by 46%, from £61, 900 to £33, 500 per QALY, for cinacalcet versus best supportive care for end-stage renal disease, and by 45%, from £31,100 to £17,000 per QALY, for imatinib versus interferon-α for chronic myeloid leukaemia. Assuming real drug prices decrease over time, the chance that a drug is publicly funded increases over time, and is greater when modelling multiple cohorts than with a single cohort. Using the methodology (compared with traditional methodology) all drugs in the UK and New
Full Text Available omorbid psychiatric disorders, frequent hospitalization, multiple outpatient treatment, prior history of hypertension, obesity and lipid dysregulation are associated with higher risk of metabolic syndrome in children. Side effects of antipsychotic drugs and their management have recently become a major subject of research due to enhanced antipsychotic drug usage in child and adolescents. Prevention strategies are usually preferred to secondary or tertiary strategies in the management of metabolic syndrome associated with antipsychotic drugs. Clinicians should present multidisciplinary approach to endocrine and metabolic side effects due to antipsychotic use in pediatric patient groups and avoid multiple drug use in such patients. In this paper, we briefly reviewed metabolic side effects of second generation antipsychotic drugs in child and adolescent population, possible mechanisms of susceptibility to metabolic syndrome and pharmacological and non pharmacological treatment approach to prevention of weight gain.
Roseman, Michelle; Turner, Erick H.; Lexchin, Joel; Coyne, James C.; Bero, Lisa A.; Thombs, Brett D.
Objectives To investigate the degree to which Cochrane reviews of drug interventions published in 2010 reported conflicts of interest from included trials and, among reviews that reported this information, where it was located in the review documents. Design Cross sectional study. Data sources
Sotgiu, Giovanni; D'Ambrosio, Lia; Centis, Rosella; Tiberi, Simon; Esposito, Susanna; Dore, Simone; Spanevello, Antonio; Migliori, Giovanni Battista
Carbapenems (ertapenem, imipenem, meropenem) are used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB), even if the published evidence is limited, particularly when it is otherwise difficult to identify the recommended four active drugs to be included in the regimen. No systematic review to date has ever evaluated the efficacy, safety, and tolerability of carbapenems. A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of carbapenem-containing regimens in individuals with pulmonary/extra-pulmonary disease which was bacteriologically confirmed as M/XDR-TB. We used PubMed to identify relevant full-text, English manuscripts up to the 20 December 2015, excluding editorials and reviews. Seven out of 160 studies satisfied the inclusion criteria: two on ertapenem, one on imipenem, and four on meropenem, all published between 2005 and 2016. Of seven studies, six were retrospective, four were performed in a single center, two enrolled children, two had a control group, and six reported a proportion of XDR-TB cases higher than 20%. Treatment success was higher than 57% in five studies with culture conversion rates between 60% and 94.8%. The safety and tolerability is very good, with the proportion of adverse events attributable to carbapenems below 15%.
Kalepu, Sandeep; Nekkanti, Vijaykumar
The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve efficacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical companies. This review covers the recent advances in the field of insoluble drug delivery and business prospects. PMID:26579474
Full Text Available The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve efficacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical companies. This review covers the recent advances in the field of insoluble drug delivery and business prospects.
Lahner, E; Annibale, B; Delle Fave, G
Impaired acid secretion may affect drug absorption and may be consequent to corporal Helicobacter pylori-gastritis, which may affect the absorption of orally administered drugs. To focus on the evidence of impaired drug absorption associated with H. pylori infection. Data sources were the systematic search of MEDLINE/EMBASE/SCOPUS databases (1980-April 2008) for English articles using the keywords: drug malabsorption/absorption, stomach, Helicobacter pylori, gastritis, gastric acid, gastric pH, hypochlorhydria, gastric hypoacidity. Study selection was made from 2099 retrieved articles, five studies were identified. Data were extracted from selected papers, investigated drugs, study type, main features of subjects, study design, intervention type and results were extracted. In all, five studies investigated impaired absorption of l-dopa, thyroxine and delavirdine in H. pylori infection. Eradication treatment led to 21-54% increase in l-dopa in Parkinson's disease. Thyroxine requirement was higher in hypochlorhydric goitre with H. pylori-gastritis and thyrotropin levels decreased by 94% after treatment. In H. pylori- and HIV-positive hypochlorhydric subjects, delavirdine absorption increased by 57% with orange juice administration and by 150% after eradication. A plausible mechanism of impaired drug absorption is decreased acid secretion in H. pylori-gastritis patients. Helicobacter pylori infection and hypochlorhydria should be considered in prescribing drugs the absorption of which is potentially affected by intragastric pH.
Full Text Available Zhi-Yu Wang,1 Meng Chen,1 Ling-Ling Zhu,2 Lu-Shan Yu,3 Su Zeng,3 Mei-Xiang Xiang,4 Quan Zhou1 1Department of Pharmacy, 2VIP Care Ward, Division of Nursing, the Second Affiliated Hospital, School of Medicine, 3Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, 4Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China Background: Coprescribing of clopidogrel and other drugs is common. Available reviews have addressed the drug–drug interactions (DDIs when clopidogrel is as an object drug, or focused on combination use of clopidogrel and a special class of drugs. Clinicians may still be ignorant of those DDIs when clopidogrel is a precipitant drug, the factors determining the degree of DDIs, and corresponding risk management.Methods: A literature search was performed using PubMed, MEDLINE, Web of Science, and the Cochrane Library to analyze the pharmacokinetic DDIs of clopidogrel and new P2Y12 receptor inhibitors.Results: Clopidogrel affects the pharmacokinetics of cerivastatin, repaglinide, ferulic acid, sibutramine, efavirenz, and omeprazole. Low efficacy of clopidogrel is anticipated in the presence of omeprazole, esomeprazole, morphine, grapefruit juice, scutellarin, fluoxetine, azole antifungals, calcium channel blockers, sulfonylureas, and ritonavir. Augmented antiplatelet effects are anticipated when clopidogrel is coprescribed with aspirin, curcumin, cyclosporin, St John’s wort, rifampicin, and angiotensin-converting enzyme inhibitors. The factors determining the degree of DDIs with clopidogrel include genetic status (eg, cytochrome P540 [CYP]2B6*6, CYP2C19 polymorphism, CYP3A5*3, CYP3A4*1G, and CYP1A2-163C>A, species differences, and dose strength. The DDI risk does not exhibit a class effect, eg, the effects of clopidogrel on cerivastatin versus other statins, the effects of proton pump
Pieper, Ines A; Bertau, Martin
Predicting drug metabolism after oral administration is highly complex, yet indispensable. Hitherto, drug metabolism mainly focuses on hepatic processes. In the intestine, drug molecules encounter the metabolic activity of microorganisms prior to absorption through the gut wall. Drug biotransformation through the gastrointestinal microflora has the potential to evoke serious problems because the metabolites formed may cause unexpected and undesired side effects in patients. Hence, in the course of drug development, the question has to be addressed if microbially formed metabolites are physiologically active, pharmaceutically active or even toxic. In order to provide answers to these questions and to keep the number of laboratory tests needed low, predictive tools - in vivo as well as in silico - are invaluable. This review gives an outline of the current state of the art in the field of predicting the drug biotransformation through the gastrointestinal microflora on several levels of modelling. A comprehensive review of the literature with a thorough discussion on assets and drawbacks of the different modelling approaches. The impact of the gastrointestinal drug biotransformation on patients' health will grow with increasing complexity of drug entities. Predicting metabolic fates of drugs by combining in vitro and in silico models provides invaluable information which will be suitable to particularly reduce in vivo studies.
Lee, Annisa Lai
This study tracks the changes of the effects of 4 information sources for direct-to-consumer drug advertising on patients' requests for prescription drugs from physicians since the inception of the "Guidance for Industry about Consumer-directed Broadcast Advertisements." The Guidance advises pharmaceuticals to use four information sources for consumers to seek further information to supplement broadcast drug advertisements: small-print information, the Internet, a toll-free number, and health-care providers (nurses, doctors, and pharmacists). Logistic models were created by using survey data collected by the Food and Drug Administration in 1999 and 2002. Results show that throughout the years, health-care providers remain the most used and strongest means associated with patients' direct requests for nonspecific and specific prescription drugs from doctors. The small-print information source gains power and changes from an indirect means associated with patients' discussing drugs with health-care providers to a direct means associated with patients' asking about nonspecific and specific drugs from their doctors. The Internet is not directly related to drug requests, but the effect of its association with patients seeking information from health-care providers grew 11-fold over the course of the study. The toll-free number lost its power altogether for both direct request for a prescription drug and further discussion with health-care providers. Patient demographics will be considered for specific policy implications.
Luigi Di Bella
Full Text Available Melatonin (N-acetyl-5-methoxytryptamine, MLT, the main hormone produced by the pineal gland, not only regulates circadian rhythm, but also has antioxidant, anti-ageing and immunomodulatory properties. MLT plays an important role in blood composition, medullary dynamics, platelet genesis, vessel endothelia, and in platelet aggregation, leukocyte formula regulation and hemoglobin synthesis. Its significant atoxic, apoptotic, oncostatic, angiogenetic, differentiating and antiproliferative properties against all solid and liquid tumors have also been documented. Thanks, in fact, to its considerable functional versatility, MLT can exert both direct and indirect anticancer effects in factorial synergy with other differentiating, antiproliferative, immunomodulating and trophic molecules that form part of the anticancer treatment formulated by Luigi Di Bella (Di Bella Method, DBM: somatostatin, retinoids, ascorbic acid, vitamin D3, prolactin inhibitors, chondroitin-sulfate. The interaction between MLT and the DBM molecules counters the multiple processes that characterize the neoplastic phenotype (induction, promotion, progression and/or dissemination, tumoral mutation. All these particular characteristics suggest the use of MLT in oncological diseases.
, dogs, rabbits, rats and mice. Encapsulation in erythrocytes drastically changes the pharmacokinetic properties of drugs in both animals and humans, enhancing liver and spleen uptake and targeting the reticulo-endothelial system (RES).
Rasmussen-Barr, Eva; Held, Ulrike; Grooten, Wilhelmus J A; Roelofs, Pepijn D D M; Koes, Bart W; van Tulder, Maurits W; Wertli, Maria M
Systematic review and meta-analysis. To determine the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) on pain reduction, overall improvement, and reported adverse effects in people with sciatica. NSAIDs are one of the most frequently prescribed drugs for sciatica. We updated a 2008 Cochrane Review through June 2015. Randomized controlled trials that compared NSAIDs with placebo, with other NSAIDs, or with other medication were included. Outcomes included pain using mean difference (MD, 95% confidence intervals [95% CI]). For global improvement and adverse effects risk ratios (RR, 95% CI) were used. We assessed level of evidence using the Grades of Recommendation, Assessment, Development and Evaluation approach. Ten trials were included (N = 1651). Nine out of 10 trials were assessed at high risk of bias. For pain reduction (visual analog scale, 0 to 100) NSAIDs were no more effective than placebo (MD -4.56, 95% CI -11.11 to 1.99, quality of evidence: very low). For global improvement NSAIDs were more effective than placebo (RR 1.14 [95% CI 1.03 to 1.27], low quality of evidence). One trial reported the effect of NSAIDs on disability with very low-quality evidence that NSAIDs are no more effective than placebo. There was low-quality evidence that the risk for adverse effects is higher for NSAID than placebo (RR 1.40, 95% CI 1.02 to 1.93). Our findings show very low-quality evidence that the efficacy of NSAIDs for pain reduction is comparable with that of placebo, low-quality evidence that NSAIDs is better than placebo for global improvement and low-quality evidence for higher risk of adverse effects using NSAIDs compared with placebo. The findings must be interpreted with caution, due to small study samples, inconsistent results, and a high risk of bias in the included trials. 1.
Morse, E E
Numerous drugs and chemicals affect the function of human blood platelets. The mechanism of action of some medications is partly understood. Aspirin is the most frequently involved drug. It appears to interfere with the platelet release reaction by acetylation of a platelet membrane protein which may be involved in the synthesis of prostaglandins. Other anti-inflammatory drugs, including indomethacin, phenylbutazone, ibuprophen (Motrin) and clonixin, also interfere with the release reaction but have a shorter acting course than aspirin. Some drugs stimulate adenylcyclase (gliclazide) or block phosphodiesterase, (dipyridamole, caffeine) both of which actions lead to an increase in adenosine cyclic 3':5' monophosphate (cAMP) and decrease aggregation by adenosine diphosphate (ADP). These interactions should be known to clinical scientists since patients using these medicaments may manifest abnormal platelet function tests in the laboratory and mild hemorrhagic syndromes in the clinic.
Lee, Joy Li-Yueh; Fischer, Micahel A; Shrank, William H; Polinski, Jennifer M; Choudhry, Niteesh K
Given rising pharmaceutical expenditures and the widespread use of reference pricing as a costcontainment instrument abroad, we systematically reviewed the evidence evaluating reference pricing policies. We performed a structured electronic search of peer-reviewed journals for studies published before that reported on the effects of reference pricing policies on medication use, payer and patient spending, and resource consumption. Our search yielded 16 studies describing 9 reference-pricing policies from 6 countries. Reference-pricing policies led to decreases in drug prices and increases in utilization of targeted medications, while also reducing payer and patient expenditures. In addition, these policies did not lead to increased use of medical services, such as physician office visits and hospitalization. These results suggest that reference pricing may be an attractive policy strategy for the US healthcare system.
Reed, Jack W [Sandia Laboratories, Albuquerque, NM (United States)
Long Range Airblast Propagation On February 2, 1951, the Atomic Energy Commission discovered that airblast from an 8-kt explosion could break many windows in Las Vegas at 60 miles range from Frenchman's Flat. Yet later, on February 6, only minor effects resulted from three times as large a yield. Atmospheric conditions were found to be responsible for this apparent anomaly. A weather watch was initiated under the direction of Everett Cox to help prevent recurrences during further atmospheric nuclear testing. Our atmosphere with its stratifications of temperature and winds acts as an acoustic lens which may trap, duct, or even focus blast waves from explosions. The basic refraction mechanism is described. Sound speed is proportional to the square root of absolute temperature, as shown in Newton's Principia, so as temperature decreases with altitude, so does sound speed. The proper coefficient was found by Laplace, using adiabatic rather than Newton's isothermal compression. Sound or blast waves propagate through moving air with this wind added or subtracted from the sound speed. This affects an initially vertical plane wave to make it increasingly distorted with time. Wave normals, or rays, are bent upward, away from ground, in layers where net sound velocity decreases with altitude and are bent downward where sound velocity increases with altitude. This bending, applied to a point sound source or explosion, gives ray paths typified. Where dueling is caused by a velocity inversion high above the ground, there is a zone of silence beyond the immediate range of the strong explosion wave, and a sound ring at some distance determined by the height and strength of the dueling layer. Calculation of ray paths has evolved with the growth in needs and computer capabilities.
Reed, Jack W.
Long Range Airblast Propagation On February 2, 1951, the Atomic Energy Commission discovered that airblast from an 8-kt explosion could break many windows in Las Vegas at 60 miles range from Frenchman's Flat. Yet later, on February 6, only minor effects resulted from three times as large a yield. Atmospheric conditions were found to be responsible for this apparent anomaly. A weather watch was initiated under the direction of Everett Cox to help prevent recurrences during further atmospheric nuclear testing. Our atmosphere with its stratifications of temperature and winds acts as an acoustic lens which may trap, duct, or even focus blast waves from explosions. The basic refraction mechanism is described. Sound speed is proportional to the square root of absolute temperature, as shown in Newton's Principia, so as temperature decreases with altitude, so does sound speed. The proper coefficient was found by Laplace, using adiabatic rather than Newton's isothermal compression. Sound or blast waves propagate through moving air with this wind added or subtracted from the sound speed. This affects an initially vertical plane wave to make it increasingly distorted with time. Wave normals, or rays, are bent upward, away from ground, in layers where net sound velocity decreases with altitude and are bent downward where sound velocity increases with altitude. This bending, applied to a point sound source or explosion, gives ray paths typified. Where dueling is caused by a velocity inversion high above the ground, there is a zone of silence beyond the immediate range of the strong explosion wave, and a sound ring at some distance determined by the height and strength of the dueling layer. Calculation of ray paths has evolved with the growth in needs and computer capabilities
Evans, Jennifer; Virgili, Gianni
Anti-vascular endothelial growth factors (anti-VEGF) are targeted biological drugs (e.g. monoclonal antibodies) that prevent the growth of new vessels by inhibiting VEGF. VEGF is a cytokine (cell-signalling protein) that promotes the growth of, and leakage from, new vessels. Currently there are three anti-VEGF drugs licensed for use in eye disease: pegaptanib, aflibercept, ranibizumab and one that is not licensed but is commonly used off-label (bevacizumab).
Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...
By analyzing the current hospital anti hepatitis drug use, dosage, indications and drug resistance, this article studied the drug inventory management and cost optimization. The author used drug utilization evaluation method, analyzed the amount and kind distribution of anti hepatitis drugs and made dynamic monitoring of inventory. At the same time, the author puts forward an effective scheme of drug classification management, uses the ABC classification method to classify the drugs according to the average daily dose of drugs, and implements the automatic replenishment plan. The design of pharmaceutical services supply chain includes drug procurement platform, warehouse management system and connect to the hospital system through data exchange. Through the statistical analysis of drug inventory, we put forward the countermeasures of drug logistics optimization. The results showed that drug replenishment plan can effectively improve drugs inventory efficiency.
West, Sophie; Bhugra, Praveen
Aims Currently, treatment for Alzheimer’s disease (AD) focuses on the cholinergic hypothesis and provides limited symptomatic effects. Research currently focuses on other factors that are thought to contribute to AD development such as tau proteins and Aβ deposits, and how modification of the associated pathology affects outcomes in patients. This systematic review summarizes and appraises the evidence for the emerging drugs affecting Aβ and tau pathology in AD. Methods A comprehensive, systematic online database search was conducted using the databases ScienceDirect and PubMed to include original research articles. A systematic review was conducted following a minimum set of standards, as outlined by The PRISMA Group 1. Specific inclusion and exclusion criteria were followed and studies fitting the criteria were selected. No human trials were included in this review. In vitro and in vivo AD models were used to assess efficacy to ensure studied agents were emerging targets without large bodies of evidence. Results The majority of studies showed statistically significant improvement (P < 0.05) of Aβ and/or tau pathology, or cognitive effects. Many studies conducted in AD animal models have shown a reduction in Aβ peptide burden and a reduction in tau phosphorylation post-intervention. This has the potential to reduce plaque formation and neuronal degeneration. Conclusions There are many emerging targets showing promising results in the effort to modify the pathological effects associated with AD. Many of the trials also provided evidence of the clinical effects of such drugs reducing pathological outcomes, which was often demonstrated as an improvement of cognition. PMID:25753046
Gómez-Gómez, Alejandro; Loza, Estíbaliz; Rosario, Maria Piedad; Espinosa, Gerard; Morales, José M García Ruiz de; Herreras, Jose M; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel
To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients.
Niu, Yanqing; Zhang, Wen
Unexpected side effects of drugs are great concern in the drug development, and the identification of side effects is an important task. Recently, machine learning methods are proposed to predict the presence or absence of interested side effects for drugs, but it is difficult to make the accurate prediction for all of them. In this paper, we transform side effect profiles of drugs as their quantitative scores, by summing up their side effects with weights. The quantitative scores may measure the dangers of drugs, and thus help to compare the risk of different drugs. Here, we attempt to predict quantitative scores of drugs, namely the quantitative prediction. Specifically, we explore a variety of drug-related features and evaluate their discriminative powers for the quantitative prediction. Then, we consider several feature combination strategies (direct combination, average scoring ensemble combination) to integrate three informative features: chemical substructures, targets, and treatment indications. Finally, the average scoring ensemble model which produces the better performances is used as the final quantitative prediction model. Since weights for side effects are empirical values, we randomly generate different weights in the simulation experiments. The experimental results show that the quantitative method is robust to different weights, and produces satisfying results. Although other state-of-the-art methods cannot make the quantitative prediction directly, the prediction results can be transformed as the quantitative scores. By indirect comparison, the proposed method produces much better results than benchmark methods in the quantitative prediction. In conclusion, the proposed method is promising for the quantitative prediction of side effects, which may work cooperatively with existing state-of-the-art methods to reveal dangers of drugs.
van der Gronde, T.; Uyl-de Groot, Carin A; Pieters, A.H.L.M.
Context. Recent public outcry has highlighted the rising cost of prescription drugs worldwide, which in several disease areas outpaces other health care expenditures and results in a suboptimal global availability of essential medicines. Method. A systematic review of Pubmed, the Financial Times,
Gronde, T.V. (Toon van der); C.A. Uyl-de Groot (Carin); Pieters, T. (Toine)
markdownabstractCONTEXT: Recent public outcry has highlighted the rising cost of prescription drugs worldwide, which in several disease areas outpaces other health care expenditures and results in a suboptimal global availability of essential medicines. METHOD: A systematic review of Pubmed, the
Schifano, Fabrizio; Chiappini, Stefania; Corkery, John M; Guirguis, Amira
Recently, a range of prescription and over-the-counter drugs have been reportedly used as Novel Psychoactive Substances (NPS), due to their potential for abuse resulting from their high dosage/idiosyncratic methods of self-administration. This paper provides a systematic review of the topic, focusing on a range of medications which have emerged as being used recreationally, either on their own or in combination with NPS. Among gabapentinoids, pregabalin may present with higher addictive liability levels than gabapentin, with pregabalin being mostly identified in the context of opioid, polydrug intake. For antidepressants, their dopaminergic, stimulant-like, bupropion activities may explain their recreational value and diversion from the therapeutic intended use. In some vulnerable clients, a high dosage of venlafaxine (‘baby ecstasy’) is ingested for recreational purposes, whilst the occurrence of a clinically-relevant withdrawal syndrome may be a significant issue for all venlafaxine-treated patients. Considering second generation antipsychotics, olanzapine appears to be ingested at very large dosages as an ‘ideal trip terminator’, whilst the immediate-release quetiapine formulation may possess proper abuse liability levels. Within the image- and performance- enhancing drugs (IPEDs) group, the beta-2 agonist clenbuterol (‘size zero pill’) is reported to be self-administered for aggressive slimming purposes. Finally, high/very high dosage ingestion of the antidiarrhoeal loperamide has shown recent increasing levels of popularity due to its central recreational, anti-withdrawal, opiatergic effects. The emerging abuse of prescription drugs within the context of a rapidly modifying drug scenario represents a challenge for psychiatry, public health and drug-control policies.
Janik, Peter; Kosticova, Michaela; Pecenak, Jan; Turcek, Michal
Precise terminology and definitions are important components of scientific language. Although the terms "hard drugs" and "soft drugs" are used widely by professionals, neither the International Classification of Diseases nor the Diagnostic and Statistical Manual classify psychoactive substances into the categories "hard" and "soft." To analyze the occurrence of the terms "hard drugs" and "soft drugs" in recent scientific literature and to establish the degree of consensus in labeling psychoactive substances as "hard" or "soft." A critical review of scientific papers listed in PubMed and Scopus between 2011 and 2015. Three hundred thirty-four articles were initially identified as potentially relevant for review, 132 of which were included in the final analysis. One hundred twenty-four articles used the term "hard drugs" and 84.7% provided examples of substances considered "hard." Forty-four articles used the term "soft drugs" and 90.9% provided examples of substances considered "soft." Citations of relevant articles supporting categorization as "hard" or "soft" were not given in 90% of the articles. The authors often provided no or only very sparse information on their reasons for considering specific drugs as "hard" or "soft." Although it initially appeared that there is substantial agreement as to which psychoactive substances should be regarded as "hard" and "soft," closer inspection shows that the dividing line is blurred without clear criteria for categorization. At this time, it remains uncertain whether these terms should persist in the scientific literature. We therefore recommend these terms should be avoided or, if used, be clearly and precisely defined.
Radha, G. V.; Rani, T. Sudha; Sarvani, B.
Proniosomes are dry formulation of water soluble carrier particles that are coated with surfactant. They are rehydrated to form niosomal dispersion immediately before use on agitation in hot aqueous media within minutes. Proniosomes are physically stable during the storage and transport. Drug encapsulated in the vesicular structure of proniosomes prolong the existence of drug in the systematic circulation and enhances the penetration into target tissue and reduce toxicity. From a technical po...
The studies described in this thesis focus on the effect of fasting, as nutritional modulator, on drug metabolism. Drug metabolism varies considerably between and within patients, which may result in treatment failure or, conversely, in untoward side effects. Many factors contribute to the
Nunez-Smith, Marcella; Wolf, Elizabeth; Huang, Helen Mikiko; Chen, Peggy G.; Lee, Lana; Emanuel, Ezekiel J.; Gross, Cary P.
The authors systematically reviewed 42 quantitative studies on the relationship between media exposure and tobacco, illicit drug, and alcohol use among children and adolescents. Overall, 83% of studies reported that media was associated with increased risk of smoking initiation, use of illicit drugs, and alcohol consumption. Of 30 studies…
Beesetti, Hemalatha; Khanna, Navin; Swaminathan, Sathyamangalam
Almost half the global population is estimated to be at risk of contracting dengue infection. Of the 400 million infections estimated to occur annually, 4 million can be potentially life-threatening leading to vascular leakage and shock. The only treatment available to severe dengue patients is fluid replacement therapy and supportive care. A drug for treating dengue is an urgent need. This article endeavors to provide an overview of the experimental dengue drugs being developed around the world as reflected in the recent patent literature spanning the last few years (2010-2014). Dengue drug development is essentially in its infancy and currently hobbled by multiple factors including a poor understanding of the molecular mechanism of severe disease and lack of reliable small animal model for preclinical drug evaluation. More intense R&D coupled to setting up product development partnerships to facilitate the efficient movement of a drug molecule from the laboratory to the clinic is needed to make antiviral therapy for dengue a reality in the coming future.
Full Text Available Background: Drug craving is considered as one of the main cores of drug dependency and addiction. Multidimensionality of drug craving, its cultural-bounded features and its intra individual rapidly changing nature makes it difficult to be measured. Nowadays, regarding different psychometric approaches, there are various instruments available for measurement of different aspects of drug craving but mainly for Latin-based languages in North America and European countries. High prevalence and special conditions, and unique subcultures in substance abuse and addiction in many countries, like Iran, make the design of culturally validated instruments for drug craving assessment priority. Materials and Methods: Comprehensive review on drug craving measurement instruments for Persian speaking subjects have been performed by searching in databases (ELSEVIER, Science Direct and Scientific Information Database (SID and investigating of related documents on regional experiences. Results: In this article seven main categories of drug craving instruments have been reviewed focusing on validated versions in Persian language including: self-reports, reinforcement “proxies”, drug self administration, psycho physiological responding, neurobiological responding, cognitive processing and expressive methods. Conclusion: Reviewing on weak and strength points of each instrument group and national and regional experiences shows that designing and validating a new series of ecologically-validated instruments for multidimensional measurement of drug craving in different addiction subcultures should be prioritized to cover current methodological gaps in substance abuse studies in Iran.
Atherly, Adam; Rubin, Paul H
In this paper we use published information to analyze the economic value of Direct to Consumer Advertising (DTCA). The reviewed research finds that DTCA leads to increased demand for the advertised drug and that the effect of the drug tends to be class-wide rather than product specific. There is weak evidence that DTCA may increase compliance and improve clinical outcomes. However, there is little research on the effect of DTCA on inappropriate prescribing or on the characteristics of patients who respond to treatment. On net, if the advertised drugs are cost effective on average and the patients using the drugs in response to the advertisement are similar to other users, DTCA is likely cost effective. Overall, the literature to date is consistent with the idea that DTCA is beneficial, but further research is needed before definitive conclusions can be drawn.
Kuhn, Michael; Letunic, Ivica; Jensen, Lars Juhl
, targets and side effects into a more complete picture of the therapeutic mechanism of actions of drugs and the ways in which they cause adverse reactions. To this end, we have created the SIDER ('Side Effect Resource', http://sideeffects.embl.de) database of drugs and ADRs. The current release, SIDER 4......% of which can be compared to the frequency under placebo treatment. SIDER furthermore contains a data set of drug indications, extracted from the package inserts using Natural Language Processing. These drug indications are used to reduce the rate of false positives by identifying medical terms that do...
Roseman, Michelle; Turner, Erick H; Lexchin, Joel; Coyne, James C; Bero, Lisa A; Thombs, Brett D
To investigate the degree to which Cochrane reviews of drug interventions published in 2010 reported conflicts of interest from included trials and, among reviews that reported this information, where it was located in the review documents. Cross sectional study. Cochrane Database of Systematic Reviews. Systematic reviews of drug interventions published in 2010 in the Cochrane Database of Systematic Reviews, with review content classified as up to date in 2008 or later and with results from one or more randomised controlled trials. Of 151 included Cochrane reviews, 46 (30%, 95% confidence interval 24% to 38%) reported information on the funding sources of included trials, including 30 (20%, 14% to 27%) that reported information on trial funding for all included trials and 16 (11%, 7% to 17%) that reported for some, but not all, trials. Only 16 of the 151 Cochrane reviews (11%, 7% to 17%) provided any information on trial author-industry financial ties or trial author-industry employment. Information on trial funding and trial author-industry ties was reported in one to seven locations within each review, with no consistent reporting location observed. Most Cochrane reviews of drug trials published in 2010 did not provide information on trial funding sources or trial author-industry financial ties or employment. When this information was reported, location of reporting was inconsistent across reviews.
Effects of anti-obesity drugs, diet, and exercise on weight-loss maintenance after a very-low-calorie diet or low-calorie diet: a systematic review and meta-analysis of randomized controlled trials123
Neovius, Martin; Hemmingsson, Erik
Background: Weight-loss maintenance remains a major challenge in obesity treatment. Objective: The objective was to evaluate the effects of anti-obesity drugs, diet, or exercise on weight-loss maintenance after an initial very-low-calorie diet (VLCD)/low-calorie diet (LCD) period (obesity drugs (3 arms; n = 658), meal replacements (4 arms; n = 322), high-protein diets (6 arms; n = 865), dietary supplements (6 arms; n = 261), other diets (3 arms; n = 564), and exercise (5 arms; n = 347). During the VLCD/LCD period, the pooled mean weight change was −12.3 kg (median duration: 8 wk; range 3–16 wk). Compared with controls, anti-obesity drugs improved weight-loss maintenance by 3.5 kg [95% CI: 1.5, 5.5 kg; median duration: 18 mo (12–36 mo)], meal replacements by 3.9 kg [95% CI: 2.8, 5.0 kg; median duration: 12 mo (10–26 mo)], and high-protein diets by 1.5 kg [95% CI: 0.8, 2.1 kg; median duration: 5 mo (3–12 mo)]. Exercise [0.8 kg; 95% CI: −1.2, 2.8 kg; median duration: 10 mo (6–12 mo)] and dietary supplements [0.0 kg; 95% CI: −1.4, 1.4 kg; median duration: 3 mo (3–14 mo)] did not significantly improve weight-loss maintenance compared with control. Conclusion: Anti-obesity drugs, meal replacements, and high-protein diets were associated with improved weight-loss maintenance after a VLCD/LCD period, whereas no significant improvements were seen for dietary supplements and exercise. PMID:24172297
Johansson, Kari; Neovius, Martin; Hemmingsson, Erik
Weight-loss maintenance remains a major challenge in obesity treatment. The objective was to evaluate the effects of anti-obesity drugs, diet, or exercise on weight-loss maintenance after an initial very-low-calorie diet (VLCD)/low-calorie diet (LCD) period (obesity drugs (3 arms; n = 658), meal replacements (4 arms; n = 322), high-protein diets (6 arms; n = 865), dietary supplements (6 arms; n = 261), other diets (3 arms; n = 564), and exercise (5 arms; n = 347). During the VLCD/LCD period, the pooled mean weight change was -12.3 kg (median duration: 8 wk; range 3-16 wk). Compared with controls, anti-obesity drugs improved weight-loss maintenance by 3.5 kg [95% CI: 1.5, 5.5 kg; median duration: 18 mo (12-36 mo)], meal replacements by 3.9 kg [95% CI: 2.8, 5.0 kg; median duration: 12 mo (10-26 mo)], and high-protein diets by 1.5 kg [95% CI: 0.8, 2.1 kg; median duration: 5 mo (3-12 mo)]. Exercise [0.8 kg; 95% CI: -1.2, 2.8 kg; median duration: 10 mo (6-12 mo)] and dietary supplements [0.0 kg; 95% CI: -1.4, 1.4 kg; median duration: 3 mo (3-14 mo)] did not significantly improve weight-loss maintenance compared with control. Anti-obesity drugs, meal replacements, and high-protein diets were associated with improved weight-loss maintenance after a VLCD/LCD period, whereas no significant improvements were seen for dietary supplements and exercise.
Kulyavtsev, Paulina A; Spencer, Roxanne P
Although silicon is more commonly associated with computer chips than with drug delivery, with the discovery that porous silicon is a viable biocompatible material, mesoporous silicon with pores between 2 and 50 nm has been loaded with small molecule and biomolecule therapeutics and safely implanted for controlled release. As porous silicon is readily oxidized, porous silica must also be considered for drug delivery applications. Since 2010, only a limited number of US patents have been granted, primarily for ophthalmologic and immunotherapy applications, in contrast to the growing body of technical literature in this area.
Takano, Ayumi; Miyamoto, Yuki; Matsumoto, Toshihiko
Over the past two decades, computerized and Internet-based interventions for the treatment of various health problems, including substance abuse, have been developed and used to resolve treatment-related issues. The purpose of this study is to review selected studies that conducted computerized and Internet-based psychosocial interventions for people with drug-use problems. We used a PubMed search to identify relevant studies to our review based on the following inclusion criteria: 1) the study participants were drug users; 2) the Internet or computer technologies were used for the interventions; 3) the study used psychosocial interventions; and 4) meta-analysis and randomized controlled trial (RCT). In total, 12 studies (meta-analysis = 1, RCT = 11) were identified and included in this review. The RCTs extracted in this study were not included in the meta-analysis. The meta-analysis showed that studies targeting people with alcohol and/or drug-use disorders (n = 11) had a small effect size (d = 0.24). However, the effect size was considered heterogeneous. Most of the reviewed RCTs assessed either drug use or abstinence as primary outcome using such methods as self-report and urine test, and showed that intervention groups exhibited greater improvement in the drug use condition than the control groups. The effect sizes (d) ranged from 0.19 to 0.54. One study revealed that a computerized intervention was more cost effective if it was added to treatment as usual. Various interventions were designed to use behavioral therapy approaches, e.g., cognitive behavioral therapy, motivational interviewing, as well as face-to-face interventions. Treatment retention, adverse events, relationship with therapists and engagement in the treatment were assessed as secondary outcomes. These outcomes were equivalent or more effective for the intervention groups compared with the control groups. Computerized and Internet-based psychosocial interventions for drug users have a small to
Full Text Available Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets.
Cheng, F W T; So, S W K; Fung, B W T; Hung, W H; Lee, V W Y
In view of the popularity of Internet usage in Hong Kong, an interactive web-based drug information platform entitled "Ask My Pharmacist - Online University Led drug Enquiry Platform" (AMPOULE) was launched in 2009 to better serve the needs of drug information in Hong Kong. This paper aimed to evaluate the utility of AMPOULE in improving drug-related knowledge among the public and to reassess the needs of the general public in Hong Kong. All enquiries sent via AMPOULE were reviewed. Demographic data, nature of questions and types of drug class covered were analyzed. The workload of pharmacists was examined with respect to the preparation time needed for the enquiry, the lag days to reply and also the timing of enquiry recipient. 2122 enquiries were received from 2009 to 2017. Most enquirers were from Hong Kong (56.6%) and female gender (49.2%). 13% of the concerned subjects were aged over 61-year-old. The most frequent types of questions and medications covered were "Drug Ingredients and Indications" (28.0%) and Adverse Drug Reactions (26.8%) and "Cardiovascular Medication" (21.9%) respectively but these varied in different age groups or enquirer groups. The median time for preparation was 40.0 min (IQR: 25-65 min) while the median time lag was found to be 2.5 days (IQR: 1.0-5.0 days). The number of enquiries received was evenly distributed throughout the day except during 1:00 am to 9:00 am and 7:00 pm to 8:00 pm. AMPOULE has demonstrated that an online platform providing patient-oriented drug information service through the Internet is promising and further promotion is warranted. Current data suggested that the need of different age groups and enquirer groups are different and should therefore be individualized. Copyright © 2018 Elsevier B.V. All rights reserved.
Wischke, Christian; Behl, Marc; Lendlein, Andreas
Shape-memory polymers (SMPs) have gained interest for temporary drug-release systems that should be anchored in the body by self-sufficient active movements of the polymeric matrix. Based on the so far published scientific literature, this review highlights three aspects that require particular attention when combining SMPs with drug molecules: i) the defined polymer morphology as required for the shape-memory function, ii) the strong effects that processing conditions such as drug-loading methodologies can have on the drug-release pattern from SMPs, and iii) the independent control of drug release and degradation by their timely separation. The combination of SMPs with a drug-release functionality leads to multifunctional carriers that are an interesting technology for pharmaceutical sciences and can be further expanded by new materials such as thermoplastic SMPs or temperature-memory polymers. Experimental studies should include relevant molecules as (model) drugs and provide a thermomechanical characterization also in an aqueous environment, report on the potential effect of drug type and loading levels on the shape-memory functionality, and explore the potential correlation of polymer degradation and drug release.
Kettenbach, Joachim; Stadler, Alfred; Katzler, Isabella v.; Schernthaner, Ruediger; Blum, Melanie; Lammer, Johannes; Rand, Thomas
Transarterial chemoembolization (TACE) involves the emulsification of a chemotherapeutic agent in a viscous drug carrier, delivered intra-arterially to liver tumor for maximum effect. TACE reduces arterial inflow, diminishes washout of the chemotherapeutic agent, and decreases systemic exposure. Despite evidence of some clinical success with TACE, a new type of microspheres with drug-eluting capabilities may offer a precisely controlled and sustainable release of the chemotherapeutic agent into the tumor bed. In animal trials tumor necrosis (approaching 100%) was greatest at 7 days, with significantly lower plasma concentrations of doxorubicin than in control animals treated with doxorubicin intra-arterially. Clinically, drug-eluting microspheres loaded with doxorubicin, either at 75 mg/m 2 or at a fixed dose of 150 mg, were used recently and no severe disorders of the hepatic function were observed postprocedure, while a substantial reduction of the fetoprotein levels occurred. An interim analysis of the first 15 patients from the Hong Kong group at 3 months showed an objective response rate of 61.54% and 53.84% according to EASL criteria and RECIST criteria, respectively, and a survival rate of 93.3%. In this paper we present how to use microspheres loaded with doxorubicin and review their clinical value and preliminary performance for treatment of unresectable liver cancer
Full Text Available Gastrointestinal disease is associated with alterations in the mouth or influence the course of the dental diseases, and the dental health care workers are expected to recognize, diagnose, and treat oral conditions associated with gastrointestinal diseases and also provide safe and appropriate dental care for afflicted individuals. Drugs used in the management of these diseases result in oral adverse effects and also are known to interact with those prescribed during dental care. Hence, this article has reviewed the drug considerations and guidelines for drug use during dental management of patients with gastrointestinal diseases.
Ivanovska, V.; Rademaker, C.M.A.; Dijk, L. van; Mantel-Teeuwisse, A.K.
Children differ from adults in many aspects of pharmacotherapy, including capabilities for drug administration, medicine-related toxicity, and taste preferences. It is essential that pediatric medicines are formulated to best suit a child’s age, size, physiologic condition, and treatment
Yonucu, Sirin; Yιlmaz, Defne; Phipps, Colin; Unlu, Mehmet Burcin; Kohandel, Mohammad
Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise. In order to explore the effect of microenvironmental conditions and drug scheduling on normalization benefit, we build a mathematical model that incorporates tumor growth, angiogenesis and IFP. We administer various theoretical combinations of antiangiogenic agents and cytotoxic nanoparticles through heterogeneous vasculature that displays a similar morphology to tumor vasculature. We observe differences in drug extravasation that depend on the scheduling of combined therapy; for concurrent therapy, total drug extravasation is increased but in adjuvant therapy, drugs can penetrate into deeper regions of tumor.
from psychiatric hospitals, drug treatment centers and emergency departments, and studies that discussed misuse of alcohol but not illicit drugs. Data collection and analysis. We created an electronic database that included study abstracts and relevant information matching the keywords and search criteria. We reviewed potentially eligible articles independently by scanning the titles, abstracts, and full texts of articles after removing duplicates. We identified studies for which eligibility was unclear and decided which studies to include after thoroughly reviewing and discussing them. Results. Of the 1649 studies that matched the search criteria, 17 met our inclusion criteria. Thirteen studies identified substance misuse as a significant predictor of leaving the hospital against medical advice. Three studies assessed the prevalence and predictors of leaving the hospital against medical advice among people who inject drugs and found that this phenomenon was commonly reported (prevalence range = 25%–30%). Factors positively associated with leaving the hospital against medical advice included recent injection drug use, Aboriginal ancestry, leaving on weekends and welfare check day. In-hospital methadone use, social support, older age, and admission to a community-based model of care were negatively associated with the outcome. Conclusions. To better understand risk factors associated with leaving the hospital against medical advice among PWUD, future research should consider the effect of individual, social, and structural characteristics on leaving the hospital against medical advice among PWUD. The development and evaluation of novel methods to address interventions to reduce the rate of leaving the hospital prematurely is necessary. PMID:26469651
Full Text Available Abstract Background The effectiveness of hepatoprotective drugs for DIH (drug induced hepatotoxicity during tuberculosis treatment is not clear. We evaluated the effectiveness of hepatoprotective drugs by comparing the period until the normalization of hepatic enzymes between patients who were prescribed with the hepatoprotective drugs after DIH was occurred and patients who were not prescribed with the hepatoprotective drugs. Methods During 2006–2010, 389 patients with active tuberculosis were included in this study. DIH was defined as elevation of peak serum aspartate aminotransferase (AST and/or alanine aminotransferase (ALT of more than twice the upper limit of normal (ULN. We divided the patients into the severe (peak serum AST and/or ALT elevation of >5 times the ULN, moderate (peak serum AST and/or ALT elevation of >3 to ≤5 times the ULN, and mild DIH groups (peak serum AST and/or ALT elevation of >2 to ≤3 times the ULN. We compared the average period until the normalization of hepatic enzymes between patient subgroups with and without hepatoprotective drugs (ursodeoxycholic acid: UDCA, stronger neo-minophagen C: SNMC, and glycyrrhizin. Results In the severe group, there was no significant difference in the average period until the normalization between subgroups with and without hepatoprotective drugs (21.4 ± 10.8 vs 21.5 ± 11.1 days, P = 0.97. In the mild group, the period was longer in the subgroup with hepatoprotective drugs than that without hepatoprotective drugs (15.7 ± 6.2 vs 12.4 ± 7.9 days, P = 0.046. Conclusion Regardless of the severity, hepatoprotective drugs did not shorten the period until the normalization of hepatic enzymes.
Barlow, Jane; Coren, Esther
Parenting practices predict important outcomes for children, and parenting programs are potentially effective means of supporting parents to promote optimal outcomes for children. This review summarizes findings of systematic reviews of parenting programs published in the Campbell Library. Six reviews evaluated the effectiveness of a range of…
Lancaster, Kari; Hughes, Caitlin E; Spicer, Bridget; Matthew-Simmons, Francis; Dillon, Paul
Illicit drugs are never far from the media gaze and although identified almost a decade ago as 'a new battleground' for the alcohol and other drug (AOD) field there has been limited research examining the role of the news media and its effects on audiences and policy. This paper draws together media theories from communication literature to examine media functions. We illustrate how each function is relevant for media and drugs research by drawing upon the existing literature examining Australian media coverage during the late 1990s of escalating heroin-related problems and proposed solutions. Media can influence audiences in four key ways: by setting the agenda and defining public interest; framing issues through selection and salience; indirectly shaping individual and community attitudes towards risk; and feeding into political debate and decision making. Each has relevance for the AOD field. For example, media coverage of the escalating heroin-related problems in Australia played a strong role in generating interest in heroin overdoses, framing public discourse in terms of a health and/or criminal issue and affecting political decisions. Implications AND CONCLUSION: Media coverage in relation to illicit drugs can have multifarious effects. Incorporating media communication theories into future research and actions is critical to facilitate understanding of the short- and long-term impacts of media coverage on illicit drugs and the avenues by which the AOD field can mitigate or inform future media debates on illicit drugs. © 2010 Australasian Professional Society on Alcohol and other Drugs.
Rackham, Daniel M; C Herink, Megan; Stevens, Ian G; Cardoza, Natalie M; Singh, Harleen
The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety Communications and Drug Alerts notifying health care practitioners and the general public of important information regarding drug therapies following FDA approval. These alerts can result in both positive and negative effects on patient care. Most clinical trials are not designed to detect long-term safety end points, and postmarketing surveillance along with patient reported events are often instrumental in signaling the potential harmful effect of a drug. Recently, many cardiovascular (CV) safety announcements have been released for FDA-approved drugs. Because a premature warning could discourage a much needed treatment or prompt a sudden discontinuation, it is essential to evaluate the evidence supporting these FDA alerts to provide effective patient care and to avoid unwarranted changes in therapy. Conversely, paying attention to these warnings in cases involving high-risk patients can prevent adverse effects and litigation. This article reviews the evidence behind recent FDA alerts for drugs with adverse CV effects and discusses the clinical practice implications. © 2013 Pharmacotherapy Publications, Inc.
Barry, David; Lassen, N A
If antihypertensive treatment, especially emergency blood pressure lowering, is always to be safe, more thought should be given to autoregulation of cerebral blood in the hypertensive patient. This topic is reviewed in the present article, in the hypertensive patient. This topic is reviewed...... in the present article, particular emphasis being placed on the resetting of the lower limit of autoregulation to higher pressure in hypertension and the effects of acute administration of anti-hypertensive drugs on CBF and CBF-autoregulation....
Vera M. Kroesen
Full Text Available Lengthy, antimicrobial therapy targeting the pathogen is the mainstay of conventional tuberculosis treatment, complicated by emerging drug resistances. Host-directed therapies, including non-steroidal anti-inflammatory drugs (NSAIDs, in contrast, target host factors to mitigate disease severity. In the present Systematic Review, we investigate whether NSAIDs display any effects as therapy of TB and discuss possible mechanisms of action of NSAIDs as adjunctive therapy of TB. Ten studies, seven preclinical studies in mice and three clinical trials, were included and systematically reviewed. Our results point toward a beneficial effect of NSAIDs as adjunct to current TB therapy regimens, mediated by decreased lung pathology balancing host-immune reaction. The determination of the best timing for their administration in order to obtain the potential beneficial effects needs further investigation. Even if the preclinical evidence requires clinical evaluation, NSAIDs might represent a potential safe, simple, and cheap improvement in therapy of TB.
Haasum, Ylva; Johnell, Kristina
The aim of this study is to systematically review the scientific literature to investigate if use of antiepileptic drugs (AEDs) is associated with falls and/or recurrent falls in old age. We searched the literature for relevant articles in PubMed and Embase published up until 3rd December 2015. Studies on people aged 60 years and over with an observational design assessing the risk of fall in people exposed to AEDs compared to people not exposed to AED were included. We found 744 studies by searching Medline and Embase and an additional 9 studies by reviewing relevant reference lists. Of these studies, 13 fulfilled our predefined criteria. The articles were of various study design, sizes and follow-up times, and presented the results in different ways. Also, confounder adjustment varied considerably between the studies. Ten studies presented results for the association between use of any AED and any fall/injurious fall. Of these studies, 6 presented adjusted estimates, of which all but one showed statistically significant associations between use of any AED and any fall/injurious fall. Six studies investigated the association between use of any AED and recurrent falls. Of these, only 3 studies presented adjusted effect estimates of which 2 reached statistical significance for the association between use of AEDs and recurrent falls in elderly people. Our results indicate an association between use of AEDs and risk of falls and recurrent falls in older people. This finding may be clinically important given that a substantial amount of older people use these drugs. However, further research is needed to increase the knowledge about the actual risk of falls when using these drugs in old age. Copyright © 2017 Elsevier B.V. All rights reserved.
Sanders, A.F. & A.A. Bunt.
Some literature is reviewed on the effect of some drugs, (amphetamine, hypnotics, alcohol), loud noise and sleep loss in test of time estimation, decision making, long term performance and short term memory. Results are most clear with respect to amphetamine, hypnotics and lack of sleep, in that
Treyer, Andrea; Mateus, André; Wiśniewski, Jacek R; Boriss, Hinnerk; Matsson, Pär; Artursson, Per
Intracellular unbound drug concentrations are the pharmacologically relevant concentrations for targets inside cells. Intracellular drug concentrations are determined by multiple processes, including the extent of drug binding to intracellular structures. The aim of this study was to evaluate the effect of neutral lipid (NL) and phospholipid (PL) levels on intracellular drug disposition. The NL and/or PL content of 3T3-L1 cells were enhanced, resulting in phenotypes (in terms of morphology and proteome) reminiscent of adipocytes (high NL and PL) or mild phospholipidosis (only high PL). Intracellular bioavailability ( F ic ) was then determined for 23 drugs in these cellular models and in untreated wild-type cells. A higher PL content led to higher intracellular drug binding and a lower F ic . The induction of NL did not further increase drug binding but led to altered F ic due to increased lysosomal pH. Further, there was a good correlation between binding to beads coated with pure PL and intracellular drug binding. In conclusion, our results suggest that PL content is a major determinant of drug binding in cells and that PL beads may constitute a simple alternative to estimating this parameter. Further, the presence of massive amounts of intracellular NLs did not influence drug binding significantly.
Pringle, Abbie; Harmer, Catherine J
Human models of emotional processing suggest that the direct effect of successful antidepressant drug treatment may be to modify biases in the processing of emotional information. Negative biases in emotional processing are documented in depression, and single or short-term dosing with conventional antidepressant drugs reverses these biases in depressed patients prior to any subjective change in mood. Antidepressant drug treatments also modulate emotional processing in healthy volunteers, which allows the consideration of the psychological effects of these drugs without the confound of changes in mood. As such, human models of emotional processing may prove to be useful for testing the efficacy of novel treatments and for matching treatments to individual patients or subgroups of patients.
Crucq, A.S.; Deridder, V.; Engalytcheff, A.; Slegers, C.; Tilquin, P.
Several drugs (ceftazidime, vancomycin, glucagon, erythromycin and dobutamine) were studied in order to determine their radiostability. The methods used to measure the degradation of the drug were the potency and the colour change after irradiation. Electron spin resonance (ESR) is currently being used to detect irradiated foodstuffs and may be a promising technique to detect irradiated drugs. Trapped radicals in cefazolin sodium were studied and quantified by ESR for this purpose. It is proposed that the trapped radicals play an important role in the formation of the final radiolytic compounds. The potency of ceftazidime was not significantly modified after an irradiation of 25 kGy, whereas the potency of erythromycin and dobutamine decreased slightly. Glucagon was revealed to be radiosensitive with a significant decrease in its potency after irradiation. The visible spectra of glucagon and dobutamine did not change significantly after irradiation. The absorbance of erythromycin and vancomycin increased after irradiation. According to European Pharmacopoeia standards, the colour change of ceftazidime is unacceptable. The ESR spectra reveal that the trapped radicals in cefazolin sodium are characteristic of an irradiation. The radical concentration is dependent on the irradiation dose and decays over time. Radical concentration in cefazolin sodium was reduced by 99% after 100 days of storage. These radicals are responsible for about 13% of the measured final radiolytic product. Ionic reactions could also lead to final radiolytic products. (author)
Kim, Ben Yb; Sharafoddini, Anis; Tran, Nam; Wen, Emily Y; Lee, Joon
General consumers can now easily access drug information and quickly check for potential drug-drug interactions (PDDIs) through mobile health (mHealth) apps. With aging population in Canada, more people have chronic diseases and comorbidities leading to increasing numbers of medications. The use of mHealth apps for checking PDDIs can be helpful in ensuring patient safety and empowerment. The aim of this study was to review the characteristics and quality of publicly available mHealth apps that check for PDDIs. Apple App Store and Google Play were searched to identify apps with PDDI functionality. The apps' general and feature characteristics were extracted. The Mobile App Rating Scale (MARS) was used to assess the quality. A total of 23 apps were included for the review-12 from Apple App Store and 11 from Google Play. Only 5 of these were paid apps, with an average price of $7.19 CAD. The mean MARS score was 3.23 out of 5 (interquartile range 1.34). The mean MARS scores for the apps from Google Play and Apple App Store were not statistically different (P=.84). The information dimension was associated with the highest score (3.63), whereas the engagement dimension resulted in the lowest score (2.75). The total number of features per app, average rating, and price were significantly associated with the total MARS score. Some apps provided accurate and comprehensive information about potential adverse drug effects from PDDIs. Given the potentially severe consequences of incorrect drug information, there is a need for oversight to eliminate low quality and potentially harmful apps. Because managing PDDIs is complex in the absence of complete information, secondary features such as medication reminder, refill reminder, medication history tracking, and pill identification could help enhance the effectiveness of PDDI apps. ©Ben YB Kim, Anis Sharafoddini, Nam Tran, Emily Y Wen, Joon Lee. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 28.03.2018.
The effect of membrane potential change on anionic drugs Indomethacin and barbitone induced human erythrocyte shape change and red cell uptake of drug has been studied using microscopy and spectrophotometry techniques respectively. The membrane potential was changed by reducing the extracellular chloride ...
Hawkins, J. David; And Others
A test was conducted of a supplemental skills training and social-network-development aftercare program with 130 drug abusers from four residential therapeutic communities. The intervention produced positive effects on subjects' performance at the conclusion of treatment. Performance improved in situations involving avoidance of drug use, coping…
Giessing, Carsten; Thiel, Christiane M.
Previous studies document that cholinergic and noradrenergic drugs improve attention, memory and cognitive control in healthy subjects and patients with neuropsychiatric disorders. In humans neural mechanisms of cholinergic and noradrenergic modulation have mainly been analyzed by investigating drug-induced changes of task-related neural activity measured with functional magnetic resonance imaging (fMRI). Endogenous neural activity has often been neglected. Further, although drugs affect the coupling between neurons, only a few human studies have explicitly addressed how drugs modulate the functional connectome, i.e., the functional neural interactions within the brain. These studies have mainly focused on synchronization or correlation of brain activations. Recently, there are some drug studies using graph theory and other new mathematical approaches to model the brain as a complex network of interconnected processing nodes. Using such measures it is possible to detect not only focal, but also subtle, widely distributed drug effects on functional network topology. Most important, graph theoretical measures also quantify whether drug-induced changes in topology or network organization facilitate or hinder information processing. Several studies could show that functional brain integration is highly correlated with behavioral performance suggesting that cholinergic and noradrenergic drugs which improve measures of cognitive performance should increase functional network integration. The purpose of this paper is to show that graph theory provides a mathematical tool to develop theory-driven biomarkers of pro-cognitive drug effects, and also to discuss how these approaches can contribute to the understanding of the role of cholinergic and noradrenergic modulation in the human brain. Finally we discuss the “global workspace” theory as a theoretical framework of pro-cognitive drug effects and argue that pro-cognitive effects of cholinergic and noradrenergic drugs
Carlo Luca Romanò
Full Text Available Purpose. Chronic low back pain (LBP is often characterized by both nociceptive and neuropathic components. While various monotherapies have been reported of only limited efficacy, combining drugs with different mechanisms of action and targets appears a rational approach. Aim of this systematic review is to assess the efficacy and safety of different combined pharmacological treatments, compared to monotherapy or placebo, for the pharmacological treatment of chronic LBP. Methods. Published papers, written or abstracted in English from 1990 through 2011, comparing combined pharmacological treatments of chronic LBP to monotherapy or placebo were reviewed. Results. Six articles met the inclusion criteria. Pregabalin combined with celecoxib or opioids was shown to be more effective than either monotherapy. Oxycodone-paracetamol versus previous treatments and tramadol-paracetamol versus placebo were also reported as effective, while morphine-nortriptyline did not show any benefit over any single agent. Conclusions. In spite of theoretical advantages of combined pharmacological treatments of chronic LBP, clinical studies are remarkably few. Available data show that combined therapy, including antinociceptive and antineuropathic agents is more effective than monotherapy, with similar side effects.
Bahar, Muh Akbar; Setiawan, Didik; Hak, Eelko; Wilffert, Bob
Currently, most guidelines on drug-drug interaction (DDI) neither consider the potential effect of genetic polymorphism in the strength of the interaction nor do they account for the complex interaction caused by the combination of DDI and drug-gene interaction (DGI) where there are multiple
Full Text Available Abstract Background As every healthcare intervention carries some risk of harm, clinical decision making needs to be supported by a systematic assessment of the balance of benefit to harm. A systematic review that considers only the favourable outcomes of an intervention, without also assessing the adverse effects, can mislead by introducing a bias favouring the intervention. Much of the current guidance on systematic reviews is directed towards the evaluation of effectiveness; but this differs in important ways from the methods used in assessing the safety and tolerability of an intervention. A detailed discussion of why, how and when to include adverse effects in a systematic review, is required. Methods This discussion paper, which presupposes a basic knowledge of systematic review methodology, was developed by consensus among experienced reviewers, members of the Adverse Effects Subgroup of The Cochrane Collaboration, and supplemented by a consultation of content experts in reviews methodology, as well as those working in drug safety. Results A logical framework for making decisions in reviews that incorporate adverse effects is provided. We explore situations where a comprehensive investigation of adverse effects is warranted and suggest strategies to identify practicable and clinically useful outcomes. The advantages and disadvantages of including observational and experimental study designs are reviewed. The consequences of including separate studies for intended and unintended effects are explained. Detailed advice is given on designing electronic searches for studies with adverse effects data. Reviewers of adverse effects are given general guidance on the assessment of study bias, data collection, analysis, presentation and the interpretation of harms in a systematic review. Conclusion Readers need to be able to recognize how strategic choices made in the review process determine what harms are found, and how the findings may affect
Shaw, M T; Spector, M H; Ladman, A J [New Mexico Univ., Albuquerque (USA)
Intestinal malabsorption and the structural changes in the small intestine in relation to cancer, radiotherapy and cytotoxic drugs are reviewed. Primary intestinal malignancies are often associated with malabsorption; further studies have shown that tumours outside the gastrointestinal tract may also be accompanied by changes in intestinal structure resulting in malabsorption. Abdominal radiotherapy of cancer patients has been shown to result in ultrastructural changes in the small intestine, a decrease in intestinal enzyme activity and malabsorption of nutrients. The effects of cytotoxic drugs on the small intestinal structure and function are reviewed in more detail. The drugs discussed include the alkylating agents such as nitrogen mustard, cyclophosphamide, iphosphamide, 1,3-bis (2-chloroethyl)-1-nitrosourea and 1(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea. The effects of antimetabolites such as aminopterin, methotrexate, 5-fluoracil, cytosine arabinoside and 6-mercaptorpurine are also reviewed. Other drugs discussed were adriamycin, vincrinstine sulfate, vinblastine and hydroxyurea. Studies of the effects of combination chemotherapy on small intestinal structure and function are also described. It is concluded that chemotherapeutic drugs and radiation therapy may aggravate a malabsorptive state in view of their toxicity to the small intestinal cell, or may by themselves be responsible for malabsorption with resultant increase in cachexia and weight loss.
Shaw, M.T.; Spector, M.H.; Ladman, A.J.
Intestinal malabsorption and the structural changes in the small intestine in relation to cancer, radiotherapy and cytotoxic drugs are reviewed. Primary intestinal malignancies are often associated with malabsorption; further studies have shown that tumours outside the gastrointestinal tract may also be accompanied by changes in intestinal structure resulting in malabsorption. Abdominal radiotherapy of cancer patients has been shown to result in ultrastructural changes in the small intestine, a decrease in intestinal enzyme activity and malabsorption of nutrients. The effects of cytotoxic drugs on the small intestinal structure and function are reviewed in more detail. The drugs discussed include the alkylating agents such as nitrogen mustard, cyclophosphamide, iphosphamide, 1,3-bis (2-chloroethyl)-1-nitrosourea and 1(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea. The effects of antimetabolites such as aminopterin, methotrexate, 5-fluoracil, cytosine arabinoside and 6-mercaptorpurine are also reviewed. Other drugs discussed were adriamycin, vincrinstine sulfate, vinblastine and hydroxyurea. Studies of the effects of combination chemotherapy on small intestinal structure and function are also described. It is concluded that chemotherapeutic drugs and radiation therapy may aggravate a malabsorptive state in view of their toxicity to the small intestinal cell, or may by themselves be responsible for malabsorption with resultant increase in cachexia and weight loss. (UK)
Silumbwe, Adam; Zulu, Joseph Mumba; Halwindi, Hikabasa; Jacobs, Choolwe; Zgambo, Jessy; Dambe, Rosalia; Chola, Mumbi; Chongwe, Gershom; Michelo, Charles
Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF) elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA) region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs) through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Mass drug administration for lymphatic filariasis elimination programmes should design their implementation strategies differently based on specific contextual factors to
Full Text Available Abstract Background Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. Methods A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. Results The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Conclusion Mass drug administration for lymphatic filariasis elimination programmes should design their implementation
Full Text Available BACKGROUND: High levels of patient adherence to antimalarial treatment are important in ensuring drug effectiveness. To achieve this goal, it is important to understand levels of patient adherence, and the range of study designs and methodological challenges involved in measuring adherence and interpreting results. Since antimalarial adherence was reviewed in 2004, there has been a major expansion in the use of artemisinin-based combination therapies (ACTs in the public sector, as well as initiatives to make them more widely accessible through community health workers and private retailers. These changes and the large number of recent adherence studies raise the need for an updated review on this topic. OBJECTIVE: We conducted a systematic review of studies reporting quantitative results on patient adherence to antimalarials obtained for treatment. RESULTS: The 55 studies identified reported extensive variation in patient adherence to antimalarials, with many studies reporting very high adherence (90-100% and others finding adherence of less than 50%. We identified five overarching approaches to assessing adherence based on the definition of adherence and the methods used to measure it. Overall, there was no clear pattern in adherence results by approach. However, adherence tended to be higher among studies where informed consent was collected at the time of obtaining the drug, where patient consultations were directly observed by research staff, and where a diagnostic test was obtained. CONCLUSION: Variations in reported adherence may reflect factors related to patient characteristics and the nature of their consultation with the provider, as well as methodological variations such as interaction between the research team and patients before and during the treatment. Future studies can benefit from an awareness of the impact of study procedures on adherence outcomes, and the identification of improved measurement methods less dependent on self-report.
Bruxvoort, Katia; Goodman, Catherine; Kachur, S Patrick; Schellenberg, David
High levels of patient adherence to antimalarial treatment are important in ensuring drug effectiveness. To achieve this goal, it is important to understand levels of patient adherence, and the range of study designs and methodological challenges involved in measuring adherence and interpreting results. Since antimalarial adherence was reviewed in 2004, there has been a major expansion in the use of artemisinin-based combination therapies (ACTs) in the public sector, as well as initiatives to make them more widely accessible through community health workers and private retailers. These changes and the large number of recent adherence studies raise the need for an updated review on this topic. We conducted a systematic review of studies reporting quantitative results on patient adherence to antimalarials obtained for treatment. The 55 studies identified reported extensive variation in patient adherence to antimalarials, with many studies reporting very high adherence (90-100%) and others finding adherence of less than 50%. We identified five overarching approaches to assessing adherence based on the definition of adherence and the methods used to measure it. Overall, there was no clear pattern in adherence results by approach. However, adherence tended to be higher among studies where informed consent was collected at the time of obtaining the drug, where patient consultations were directly observed by research staff, and where a diagnostic test was obtained. Variations in reported adherence may reflect factors related to patient characteristics and the nature of their consultation with the provider, as well as methodological variations such as interaction between the research team and patients before and during the treatment. Future studies can benefit from an awareness of the impact of study procedures on adherence outcomes, and the identification of improved measurement methods less dependent on self-report.
Ponticelli, Claudio; Sala, Gabriele; Glassock, Richard J
With advancing age, the functional reserve of many organs tends to decrease. In particular, the lean body mass, the levels of serum albumin, the blood flow to the liver, and the glomerular filtration rate are reduced in elderly individuals and can be further impaired by the concomitant presence of acute or chronic kidney disease. Moreover, patients with kidney disease are often affected by comorbid processes and are prescribed multiple medications. The aging process also modifies some drug interactions, including the affinity of some drugs for their receptor, the number of receptors, and the cell responses upon receptor activation. Therefore, older patients with kidney disease are particularly susceptible to the risks of adverse drug reactions. Planning a pharmacological regimen in such patients is confounded by the paucity of information available on the pharmacokinetic and pharmacodynamic profiles of a large number of drugs commonly used in this group of patients. Finally, many aged patients suffer from unintentional poor compliance. In this review, the problems physicians face in designing safe and effective medication management in elderly individuals are discussed, paying attention to those more frequently used, which may be potentially harmful in patients with kidney disease. The risks of overdosing and underdosing are outlined, and some recommendations to reduce the risk of adverse drug reactions are provided. A review of the literature covering the field of drug management in older patients with kidney disease was performed by selecting those articles published between January 1, 1990, and December 1, 2014, using PubMed as a search engine with the keywords elderly, kidney disease, drugs, drug interaction, and renal function. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
Serna, Clara; Vicente, Ascensión; Finke, Christian; Ortiz, Antonio J
Molar incisor hypomineralization (MIH) is an idiopathic syndrome that has been associated with several etiologic factors. The authors' objective was to systematically review studies in which the investigators had studied how the etiology of MIH was related to medication intake. The search covered a period from January 1, 1965, to September 29, 2014. The search revealed 1,042 articles, to which the authors applied eligibility criteria and selected 20 studies for review. The authors considered 9 of the 20 studies to be high quality. The drugs used in these studies were chemotherapeutic drugs, antibiotics, asthma drugs, antiepileptic drugs, antiviral drugs, antifungal drugs, and antiparasitic drugs. Two reviewers independently performed risk-of-bias assessment and data extraction. The investigators of all of the studies had reported enamel defects, but only 2 sets of investigators had used the term "molar incisor hypomineralization." Owing to the different methodologies used by the investigators of the selected studies, the authors could not perform a meta-analysis of the study results. More well-designed prospective studies are needed to clarify the relationship between MIH and medication. It would be convenient to establish a preventive protocol in patients with a potential risk of developing MIH to avoid the complications that are characteristic of this disease. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.
Hecq, J-D; Godet, M; Jamart, J; Galanti, L
Microwave freeze-thaw treatment (MFTT) of injectable drugs can support the development of centralized intravenous admixtures services (CIVAS). The aim of the review is to collect information and results about this method. A systematic review of the scientific literature about injectable drug stability studies was performed. The data are presented in a table and describe name of the drug, producer, final concentration, temperature and time of freezing storage, type of microwave oven, thawing power, method of dosage and results after treatment or final long-term storage at 5±3 °C. From 1980 to 2014, 59 drugs were studied by MFTT and the results were presented in 49 publications. Forty papers were presented by 8 teams (2 to 18 by team). The temperatures of freezing storage vary from -70 °C to -10 °C, the time storage from 4 hours to 12 months, the thaw from low to full power. Dosages are mainly made by high performance liquid chromatography. Most of the 59 drugs are stable during and after treatment. Only 3 teams have tested the long-term stability after MFTT, the first for ganciclovir after 7 days, the second for ceftizoxime after 30 days and the third for 19 drugs after 11 to 70 days. This review can help CIVAS to take in charge the productions of ready-to-use injectable drugs. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.
Pandit, Vinay; Kumar, Ajay; Ashawat, Mahendra S; Verma, Chander P; Kumar, Pravin
Pulsatile drug delivery system (PDDS) shows potential significance in the field of drug delivery to release the maximum amount of drug at a definite site and at specific time. PDDS are mainly time controlled delivery devices having a definite pause period for drug release, which is not affected by acidity, alkalinity, motility and enzymes present in the gastrointestinal tract. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. The review article, discuss the general concepts, marketed formulations and patents or any other recent advancement in pulsatile release technology. It also highlights on diseases requiring therapy by pulsatile release, various researches on herbal pulsatile formulations and quality control aspects of PDDS. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Oil and emulsion vehicles have been shown to alter the oral absorption of many drugs. This may be due to enhanced lymph flow and/or altered gastro-intestinal motility in the presence of the oils. The oral absorption of a model compound (DOT) in the presence of three chemically different oils, arachis oil, Miglyol 812 and liquid paraffin was investigated in rats, the influence of lymphatic absorption and gastro-intestinal motility being determined. The findings were applied to the for.mulation...
Light, Donald W; Lexchin, Joel; Darrow, Jonathan J
Over the past 35 years, patients have suffered from a largely hidden epidemic of side effects from drugs that usually have few offsetting benefits. The pharmaceutical industry has corrupted the practice of medicine through its influence over what drugs are developed, how they are tested, and how medical knowledge is created. Since 1906, heavy commercial influence has compromised congressional legislation to protect the public from unsafe drugs. The authorization of user fees in 1992 has turned drug companies into the FDA's prime clients, deepening the regulatory and cultural capture of the agency. Industry has demanded shorter average review times and, with less time to thoroughly review evidence, increased hospitalizations and deaths have resulted. Meeting the needs of the drug companies has taken priority over meeting the needs of patients. Unless this corruption of regulatory intent is reversed, the situation will continue to deteriorate. We offer practical suggestions including: separating the funding of clinical trials from their conduct, analysis, and publication; independent FDA leadership; full public funding for all FDA activities; measures to discourage R&D on drugs with few, if any, new clinical benefits; and the creation of a National Drug Safety Board. © 2013 American Society of Law, Medicine & Ethics, Inc.
Small, Will; Maher, Lisa; Kerr, Thomas
Ethnographic research among people who inject drugs (PWID) involves complex ethical issues. While ethical review frameworks have been critiqued by social scientists, there is a lack of social science research examining institutional ethical review processes, particularly in relation to ethnographic work. This case study describes the institutional ethical review of an ethnographic research project using observational fieldwork and in-depth interviews to examine injection drug use. The review process and the salient concerns of the review committee are recounted, and the investigators' responses to the committee's concerns and requests are described to illustrate how key issues were resolved. The review committee expressed concerns regarding researcher safety when conducting fieldwork, and the investigators were asked to liaise with the police regarding the proposed research. An ongoing dialogue with the institutional review committee regarding researcher safety and autonomy from police involvement, as well as formal consultation with a local drug user group and solicitation of opinions from external experts, helped to resolve these issues. This case study suggests that ethical review processes can be particularly challenging for ethnographic projects focused on illegal behaviours, and that while some challenges could be mediated by modifying existing ethical review procedures, there is a need for legislation that provides legal protection of research data and participant confidentiality. Copyright © 2013 Elsevier Ltd. All rights reserved.
Barrio, Pablo; Reynolds, Jillian; García-Altés, Anna; Gual, Antoni; Anderson, Peter
Drug use accounts for one of the main disease groups in Europe, with relevant consequences to society. There is an increasing need to evaluate the economic consequences of drug use in order to develop appropriate policies. Here, we review the social costs of illegal drugs, alcohol and tobacco in the European Union. A systematic search of relevant databases was conducted. Grey literature and previous systematic reviews were also searched. Studies reporting on social costs of illegal drugs, alcohol and tobacco were included. Methodology, cost components as well as costs were assessed from individual studies. To compare across studies, final costs were transformed to 2014 Euros. Forty-five studies reported in 43 papers met the inclusion criteria (11 for illegal drugs, 26 for alcohol and 8 for tobacco). While there was a constant inclusion of direct costs related to treatment of substance use and comorbidities, there was a high variability for the rest of cost components. Total costs showed also a great variability. Price per capita for the year 2014 ranged from €0.38 to €78 for illegal drugs, from €26 to €1500 for alcohol and from €10.55 to €391 for tobacco. Drug use imposes a heavy economic burden to Europe. However, given the high existing heterogeneity in methodologies, and in order to better assess the burden and thus to develop adequate policies, standardised methodological guidance is needed. [Barrio P, Reynolds J, García-Altés A, Gual A, Anderson P. Social costs of illegal drugs, alcohol and tobacco in the European Union: A systematic review. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.
... recipient or the recipient's caregiver. The State must provide pharmacies with detailed information as to what they must do to comply with prospective DUR requirements, including guidelines on counseling... prescription is filled or delivered to the recipient or the recipient's caregiver. The review must include...
Guerrini, Renzo; Parmeggiani, Lucio
Background: The aim in treating epilepsy is to minimise or control seizures with full respect of quality-of-life issues, especially of cognitive functions. Optimal treatment first demands a correct recognition of the major type of seizures, followed by a correct diagnosis of the type of epilepsy or of the specific syndrome. Methods: Review of data…
Zhao, Boyang; Hemann, Michael T; Lauffenburger, Douglas A
The substantial spatial and temporal heterogeneity observed in patient tumors poses considerable challenges for the design of effective drug combinations with predictable outcomes. Currently, the implications of tissue heterogeneity and sampling bias during diagnosis are unclear for selection and subsequent performance of potential combination therapies. Here, we apply a multiobjective computational optimization approach integrated with empirical information on efficacy and toxicity for individual drugs with respect to a spectrum of genetic perturbations, enabling derivation of optimal drug combinations for heterogeneous tumors comprising distributions of subpopulations possessing these perturbations. Analysis across probabilistic samplings from the spectrum of various possible distributions reveals that the most beneficial (considering both efficacy and toxicity) set of drugs changes as the complexity of genetic heterogeneity increases. Importantly, a significant likelihood arises that a drug selected as the most beneficial single agent with respect to the predominant subpopulation in fact does not reside within the most broadly useful drug combinations for heterogeneous tumors. The underlying explanation appears to be that heterogeneity essentially homogenizes the benefit of drug combinations, reducing the special advantage of a particular drug on a specific subpopulation. Thus, this study underscores the importance of considering heterogeneity in choosing drug combinations and offers a principled approach toward designing the most likely beneficial set, even if the subpopulation distribution is not precisely known.
Andrade, Luiz Flavio; Sermet, Catherine; Pichetti, Sylvain
Pharmaceutical firms have been criticized for concentrating efforts of R&D on the so-called me-too or follow-on drugs. There have been many comments for and against the dissemination of these incremental innovations but few papers have broached the subject from an econometric point of view, possibly because identification of me-too or follow-on drugs is not so obvious. This paper focuses on the impact of entry order on follow-on drug competition in the French market between the years 2001 and 2007. More precisely, this study examines the effects on market share of first entrants in the follow-on drug market and how this possible competitive advantage changes over time. First results are coherent with theoretical microeconomic issues concerning the importance of being first. We find evidence that first movers in the follow-on drug market have the ability to capture and maintain greater market share for a long period of time. The hierarchical market position of follow-on drugs does not seem to be affected by generic drug emergence. From a dynamic perspective, our analysis shows that market share is positively correlated with the ability of follow-on drugs to set prices higher than the average follow-on drug prices in a specific therapeutic class, which means that market power remains considerably important for first movers. Moreover, we found that the optimum level of innovation to maximize market share is the highest one.
Pivette, Mathilde; Mueller, Judith E; Crépey, Pascal; Bar-Hen, Avner
This systematic literature review aimed to summarize evidence for the added value of drug sales data analysis for the surveillance of infectious diseases. A search for relevant publications was conducted in Pubmed, Embase, Scopus, Cochrane Library, African Index Medicus and Lilacs databases. Retrieved studies were evaluated in terms of objectives, diseases studied, data sources, methodologies and performance for real-time surveillance. Most studies compared drug sales data to reference surveillance data using correlation measurements or indicators of outbreak detection performance (sensitivity, specificity, timeliness of the detection). We screened 3266 articles and included 27 in the review. Most studies focused on acute respiratory and gastroenteritis infections. Nineteen studies retrospectively compared drug sales data to reference clinical data, and significant correlations were observed in 17 of them. Four studies found that over-the-counter drug sales preceded clinical data in terms of incidence increase. Five studies developed and evaluated statistical algorithms for selecting drug groups to monitor specific diseases. Another three studies developed models to predict incidence increase from drug sales. Drug sales data analyses appear to be a useful tool for surveillance of gastrointestinal and respiratory disease, and OTC drugs have the potential for early outbreak detection. Their utility remains to be investigated for other diseases, in particular those poorly surveyed.
Kennedy, Deborah A.; Cooley, Kieran; Skidmore, Becky; Fritz, Heidi; Campbell, Tara; Seely, Dugald
Vitamin D has reported anti-cancer and anti-inflammatory properties modulated through gene transcription and non-genomic signaling cascades. The purpose of this review was to summarize the available research on interactions and pharmacokinetics between vitamin D and the pharmaceutical drugs used in patients with cancer. Hypercalcemia was the most frequently reported side effect that occurred in high dose calcitriol. The half-life of 25(OH)D 3 and/or 1,25(OH) 2 D 3 was found to be impacted by cimetidine; rosuvastatin; prednisone and possibly some chemotherapy drugs. No unusual adverse effects in cancer patients; beyond what is expected from high dose 1,25(OH) 2 D 3 supplementation, were revealed through this review. While sufficient evidence is lacking, supplementation with 1,25(OH) 2 D 3 during chemotherapy appears to have a low risk of interaction. Further interactions with vitamin D 3 have not been studied
Kesselheim, Aaron S; Misono, Alexander S; Lee, Joy L; Stedman, Margaret R; Brookhart, M Alan; Choudhry, Niteesh K; Shrank, William H
Use of generic drugs, which are bioequivalent to brand-name drugs, can help contain prescription drug spending. However, there is concern among patients and physicians that brand-name drugs may be clinically superior to generic drugs. To summarize clinical evidence comparing generic and brand-name drugs used in cardiovascular disease and to assess the perspectives of editorialists on this issue. Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1984 to August 2008. Studies compared generic and brand-name cardiovascular drugs using clinical efficacy and safety end points. We separately identified editorials addressing generic substitution. We extracted variables related to the study design, setting, participants, clinical end points, and funding. Methodological quality of the trials was assessed by Jadad and Newcastle-Ottawa scores, and a meta-analysis was performed to determine an aggregate effect size. For editorials, we categorized authors' positions on generic substitution as negative, positive, or neutral. We identified 47 articles covering 9 subclasses of cardiovascular medications, of which 38 (81%) were randomized controlled trials (RCTs). Clinical equivalence was noted in 7 of 7 RCTs (100%) of beta-blockers, 10 of 11 RCTs (91%) of diuretics, 5 of 7 RCTs (71%) of calcium channel blockers, 3 of 3 RCTs (100%) of antiplatelet agents, 2 of 2 RCTs (100%) of statins, 1 of 1 RCT (100%) of angiotensin-converting enzyme inhibitors, and 1 of 1 RCT (100%) of alpha-blockers. Among narrow therapeutic index drugs, clinical equivalence was reported in 1 of 1 RCT (100%) of class 1 antiarrhythmic agents and 5 of 5 RCTs (100%) of warfarin. Aggregate effect size (n = 837) was -0.03 (95% confidence interval, -0.15 to 0.08), indicating no evidence of superiority of brand-name to generic drugs. Among 43 editorials, 23 (53%) expressed a negative view of generic drug substitution. Whereas evidence does not
Shan, Ning; Perry, Miranda L; Weyna, David R; Zaworotko, Michael J
Pharmaceutical cocrystallization has emerged in the past decade as a new strategy to enhance the clinical performance of orally administered drugs. A pharmaceutical cocrystal is a multi-component crystalline material in which the active pharmaceutical ingredient is in a stoichiometric ratio with a second compound that is generally a solid under ambient conditions. The resulting cocrystal exhibits different solid-state thermodynamics, leading to changes in physicochemical properties that offer the potential to significantly modify drug pharmacokinetics. The impact of cocrystallization upon drug pharmacokinetics has not yet been well delineated. Herein, we compile previously published data to address two salient questions: what effect does cocrystallization impart upon physicochemical properties of a drug substance and to what degree can those effects impact its pharmacokinetics. Cocrystals can impact various aspects of drug pharmacokinetics, including, but not limited to, drug absorption. The diversity of solid forms offered through cocrystallization can facilitate drastic changes in solubility and pharmacokinetics. Therefore, it is unsurprising that cocrystal screening is now a routine step in early-stage drug development. With the increasing recognition of pharmaceutical cocrystals from clinical, regulatory and legal perspectives, the systematic commercialization of cocrystal containing drug products is just a matter of time.
Shord, Stacy S; Shah, Kanan; Lukose, Alvina
Many Americans use complementary and alternative medicine (CAM) to prevent or alleviate common illnesses, and these medicines are commonly used by individuals with cancer.These medicines or botanicals share the same metabolic and transport proteins, including cytochrome P450 enzymes (CYP), glucuronosyltransferases (UGTs), and P-glycoprotein (Pgp), with over-the-counter and prescription medicines increasing the likelihood of drug-botanical interactions.This review provides a brief description of the different proteins, such as CYPs, UGTs, and Pgp.The potential effects of drug-botanical interactions on the pharmacokinetics and pharmacodynamics of the drug or botanical and a summary of the more common models used to study drug metabolism are described.The remaining portion of this review summarizes the data extracted from several laboratory, animal, and clinical studies that describe the metabolism, transport, and potential interactions of 8 selected botanicals. The 8 botanicals include black cohosh, Echinacea, garlic, Gingko biloba, green tea, kava, milk thistle, and St John's wort; these botanicals are among some of the more common botanicals taken by individuals with cancer.These examples are included to demonstrate how to interpret the different studies and how to use these data to predict the likelihood of a clinically significant drug-botanical interaction.
Rani, Susheela; Malik, Ashok Kumar; Kaur, Ramandeep; Kaur, Ripneel
The analysis of drugs in various biological fluids is an important criterion for the determination of the physiological performance of a drug. After sampling of the biological fluid, the next step in the analytical process is sample preparation. Sample preparation is essential for isolation of desired components from complex biological matrices and greatly influences their reliable and accurate determination. The complexity of biological fluids adds to the challenge of direct determination of the drug by chromatographic analysis, therefore demanding a sample preparation step that is often time consuming, tedious and frequently overlooked. However, direct online injection methods offer the advantage of reducing sample preparation steps and enabling effective pre-concentration and clean-up of biological fluids. These procedures can be automated and therefore reduce the requirements for handling potentially infectious biomaterial, improve reproducibility, and minimize sample manipulations and potential contamination. This review is focused on the discovery and development of high-performance liquid chromatography (HPLC) and gas chromatography (GC) with different detectors. The drugs covered in this review are antiepileptics, antidepressant (AD), and quinolones. The application of these methods for determination of these drugs in biological, environmental and pharmaceutical samples has also been discussed.
Full Text Available Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy.Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed.During the study period, 1038 patients (450 girls, 588 boys were enrolled. Among them, 44.6% (463 had seizures in the acute phase, 33% had status epilepticus, and 26% (251 developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects.Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy.
Naidoo, Anushka; Naidoo, Kogieleum; McIlleron, Helen; Essack, Sabiha; Padayatchi, Nesri
Moxifloxacin, an 8-methoxy quinolone, is an important drug in the treatment of multidrug-resistant tuberculosis and is being investigated in novel drug regimens with pretomanid, bedaquiline, and pyrazinamide, or rifapentine, for the treatment of drug-susceptible tuberculosis. Early results of these studies are promising. Although current evidence does not support the use of moxifloxacin in treatment-shortening regimens for drug-susceptible tuberculosis, it may be recommended in patients unable to tolerate standard first-line drug regimens or for isoniazid monoresistance. Evidence suggests that the standard 400-mg dose of moxifloxacin used in the treatment of tuberculosis may be suboptimal in some patients, leading to worse tuberculosis treatment outcomes and emergence of drug resistance. Furthermore, a drug interaction with the rifamycins results in up to 31% reduced plasma concentrations of moxifloxacin when these are combined for treatment of drug-susceptible tuberculosis, although the clinical relevance of this interaction is unclear. Moxifloxacin exhibits extensive interindividual pharmacokinetic variability. Higher doses of moxifloxacin may be needed to achieve drug exposures required for improved clinical outcomes. Further study is, however, needed to determine the safety of proposed higher doses and clinically validated targets for drug exposure to moxifloxacin associated with improved tuberculosis treatment outcomes. We discuss in this review the evidence for the use of moxifloxacin in drug-susceptible tuberculosis and explore the role of moxifloxacin pharmacokinetics, pharmacodynamics, and drug interactions with rifamycins, on tuberculosis treatment outcomes when used in first-line tuberculosis drug regimens. © 2017, The American College of Clinical Pharmacology.
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Micro RNAs (miRNAs are non-coding RNAs that can regulate gene expression to target several mRNAs in a gene regulatory network. MiRNA related Single Nucleotide Polymorphisms (S.N.P.s represent a newly identified type of genetic variability that can be of influence to the risk of certain human diseases and also affect how drugs can be activated and metabolized by patients. This will help in personalized medicines which are used for administrating the correct dosage of drug and drug efficacy. miRNA deregulated expression has been extensively described in a variety of diseases such as Cancer, Obesity , Diabetes, Schizophrenia and control and self renewal of stem cells. MiRNA can function as oncogenes and/or tumor suppressors. MiRNAs may act as key regulators of processes as diverse as early development, cell proliferation and cell death, apoptosis and fat metabolism and cell differentiation .miRNA expression have shown their role in brain development chronic lymphocytic leukemia, colonic adeno carcinoma, Burkiff’s lymphoma and viral infection. These show their links with viral disease, neurodevelopment and cancer. It has been shown that they play a key role in melanoma metastasis. These may be
Classen, David C; Phansalkar, Shobha; Bates, David W
Medications represent the most common intervention in health care, despite their benefits; they also lead to an estimated 1.5 million adverse drug events and tens of thousands of hospital admissions each year. Although some are not preventable given what is known today, many types are, and one key cause which is preventable is drug-drug interactions (DDIs). Most electronic health record systems include programs that can check and prevent these types of interactions as a routine part of medication ordering. Studies suggest that these systems as implemented often do not effectively screen for these DDIs. A major reason for this deficiency is the lack of any national standard for the critical DDIs that should be routinely operationlized in these complex systems. We review the leading critical DDI lists from multiple sources including several leading health systems, a leading commercial content provider, the Leapfrog CPOE Testing Standard, and the new Office of the National Coordinator (ONC) DDI List. Implementation of strong DDI checking is one of the important steps in terms of realizing the benefits of electronic prescribing with respect to safety. Hopefully, the ONC list will make it easier for organizations to ensure they are including the most important interactions, and the Leapfrog List may help these organizations develop an operational DDI list that can be practically implemented. In addition, this review has identified 7 common DDIs that can be the starting point for all organizations in this area of medication safety.
Full Text Available Background. Nonsteroidal anti-inflammatory drugs (NSAIDs are the most widely used medication in several countries, including Thailand. NSAIDs have been associated with hepatic side effects; however, the frequency of these side effects is uncertain. Aim of the Review. To systematically review published literature on randomized, controlled trials that assessed the risk of clinically significant hepatotoxicity associated with NSAIDs. Methods. Searches of bibliographic databases EMBASE, PubMed, and the Cochrane Library were conducted up to July 30, 2016, to identify randomized controlled trials of ibuprofen, naproxen, diclofenac, piroxicam, meloxicam, mefenamic acid, indomethacin, celecoxib, and etoricoxib in adults with any disease that provide information on hepatotoxicity outcomes. Results. Among the 698 studies, 18 studies met the selection criteria. However, only 8 studies regarding three NSAIDs (celecoxib, etoricoxib, and diclofenac demonstrated clinically significant hepatotoxic evidence based on hepatotoxicity justification criteria. Of all the hepatotoxicity events found from the above-mentioned three NSAIDs, diclofenac had the highest proportion, which ranged from 0.015 to 4.3 (×10−2, followed by celecoxib, which ranged from 0.13 to 0.38 (×10−2, and etoricoxib, which ranged from 0.005 to 0.930 (×10−2. Conclusion. Diclofenac had higher rates of hepatotoxic evidence compared to other NSAIDs. Hepatotoxic evidence is mostly demonstrated as aminotransferase elevation, while liver-related hospitalization or discontinuation was very low.
Ruiz-Colón, Kazandra; Chavez-Arias, Carlos; Díaz-Alcalá, José Eric; Martínez, María A
Xylazine is not a controlled substance; it is marketed as a veterinary drug and used as a sedative, analgesic and muscle relaxant. In humans, it could cause central nervous system depression, respiratory depression, bradycardia, hypotension, and even death. There have been publications of 43 cases of xylazine intoxication in humans, in which 21 (49%) were non-fatal scenarios and 22 (51%) resulted in fatalities. Most of the non-fatal cases required medical intervention. Over recent years xylazine has emerged as an adulterant in recreational drugs, such as heroin or speedball (a cocaine and heroin mixture). From the 43 reported cases, 17 (40%) were associated with the use of xylazine as an adulterant of drugs of abuse. Its chronic use is reported to be associated with physical deterioration and skin ulceration. Literature shows some similar pharmacologic effects between xylazine and heroin in humans. These similar pharmacologic effects may create synergistic toxic effects in humans. Therefore, fatalities among drug users may increase due to the use of xylazine as an adulterant. Xylazine alone has proven harmful to humans and even more when it is combined with drugs of abuse. A comprehensive review of the literature of non-fatal and fatal xylazine intoxication cases including those in which the substance was used as adulterant is presented, in order to increase the awareness in the forensic community, law enforcement, and public health agencies. Published by Elsevier Ireland Ltd.
López-Álvarez, Jorge; Zea Sevilla, María Ascensión; Agüera Ortiz, Luis; Fernández Blázquez, Miguel Ángel; Valentí Soler, Meritxell; Martínez-Martín, Pablo
The use of anticholinergic drugs is common in the elderly, even in people with cognitive impairment. A systematic search was conducted in PubMed (anticholinergic effects, anticholinergic and dementia) to define the effects of anticholinergic drugs in the elderly. We emphasized the search in patterns of use, the combined use with AChEIs, the measurement of the Serum Anticholinergic Activity, and the short-term and long-term cognitive effects. The conclusions are that the use of anticholinergic drugs is common in the elderly, even more so than the medical prescription of AChEIs in Alzheimer's disease. The use of anticholinergic drugs may result in cognitive impairment. In long-term use it may generate a worsening of cognitive functions. It can lead to a wrong diagnosis of mild cognitive impairment or dementia, and they can also initiate signs of dementia. Greater cognitive effects appear when there is a previous deficit, but cognitive effects from anticholinergic drugs disappear in severe dementia. The presence of ApoEɛ4 increases the vulnerability for cognitive impairment when these drugs are employed. Copyright © 2013 SEP y SEPB. Published by Elsevier España. All rights reserved.
Reddy, B Pavan Kumar; Yadav, Hemant K S; Nagesha, Dattatri K; Raizaday, Abhay; Karim, Abdul
Polymeric micelles are used as 'smart drug carriers' for targeting certain areas of the body by making them stimuli-sensitive or by attachment of a specific ligand molecule onto their surface. The main aim of using polymeric micelles is to deliver the poorly water soluble drugs. Now-a-days they are used especially in the areas of cancer therapy also. In this article we have reviewed several aspects of polymeric micelles concerning their mechanism of formation, chemical nature, preparation and characterization techniques, and their applications in the areas of drug delivery.
Sokal, Agnieszka; Pindelska, Edyta
The properties of many drugs which have been available on the pharmaceutical market for a long time still need to be improved. Cocrystals are the solid state drug modification which can improve such properties as low solubility, stability and mechanical properties (e.g. compressibility). In this paper examples how to use cocrystals to modify properties of API (Active Pharmaceutical Ingredient) will be reported. Additionally, in this review the way from an idea of the new cocrystal to drug dosage form registration will be shortly described. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Pillay, Viness; Tsai, Tong-Sheng; Choonara, Yahya E; du Toit, Lisa C; Kumar, Pradeep; Modi, Girish; Naidoo, Dinesh; Tomar, Lomas K; Tyagi, Charu; Ndesendo, Valence M K
Electroactive polymers (EAPs) are promising candidate materials for the design of drug delivery technologies, especially in conditions where an "on-off" drug release mechanism is required. To achieve this, EAPs such as polyaniline, polypyrrole, polythiophene, ethylene vinyl acetate, and polyethylene may be blended into responsive hydrogels in conjunction with the desired drug to obtain a patient-controlled drug release system. The "on-off" drug release mechanism can be achieved through the environmental-responsive nature of the interpenetrating hydrogel-EAP complex via (i) charged ions initiated diffusion of drug molecules; (ii) conformational changes that occur during redox switching of EAPs; or (iii) electroerosion. These release mechanisms are not exhaustive and new release mechanisms are still under investigation. Therefore, this review seeks to provide a concise incursion and critical overview of EAPs and responsive hydrogels as a strategy for advanced drug delivery, for example, controlled release of neurotransmitters, sulfosalicyclic acid from cross-linked hydrogel, and vaccine delivery. The review further discusses techniques such as linear sweep voltammetry, cyclic voltammetry, impedance spectroscopy, and chronoamperometry for the determination of the redox capability of EAPs. The future implications of the hydrogel-EAP composites include, but not limited to, application toward biosensors, DNA hybridizations, microsurgical tools, and miniature bioreactors and may be utilized to their full potential in the form of injectable devices as nanorobots or nanobiosensors. Copyright © 2013 Wiley Periodicals, Inc.
Kanamala, Manju; Wilson, William R; Yang, Mimi; Palmer, Brian D; Wu, Zimei
As the mainstay in the treatment of various cancers, chemotherapy plays a vital role, but still faces many challenges, such as poor tumour selectivity and multidrug resistance (MDR). Targeted drug delivery using nanotechnology has provided a new strategy for addressing the limitations of the conventional chemotherapy. In the last decade, the volume of research published in this area has increased tremendously, especially with functional nano drug delivery systems (nanocarriers). Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for improving therapeutic outcomes. Among the various stimuli, pH triggered delivery is regarded as the most general strategy, targeting the acidic extracellular microenvironment and intracellular organelles of solid tumours. In this review, we discuss recent advances in the development of pH-sensitive nanocarriers for tumour-targeted drug delivery. The review focuses on the chemical design of pH-sensitive biomaterials, which are used to fabricate nanocarriers for extracellular and/or intracellular tumour site-specific drug release. The pH-responsive biomaterials bring forth conformational changes in these nanocarriers through various mechanisms such as protonation, charge reversal or cleavage of a chemical bond, facilitating tumour specific cell uptake or drug release. A greater understanding of these mechanisms will help to design more efficient drug delivery systems to address the challenges encountered in conventional chemotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.
Full Text Available Mallik Angalakuditi1, Joseph Gomes21Georgia State University, Atlanta, GA, USA; 2Baxter Health Care, Deerfield, IL, USAObjectives: To evaluate the impact of retrospective drug utilization review (RDUR, pharmacist’s interventions on physician prescribing, and the level of spillover effect on future prescriptions following the intervention.Methods: A retrospective case–control study was conducted at a pharmacy benefits management company using the available prescription data from April 2004 to August 2005. RDUR conflicts evaluated and intervened by a clinical pharmacist served as a case group, whereas conflicts that were not evaluated and intervened by a clinical pharmacist served as a control group.Results: A total of 40,284 conflicts in cases and 13,044 in controls were identified. For cases, 32,780 interventions were considered nonrepetitive, and 529 were repetitive. There were 22,870 physicians in cases that received intervention letters and 2348 physicians in the control group that would have received intervention letters during the study period. Each physician received on average 1.4 interventions for cases vs 3.0 for controls. Among the case physicians who were intervened during the study period, 2.2% (505 were involved in a repeated intervention vs 18.2% (428 in controls (P < 0.001, which is an eight-fold difference. The most common conflict intervened on in cases was therapeutic appropriateness (8277, 25.3%, and for controls it was drug–drug interactions (1796, 25.4%. The overall interventional spillover effect in cases was 98.4% vs 89.4% in controls (P = 0.01.Conclusion: RDUR is an effective interventional program which results in decreased numbers of interventions per physician and provides a significant impact on future prescribing habits.Keywords: pharmacy management, spillover effect, RDUR, DUR
Schmidt, Lars E; Dalhoff, Kim
Interactions between food and drugs may inadvertently reduce or increase the drug effect. The majority of clinically relevant food-drug interactions are caused by food-induced changes in the bioavailability of the drug. Since the bioavailability and clinical effect of most drugs are correlated......, the bioavailability is an important pharmacokinetic effect parameter. However, in order to evaluate the clinical relevance of a food-drug interaction, the impact of food intake on the clinical effect of the drug has to be quantified as well. As a result of quality review in healthcare systems, healthcare providers...... are increasingly required to develop methods for identifying and preventing adverse food-drug interactions. In this review of original literature, we have tried to provide both pharmacokinetic and clinical effect parameters of clinically relevant food-drug interactions. The most important interactions are those...
Schafer, John; Brown, Sandra A.
Content analyzed self-reports from 704 college students and used results to develop Marijuana Effect Expectancy Questionnaire and Cocaine Effect Expectancy Questionnaire. Identified six marijuana expectancies and five cocaine expectancies. Drug effect expectancies distinguished between patterns of nonuse and varying degrees of use of these two…
Teixeira, Marcus Zulian
Employing the secondary action or adaptative reaction of the organism as therapeutic response, homeopathy uses the treatment by similitude (similia similibus curentur) administering to sick individuals the medicines that caused similar symptoms in healthy individuals. Such homeostatic or paradoxical reaction of the organism is scientifically explained through the rebound effect of drugs, which cause worsening of symptoms after withdrawal of several palliative treatments. Despite promoting an improvement in psoriasis at the beginning of the treatment, modern biological therapies provoke worsening of the psoriasis (rebound psoriasis) after discontinuation of drugs. Exploratory qualitative review of the literature on the occurrence of the rebound effect with the use of immunomodulatory drugs [T-cell modulating agents and tumor necrosis factor (TNF) inhibitors drugs] in the treatment of psoriasis. Several researches indicate the rebound effect as the mechanism of worsening of psoriasis with the use of efalizumab causing the suspension of its marketing authorization in 2009, in view of some severe cases. Other studies also have demonstrated the occurrence of rebound psoriasis with the use of alefacept, etanercept and infliximab. As well as studied in other classes of drugs, the rebound effect of biologic agents supports the principle of similitude (primary action of the drugs followed by secondary action and opposite of the organism). Copyright Â© 2016 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.
Tou, Weng Ieong; Chen, Calvin Yu-Chian
Insomnia is a self-reported disease where patients lose their ability to initiate and maintain sleep, leading to daytime performance impairment. Several drug targets to ameliorate insomnia symptoms have been discovered; however, these drug targets lead to serious side effects. Thus, we characterize the structural properties of these sleep-related receptors and the clock complex and discuss a possible drug design that will reduce side effects. Computational prediction shows that disordered property is shared. Over 30% of the structure of CLOCK, PER1/2/3, BMAL-1, muscarinic acetylcholine receptor-M1, melatonin receptor and casein kinase I are structurally disordered (the remaining proteins represent insomnia drugs might be closely related to the protein architecture. Copyright © 2013 Elsevier Ltd. All rights reserved.