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Sample records for approval clinical pharmacology

  1. Pharmacological and clinical profile of recently approved second-generation antipsychotics: implications for treatment of schizophrenia in older patients.

    Science.gov (United States)

    Rado, Jeffrey; Janicak, Philip G

    2012-10-01

    Antipsychotics are frequently used in elderly patients to treat a variety of conditions, including schizophrenia. While extensively studied for their impact in younger populations, there is comparatively limited evidence about the effectiveness of these agents in older patients. Further complicating this situation are the high comorbidity rates (both psychiatric and medical) in the elderly; age-related changes in pharmacokinetics that lead to a heightened proclivity for adverse effects; and the potential for multiple, clinically relevant drug interactions. With this background in mind, we review diagnostic and treatment-related issues specific to elderly patients suffering from schizophrenia. We then focus on the potential role of the most recently approved second-generation antipsychotics, paliperidone (both the extended-release oral formulation and the long-acting injectable formulation), iloperidone, asenapine and lurasidone, given the limited clinical experience with these agents in the elderly. While there is limited data to support their safety, tolerability and efficacy in older patients with schizophrenia, each has unique characteristics that should be considered when used in this population.

  2. Integrating pharmacology and clinical pharmacology in universities.

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    Buckingham, Julia C

    2012-06-01

    Continuing development of safe and effective new medicines is critically important for global health, social prosperity and the economy. The drug discovery-development pipeline depends critically on close partnerships between scientists and clinicians and on educational programmes that ensure that the pharmacological workforce, in its broadest sense, is fit for purpose. Here I consider factors that have influenced the development of basic and clinical pharmacology in UK universities over the past 40 years and discuss ways in which basic pharmacologists, clinical pharmacologists and scientists from different disciplines can work together effectively, while retaining their professional identities and fostering developments in their disciplines. Specifically, I propose the establishment of Institutes of Drug Discovery and Development, whose activities could include development and implementation of a translational pharmacology research strategy, drawing on the collective expertise of the membership and the university as whole; provision of a forum for regular seminars and symposia to promote the discipline, encourage collaboration and develop a cohesive community; provision of a research advisory service, covering, for example, data management, applications for ethics permission, clinical trials design, statistics and regulatory affairs; liaison with potential funders and leadership of major funding bids, including funding for doctoral training; provision of advice on intellectual property protection and the commercialization of research; liaison with corporate partners to facilitate collaboration, knowledge transfer and effective translation; and leadership of undergraduate and postgraduate education in basic and clinical pharmacology and related sciences for medical and science students, including continuing professional development and transferable skills.

  3. Clinical pharmacology of deferasirox.

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    Tanaka, Chiaki

    2014-08-01

    Iron accumulation is a consequence of regular red cell transfusions, and can occur as a result of ineffective erythropoiesis secondary to increased intestinal iron absorption, in patients with various anemias. Without appropriate treatment, iron overload can lead to increased morbidity and mortality. Deferasirox is an oral iron chelator effective for reduction of body iron in iron-overloaded patients with transfusion-dependent anemias and non-transfusion-dependent thalassemia, with a well-established safety profile. This review summarizes the clinical pharmacokinetics, pharmacodynamics, and drug-drug interaction profile of deferasirox, and the claims supporting once-daily dosing for effective chelation. Sustained labile plasma iron suppression is observed with no rebound between doses, protecting organs from potential tissue damage. Increased iron excretion positively correlates with increased deferasirox exposure; to optimize iron removal transfusional iron intake, body iron burden and safety parameters should also be considered. Deferasirox dispersible tablets should be taken ≥30 min before food due to an effect of food on bioavailability. Dosing is consistent across pediatric and adult patients and there is no ethnic sensitivity. Dose adjustment is required for patients with hepatic impairment and may be considered upon coadministration with strong uridine diphosphate glucuronosyltransferase inducers or bile acid sequestrants (coadministration should be avoided where possible), and patients should be monitored upon coadministration with cytochrome P450 (CYP) 3A4/5, CYP2C8, or CYP1A2 substrates. Coadministration with hydroxyurea, a fetal hemoglobin modulator, does not appear to impact deferasirox pharmacokinetics. In summary, a substantial body of clinical and pharmacokinetic data are available for deferasirox to guide its optimal use in multiple patient populations and clinical circumstances.

  4. Clinical pharmacology of homoharringtonine

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    Savaraj, N.; Lu, K.; Dimery, I.; Feun, L.G.; Burgess, M.; Keating, M.; Loo, T.L.

    1986-12-01

    Clinical pharmacokinetics of homoharringtonine (HHT) were studied in eight patients who received uniformly labeled HHT at 3-4 mg/m2 (150 mu Ci) by continuous 6-hour infusion. The drug and metabolites were quantified by radiochemical and high-performance liquid chromatographic techniques. Computerized nonlinear least-square regression and curve stripping were used to characterize HHT and total (/sup 3/H)HHT equivalent pharmacokinetics. Unchanged HHT in the plasma declined biphasically, with an alpha-half-life of 0.5 +/- 0.1 hours and a beta-half-life of 9.3 +/- 1.4 hours. The total clearance of HHT was 177.4 +/- 27.7 ml X hour-1 X kg-1, and the apparent volume of distribution, estimated from the area under the drug concentration versus time curve, was 2.4 +/- 0.4 L X kg-1. Correspondingly, the total (/sup 3/H)HHT equivalent disappeared from the plasma in a triphasic manner. Compared with the pharmacokinetic parameters of unchanged HHT, the terminal half-life of total /sup 3/H was 67.5 +/- 7.5 hours, 7.4 times longer; the total clearance was 30.9 +/- 3.1 ml X hour-1 X kg-1, 5.5 times slower; but the volume of distribution by area was 2.7 +/- 0.1 L X kg-1, nearly the same. The 72-hour cumulative urinary excretion of total tritium was 28.2% of the administered dose and only 38.3% of this resided in unchanged HHT. Thus, urinary excretion was not a major route of elimination of HHT. Moreover, HHT underwent extensive metabolism; one major and two minor unidentified products were detected in both plasma and urine.

  5. History of clinical pharmacy and clinical pharmacology.

    Science.gov (United States)

    Miller, R R

    1981-04-01

    The purpose of the Symposium on Clinical Pharmacy and Clinical Pharmacology is to describe the present and future functional roles of clinical pharmacists and clinical pharmacologists in drug research, professional education, and patient care. Clinical pharmacy is a relatively new professional discipline, being only about 15 years old. This new breed of pharmacists is patient rather than drug product oriented. The discipline arose out of dissatisfaction with old practice norms and the pressing need for a health professional with a comprehensive knowledge of the therapeutic use of drugs. The clinical pharmacy movement began at the University of Michigan in the early 1960s, but much of the pioneering work was done by David Burkholder, Paul Parker, and Charles Walton at the University of Kentucky in the latter part of the 1960s. Clinical pharmacology is a professional discipline that combines basic pharmacology and clinical medicine. Its development began in the early 1950s, primarily as a result of the efforts of Harry Gold. It has had a slower growth than clinical pharmacy but it has made many important contributions to our knowledge of human pharmacology and the rational use of drugs.

  6. Clinical pharmacology in Russia-historical development and current state.

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    Zagorodnikova Goryachkina, Ksenia; Burbello, Aleksandra; Sychev, Dmitry; Frolov, Maxim; Kukes, Vladimir; Petrov, Vladimir

    2015-02-01

    Clinical pharmacology in Russia has long history and is currently active, but rather unrecognized internationally. It is governmentally approved as a teaching/scientific specialty since 1983 and as a medical specialty since 1997. Courses of clinical pharmacology are included in the undergraduate curricula in the 5th and/or 6th year of education at all medical schools in the Russian Federation. Postgraduate education includes initial specialization in internal medicine with further residency in clinical pharmacology. Governmental legislation recommends that every healthcare institution has either a department or a single position of clinical pharmacologist. Major routine duties include information about and monitoring of medication use, consultations in difficult clinical situations, pharmacogenetic counseling, therapeutic drug monitoring, pharmacovigilance, and participation in drug and therapeutics (formulary) committees. There are official experts in clinical pharmacology in Russia responsible for coordinating relevant legislative issues. The chief expert clinical pharmacologist represents the discipline directly at the Ministry of Health. Research in clinical pharmacology in Russia is extensive and variable, but only some of it is published internationally. Russia is a participant of international societies of clinical pharmacology and therapeutics and collaboration is actively ongoing. There are still certain problems related to the development of the discipline in Russia-some healthcare institutions do not see the need for clinical pharmacology. However, the number of clinical pharmacologists in Russia is increasing as well as their role in physicians' education, national healthcare, and research.

  7. Applications of stable isotopes in clinical pharmacology

    NARCIS (Netherlands)

    Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

    2011-01-01

    This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the pharmacok

  8. Applications of stable isotopes in clinical pharmacology

    NARCIS (Netherlands)

    Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

    2011-01-01

    This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the

  9. Pharmacology Portal: An Open Database for Clinical Pharmacologic Laboratory Services.

    Science.gov (United States)

    Karlsen Bjånes, Tormod; Mjåset Hjertø, Espen; Lønne, Lars; Aronsen, Lena; Andsnes Berg, Jon; Bergan, Stein; Otto Berg-Hansen, Grim; Bernard, Jean-Paul; Larsen Burns, Margrete; Toralf Fosen, Jan; Frost, Joachim; Hilberg, Thor; Krabseth, Hege-Merete; Kvan, Elena; Narum, Sigrid; Austgulen Westin, Andreas

    2016-01-01

    More than 50 Norwegian public and private laboratories provide one or more analyses for therapeutic drug monitoring or testing for drugs of abuse. Practices differ among laboratories, and analytical repertoires can change rapidly as new substances become available for analysis. The Pharmacology Portal was developed to provide an overview of these activities and to standardize the practices and terminology among laboratories. The Pharmacology Portal is a modern dynamic web database comprising all available analyses within therapeutic drug monitoring and testing for drugs of abuse in Norway. Content can be retrieved by using the search engine or by scrolling through substance lists. The core content is a substance registry updated by a national editorial board of experts within the field of clinical pharmacology. This ensures quality and consistency regarding substance terminologies and classification. All laboratories publish their own repertoires in a user-friendly workflow, adding laboratory-specific details to the core information in the substance registry. The user management system ensures that laboratories are restricted from editing content in the database core or in repertoires within other laboratory subpages. The portal is for nonprofit use, and has been fully funded by the Norwegian Medical Association, the Norwegian Society of Clinical Pharmacology, and the 8 largest pharmacologic institutions in Norway. The database server runs an open-source content management system that ensures flexibility with respect to further development projects, including the potential expansion of the Pharmacology Portal to other countries. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  10. The Dutch vision of clinical pharmacology

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    Schellens, J H M; Grouls, R; Guchelaar, H J; Touw, D J; Rongen, G A; de Boer, A; Van Bortel, L M

    Recent position papers addressing the profession of clinical pharmacology have expressed concerns about the decline of interest in the field among clinicians and medical educators in the United Kingdom and other Western countries, whether clinical pharmacology is actually therapeutics, and whether

  11. Clinical Pharmacology & Therapeutics: Past, Present, and Future.

    Science.gov (United States)

    Waldman, S A; Terzic, A

    2017-03-01

    Clinical Pharmacology & Therapeutics (CPT), the definitive and timely source for advances in human therapeutics, transcends the drug discovery, development, regulation, and utilization continuum to catalyze, evolve, and disseminate discipline-transformative knowledge. Prioritized themes and multidisciplinary content drive the science and practice of clinical pharmacology, offering a trusted point of reference. An authoritative herald across global communities, CPT is a timeless information vehicle at the vanguard of discovery, translation, and application ushering therapeutic innovation into modern healthcare.

  12. Pharmacological and clinical properties of curcumin

    Directory of Open Access Journals (Sweden)

    Huang S

    2011-06-01

    Full Text Available Christopher S Beevers¹, Shile Huang²¹Department of Pharmacology, Ross University School of Medicine, Picard-Portsmouth, Commonwealth of Dominica; ²Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, USAAbstract: The polyphenol natural product curcumin has been the subject of numerous studies over the past decades, which have identified and characterized the compound's pharmacokinetic, pharmacodynamic, and clinical pharmacological properties. In in vitro and in vivo model systems, curcumin displays potent pharmacological effects, by targeting many critical cellular factors, through a diverse array of mechanisms of action. Despite this tremendous molecular versatility, however, the clinical application of curcumin remains limited due to poor pharmacokinetic characteristics in human beings. The current trend is to develop and utilize unique delivery systems, chemical derivatives, and chemical analogs to circumvent these pharmacological obstacles, in order to optimize the conditions for curcumin as a chemopreventive and chemotherapeutic agent in diseases such as cancer, diabetes, obesity, Alzheimer's disease, and inflammatory disorders. The present work seeks to review recent studies in the basic pharmacological principles and potential clinical applications of curcumin.Keywords: curcumin, pharmacological properties, signal transduction, cellular targets, cancer, inflammation

  13. Clinical Pharmacology and Pharmacokinetics of Levetiracetam

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    Chanin Clark Wright

    2013-12-01

    Full Text Available Status epilepticus and acute repetitive seizures still pose a management challenge despite the recent advances in the field of epilepsy. Parenteral formulations of old anticonvulsants are still a cornerstone in acute seizure management and are approved by the FDA. Intravenous levetiracetam, a second generation anticonvulsant, is approved by the FDA as an adjunctive treatment in patients 16 years or older when oral administration is not available. Data have shown that it has a unique mechanism of action, linear pharmacokinetics and no known drug interactions with other anticonvulsants. In this paper, we will review the current literature about the pharmacology and pharmacokinetics of intravenous levetiracetam and the safety profile of this new anticonvulsant in acute seizure management of both adults and children.

  14. Chrysotherapy: pharmacological and clinical correlates.

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    Lorber, A; Simon, T M; Leeb, J; Carroll, P E

    1975-12-01

    Relationships between gold administration and serum gold content were observed in 56 RA subjects receiving up to five years of weekly chrysotherapy. Wide fluctuations in serum gold responses to standard 50 mg IM injections were noted. Individual adjustments to dosage schedules were made as dictated by patient serum gold responses. Enhanced clinical and laboratory response was prolonged with higher sustained serum gold concentration greater than 300 mug per cent. Maintaining serum levels greater than 300 mug per cent is postulated to facilitate access of gold to "effector sites" within the deeper compartments by providing higher sustained gradients between superficial (blood) and deeper body compartments. The complexity of the system of effector sites responsive to gold and their divergent location within the body likely affects the accessibility of the agent for these sites; hence, affecting the correlation between gold levels and therapeutic response. The application of pharmacokinetic principles in chrysotherapy, nevertheless, provides the basis for optimizing accessibility of the agent and the therapeutic response. (J Rheumatol 2: 401-410, 1975).

  15. Clinical pharmacology considerations in biologics development

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    Zhao, Liang; Ren, Tian-hua; Wang, Diane D

    2012-01-01

    Biologics, including monoclonal antibodies (mAbs) and other therapeutic proteins such as cytokines and growth hormones, have unique characteristics compared to small molecules. This paper starts from an overview of the pharmacokinetics (PK) of biologics from a mechanistic perspective, the determination of a starting dose for first-in-human (FIH) studies, and dosing regimen optimisation for phase II/III clinical trials. Subsequently, typical clinical pharmacology issues along the corresponding pathways for biologics development are summarised, including drug-drug interactions, QTc prolongation, immunogenicity, and studies in specific populations. The relationships between the molecular structure of biologics, their pharmacokinetic and pharmacodynamic characteristics, and the corresponding clinical pharmacology strategies are summarised and depicted in a schematic diagram. PMID:23001474

  16. Clinical pharmacology considerations in biologics development

    Institute of Scientific and Technical Information of China (English)

    Liang ZHAO; Tian-hua REN; Diane D WANG

    2012-01-01

    Biologics,including monoclonal antibodies (mAbs) and other therapeutic proteins such as cytokines and growth hormones,have unique characteristics compared to small molecules.This paper starts from an overview of the pharmacokinetics (PK) of biologics from a mechanistic perspective,the determination of a starting dose for first-in-human(FIH) studies,and dosing regimen optimisation for phase Ⅱ/Ⅲ clinical trials.Subsequently,typical clinical pharmacology issues along the corresponding pathways for biologics development are summarised,including drug-drug interactions,QTc prolongation,immunogenicity,and studies in specific populations.The relationships between the molecular structure of biologics,their pharmacokinetic and pharmacodynamic characteristics,and the corresponding clinical pharmacology strategies are summarised and depicted in a schematic diagram.

  17. Clinical Pharmacology & Therapeutics: the next five years.

    Science.gov (United States)

    Waldman, S A; Terzic, A

    2015-01-01

    It has been nearly ten years since we joined the editorial organization of Clinical Pharmacology & Therapeutics (CPT), as part of the American Society for Clinical Pharmacology and Therapeutics (ASCPT) family. During that tenure, the primary mandate has been the growth of CPT, recognized as one of the key voices of the discipline and the Society. Set goals were realized in concert with a strong editorial team, a diverse editorial board, a dedicated editorial staff, and outstanding authors, leveraging a leading publishing infrastructure and responding to the needs of a global readership, expanding membership, and the discipline as a whole. The impending decade anniversary, and the transition to a new publisher, offers a natural juncture to reflect on progress, and chart plans for the future of the Journal.

  18. Citicoline: pharmacological and clinical review, 2016 update.

    Science.gov (United States)

    Secades, J J

    2016-12-23

    This review is based on the previous one published in 2010 -Secades JJ. Citicoline: pharmacological and clinical review, 2010 update. Rev Neurol 2011; 52 (Suppl 2): S1-62-, incorporating 183 new references, having all the information available to facilitate the access to the information in one document. This review is focused on the main indications of the drug, as acute stroke and its sequelae, including the cognitive impairment, and traumatic brain injury and its sequelae. There are retrieved the most important experimental and clinical data in both indications.

  19. Citicoline: pharmacological and clinical review, 2010 update.

    Science.gov (United States)

    Secades, J J

    2011-03-14

    This review is based on the previous one published in 2006 -Secades JJ, Lorenzo JL. Citicoline: pharmacological and clinical review, 2006 update. Methods Find Exp Clin Pharmacol 2006; 28 (Suppl B): S1-56-, incorporating the new references until now, having all the information available to facilitate the access to the informacion in one document. This review is focused on the main indications of the drug, as acute stroke and its sequelae, including the cognitive impairment, and traumatic brain injury and its sequelae. There are retrieved the most important experimental and clinical data in both indications.

  20. Pharmacologic and clinical evaluation of posaconazole.

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    Moore, Jason N; Healy, Jason R; Kraft, Walter K

    2015-05-01

    Posaconazole, a broad-spectrum triazole antifungal agent, is approved for the prevention of invasive aspergillosis and candidiasis in addition to the treatment of oropharyngeal candidiasis. There is evidence of efficacy in the treatment and prevention of rarer, more difficult-to-treat fungal infections. Posaconazole oral suspension solution has shown limitations with respect to fasting state absorption, elevated gastrointestinal pH and increased motility. The newly approved delayed-release oral tablet and intravenous solution formulations provide an attractive treatment option by reducing interpatient variability and providing flexibility in critically ill patients. On the basis of clinical experience and further clinical studies, posaconazole was found to be a valuable pharmaceutical agent for the treatment of life-threatening fungal infections. This review will examine the development history of posaconazole and highlight the most recent advances.

  1. Radioimmunoassay in basic and clinical pharmacology

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    Patrono, C.; Peskar, B.A.

    1987-01-01

    The subject of the book is the development, validation and application of radioimmunoassay (RIA) techniques for the measurement of a variety of substances in animal and human body fluids. The book discusses methodological and conceptual issues related to the main classes of mediators of drug action and to drugs themselves, as assayed by this particular analytical technique. A number of introductory chapters provide basic information concerning production and characterization of antibodies, labeling techniques, statistical aspects and validation criteria, insight into problems related to the development and validation of RIA for the newly discovered mediator(s). In the following chapters, the emphasis is placed on the technical details relevant to each class of compounds and on specific aspects of their applications to basic and/or clinical pharmacological studies. New developments in this area, such as monoclonal antibodies and non-radioactive labeling techniques, are also covered.

  2. Chlorhexidine--pharmacology and clinical applications.

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    Lim, K-S; Kam, P C A

    2008-07-01

    Chlorhexidine is a widely used skin antisepsis preparation and is an ingredient in toothpaste and mouthwash. It is an especially effective antiseptic when combined with alcohol. Its antimicrobial effects persist because it is binds strongly to proteins in the skin and mucosa, making it an effective antiseptic ingredient for handwashing, skin preparation for surgery and the placement of intravascular access. Catheters impregnated with chlorhexidine and antimicrobial agents can reduce the incidence of catheter-related bloodstream infections. Contact dermatitis related to chlorhexidine is not common in health care workers. The incidence of contact dermatitis to chlorhexidine in atopic patients is approximately 2.5 to 5.4%. Acute hypersensitivity reactions to chlorhexidine are often not recognised and therefore may be underreported. This review discusses the pharmacology, microbiology, clinical applications and adverse effects of chlorhexidine.

  3. Drug repurposing: translational pharmacology, chemistry, computers and the clinic.

    Science.gov (United States)

    Issa, Naiem T; Byers, Stephen W; Dakshanamurthy, Sivanesan

    2013-01-01

    The process of discovering a pharmacological compound that elicits a desired clinical effect with minimal side effects is a challenge. Prior to the advent of high-performance computing and large-scale screening technologies, drug discovery was largely a serendipitous endeavor, as in the case of thalidomide for erythema nodosum leprosum or cancer drugs in general derived from flora located in far-reaching geographic locations. More recently, de novo drug discovery has become a more rationalized process where drug-target-effect hypotheses are formulated on the basis of already known compounds/protein targets and their structures. Although this approach is hypothesis-driven, the actual success has been very low, contributing to the soaring costs of research and development as well as the diminished pharmaceutical pipeline in the United States. In this review, we discuss the evolution in computational pharmacology as the next generation of successful drug discovery and implementation in the clinic where high-performance computing (HPC) is used to generate and validate drug-target-effect hypotheses completely in silico. The use of HPC would decrease development time and errors while increasing productivity prior to in vitro, animal and human testing. We highlight approaches in chemoinformatics, bioinformatics as well as network biopharmacology to illustrate potential avenues from which to design clinically efficacious drugs. We further discuss the implications of combining these approaches into an integrative methodology for high-accuracy computational predictions within the context of drug repositioning for the efficient streamlining of currently approved drugs back into clinical trials for possible new indications.

  4. Memantine: Pharmacological properties and clinical uses

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    Kumar Sudhir

    2004-07-01

    Full Text Available Memantine is a relatively new drug specially developed for use in moderate-to-severe dementia. It is an uncompetitive N-methyl-D-aspartate receptor antagonist and reduces glutamatergic excitotoxicity. Though Alzheimer's disease (AD is the commonest cause of dementia in the world, there is no 'cure' available for the same. Cholinesterase inhibitors such as donepezil and rivastigmine have been shown to provide symptomatic relief in patients with AD but have no effect on disease progression or survival. Moreover, they are not helpful in more severe stages of dementia. Memantine has been shown to cause modest improvement in clinical symptoms in severe stages of AD and may retard the disease progression. Moreover, it has been shown to be useful in various forms of dementia including AD, vascular dementia and Wernicke-Korsakoff psychosis. It is also the first drug to cause complete disappearance of pendular nystagmus due to multiple sclerosis. The current review focuses on the pharmacological properties of memantine and examines the recent evidence in favor of memantine.

  5. Clinical and practical considerations in the pharmacologic management of narcolepsy.

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    Thorpy, Michael J; Dauvilliers, Yves

    2015-01-01

    Despite published treatment recommendations and the availability of approved and off-label pharmacologic therapies for narcolepsy, the clinical management of this incurable, chronic neurologic disorder remains challenging. While treatment is generally symptomatically driven, decisions regarding which drug(s) to use need to take into account a variety of factors that may affect adherence, efficacy, and tolerability. Type 1 narcolepsy (predominantly excessive daytime sleepiness with cataplexy) or type 2 narcolepsy (excessive daytime sleepiness without cataplexy) may drive treatment decisions, with consideration given either to a single drug that targets multiple symptoms or to multiple drugs that each treat a specific symptom. Other drug-related characteristics that affect drug choice are dosing regimens, tolerability, and potential drug-drug interactions. Additionally, the patient should be an active participant in treatment decisions, and the main symptomatic complaints, treatment goals, psychosocial setting, and use of lifestyle substances (ie, alcohol, nicotine, caffeine, and cannabis) need to be discussed with respect to treatment decisions. Although there is a lack of narcolepsy-specific instruments for monitoring therapeutic effects, clinically relevant subjective and objective measures of daytime sleepiness (eg, Epworth Sleepiness Scale and Maintenance of Wakefulness Test) can be used to provide guidance on whether treatment goals are being met. These considerations are discussed with the objective of providing clinically relevant recommendations for making treatment decisions that can enhance the effective management of patients with narcolepsy.

  6. A manifesto for clinical pharmacology from principles to practice.

    Science.gov (United States)

    Aronson, Jeffrey K

    2010-07-01

    1. This is a manifesto for UK clinical pharmacology. 2. A clinical pharmacologist is a medically qualified practitioner who teaches, does research, frames policy, and gives information and advice about the actions and proper uses of medicines in humans and implements that knowledge in clinical practice. Those without medical qualifications who practise some aspect of clinical pharmacology could be described as, say, 'applied pharmacologists'. 3. Clinical pharmacology is operationally defined as a translational discipline in terms of the basic tools of human pharmacology (e.g. receptor pharmacology) and applied pharmacology (e.g. pharmacokinetics) and how they are used in drug discovery and development and in solving practical therapeutic problems in individuals and populations. 4. Clinical pharmacologists are employed by universities, health-care services, private organizations (such as drug companies), and regulatory agencies. They are mentors and teachers, teaching laboratory science, clinical science, and all aspects of practical drug therapy as underpinned by the science of pharmacology; they write and edit didactic and reference texts; researchers, covering research described by the operational definition; clinicians, practising general medicine, clinical toxicology, other medical specialties, and general practice; policy makers, framing local, national, and international medicines policy, including formularies, licensing of medicines and prescribing policies. 5. The future of clinical pharmacology depends on the expansion and maintenance of a central core of practitioners (employed by universities or health-care services), training clinical pharmacologists to practise in universities, health-care services, private organizations, and regulatory agencies, and training other clinicians in the principles and practice of clinical pharmacology.

  7. Clinical pharmacology of bruceantin by radioimmunoassay

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    Fong, K.L.L.; Ho, D.H.W.; Benjamin, R.S.; Brown, N.S.; Bedikian, A.; Yap, B.S.; Wiseman, C.L.; Bodey, G.P.; Kramer W.

    1982-01-01

    During the phase Y clinical trial of a new antitumor agent, bruceantin, the pharmacology was studied in 18 cancer patients. The drug was infused i.v. for 3 h at doses ranging from 1 to 3.6 mg/m/sup 2/ per for 5. The plasma drug disappearance curves were biphasic, with a fast initial half-life of less than 15 min. The second half-life varied from 0.7 to 38 h among different patients and was not dose-related. The difference between the tsub(1/2..beta..) on day 1 and that on day 5 was not significant. In patients with normal liver function, the mean plasma concentration at the end of infusion was 22 ng/ml, and the value of the area under the concentration x time curve (AUC) was 111 (ng/ml)h. In contrast, in patients with abnormal liver function the corresponding values were 115 ng/ml and 830 (ng/ml)h, respectively. In addition, these patients had a slower elimination half-life of 10.9 h and a decreased total clearance of 157 ml/min/m/sup 2/, as compared with 2.6 h and 671 ml/min/m/sup 2/, respectively, for the normal group. All these differences were statistically significant. Patients with abnormal liver function developed more severe toxicity, including fever, severe nausea, vomiting, and hypotension. Two patients with severe hepatic dysfunction received a reduced dose and developed no toxicity. These results demonstrated the importance of the effects of liver dysfunction on drug disposition and showed that the dosage should be reduced in patients with hepatic dysfunction.

  8. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The

  9. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The major

  10. Clinical pharmacology of novel anticancer drug formulations

    OpenAIRE

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The majority of new anti-cancer drugs are oral pharmaceutical formulations, consisting of new chemical entities, like molecular targeted agents and novel variants of existing drugs. The development of oral ...

  11. [Clinical report on pharmacological treatment of autism].

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    Thivierge, J

    1998-01-01

    This article reviews the pharmacology of autism and briefly overviews its use, history and novelties. "Autism" does not refer to any pathophysiology currently known. And no drug or class of drugs can cure this illness which includes many. Before using drugs, efficient in relieving symptoms, it is important to consider the potential benefit of behavioral approaches. Developments in research give hope that drugs will cure or prevent this brain illness.

  12. 76 FR 3912 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2011-01-21

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and... how to optimally utilize mechanistic biomarkers and apply clinical pharmacology tools, such as...

  13. Basic and Clinical Pharmacology of Glucocorticosteroids

    OpenAIRE

    Becker, Daniel E.

    2013-01-01

    Glucocorticosteroids are a product of the adrenal cortex and perform a staggering number of physiological effects essential for life. Their clinical use is largely predicated on their anti-inflammatory and immunosuppressive properties, but they also have notable efficacy in the prophylaxis of postoperative nausea and vomiting. This article reviews the basic functions of glucocorticoids and their clinical use in dental practice.

  14. Clinical Pharmacology of Chemotherapy Agents in Older People with Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoye He

    2011-01-01

    Full Text Available Populations around the world are aging, and the associated increase in cancer incidence has led to the recognition of the importance of geriatric oncology. Chronological age is a poor determinant of pharmacological response to cancer chemotherapy agents. Age-associated changes in physiology and organ function have a significant impact on the clinical pharmacology of cancer chemotherapy agents used in cancer treatment. Altered response to medicines in older people is a consequence of changes in body composition, organ function, concomitant pathophysiology, multiple medications, genetic determinants of drug response, and patient's clinical status. These issues highlight the need to individualize the management of cancer in the older people with consideration of age-related changes in the clinical pharmacology of cancer drugs, analgesics, and adjunctive therapies.

  15. ORIGINAL ARTICLES Pharmacologically active: clinical trials and ...

    African Journals Online (AJOL)

    2008-01-22

    Jan 22, 2008 ... Manufacturers Association, on the basis of a survey of its members ... from this information. The US database, on the other hand, clearly identifies 172 ... workforce involved in clinical trials outside the public sector. This figure ...

  16. Citicoline: pharmacological and clinical review, 2006 update.

    Science.gov (United States)

    Secades, Julio J; Lorenzo, José Luis

    2006-09-01

    Cytidine 5'-diphosphocholine, CDP-choline, or citicoline is an essential intermediate in the biosynthetic pathway of structural phospholipids in cell membranes, particularly phosphatidylcholine. Following administration by both the oral and parenteral routes, citicoline releases its two main components, cytidine and choline. Absorption by the oral route is virtually complete, and bioavailability by the oral route is therefore approximately the same as by the intravenous route. Once absorbed, citicoline is widely distributed throughout the body, crosses the blood-brain barrier and reaches the central nervous system (CNS), where it is incorporated into the membrane and microsomal phospholipid fraction. Citicoline activates biosynthesis of structural phospholipids of neuronal membranes, increases brain metabolism, and acts upon the levels of different neurotransmitters. Thus, citicoline has been experimentally shown to increase norepinephrine and dopamine levels in the CNS. Owing to these pharmacological mechanisms, citicoline has a neuroprotective effect in hypoxic and ischemic conditions, decreasing the volume of ischemic lesion, and also improves learning and memory performance in animal models of brain aging. In addition, citicoline has been shown to restore the activity of mitochondrial ATPase and membrane Na+/K+ATPase, to inhibit activation of certain phospholipases, and to accelerate reabsorption of cerebral edema in various experimental models. Citicoline has also been shown to be able to inhibit mechanisms of apoptosis associated to cerebral ischemia and in certain neurodegeneration models, and to potentiate neuroplasticity mechanisms. Citicoline is a safe drug, as shown by the toxicological tests conducted, that has no significant systemic cholinergic effects and is a well tolerated product. These pharmacological characteristics and the action mechanisms of citicoline suggest that this product may be indicated for treatment of cerebral vascular disease, head

  17. The internet as a tool in clinical pharmacology

    Science.gov (United States)

    Castel, Josep-Maria; Figueras, Albert; Vigo, Joan-Miquel

    2006-01-01

    The invention of the internet and the world-wide web was a landmark that has affected many aspects of everyday life, but is so recent and dynamic that many of its potential uses are still being explored. Aside from its purely commercial use as a virtual pharmacy (e-commerce), the internet is useful in at least three aspects related to clinical pharmacology: communication, training and research. In this paper we briefly review several internet applications related to clinical pharmacology and describe, as an example, the logistics of a multicentre research collaboration related to the promotion of rational drug use in the prevention of postpartum haemorrhage. PMID:16722847

  18. 75 FR 10488 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2010-03-08

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  19. 78 FR 42966 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2013-07-18

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  20. 78 FR 58315 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2013-09-23

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  1. 77 FR 41790 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2012-07-16

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  2. 75 FR 11551 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2010-03-11

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  3. 77 FR 42746 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2012-07-20

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  4. 78 FR 58314 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2013-09-23

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  5. 76 FR 38188 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2011-06-29

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  6. A Clinical Pharmacology Course for Veterinary Students.

    Science.gov (United States)

    Paulsen, Lynn Mulcahy

    1983-01-01

    A one-semester, two-credit course is described that was developed cooperatively by the colleges of pharmacy and veterinary medicine at Washington State University to help resolve an acute shortage of clinical pharmacologists in veterinary medicine and veterinary medical education. Course procedures, content, and evaluation are outlined (MSE)

  7. Pharmacology and clinical pharmacology of methylarginines used as inhibitors of nitric oxide synthases.

    Science.gov (United States)

    Kittel, Anja; Maas, Renke

    2014-01-01

    The methylarginines asymmetric dimethylarginine (ADMA) and monomethylarginine (L-NMMA) are endogenously formed inhibitors of nitric oxide synthases (NOS), which have extensively been investigated as risk markers and used as pharmacological tools to study the L-arginine-nitric oxide (NO) pathway in vitro and in vivo. It is the aim of the present review to summarize the clinical and experimental data on the pharmacological properties that are of relevance when planning and conducting experiments and clinical studies involving methylarginines. Key pharmacodynamic and pharmacokinetic data including IC50 values of ADMA and L-NMMA for NOS isoforms and transport proteins, as well as metabolism by dimethylarginine dimethylaminohydrolases (DDAH1 and DDAH2) and alanine-glyoxylate aminotransferase 2 (AGXT2) are discussed.

  8. Pharmacological effect on pyeloureteric dynamics with a clinical perspective

    DEFF Research Database (Denmark)

    Jung, Helene U; Frimodt-Møller, Poul C; Osther, Palle J;

    2006-01-01

    We searched to review experimental and clinical trials concerning the capabilities of impacting on the ureteric and pelvic activity by means of pharmacological stimulation. Ureteropyeloscopy may cause high renal pelvic pressure. The normal pressure is in the range of 5-15 mmHg whereas pressure...

  9. [Clinical pharmacology of current antiplatelet drugs].

    Science.gov (United States)

    Trenk, D; Nührenberg, T; Stratz, C; Valina, C M; Hochholzer, W

    2014-11-01

    Dual antiplatelet therapy with low-dose acetylsalicylic acid (ASA) and an inhibitor of the P2Y12 adenosine diphosphate (ADP) receptor is the standard treatment for patients presenting with acute coronary syndrome (ACS) or undergoing elective coronary interventions according to the current guidelines published by the European Society of Cardiology (ESC). New generation P2Y12 inhibitors, such as prasugrel and ticagrelor exert stronger and more consistent inhibition of the P2Y12 receptor. In clinical studies enrolling patients with ACS these drugs decreased the incidence of ischemic events compared to the standard therapy with clopidogrel and ASA; however, this beneficial effect was associated with an increase in bleeding events. Alternative therapeutic approaches via addition of drugs with different modes of action showed an overall reduction of ischemic events but also failed to uncouple this beneficial effect from an increased bleeding risk.

  10. Topical corticosteroids: clinical pharmacology and therapeutic use.

    Science.gov (United States)

    Miller, J A; Munro, D D

    1980-02-01

    The development of topical corticosteroids has enabled many dermatoses to be more effectively treated than previously, but there is also no doubt that misuse of these preparations can lead to troublesome local effects and potentially serious systemic problems. The most effective assay for comparing different compounds has been their vasoconstrictive activity, and this on the whole correlates well with clinical effect. To be effective, corticosteroid must be absorbed and the importance of concentration, occlusion, the type of vehicle, added penetrants such as urea and the anatomical site, on the amount of absorption and therefore on clinical activity has been demonstrated. Ointments have been shown to be more effective than creams but because of the considerable choice of potencies now available most dermatologists tend to prescribe the different formulations according to the wishes of the patient. For the same reason, dilution of the commercially marketed preparations is now not generally recommended. The main therapeutic activity of topical corticosteroids is their nonspecific anti-inflammatory effect, thought to be primarily a result of their action on the chemical mediators of inflammation. They have also been shown to be antimitotic which may well be relevant not only to the treatment of scaling dermatoses but also to their dermal thinning effect resulting from inhibition of fibroblasts. Combinations of corticosteroids with antibacterial and antifungal agents have been shown to be very effective in flexural eruptions and secondarily infected dermatoses. As a general rule, the use of topical corticosteroids in outpatients, unless badly misused, is not associated with any significant risk of adrenal axis suppression, but care must be exercised as to the amount prescribed, especially if large areas of the body are to be treated with highly potent preparations. Certain groups such as young children and patients with liver failure, and certain anatomical sites such

  11. Clinical pharmacology of carbapenems in neonates.

    Science.gov (United States)

    Pacifici, Gian Maria; Allegaert, Karel

    2014-04-01

    Carbapenems are an effective tool to treat complicated bacterial infections. This review aims to summarize the available information on carbapenems in neonates to guide clinicians on drug choice and indications in neonates. Moreover, identification of knowledge gaps may stimulate researchers to design studies to further improve pharmacotherapy in neonates. To do so, a bibliographic search [infant/newborn and meropenem, imipenem, panipenem, ertapenem, doripenem or imipenem] was performed (PubMed, EMBASE) and public clinical trial registries (clinicaltrials.gov, EU registry) were searched to summarize the available information. Carbapenem clearance in neonates is low. Variability relates to maturation (weight, age) and renal function (creatinine clearance), while observations in neonates with renal failure are absent. Pharmacodynamics are almost exclusively limited to meropenem, and the available information will further increase (NeoMero-1-2, necrotizing enterocolitis, meningitis). Finally, there are also some ongoing doripenem pharmacokinetics (PK) studies in neonates. It was concluded that observations on carbapenems in neonates are limited, but studies (NeoMero, doripenem) are ongoing. Until this information becomes available, off label prescription of meropenem seems to be the most reasonable choice when a carbapenem is appropriate. Knowledge gaps relate to PK in neonates with renal failure and to the potential benefit of prolonged compared to short duration of infusion.

  12. Clinical Pharmacology in Denmark in 2016 - 40 Years with the Danish Society of Clinical Pharmacology and 20 Years as a Medical Speciality

    DEFF Research Database (Denmark)

    Brøsen, Kim; Andersen, Stig Ejdrup; Borregaard, Jeanett

    2016-01-01

    The Danish Society of Clinical Pharmacology was founded in 1976, and mainly thanks to the persistent efforts of the society, clinical pharmacology became an independent medical speciality in Denmark in 1996. Since then, clinical pharmacology has gone from strength to strength. In the Danish...... healthcare system, clinical pharmacology has established itself as an indispensible part of the efforts to promote the rational, safe and economic use of drugs. Clinical pharmacologists are active in drug committees both in hospitals and in the primary sector. All clinical pharmacology centres offer a local...... in the Capital Region. The Department of Clinical Pharmacology at Aarhus University Hospital works closely together with forensic toxicologists and pathologists, covering issues regarding illicit substances, forensic pharmacology, post-mortem toxicology, expert testimony and research. Therapeutic geriatric...

  13. Corticosteroids: clinical pharmacology and therapeutic use.

    Science.gov (United States)

    Swartz, S L; Dluhy, R G

    1978-09-01

    The widespread use of corticosteroids in clinical practice emphasises the need for a thorough understanding of their metabolic effects. In general, the actions of corticosteroids on carbohydrate, protein, and lipid metabolism result in increased hepatic capacity for gluconeogenesis and enhanced catabolic actions upon muscle, skin, lymphoid, adipose and connective tissues. Because of the morbidity associated with steroid therapy, the clinician must carefully consider in each case the gains that can reasonably be expected from corticosteroid therapy versus the inevitable undesirable side effects of prolonged therapy. Thus, it is important to remember that the enhanced anti-inflammatory activity of the various synthetic analogues of cortisol is not dissociated from the expected catabolic actions of glucocorticoid hormones. Replacement therapy with physiological doses of cortisol in primary or secondary adrenal insufficiency is intended to simulate the normal daily secretion of cortisol. Short term, high dose suppressive glucocorticoid therapy is indicated in the treatment of medical emergencies such as necrotising vasculitis, status asthmaticus and anaphylactic shock. With improvement of the underlying disorder, the steroid dosage can be rapidly tapered and then discontinued over a 2 to 3 day period. Long term, high dose suppressive therapy is often commonly used to treat certain diseases (see sections 4.7.2 and 4.7.3). In this setting, suppression of the hypothalamic-pituitary-adrenal axis may persist for as long as 9 to 12 months following steroid withdrawal if steroid doses are administered in the supraphysiological range for longer than 2 weeks. In general, higher doses, longer duration of usage, and frequent daily administration are all correlated with the severity of pituitary ACTH suppression. When steroid therapy is to be withdrawn, gradual tapering of the dosage is necessary; the steroid dosage should also be given as a single morning dose if possible. Rapid

  14. Extending worldwide clinical pharmacology education through a pricing approach.

    Science.gov (United States)

    Ameer, Barbara

    2005-09-01

    Financial instruments, such as professional membership fees, are part of the science and technology policy toolkit for creating an environment conducive to developing an international health knowledge network. To minimize a hurdle to global knowledge exchange in clinical pharmacology, the American College of Clinical Pharmacology reevaluated fees for its international members. Secondary market research was conducted on salary data available from US-based multinational firms. Salary comparisons for the same position based in the United States and in a developing economy were used to generate an index ratio. Applying this ratio, a tiered-membership fee structure was constructed for the approximately 120 countries where gross national income meets the World Bank classification of "developing economy." The index ratio serves as a paradigm for structuring fees across a variety of programs. With the implementation of an adjusted dues structure, information and networks of colleagues are now more accessible to clinical pharmacologists in developing economies.

  15. Phytochemistry, pharmacology, and clinical trials of Morus alba.

    Science.gov (United States)

    Chan, Eric Wei-Chiang; Lye, Phui-Yan; Wong, Siu-Kuin

    2016-01-01

    The present review is aimed at providing a comprehensive summary on the botany, utility, phytochemistry, pharmacology, and clinical trials of Morus alba (mulberry or sang shu). The mulberry foliage has remained the primary food for silkworms for centuries. Its leaves have also been used as animal feed for livestock and its fruits have been made into a variety of food products. With flavonoids as major constituents, mulberry leaves possess various biological activities, including antioxidant, antimicrobial, skin-whitening, cytotoxic, anti-diabetic, glucosidase inhibition, anti-hyperlipidemic, anti-atherosclerotic, anti-obesity, cardioprotective, and cognitive enhancement activities. Rich in anthocyanins and alkaloids, mulberry fruits have pharmacological properties, such as antioxidant, anti-diabetic, anti-atherosclerotic, anti-obesity, and hepatoprotective activities. The root bark of mulberry, containing flavonoids, alkaloids and stilbenoids, has antimicrobial, skin-whitening, cytotoxic, anti-inflammatory, and anti-hyperlipidemic properties. Other pharmacological properties of M. alba include anti-platelet, anxiolytic, anti-asthmatic, anthelmintic, antidepressant, cardioprotective, and immunomodulatory activities. Clinical trials on the efficiency of M. alba extracts in reducing blood glucose and cholesterol levels and enhancing cognitive ability have been conducted. The phytochemistry and pharmacology of the different parts of the mulberry tree confer its traditional and current uses as fodder, food, cosmetics, and medicine. Overall, M. alba is a multi-functional plant with promising medicinal properties.

  16. The pharmacology and clinical outcomes of amphetamines to treat ADHD: does composition matter?

    Science.gov (United States)

    Hodgkins, Paul; Shaw, Monica; McCarthy, Suzanne; Sallee, Floyd R

    2012-03-01

    Attention-deficit hyperactivity disorder (ADHD) treatment options include pharmacological and nonpharmacological approaches. In North America, psychostimulants (amphetamine and methylphenidate) are considered first-line pharmacological treatments for patients (children, adolescents and adults) with ADHD. However, in the UK, National Institute for Health and Clinical Excellence (NICE) guidelines have placed short-acting d-amphetamine as a third-line treatment option due to a lack of contemporary, published clinical trials on its efficacy and the concerns from clinical and patient experts regarding the potential for increased abuse and/or misuse compared with methylphenidate. These guidelines do not account for some of the more recent amphetamine products that have been developed to alleviate some of these concerns, but that are not currently approved in the UK or other European countries. The purpose of this review is to describe the pharmacology and clinical efficacy of various amphetamine compositions, as well as to explore the apparent differences in these compositions and their associated risks and benefits. A PubMed literature search was conducted to investigate amphetamine pharmacology, clinical efficacy and safety and ADHD outcomes in the published literature from 1980 through March 2011. Search terms included the keywords 'ADHD' or 'ADD' or 'hyperkinetic disorder' and any of the following keywords combined with 'or': 'amphetamine', 'dexamphetamine', 'mixed amphetamine salts', 'lisdexamfetamine' and 'methamphetamine'. The search included English-language primary research articles and review articles but excluded editorial articles and commentaries. The literature search resulted in 330 articles. Pertinent articles relating to amphetamine pharmacology, compositions, clinical efficacy and safety, effectiveness and tolerability, ADHD outcomes and abuse liability were included in this review. The different delivery profiles of amphetamine compositions result in

  17. Clinical development of fenretinide as an antineoplastic drug: Pharmacology perspectives.

    Science.gov (United States)

    Cooper, Jason P; Reynolds, C Patrick; Cho, Hwangeui; Kang, Min H

    2017-06-01

    Fenretinide (4-HPR) is a synthetic retinoid that has cytotoxic activity against cancer cells. Despite substantial in vitro cytotoxicity, response rates in early clinical trials with 4-HPR have been less than anticipated, likely due to the low bioavailability of the initial oral capsule formulation. Several clinical studies have shown that the oral capsule formulation at maximum tolerated dose (MTD) achieved drugs. Impact statement One of the critical components in drug development is understanding pharmacology (especially pharmacokinetics) of the drugs being developed. Often the pharmacokinetic properties, such as poor solubility leading to poor bioavailability, of the drug can limit further development of the drug. The development of numerous drugs has often halted at clinical testing stages, and several of them were due to the pharmacological properties of the agents, resulting in increased drug development cost. The current review provides an example of how improved clinical activity can be achieved by changing the formulations of a drug with poor bioavailability. Thus, it emphasizes the importance of understanding pharmacologic characteristics of the drug in drug development.

  18. Peer review in Clinical Pharmacology using the 8-D Assessment

    Science.gov (United States)

    Woodcock, Barry G.

    2017-01-01

    The requirement for editors of clinical pharmacology journals to maintain an overview of the peer review process for manuscripts submitted can be facilitated by use of the 8-D Assessment. The 8-D Assessment comprises peer review criteria to determine if the:1. Design of the study, 2. Diagnoses employed, 3. Drug molecules involved, 4. Dosages applied, 5. Data collected, 6. Discussion of the findings, 7. Deductions made, and 8. Documentation are in accord with the objectives of the study and meet the requirements of evidence-based medicine. This tool, although easy to apply, requires a high level of clinical pharmacology expertise, especially in the fields of drug disposition, pharmacokinetics, and drug action. PMID:28218890

  19. Nadroparin calcium: a review of its basic and clinical pharmacology

    OpenAIRE

    Ospina-González, Diego Alexander; Universidad de los Andes; Martínez, Jairo Andrés; Universidad de los Andes; Cifuentes, Luis Fernando; Universidad de los Andes

    2011-01-01

    Objective: To evaluate critically the evidence on the basic and clinical pharmacology of nadroparin calcium. Data source: We conducted a literature review from October 1985 to September 2010 in the electronic databases: Pubmed, Cochrane, MD Cosult, Medscape, Scielo and Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA).Study selection: Studies published in English, Spanish or French made in humans and animals for experimentation which reviewed the basic and clinical pharmac...

  20. Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use.

    Science.gov (United States)

    Taylor, Charles P; Traynelis, Stephen F; Siffert, Joao; Pope, Laura E; Matsumoto, Rae R

    2016-08-01

    Dextromethorphan (DM) has been used for more than 50years as an over-the-counter antitussive. Studies have revealed a complex pharmacology of DM with mechanisms beyond blockade of N-methyl-d-aspartate (NMDA) receptors and inhibition of glutamate excitotoxicity, likely contributing to its pharmacological activity and clinical potential. DM is rapidly metabolized to dextrorphan, which has hampered the exploration of DM therapy separate from its metabolites. Coadministration of DM with a low dose of quinidine inhibits DM metabolism, yields greater bioavailability and enables more specific testing of the therapeutic properties of DM apart from its metabolites. The development of the drug combination DM hydrobromide and quinidine sulfate (DM/Q), with subsequent approval by the US Food and Drug Administration for pseudobulbar affect, led to renewed interest in understanding DM pharmacology. This review summarizes the interactions of DM with brain receptors and transporters and also considers its metabolic and pharmacokinetic properties. To assess the potential clinical relevance of these interactions, we provide an analysis comparing DM activity from in vitro functional assays with the estimated free drug DM concentrations in the brain following oral DM/Q administration. The findings suggest that DM/Q likely inhibits serotonin and norepinephrine reuptake and also blocks NMDA receptors with rapid kinetics. Use of DM/Q may also antagonize nicotinic acetylcholine receptors, particularly those composed of α3β4 subunits, and cause agonist activity at sigma-1 receptors.

  1. Basic and clinical pharmacology contribution to extend anthelmintic molecules lifespan.

    Science.gov (United States)

    Lanusse, Carlos; Lifschitz, Adrian; Alvarez, Luis

    2015-08-15

    The correct use of pharmacology-based information is critical to design successful strategies for the future of parasite control in livestock animals. Integrated pharmaco-parasitological research approaches have greatly contributed to optimize drug activity. In an attempt to manage drug resistance in helminths of ruminants, combinations of two or more anthelmintics are being used or promoted, based on the fact that individual worms may have a lower degree of resistance to a multiple component formulation, when each chemical has a different mode of action compared to that observed when a single compound is used. However, as emphasized in the current review, the occurrence of potential pharmacokinetic and/or pharmacodynamic interactions between drug components highlights the need for deeper and integrated research to identify the advantages or disadvantages associated with the use of combined drug preparations. This review article provides integrated pharmacokinetic/pharmacodynamic and clinical pharmacology information pertinent to preserve the traditional and modern active ingredients as practical tools for parasite control. Novel pharmacological data on derquantel and monepantel, as representatives of modern anthelmintics for use in livestock, is summarized here. The article also summarizes the pharmaco-parasitological knowledge considered critical to secure and/or extend the lifespan of the recently available novel molecules. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Pharmacological basis and clinical evidence of dabigatran therapy

    Directory of Open Access Journals (Sweden)

    Redondo Santiago

    2011-12-01

    Full Text Available Abstract Dabigatran is an emerging oral anticoagulant which is a direct inhibitor of thrombin activity. It has been approved in the European Union and the United States of America for the prevention of thrombosis after major orthopedic surgery. It has also been approved by the American Food and Drug Administration and the European Medicines Agency for the prevention of stroke in chronic atrial fibrillation. Dabigatran provides a stable anticoagulation effect without any need to perform periodical laboratory controls. Of note, there is a growing amount of clinical evidence which shows its safety and efficacy. For these reasons, dabigatran may suppose a revolution in oral anticoagulation. However, two important limitations remain. First, it is contraindicated in patients with end-stage renal disease. Second, there is no evidence of the prevention of thrombosis in mechanical heart valves.

  3. Peer Review Certifies Quality and Innovation in Clinical Pharmacology & Therapeutics.

    Science.gov (United States)

    Waldman, S A; Terzic, A

    2017-09-01

    Clinical Pharmacology & Therapeutics (CPT) is an established voice of the discipline, a trusted source of new knowledge showcasing discovery, translation, and application of novel therapeutic paradigms to advance the management of patients and populations. Identifying, evaluating, prioritizing, and disseminating the best science along the discovery-development-regulatory-utilization continuum are responsibilities shared through peer review. To enhance the uniformity of this essential component of quality assurance and innovation, and maximize the value of the journal and its contents to authors, reviewers, and the readership, we review key concepts concerning peer review as it specifically relates to CPT. © 2017 ASCPT.

  4. Approach to pharmacological and clinical applications of Anisi aetheroleum

    Directory of Open Access Journals (Sweden)

    Khaled Mohamed Mohamed Koriem

    2015-01-01

    Full Text Available Anisi aetheroleum is the oil obtained from Pimpinella anisum L. (P. anisum by steam distillation. P. anisum seeds were air-dried, and then the dry seeds were crushed, pulverized, and weighed in sequence for anise oil preparation. P. anisum is one of the oldest medicinal plants that belong to family Apiaceae. The fruit of P. anisum is harvested in August and September. P. anisum is widespread in Asia, Africa and Europe. Local names of P. anisum include anise, anisoon, roomy, saunf, sweet cumin and yansoon. The anise oil odour is aromatic while the oil tastes sweet. The average daily dose of Anisi aetheroleum is 0.3 g. trans-Anethole is the major ingredient of the anise oil. Anisi aetheroleum also displays a protective action against neurotoxicity. In addition, Anisi aetheroleum increases glucose absorption and reduces urine output in the rat. The plant oil have pharmacological (antimicrobial, hepatoprotective, anticonvulsant, anti-inflammatory, antispasmodic, bronchodilator, estrogenic, expectorant and insecticidal effects and clinical effects on nausea, constipation, menopausal period, virus, diabetes, obesity and sedative action. Owing to the wide application of Anisi aetheroleum in pharmacological and clinical fields, it is recommended for more clinical trails to discover a new medication from the active constituents of the plant oil in the future to treat human diseases especially chronic ones.

  5. Approach to pharmacological and clinical applications of Anisi aetheroleum

    Institute of Scientific and Technical Information of China (English)

    Khaled; Mohamed; Mohamed; Koriem

    2015-01-01

    Anisi aetheroleum is the oil obtained from Pimpinella anisuin L.(P.anisuin) by steam distillation.P.anisuin seeds were air-dried,and then the dry seeds were crushed,pulverized,and weighed in sequence for anise oil preparation.P.anisuin is one of the oldest medicinal plants that belong to family Apiaceae.The fruit of P.anisuin is harvested in August and September.P.anisuin is widespread in Asia,Africa and Europe.Local names of P.anisuin include anise,anisoon,roomy,saunf,sweet cumin and yansoon.The anise oil odour is aromatic while the oil tastes sweet.The average daily dose of Anisi aetheroleum is 0.3 g.transAnethole is the major ingredient of the anise oil.Anisi aetheroleum also displays a protective action against neurotoxicity.In addition.Anisi aetheroleum increases glucose absorption and reduces urine output in the rat.The plant oil have pharmacological(antimicrobial,hepatoprotective.anticonvulsant,anti-inflammatory,antispasmodic,bronchodilator.estrogenic,expectorant and insecticidal) effects and clinical effects on nausea,constipation,menopausal period,virus,diabetes,obesity and sedative action.Owing to the wide application of Anisi aetheroleum in pharmacological and clinical fields,it is recommended for more clinical trails to discover a new medication from the active constituents of the plant oil in the future to treat human diseases especially chronic ones.

  6. Clinical Pharmacology in Denmark in 2016 - 40 Years with the Danish Society of Clinical Pharmacology and 20 Years as a Medical Speciality.

    Science.gov (United States)

    Brøsen, Kim; Andersen, Stig Ejdrup; Borregaard, Jeanett; Christensen, Hanne Rolighed; Christensen, Palle Mark; Dalhoff, Kim Peder; Damkier, Per; Hallas, Jesper; Heisterberg, Jens; Jessen, Niels; Jürgens, Gesche; Kampmann, Jens Peter Konnerup; Laursen, Britt Elmedal; Laursen, Torben; Nielsen, Lars Peter; Poulsen, Birgitte Klindt; Poulsen, Henrik Enghusen; Andersen, Ljubica Vukelic; Senderovitz, Thomas; Sonne, Jesper

    2016-12-01

    The Danish Society of Clinical Pharmacology was founded in 1976, and mainly thanks to the persistent efforts of the society, clinical pharmacology became an independent medical speciality in Denmark in 1996. Since then, clinical pharmacology has gone from strength to strength. In the Danish healthcare system, clinical pharmacology has established itself as an indispensible part of the efforts to promote the rational, safe and economic use of drugs. Clinical pharmacologists are active in drug committees both in hospitals and in the primary sector. All clinical pharmacology centres offer a local medicines information service. Some centres have established an adverse drug effect manager function. Only one centre offers a therapeutic drug monitoring service. Clinical pharmacologists are responsible for the toxicological advice at the Danish Poison Information Centre at Bispebjerg University Hospital in the Capital Region. The Department of Clinical Pharmacology at Aarhus University Hospital works closely together with forensic toxicologists and pathologists, covering issues regarding illicit substances, forensic pharmacology, post-mortem toxicology, expert testimony and research. Therapeutic geriatric and psychiatric teach-inns for specialist and junior doctors are among the newest initiatives organized by clinical pharmacologists. Clinical pharmacologists work also in the Danish Medicines Agency and in the Danish pharmaceutical industry, and the latter has in particular a great growth potential for creating new jobs and career opportunities for clinical pharmacologists. As of July 2016, the Danish Society of Clinical Pharmacology has 175 members, and 70 of these are specialists in clinical pharmacology corresponding to approximately 2.5 specialists per 1000 doctors (Denmark has in total 28,000 doctors) or approximately 12 specialists per one million inhabitants. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  7. The pharmacologic and clinical effects of medical cannabis.

    Science.gov (United States)

    Borgelt, Laura M; Franson, Kari L; Nussbaum, Abraham M; Wang, George S

    2013-02-01

    Cannabis, or marijuana, has been used for medicinal purposes for many years. Several types of cannabinoid medicines are available in the United States and Canada. Dronabinol (schedule III), nabilone (schedule II), and nabiximols (not U.S. Food and Drug Administration approved) are cannabis-derived pharmaceuticals. Medical cannabis or medical marijuana, a leafy plant cultivated for the production of its leaves and flowering tops, is a schedule I drug, but patients obtain it through cannabis dispensaries and statewide programs. The effect that cannabinoid compounds have on the cannabinoid receptors (CB(1) and CB(2) ) found in the brain can create varying pharmacologic responses based on formulation and patient characteristics. The cannabinoid Δ(9) -tetrahydrocannabinol has been determined to have the primary psychoactive effects; the effects of several other key cannabinoid compounds have yet to be fully elucidated. Dronabinol and nabilone are indicated for the treatment of nausea and vomiting associated with cancer chemotherapy and of anorexia associated with weight loss in patients with acquired immune deficiency syndrome. However, pain and muscle spasms are the most common reasons that medical cannabis is being recommended. Studies of medical cannabis show significant improvement in various types of pain and muscle spasticity. Reported adverse effects are typically not serious, with the most common being dizziness. Safety concerns regarding cannabis include the increased risk of developing schizophrenia with adolescent use, impairments in memory and cognition, accidental pediatric ingestions, and lack of safety packaging for medical cannabis formulations. This article will describe the pharmacology of cannabis, effects of various dosage formulations, therapeutics benefits and risks of cannabis for pain and muscle spasm, and safety concerns of medical cannabis use. © 2013 Pharmacotherapy Publications, Inc.

  8. 75 FR 8368 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2010-02-24

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and... certain drugs; (2) a new patient-centric clinical pharmacology approach to drug safety; (3) the design and...

  9. 77 FR 1696 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2012-01-11

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and... pharmacology aspects of pediatric clinical trial design and dosing to optimize pediatric drug development. FDA...

  10. Psychodiagnostic Testing in APA-Approved Clinical Psychology Programs.

    Science.gov (United States)

    Piotrowski, Chris; Keller, John W.

    The utility and popularity of psychodiagnostic testing has been investigated in applied clinical settings, but little data exist concerning academicians' attitudes toward psychological testing. To assess attitudes toward psychodiagnostic training in doctoral, clinical psychology programs, all fully APA-approved (American Psychological Association)…

  11. The BPS Diploma in Advanced Pharmacology: a training opportunity for clinical pharmacologists.

    Science.gov (United States)

    Hall, Judith M

    2007-04-01

    Coinciding with its 75th anniversary, the British Pharmacological Society (BPS) has launched a Diploma in Advanced Pharmacology (BPS Dip Pharmacol). This award is open to clinical and non-clinical scientists and those in related occupations. The Diploma is designed to appeal to those who want to further their pharmacological knowledge or gain an appreciation of basic and clinical aspects of the subject through participation in an advanced programme of non-clinical and clinical pharmacological study. The Diploma is unique in the UK. It provides not only a mechanism for continuing and updating education in basic pharmacology, clinical pharmacology, and therapeutics, but also a range of networking opportunities for non-clinical and clinical scientists in industry and academia.

  12. Clinical pharmacology profile of care in Hepatology clinic

    Directory of Open Access Journals (Sweden)

    Talita Rocha Passos

    Full Text Available Summary Since 2010, the Clinical Gastroenterology and Hepatology Division of the Central Institute of Hospital das Clínicas of the University of São Paulo Medical School (HC-FMUSP, in the Portuguese acronym has been developing specialized electives assistance activities in the Outpatient Specialty Clinic, Secondary Level, in São Paulo NGA-63 Várzea do Carmo. The objective of this study was to analyze the pharmacotherapeutic profile of patients. This is a cross-sectional and retrospective study in which patients were seen at the Hepatology sector and the results were submitted to descriptive statistics. During the study period, 492 patients were treated at the clinic, with a mean age of 58.9 years and frequency of 61.2% female and 74.8% living in São Paulo. This population was served by various other medical specialties (cardiology and endocrine among others and the major liver diagnoses were: chronic hepatitis B and C and fatty liver. Comorbidities were also identified, such as diabetes, hypertension and dyslipidemia. Most patients took their medication in the Basic Health Units. We found that 30% of patients use of more than five medications and the most prescribed were omeprazole 208 (42.3%, metformin 132 (26.8% and losartan 80 (16.3%. Because it is an adult/elderly population, with several comorbidities and polymedication, it is important to be aware of the rational use of medication. The multidisciplinary team is important in applying correct conducts for the safe use of medicines, to reduce the burden on health spending and improving the quality of life of patients.

  13. Clinical pharmacology and efficacy of sugammadex in the reversal of neuromuscular blockade.

    Science.gov (United States)

    Schaller, Stefan Josef; Lewald, Heidrun

    2016-09-01

    Sugammadex is the first clinical representative of a class of drugs called steroidal muscle relaxant encapsulators. Due to its 1:1 binding of rocuronium or vecuronium, sugammadex can reverse any depth of neuromuscular block and has therefore revolutionized the way anesthetists think about drug reversal. This review gives an overview of the clinical pharmacology and efficacy of sugammadex in healthy patients as well as in patients with pre-existing diseases. After approval in Europe in 2008 and Asia in 2010, sugammadex has recently been approved in the USA and Canada. This will open the field for further research especially for the use in special patient populations and specific diseases. Due to its pharmacodynamic profile, sugammadex in combination with rocuronium might have the potential to displace succinylcholine as the gold standard muscle relaxant for rapid sequence inductions. The use of rocuronium or vecuronium with the potential to reverse its action with sugammadex seems to be safe in patients with impaired neuromuscular transmission, i.e. (neuro)muscular diseases including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence towards an economic advantage of using sugammadex, justifying the relatively high costs for an anesthesia-related drug, is missing.

  14. Considerations for clinical pharmacology studies for biologics in emerging markets.

    Science.gov (United States)

    Damle, Bharat; White, Robert; Wang, Huifen Faye

    2015-03-01

    Registration of innovative biologics in Emerging Markets (EMs) poses many opportunities and challenges. The BRIC-MT countries (Brazil, Russia, India, China, Mexico, and Turkey) that are the fastest growing markets and regulators in these countries have imposed certain requirements, including the need for local clinical studies, for registration of biologics. The regulatory landscape in these countries is rapidly evolving, which necessitates an up-to-date understanding of such requirements. There is growing evidence which suggests that race, after accounting for body weight differences, may not influence the pharmacokinetics of biologics to the same extent that it does for small molecules. Thus, the requirements for clinical pharmacology trials in EMs are driven mainly by regulatory needs set forth by local Ministry of Health. In addition to the clinical Phase I to III studies done in the global program that supports registration in large geographies, countries such as China require local single and multiple dose Phase I studies. Participating in global studies with clinical sites within their country may be sufficient for some markets, while other regulators may be satisfied with a Certificate of Pharmaceutical Product. This paper discusses the current requirements for registration of innovative biologics in key EMs.

  15. CNS pharmacology and clinical therapeutic effects of oxiracetam.

    Science.gov (United States)

    Itil, T M; Menon, G N; Songar, A; Itil, K Z

    1986-01-01

    Oxiracetam, a new substance found to be a nootropic in experimental pharmacological studies, was tested in three clinical trials: a single rising dose tolerance and dose-finding study with quantitative pharmaco-electroencephalogram (pharmaco-EEG) and quantitative pharmacopsychology in healthy volunteers; a dose-finding study, at three dose levels for 3 months, with quantitative pharmaco-EEG in mild to moderate dementia patients; and a safety and efficacy study with increasing dosages for 12 weeks with subjective and objective tests in elderly patients with dementia. In single and repeated oral dosages up to 2,400 mg, oxiracetam is a safe compound. According to HZI Data Bank Classification Systems, oxiracetam is a vigilance-enhancing compound with some effects on spontaneous memory. The therapeutic effect of oxiracetam can be discriminated from placebo, and in comparison with piracetam, oxiracetam exhibits greater improvement in memory factor.

  16. World Antimalarial Resistance Network (WARN IV: Clinical pharmacology

    Directory of Open Access Journals (Sweden)

    Gbotosho Grace O

    2007-09-01

    Full Text Available Abstract A World Antimalarial Resistance Network (WARN database has the potential to improve the treatment of malaria, through informing current drug selection and use and providing a prompt warning of when treatment policies need changing. This manuscript outlines the contribution and structure of the clinical pharmacology component of this database. The determinants of treatment response are multi-factorial, but clearly providing adequate blood concentrations is pivotal to curing malaria. The ability of available antimalarial pharmacokinetic data to inform optimal dosing is constrained by the small number of patients studied, with even fewer (if any studies conducted in the most vulnerable populations. There are even less data relating blood concentration data to the therapeutic response (pharmacodynamics. By pooling all available pharmacokinetic data, while paying careful attention to the analytical methodologies used, the limitations of small (and thus underpowered individual studies may be overcome and factors that contribute to inter-individual variability in pharmacokinetic parameters defined. Key variables for pharmacokinetic studies are defined in terms of patient (or study subject characteristics, the formulation and route of administration of the antimalarial studied, the sampling and assay methodology, and the approach taken to data analysis. Better defining these information needs and criteria of acceptability of pharmacokinetic-pharmacodynamic (PK-PD studies should contribute to improving the quantity, relevance and quality of these studies. A better understanding of the pharmacokinetic properties of antimalarials and a more clear definition of what constitutes "therapeutic drug levels" would allow more precise use of the term "antimalarial resistance", as it would indicate when treatment failure is not caused by intrinsic parasite resistance but is instead the result of inadequate drug levels. The clinical pharmacology component

  17. Review of the pharmacology and clinical studies of micafungin

    Directory of Open Access Journals (Sweden)

    Alison M Bormann

    2009-12-01

    Full Text Available Alison M Bormann1, Vicki A Morrison21Division of Infectious Diseases, University of Minnesota, Minneapolis, MN, USA; 2Division of Hematology/Oncology and Infectious Disease, Minneapolis Veterans Affairs Medical Center, Minneapolis, MN, USAAbstract: Micafungin, like other members of the echinocandin class, has a unique mechanism of action that inhibits the synthesis of 1,3-β-D glucans in the fungal cell wall. It has been approved for treatment of esophageal candidiasis, invasive candidiasis including candidemia, and for prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation. Although efficacy and safety have also been demonstrated in pediatric populations, micafungin is approved for this indication in Europe and Japan, but not in the United States. It has demonstrated activity against Candida spp. including those that are azole-resistant as well as Aspergillus and a few other clinically important molds. It is administered intravenously as a once daily infusion and does not require dose adjustments for renal or moderate hepatic dysfunction. Its safety record, favorable tolerability profile, and few drug interactions make it an important agent for the treatment of invasive fungal infections.Keywords: micafungin, antifungal therapy, echinocandins, fungal infections, Candida, Aspergillus

  18. ASPECTS OF THE AMLODIPINE PLEIOTROPY IN BIOCHEMISTRY, PHARMACOLOGY AND CLINICS

    Directory of Open Access Journals (Sweden)

    Rasma Vitolina, Aivars Krauze, Gunars Duburs and Astrida Velena*

    2012-05-01

    Full Text Available Amlodipine is the third generation calcium antagonist, 1,4-dihydropyridine derivative with the prolonged duration of the antihypertensive action, especially blocking L-type Ca2+ ion channels. It promotes beneficial therapeutic effect by coronary and other blood vessel diseases and thus delays development of the atherosclerosis. It has several known trade names, the most mentioned is Norvasc. Amlodipine is well tolerated in the clinics, it could be used in combinations with other drugs – diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, statins. Amlodipine at nanomolar concentrations binds to the voltage-dependent L-type calcium channels. It possesses optimal lipophylicity. Amlodipine also influences the NO-dependent metabolic processes, stimulates NO synthesis and prolongs NO action duration. Results of the studies of the amlodipine pharmacological and clinical properties are summarized in several reviews. The present review contains opinion from the scientific works of the last decades about the multisided or pleiotropic amlodipine mechanisms of action, it contains information about sometimes controversial clinical studies of the amlodipine vaso- and cardioprotective activity.

  19. Repurposing clinically approved cephalosporins for tuberculosis therapy

    Science.gov (United States)

    Ramón-García, Santiago; González del Río, Rubén; Villarejo, Angel Santos; Sweet, Gaye D.; Cunningham, Fraser; Barros, David; Ballell, Lluís; Mendoza-Losana, Alfonso; Ferrer-Bazaga, Santiago; Thompson, Charles J.

    2016-01-01

    While modern cephalosporins developed for broad spectrum antibacterial activities have never been pursued for tuberculosis (TB) therapy, we identified first generation cephalosporins having clinically relevant inhibitory concentrations, both alone and in synergistic drug combinations. Common chemical patterns required for activity against Mycobacterium tuberculosis were identified using structure-activity relationships (SAR) studies. Numerous cephalosporins were synergistic with rifampicin, the cornerstone drug for TB therapy, and ethambutol, a first-line anti-TB drug. Synergy was observed even under intracellular growth conditions where beta-lactams typically have limited activities. Cephalosporins and rifampicin were 4- to 64-fold more active in combination than either drug alone; however, limited synergy was observed with rifapentine or rifabutin. Clavulanate was a key synergistic partner in triple combinations. Cephalosporins (and other beta-lactams) together with clavulanate rescued the activity of rifampicin against a rifampicin resistant strain. Synergy was not due exclusively to increased rifampicin accumulation within the mycobacterial cells. Cephalosporins were also synergistic with new anti-TB drugs such as bedaquiline and delamanid. Studies will be needed to validate their in vivo activities. However, the fact that cephalosporins are orally bioavailable with good safety profiles, together with their anti-mycobacterial activities reported here, suggest that they could be repurposed within new combinatorial TB therapies. PMID:27678056

  20. Pharmacological and clinical overview of cloperastine in treatment of cough

    Directory of Open Access Journals (Sweden)

    Maria Antonietta Catania

    2011-03-01

    Full Text Available Maria Antonietta Catania1, Salvatore Cuzzocrea1,21Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina; 2IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, ItalyAbstract: Cough constitutes an impressive expression of the normal defense mechanisms of the respiratory system. Productive cough associated with catarrh is an important protective system for the lung because it favors the upward movement of secretions and foreign bodies to the larynx and mouth. Cough may also appear without bronchial secretions, as dry cough, which may be persistent when inflammatory disease is chronic or when, in the early stages of respiratory disease, bronchial secretions are not yet fluid. Sometimes bronchitis-induced cough does not significantly affect quality of life, whilst in other cases cough may become so intense as to impair daily activities severely, resulting in permanent disability. This type of cough is one of the most frequent reasons for seeking medical advice. The use of cough suppressants may be appropriate for reaching a precise diagnosis and when dry cough is persistent. Cloperastine has been investigated in various types of cough and, unlike codeine, has been shown to possess dual activity. It also acts as a mild bronchorelaxant and has antihistaminic activity, without acting on the central nervous system or the respiratory center. Here we review the preclinical and clinical evidence of the efficacy and tolerability of cloperastine.Keywords: cough, cloperastine, inflammation, bronchitis

  1. MR arthrography: pharmacology, efficacy and safety in clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Schulte-Altedorneburg, G.; Gebhard, M.; Wohlgemuth, W.A.; Fischer, W.; Zentner, J.; Bohndorf, K. [Department of Radiology, Klinikum Augsburg, Stenglinstrasse 2, 86156 Augsburg (Germany); Wegener, R.; Balzer, T. [Clinical Development Diagnostics and Radiopharmaceuticals II, Schering AG, Berlin (Germany)

    2003-01-01

    A meta-analysis was carried out of clinical trials published between 1987 and 2001 in respect of the clinical pharmacology and safety as well as the diagnostic efficacy of gadolinium-DTPA (Gd-DTPA) for direct intra-articular injection before MRI examination.Design. Scientific papers (clinical, postmortem and experimental studies) and information from the manufacturer regarding intra-articular injection of Gd-DTPA that addressed questions of mode of action, optimal concentration and dose, elimination and safety were reviewed. Clinical studies were classified according to their study design. The sensitivity, specificity and accuracy of MR arthrography (MRA) were compared with a ''gold standard'' (arthroscopy, arthrotomy) and other radiological evidence for different joints.Results. Fifty-two clinical studies of the overall 112 studies addressed aspects of diagnostic efficacy of MRA in patients or in healthy volunteers. The shoulder was the most assessed joint (29 of 52 studies). Good (>80%) or even excellent (90-100%) sensitivity, specificity and accuracy were found for MRA in most indications, especially for the shoulder and knee joints and induced extension of rotator cuff lesions, labrum abnormalities and postoperative meniscal tears. Two millimoles per liter has proven to be the best concentration for intra-articular administration of Gd-DTPA. After passive complete diffusion from the joint within 6-24 h, complete and rapid renal elimination takes place after intra-articular injection. Local safety proved to be excellent after intra-articular administration of Gd-DTPA. Regarding systemic tolerance almost no side effects have been reported, but the same safety considerations apply for intra-articular administration of Gd-DTPA as for intravenous injection.Conclusions. The diagnostic efficacy of intra-articular MRA in most clinical conditions affecting major joints is greater than that of plain MRI. In some diagnostic problems MRA achieves almost

  2. Application of optimal design methodologies in clinical pharmacology experiments.

    Science.gov (United States)

    Ogungbenro, Kayode; Dokoumetzidis, Aristides; Aarons, Leon

    2009-01-01

    Pharmacokinetics and pharmacodynamics data are often analysed by mixed-effects modelling techniques (also known as population analysis), which has become a standard tool in the pharmaceutical industries for drug development. The last 10 years has witnessed considerable interest in the application of experimental design theories to population pharmacokinetic and pharmacodynamic experiments. Design of population pharmacokinetic experiments involves selection and a careful balance of a number of design factors. Optimal design theory uses prior information about the model and parameter estimates to optimize a function of the Fisher information matrix to obtain the best combination of the design factors. This paper provides a review of the different approaches that have been described in the literature for optimal design of population pharmacokinetic and pharmacodynamic experiments. It describes options that are available and highlights some of the issues that could be of concern as regards practical application. It also discusses areas of application of optimal design theories in clinical pharmacology experiments. It is expected that as the awareness about the benefits of this approach increases, more people will embrace it and ultimately will lead to more efficient population pharmacokinetic and pharmacodynamic experiments and can also help to reduce both cost and time during drug development.

  3. Multiple System Atrophy. Using Clinical Pharmacology to Reveal Pathophysiology

    Science.gov (United States)

    Jordan, Jens; Shibao, Cyndya; Biaggioni, Italo

    2015-01-01

    Despite similarities in their clinical presentation, patients with multiple system atrophy (MSA) have residual sympathetic tone and intact post-ganglionic noradrenergic fibers, whereas patients with pure autonomic failure (PAF) and Parkinson’s disease (PD) have efferent post-ganglionic autonomic denervation. These differences are apparent biochemically, with near normal plasma norepinephrine in MSA but very low levels in PAF, and in neurophysiological testing. These differences are also reflected in the response patients have to drugs that interact with the autonomic nervous system. E.g., the ganglionic blocker trimethaphan reduce residual sympathetic tone and lower blood pressure in MSA but less so in PAF. Conversely, the α2-antagonist yohimbine produces a greater increase in blood pressure in MSA compared to PAF, although significant overlap exists. In normal subjects the norepinephrine reuptake (NET) inhibitor atomoxetine has little effect on blood pressure because the peripheral effects of NET inhibition that result in noradrenergic vasoconstriction, are counteracted by the increase in brain norepinephrine which reduces sympathetic outflow (a clonidine-like effect). In patients with autonomic failure and intact peripheral noradrenergic fibers only the peripheral vasoconstriction is apparent. This translates to a significant pressor effect of atomoxetine in MSA, but not in PAF patients. Thus, pharmacological probes can be used to understand the pathophysiology of the different forms of autonomic failure, assist in the diagnosis, and aid in the management of orthostatic hypotension. PMID:25757803

  4. Clinical Pharmacology of Furosemide in Neonates: A Review

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    2013-09-01

    Full Text Available Furosemide is the diuretic most used in newborn infants. It blocks the Na+-K+-2Cl− symporter in the thick ascending limb of the loop of Henle increasing urinary excretion of Na+ and Cl−. This article aimed to review the published data on the clinical pharmacology of furosemide in neonates to provide a critical, comprehensive, authoritative and, updated survey on the metabolism, pharmacokinetics, pharmacodynamics and side-effects of furosemide in neonates. The bibliographic search was performed using PubMed and EMBASE databases as search engines; January 2013 was the cutoff point. Furosemide half-life (t1/2 is 6 to 20-fold longer, clearance (Cl is 1.2 to 14-fold smaller and volume of distribution (Vd is 1.3 to 6-fold larger than the adult values. t1/2 shortens and Cl increases as the neonatal maturation proceeds. Continuous intravenous infusion of furosemide yields more controlled diuresis than the intermittent intravenous infusion. Furosemide may be administered by inhalation to infants with chronic lung disease to improve pulmonary mechanics. Furosemide stimulates prostaglandin E2 synthesis, a potent dilator of the patent ductus arteriosus, and the administration of furosemide to any preterm infants should be carefully weighed against the risk of precipitation of a symptomatic patent ductus arteriosus. Infants with low birthweight treated with chronic furosemide are at risk for the development of intra-renal calcifications.

  5. Clinical pharmacology of fentanyl in preterm infants. A review.

    Science.gov (United States)

    Pacifici, Gian Maria

    2015-06-01

    Fentanyl is a synthetic opioid that is very important in anesthetic practice because of its relatively short time to peak analgesic effect and the rapid termination of action after small bolus doses. The objective of this survey is to review the clinical pharmacology of fentanyl in preterm infants. The bibliographic search was performed using PubMed and EMBASE databases as search engines. In addition, the books Neofax: A manual of drugs used in neonatal care and Neonatal formulary were consulted. Fentanyl is N-dealkylated by CYP3A4 into the inactive norfentanyl. Fentanyl may be administered as bolus doses or as a continuous infusion. In neonates, there is a remarkable interindividual variability in the kinetic parameters. In neonates, fentanyl half-life ranges from 317 minutes to 1266 minutes and in adults it is 222 minutes. Respiratory depression occurs when fentanyl doses are >5 μg/kg. Chest wall rigidity may occur in neonates and occasionally is associated with laryngospasm. Tolerance to fentanyl may develop after prolonged use of this drug. Significant withdrawal symptoms have been reported in infants treated with continuous infusion for 5 days or longer. Fentanyl is an extremely potent analgesic and is the opioid analgesic most frequently used in the neonatal intensive care unit.

  6. Canagliflozin use in patients with renal impairment-Utility of quantitative clinical pharmacology analyses in dose optimization.

    Science.gov (United States)

    Khurana, Manoj; Vaidyanathan, Jayabharathi; Marathe, Anshu; Mehrotra, Nitin; Sahajwalla, Chandrahas G; Zineh, Issam; Jain, Lokesh

    2015-06-01

    Canagliflozin (INVOKANA™) is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). Canagliflozin inhibits renal sodium-glucose co-transporter 2 (SGLT2), thereby, reducing reabsorption of filtered glucose and increasing urinary glucose excretion. Given the mechanism of action of SGLT2 inhibitors, we assessed the interplay between renal function, efficacy (HbA1c reduction), and safety (renal adverse reactions). The focus of this article is to highlight the FDA's quantitative clinical pharmacology analyses that were conducted to support the regulatory decision on dosing in patients with renal impairment (RI). The metrics for assessment of efficacy for T2DM drugs is standard; however, there is no standard method for evaluation of renal effects for diabetes drugs. Therefore, several analyses were conducted to assess the impact of canagliflozin on renal function (as measured by eGFR) based on available data. These analyses provided support for approval of canagliflozin in T2DM patients with baseline eGFR ≥ 45 mL/min/1.73 m(2) , highlighting a data-driven approach to dose optimization. The availability of a relatively rich safety dataset (ie, frequent and early measurements of laboratory markers) in the canagliflozin clinical development program enabled adequate assessment of benefit-risk balance in various patient subgroups based on renal function. © 2015, The American College of Clinical Pharmacology.

  7. Children with schizophrenia: clinical picture and pharmacological treatment.

    Science.gov (United States)

    Masi, Gabriele; Mucci, Maria; Pari, Cinzia

    2006-01-01

    these clinical patterns, such as multidimensionally impaired disorder and multiple complex developmental disorder. In the context of a multimodal approach, including behavioral, social, scholastic and familial interventions, a pharmacological treatment is usually the core treatment. Available experience from the few controlled studies, open studies and case reports on pharmacotherapy in children with schizophrenia aged <12 years is critically analysed in this review, with particular reference to the use of atypical antipsychotics in clinical practice. To date, the major evidence supports the efficacy of risperidone and olanzapine, while clozapine seems an effective option in treatment-refractory cases. Published experience with newer atypical antipsychotics (quetiapine, ziprasidone, aripiprazole) is still lacking in this age range. Safety data (namely extrapyramidal symptoms, weight gain, hyperprolactinaemia, haematological adverse effects, seizures, hepatotoxicity, metabolic effects, neuroleptic malignant syndrome and cardiovascular effects) are reviewed and discussed, along with strategies for management.

  8. The current status and trend of clinical pharmacology in developing countries

    Science.gov (United States)

    2013-01-01

    Background Several international forums for promoting clinical pharmacology in developing countries have been held since 1980, and several clinical pharmacology programmes targeting developing countries were instituted such that the status of clinical pharmacology in developing countries is not where it was 50 years ago. Therefore, a survey and an appraisal of the literature on the current status of clinical pharmacology in developing countries were undertaken with a hope that it would enable development of appropriate strategies for further promotion of clinical pharmacology in these countries. Methods First, nine determinants (or enabling factors) for running a successful clinical pharmacology programme were identified, i.e., disease burden, drug situation, economic growth, clinical pharmacology activities, recognition, human capital, government support, international collaboration, and support for traditional/alternative medicines. These factors were then evaluated with regard to their current status in the developing countries that responded to an electronic questionnaire, and their historical perspective, using the literature appraisal. From these, a projected trend was constructed with recommendations on the way forward. Results Clinical pharmacology services, research and teaching in developing countries have improved over the past 50 years with over 90% of countries having the appropriate policies for regulation and rational use of medicines in place. Unfortunately, policy implementation remains a challenge, owing to a worsening disease burden and drug situation, versus fewer clinical pharmacologists and other competing priorities for the national budgets. This has led to a preference for training ‘a physician clinical pharmacologist’ in programmes emphasizing local relevancy and for a shorter time, and the training of other professionals in therapeutics for endemic diseases (task shifting), as the most promising strategies of ensuring rational use of

  9. Clinical Pharmacology of Ciprofloxacin in Neonates: Effects and Pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    2017-06-01

    Full Text Available Ciprofloxacin is the most commonly used fluoroquinolone. Ciprofloxacin is prescribed for 1 in 44 Americans. Ciprofloxacin is a broad-spectrum bactericidal antibiotic, effective against both gram-positive and gram-negative bacteria, being especially active against the Enterobacteriacae, including many microorganisms resistant to penicillins, cephalosporins and aminoglycosides, and also is effective against Haemophilus influenzae, penicillinase-producing Neisseria gonorrhea, Campylobacter and Pseudomonas aeruginosa. Streptococci and pneumococci are weakly inhibited and there is a high incidence of staphylococcal resistance to ciprofloxacin. In neonates, the dose of ciprofloxacin is 10 mg/kg intravenously over 30-60 min infusion, and 20 mg/kg is used to treat Pseudomonas aeruginosa infection. Ciprofloxacin treatment is effective in life-threatening multi-drug resistant Pseudomonas aeruginosa. Ciprofloxacin may be administered by mouth and has a bioavailability of 70% and is mainly recovered unchanged in the urine. Ciprofloxacin is safe and well tolerated in infants. In neonates, the half-life of ciprofloxacin is 3-4 hours. For meningococcal prophylaxis, give a single dose of 30 mg/kg (up to a maximum of 125 mg orally. Ciprofloxacin is active against Citrobacter kosery that produces brain abscesses. The mortality rate for meningitis due to Citrobacter kosery is approximately 30%. Third-generation cephalosporins and aminoglycosides failed to prevent the high rates of morbidity and mortality caused by Citrobacter infections. Ciprofloxacin is the antibiotic treatment option for systemic infection or meningitis caused by Citrobacter kosery. Ciprofloxacin has been used to treat neonatal pneumonia, meningitis, and septicemia and was effective in all cases. The aim of this study is to review the clinical pharmacology of ciprofloxacin in neonates.

  10. An Endocrine Pharmacology Course for the Clinically-Oriented Pharmacy Curriculum

    Science.gov (United States)

    Rahwan, Ralf G.

    1976-01-01

    In view of trends in clinical pharmacy education, the role of the traditional basic sciences has to be reassessed. An endocrine pharmacology course comprised of 49 clock-hours and open for professional undergraduate and graduate credit is described that blends basic and applied pharmacology. (LBH)

  11. Clinical relevance of pharmacological and physiological data in intrathecal baclofen therapy

    NARCIS (Netherlands)

    Heetla, Herre W; Staal, Michael; Proost, Johannes H; van Laar, Teus

    2014-01-01

    Objective: To review all pharmacological and physiological data available on intrathecal baclofen (ITB) therapy and to evaluate its use in clinical practice and future research. Data Sources: PubMed was searched for relevant anatomic, physiological, and pharmacological data available on ITB. Study S

  12. How should training of graduates in clinical pharmacology and therapeutics be delivered and assessed?

    Science.gov (United States)

    Jackson, Peter

    2012-06-01

    The UK postgraduate curriculum in clinical pharmacology and therapeutics (CPT) incorporates the common competencies required of all physicians and shows how trainees from other specialties, including primary care, can train in CPT. Various models of training and assessment are possible. Evolution of the current system to meet new challenges would maintain an established tradition, with a ready source of training funds. However, this would require greater input from all consultants in CPT, including the training and assessment of trainees. A joint venture with the Faculty of Pharmaceutical Medicine would have the advantage, if the Faculty agreed, of introducing ready-made curriculum modules and assessment tools that have been accepted by the General Medical Council. However, extra modules relevant to CPT would have to be constructed to complement the common areas already in the pharmaceutical medicine curriculum, and there would be a perceived loss of the independence that clinical pharmacologists currently enjoy when making decisions about manufacturers' products. Abandoning externally approved training in CPT would allow the specialty to devise its own training and assessment in the necessary skills. Critically, however, this would impair the status of the specialty and would incur loss of financial support from postgraduate Deaneries. To attract high-calibre trainees, we must completely define CPT training and assessment structures. Most clinical pharmacologists seem to prefer to allow the current structures to evolve under external guidance. However, this will not succeed unless all trained clinical pharmacologists contribute to development of both the curriculum and specific assessment tools, and open their teaching and assessment skills to scrutiny.

  13. Safety pharmacology: an essential interface of pharmacology and toxicology in the non-clinical assessment of new pharmaceuticals.

    Science.gov (United States)

    Claude, Jean-Roger; Claude, Nancy

    2004-06-15

    Safety pharmacology studies are defined as the studies that investigate the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure. In consequence, these studies are an integral part of the non-clinical safety assessment of new pharmaceuticals, in association with toxicological studies. A retrospective shows the evolution of the discipline in these last years. Safety pharmacology studies are of special interest, and some drawbacks and pitfalls must be considered (i.e. invasive methods, difficulties related to GLP (good laboratory practices) requirements, choice of a strategy). In the future, some priority should be given to education, promotion of scientific activities, reinforcement of the links between pharmacologists and toxicologists and implementation of relevant guidelines.

  14. Evaluation of impact of teaching clinical pharmacology and rational therapeutics to medical undergraduates and interns

    Science.gov (United States)

    Desai, Mira K; Panchal, Jigar R; Shah, Samdih; Iyer, Geetha

    2016-01-01

    Objectives: To find out the impact of teaching clinical pharmacology and rational therapeutics (CPT) to medical undergraduates (UGs) and interns. Materials and Methods: This cross-sectional, prospective study was conducted on three UGs batches and interns using two pretested validated structured questionnaires, modified from the work of Tobaiqy et al. The study was approved by the Institutional Ethics Committee. ANOVA and Chi-square test were used for statistical analysis. The value of P < 0.05 was considered statistically significant. Results: A total of 379 UGs and 96 interns participated in this study. Mean knowledge score of interns was significantly reduced as compared to UGs (P < 0.0001). A significant increase in confidence for unsupervised prescribing of nonsteroidal anti-inflammatory drugs (99%), oral rehydration salt, iron salts was perceived among interns as compared to UGs (P < 0.05). However, 63.5% confessed problems in selection of drugs, drug–drug interactions, prescribing in special patient population. Although they were confident prescribing fixed dose combination for adult patients (89.5%), majority were hesitant to prescribe opioids (77%), steroids (76%), vaccines (75%), and antihypertensives (62%). Conclusion: The theoretical CPT teaching transfers knowledge to UGs; however, it is not retained in internship and does not adequately prepare interns to prescribe safe and rational drugs. PMID:27563589

  15. [Clinical-pharmacological aspects to accelerate the development process from the preclinical to the clinical phase/1st communication: The contribution of clinical pharmacology].

    Science.gov (United States)

    Kuhlmann, Jochen

    2004-01-01

    To improve the transition from research to development a critical evaluation of the individual project by research and disease area teams is required to include input from pharmacology, toxicology, pharmacokinetics, galenics, clinical pharmacology, clinical as well as regulatory experts and marketing. Decisions on the individual development strategy should be made prior to the start of development and all projects should be reviewed at predefined stages throughout the product development life cycle. This ensures consistency of decision-making not only during the development of individual products but throughout the entire development pipeline. Studies in the exploratory stage of drug development should be designed for decision making in contrast to later clinical trials in the confirmatory stage that require power for proof-of-safety and proof-of-efficacy. The more thorough and profound studies have been carried out during this exploratory stage of drug development, the earlier a decision can be made on the continuation or discontinuation of further development, thus saving development time and money and assessing and considerably reducing the risk for the patients and increasing the success rate of the project in the later confirmatory effectiveness trial with an adequate number of subjects receiving the new therapy under typical conditions of use. Strategies which may be helpful to improve the quality of decisions in drug discovery and drug development are: discovery experiments should be done to critically evaluate the compound, the "killer" experiments should be done as early as possible, continuous effort on preclinical disease models is necessary to improve predictability of efficacy in patients ("humanized" research): genomic technology should be used to identify novel, disease-related targets and to characterise preclinical test systems, improvement of knowledge and experience concerning the relevance of new technologies for the clinical picture; genotyping

  16. The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication

    Science.gov (United States)

    Sacramento, Carolina Q.; de Melo, Gabrielle R.; de Freitas, Caroline S.; Rocha, Natasha; Hoelz, Lucas Villas Bôas; Miranda, Milene; Fintelman-Rodrigues, Natalia; Marttorelli, Andressa; Ferreira, André C.; Barbosa-Lima, Giselle; Abrantes, Juliana L.; Vieira, Yasmine Rangel; Bastos, Mônica M.; de Mello Volotão, Eduardo; Nunes, Estevão Portela; Tschoeke, Diogo A.; Leomil, Luciana; Loiola, Erick Correia; Trindade, Pablo; Rehen, Stevens K.; Bozza, Fernando A.; Bozza, Patrícia T.; Boechat, Nubia; Thompson, Fabiano L.; de Filippis, Ana M. B.; Brüning, Karin; Souza, Thiago Moreno L.

    2017-01-01

    Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues. Sofosbuvir inhibited ZIKV replication in different cellular systems, such as hepatoma (Huh-7) cells, neuroblastoma (SH-Sy5y) cells, neural stem cells (NSC) and brain organoids. In addition to the direct inhibition of the viral RNA polymerase, we observed that sofosbuvir also induced an increase in A-to-G mutations in the viral genome. Together, our data highlight a potential secondary use of sofosbuvir, an anti-HCV drug, against ZIKV. PMID:28098253

  17. Integration of new technology into clinical practice after FDA approval.

    Science.gov (United States)

    Govil, Ashul; Hao, Steven C

    2016-10-01

    Development of new medical technology is a crucial part of the advancement of medicine and our ability to better treat patients and their diseases. This process of development is long and arduous and requires a significant investment of human, financial and material capital. However, technology development can be rewarded richly by its impact on patient outcomes and successful sale of the product. One of the major regulatory hurdles to technology development is the Food and Drug Administration (FDA) approval process, which is necessary before a technology can be marketed and sold in the USA. Many businesses, medical providers and consumers believe that the FDA approval process is the only hurdle prior to use of the technology in day-to-day care. In order for the technology to be adopted into clinical use, reimbursement for both the device as well as the associated work performed by physicians and medical staff must be in place. Work and coverage decisions require Current Procedural Terminology (CPT) code development and Relative Value Scale Update Committee (RUC) valuation determination. Understanding these processes is crucial to the timely availability of new technology to patients and providers. Continued and better partnerships between physicians, industry, regulatory bodies and payers will facilitate bringing technology to market sooner and ensure appropriate utilization.

  18. International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

    OpenAIRE

    Ushkaryov, Yuri

    2015-01-01

    The Adhesion family forms a large branch of the pharmacologically important superfamily of G protein–coupled receptors (GPCRs). As Adhesion GPCRs increasingly receive attention from a wide spectrum of biomedical fields, the Adhesion GPCR Consortium, together with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification, proposes a unified nomenclature for Adhesion GPCRs. The new names have ADGR as common dominator followed by a lett...

  19. International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors.

    Science.gov (United States)

    Panula, Pertti; Chazot, Paul L; Cowart, Marlon; Gutzmer, Ralf; Leurs, Rob; Liu, Wai L S; Stark, Holger; Thurmond, Robin L; Haas, Helmut L

    2015-07-01

    Histamine is a developmentally highly conserved autacoid found in most vertebrate tissues. Its physiological functions are mediated by four 7-transmembrane G protein-coupled receptors (H1R, H2R, H3R, H4R) that are all targets of pharmacological intervention. The receptors display molecular heterogeneity and constitutive activity. H1R antagonists are long known antiallergic and sedating drugs, whereas the H2R was identified in the 1970s and led to the development of H2R-antagonists that revolutionized stomach ulcer treatment. The crystal structure of ligand-bound H1R has rendered it possible to design new ligands with novel properties. The H3R is an autoreceptor and heteroreceptor providing negative feedback on histaminergic and inhibition on other neurons. A block of these actions promotes waking. The H4R occurs on immuncompetent cells and the development of anti-inflammatory drugs is anticipated.

  20. Pre-clinical pharmacology training in a student-centered veterinary curriculum.

    Science.gov (United States)

    Buur, Jennifer L

    2009-01-01

    The appropriate use of therapeutics is important to both human and animal health. The field of pharmacology is rapidly progressing such that it is impossible to convey to students every possible piece of information they will need to know throughout their veterinary careers. Instead, it is more important to train students for lifelong and self-directed learning so that they will be able to adapt to the ever-changing pharmaceutical landscape. Western University of Health Sciences College of Veterinary Medicine teaches pharmacology using a student-centered and problem-based curriculum designed to teach students not only the basics of pharmacology and clinical pharmacology, but also the personal skills needed to continue to learn beyond their formal education. The aim of this manuscript is to document the pharmacology curriculum during phase I of the veterinary curriculum. Review of the graduating class of 2010's exposure to pharmacology learning issues reveals broad-based coverage of major functional and mechanistic drug classes as well as peripheral topics, including pharmacokinetics, legal and ethical issues, and dosing regimen calculations. Previous classes have scored well on external examinations leading to a belief that this pharmacology curriculum provides adequate training for graduate veterinarians.

  1. A new generation of antipsychotics: pharmacology and clinical utility of cariprazine in schizophrenia

    Directory of Open Access Journals (Sweden)

    Caccia S

    2013-08-01

    Full Text Available Silvio Caccia, Roberto William Invernizzi, Alessandro Nobili, Luca Pasina IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy Abstract: Cariprazine is a potential antipsychotic awaiting approval from the US Food and Drug Administration. It is a dopamine D2- and D3-receptor partial agonist, with higher affinity for D3 receptors, as opposed to the D2 antagonism of most older antipsychotic agents. Like most lipophilic antipsychotics, it undergoes extensive hepatic metabolism by cytochrome P450 (CYP, mainly the highly variable 3A4, with the formation of active metabolites. However, the parent compound – particularly its active didesmethyl derivative – is cleared very slowly, with elimination half-lives in schizophrenic patients ranging from 2–5 days for cariprazine to 2–3 weeks for didesmethyl-cariprazine. Exposure to the latter was several times that for cariprazine, although didesmethyl-cariprazine did not reach steady state within the 3 weeks of 12.5 mg/day dosing. Preliminary information on its therapeutic role comes from press releases and a few abstracts presented at scientific meetings. In short-term controlled trials, it was more effective than placebo in reducing positive and negative symptoms of schizophrenia, with an effective dose range of 1.5–12 mg/day. Although cariprazine was associated with a higher incidence of akathisia and extrapyramidal side effects than placebo, it did not cause weight gain, metabolic abnormalities, prolactin increase, or corrected QT prolongation. Similarly, cariprazine's efficacy and tolerability for the treatment of bipolar disorder (manic/mixed and depressive episodes was established in the dose range of 3–12 mg/day, although again no long-term data are available. Well-designed clinical trials, mainly direct "head-to-head" comparisons with other second-generation antipsychotic agents, are needed to define the therapeutic role and safety profile of cariprazine in schizophrenia and

  2. Pharmacologic sensitivity of paclitaxel to its delivery vehicles drives distinct clinical outcomes of paclitaxel formulations.

    Science.gov (United States)

    Li, Yan; Chen, Nianhang; Palmisano, Maria; Zhou, Simon

    2015-04-01

    Paclitaxel, an effective antitumor agent, is formulated in various vehicles serving as carriers to deliver the hydrophobic paclitaxel to tissue. The approved formulations in the U.S. are paclitaxel formulated in Cremophor EL (currently known as Kolliphor EL) and nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Despite having the same active ingredient (paclitaxel), different formulations produce distinct products with unique efficacy and safety profiles. A semimechanistic model was developed to describe the pharmacologic sensitivity of paclitaxel under different formulations. Circulating paclitaxel concentration data from patients treated with nab-paclitaxel or Cremophor EL-paclitaxel were analyzed in NONMEM using a semimechanistic model with simultaneous disposition of paclitaxel-carrier complexes and the total paclitaxel released from the complexes. The key factors driving paclitaxel exposure in circulation and peripheral tissues were explored via sensitivity analysis. The rapid decline of total paclitaxel concentration following intravenous administration of nab-paclitaxel and Cremophor EL-paclitaxel was attributed to rapid tissue distribution of the paclitaxel-carrier complexes, with minor contribution of free and protein-bound paclitaxel. Distribution of nab-paclitaxel to peripheral tissue was 4-fold faster and 10-fold more extensive than that of Cremophor EL-paclitaxel micelles, resulting in distinct tissue paclitaxel profiles. Sensitivity analyses showed the plasma paclitaxel-time profile was insensitive to the rapid rates of tissue distribution and decomposition of paclitaxel-carrier complexes but that the tissue distribution profile of paclitaxel was highly sensitive. Tissue distribution of paclitaxel is carrier complex system-dependent. Different delivery systems result in distinct tissue paclitaxel profiles but similar paclitaxel concentration-time profiles in plasma or blood, rendering the paclitaxel plasma profile a poor surrogate for its

  3. Clinical pharmacology in leishmaniasis: treatment optimization of a neglected disease

    NARCIS (Netherlands)

    Dorlo, T.P.C.

    2013-01-01

    This thesis presents various novel applications of clinical pharmacokinetics and pharmacodynamics in the treatment of leishmaniasis, by which diverse clinically relevant issues, mainly related to the efficacy and safety of miltefosine, could be elucidated. Throughout this thesis, the added value of

  4. CLINICAL PHARMACOLOGY OF A NEW COMPLEX HEPATOPROTECTIVE PREPARATION

    Directory of Open Access Journals (Sweden)

    Semenenko M. P.

    2016-05-01

    Full Text Available This article presents the results of the studies of the influence of a new complex hepatoprotective preparation on the basic system of the body, the mechanism of occurrence and manifestation of its biological effects, the dependence of this action from the components that are parts of the preparation, the dose, as well as the regularity of manifestation of possible side effects. The effect of the different doses of the preparation (1% and 2% on the average daily weight gain and morphological and biochemical indices of the birds’ blood was studied. The conducted research determined a stimulatory influence of the preparation on the growth, development and safety of broiler chickens. The new hepatoprotector exhibits the properties aimed on revitalizing the erythro- and hematopoiesis and magnification of the cellular immunity against the exogenous influence. The use of the preparation helps to improve liver function and reduce the toxic load on hepatocytes, which manifests an increase in a number of metabolic parameters, such as total protein, glucose, calcium, phosphorus. We have noted an expressed hepatoprotective effect on the enzyme activity of AST and the remission of the cytolytic syndrome of the experimental chickens. Thereby it was found out that the complex hepatoprotective preparation has a pronounced pharmacological activity, providing a significant impact on the energy of the broiler chickens’ growth and their safety, morphological and biochemical indices of the blood and metabolic processes in the body of the bird

  5. The enduring legacy of Alfred Gilman senior (1908-1984) to pharmacology and clinical medicine.

    Science.gov (United States)

    Rubin, Ronald P

    2016-09-28

    Alfred Gilman was best known for his co-authorship with Louis Goodman of the seminal textbook on pharmacology The Pharmacological Basis of Therapeutics in 1941. The book made the discipline of pharmacology relevant to clinical medicine by providing a link between the basic medical sciences and the practice of medicine. Gilman was also instrumental in establishing the use of chemotherapy in the treatment of cancer and made important contributions in areas related to renal function, acid-base balance, and diuretics. During the 1960s, he created a first rate department at the newly formed Albert Einstein College of Medicine. A superb lecturer, he commented incisively on issues related to pharmacology, therapeutics, and pathophysiology. Dr Gilman also provided a key link between academia and the pharmaceutical industry by serving as a consultant to several drug firms. The legacy of Alfred Gilman senior was continued by his son, Alfred Goodman Gilman, who became a Nobel Laureate. © The Author(s) 2016.

  6. Integrating historical clinical and financial data for pharmacological research

    OpenAIRE

    Deshmukh Vikrant G; Sower N Brett; Hunter Cheri Y; Mitchell Joyce A

    2011-01-01

    Abstract Background Retrospective research requires longitudinal data, and repositories derived from electronic health records (EHR) can be sources of such data. With Health Information Technology for Economic and Clinical Health (HITECH) Act meaningful use provisions, many institutions are expected to adopt EHRs, but may be left with large amounts of financial and historical clinical data, which can differ significantly from data obtained from newer systems, due to lack or inconsistent use o...

  7. Pharmacological vs. classical approaches in the design of first in man clinical drug trials.

    Science.gov (United States)

    van den Bogert, Cornelis A; Cohen, Adam F; Leufkens, Hubert G M; van Gerven, Joop M A

    2017-10-04

    The aims of the present study were to investigate the role of pharmacology in the design of first-in-man (FIM) trials in the Netherlands, and to evaluate the change in design approaches between 2007 and 2015. All FIM drug trials approved by all Dutch Institutional Review Boards (IRBs) in 2007 and in 2015 were selected. The original trial protocols, investigator's brochures and investigational medicinal product dossiers were the data sources. The following four design elements were assessed on the justification of the chosen approaches: preclinical information, dose calculation, endpoints, and dose escalation. In 2007, the Dutch IRBs approved 21 FIM trials, and in 2015 they approved 34 FIM trials (55 in total). Seven out of 21 (33%) of the FIM trials from 2007, and 14 out of the 34 (41%) FIM trials from 2015 discussed only the no-observed-adverse-effect level or no-observed-effect level as preclinical information. Furthermore, five of the 21 (24%) 2007 FIM trials and 12 of the 34 (35%) 2015 FIM trials used unexplained allometric scaling. Pharmacodynamic (PD) parameters were measured in 15 of the 21 (71%) 2007 FIM trials and in 31 of the 34 (91%) of the 2015 FIM trials, and allometric scaling was only guided by safety/tolerability in 11 of the 20 (55%) dose escalation trials in 2007 and in nine of the 33 (27%) dose escalation trials in 2015. Trial protocols and investigator's brochures commonly lack pharmacokinetic/PD approaches. Investigators, sponsors and IRBs should require an upfront consideration of pharmacology in these aspects for all FIM trials. © 2017 The British Pharmacological Society.

  8. Clinical Pharmacology of Alpha-1 Blockers Improving Drug-profile through Novel Formulations.

    Science.gov (United States)

    Nerurkar, Rajan P; Ved, Jignesh K

    2014-09-01

    Clinical pharmacology is an essential consideration in chronic therapies, and may play a significant role in modifying the pharmacological characteristics of drug formulations. Improvement in drug formulations may ensure their safe and effective use over a period of time. This has been particularly observed with α-1 adrenergic blockers in hypertension management. Advancements in formulations like prazosin GITS, have resulted in improvement in tolerability profile and smoother, more effective blood pressure control, which reasonably translate into improvement in patient compliance and better clinical outcomes.

  9. Pediatric Clinical Pharmacology and Child Health:A Canadian Perspective

    Institute of Scientific and Technical Information of China (English)

    Stuart Macleod

    2011-01-01

    @@ Introduction Canadian academic centres and children's hospitals have had a longstanding interest in the improvement of drug therapy for children through research conducted across the four pillars of activity identified as being of critical importance by the Canadian Institutes of Health Research(viz,basic research,clinical research,population health research,applied health and policy research)[1].

  10. Clinical Pharmacology of Citrus bergamia: A Systematic Review.

    Science.gov (United States)

    Mannucci, Carmen; Navarra, Michele; Calapai, Fabrizio; Squeri, Raffaele; Gangemi, Sebastiano; Calapai, Gioacchino

    2017-01-01

    Citrus bergamia Risso et Poiteau ("Bergamot") originated from the Mediterranean ecoregion (southern Italy, Calabria). Bergamot essential oil (BEO) is used in perfumes, cosmetics, and for stress reduction. Juice from C. bergamia has been used for hyperlipidemia. We evaluated literature published on C. bergamia clinical applications. Clinical trials on C. bergamia not combined with other substances, published in English, were searched. We selected ten articles, six describing BEO effects on stress, three reporting effects of polyphenolic fraction of C. bergamia juice in hyperlipidemia and the last describing BEO effects in chronic psoriasis. Clinical studies were analyzed following Consolidated Standards of Reporting Trials for herbal therapy. Studies were conducted on small sample sizes and not have high quality level. Analysis indicates that BEO aromatherapy could be safe and useful to reduce stress symptoms. One study suggests its potential supportive role in ultraviolet B therapy against psoriasis. Supplementation with polyphenols from bergamot juice reduces plasma lipids and improves lipoprotein profile in moderate hyperlipidemia. Effectiveness and safety of C. bergamia cannot be definitively drawn because of publication bias and low quality level of the majority of studies. Further large-scale trials with rigorous design are required to define the role of C. bergamia in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Integrating historical clinical and financial data for pharmacological research

    Directory of Open Access Journals (Sweden)

    Deshmukh Vikrant G

    2011-11-01

    Full Text Available Abstract Background Retrospective research requires longitudinal data, and repositories derived from electronic health records (EHR can be sources of such data. With Health Information Technology for Economic and Clinical Health (HITECH Act meaningful use provisions, many institutions are expected to adopt EHRs, but may be left with large amounts of financial and historical clinical data, which can differ significantly from data obtained from newer systems, due to lack or inconsistent use of controlled medical terminologies (CMT in older systems. We examined different approaches for semantic enrichment of financial data with CMT, and integration of clinical data from disparate historical and current sources for research. Methods Snapshots of financial data from 1999, 2004 and 2009 were mapped automatically to the current inpatient pharmacy catalog, and enriched with RxNorm. Administrative metadata from financial and dispensing systems, RxNorm and two commercial pharmacy vocabularies were used to integrate data from current and historical inpatient pharmacy modules, and the outpatient EHR. Data integration approaches were compared using percentages of automated matches, and effects on cohort size of a retrospective study. Results During 1999-2009, 71.52%-90.08% of items in use from the financial catalog were enriched using RxNorm; 64.95%-70.37% of items in use from the historical inpatient system were integrated using RxNorm, 85.96%-91.67% using a commercial vocabulary, 87.19%-94.23% using financial metadata, and 77.20%-94.68% using dispensing metadata. During 1999-2009, 48.01%-30.72% of items in use from the outpatient catalog were integrated using RxNorm, and 79.27%-48.60% using a commercial vocabulary. In a cohort of 16304 inpatients obtained from clinical systems, 4172 (25.58% were found exclusively through integration of historical clinical data, while 15978 (98% could be identified using semantically enriched financial data. Conclusions

  12. Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents.

    Science.gov (United States)

    Miyamoto, S; Miyake, N; Jarskog, L F; Fleischhacker, W W; Lieberman, J A

    2012-12-01

    of comparable or superior efficacy and side-effect profiles to existing APDs; (2) development of novel (and presumably non-D(2)) mechanism APDs; (3) development of compounds to be used as adjuncts to APDs to augment efficacy by targeting specific symptom dimensions of schizophrenia and particularly those not responsive to traditional APD treatment. In addition, efforts are being made to determine if the products of susceptibility genes in schizophrenia, identified by genetic linkage and association studies, may be viable targets for drug development. Finally, a focus on early detection and early intervention aimed at halting or reversing progressive pathophysiological processes in schizophrenia has gained great influence. This has encouraged future drug development and therapeutic strategies that are neuroprotective. This article provides an update and critical review of the pharmacology and clinical profiles of current APDs and drugs acting on novel targets with potential to be therapeutic agents in the future.

  13. Clinical pharmacology and pharmacokinetics of cis-platinum and analogs.

    Science.gov (United States)

    Ribaud, P; Gouveia, J; Bonnay, M; Mathe, G

    1981-01-01

    cis-Platinum (DDP), the first metal coordination complex introduced into clinical trials, is remarkable for its therapeutic index. A short review of the numerator of this index, ie, the clinical activities of DDP given as a single agent or in combination therapy is presented. Toxicity of DDP, the denominator of the index, is given more attention, particularly nephrotoxicity, whose cumulative character and molecular mechanism are still in question and which can most often be prevented by following certain safety rules that are detailed in this paper. Pharmacokinetics data of free and filterable platinum are reviewed and discussed according to the different modalities of administration of DDP, and to what is known about its toxicity and its mechanism of cell kill. The rationale for using DDP in combination treatment is presented and the question of possible long-term toxicities is raised. cis-platinum analogs are sought for the purpose of enlarging the spectrum of activity, increasing selectivity and diminishing toxicity. Malonato-platinum has been shown not to be cross-resistant with DDP and to be clinically effective in adult acute leukemia. In a phase I study, malonato-platinum, which is poorly soluble, was administered in 6-24-hour infusions to 49 patients in doses ranging from 3 to 32 mg/kg. GI toxicity was universal. Hematological toxicity appeared to be mild and not clearly dose-related (the 3-32 mg/kg patients were not yet evaluable). Platinum pharmacokinetics in urine and plasma were performed using flameless absorption spectrophotometry. Preliminary results have suggested that malonato-platinum presented several pharmacokinetic features in common with DDP. Minor responses were seen in four solid tumor patients, three of whom were refractory to DDP. Other analogs soon to be introduced into clinical trials are listed.

  14. Antiplatelet agents and Anticoagulants: from pharmacology to clinical practice.

    Science.gov (United States)

    Tsoumani, Maria E; Tselepis, Alexandros D

    2017-01-24

    Thrombosis is the formation of potentially deadly blood clots in the artery (arterial thrombosis) or vein (venous thrombosis). Since thrombosis is one of the main causes of death worldwide, the development of antithrombotic agents is a global medical priority. They are subdivided into antiplatelet agents and anticoagulants. Antiplatelet agents inhibit clot formation by preventing platelet activation and aggregation, while anticoagulants primarily inhibit the coagulation cascade and fibrin formation. Therapeutics within each category differs with respect to the mechanism of action, time to onset, duration of effect and route of administration. In this review, we critically discuss their main pharmacodynamic and pharmacokinetic characteristics as well as recent advances in daily clinical practice.

  15. Clinical, molecular, and pharmacological aspects of FMR1 related disorders.

    Science.gov (United States)

    Pugin, A; Faundes, V; Santa María, L; Curotto, B; Aliaga, S; Salas, I; Soto, P; Bravo, P; Peña, M I; Alliende, M A

    2017-05-01

    Fragile X syndrome, the most common inherited cause of intellectual disability, is associated with a broad spectrum of disorders across different generations of a single family. This study reviews the clinical manifestations of fragile X-associated disorders as well as the spectrum of mutations of the fragile X mental retardation 1 gene (FMR1) and the neurobiology of the fragile X mental retardation protein (FMRP), and also provides an overview of the potential therapeutic targets and genetic counselling. This disorder is caused by expansion of the CGG repeat (>200 repeats) in the 5 prime untranslated region of FMR1, resulting in a deficit or absence of FMRP. FMRP is an RNA-binding protein that regulates the translation of several genes that are important in synaptic plasticity and dendritic maturation. It is believed that CGG repeat expansions in the premutation range (55 to 200 repeats) elicit an increase in mRNA levels of FMR1, which may cause neuronal toxicity. These changes manifest clinically as developmental problems such as autism and learning disabilities as well as neurodegenerative diseases including fragile X-associated tremor/ataxia syndrome (FXTAS). Advances in identifying the molecular basis of fragile X syndrome may help us understand the causes of neuropsychiatric disorders, and they will probably contribute to development of new and specific treatments. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. North-south collaboration in clinical pharmacological research of HIV treatment

    NARCIS (Netherlands)

    L'homme, Rafaëlla Francisca Anna

    2008-01-01

    This thesis presents the first output of a North-South (Europe-Africa) collaboration in clinical pharmacological research of HIV treatment. Pharmacokinetics of antiretroviral drugs are highly variable in the paediatric population as children mature and grow rapidly and individually until they are ad

  17. [Clinical and pharmacological aspects of pancreatic enzyme substitution therapy].

    Science.gov (United States)

    Löser, C; Fölsch, U R

    1991-03-01

    The adequate therapy of pancreatic enzyme replacement in patients with exocrine pancreatic insufficiency is still a difficult clinical problem especially in patients following pancreatectomys, with chronic alcoholic pancreatitis or cystic fibrosis. The substitution of lipase to eliminate steatorrhoea is the most important aim but due to its acid lability even the most serious problem in pancreatic enzyme replacement therapy. Various different medications are meanwhile available: conventional preparations from porcine pancreatin or fungal enzymes as rizolipase, enteric-coated tablets or even enteric-coated microspheres or adjunctive therapy with H2-receptor antagonists. While dosage requirements vary widely and therefore have to be tried out individually, the choice of the adequate preparation should be influenced by the realization of the physiological and pathophysiological characteristics of the individual patient and the pharmaceutical characteristics of the different supplements. The advantages and disadvantages of the various medications for enzyme replacement therapy in patients with exocrine pancreatic insufficiency are reviewed in this article.

  18. Preliminary clinical pharmacological investigations of tylosin and tiamulin in chickens.

    Science.gov (United States)

    Ziv, G

    1980-10-15

    The minimal inhibitory concentrations (MIC) of tiamulin and tylosin for mycoplasma, Gram-positive, and Gram-negative micro-organisms isolated from chickens were determinated by the agar dilution method. Median MIC values for tiamulin against Mycoplasma gallisepticum (0.05 microgram/ml) and Mycoplasma synoviae (0.10 microgram/ml) were 2 to 4 times lower than the corresponding values for tylosin. Tiamulin was also slightly more effective in vitro in inhibiting Escherichia coli, Pasteurella multocida, and beta-haemolytic streptococci than was tylosin. Groups of chicken were offered tiamulin medicated drinking water at rates of 125 and 250 mg/litre for 48 hours. Average serum tiamulin concentrations were 0.38 and 0.78 microgram/ml, respectively. When tylosin tartrate was added to the drinking water at 500 and 700 mg/litre, average serum drug levels were 0.12 and 0.17 microgram/ml, respectively. Tiamulin was 45% bound in chicken serum, as against 30% serum protein binding for tylosin. Correlations were made between free (non protein bound) serum drug levels and the MIC values of the two drugs. Such comparisons suggest that when tiamulin is given in the drinking water at rates of 125 to 250 mg/litre, better antimycoplasmal activity is to be expected in vivo than by giving tylosin tartrate in the drinking water at 500 to 700 mg/litre. Based on these data, no clinical efficacy of these dose rates can be expected in flocks infected by gram-negative micro-organisms such as E. coli or P. multocida. The tylosin tartrate rate of 500 to 700 mg/litre, may be clinical ineffective the treatment of Staphylococcus aureus infections.

  19. [History of clinical pharmacology in France: adaptation, evaluation, defense and illustration of drug in France 1978-1981].

    Science.gov (United States)

    Montastruc, Paul

    2014-01-01

    This text illustrates some unknown aspects of the history and beginnings of clinical pharmacology in France in the late 1970s and early 1980s From the current situation, development and objectives of clinical pharmacology are recalled as well as obstacles necessary to overcome to change the paradigm in the field of drug evaluation and appropriate use in France. The text recalls this important moment where French medicine and medical pharmacology entered the modern era.

  20. Impulse control disorders: updated review of clinical characteristics and pharmacological management

    Directory of Open Access Journals (Sweden)

    Jon E Grant

    2011-02-01

    Full Text Available Impulse control disorders (ICDs are characterized by urges and behaviors that are excessive and/or harmful to oneself or others and cause significant impairment in social and occupational functioning, as well as legal and financial difficulties. ICDs are relatively common psychiatric conditions, yet are poorly understood by the general public, clinicians, and individuals struggling with the disorder. Although ICD treatment research is limited, studies have shown ICDs may respond well to pharmacological treatment. This article presents a brief overview about the clinical characteristics of ICDs and pharmacological treatment options for individuals with ICDs.

  1. [Main progress on studies of pharmacological activities and clinical applications of Guizhi Fuling capsule].

    Science.gov (United States)

    Su, Zhen-zhen; Li, Na; Cao, Liang; Wang, Tuan-jie; Zhang, Chen-feng; Ding, Gang; Wang, Zhen-zhong; Xiao, Wei

    2015-03-01

    Guizhi Fuling capsule is a traditional Chinese medicine composed of five kinds of medicinal plants, Cinnamomi Ramulus, Poria, Moutan Cortex, Persicae Semen, and Paeoniae Radix Alba. Pharmacology studies have shown that Guizhi Fuling capsule has many activities: anti-inflammatory, analgesic, anti-tumor, regulating smooth muscle, endocrine regulation and enhancing immunity. It achieved obvious effects in the treatment of uterine fibroids, pelvic inflammatory disease, dysmenorrheal, endometriosis, ovarian cysts, breast hyperplasia and other gynecological diseases. This paper reviewed the main progress on studies of pharmacological activities and clinical applications of Guizhi Fuling capsule in recent years.

  2. Clinical Pharmacology of Phenobarbital in Neonates: Effects, Metabolism and Pharmacokinetics.

    Science.gov (United States)

    Pacifici, Gian M

    2016-01-01

    Phenobarbital is an effective and safe anticonvulsant drug introduced in clinical use in 1904. Its mechanism of action is the synaptic inhibition through an action on GABAA. The loading dose of phenobarbital is 20 mg/kg intravenously and the maintenance dose is 3 to 4 mg/kg by mouth. The serum concentration of phenobarbital is up to 40 µg/ml. Nonresponders should receive additional doses of 5 to 10 mg/kg until seizures stop. Infants with refractory seizures may have a serum concentration of phenobarbital of 100 µg/ml. Phenobarbital is metabolized in the liver by CYP2C9 with minor metabolism by CYP2C19 and CYP2E1. A quarter of the dose of phenobarbital is excreted unchanged in the urine. In adults, the half-life of phenobarbital is 100 hours and in term and preterm infants is 103 and 141 hours, respectively. The half-life of phenobarbital decreases 4.6 hours per day and it is 67 hours in infants 4 week old.

  3. [Note on the epistemology of clinical pharmacology: comparison with the approach of Karl Popper].

    Science.gov (United States)

    Boissel, J P

    1999-01-01

    Is clinical pharmacology a science or only an application of science? Karl Popper suggested a method to identify science and to sort it out from other logical activities such as metaphysics, whereby the falsification criterion he proposed can apply to the theory in such a way that the theory could be refuted. The clinical pharmacologist's approach requires the build-up of a therapeutic model on the basis of two other models: the physiopathologic and the pharmacological. The three-model construct is a theory. Is it scientific in the Popperian sense? From the therapeutic model, one can predict the efficacy of a drug, and the corresponding statement is tested by a clinical trial. Whatever the original statement, it is modified into a refutable one because of the use of the statistical approach in clinical trials. Furthermore, the predicate represents a hypothesis of the model validity, which will then be confronted with 'reality' through clinical experiment. As the therapeutic model is refutable, clinical pharmacology is a science in the Popperian sense.

  4. A Blended Learning Course Design in Clinical Pharmacology for Post-graduate Dental Students.

    Science.gov (United States)

    Rosenbaum, Paul-Erik Lillholm; Mikalsen, Oyvind; Lygre, Henning; Solheim, Einar; Schjøtt, Jan

    2012-01-01

    Postgraduate courses in clinical pharmacology are important for dentists to be updated on drug therapy and information related to their clinical practice, as well as knowledge of relevant adverse effects and interactions. A traditional approach with classroom delivery as the only method to teaching and learning has shortcomings regarding flexibility, individual learning preferences, and problem based learning (PBL) activities compared to online environments. This study examines a five week postgraduate course in clinical pharmacology with 15 hours of lectures and online learning activities, i.e. blended course design. Six postgraduate dental students participated and at the end of the course they were interviewed. Our findings emphasize that a blended learning course design can be successfully used in postgraduate dental education. Key matters for discussion were time flexibility and location convenience, change in teacher's role, rein-forced learning strategies towards professional needs, scarcity in online communication, and proposed future utilization of e-learning components.

  5. A Blended Learning Course Design in Clinical Pharmacology for Post-graduate Dental Students

    Science.gov (United States)

    Rosenbaum, Paul-Erik Lillholm; Mikalsen, Øyvind; Lygre, Henning; Solheim, Einar; Schjøtt, Jan

    2012-01-01

    Postgraduate courses in clinical pharmacology are important for dentists to be updated on drug therapy and information related to their clinical practice, as well as knowledge of relevant adverse effects and interactions. A traditional approach with classroom delivery as the only method to teaching and learning has shortcomings regarding flexibility, individual learning preferences, and problem based learning (PBL) activities compared to online environments. This study examines a five week postgraduate course in clinical pharmacology with 15 hours of lectures and online learning activities, i.e. blended course design. Six postgraduate dental students participated and at the end of the course they were interviewed. Our findings emphasize that a blended learning course design can be successfully used in postgraduate dental education. Key matters for discussion were time flexibility and location convenience, change in teacher’s role, rein-forced learning strategies towards professional needs, scarcity in online communication, and proposed future utilization of e-learning components. PMID:23248716

  6. Under graduate student feedback on teaching and evaluation method in clinical pharmacology

    Directory of Open Access Journals (Sweden)

    SK Deo

    2014-04-01

    Full Text Available Background Any teaching and evaluation method can be considered as effective once they are judged by students. Objective This study was designed to obtain feedback on teaching and evaluation methods in the subject of clinical pharmacology among under graduate students Methods Feedback on teaching and evaluation method was taken from undergraduate students of 2009 batch and various approaches to teaching and evaluation are identified. To know the effect of these novel approaches of teaching and evaluation, student feedback was taken from subsequent batch 2010 and 2011 using a written validated questionnaire covering various aspects of teaching and evaluation methods. Results Under graduate students were satisfied with all teaching methods like lecture and pharmacological exercises. They showed preference for tutorials, short answer questions and revision classes where as they were not satisfied with seminar method of learning. All students felt that there should be more time for clinical pharmacology and pharmacological problem based exercises.. The pass percentage of the subsequent batch in university examinations improved from 75 % to 90%. Conclusion Based upon the student’s feedback, incorporation of suggestion obtained from the students resulted in improvement in performance of the students. Hence, it is very essential to take regular feedback from the students to synchronize teaching and evaluation method of the students. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-3, 31-34 DOI: http://dx.doi.org/10.3126/jcmsn.v9i3.10220

  7. Bryophyllum pinnatum and Related Species Used in Anthroposophic Medicine: Constituents, Pharmacological Activities, and Clinical Efficacy.

    Science.gov (United States)

    Fürer, Karin; Simões-Wüst, Ana Paula; von Mandach, Ursula; Hamburger, Matthias; Potterat, Olivier

    2016-07-01

    Bryophyllum pinnatum (syn. Kalanchoe pinnata) is a succulent perennial plant native to Madagascar that was introduced in anthroposophic medicine in the early 20th century. In recent years, we conducted a large collaborative project to provide reliable data on the chemical composition, pharmacological properties, and clinical efficacy of Bryophyllum. Here, we comprehensively review the phytochemistry, as well as the pharmacological and clinical data. As to the pharmacology, special emphasis is given to properties related to the use in anthroposophic medicine as a treatment for "hyperactivity diseases", such as preterm labor, restlessness, and sleep disorders. Studies suggesting that B. pinnatum may become a new treatment option for overactive bladder syndrome are also reviewed. Tolerability is addressed, and toxicological data are discussed in conjunction with the presence of potentially toxic bufadienolides in Bryophyllum species. The few data available on two related species with medicinal uses, Bryophyllum daigremontianum and Bryophyllum delagoense, have also been included. Taken together, current data support the use of B. pinnatum for the mentioned indications, but further studies are needed to fully understand the modes of action, and to identify the pharmacologically active constituents.

  8. ORIGINAL ARTICLE: Identification of Practical Pharmacology Skills Useful for Good Clinical Practice

    Directory of Open Access Journals (Sweden)

    V. Shilpa, R. Divya

    2012-07-01

    Full Text Available Background: Awareness about animal ethics is increasing everywhere. This increased awareness coupled with strict regulations discouraging the use of animals for routine experiments have tied the hands of many pharmacologists. They are now forced to develop alternative experiments without using animals. At present, there is acute need to come out with more innovative and useful practical exercises for pharmacology practical sessions. In this background, the present study was undertaken to develop the much-needed alternative experiments. Aims and Objective: To identify new pharmacological practical skills useful for good clinical practice. Material and Methods: A pre-tested questionnaire was administered to 110 doctors of different categories like house surgeons, postgraduate students, assistant professors and professors who are working in a tertiary care hospital. They were asked to give their suggestions regarding new pharmacology practical skills useful for good clinical practice. Statistical analysis: Responses of the participants to the questions asked were tabulated and analyzed. Suggestions given by them were listed out and studied. Results: Use of emergency drugs, dosage calculation, drugs used in pregnancy, case discussions and prescription writing exercises received a lot of support from the participants. Research methodology, cost calculation, animal experiments and interpretation of data of animal experiments did not receive support from the participants. Suggestions given by the participants regarding useful pharmacological skills belonged to the areas like therapeutics, safe use of drugs, recent advances, analysis of information given by the medical representatives and analyzing articles in journals for knowing the efficacy of drugs. Conclusion: Exercises relevant to the clinical practice, as identified in this study, can be introduced as practical pharmacology exercises. Steps are to be taken to highlight the importance of research

  9. Clinical pharmacology

    African Journals Online (AJOL)

    Acute pain management in children. Early and appropriate pain management, and the ... irritability or apathy are often the only way to assess .... where use of antiretrovirals is expected to increase massively, resistance could also be boosted.

  10. [Discussion on strengthening yin of chinese herbs with bitter-flavor clinical traditional Chinese pharmacology noun terminology standardization research].

    Science.gov (United States)

    Liu, Xiao-Mei; Bao; Zhaorigetu; Zhuang, Xin-Ying; Que, Ling; Tian, Chang-Jiang

    2013-10-01

    Clinical traditional Chinese pharmacology is the subject that study of basic theory of traditional Chinese medicine, property of Chinese materia medica and clinical application. The study on the standardization research of the terminology of clinical traditional Chinese pharmacology is an important premise and foundation to standardization, modernization and internationalization, informationization construction of clinical traditional Chinese pharmacology and is also the important content of the subject construction. To provide some exploring ideas for clinical traditional Chinese pharmacology noun terminology standardization, this article elaborates the concept of strengthening Yin with bitter-flavor herbs in several aspects, such as connotation and the historical origin, the clinical application in the traditional, modern clinic application, and the modern basic research and so on.

  11. Development and validation of evaluation tools of nursing students’ clinical pharmacology unit

    Science.gov (United States)

    Navabi, Nasrin; Ghaffari, Fatemeh; Shamsalinia, Abbas; Faghani, Safieh

    2016-01-01

    Introduction The need for valid, reliable, and objective tools has always been emphasized in studies related to the clinical assessment of nursing students. The aims of this study were to develop and assess the validity and reliability of the tools used to evaluate the clinical pharmacology unit. Methods This study was a methodological one, conducted in 2016. An item pool was developed based on the literature review and personal interviews with faculty members. The tool’s validity was determined through assessment of face validity, content validity, and construct validity, using exploratory factor analysis on the data provided by 264 second- and third-semester nursing students of the Islamic Azad University of Babol University of Medical Sciences. Reliability was determined through internal and external consistency, using a Cronbach’s coefficient of the correlation between classes. Results Based on the exploratory factor analysis, all items with a special value of >1 were grouped into six factors: 1) professional behavior; 2) effective communication; 3) recognition of medical terminology; 4) nursing actions before administering medicine; 5) nursing actions while administering medicine; and 6) nursing actions after administering medicine. These factors explained 77% of the total variance of the concept of assessment of the clinical pharmacology unit. In this study, reliability was demonstrated by a Cronbach’s alpha coefficient of 0.96; the correlation coefficient between floors for the total tool was 0.91, ranging from 0.64 to 0.89 in its dimensions. Conclusion The evaluation tool of the clinical pharmacology unit has an acceptable construct validity and satisfactory reliability and validity. Therefore, it can be used to evaluate the clinical pharmacology unit in the nursing education system in Iran. PMID:28008285

  12. Gastrointestinal Pharmacology.

    Science.gov (United States)

    Saps, Miguel; Miranda, Adrian

    2017-02-25

    There is little evidence for most of the medications currently used to treat functional abdominal pain disorders (FAPDs) in children. Not only are there very few clinical trials, but also most have significant variability in the methods used and outcomes measured. Thus, the decision on the most appropriate pharmacological treatment is frequently based on adult studies or empirical data. In children, peppermint oil, trimebutine, and drotaverine have shown significant benefit compared with placebo, each of them in a single randomized clinical trial. A small study found that cyproheptadine was beneficial in the treatment of FAPDs in children. There are conflicting data regarding amitriptyline. While one small study found a significant benefit in quality of life compared with placebo, a large multicenter study found no benefit compared with placebo. The antidepressant, citalopram, failed to meet the primary outcomes in intention-to-treat and per-protocol analysis. Rifaximin has been shown to be efficacious in the treatment of adults with IBS. Those findings differ from studies in children where no benefit was found compared to placebo. To date, there are no placebo-controlled trials published on the use of linaclotide or lubiprostone in children. Alpha 2 delta ligands such as gabapentin and pregabalin are sometimes used in the care of this group of children, but no clinical trials are available in children with FAPDs. Similarly, novel drugs that have been approved for the care of irritable bowel with diarrhea in adults such as eluxadoline have yet to be studied in children.

  13. Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas

    Directory of Open Access Journals (Sweden)

    Jain S

    2017-03-01

    Full Text Available Sachin Jain,1 Ruolan Song,2 Jingwu Xie2 1Indiana University School of Medicine, 2Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN, USA Abstract: The Hedgehog (Hh pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC, medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administration (FDA approved sonidegib, a smoothened (SMO antagonist, for treatment of advanced BCC (aBCC after a successful Phase II clinical trial. Sonidegib, also named Odomzo, is the second Hh signaling inhibitor approved by the FDA to treat BCCs following approval of the first SMO antagonist vismodegib in 2012. What are the major features of sonidegib (mechanism of action; metabolic profiles, clinical efficacy, safety, and tolerability profiles? Will the sonidegib experience help other clinical trials using Hh signaling inhibitors in the future? In this review, we will summarize current understanding of BCCs and Hh signaling. We will focus on sonidegib and its use in the clinic, and we will discuss ways to improve its clinical application in cancer therapeutics. Keywords: Hedgehog, smoothened, inhibitor, cancer, basal cell carcinoma, sonidegib

  14. How should teaching of undergraduates in clinical pharmacology and therapeutics be delivered and assessed?

    Science.gov (United States)

    Maxwell, Simon R J

    2012-06-01

    Clinical pharmacology and therapeutics is the academic discipline that informs rational prescribing of medicines. There is accumulating evidence that a significant minority of prescriptions in the UK National Health Service contain errors. This comes at a time when the approach to and success of undergraduate education in this area has been called into question. Various stakeholders are now in agreement that this challenging area of undergraduate education needs to be strengthened. The principles that should form the basis of future educational strategy include greater visibility of clinical pharmacology and therapeutics in the curriculum, clear learning outcomes that are consistent with national guidance, strong and enthusiastic leadership, a student formulary, opportunities to practice prescribing, a robust assessment of prescribing competencies and external quality control. Important new developments in the UK are Prescribe, a repository of e-learning materials to support education in clinical pharmacology and prescribing, and the Prescribing Skills Assessment, a national online assessment designed to allow medical students to demonstrate that they have achieved the core competencies required to begin postgraduate training.

  15. Feedback in clinical education, part I: Characteristics of feedback provided by approved clinical instructors.

    Science.gov (United States)

    Nottingham, Sara; Henning, Jolene

    2014-01-01

    Providing students with feedback is an important component of athletic training clinical education; however, little information is known about the feedback that Approved Clinical Instructors (ACIs; now known as preceptors) currently provide to athletic training students (ATSs). To characterize the feedback provided by ACIs to ATSs during clinical education experiences. Qualitative study. One National Collegiate Athletic Association Division I athletic training facility and 1 outpatient rehabilitation clinic that were clinical sites for 1 entry-level master's degree program accredited by the Commission on Accreditation of Athletic Training Education. A total of 4 ACIs with various experience levels and 4 second-year ATSs. Extensive field observations were audio recorded, transcribed, and integrated with field notes for analysis. The constant comparative approach of open, axial, and selective coding was used to inductively analyze data and develop codes and categories. Member checking, triangulation, and peer debriefing were used to promote trustworthiness of the study. The ACIs gave 88 feedback statements in 45 hours and 10 minutes of observation. Characteristics of feedback categories included purpose, timing, specificity, content, form, and privacy. Feedback that ACIs provided included several components that made each feedback exchange unique. The ACIs in our study provided feedback that is supported by the literature, suggesting that ACIs are using current recommendations for providing feedback. Feedback needs to be investigated across multiple athletic training education programs to gain more understanding of certain areas of feedback, including frequency, privacy, and form.

  16. Optimizing oncology therapeutics through quantitative translational and clinical pharmacology: challenges and opportunities.

    Science.gov (United States)

    Venkatakrishnan, K; Friberg, L E; Ouellet, D; Mettetal, J T; Stein, A; Trocóniz, I F; Bruno, R; Mehrotra, N; Gobburu, J; Mould, D R

    2015-01-01

    Despite advances in biomedical research that have deepened our understanding of cancer hallmarks, resulting in the discovery and development of targeted therapies, the success rates of oncology drug development remain low. Opportunities remain for objective dose selection informed by exposure-response understanding to optimize the benefit-risk balance of novel therapies for cancer patients. This review article discusses the principles and applications of modeling and simulation approaches across the lifecycle of development of oncology therapeutics. Illustrative examples are used to convey the value gained from integration of quantitative clinical pharmacology strategies from the preclinical-translational phase through confirmatory clinical evaluation of efficacy and safety.

  17. Approval of high-risk medical devices in the US: implications for clinical cardiology.

    Science.gov (United States)

    Rome, Benjamin N; Kramer, Daniel B; Kesselheim, Aaron S

    2014-01-01

    Since 1976, the US Food and Drug Administration (FDA) has used the premarket approval (PMA) process to approve high-risk medical devices, including implantable cardioverter defibrillators (ICDs), coronary stents, and artificial heart valves. The PMA process is widely viewed as a rigorous evaluation of device safety and effectiveness, though recent recalls-most notably related to underperforming ICD leads-have raised concerns about whether physicians and patients should sometimes be more wary about devices approved via this pathway. The FDA must utilize a "least burdensome" approach to approve new medical devices, and many widely used device models have been approved as supplements to existing PMA-approved devices with limited clinical testing. A recent Supreme Court ruling has made it difficult for patients harmed by unsafe PMA-approved devices to seek damages in court. Cardiologists who utilize high-risk medical devices should be aware that FDA approval of new devices relies on variable levels of evidence and does not necessarily indicate improved effectiveness over existing models. Clinician and patient engagement in postmarket surveillance and comparative effectiveness research remains imperative.

  18. A Survey of Rorschach Teaching in APA-Approved Clinical Graduate Programs

    Science.gov (United States)

    Del Gaudio, Andrew C.; Ritzler, Barry A.

    1976-01-01

    This survey of APA-approved doctoral programs in clinical psychology provides a status assessment of the Rorschach technique. Eighty-one percent emphasized the technique; a quarter offered the course for a full year; respondents with more experience rated the technique higher; and its was rated highly as a clinical tool and teaching aid, but low…

  19. Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation.

    Science.gov (United States)

    Busby, Robert W; Kessler, Marco M; Bartolini, Wilmin P; Bryant, Alexander P; Hannig, Gerhard; Higgins, Carolyn S; Solinga, Robert M; Tobin, Jenny V; Wakefield, James D; Kurtz, Caroline B; Currie, Mark G

    2013-01-01

    Linaclotide, a potent guanylate cyclase C agonist, is a therapeutic peptide approved in the United States for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. We present for the first time the metabolism, degradation, and disposition of linaclotide in animals and humans. We examined the metabolic stability of linaclotide in conditions that mimic the gastrointestinal tract and characterized the metabolite MM-419447 (CCEYCCNPACTGC), which contributes to the pharmacologic effects of linaclotide. Systemic exposure to these active peptides is low in rats and humans, and the low systemic and portal vein concentrations of linaclotide and MM-419447 observed in the rat confirmed both peptides are minimally absorbed after oral administration. Linaclotide is stable in the acidic environment of the stomach and is converted to MM-419447 in the small intestine. The disulfide bonds of both peptides are reduced in the small intestine, where they are subsequently proteolyzed and degraded. After oral administration of linaclotide, intestinal loops, increased intraluminal cGMP, and caused a dose-dependent acceleration in gastrointestinal transit. These results demonstrate the importance of the active metabolite in contributing to linaclotide's pharmacology.

  20. A clinical pharmacology-regulatory perspective on the approval of drugs for rare diseases.

    Science.gov (United States)

    Bashaw, E D

    2016-10-01

    Orphan drugs or drugs for rare diseases represents a particular regulatory conundrum. There is a desperate need for effective therapies for these patients, who have been historically underserved by the drug development community. However, there is also a need to make sure these therapies are both safe and effective. In response, the US Food and Drug Administration (FDA) has evolved new approaches to facilitate drug development in this area.

  1. Role of Clinical Pharmacology in the Development and Approval of Immunotherapies Targeting Immune Checkpoints.

    Science.gov (United States)

    Rahman, A

    2016-12-01

    Immune surveillance plays a critical role in preventing the development and progression of cancer. Immune modulators, such as interferon-gamma or interleukin-2, have been a part of the cancer treatment armament over the past few decades. However, new understandings regarding the role of the costimulatory and coinhibitory molecules associated with T-cells and antigen-presenting cells as well as tumor necrosis factor receptors and ligands have ushered the new era of immunotherapy for cancer treatment. We now know that primary cancer cells evade screening by the innate immune system, proliferate, and form metastases by upregulating immune inhibitory pathways referred to as immune checkpoints. The recent development of therapies that target immune checkpoints, such as cytotoxic T lymphocyte antigen 4, programmed cell death 1, programmed cell death ligand 1, indoleamine 2,3-dioxygenase, T-cell immunoglobulin and mucin domain 3, and lymphocyte activation gene 3 precisely target the immune system and give new hope for treating various types of cancer. In select marker-enriched populations, immunotherapies provide high response rates as well as durable responses in terms of progression-free survival and overall survival. Numerous factors, such as patient's immune system, the expression of targets on both immune and cancer cells, maintenance of an effective drug exposure, and tolerability to these agents may play a role in this unique observation.

  2. International Union of Basic and Clinical Pharmacology. XC. multisite pharmacology: recommendations for the nomenclature of receptor allosterism and allosteric ligands.

    Science.gov (United States)

    Christopoulos, Arthur; Changeux, Jean-Pierre; Catterall, William A; Fabbro, Doriano; Burris, Thomas P; Cidlowski, John A; Olsen, Richard W; Peters, John A; Neubig, Richard R; Pin, Jean-Philippe; Sexton, Patrick M; Kenakin, Terry P; Ehlert, Frederick J; Spedding, Michael; Langmead, Christopher J

    2014-10-01

    Allosteric interactions play vital roles in metabolic processes and signal transduction and, more recently, have become the focus of numerous pharmacological studies because of the potential for discovering more target-selective chemical probes and therapeutic agents. In addition to classic early studies on enzymes, there are now examples of small molecule allosteric modulators for all superfamilies of receptors encoded by the genome, including ligand- and voltage-gated ion channels, G protein-coupled receptors, nuclear hormone receptors, and receptor tyrosine kinases. As a consequence, a vast array of pharmacologic behaviors has been ascribed to allosteric ligands that can vary in a target-, ligand-, and cell-/tissue-dependent manner. The current article presents an overview of allostery as applied to receptor families and approaches for detecting and validating allosteric interactions and gives recommendations for the nomenclature of allosteric ligands and their properties.

  3. Genetic variability of pain perception and treatment--clinical pharmacological implications.

    Science.gov (United States)

    Lötsch, Jörn

    2011-06-01

    Evidence of a genetic control of pain has led to efforts to exploit genotyping information from pain patients for the development of analgesics and for the selection of pharmacological approaches to pain. Research on translating the genetic bases of familial insensitivity to pain has contributed to the discovery of crucial molecular pathways of pain and to the identification of new analgesic targets (e.g., the Na(v)1.7 sodium channel, neurotrophic tyrosine kinase receptors, nerve growth factor). Moreover, human genetic variants leading to enhanced or reduced function of specific molecular pathways are employed as substitutes for the lack of modulator molecules usable in humans, enabling nociceptive or anti-nociceptive pathways in humans to be studied before drug development. Translational approaches have also been used to verify the importance of experimentally discovered pain pathways in humans, such as GTP cyclohydrolase 1 and the potassium channel K(v)9.1. In addition to these uses of genetics as a research tool, an individualized pharmacological therapy based on the patient's genotype has been attempted. In terms of analgesics in clinical use, such an approach is at the present time only marginally available. For future analgesic targeting, for example, Na(v)1.7 or TRPA1, the genotype may be the target of a selective cure for syndromes caused by increased-function mutations in the coding genes. The consideration of human genetics in drug studies may accelerate analgesic drug development while reducing cost because the clinical success may be partly anticipated by including information of functional genetic variants that mimic the action of future analgesics. These developments show that genotyping information obtained from studies on pain patients plays a role in the clinical pharmacology of pain.

  4. Genetic, clinical and pharmacological determinants of out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Blom, M T; van Hoeijen, D A; Bardai, A

    2014-01-01

    victims since June 2005, we prospectively collect medical history (through hospital and general practitioner), and current and previous medication use (through community pharmacy). In addition, we include DNA samples from OHCA victims with documented ventricular tachycardia/fibrillation during......INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is a major public health problem. Recognising the complexity of the underlying causes of OHCA in the community, we aimed to establish the clinical, pharmacological, environmental and genetic factors and their interactions that may cause OHCA...

  5. International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin Receptor Nomenclature, Distribution, and Function

    OpenAIRE

    Kirby, Helen R.; Maguire, Janet J.; Colledge, William H.; Davenport, Anthony P

    2010-01-01

    Kisspeptins are members of the Arg-Phe amide family of peptides, which have been identified as endogenous ligands for a G-protein-coupled receptor encoded by a gene originally called GPR54 (also known as AXOR12 or hOT7T175). After this pairing, the gene has been renamed KISS1R. The International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification recommends that the official name for the receptor is the kisspeptin receptor to follow the conventi...

  6. Berberine: New Insights from Pharmacological Aspects to Clinical Evidences in the Management of Metabolic Disorders.

    Science.gov (United States)

    Caliceti, Cristiana; Franco, Placido; Spinozzi, Silvia; Roda, Aldo; Cicero, Arrigo F G

    2016-01-01

    Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids found in such plants as gender Berberis. Berberine is recognised to improve glucose and lipid metabolism disorders and preliminary clinical evidences suggest the ability of berberine to reduce endothelial inflammation improving vascular health, even in patients already affected by cardiovascular diseases, suggesting a possible interesting role of berberine and its metabolites in clinical practice. However, its physicochemical properties, pharmacokinetic, and metabolism are not fully elucidated and contradictory data have been reported. This review provides a summary regarding the pharmacological and biological features of berberine, with a focus on berberine as well as their pharmacologically active metabolites and the different mechanisms underlying their activities in order to clarify the correct use of berberine supplementation, alone or in association with other nutraceuticals, for the management of metabolic disorders associated to increased cardiovascular disease risk. A particular attention has also been given to the available clinical trials assessing its short- and middle- term use tolerability, safety and efficacy in various conditions, such as dyslipidaemia, impaired fasting glucose, metabolic syndrome and type 2 diabetes.

  7. The pharmacokinetic/pharmacodynamic pipeline: translating anticancer drug pharmacology to the clinic.

    Science.gov (United States)

    Zhou, Qingyu; Gallo, James M

    2011-03-01

    Progress in an understanding of the genetic basis of cancer coupled to molecular pharmacology of potential new anticancer drugs calls for new approaches that are able to address key issues in the drug development process, including pharmacokinetic (PK) and pharmacodynamic (PD) relationships. The incorporation of predictive preclinical PK/PD models into rationally designed early-stage clinical trials offers a promising way to relieve a significant bottleneck in the drug discovery pipeline. The aim of the current review is to discuss some considerations for how quantitative PK and PD analyses for anticancer drugs may be conducted and integrated into a global translational effort, and the importance of examining drug disposition and dynamics in target tissues to support the development of preclinical PK/PD models that can be subsequently extrapolated to predict pharmacologic characteristics in patients. In this article, we describe three different physiologically based (PB) PK modeling approaches, i.e., the whole-body PBPK model, the hybrid PBPK model, and the two-pore model for macromolecules, as well as their applications. General conclusions are that greater effort should be made to generate more clinical data that could validate scaled preclinical PB-PK/PD tumor-based models and, thus, stimulate a framework for preclinical to clinical translation. Finally, given the innovative techniques to measure tissue drug concentrations and associated biomarkers of drug responses, development of predictive PK/PD models will become a standard approach for drug discovery and development.

  8. Ethynilestradiol 20 mcg plus Levonorgestrel 100 mcg: Clinical Pharmacology

    Directory of Open Access Journals (Sweden)

    Stefano Lello

    2014-01-01

    Full Text Available Estroprogestins (EPs are combinations of estrogen and progestin with several actions on women’s health. The different pharmacological composition of EPs is responsible for different clinical effects. One of the most used low-dose EP associations is ethinylestradiol 20 mcg plus levonorgestrel 100 mcg in monophasic regimen (EE20/LNG100. This review summarizes clinical pharmacology, cycle control, and effects on lipid and glucose metabolism, coagulation, body weight/body composition, acne, and sexuality of EE20/LNG100. Overall, EE20/LNG100 combination is safe and well tolerated, and in several studies the incidence of adverse events in the treated group was comparable to that of the placebo group. Cycle control was effective and body weight/body composition did not vary among treated and untreated groups in most studies. The EE20/LNG100 combination shows mild or no effect on lipid and glucose metabolism. Lastly, EE20/LNG100 is associated with a low risk of venous thromboembolism (VTE. In conclusion, in the process of decision making for the individualization of EPs choice, EE20/LNG100 should be considered for its favorable clinical profile.

  9. 78 FR 7784 - Draft Guidance for Industry on Enrichment Strategies for Clinical Trials To Support Approval of...

    Science.gov (United States)

    2013-02-04

    ... Clinical Trials To Support Approval of Human Drugs and Biological Products; Extension of Comment Period... entitled ``Enrichment Strategies for Clinical Trials to Support Approval of Human Drugs and Biological... guidance to industry on enrichment strategies that can be used in clinical trials intended to...

  10. Recent developments in studies of l-stepholidine and its analogs: chemistry, pharmacology and clinical implications.

    Science.gov (United States)

    Mo, Jiao; Guo, Yang; Yang, Yu-She; Shen, Jing-Shan; Jin, Guo-Zhang; Zhen, Xuechu

    2007-01-01

    Tetrahydroprotoberberines (THPBs) represent a series of compounds extracted from the Chinese herb Corydalis ambigua and various species of Stephania. THPBs, dependent on the presence of hydroxyl groups in its structure, are divided into three types: nonhydroxyl-THPBs, monohydroxyl-THPBs and dihydroxyl-THPBs. THPBs are identified as a new category of dopamine receptor ligands. Among all THPBs, dihydroxyl-THPBs attracted particular attention because of their dual actions on dopamine (DA) receptors. They exhibit D(1) receptor agonistic activity while acting as D(2) receptor antagonists. This unique pharmacological profile made dihydroxyl-THPBs such as l-stepholidine (l-SPD) potential agents in the treatment of drug addiction, Parkinson's disease, and especially, schizophrenia. Clinical studies have shown that co-administration of l-SPD with a typical antipsychotic drug significantly enhances the therapeutic effects and remarkably reduces the tardive dyskinesia induced by the typical antipsychotic drug used with schizophrenic patients. Moreover, l-SPD alone was shown to have therapeutic value without inducing significant extrapyramidal side effects and also seemed to reduce the negative symptoms of schizophrenia. This is confirmed in experimental studies using animal models of schizophrenia, in which l-SPD improved social interaction and cognitive function, inhibited hyperactivity in schizophrenic animals. This review discusses the chemistry, pharmacology and clinical implications of l-THPBs in the drug development for psychosis and neurobiological diseases.

  11. Rigour of development of clinical practice guidelines for the pharmacological treatment of bipolar disorder: systematic review.

    Science.gov (United States)

    Castellani, Arianna; Girlanda, Francesca; Barbui, Corrado

    2015-03-15

    There is an increasing concern about the quality of clinical practice guidelines. Because no information is available on the rigour of development of clinical practice guidelines for bipolar disorder, we carried out a systematic review of those focusing on its pharmacological treatment. We searched the National Guideline Clearinghouse, MEDLINE, EMBASE, PsychINFO and CINHAL for guidelines published from 2003 to 2014. The quality of each guideline was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II). Fourteen guidelines were appraised. The overall quality of included guidelines varied considerably, both within and across AGREE II domains. Overall, six guidelines were rated as "recommended", two "recommended with modifications", and six were not recommended according to AGREE II ratings. The mean score for rigour of development was 46.8% of the maximum possible score, with no guidelines scoring the maximum score in this domain. Guidelines with lower editorial independence scores also had lower rigour of development scores, whereas those with higher-quality domain scores scored high in both domains. As current appraisal focused on guidelines for the pharmacological treatment of bipolar disorder, it will be important to critically assess the rigour of development of other guidelines for bipolar and other psychiatric disorders. Health care providers, policy makers, physicians and patients alike need to be aware of the variability in guideline quality and identify the high-quality guidelines that meet their needs. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Clinical pharmacology of tyrosine kinase inhibitors becoming generic drugs: the regulatory perspective.

    Science.gov (United States)

    Eckstein, Niels; Röper, Lea; Haas, Bodo; Potthast, Henrike; Hermes, Ulrike; Unkrig, Christoph; Naumann-Winter, Frauke; Enzmann, Harald

    2014-02-07

    Over the last decades, billions have been spent and huge efforts have been taken in basic and clinical cancer research [CA Cancer J Clin63:11-30]. About a decade ago, the arms race between drugs and cancer cells reached a new level by introduction of tyrosine kinase inhibitors (TKI) into pharmacological anti-cancer therapy. According to their molecular mechanism of action, TKI in contrast to so-called "classic" or "conventional" cytostatics belong to the group of targeted cancer medicines, characterized by accurately fitting with biological structures (i.e. active centers of kinases). Numerous (partly orphan) indications are covered by this new class of substances. Approximately ten years after the first substances of this class of medicines were authorized, patent protection will end within the next years. The following article covers clinical meaning and regulatory status of anti-cancer TKI and gives an outlook to what is expected from the introduction of generic anti-cancer TKI.

  13. CLINICAL AND PHARMACOLOGICAL PECULIARITIES OF CETIRIZINE USE FOR THE THERAPY OF ALLERGIC DISEASES IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Yu. G. Levina

    2014-01-01

    Full Text Available The review is dedicated to treatment of allergic diseases in children, particularly to the use of the 2nd generation antihistamine. It demonstrates that mediator histamine has the crucial role in pathophysiology of the allergic reaction. Antihistamines block histamine action aimed at H1 receptors by way of competitive inhibition. The 2nd generation antihistamines are the drugs of choice for the treatment of allergic diseases due to the absence of sedative effect. The review presents clinical and pharmacological description of the selective 2nd generation antihistamine cetirizine, efficacy and safety of which have been appraised in numerous long-term clinical studies in children with allergic rhinitis, urticaria and atopic dermatitis. 

  14. The clinical pharmacology profile of the new antiepileptic drug perampanel: A novel noncompetitive AMPA receptor antagonist.

    Science.gov (United States)

    Patsalos, Philip N

    2015-01-01

    The clinical pharmacology profile of a drug critically determines its therapeutics, and this review summarizes the characteristics associated with the antiepileptic drug (AED) perampanel. A PubMed literature search was performed for perampanel. Congress abstract data are included where necessary and Eisai Ltd provided access to unpublished data on file. After oral ingestion, perampanel is rapidly absorbed and peak plasma concentrations occur 0.5-2.5 h later; its bioavailability is ~100%. Although the rate of perampanel absorption is slowed by food co-ingestion, the extent absorbed remains unchanged; therefore, perampanel can be administered without regard to meal times. The pharmacokinetics of perampanel are linear and predictable over the clinically relevant dose range (2-12 mg); perampanel is 95% protein-bound to albumin and α1-acid glycoprotein. Perampanel is extensively metabolized (>90%) in the liver, primarily by cytochrome P450 (CYP) 3A4, to various pharmacologically inactive metabolites. In healthy volunteers, the apparent terminal half-life is ~105 h, whereas the calculated effective half-life is 48 h. These half-life values allow for once-daily dosing, which will aid patient compliance and in the event of a missed dose, will have minimal impact on seizure control. In healthy volunteers prescribed carbamazepine, half-life decreases to 25 h. Clearance values are not significantly different in adolescents (~13.0 ml/min) and the elderly (~10.5 ml/min) compared with adults (10.9 ml/min). Perampanel has minimal propensity to cause pharmacokinetic interactions. However, it is the target of such interactions and CYP3A4-inducing AEDs enhance its clearance; this can be used to advantage because dose titration can be faster and thus optimum therapeutic outcome can be achieved sooner. Perampanel 12 mg, but not 4 or 8 mg, enhances the metabolism of the progesterone component of the oral contraceptive pill, necessitating the need for an additional reliable

  15. International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the Formyl Peptide Receptor (FPR) Family

    Science.gov (United States)

    YE, RICHARD D.; BOULAY, FRANÇOIS; WANG, JI MING; DAHLGREN, CLAES; GERARD, CRAIG; PARMENTIER, MARC; SERHAN, CHARLES N.; MURPHY, PHILIP M.

    2009-01-01

    Formyl peptide receptors (FPRs) are a small group of seven-transmembrane domain, G protein-coupled receptors that are expressed mainly by mammalian phagocytic leukocytes and are known to be important in host defense and inflammation. The three human FPRs (FPR1, FPR2/ALX, and FPR3) share significant sequence homology and are encoded by clustered genes. Collectively, these receptors bind an extraordinarily numerous and structurally diverse group of agonistic ligands, including N-formyl and nonformyl peptides of different composition, that chemoattract and activate phagocytes. N-formyl peptides, which are encoded in nature only by bacterial and mitochondrial genes and result from obligatory initiation of bacterial and mitochondrial protein synthesis with N-formylmethionine, is the only ligand class common to all three human receptors. Surprisingly, the endogenous anti-inflammatory peptide annexin 1 and its N-terminal fragments also bind human FPR1 and FPR2/ALX, and the anti-inflammatory eicosanoid lipoxin A4 is an agonist at FPR2/ALX. In comparison, fewer agonists have been identified for FPR3, the third member in this receptor family. Structural and functional studies of the FPRs have produced important information for understanding the general pharmacological principles governing all leukocyte chemoattractant receptors. This article aims to provide an overview of the discovery and pharmacological characterization of FPRs, to introduce an International Union of Basic and Clinical Pharmacology (IUPHAR)-recommended nomenclature, and to discuss unmet challenges, including the mechanisms used by these receptors to bind diverse ligands and mediate different biological functions. PMID:19498085

  16. International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors.

    Science.gov (United States)

    Hamann, Jörg; Aust, Gabriela; Araç, Demet; Engel, Felix B; Formstone, Caroline; Fredriksson, Robert; Hall, Randy A; Harty, Breanne L; Kirchhoff, Christiane; Knapp, Barbara; Krishnan, Arunkumar; Liebscher, Ines; Lin, Hsi-Hsien; Martinelli, David C; Monk, Kelly R; Peeters, Miriam C; Piao, Xianhua; Prömel, Simone; Schöneberg, Torsten; Schwartz, Thue W; Singer, Kathleen; Stacey, Martin; Ushkaryov, Yuri A; Vallon, Mario; Wolfrum, Uwe; Wright, Mathew W; Xu, Lei; Langenhan, Tobias; Schiöth, Helgi B

    2015-01-01

    The Adhesion family forms a large branch of the pharmacologically important superfamily of G protein-coupled receptors (GPCRs). As Adhesion GPCRs increasingly receive attention from a wide spectrum of biomedical fields, the Adhesion GPCR Consortium, together with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification, proposes a unified nomenclature for Adhesion GPCRs. The new names have ADGR as common dominator followed by a letter and a number to denote each subfamily and subtype, respectively. The new names, with old and alternative names within parentheses, are: ADGRA1 (GPR123), ADGRA2 (GPR124), ADGRA3 (GPR125), ADGRB1 (BAI1), ADGRB2 (BAI2), ADGRB3 (BAI3), ADGRC1 (CELSR1), ADGRC2 (CELSR2), ADGRC3 (CELSR3), ADGRD1 (GPR133), ADGRD2 (GPR144), ADGRE1 (EMR1, F4/80), ADGRE2 (EMR2), ADGRE3 (EMR3), ADGRE4 (EMR4), ADGRE5 (CD97), ADGRF1 (GPR110), ADGRF2 (GPR111), ADGRF3 (GPR113), ADGRF4 (GPR115), ADGRF5 (GPR116, Ig-Hepta), ADGRG1 (GPR56), ADGRG2 (GPR64, HE6), ADGRG3 (GPR97), ADGRG4 (GPR112), ADGRG5 (GPR114), ADGRG6 (GPR126), ADGRG7 (GPR128), ADGRL1 (latrophilin-1, CIRL-1, CL1), ADGRL2 (latrophilin-2, CIRL-2, CL2), ADGRL3 (latrophilin-3, CIRL-3, CL3), ADGRL4 (ELTD1, ETL), and ADGRV1 (VLGR1, GPR98). This review covers all major biologic aspects of Adhesion GPCRs, including evolutionary origins, interaction partners, signaling, expression, physiologic functions, and therapeutic potential. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  17. Long-term randomized clinical trials of pharmacological treatment of obesity: Systematic review

    Directory of Open Access Journals (Sweden)

    Lidia Castañeda-González

    2010-09-01

    Full Text Available Introduction: Obesity has become a public health problem. The increment in energy intake and the reduction of caloric expenditure as a result of sedentary lifestyles promotes a positive energetic balance resulting in the increase of fat deposits. In response to this, the prescription of pharmacological treatments has also increased. Objective: To evaluate the long-term weight loss effectiveness of pharmacological treatments. Methodology: A systematic review was conducted on randomized clinical trials registered in Pub Med, Scielo, and EBSCOHOST from January 1st 1999 to December 31st 2008, including those with an intervention program with orlistat, sibutramine, and rimonabant equal or greater to two years. Two hundred and twelve articles were identified, 201 studies were excluded, and eleven were analyzed; seven from orlistat, two from sibutramine, and two from rimonabant. Information of design, intervention time, number of patients, age, body mass index and weight loss, difference between the intervention group versus the placebo, significance level, and methodological quality were obtained. Main findings: The percentage of weight loss with orlistat ranged between 5 and 12%, the mean weight loss was 8 kg, and a difference between IG vs. placebo of 3.7 kg. Weight loss with sibutramine ranged between 4 and 10%, the mean weight loss was 7.4 kg and a difference between the intervention group versus placebo was 5.5 kg. Weight loss with rimonabant was 7% with a mean weight loss of 7.3 kg, and the difference compared with the placebo was 4.4 kg. Conclusions: Weight loss with pharmacotherapy is modest; weight regain after interruption of treatment, adverse effects, costs and lack of evidence related to long-term morbi-mortality, do not justify the generalized use of pharmacological treatment of obesity.

  18. Long-term randomized clinical trials of pharmacological treatment of obesity: Systematic review

    Directory of Open Access Journals (Sweden)

    Lidia Castañeda-González

    2010-03-01

    Full Text Available Introduction: Obesity has become a public health problem. The increment in energy intake and the reduction of caloric expenditure as a result of sedentary lifestyles promotes a positive energetic balance resulting in the increase of fat deposits. In response to this, the prescription of pharmacological treatments has also increased.Objective: To evaluate the long-term weight loss effectiveness of pharmacological treatments.Methodology: A systematic review was conducted on randomized clinical trials registered in Pub Med, Scielo, and EBSCOHOST from January 1st 1999 to December 31st 2008, including those with an intervention program with orlistat, sibutramine, and rimonabant equal or greater to two years. Two hundred and twelve articles were identified, 201 studies were excluded, and eleven were analyzed; seven from orlistat, two from sibutramine, and two from rimonabant. Information of design, intervention time, number of patients, age, body mass index and weight loss, difference between the intervention group versus the placebo, significance level, and methodological quality were obtained.Main findings: The percentage of weight loss with orlistat ranged between 5 and 12%, the mean weight loss was 8 kg, and a difference between IG vs. placebo of 3.7 kg. Weight loss with sibutramine ranged between 4 and 10%, the mean weight loss was 7.4 kg and a difference between the intervention group versus placebo was 5.5 kg. Weight loss with rimonabant was 7% with a mean weight loss of 7.3 kg, and the difference compared with the placebo was 4.4 kg.Conclusions: Weight loss with pharmacotherapy is modest; weight regain after interruption of treatment, adverse effects, costs and lack of evidence related to long-term morbi-mortality, do not justify the generalized use of pharmacological treatment of obesity.

  19. Review of Clinical Pharmacology of Aloe vera L. in the Treatment of Psoriasis.

    Science.gov (United States)

    Miroddi, Marco; Navarra, Michele; Calapai, Fabrizio; Mancari, Ferdinando; Giofrè, Salvatore Vincenzo; Gangemi, Sebastiano; Calapai, Gioacchino

    2015-05-01

    Aloe vera L., is a plant used worldwide as folk remedy for the treatment of various ailments, including skin disorders. Its gel is present in cosmetics, medicinal products and food supplements. Psoriasis, an immune-mediated chronic inflammatory disease, involving mainly the skin, affects about the 2-3% of general population. Conventional pharmacological treatments for psoriasis can have limited effectiveness and can cause adverse reactions. For this reason often psoriatic patients look for alternative treatments based on natural products containing Aloe vera. We conducted a systematic review of clinical trials assessing effectiveness and safety of aloe for the treatment of psoriasis. Clinical studies published in English were considered; a total of four clinical trials met inclusion criteria. Studies were also evaluated by using the Jadad scale and Consort Statement in Reporting Clinical trials of Herbal Medicine Intervention. Quality and methodological accuracy of considered studies varied considerably, and some crucial information to reproduce clinical results was missing. We conclude that administration of aloe as cutaneous treatment is generally well tolerated, as no serious side effects were reported. Results on the effectiveness of Aloe vera are contradictory; our analysis reveals the presence of methodological gaps preventing to reach final conclusions.

  20. Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

    Science.gov (United States)

    2015-10-01

    Award Number: W81XWH-11-1-0639 TITLE: Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval PRINCIPAL...SEP 2014 – 29 SEP 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-11-1-0639 Development of Pain Endpoint Models for Use in Prostate Cancer...standard methods for measuring pain palliation and pain progression in prostate cancer clinical trials that are feasible, methodologically rigorous, and

  1. Carthami flos: a review of its ethnopharmacology, pharmacology and clinical applications

    Directory of Open Access Journals (Sweden)

    Yanhua Tu

    2015-10-01

    Full Text Available ABSTRACTCarthami flos, the dried floret of Carthamus tinctorius L., Asteraceae (safflower, has been widely used in traditional Chinese medicine to treat a broad range of ailments, such as coronary heart disease, angina pectoris, gynecologic disease, stroke, and hypertension. However, although several studies on Carthami flos have been done consecutively, the results are usually scattered across various documents. This review aims to provide up-to-date information on the traditional uses, pharmacology, clinical applications, and toxicology of Carthami flos in China and thereby to provide a basis for further investigation of its use to treat dissimilar diseases. Various ethnomedical uses of Carthami flos have been documented in many ancient Chinese books. Crude extracts and isolated compounds from Carthami flos show a broad range of pharmacological properties, such as protective effects on brain tissue, on osteoblasts, and in myocardial ischemia, as well as anti-inflammatory, antithrombotic, antitumor, and antidiabetic activities. To date, safflower and safflor yellow injections have been used to treat coronary heart disease, chronic pulmonary heart disease, cerebrovascular diseases, orthopedic diseases, and diabetes mellitus. Regarding the toxicology of Carthami flos, among the side effects that have been observed are allergic reaction, spermatogenetic failure, fatty liver, and nephrotoxicity.

  2. Levodopa-induced dyskinesias in Parkinson's disease: clinical and pharmacological classification.

    Science.gov (United States)

    Luquin, M R; Scipioni, O; Vaamonde, J; Gershanik, O; Obeso, J A

    1992-01-01

    Levodopa-induced dyskinesias (LID) in Parkinson's disease (PD) may be classified into three main categories: "On" dyskinesias, diphasic dyskinesias (DD), and "off" periods. The study of 168 parkinsonian patients showed that about half (n = 84) showed one pattern of LID only. A combination of two was present in 68, and 16 had the three presentation patterns. A fairly good correlation between type of dyskinesia and presentation pattern was established. Chorea, myoclonus, and dystonic movements occurred during the "on" period. Dystonic postures, particularly affecting the feet, were mainly present in the "off" period, but a few patients had a diphasic presentation. Repetitive stereotyped movements of the lower limbs always corresponded to DD. Acute pharmacological tests using dopamine agonists (subcutaneous apomorphine 3-8 mg; intravenous lisuride 0.1-0.15 mg) and dopamine antagonists (intravenous sulpiride 200-400 mg and intravenous chlorpromazine 25 mg) were performed in 40 patients. Dopamine agonists enhanced "on" dyskinesias and markedly reduced or abolished "off" period dystonia and DD. Dopamine antagonists reduced all types of LID but usually aggravated parkinsonism. These clinical and pharmacological results indicate that LID in PD are a heterogeneous phenomenon difficult to explain on the basis of a single pathophysiological mechanism.

  3. An Updated Review on the Phytochemistry, Pharmacology, and Clinical Trials of Salacia oblonga

    Science.gov (United States)

    Kushwaha, Priya Singh; Singh, Ashok K.; Keshari, Amit K.; Maity, Siddhartha; Saha, Sudipta

    2016-01-01

    Salacia oblonga (S. oblonga), a perennial herb, has been used for thousands of years in ayurvedic medicine and is closely associated with prevention, treatment, and cure of various human ailments such as obesity and diabetes. A vast and wide range of chemical compounds such as polyphenols, friedelane-type triterpenes, norfriedelane-type triterpenes, eudesmane-type sesquiterpenes including various glycosides had been isolated from this plant. This review is aimed to survey the literature covering the phytochemistry and pharmacology of S. oblonga and to review the scientific data including active components and their multi-targeted mechanisms of action against various metabolic syndromes. We also included clinical trials related to this plant in this review. The overview would assist researchers to gather scientific information related to S. oblonga in future. PMID:28082793

  4. An updated review on the phytochemistry, pharmacology, and clinical trials of Salacia oblonga

    Directory of Open Access Journals (Sweden)

    Priya Singh Kushwaha

    2016-01-01

    Full Text Available Salacia oblonga (S. oblonga, a perennial herb, has been used for thousands of years in ayurvedic medicine and is closely associated with prevention, treatment, and cure of various human ailments such as obesity and diabetes. A vast and wide range of chemical compounds such as polyphenols, friedelane-type triterpenes, norfriedelane-type triterpenes, eudesmane-type sesquiterpenes including various glycosides had been isolated from this plant. This review is aimed to survey the literature covering the phytochemistry and pharmacology of S. oblonga and to review the scientific data including active components and their multi-targeted mechanisms of action against various metabolic syndromes. We also included clinical trials related to this plant in this review. The overview would assist researchers to gather scientific information related to S. oblonga in future.

  5. The Japanese Postmarketing Adverse Event Relief System: A Confluence of Regulatory Science, the Legal System, and Clinical Pharmacology.

    Science.gov (United States)

    Tominaga, T; Miyazaki, S; Oniyama, Y; Weber, A D; Kondo, T

    2017-08-01

    The Japanese Postmarketing Relief System provides for compensation to patients with adverse reactions, based on the acknowledgment that unpredicted adverse events occur inevitably once a drug is marketed. The system also provides new knowledge about the benefit-risk profile of a drug that may be incorporated into product labeling. The system relies on causality assessments that are based on sound clinical pharmacology principles. The system may serve as a model for other countries' healthcare systems. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  6. Comparison of the pharmacologic and clinical profiles of new combined oral contraceptives containing estradiol

    Directory of Open Access Journals (Sweden)

    Jensen JT

    2013-11-01

    Full Text Available Jeffrey T Jensen,1 Johannes Bitzer,2 Marco Serrani3 1Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA; 2Department of Social Medicine and Psychosomatics, Women’s Hospital, University Hospital of Basel, Basel, Switzerland; 3Global Medical Affairs, Women’s Healthcare, Bayer HealthCare Pharmaceuticals, Berlin, Germany Abstract: Three estradiol (E2-containing oral contraceptives, estradiol valerate/cyproterone acetate (E2V/CPA, Femilar®, estradiol valerate/dienogest (E2V/DNG, Qlaira®/Natazia™, and estradiol/nomegestrol acetate (E2/NOMAC; Zoely®, have received approval for use in general practice. Only Finnish women currently have access to all three E2-based formulations. E2/NOMAC is currently approved only in Europe, while E2V/DNG is approved globally. To assist clinicians counseling women considering use of one of these formulations, we conducted a review of the published information about the current E2-containing oral contraceptives. A literature search was conducted using the Ovid interface and a combination of free search terms relevant to estradiol and oral contraception to identify suitable articles for inclusion in this review. The available data show that E2V/DNG, E2/NOMAC, and E2V/CPA are all effective oral contraceptives. While direct comparisons are lacking, indirect evidence suggests that E2V/DNG and E2/NOMAC may have better bleeding profiles than E2V/CPA. E2V/DNG is also approved for the treatment of heavy menstrual bleeding. Both E2V/DNG and E2/NOMAC have minimal influence on hemostatic, lipid, and carbohydrate metabolism parameters, or induce less change in these parameters relative to ethinylestradiol-based oral contraceptives. However, the predictive value of these surrogate parameters is a matter of debate, and whether these differences can be translated into meaningful clinical outcomes needs to be established in large-scale, post-marketing, prospective, Phase IV cohort

  7. Autosomal dominant polycystic kidney disease: recent advances in clinical management [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Zhiguo Mao

    2016-08-01

    Full Text Available The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD go back at least 500 years to the late 16th century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21st century. In this commentary, we consider how clinical management is likely to change in the coming decade.

  8. Applied clinical pharmacology and public health in rural Asia – preventing deaths from organophosphorus pesticide and yellow oleander poisoning

    OpenAIRE

    Eddleston, Michael

    2012-01-01

    Self-poisoning with pesticides or plants is a major clinical problem in rural Asia, killing several hundred thousand people every year. Over the last 17 years, our clinical toxicology and pharmacology group has carried out clinical studies in the North Central Province of Sri Lanka to improve treatment and reduce deaths. Studies have looked at the effectiveness of anti-digoxin Fab in cardiac glycoside plant poisoning, multiple dose activated charcoal in all poisoning, and pralidoxime in moder...

  9. Design and practice of the integrated pharmacology course in the organ- and system-based clinical medicine undergraduate teaching

    Institute of Scientific and Technical Information of China (English)

    Liang ZHU; Zheng-xing RONG; Yong-yao CUI; Hong CHEN; Juan LI; Hong-zhuan CHEN

    2015-01-01

    Pharmacology is a discipline bridging basic medicine and clinical medicine. Under the disciplinebased structure,derived from the characteristics of drugs,students study pharmacology for the rational use of the drugs targeting pathophysiological status according to the diseases and the symptoms. Under the organsystem-based teaching systems,the part of the principle of pharmacology is put into the basic medicine integrated module system and the other parts are divided into the according organ-system integrated courses,respectively. It is important for clinical teaching that the domestic and international status,the role and mutual relationship in and between the integrated course system,the designation and practice of the course,the problems to be addressed of the course can be understood.

  10. International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

    Science.gov (United States)

    Aust, Gabriela; Araç, Demet; Engel, Felix B.; Formstone, Caroline; Fredriksson, Robert; Hall, Randy A.; Harty, Breanne L.; Kirchhoff, Christiane; Knapp, Barbara; Krishnan, Arunkumar; Liebscher, Ines; Lin, Hsi-Hsien; Martinelli, David C.; Monk, Kelly R.; Peeters, Miriam C.; Piao, Xianhua; Prömel, Simone; Schöneberg, Torsten; Schwartz, Thue W.; Singer, Kathleen; Stacey, Martin; Ushkaryov, Yuri A.; Vallon, Mario; Wolfrum, Uwe; Wright, Mathew W.; Xu, Lei; Langenhan, Tobias

    2015-01-01

    The Adhesion family forms a large branch of the pharmacologically important superfamily of G protein–coupled receptors (GPCRs). As Adhesion GPCRs increasingly receive attention from a wide spectrum of biomedical fields, the Adhesion GPCR Consortium, together with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification, proposes a unified nomenclature for Adhesion GPCRs. The new names have ADGR as common dominator followed by a letter and a number to denote each subfamily and subtype, respectively. The new names, with old and alternative names within parentheses, are: ADGRA1 (GPR123), ADGRA2 (GPR124), ADGRA3 (GPR125), ADGRB1 (BAI1), ADGRB2 (BAI2), ADGRB3 (BAI3), ADGRC1 (CELSR1), ADGRC2 (CELSR2), ADGRC3 (CELSR3), ADGRD1 (GPR133), ADGRD2 (GPR144), ADGRE1 (EMR1, F4/80), ADGRE2 (EMR2), ADGRE3 (EMR3), ADGRE4 (EMR4), ADGRE5 (CD97), ADGRF1 (GPR110), ADGRF2 (GPR111), ADGRF3 (GPR113), ADGRF4 (GPR115), ADGRF5 (GPR116, Ig-Hepta), ADGRG1 (GPR56), ADGRG2 (GPR64, HE6), ADGRG3 (GPR97), ADGRG4 (GPR112), ADGRG5 (GPR114), ADGRG6 (GPR126), ADGRG7 (GPR128), ADGRL1 (latrophilin-1, CIRL-1, CL1), ADGRL2 (latrophilin-2, CIRL-2, CL2), ADGRL3 (latrophilin-3, CIRL-3, CL3), ADGRL4 (ELTD1, ETL), and ADGRV1 (VLGR1, GPR98). This review covers all major biologic aspects of Adhesion GPCRs, including evolutionary origins, interaction partners, signaling, expression, physiologic functions, and therapeutic potential. PMID:25713288

  11. Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

    Science.gov (United States)

    2016-10-01

    substantially impair functioning and quality of life. Regulatory standards for the design of symptom endpoints have evolved substantially over the...1d. Submit protocol to departmental review committees at UNC (Month 14) Completed – NOV 2012 1e. Obtain IRB approval at UNC (Months 19) Note...Cabozantinib demonstrated clinically meaningful pain palliation, reduced or eliminated patients’ narcotic use, and improved patient functioning , thus

  12. Special issue of clinical pharmacology: advances and applications in new protein therapeutics modulating tumor immunity

    Directory of Open Access Journals (Sweden)

    Frankel AE

    2013-11-01

    Full Text Available Arthur E Frankel Department of Internal Medicine, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA Until recent decades, the role of the immune system in harnessing tumor growth was based on anecdotal observations of increased cancers in immune-compromised patients, the benefits of graft-versus-leukemia in allogeneic stem cell transplants, and the limited but reproducible anticancer activity of several lymphokines, including interferon and interleukin (IL-2. Vaccine studies and infusions of "activated" lymphocytes yielded variable clinical responses and disease control. An improved understanding of the molecular and cell mechanisms of the innate and adaptive immune system in cancer-bearing animals and the discovery of an immune-suppressive tumor microenvironment then led to development and testing of a battery of new drug and cell-based approaches to trigger antitumor immunity. This issue of Clinical Pharmacology: Advances and Applications highlights some of the new protein-based compounds that are radically changing the cancer therapeutic landscape. The purpose of this collection of reviews is to inform the readership regarding the importance of the seismic change in cancer therapeutics and stimulate efforts to find novel niches and combinations of agents similar to recent advances in the application of cancer pathway inhibitors.

  13. Pharmacological treatment of bipolar depression: qualitative systematic review of double-blind randomized clinical trials.

    Science.gov (United States)

    Spanemberg, Lucas; Massuda, Raffael; Lovato, Lucas; Paim, Leonardo; Vares, Edgar Arrua; Sica da Rocha, Neusa; Ceresér, Keila Maria Mendes

    2012-06-01

    Randomized clinical trial (RCT) is the best study design for treatment-related issues, yet these studies may present a number of biases and limitations. The objective of this study is to carry out a qualitative analysis of RCT methodology in the treatment of bipolar depression (BD). A systematic review covering the last 20 years was performed on PubMed selecting double-blind RCTs for BD. The identification items of the articles, their design, methodology, outcome and grant-related issues were all analyzed. Thirty articles were included, all of which had been published in journals with an impact factor >3. While almost half studies (46.7%) used less than 50 patients as a sample, 70% did not describe or did not perform sample size calculation. The Last Observation Carried Forward (LOCF) method was used in 2/3 of the articles and 53.4% of the studies had high sample losses (>20%). Almost half the items were sponsored by the pharmaceutical industry and 33.3% were sponsored by institutions or research foundations. Articles on the pharmacological treatment of BD have several limitations which hinder the extrapolation of the data to clinical practice. Methodological errors and biases are common and statistical simplifications compromise the consistency of the findings.

  14. The coxib NSAIDs: potential clinical and pharmacologic importance in veterinary medicine.

    Science.gov (United States)

    Bergh, Mary Sarah; Budsberg, Steven C

    2005-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to control acute and chronic pain as well as to manage oncologic and neurologic diseases in human and veterinary patients. Despite ongoing research and efforts to improve the safety and efficacy of existing drugs, adverse effects such as gastrointestinal irritation, renal and hepatic toxicity, interference with hemostasis, and reproductive problems persist. The true incidence of NSAID-induced adverse effects in animals is unknown, but is likely underestimated, because cats and dogs may be more sensitive than humans to NSAIDs due to alterations in drug metabolism, absorption, and enterohepatic recirculation. NSAIDs produce both analgesia and toxic adverse effects primarily by inhibiting cyclooxygenase (COX), thereby decreasing the production of prostaglandins that signal inflammation and pain as well as mediate physiologic functions such as platelet aggregation, gastric protection, and electrolyte balance in the kidney. The presence of at least 2 COX isoforms may account for variability in NSAID efficacy and toxicity both within and among species. This paper reviews and evaluates the published literature on the safety, pharmacology, uses, and complications of a subclass of COX-1-sparing drugs, the coxibs, in veterinary medicine. Coxibs and other COX-1-sparing drugs provide a clinically useful improvement over traditional NSAIDs, but data are incomplete and more in vivo species-specific, target-tissue, and clinical studies are needed.

  15. Betahistine in the treatment of vertigo. History and clinical implications of recent pharmacological researches.

    Science.gov (United States)

    Mira, E

    2001-06-01

    A short profile of betahistine and its activity in treatment of Menière's disease and other forms of peripheral vertigo is presented. The clinical efficacy of betahistine is documented by a series of more than twenty controlled clinical studies, performed in the years 1966-2000. Basic researches initially proved that bethaistine acts trough a vasodilating action on inner ear and cerebral blood flow (Suga and Snow, 1969; Martinez, 1972). In the following years this activity was confirmed using the modern laser doppler flowmetry technique (Laurikainen et al, 1998). Further recent studies proved that betahistine acts on the central vestibular histaminergic system as a weak H1 agonist and a strong H3 antagonist (Arrang et al., 1985), improving the process of vestibular compensation (Tighilet et al., 1995) as well as on peripheral labyrinthine receptors, reducing the spontaneous firing rate but not the activity induced by thermal or mechanical stimulation (Botta et al., 1998). More than forty years after its discovery, this series of studies carried out in the second half of the 90s leads to the conclusion that betahistine is a drug which maintains its scientific interest and its pharmacological potential in the treatment of vertigo.

  16. [Pharmacological treatment].

    Science.gov (United States)

    Arriola Manchola, Enrique; Álaba Trueba, Javier

    2016-06-01

    Alzheimer's disease (AD) is a chronic degenerative and inflammatory process leading to synapticdysfunction and neuronal death. A review about the pharmacological treatment alternatives is made: acetylcholinesterase inhibitors (AChEI), a nutritional supplement (Souvenaid) and Ginkgo biloba. A special emphasis on Ginkgo biloba due to the controversy about its use and the approval by the European Medicines Agency is made. Copyright © 2016 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Comments on: Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline From the American College of Physicians

    OpenAIRE

    2012-01-01

    Comments on:Qaseem A., Humphrey L.L., Sweet D.E., Starkey M., Shekelle P. Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2012 Feb 7;156(3):218-31.

  18. Comments on: Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline From the American College of Physicians

    Directory of Open Access Journals (Sweden)

    Ekaterina A Pigarova

    2012-06-01

    Full Text Available Comments on:Qaseem A., Humphrey L.L., Sweet D.E., Starkey M., Shekelle P. Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2012 Feb 7;156(3:218-31.

  19. Clinical and Pharmacologic Study of the Novel Prodrug Delimotecan (MEN 4901/T-0128) in Patients with Solid Tumors

    NARCIS (Netherlands)

    Veltkamp, Stephan A.; Witteveen, Els O.; Capriati, Angela; Crea, Attilio; Animati, Fabio; Voogel-Fuchs, Marja; van den Heuvel, Ingeborg J. G. M.; Beijnen, Jos H.; Voest, Emile E.; Schellens, Jan H. M.

    2008-01-01

    Purpose: To investigate i.v. administration of delimotecan (MEN 4901/T-0128), a carboxymethyldextran polymer prodrug of the active camptothecin derivative T-2513, and to assess the maximum tolerated dose, safety profile, clinical pharmacology, and antitumor activity of delimotecan and metabolites. E

  20. Advancing pharmacometrics and systems pharmacology.

    Science.gov (United States)

    Waldman, S A; Terzic, A

    2012-11-01

    Pharmacometrics and systems pharmacology are emerging as principal quantitative sciences within drug development and experimental therapeutics. In recognition of the importance of pharmacometrics and systems pharmacology to the discipline of clinical pharmacology, the American Society for Clinical Pharmacology and Therapeutics (ASCPT), in collaboration with Nature Publishing Group and Clinical Pharmacology & Therapeutics, has established CPT: Pharmacometrics & Systems Pharmacology to inform the field and shape the discipline.

  1. Differential pharmacology and clinical utility of long-acting bronchodilators in COPD – focus on olodaterol

    Directory of Open Access Journals (Sweden)

    Matera MG

    2015-12-01

    Full Text Available Maria Gabriella Matera,1 Josuel Ora,2 Mario Cazzola2,3 1Department of Experimental Medicine, Unit of Pharmacology, Second University of Naples, Naples, 2Division of Respiratory Medicine, University Hospital Tor Vergata, 3Department of Systems Medicine, Respiratory Pharmacology Research Unit, University of Rome Tor Vergata, Rome, Italy Abstract: Olodaterol (BI 1744 CL is a novel, once-daily long-acting β2-agonist (LABA designed with the aim of improving β2-adrenoreceptor selectivity and intrinsic activity. Phase III pivotal trials have documented that olodaterol Respimat Soft Mist inhaler 5 µg induces fast onset of bronchodilation, comparable with formoterol at day 1. Moreover, significant lung function improvements have been documented up to 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease (COPD. Olodaterol was generally well tolerated and had an acceptable cardiovascular and respiratory adverse event profile. Regrettably, the clinical development of olodaterol is however still too partial to draw any firm conclusions on the positioning of this ultra-LABA as monotherapy in the management of COPD. Waiting for further data on the impact of olodaterol on different patient-reported outcomes, which however are widely available for indacaterol, and mainly for a head-to-head comparison between these two ultra-LABAs and between olodaterol long-acting antimuscarinic antagonists other than tiotropium, we believe it is correct to follow the clinical indications of indacaterol also for olodaterol. In any case, the parallel bronchodilating modes of action of olodaterol and tiotropium make them an attractive combination in COPD. The results from the ongoing large TOviTO Phase III trial program have documented the efficacy and safety of olodaterol/tiotropium fixed-dose combination as maintenance therapy in patients with moderate to very severe COPD. In particular, olodaterol/tiotropium fixed-dose combination provides

  2. Pharmacological and clinical evidence of nevirapine immediate- and extended-release formulations

    Directory of Open Access Journals (Sweden)

    Ena J

    2012-11-01

    Full Text Available Javier Ena, Concepción Amador, Conxa Benito, Francisco PasquauHIV Unit, Hospital Marina Baixa, Villajoyosa, SpainAbstract: We reviewed the current information available on nevirapine immediate- and extended-release formulations and its role in single-dose and combination antiretroviral therapy. Nevirapine was approved in 1996 and was the first non-nucleoside reverse-transcriptase inhibitor available for the treatment of HIV-1 infection. Nevirapine has demonstrated good efficacy and a well-characterized safety profile. A major drawback is the low genetic barrier, allowing the emergence of resistance in the presence of single mutations in the reverse-transcriptase gene. This shortcoming is particularly relevant when nevirapine is administered in a single dose to prevent mother-to-child transmission of HIV-1 infection, compromising the efficacy of future non-nucleoside reverse transcriptase–inhibitor regimens. Studies published recently have probed the noninferiority of nevirapine compared to ritonavir-boosted atazanavir with both tenofovir disoproxil fumarate and emtricitabine in antiretroviral treatment–naïve patients. In 2011, a new formulation of nevirapine (nevirapine extended release that allowed once-daily dosing was approved by the Food and Drug Administration and by the European Medicines Agency. VERxVe, a study comparing nevirapine extended release with nevirapine immediate release in antiretroviral treatment–naïve patients, and TRANxITION, a study carried out in antiretroviral treatment–experienced patients who switched therapy from nevirapine immediate release to nevirapine extended release, provided data on the noninferiority of the new formulation of nevirapine compared with nevirapine immediate release in terms of efficacy and safety. Nevirapine extended release will further increase the durability and persistence of nevirapine-containing antiretroviral therapy, allowing once-daily dosing regimens.Keywords: nevirapine

  3. European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

    DEFF Research Database (Denmark)

    Roessner, Veit; Plessen, Kerstin J; Rothenberger, Aribert

    2011-01-01

    provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary...

  4. Clinical Characteristics and Pharmacological Treatment of Psychotic Patients Attending the Mental Health Services of the Pediatric Hospital of Cienfuegos

    OpenAIRE

    Beatriz Sabina Roméu; Daimí Sarmiento González; Mario Isaías Alzuri Falcato; Anais Leyva Madrigales

    2016-01-01

    Background: the mental health services of the Pediatric Hospital of Cienfuegos receive all patients in the province that need to be hospitalized. Among them, children and adolescents functioning at the psychotic level are of great clinical and social importance. Objective: to describe the clinical characteristics and pharmacological treatment of psychotic patients treated in the mental health services. Methods: a case series study of 35 psychotic patients admitted to the mental health unit of...

  5. Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic.

    Science.gov (United States)

    Meyskens, Frank L; Curt, Gregory A; Brenner, Dean E; Gordon, Gary; Herberman, Ronald B; Finn, Olivera; Kelloff, Gary J; Khleif, Samir N; Sigman, Caroline C; Szabo, Eva

    2011-03-01

    This article endeavors to clarify the current requirements and status of regulatory approval for chemoprevention (risk reduction) drugs and discusses possible improvements to the regulatory pathway for chemoprevention. Covering a wide range of topics in as much depth as space allows, this report is written in a style to facilitate the understanding of nonscientists and to serve as a framework for informing the directions of experts engaged more deeply with this issue. Key topics we cover here are as follows: a history of definitive cancer chemoprevention trials and their influence on the evolution of regulatory assessments; a brief review of the long-standing success of pharmacologic risk reduction of cardiovascular diseases and its relevance to approval for cancer risk reduction drugs; the use and limitations of biomarkers for developing and the approval of cancer risk reduction drugs; the identification of individuals at a high(er) risk for cancer and who are appropriate candidates for risk reduction drugs; business models that should incentivize pharmaceutical industry investment in cancer risk reduction; a summary of scientific and institutional barriers to development of cancer risk reduction drugs; and a summary of major recommendations that should help facilitate the pathway to regulatory approval for pharmacologic cancer risk reduction drugs.

  6. Morinda citrifolia (Noni: A comprehensive review on its industrial uses, pharmacological activities, and clinical trials

    Directory of Open Access Journals (Sweden)

    Reem Abou Assi

    2017-07-01

    Full Text Available Traditional medical practitioners in Hawaii and Polynesia have used Morinda citrifolia L. (Noni for centuries to cure or prevent varieties of illnesses. The popularity of M. citrifolia as a dietary supplement, a food functional ingredient, or as a natural health enhancer is increasing throughout the world. M. citrifolia contains phytochemicals that own antibacterial, antiviral, antifungal, antitumor, anthelminthic, analgesic, hypotensive, anti-inflammatory and immune enhancing effects. Moreover, the increasing vogue of M. citrifolia has attracted industries to employ it as a part of various products and for wide applications such as a natural source of medicines and chemical reagents as well as a green insecticidal. The wide spread of M. citrifolia in tropical climate of the globe, from USA to Brazil reaching to Tahiti, Malaysia and Australia, contributed in enriching its uses and potentials due to the variation in harvest locations. M. citrifolia parts including fruits, seeds, barks, leaves, and flowers are utilized on their own for individual nutritional and therapeutical values, however, the fruit is considered to contain the most valuable chemical compounds. This review discusses in details the industrial uses and the pharmacological activities of M. citrifolia fruit, seed, leaf and root, along with their isolated phytochemical compounds, through describing the conducted in vitro and in vivo studies as well as clinical data.

  7. A Systemic Review on Aloe arborescens Pharmacological Profile: Biological Activities and Pilot Clinical Trials.

    Science.gov (United States)

    Singab, Abdel-Naser B; El-Hefnawy, Hala M; Esmat, Ahmed; Gad, Haidy A; Nazeam, Jilan A

    2015-12-01

    Since ancient times, plants and herbal preparations have been used as medicine. Research carried out in the last few decades has verified several such claims. Aloe arborescens Miller, belonging to the Aloe genus (Family Asphodelaceae), is one of the main varieties of Aloe used worldwide. The popularity of the plant in traditional medicine for several ailments (antitumor, immunomodulatory, antiinflammatory, antiulcer, antimicrobial and antifungal activity) focused the investigator's interest on this plant. Most importantly, the reported studies have shown the plant effectiveness on various cancer types such as liver, colon, duodenal, skin, pancreatic, intestinal, lung and kidney types. These multiple biological actions make Aloe an important resource for developing new natural therapies. However, the biological activities of isolated compounds such as glycoprotein, polysaccharides, enzyme and phenolics were insufficient. Considering all these, this contribution provides a systematic review outlining the evidence on the biological efficacy of the plant including the pharmacology and the related mechanisms of action, with specific attention to the various safety precautions, and preclinical and clinical studies, indicating the future research prospects of this plant.

  8. Evolving paradigms in clinical pharmacology and therapeutics for the treatment of Duchenne muscular dystrophy.

    Science.gov (United States)

    Huard, J; Mu, X; Lu, A

    2016-08-01

    Progressive muscle weakness and degeneration due to the lack of dystrophin eventually leads to the loss of independent ambulation by the middle of the patient's second decade, and a fatal outcome due to cardiac or respiratory failure by the third decade. More specifically, loss of sarcolemmal dystrophin and the dystrophin-associated glycoprotein (DAG) complex promotes muscle fiber damage during muscle contraction. This process results in an efflux of creatine kinase (CK), an influx of calcium ions, and the recruitment of T cells, macrophages, and mast cells to the damaged muscle, causing progressive myofiber necrosis. For the last 20 years, the major goal in the development of therapeutic approaches to alleviate muscle weakness in DMD has been centered on the restoration of dystrophin or proteins that are analogous to dystrophin, such as utrophin, through a variety of modalities including cell therapy, gene therapy, gene correction, and the highly promising techniques utilizing CRISPR/Cas9 technology. Despite the development of new therapeutic options, there still exist numerous challenges that we must face with regard to these new strategies and, consequently, we still do not have any feasible options available to ultimately slow the progression of this devastating disease. The purpose of this article is to highlight the current knowledge and advancements in the evolving paradigms in clinical pharmacology and therapeutics for this devastating musculoskeletal disease.

  9. Photoacoustic intra-operative nodal staging using clinically approved superparamagnetic iron oxide nanoparticles

    Science.gov (United States)

    Grootendorst, Diederik J.; Fratila, Raluca M.; Visscher, Martijn; Ten Haken, Bennie; van Wezel, Richard; Steenbergen, Wiendelt; Manohar, Srirang; Ruers, Theo J. M.

    2013-02-01

    Detection of tumor metastases in the lymphatic system is essential for accurate staging of various malignancies, however fast, accurate and cost-effective intra-operative evaluation of the nodal status remains difficult to perform with common available medical imaging techniques. In recent years, numerous studies have confirmed the additional value of superparamagnetic iron oxide dispersions (SPIOs) for nodal staging purposes, prompting the clearance of different SPIO dispersions for clinical practice. We evaluate whether a combination of photoacoustic (PA) imaging and a clinically approved SPIO dispersion, could be applied for intra-operative nodal staging. Metastatic adenocarcinoma was inoculated in Copenhagen rats for 5 or 8 days. After SPIO injection, the lymph nodes were photoacoustically imaged both in vivo and ex vivo whereafter imaging results were correlated with MR and histology. Results were compared to a control group without tumor inoculation. In the tumor groups clear irregularities, as small as 1 mm, were observed in the PA contrast pattern of the nodes together with an decrease of PA response. These irregularities could be correlated to the absence of contrast in the MR images and could be linked to metastatic deposits seen in the histological slides. The PA and MR images of the control animals did not show these features. We conclude that the combination of photoacoustic imaging with a clinically approved iron oxide nanoparticle dispersion is able to detect lymph node metastases in an animal model. This approach opens up new possibilities for fast intra-operative nodal staging in a clinical setting.

  10. Clinical pharmacology study of cariprazine (MP-214) in patients with schizophrenia (12-week treatment)

    Science.gov (United States)

    Nakamura, Tadakatsu; Kubota, Tomoko; Iwakaji, Atsushi; Imada, Masayoshi; Kapás, Margit; Morio, Yasunori

    2016-01-01

    Purpose Cariprazine is a potent dopamine D3-preferring D3/D2 receptor partial agonist in development for the treatment of schizophrenia, bipolar mania, and depression. Pharmacokinetics of cariprazine and the two clinically relevant metabolites (desmethyl- and didesmethyl-cariprazine) was evaluated in a clinical pharmacology study. Methods This was a multicenter, randomized, open-label, parallel-group, fixed-dose (3, 6, or 9 mg/day) study of 28-week duration (≤4-week observation, 12-week open-label treatment, and 12-week follow-up). Once-daily cariprazine was administered to 38 adult patients with schizophrenia. The pharmacokinetics of cariprazine, metabolites, and total active moieties (sum of cariprazine and two metabolites) was evaluated; efficacy and safety were also assessed. Results Steady state was reached within 1–2 weeks for cariprazine and desmethyl-cariprazine, 4 weeks for didesmethyl-cariprazine, and 3 weeks for total active moieties. Cariprazine and desmethyl-cariprazine levels decreased >90% within 1 week after the last dose, didesmethyl-cariprazine decreased ~50% at 1 week, and total active moieties decreased ~90% within 4 weeks. Terminal half-lives of cariprazine, desmethyl-cariprazine, and didesmethyl-cariprazine ranged from 31.6 to 68.4, 29.7 to 37.5, and 314 to 446 hours, respectively. Effective half-life (calculated from time to steady state) of total active moieties was ~1 week. Incidence of treatment-emergent adverse events was 97.4%; 15.8% of patients discontinued due to adverse events. No abnormal laboratory values or major differences from baseline in extrapyramidal symptoms were observed. Conclusion Cariprazine and its active metabolites reached steady state within 4 weeks, and exposure was dose proportional over the range of 3–9 mg/day. Once-daily cariprazine was generally well tolerated in adult patients with schizophrenia. PMID:26834462

  11. The Pharmacokinetic/Pharmacodynamic Pipeline: Translating Anticancer Drug Pharmacology to the Clinic

    National Research Council Canada - National Science Library

    Zhou, Qingyu; Gallo, James M

    2011-01-01

    Progress in an understanding of the genetic basis of cancer coupled to molecular pharmacology of potential new anticancer drugs calls for new approaches that are able to address key issues in the drug...

  12. [Nursing care for patients undergoing pharmacological stress echocardiography: implications for clinical practice].

    Science.gov (United States)

    de Goes, Marta Georgina Oliveira; Lautert, Liana; Lucena, Amália Fátima

    2012-06-01

    The study aim was both to identify signs and symptoms previous to and during the pharmacological stress echocardiography test and to describe the nurse's role and nursing care principles for this exam. This is a descriptive study, carried out in cardiac care unit in a University Hospital in Porto Alegre, RS. Two hundred forty-six records of patients submitted to stress echocardiography were retrospectively reviewed, according to four different pharmacological schedules. The statistical comparison showed that signs and symptoms were related to the type of drug used during the exam, namely: typical angina, precordial ache, tiredness, headache and premature complexes. These results enabled a better understanding of pharmacological stress echocardiography and the instrumentalization of nurses in order to plan individualized and qualified nursing care assistance. Aside from helping develop nursing practices for the pharmacological stress echocardiography test this knowledge could also be used by nurses who carry out their activities in institutions that use this diagnostic method.

  13. 77 FR 74670 - Draft Guidance for Industry on Enrichment Strategies for Clinical Trials to Support Approval of...

    Science.gov (United States)

    2012-12-17

    ... Clinical Trials to Support Approval of Human Drugs and Biological Products; Availability AGENCY: Food and... the availability of a draft guidance for industry entitled ``Enrichment Strategies for Clinical Trials... provide guidance to industry on enrichment strategies that can be used in clinical trials intended...

  14. Pharmacological versus microvascular decompression approaches for the treatment of trigeminal neuralgia: clinical outcomes and direct costs

    Directory of Open Access Journals (Sweden)

    Almeida A

    2011-08-01

    therapies, while after MDV surgery several patients showed important side effects. Data reinforce that, (1 TN patients should be carefully evaluated before choosing therapy for pain control, (2 different pharmacological approaches are available to initiate pain control at low costs, and (3 criteria for surgical interventions should be clearly defined due to important side effects, with the initial higher costs being strongly reduced with time.Keywords: trigeminal neuralgia, carbamazepine, gabapentin associated with ropivacaine, microvascular decompression, clinical outcomes, direct costs 

  15. Acetylsalicylic acid (ASA) - How much, how often, and when? A clinical-pharmacological perspective.

    Science.gov (United States)

    Loew, Dieter; Belz, Gustav G

    2016-08-01

    The dose of acetylsalicylic acid (ASA) commonly used in the prevention and treatment of arteriosclerotic angiopathies is equal to or less than 100 mg daily. This choice of dose is predominantly based on molecular-pharmacological findings showing an inhibition in synthesis of the prothrombotic thromboxane (TXB2) and an irreversible inhibition in blood platelet aggregation. However, an analysis of ASA dose-effect relationships for doses of 50 - 500 mg (PO and IV) shows that doses of ASA up to 100 mg daily produce only a small or moderate inhibition in collagen/epinephrine-induced platelet aggregation and have no significant effect on the important platelet factors, PF3 and PF4. Doses of ASA 300 - 500 mg, on the other hand, inhibit platelet aggregation almost completely and, in addition, produce a 50 - 70% inhibition in PF3 and PF4 lasting at least 24 hours. There is also evidence that doses of ASA above 100 mg daily markedly inhibit thromboxane synthesis for up to 24 hours and that doses of 500 mg daily produce a clinically relevant inhibition in platelet adhesion to vessel walls for up 72 hours and prevent procoagulatory shape changes for up to 12 hours. These findings suggest that a dose of ≥ 300 mg at intervals of 2 - 3 days would be more appropriate for primary and secondary prophylaxis of arteriosclerotic angiopathies and that the benefit-risk ratio would be greater because of the increased availability of mucoprotective prostaglandins, PGI2 (prostacyclin) and the gastroprotective, PGE2. Our viewpoint, predominantly based on findings with biomarkers, could serve as a basis for further randomized controlled studies.

  16. AMCP Partnership Forum: Enabling the Exchange of Clinical and Economic Information Pre-FDA Approval.

    Science.gov (United States)

    2017-01-01

    Current federal laws and FDA regulations have significantly restricted the sharing of clinical and health economic information on biopharmaceuticals that have yet to receive FDA approval. Over the past several years, organizations that make health care coverage decisions, including those that set copayments, premiums, and formulary placement, have expressed a need for receiving this information before approval, as long as appropriate safeguards exist to prevent this information from reaching unintended entities. Population health decision makers have indicated that waiting until FDA approval is often too late for the critical planning, budgeting, and forecasting associated with health benefit design, especially given the recent influx of high-cost medications and scrutiny for better evaluation and preparation. Recognizing that securities laws restrict the disclosure of nonpublic information and may need to be amended, permissible early dissemination would allow population health decision makers to incorporate clinical and economic information for pipeline drugs or expanded indications into financial forecasting for the following year's plan. Access to this information is needed 12-18 months before FDA approval when organizations are deciding on terms of coverage and budgetary assumptions for state health insurance rate filings, Medicare and Medicaid bids, contracts with health care purchasers, and other financial arrangements. The need for exchange of clinical economic information before FDA approval was first introduced at a previous Academy of Managed Care (AMCP) forum in March 2016, which addressed section 114 of the Food and Drug Administration Modernization Act and the communication of such information after FDA approval. To address preapproval information specifically, AMCP convened a Partnership Forum on September 13-14, 2016. This forum included a diverse group of stakeholders representing managed care, the biopharmaceutical industry, providers, patients

  17. The use of functional neuroimaging to evaluate psychological and other non-pharmacological treatments for clinical pain

    OpenAIRE

    Jensen, Karin B.; Berna, Chantal; Loggia, Marco L.; Wasan, Ajay; Edwards, Robert R; Randy L Gollub

    2012-01-01

    A large number of studies have provided evidence for the efficacy of psychological and other non-pharmacological interventions in the treatment of chronic pain. While these methods are increasingly used to treat pain, remarkably few studies focused on the exploration of their neural correlates. The aim of this article was to review the findings from neuroimaging studies that evaluated the neural response to distraction-based techniques, cognitive behavioral therapy (CBT), clinical hypnosis, m...

  18. Thiopurine treatment in inflammatory bowel disease: clinical pharmacology and implication of pharmacogenetically guided dosing.

    Science.gov (United States)

    Teml, Alexander; Schaeffeler, Elke; Herrlinger, Klaus R; Klotz, Ulrich; Schwab, Matthias

    2007-01-01

    This review summarises clinical pharmacological aspects of thiopurines in the treatment of chronic inflammatory bowel disease (IBD). Current knowledge of pharmacogenetically guided dosing is discussed for individualisation of thiopurine therapy, particularly to avoid severe adverse effects. Both azathioprine and mercaptopurine are pro-drugs that undergo extensive metabolism. The catabolic enzyme thiopurine S-methyltransferase (TPMT) is polymorphically expressed, and currently 23 genetic variants have been described. On the basis of an excellent phenotype-genotype correlation for TPMT, genotyping has become a safe and reliable tool for determination of a patient's individual phenotype. Thiopurine-related adverse drug reactions are frequent, ranging from 5% up to 40%, in both a dose-dependent and -independent manner. IBD patients with low TPMT activity are at high risk of developing severe haematotoxicity if pharmacogenetically guided dosing is not performed. Based on several cost-benefit analyses, assessment of TPMT activity is recommended prior to thiopurine therapy in patients with IBD. The underlying mechanisms of azathioprine/mercaptopurine-related hepatotoxicity, pancreatitis and azathioprine intolerance are still unknown. Although the therapeutic response appears to be related to 6-thioguanine nucleotide (6-TGN) concentrations above a threshold of 230-260 pmol per 8 x 10(8) red blood cells, at present therapeutic drug monitoring of 6-TGN can be recommended only to estimate patients' compliance.Drug-drug interactions between azathioprine/mercaptopurine and aminosalicylates, diuretics, NSAIDs, warfarin and infliximab are discussed. The concomitant use of allopurinol without dosage adjustment of azathioprine/mercaptopurine leads to clinically relevant severe haematotoxicity due to elevated thiopurine levels. Several studies indicate that thiopurine therapy in IBD during pregnancy is safe. Thus, azathioprine/mercaptopurine should not be withdrawn in strictly

  19. Alirocumab for hyperlipidemia: ODYSSEY Phase III clinical trial results and US FDA approval indications.

    Science.gov (United States)

    Roth, Eli M

    2016-03-01

    A new class of lipid-lowering drugs, inhibitors of PCSK9 has been generating impressive clinical trial data over the last several years, and alirocumab (Praluent) has become the first to be approved by the US FDA. Alirocumab has been shown to lower low density lipoprotein cholesterol by 45-62% with a safety profile generally comparable to placebo. Alirocumab is a monoclonal antibody to PCSK9 administered subcutaneously and has been evaluated in 16 Phase III clinical trials, the majority of which have been enrolled or completed. This article will be a review of the available Phase III safety and efficacy data of the ODYSSEY studies including a brief description of each of the 16 studies.

  20. Recent developments in the clinical pharmacology of rolapitant: subanalyses in specific populations

    Directory of Open Access Journals (Sweden)

    Rapoport BL

    2017-09-01

    Full Text Available Bernardo Leon Rapoport,1 Matti Aapro,2 Martin R Chasen,3 Karin Jordan,4 Rudolph M Navari,5 Ian Schnadig,6 Lee Schwartzberg7 1The Medical Oncology Centre of Rosebank, Johannesburg, South Africa; 2Breast Center, Genolier Cancer Center, Genolier, Switzerland; 3Palliative Care, William Osler Health Services, Brampton, ON, Canada; 4Department of Medicine V, University of Heidelberg, Heidelberg, Germany; 5Division of Hematology Oncology, University of Alabama School of Medicine, Birmingham, AL, USA; 6Compass Oncology, US Oncology Research, Tualatin, OR, USA; 7West Clinic, Memphis, TN, USA Abstract: Knowledge of the involvement of the neurokinin substance P in emesis has led to the development of the neurokinin-1 receptor antagonists (NK-1 RAs for control of chemotherapy-induced nausea and vomiting (CINV, in combination with serotonin type 3 receptor antagonists and corticosteroids. The NK-1 RA rolapitant, recently approved in oral formulation, has nanomolar affinity for the NK-1 receptor, as do the other commercially available NK-1 RAs, aprepitant and netupitant. Rolapitant is rapidly absorbed and has a long half-life in comparison to aprepitant and netupitant. All three NK-1 RAs undergo metabolism by cytochrome P450 (CYP 3A4, necessitating caution with the concomitant use of CYP3A4 inhibitors, but in contrast to aprepitant and netupitant, rolapitant does not inhibit or induce CYP3A4. However, rolapitant is a moderate inhibitor of CYP2D6, and concomitant use with CYP2D6 substrates with narrow therapeutic indices should be avoided. Aprepitant, netupitant, and rolapitant have all demonstrated efficacy in the control of delayed CINV in patients receiving moderately and highly emetogenic chemotherapy in randomized controlled trials, including over multiple cycles of chemotherapy. We reviewed recent post hoc analyses of clinical trial data demonstrating that rolapitant is efficacious in the control of CINV in patient populations with specific tumor types

  1. Clinical pharmacology of indomethacin in preterm infants: implications in patent ductus arteriosus closure.

    Science.gov (United States)

    Pacifici, Gian Maria

    2013-10-01

    Indomethacin is a non-steroidal anti-inflammatory drug that is a potent inhibitor of prostaglandin E(2) synthesis. After birth, the ductus arteriosus closes spontaneously within 2-4 days in term infants. The major factor closing the ductus arteriosus is the tension of oxygen, which increases significantly after birth. Prostaglandin E(2) has the opposite effect to that of oxygen; it relaxes smooth muscle and tends to inhibit the closure of the ductus arteriosus. In preterm infants with respiratory distress syndrome, the ductus arteriosus fails to close (patent ductus arteriosus [PDA]) because the concentration of prostaglandin E2 is relatively high. PDA occurs in more than 70 % of neonates weighing less than 1,500 g at birth. The aim of this article was to review the published data on the clinical pharmacology of indomethacin in preterm infants in order to provide a critical analysis of the literature and a useful tool for physicians. The bibliographic search was performed electronically using the PubMed and EMBASE databases as search engines and February 2012 was the cutoff point. A remarkable interindividual variability was observed for the half-life (t(½)), clearance (CL), and volume of distribution (V(d)) of indomethacin. Prophylactic indomethacin consists of a continuous infusion of low levels of indomethacin and may be useful in preterm infants. Extremely preterm infants are less likely to respond to indomethacin. Infants with a postnatal age of 2 months do not respond to treatment with indomethacin. Indomethacin has several adverse effects, the most common of which is renal failure. An increase in serum creatinine of ≥0.5 % mg/dL after indomethacin was observed in about 10-15 % of the patients and creatinine returns to a normal level about 1 week after cessation of therapy. Indomethacin should be administered intravenously by syringe pump for at least 30 min to minimize adverse effects on cerebral, gastrointestinal, and renal blood flow velocities. A

  2. Ethics approval in applications for open-access clinical trial data: An analysis of researcher statements to clinicalstudydatarequest.com.

    Science.gov (United States)

    So, Derek; Knoppers, Bartha M

    2017-01-01

    Although there are a number of online platforms for patient-level clinical trial data sharing from industry sponsors, they are not very harmonized regarding the role of local ethics approval in the research proposal review process. The first and largest of these platforms is ClinicalStudyDataRequest.com (CSDR), which includes over three thousand trials from thirteen sponsors including GlaxoSmithKline, Novartis, Roche, Sanofi, and Bayer. CSDR asks applicants to state whether they have received ethics approval for their research proposal, but in most cases does not require that they submit evidence of approval. However, the website does require that applicants without ethical approval state the reason it was not required. In order to examine the perspectives of researchers on this topic, we coded every response to that question received by CSDR between June 2014 and February 2017. Of 111 applicants who stated they were exempt from ethics approval, 63% mentioned de-identification, 57% mentioned the use of existing data, 33% referred to local or jurisdictional regulations, and 20% referred to the approvals obtained by the original study. We conclude by examining the experience of CSDR within the broader context of the access mechanisms and policies currently being used by other data sharing platforms, and discuss how our findings might be used to help clinical trial data providers design clear and informative access documents.

  3. Blended learning for reinforcing dental pharmacology in the clinical years: A qualitative analysis.

    Science.gov (United States)

    Eachempati, Prashanti; Kiran Kumar, K S; Sumanth, K N

    2016-10-01

    Blended learning has become the method of choice in educational institutions because of its systematic integration of traditional classroom teaching and online components. This study aims to analyze student's reflection regarding blended learning in dental pharmacology. A cross-sectional study was conducted in Faculty of Dentistry, Melaka-Manipal Medical College among 3(rd) and 4(th) year BDS students. A total of 145 dental students, who consented, participate in the study. Students were divided into 14 groups. Nine online sessions followed by nine face-to-face discussions were held. Each session addressed topics related to oral lesions and orofacial pain with pharmacological applications. After each week, students were asked to reflect on blended learning. On completion of 9 weeks, reflections were collected and analyzed. Qualitative analysis was done using thematic analysis model suggested by Braun and Clarke. The four main themes were identified, namely, merits of blended learning, skill in writing prescription for oral diseases, dosages of drugs, and identification of strengths and weakness. In general, the participants had a positive feedback regarding blended learning. Students felt more confident in drug selection and prescription writing. They could recollect the doses better after the online and face-to-face sessions. Most interestingly, the students reflected that they are able to identify their strength and weakness after the blended learning sessions. Blended learning module was successfully implemented for reinforcing dental pharmacology. The results obtained in this study enable us to plan future comparative studies to know the effectiveness of blended learning in dental pharmacology.

  4. PRESENTING CLINICAL-PHARMACOLOGY AND THERAPEUTICS - A PROBLEM-BASED APPROACH FOR CHOOSING AND PRESCRIBING DRUGS

    NARCIS (Netherlands)

    DEVRIES, TPGM

    1993-01-01

    As a guide to the rational choice and prescribing of drugs a normative (ideal) problem-solving model has been developed. This model combines medical problem solving and decision analysis, practical medical aspects, and pharmacological facts and basic principles. It consists of a set of actions or st

  5. Feedback in clinical education, part II: Approved clinical instructor and student perceptions of and influences on feedback.

    Science.gov (United States)

    Nottingham, Sara; Henning, Jolene

    2014-01-01

    Approved Clinical Instructors (ACIs; now known as preceptors) are expected to provide feedback to athletic training students (ATSs) during clinical education experiences. Researchers in other fields have found that clinical instructors and students often have different perceptions of actual and ideal feedback and that several factors may influence the feedback exchanges between instructors and students. However, understanding of these issues in athletic training education is minimal. To investigate the current characteristics and perceptions of and the influences on feedback exchanges between ATSs and ACIs. Qualitative study. One entry-level master's degree program accredited by the Commission on Accreditation of Athletic Training Education. Four ACIs and 4 second-year ATSs. Individual, semistructured interviews were conducted with participants and integrated with field notes and observations for analysis. We used the constant comparative approach to inductively analyze data and develop codes and categories. Member checking, triangulation, and peer debriefing were used to promote trustworthiness of the study. Participants described that feedback plays an important role in clinical education and has several purposes related to improving performance. The ACIs and ATSs also discussed several preferred characteristics of feedback. Participants identified 4 main influences on their feedback exchanges, including the ACI, the ATS, personalities, and the learning environment. The ACIs and ATSs had similar perceptions of ideal feedback in addition to the actual feedback that was provided during their clinical education experiences. Most of the preferences for feedback were aligned with recommendations in the literature, suggesting that existing research findings are applicable to athletic training clinical education. Several factors influenced the feedback exchanges between ACIs and ATSs, which clinical education coordinators should consider when selecting clinical sites

  6. Establishing a clinical pharmacology fellowship program for physicians, pharmacists, and pharmacologists: a newly accredited interdisciplinary training program at the Ohio State University

    Directory of Open Access Journals (Sweden)

    Kitzmiller JP

    2014-06-01

    Full Text Available Joseph P Kitzmiller,1,4 Mitch A Phelps,2 Marjorie V Neidecker,3 Glen Apseloff41Center for Pharmacogenomics, Colleges of Medicine and of Engineering, The Ohio State University Medical Center, 2Colleges of Pharmacy and Medicine, Pharmacoanalytic Shared Resources Laboratory, The Ohio State University, 3Colleges of Medicine, Nursing, and Pharmacy, The Ohio State University, 4Department of Pharmacology, The Ohio State University College of Medicine, Columbus, OH, USAAbstract: Studying the effect of drugs on humans, clinical pharmacologists play an essential role in many academic medical and research teams, within the pharmaceutical industry and as members of government regulatory entities. Clinical pharmacology fellowship training programs should be multidisciplinary and adaptable, and should combine didactics, applied learning, independent study, and one-on-one instruction. This article describes a recently developed 2 year clinical pharmacology fellowship program – one of only nine accredited by the American Board of Clinical Pharmacology – that is an integrative, multi faceted, adaptable method for training physicians, pharmacists, and scientists for leadership roles in the pharmaceutical industry, in academia, or with regulatory or accreditation agencies. The purpose of this article is to provide information for academic clinicians and researchers interested in designing a similar program, for professionals in the field of clinical pharmacology who are already affiliated with a fellowship program and may benefit from supplemental information, and for clinical researchers interested in clinical pharmacology who may not be aware that such training opportunities exist. This article provides the details of a recently accredited program, including design, implementation, accreditation, trainee success, and future directions.Keywords: clinical pharmacology education, clinical pharmacology fellowship

  7. Reducing medication errors and increasing patient safety: case studies in clinical pharmacology.

    Science.gov (United States)

    Benjamin, David M

    2003-07-01

    Today, reducing medication errors and improving patient safety have become common topics of discussion for the president of the United States, federal and state legislators, the insurance industry, pharmaceutical companies, health care professionals, and patients. But this is not news to clinical pharmacologists. Improving the judicious use of medications and minimizing adverse drug reactions have always been key areas of research and study for those working in clinical pharmacology. However, added to the older terms of adverse drug reactions and rational therapeutics, the now politically correct expression of medication error has emerged. Focusing on the word error has drawn attention to "prevention" and what can be done to minimize mistakes and improve patient safety. Webster's New Collegiate Dictionary has several definitions of error, but the one that seems to be most appropriate in the context of medication errors is "an act that through ingnorance, deficiency, or accident departs from or fails to achieve what should be done." What should be done is generally known as "the five rights": the right drug, right dose, right route, right time, and right patient. One can make an error of omission (failure to act correctly) or an error of commission (acted incorrectly). This article now summarizes what is currently known about medication errors and translates the information into case studies illustrating common scenarios leading to medication errors. Each case is analyzed to provide insight into how the medication error could have been prevented. "System errors" are described, and the application of failure mode effect analysis (FMEA) is presented to determine the part of the "safety net" that failed. Examples of reengineering the system to make it more "error proof" are presented. An error can be prevented. However, the practice of medicine, pharmacy, and nursing in the hospital setting is very complicated, and so many steps occur from "pen to patient" that there

  8. Pharmacological and clinical evaluation of the antiepileptic drug clobazam%癫痫治疗新药氯巴占的药理与临床评价

    Institute of Scientific and Technical Information of China (English)

    高君伟; 孙搏; 李晓宇; 吴佳琪; 刘皋林

    2013-01-01

    氯巴占为1,5-苯二氮草类药物,具有抗癫痫作用,FDA于2011年10月21日批准其用于难治性癫痫——林-戈综合征(Lennox-Gastaut syndrome)的辅助治疗.本文通过Medline对氯巴占进行文献检索,并对其药理作用、药动学、药物相互作用、临床研究和安全性进行了综述.%Clobazam, a 1 ,5-benzodiazepine, possesses antiepileptic activity. It has been approved by the FDA for treatment of Lennox-Gastaut syndrome, one of the refractory epilepsies, in October 21th, 2011. Literature search was conducted by searching MEDLINE with the key words clobazam. The pharmacology, pharmacokinetics, drug interactions, clinical trials and side effects of clobazam were reviewed in this paper.

  9. Clinical management of multiple sclerosis and neuromyelitis optica with therapeutic monoclonal antibodies: approved therapies and emerging candidates.

    Science.gov (United States)

    Dubey, Divyanshu; Kieseier, Bernd C; Hartung, Hans Peter; Hemmer, Bernhard; Miller-Little, William A; Stuve, Olaf

    2015-01-01

    Therapeutic monoclonal antibodies (mAbs) are a relatively novel class of drugs that has substantially advanced immunotherapy for patients with multiple sclerosis. The advantage of these agents is that they bind specifically and exclusively to predetermined proteins or cells. Natalizumab was the first mAb in neurology to obtain approval. It is also considered one of the most potent options for annualized relapse rate reduction among available therapeutic options. Alemtuzumab is currently also approved in several countries. Several mAbs have been tested in clinical studies in multiple sclerosis. Here, we review the history of drug development of therapeutic mAbs and their classification. Furthermore, we outline the putative mechanisms of action, clinical evidence and safety of approved mAbs and those in different stages of clinical development in multiple sclerosis and neuromyelitis optica.

  10. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands

    DEFF Research Database (Denmark)

    Pertwee, R G; Howlett, A C; Abood, M E

    2010-01-01

    There are at least two types of cannabinoid receptors (CB(1) and CB(2)). Ligands activating these G protein-coupled receptors (GPCRs) include the phytocannabinoid ¿(9)-tetrahydrocannabinol, numerous synthetic compounds, and endogenous compounds known as endocannabinoids. Cannabinoid receptor...... antagonists have also been developed. Some of these ligands activate or block one type of cannabinoid receptor more potently than the other type. This review summarizes current data indicating the extent to which cannabinoid receptor ligands undergo orthosteric or allosteric interactions with non-CB(1), non....../or CB(2) receptors are likely to display significantly different pharmacological profiles. The review also lists some criteria that any novel "CB(3)" cannabinoid receptor or channel should fulfil and concludes that these criteria are not currently met by any non-CB(1), non-CB(2) pharmacological receptor...

  11. Blended learning for reinforcing dental pharmacology in the clinical years: A qualitative analysis

    Science.gov (United States)

    Eachempati, Prashanti; Kiran Kumar, K. S.; Sumanth, K. N.

    2016-01-01

    Objectives: Blended learning has become the method of choice in educational institutions because of its systematic integration of traditional classroom teaching and online components. This study aims to analyze student’s reflection regarding blended learning in dental pharmacology. Subjects and Methods: A cross-sectional study was conducted in Faculty of Dentistry, Melaka-Manipal Medical College among 3rd and 4th year BDS students. A total of 145 dental students, who consented, participate in the study. Students were divided into 14 groups. Nine online sessions followed by nine face-to-face discussions were held. Each session addressed topics related to oral lesions and orofacial pain with pharmacological applications. After each week, students were asked to reflect on blended learning. On completion of 9 weeks, reflections were collected and analyzed. Statistical Analysis: Qualitative analysis was done using thematic analysis model suggested by Braun and Clarke. Results: The four main themes were identified, namely, merits of blended learning, skill in writing prescription for oral diseases, dosages of drugs, and identification of strengths and weakness. In general, the participants had a positive feedback regarding blended learning. Students felt more confident in drug selection and prescription writing. They could recollect the doses better after the online and face-to-face sessions. Most interestingly, the students reflected that they are able to identify their strength and weakness after the blended learning sessions. Conclusions: Blended learning module was successfully implemented for reinforcing dental pharmacology. The results obtained in this study enable us to plan future comparative studies to know the effectiveness of blended learning in dental pharmacology. PMID:28031603

  12. Molecular targets of Chinese herbs: a clinical study of hepatoma based on network pharmacology

    Science.gov (United States)

    Gao, Li; Wang, Xiao-dong; Niu, Yang-yang; Duan, Dan-dan; Yang, Xue; Hao, Jian; Zhu, Cui-hong; Chen, Dan; Wang, Ke-xin; Qin, Xue-mei; Wu, Xiong-zhi

    2016-01-01

    Traditional Chinese medicine (TCM) has been used to treat tumors for years and has been demonstrated to be effective. However, the underlying molecular mechanisms of herbs remain unclear. This study aims to ascertain molecular targets of herbs prolonging survival time of patients with advanced hepatocellular carcinoma (HCC) based on network pharmacology, and to establish a research method for accurate treatment of TCM. The survival benefit of TCM treatment with Chinese herbal medicine (CHM) was proved by Kaplan–Meier method and Cox regression analysis among 288 patients. The correlation between herbs and survival time was performed by bivariate correlation analysis. Network pharmacology method was utilized to construct the active ingredient-target networks of herbs that were responsible for the beneficial effects against HCC. Cox regression analysis showed CHM was an independent favorable prognostic factor. The median survival time was 13 months and the 5-year overall survival rates were 2.61% in the TCM group, while there were 6 months, 0 in the non-TCM group. Correlation analysis demonstrated that 8 herbs closely associated with prognosis. Network pharmacology analysis revealed that the 8 herbs regulated multiple HCC relative genes, among which the genes affected proliferation (KRAS, AKT2, MAPK), metastasis (SRC, MMP), angiogenesis (PTGS2) and apoptosis (CASP3) etc. PMID:27143508

  13. 交叉过敏的临床药学干预%Clinical Pharmacological Intervention on Cross Allergy

    Institute of Scientific and Technical Information of China (English)

    严磊; 寿军; 周权; 王华芬

    2012-01-01

    OBJECTIVE To promote the clinical awareness of cross allergy and prevent the occurrence of medical errors. METHODS Prescribing information on cross allergy in "Contraindications" was derived from a software. Records of drug counseling, cases of medical errors and near misses in an online reporting system were analyzed. Data mining was performed. Clinical pharmacological interventions were conducted and the effects were evaluated. RESULTS Besides 27 kinds of drugs within pharmacologically similar class involving cross allergy, there were seven kinds of drugs with complete different pharmacological effects. Similarity in chemical structures was the main case of cross allergy. Excipients were related with cross allergy. Prescribing information in some drugs had unscientific descriptions on cross allergy associated contraindications, lacking clinical value in guiding safe use of medication. There were difference in descriptions on cross allergy in some drugs within pharmacologically similar clas, and some domestic and imported products. The problem of cross allergy of drugs involving different pharmacological effects was dangerous and not easy to be detected. After pharmacological interventions, awareness was greatly increased and the occurrence rate of medical errors and similar mistake decreased by 97%. CONCLISION Severe potential safety hazard might exist if more attentions are not paid to cross allergy aspect. The comprehensive pharmacological interventions are very effective. Applications of information technology and data maintenance are pivotal for continuous quality improvement in cross allergy aspect.%目的 促进临床医护人员对药物交叉过敏的意识,防范用药失误发生.方法 对药物说明书禁忌症中有关交叉过敏的描述进行信息分析和数据挖掘.对药物咨询、用药失误和近似错误在线呈报系统记录进行分析.实施临床药学综合性干预措施,并评估干预效果.结果 除药理作用相似的27

  14. American Society for Clinical Pharmacology and Therapeutics (ASCPT)-111th annual meeting. 17-20 March 2010, Atlanta, GA, USA.

    Science.gov (United States)

    Veryard, Claire

    2010-05-01

    The 111th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, held in Atlanta, included topics covering disclosures of new data in the field of pharmacokinetics and drug interactions. This conference report highlights selected presentations on pharmacokinetic studies of several investigational drugs, including evatanepag (Pfizer Inc), AEG-33773 (Aegera Therapeutics Inc), JNJ-16269110 (Johnson & Johnson Pharmaceutical Research & Development LLC), PF-3716539 (ViiV Healthcare), MK-0736 (Merck & Co Inc), a combination of Ginkgo biloba and cilostazol (Renexin SK Chemicals Co Ltd), PP-101 (Pacific Pharmaceuticals Co Ltd), ACT-178882 (Acetlion Ltd/Merck & Co Inc) and edoxaban (Daiichi Sankyo Co Ltd).

  15. Application of a utility analysis to evaluate a novel assessment tool for clinically oriented physiology and pharmacology.

    Science.gov (United States)

    Cramer, Nicholas; Asmar, Abdo; Gorman, Laurel; Gros, Bernard; Harris, David; Howard, Thomas; Hussain, Mujtaba; Salazar, Sergio; Kibble, Jonathan D

    2016-09-01

    Multiple-choice questions are a gold-standard tool in medical school for assessment of knowledge and are the mainstay of licensing examinations. However, multiple-choice questions items can be criticized for lacking the ability to test higher-order learning or integrative thinking across multiple disciplines. Our objective was to develop a novel assessment that would address understanding of pathophysiology and pharmacology, evaluate learning at the levels of application, evaluation and synthesis, and allow students to demonstrate clinical reasoning. The rubric assesses student writeups of clinical case problems. The method is based on the physician's traditional postencounter Subjective, Objective, Assessment and Plan note. Students were required to correctly identify subjective and objective findings in authentic clinical case problems, to ascribe pathophysiological as well as pharmacological mechanisms to these findings, and to justify a list of differential diagnoses. A utility analysis was undertaken to evaluate the new assessment tool by appraising its reliability, validity, feasibility, cost effectiveness, acceptability, and educational impact using a mixed-method approach. The Subjective, Objective, Assessment and Plan assessment tool scored highly in terms of validity and educational impact and had acceptable levels of statistical reliability but was limited in terms of acceptance, feasibility, and cost effectiveness due to high time demands on expert graders and workload concerns from students. We conclude by making suggestions for improving the tool and recommend deployment of the instrument for low-stakes summative assessment or formative assessment.

  16. New advances in pharmacological mechanism of silymarin and re-investigation of its clinical values

    Directory of Open Access Journals (Sweden)

    LI Qingquan

    2015-02-01

    Full Text Available Silymarin is a traditional hepatoprotective herb for the adjuvant therapy of liver diseases, which shows marked pharmacological activities such as antioxidant and anti-inflammatory properties. This paper introduces the action mechanism of silymarin in regulating liver function, ameliorating hepatic fibrosis, protecting pancreatic cells, suppressing the growth of tumor cells, and inhibiting the replication of hepatitis C virus. Silymarin is considered to be a natural medicine with little toxic or side effect at a high dose. It holds promise for anti-tumor, antioxidant, anti-inflammatory, and antiviral application.

  17. Establishing a clinical pharmacology fellowship program for physicians, pharmacists, and pharmacologists: a newly accredited interdisciplinary training program at the Ohio State University

    Science.gov (United States)

    Kitzmiller, Joseph P; Phelps, Mitch A; Neidecker, Marjorie V; Apseloff, Glen

    2014-01-01

    Studying the effect of drugs on humans, clinical pharmacologists play an essential role in many academic medical and research teams, within the pharmaceutical industry and as members of government regulatory entities. Clinical pharmacology fellowship training programs should be multidisciplinary and adaptable, and should combine didactics, applied learning, independent study, and one-on-one instruction. This article describes a recently developed 2 year clinical pharmacology fellowship program – one of only nine accredited by the American Board of Clinical Pharmacology – that is an integrative, multi faceted, adaptable method for training physicians, pharmacists, and scientists for leadership roles in the pharmaceutical industry, in academia, or with regulatory or accreditation agencies. The purpose of this article is to provide information for academic clinicians and researchers interested in designing a similar program, for professionals in the field of clinical pharmacology who are already affiliated with a fellowship program and may benefit from supplemental information, and for clinical researchers interested in clinical pharmacology who may not be aware that such training opportunities exist. This article provides the details of a recently accredited program, including design, implementation, accreditation, trainee success, and future directions. PMID:25018660

  18. Establishing a clinical pharmacology fellowship program for physicians, pharmacists, and pharmacologists: a newly accredited interdisciplinary training program at the Ohio State University.

    Science.gov (United States)

    Kitzmiller, Joseph P; Phelps, Mitch A; Neidecker, Marjorie V; Apseloff, Glen

    2014-01-01

    Studying the effect of drugs on humans, clinical pharmacologists play an essential role in many academic medical and research teams, within the pharmaceutical industry and as members of government regulatory entities. Clinical pharmacology fellowship training programs should be multidisciplinary and adaptable, and should combine didactics, applied learning, independent study, and one-on-one instruction. This article describes a recently developed 2 year clinical pharmacology fellowship program - one of only nine accredited by the American Board of Clinical Pharmacology - that is an integrative, multi faceted, adaptable method for training physicians, pharmacists, and scientists for leadership roles in the pharmaceutical industry, in academia, or with regulatory or accreditation agencies. The purpose of this article is to provide information for academic clinicians and researchers interested in designing a similar program, for professionals in the field of clinical pharmacology who are already affiliated with a fellowship program and may benefit from supplemental information, and for clinical researchers interested in clinical pharmacology who may not be aware that such training opportunities exist. This article provides the details of a recently accredited program, including design, implementation, accreditation, trainee success, and future directions.

  19. The use of functional neuroimaging to evaluate psychological and other non-pharmacological treatments for clinical pain.

    Science.gov (United States)

    Jensen, Karin B; Berna, Chantal; Loggia, Marco L; Wasan, Ajay D; Edwards, Robert R; Gollub, Randy L

    2012-06-29

    A large number of studies have provided evidence for the efficacy of psychological and other non-pharmacological interventions in the treatment of chronic pain. While these methods are increasingly used to treat pain, remarkably few studies focused on the exploration of their neural correlates. The aim of this article was to review the findings from neuroimaging studies that evaluated the neural response to distraction-based techniques, cognitive behavioral therapy (CBT), clinical hypnosis, mental imagery, physical therapy/exercise, biofeedback, and mirror therapy. To date, the results from studies that used neuroimaging to evaluate these methods have not been conclusive and the experimental methods have been suboptimal for assessing clinical pain. Still, several different psychological and non-pharmacological treatment modalities were associated with increased pain-related activations of executive cognitive brain regions, such as the ventral- and dorsolateral prefrontal cortex. There was also evidence for decreased pain-related activations in afferent pain regions and limbic structures. If future studies will address the technical and methodological challenges of today's experiments, neuroimaging might have the potential of segregating the neural mechanisms of different treatment interventions and elucidate predictive and mediating factors for successful treatment outcomes. Evaluations of treatment-related brain changes (functional and structural) might also allow for sub-grouping of patients and help to develop individualized treatments.

  20. The use of functional neuroimaging to evaluate psychological and other non-pharmacological treatments for clinical pain

    Science.gov (United States)

    Jensen, Karin B.; Berna, Chantal; Loggia, Marco L.; Wasan, Ajay; Edwards, Robert R.; Gollub, Randy L.

    2013-01-01

    A large number of studies have provided evidence for the efficacy of psychological and other non-pharmacological interventions in the treatment of chronic pain. While these methods are increasingly used to treat pain, remarkably few studies focused on the exploration of their neural correlates. The aim of this article was to review the findings from neuroimaging studies that evaluated the neural response to distraction-based techniques, cognitive behavioral therapy (CBT), clinical hypnosis, mental imagery, physical therapy/exercise, biofeedback, and mirror therapy. To date, the results from studies that used neuroimaging to evaluate these methods have not been conclusive and the experimental methods have been suboptimal for assessing clinical pain. Still, several different psychological and non-pharmacological treatment modalities were associated with increased painrelated activations of executive cognitive brain regions, such as the ventral- and dorsolateral prefrontal cortex. There was also evidence for decreased pain-related activations in afferent pain regions and limbic structures. If future studies will address the technical and methodological challenges of today’s experiments, neuroimaging might have the potential of segregating the neural mechanisms of different treatment interventions and elucidate predictive and mediating factors for successful treatment outcomes. Evaluations of treatment-related brain changes (functional and structural) might also allow for sub-grouping of patients and help to develop individualized treatments. PMID:22445888

  1. Training pediatric clinical pharmacology and therapeutics specialists of the future: the needs, the reality, and opportunities for international networking.

    Science.gov (United States)

    Gazarian, Madlen

    2009-01-01

    In recent years there has been a rapid and marked increase in global recognition of the need for better medicines for children, with various initiatives being implemented at global and regional levels. These exciting developments are matched by recognition of the need to build greater capacity in the field of pediatric clinical pharmacology and therapeutics to help deliver on the promise of better medicines for children. A range of pediatric medicines researchers, educators, clinical therapeutics practitioners, and experts in drug evaluation, regulation, and broader medicines policy are needed on a larger scale, in both developed and developing world settings. The current and likely future training needs to meet these diverse challenges, the current realities of trying to meet such needs, and the opportunities for international networking to help meet future training needs are discussed from a global perspective.

  2. Identification of selective inhibitors of RET and comparison with current clinical candidates through development and validation of a robust screening cascade [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Amanda J. Watson

    2016-05-01

    Full Text Available RET (REarranged during Transfection is a receptor tyrosine kinase, which plays pivotal roles in regulating cell survival, differentiation, proliferation, migration and chemotaxis. Activation of RET is a mechanism of oncogenesis in medullary thyroid carcinomas where both germline and sporadic activating somatic mutations are prevalent.   At present, there are no known specific RET inhibitors in clinical development, although many potent inhibitors of RET have been opportunistically identified through selectivity profiling of compounds initially designed to target other tyrosine kinases. Vandetanib and cabozantinib, both multi-kinase inhibitors with RET activity, are approved for use in medullary thyroid carcinoma, but additional pharmacological activities, most notably inhibition of vascular endothelial growth factor - VEGFR2 (KDR, lead to dose-limiting toxicity. The recent identification of RET fusions present in ~1% of lung adenocarcinoma patients has renewed interest in the identification and development of more selective RET inhibitors lacking the toxicities associated with the current treatments.   In an earlier publication [Newton et al, 2016; 1] we reported the discovery of a series of 2-substituted phenol quinazolines as potent and selective RET kinase inhibitors. Here we describe the development of the robust screening cascade which allowed the identification and advancement of this chemical series.  Furthermore we have profiled a panel of RET-active clinical compounds both to validate the cascade and to confirm that none display a RET-selective target profile.

  3. An overview of the clinical pharmacology of N-phosphonacetyl-L-aspartate (PALA), a new antimetabolite.

    Science.gov (United States)

    Erlichman, C

    1980-01-01

    N-Phosphonacetyl-L-aspartic acid (PALA) is new synthetic antimetabolite which inhibits de novo pyrimidine biosynthesis. Its significant activity against Lewis lung carcinoma, B16 melanoma, and glioma 26 suggested that it might be useful in the treatment of human solid tumors. Phase I trials revealed that dose-limiting toxicity included skin reactions, diarrhea, and stomatitis. Pharmacologic studies demonstrated rapid renal excretion of more than 70% of the unmetabolized drug in 24 h. Peak plasma levels correlated with dose of PALA administered. Partial responses to PALA were seen in one patient with melanoma, one with chondrosarcoma, and one with colon carcinoma. The potential for PALA's use in combination chemotherapy, particularly with 5-fluorouracil, is discussed.

  4. 护理药理学教学改革探讨%Pharmacological action and clinical

    Institute of Scientific and Technical Information of China (English)

    覃梦岚

    2015-01-01

    Through finding the problems encountered in nursing pharmacology teaching, from rational use of materials, training of teachers team, teaching skills and memory, enrich the teaching means, to achieve the goal of emotion etc. five aspects put forward and to explore the effective methods of teaching reform, provides the reference for other teachers.%文章通过寻找护理药理学教学中遇到的问题,从合理使用教材、培养师资团队、传授技巧记忆、充实教学手段、实现情感目标等5个方面提出和探讨行之有效的教学改革方法,为其他教师提供参考。

  5. Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry, and Clinical Implications.

    Science.gov (United States)

    Pei, Yue; Asif-Malik, Aman; Canales, Juan J

    2016-01-01

    Biogenic amines are a collection of endogenous molecules that play pivotal roles as neurotransmitters and hormones. In addition to the "classical" biogenic amines resulting from decarboxylation of aromatic acids, including dopamine (DA), norepinephrine, epinephrine, serotonin (5-HT), and histamine, other biogenic amines, present at much lower concentrations in the central nervous system (CNS), and hence referred to as "trace" amines (TAs), are now recognized to play significant neurophysiological and behavioral functions. At the turn of the century, the discovery of the trace amine-associated receptor 1 (TAAR1), a phylogenetically conserved G protein-coupled receptor that is responsive to both TAs, such as β-phenylethylamine, octopamine, and tyramine, and structurally-related amphetamines, unveiled mechanisms of action for TAs other than interference with aminergic pathways, laying the foundations for deciphering the functional significance of TAs and its mammalian CNS receptor, TAAR1. Although, its molecular interactions and downstream targets have not been fully elucidated, TAAR1 activation triggers accumulation of intracellular cAMP, modulates PKA and PKC signaling and interferes with the β-arrestin2-dependent pathway via G protein-independent mechanisms. TAAR1 is uniquely positioned to exert direct control over DA and 5-HT neuronal firing and release, which has profound implications for understanding the pathophysiology of, and therefore designing more efficacious therapeutic interventions for, a range of neuropsychiatric disorders that involve aminergic dysregulation, including Parkinson's disease, schizophrenia, mood disorders, and addiction. Indeed, the recent development of novel pharmacological tools targeting TAAR1 has uncovered the remarkable potential of TAAR1-based medications as new generation pharmacotherapies in neuropsychiatry. This review summarizes recent developments in the study of TAs and TAAR1, their intricate neurochemistry and

  6. Additional safety risk to exceptionally approved drugs in Europe?

    Science.gov (United States)

    Arnardottir, Arna H; Haaijer-Ruskamp, Flora M; Straus, Sabine M J; Eichler, Hans-Georg; de Graeff, Pieter A; Mol, Peter G M

    2011-09-01

    Regulatory requirements for new drugs have increased. Special approval procedures with priority assessment are possible for drugs with clear 'unmet medical need'. We question whether these Exceptional Circumstances (EC) or Conditional Approval (CA) procedures have led to a higher probability of serious safety issues. A retrospective cohort study was performed of new drugs approved in Europe between 1999 and 2009. The determinant was EC/CA vs. standard procedure approval. Outcome variables were frequency and timing of a first Direct Healthcare Professional Communication (DHPC). An association between approval procedure and the time from market approval to DHPC was assessed using Kaplan-Meyer survival analysis and Cox-regression to correct for covariates. In total 289 new drugs were approved. Forty-six (16.4%) were approved under EC or CA, of which seven received a DHPC (15%). This was similar to the standard approval drugs (243), of which 33 received one or more DHPC (14%, P= 0.77). The probability of acquiring a DHPC for standard approval drugs vs. EC/CA drugs during 11-year follow-up is 22% (95% CI 14%, 29%) and 26% (95% CI 8%, 44%), respectively (log-rank P= 0.726). This difference remained not significant in the Cox-regression model: hazard ratio 0.94 (95% CI 0.40, 2.20). Only drug type was identified as a confounding covariate. The EC/CA procedure is not associated with a higher probability of DHPCs despite limited clinical development data. These data do not support the view that early drug approval increases the risk of serious safety issues emerging after market approval. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  7. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations.

    Science.gov (United States)

    Mold, Matthew; Shardlow, Emma; Exley, Christopher

    2016-08-12

    Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al(3+) in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

  8. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations

    Science.gov (United States)

    Mold, Matthew; Shardlow, Emma; Exley, Christopher

    2016-08-01

    Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al3+ in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

  9. 抗精神病新药鲁拉西酮的药理与临床研究进展%Progress in pharmacological and clinical studies of antipsychotic drug:lurasidone

    Institute of Scientific and Technical Information of China (English)

    封宇飞

    2011-01-01

    Lurasidone is a novel psychotropic agent with high affinity for dopamine D2 and serotonin 5-HT2A receptors. Lurasidone has received accelerated approval from the FDA for the treatment of schizophrenia. A literature search was conducted using Medline with the key word lurasidone. Its pharmacology, pharmacokinetics and drug interactions, clinical study and safety were reviewed in this paper.%鲁拉西酮是一种新型抗精神病药,对多巴胺D和5-HT受体具有高度的亲和性.FDA批准其用于精神分裂症的治疗.文中通过Medline对鲁拉西酮进行文献检索,并对其药理作用、药动学、药物相互作用、临床研究和安全性进行了综述.

  10. [Clinical-pharmacological aspects to accelerate the development process from the preclinical to the clinical phase/2nd communication: promising strategies].

    Science.gov (United States)

    Kuhlmann, Jochen

    2004-01-01

    To improve the transition from research to development a critical evaluation of the individual project by research and disease area teams is required to include input from pharmacology, toxicology, pharmacokinetics, galenics, clinical pharmacology, clinical as well as regulatory experts and marketing. Decisions on the individual development strategy should be made prior to the start of development and all projects should be reviewed at predefined stages throughout the product development life cycle. This ensures consistency of decision-making not only during the development of individual products but throughout the entire development pipeline. Studies in the exploratory stage of drug development should be designed for decision making in contrast to later clinical trials in the confirmatory stage that require power for proof-of-safety and proof-of-efficacy. The more thorough and profound studies have been carried out during this exploratory stage of drug development, the earlier a decision can be made on the continuation or discontinuation of further development, thus saving development time and money and assessing and considerably reducing the risk for the patients and increasing the success rate of the project in the later confirmatory effectiveness trial with an adequate number of subjects receiving the new therapy under typical conditions of use. Strategies which may be helpful to improve the quality of decisions in drug discovery and drug development are: discovery experiments should be done to critically evaluate the compound, the "killer" experiments should be done as early as possible, continuous effort on preclinical disease models is necessary to improve predictability of efficacy in patients ("humanized" research): genomic technology should be used to identify novel, disease-related targets and to characterise preclinical test systems, improvement of knowledge and experience concerning the relevance of new technologies for the clinical picture, genotyping

  11. 抗惊厥新药依佐加滨的药理与临床评价%Pharmacology and clinical evaluation of a new anticonvulsant, ezogabine

    Institute of Scientific and Technical Information of China (English)

    王来海; 张瑞岭; 张萍

    2012-01-01

    依佐加滨是首个治疗癫痫的神经元钾离子通道开放剂,己于2011年6月13日被美国FDA批准用于成人惊厥部分发作的治疗.其作用机制并未完全阐明,可能是通过稳定神经元钾离子通道使其保持“开放”状态,降低其若奋性而产生抗惊厥作用.其常见的不良反应有眩晕、嗜睡、乏力、意识错乱等.本文对依佐加滨的药理作用、药代动力学、药物相互作用、临床评价和安全性等进行介绍.%Ezogabine is the first neuronal potassium channel opener developed for the treatment of epilepsy. It was approved by the U. S. Food and Drug Administration on June 13, 2011 as an add-on medication to treat seizures associated with epilepsy in adults. The mechanism by which ezogabine exerts its therapeutic effects has not been fully elucidated. The drug may act as an anticonvulsant by reducing excitability through the stabilization of neuronal potassium channels in an "open" state. Studies indicate that ezogabine enhances transmembrane potassium currents mediated by the KCNQ family ion channels. By activating KCNQ channels, ezogabine is thought to stabilize the resting membrane potential and reduce brain excitability. The most common adverse effects were dizziness, drowsiness, fatigue and confusion, etc. The pharmacology, pharmaeokinetics, clinical evaluation, safety and drug interactions of ezogabine were reviewed in this paper.

  12. Pharmacological management of obesity.

    Science.gov (United States)

    Velazquez, Amanda; Apovian, Caroline M

    2017-04-28

    Current management of obesity includes three main arms: behavioral modification, pharmacologic therapy, and bariatric surgery. Decades prior, the only pharmacological agents available to treat obesity were approved only for short-term use (≤ 12 weeks) by the Food and Drug Administration (FDA). However, in the last several years, the FDA has approved several medications for longer term treatment of obesity. This highlights the important progression that we, as a society, better appreciate now the chronicity and complexity of obesity as a disease. Also, availability of more medication options gives healthcare providers more possibilities to consider in the management of obesity. Medications for obesity can be simply categorized as FDA approved short-term use (diethylproprion, phendimetrazine, benzphetamine, and phentermine) and long-term use (orlistat, phentermine/topiramate ER, lorcaserin, naltrexone/bupropion ER and liraglutide). Additionally, type 2 diabetes (T2DM) is commonly seen in patients with obesity and necessitates consideration of pharmacological options that do not hinder patients' weight loss. Finally, weight-centric prescribing is also an important component to pharmacological management of obesity. It warrants that healthcare providers thoroughly review their patients' medication lists to determine if any of these agents could be contributing to weight gain.

  13. Prescribing knowledge in the light of undergraduate clinical pharmacology and therapeutics teaching in India: views of first-year postgraduate students

    Directory of Open Access Journals (Sweden)

    Upadhyaya P

    2012-06-01

    Full Text Available Prerna Upadhyaya,1 Vikas Seth,2 Monika Sharma,1 Mushtaq Ahmed,1 Vijay Vasant Moghe,1 Zafar Yab Khan,1 Vinay Kumar Gupta,1 Shipra Vikram Jain,1 Utkarsh Soni,1 Manohar Bhatia,1 Kumar Abhijit,1 Jaswant Goyal11Department of Pharmacology, Mahatma Gandhi Medical College, Jaipur, 2Department of Pharmacology, Hind Institute of Medical Sciences, Lucknow, IndiaObjectives: The study aimed to review the prescribing knowledge of first-year postgraduate doctors in a medical college in India, using the principles of good prescribing, to suggest strategies to improve rational prescribing, and to recommend what curriculum planners can do to accomplish this objective.Methods: Fifty first-year postgraduate doctors were asked to fill in a structured questionnaire that sought information regarding their undergraduate training in clinical pharmacology and therapeutics, prescribing habits, and commonly consulted drug information sources. Also, the questionnaire assessed any perceived deficiencies in their undergraduate clinical pharmacology teaching and sought feedback regarding improvement in the teaching.Results: Eighty-eight percent of residents said that they were taught prescription writing in undergraduate pharmacology teaching; 48% of residents rated their prescribing knowledge at graduation as average, 28% good, 4% excellent, 14% poor, and 4% very poor; 58% felt that their undergraduate training did not prepare them to prescribe safely, and 62% felt that their training did not prepare them to prescribe rationally. Fifty-eight percent of residents felt that they had some specific problems with writing a prescription during their internship training, while 92% thought that undergraduate teaching should be improved. Their suggestions for improving teaching methods were recorded.Conclusions: This study concludes that efforts are needed to develop a curriculum that encompasses important aspects of clinical pharmacology and therapeutics along with incorporation of

  14. Effect of clinically approved HDAC inhibitors on Plasmodium, Leishmania and Schistosoma parasite growth

    Directory of Open Access Journals (Sweden)

    Ming Jang Chua

    2017-04-01

    Full Text Available Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L. donovani parasites and two for in vivo activity in a mouse malaria model. All four compounds were potent inhibitors of P. knowlesi malaria parasites (IC50 9–370 nM, with belinostat, panobinostat and vorinostat having 8–45 fold selectivity for the parasite over human neonatal foreskin fibroblast (NFF or human embryonic kidney (HEK 293 cells, while romidepsin was not selective. Each of the HDAC inhibitor drugs caused hyperacetylation of P. knowlesi histone H4. None of the drugs was active against Leishmania amastigote or promastigote parasites (IC50 > 20 μM or S. mansoni schistosomula (IC50 > 10 μM, however romidepsin inhibited S. mansoni adult worm parings and egg production (IC50 ∼10 μM. Modest in vivo activity was observed in P. berghei infected mice dosed orally with vorinostat or panobinostat (25 mg/kg twice daily for four days, with a significant reduction in parasitemia observed on days 4–7 and 4–10 after infection (P < 0.05, respectively.

  15. Clinical approved fluorescent dyes coupled to endomicroscopy for in vivo diagnostic of peritoneal carcinomatosis

    Science.gov (United States)

    Abbaci, Muriel; Dartigues, Peggy; Soufan, Ranya; De Leeuw, Frederic; Fabre, Monique; Laplace-Builhé, Corinne

    2015-03-01

    Peritoneal carcinomatosis is metastatic stage aggravating digestive, gynecological or bladder cancer dissemination and the preoperative evaluation of lesions remains difficult. There is therefore a need for minimal invasive innovative techniques to establish a precise preoperative assessment of cancer peritoneal cavity. Probe-based confocal laser endomicroscopy (pCLE) provides dynamic images of the microarchitecture of tissues during an endoscopy. The PERSEE project proposes new developments in robotics and pCLE for the exploration of the peritoneal cavity during laparoscopy. Two fluorescent dyes, Patent blue V and Indocyanine green have been evaluated on human ex vivo samples to improve the contrast of pCLE images. For a future implementation in clinical study, two topically staining protocols operable in vivo have been validated on 70 specimens from 25 patients with a peritoneal carcinomatosis. The specimens were then imaged by pCLE with an optical probe designed for the application. A histo-morphological correlative study was performed on 350 pCLE images and 70 standard histological preparations. All images were interpreted in a random way by two pathologists. Differential histological diagnostics such as normal peritoneum or pseudomyxoma could be recognized on fluorescence images. The statistical analysis of the correlative study is underway. These dyes already approved for human use are interesting for pCLE imaging because some micromorphological criteria look like to conventional histology and are readable by pathologist. Thus pCLE images using both dyes do not require a specific semiology unlike to what is described in the literature, for pCLE associated with fluorescein for the in vivo imaging of pancreatic cysts.

  16. High-resolution label-free vascular imaging using a commercial, clinically approved dermatological OCT scanner

    Science.gov (United States)

    Byers, R. A.; Tozer, G.; Brown, N. J.; Matcher, S. J.

    2016-02-01

    Background and Aim: Recently developed decorrelative techniques such as speckle-variance optical coherence tomography (svOCT) have demonstrated non-invasive depth-resolved imaging of the microcirculation in-vivo. However, bulk tissue motion (BTM) originating from the subject's breathing or heartbeat remains problematic at low imaging speeds, often resulting in full frame decorrelation and a loss of vascular contrast. The aim of this study was to build upon existing svOCT techniques through utilisation of a commercially available, probe-based VivoSight OCT system running at 20 kHz Axial-scan rate. Methods and results: Custom four-dimensional scanning strategies were developed and utilised in order to maximise the interframe correlation during image acquisition. Volumes of structural OCT data were collected from various anatomical regions and processed using the aforementioned svOCT algorithm to reveal angiographic information. Following data collection, three dimensional image registration and novel filtering algorithms were applied to each volume in order to ensure that BTM artefacts were sufficiently suppressed. This enabled accurate visualisation of the microcirculation within the papillary dermis, to a depth of approximately 2mm. Applications of this technique, including quantitative capillary loop density measurement and visualisation of wound healing are demonstrated and enhanced through widefield mosaicing of the svOCT data. Conclusions: Non-invasive microcirculation imaging using an FDA 510(k) approved OCT scanner such as the VivoSight allows direct clinical utilisation of these techniques, in particular for the pathological analysis of skin diseases. This research was supported by BBSRC Doctoral Training Grant: BB/F016840/1. The authors also gratefully acknowledge the use of equipment funded by MRC grant: MR/L012669/1.

  17. Systematic review of clinical trials assessing pharmacological properties of Salvia species on memory, cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Miroddi, Marco; Navarra, Michele; Quattropani, Maria C; Calapai, Fabrizio; Gangemi, Sebastiano; Calapai, Gioacchino

    2014-06-01

    Salvia officinalis L. and Salvia lavandulaefolia L. have a longstanding use as traditional herbal remedies that can enhance memory and improve cognitive functions. Pharmacological actions of S. officinalis and S. lavandulaefolia on healthy subjects and on patients suffering of cognitive decline have been investigated. Aim of this review was to summarize published clinical trials assessing effectiveness and safety of S. officinalis and S. lavandulaefolia in the enhancement of cognitive performance in healthy subjects and neurodegenerative illnesses. Furthermore, to purchase a more complete view on safety of S. officinalis and S. lavandulaefolia, we collected and discussed articles regarding toxicity and adverse reactions. Eight clinical studies investigating on acute effects of S. officinalis on healthy subjects were included in the review. Six studies investigated on the effects of S. officinalis and S. lavandaeluaefolia on cognitive performance in healthy subjects. The two remaining were carried out to study the effects of sage on Azheimer's disease. Our review shows that S. officinalis and S. lavandulaefolia exert beneficial effects by enhancing cognitive performance both in healthy subjects and patients with dementia or cognitive impairment and is safe for this indication. Unfortunately, promising beneficial effects are debased by methodological issues, use of different herbal preparations (extracts, essential oil, use of raw material), lack of details on herbal products used. We believe that sage promising effects need further higher methodological standard clinical trials.

  18. Clinical Characteristics and Pharmacological Treatment of Psychotic Patients Attending the Mental Health Services of the Pediatric Hospital of Cienfuegos

    Directory of Open Access Journals (Sweden)

    Beatriz Sabina Roméu

    2016-06-01

    Full Text Available Background: the mental health services of the Pediatric Hospital of Cienfuegos receive all patients in the province that need to be hospitalized. Among them, children and adolescents functioning at the psychotic level are of great clinical and social importance. Objective: to describe the clinical characteristics and pharmacological treatment of psychotic patients treated in the mental health services. Methods: a case series study of 35 psychotic patients admitted to the mental health unit of the Pediatric Hospital of Cienfuegos was conducted between 2008 and 2012. Demographic variables, in addition to variables related to clinical data and pharmacotherapeutic aspects were analyzed. Results: sixty five point seven percent of patients were adolescents and 77.1% were of urban origin. The most common diagnoses were acute and transient psychotic disorder and schizophrenia. Sixty three percent had a family history of psychiatric disorder. Forty percent were treated with trifluoperazine and an equal percent took haloperidol. Psychotic symptoms were controlled in 58% of patients during the first weeks. Conclusion: white adolescent patients from urban areas with a family history of psychiatric illness predominated. They received regular psychiatric attention and experienced the symptoms for a short time before being treated. The most frequently prescribed medications were typical antipsychotic drugs, which caused adverse reactions in a third of the patients. In the first few weeks, psychotic symptoms were controlled in most patients, although half of them experienced a recurrence of symptoms, which evolved into conditions with worse prognosis.

  19. [Cerebral hemorrhage induced by low-dose streptokinase: a pharmacologic paradox? Report of a clinical case].

    Science.gov (United States)

    Fedeli, F; Skouse, D; Messina, A

    1997-01-01

    A case of an important intracranial hemorrhage after a low dose (approx. 500,000 UI) of streptokinase in a 60 year-old woman suffering from myocardial infarction is presented. Clinical, electrocardiographic, echocardiographic, lab and tomographic findings are described. The authors suggest a pharmacokinetic mechanism which could be responsible of a "paradox effect" (a powerful and dangerous effect of the drug when given in low dose) and they wonder whether in case of allergic reactions should it be better not to stop the infusion of the thrombolytic drug and be more liberal with the "symptomatic" drugs. Tha patient is still alive and the clinical conditions slowly progressing.

  20. Ziprasidone: from pharmacology to the clinical practice. One year of experience.

    Science.gov (United States)

    Baca, E; Azanza, J R; Giner, J; Saiz-Ruiz, J; Vallejo, J; Diez, T; Madrigal, M

    2005-01-01

    More than a year after the marketing of the atypical anti-psychotic ziprasidone, data from research studies and clinical practice have provided a fair amount of useful information for its practical use in the treatment of schizophrenia. Its pharmacodynamical characteristics and the results from clinical trials with a flexible dose seem to justify the need to administer doses in a range higher than what was initially foreseen, with an initial minimum of 120 mg per day and a fast titulation up to 160 mg per day. Such doses make it possible to achieve sufficient plasma concentrations to occupy at least 60 % of the D2 receptors from which the anti-psychotic effect derives. Moreover, its anti-depressive activity and its non-sedative profile have been confirmed, with a favorable effect on attention and other cognitive functions of the patient, according to its high affinity for 5HT1A and D1 receptors and the inhibition of serotonin and noradrenaline re-uptake. Finally, the low affinity of this drug for alpha-adrenergic, histaminergic and muscarinic receptors favors a good tolerability profile, with a neutral effect on weight, and a lack of anti-cholinergic effects. Results from different clinical trials show that the use of doses in the higher range is associated to a faster and more pronounced clinical improvement without adding a higher risk of adverse events.

  1. Simulated drug administration : An emerging tool for teaching clinical pharmacology during anesthesiology training

    NARCIS (Netherlands)

    Struys, M. M. R. F.; De Smet, T.; Mortier, E. P.

    A thorough understanding of the dose-response relationship is required for optimizing the efficacy of anesthetics while minimizing adverse drug effects.(1) Nowadays, except for the inhaled anesthetics (for which end-tidal concentrations can be measured online), most of the drugs used in clinical

  2. Early Clinical Detection of Pharmacologic Response in Insulin Action in a Nondiabetic Insulin-Resistant Population

    Directory of Open Access Journals (Sweden)

    Sudha S. Shankar, MD

    2015-12-01

    Conclusions: Significant changes in insulin action across multiple insulin-sensitive tissues can be detected within 2 weeks of initiation of insulin-sensitizing therapy with pioglitazone in obese patients with nondiabetic insulin resistance. ClinicalTrials.gov identifier: NCT01115712.

  3. Simulated drug administration : An emerging tool for teaching clinical pharmacology during anesthesiology training

    NARCIS (Netherlands)

    Struys, M. M. R. F.; De Smet, T.; Mortier, E. P.

    2008-01-01

    A thorough understanding of the dose-response relationship is required for optimizing the efficacy of anesthetics while minimizing adverse drug effects.(1) Nowadays, except for the inhaled anesthetics (for which end-tidal concentrations can be measured online), most of the drugs used in clinical ane

  4. Pharmacologic management of overactive bladder

    Directory of Open Access Journals (Sweden)

    Sum Lam

    2007-10-01

    Full Text Available Sum Lam1,2, Olga Hilas1,31St. John’s University, College of Pharmacy and Allied Health Professions, Department of Clinical Pharmacy Practice, Queens, New York, USA; 2Division of Geriatric Medicine, Winthrop University Hospital, Mineola, New York, USA; 3Department of Pharmacy, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, New York, USAAbstract: Overactive bladder (OAB is a prevalent and costly condition that can affect any age group. Typical symptoms include urinary urgency, frequency, incontinence and nocturia. OAB occurs as a result of abnormal contractions of the bladder detrusor muscle caused by the stimulation of certain muscarinic receptors. Therefore, antimuscarinic agents have long been considered the mainstay of pharmacologic treatment for OAB. Currently, there are five such agents approved for the management of OAB in the United States: oxybutynin, tolterodine, trospium, solifenacin and darifenacin. This article summarizes the efficacy, contraindications, precautions, dosing and common side effects of these agents. All available clinical trials on trospium, solifenacin and darifenacin were reviewed to determine its place in therapy.Keywords: overactive bladder, urinary incontinence, pharmacologic management, antimuscarinic agents, anticholinergics

  5. Time-Intensity Curves Obtained after Microbubble Injection Can Be Used to Differentiate Responders from Nonresponders among Patients with Clinically Active Crohn Disease after 6 Weeks of Pharmacologic Treatment.

    Science.gov (United States)

    Quaia, Emilio; Sozzi, Michele; Angileri, Roberta; Gennari, Antonio Giulio; Cova, Maria Assunta

    2016-11-01

    Purpose To assess whether contrast material-enhanced ultrasonography (US) can be used to differentiate responders from nonresponders among patients with clinically active Crohn disease after 6 weeks of pharmacologic treatment. Materials and Methods This prospective study was approved by our ethics committee, and written informed consent was obtained from all patients. Fifty consecutive patients (26 men and 24 women; mean age, 34.76 years ± 9) with a proved diagnosis of active Crohn disease who were scheduled to begin therapy with biologics (infliximab or adalimumab) were included, with enrollment from June 1, 2013, to June 1, 2015. In each patient, the terminal ileal loop was imaged with contrast-enhanced US before the beginning and at the end of week 6 of pharmacologic treatment. Time-intensity curves obtained in responders (those with a decrease in the Crohn disease endoscopic index of severity score of 25-44 before treatment to 10-15 after treatment, an inflammatory score Crohn disease activity index score compared with baseline) and nonresponders were compared with Mann-Whitney test. Results Responders (n = 31) and nonresponders (n = 19) differed (P Crohn disease. (©) RSNA, 2016.

  6. The matching quality of experimental and control interventions in blinded pharmacological randomised clinical trials

    DEFF Research Database (Denmark)

    Bello, Segun; Wei, Maoling; Hilden, Jørgen

    2016-01-01

    to systematically identify and analyse studies of matching quality in drug trials. Our primary objective was to assess the proportion of studies that concluded that the matching was inadequate; our secondary objective was to describe mechanisms for inadequate matching. Methods: Systematic review. We searched Pub......Background: Blinding is a pivotal method to avoid bias in randomised clinical trials. In blinded drug trials, experimental and control interventions are often designed to be matched, i.e. to appear indistinguishable. It is unknown how often matching procedures are inadequate, so we decided......Med, Google Scholar and Web of Science Citation Index for studies that assessed whether supposedly indistinguishable interventions (experimental and control) in randomized clinical drug trials could be distinguished based on physical properties (e.g. appearance or smell). Two persons decided on study...

  7. Suprofen: the pharmacology and clinical efficacy of a new non-narcotic peripheral analgesic.

    Science.gov (United States)

    Tolman, E L; Rosenthale, M E; Capetola, R J; McGuire, J L

    1984-08-01

    Suprofen is a potent, peripherally-acting, non-narcotic analgesic agent. The mechanism of action of the compound involves inhibition of prostaglandin biosynthesis and, perhaps, direct antagonism of the peripheral, pain inducing actions of prostaglandins, bradykinin and other pain mediators. Suprofen at a dose of 200 mg appears to be equal or greater in efficacy as an analgesic modality than those of ibuprofen, propoxyphene, naproxen and diflunisal or a combination of 650 mg aspirin plus 60 mg codeine. Its clinical utility has been amply demonstrated in the treatment of a number of types of pain including general and orthopedic surgery, episiotomy, post-partum pain, dysmenorrhea, dental pain and musculoskeletal disorders. Suprofen represents a new class of orally effective nonnarcotic analgesics with potential for effective clinical use in the treatment of pain.

  8. [Ten years experience with the first approved biosimilar recombinant human growth hormone drug in normal clinical practice].

    Science.gov (United States)

    López-Siguero, Juan Pedro; Palla García, Margarida; Martínez Busto, Elena; Rebollo, Francisco José; Pombo, Manuel

    2017-06-28

    Recombinant human growth hormone (rhGH) is the first biosimilar drug approved by the European Medicines Agency in 2006, using the biosimilar registration process. It was authorised for the treatment of growth hormone deficiency, and growth disorders associated with Turner's syndrome, chronic renal failure, Prader-Willi syndrome, and growth disorders in children/adolescents born small for gestational age, and replacement therapy in adults with pronounced growth hormone deficiency. This review is focused on the scientific evidence published about this drug in the last ten years, including the clinical trials on which the approval of the regulatory authority is based, and the most relevant studies evaluating the clinical impact of the drug in clinical practice. The equivalence between biosimilar and original product has been confirmed in the clinical trials published by Romer et al. and López-Siguero et al. Furthermore, studies carried out in real-life conditions confirm its long-term efficacy and safety, as well as the absence of clinical impact by switching treatment from the original to the biosimilar product. The number of patients receiving this medication has continuously increased since its approval. Its equivalence with the original product has been verified. Preliminary data from the post-authorisation PATRO study confirm the efficacy and safety of the biosimilar product in comparison with data from clinical trials. However, final results must be evaluated at the end of the study, which will provide additional information about the long-term efficacy and safety of the biosimilar drug. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  9. Discovery, pharmacology, and clinical profile of omadacycline, a novel aminomethylcycline antibiotic.

    Science.gov (United States)

    Tanaka, S Ken; Steenbergen, Judith; Villano, Stephen

    2016-12-15

    Omadacycline is novel, aminomethyl tetracycline antibiotic being developed for oral and intravenous (IV) administration for the treatment of community-acquired bacterial infections. Omadacycline is characterized by an aminomethyl substituent at the C9 position of the core 6-member ring. Modifications at this position result in an improved spectrum of antimicrobial activity by overcoming resistance known to affect older generation tetracyclines via ribosomal protection proteins and efflux pump mechanisms. In vitro, omadacycline has activity against Gram-positive and Gram-negative aerobes, anaerobes, and atypical pathogens including Legionella and Chlamydia spp. Omadacycline offers once daily oral and IV dosing and a clinical tolerability and safety profile that compares favorably with contemporary antibiotics used across serious community-acquired infections where resistance has rendered many less effective. In studies in patients with complicated skin and skin structure infections, including those with MRSA infections, omadacycline exhibited an efficacy and tolerability profile that was comparable to linezolid. Ongoing and planned clinical studies are evaluating omadacycline as monotherapy for treating serious community-acquired bacterial infections including Acute Bacterial Skin and Skin Structure Infections (ABSSSI) and Community-Acquired Bacterial Pneumonia (CABP). This review provides an overview of the discovery, microbiology, nonclinical data, and available clinical safety and efficacy data for omadacycline, with reference to other contemporary tetracycline-derived antibiotics. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Nosocomial methicillin-resistant staphylococcus aureus (MRSA pneumonia: linezolid or vancomycin? - comparison of pharmacology and clinical efficacy

    Directory of Open Access Journals (Sweden)

    Pletz Mathias W

    2010-11-01

    Full Text Available Abstract The incidence of nosocomial pneumonia involving methicillin-resistant Staphylococcus aureus strains (MRSA is on the rise worldwide. For years, vancomycin has been used as the drug of choice in the treatment of MRSA infections and was recommended as such by clinical guidelines. There is growing evidence that vancomycin, despite low resistance rates is a suboptimal therapeutic option in critically ill patients, particularly in patients with pneumonia. Disadvantages of vancomycin are i slow bactericide action, ii poor penetration into pulmonary tissue, iii the globally slowly increasing vancomycin MICs ("creep" that result in increased clinical failure despite being susceptible according to defined break points and iv nephrotoxicity. In contrast to other novel antibiotics with MRSA activity, Linezolid is currently approved for the treatment of nosocomial pneumonia in the USA and Europe. Several studies have compared vancomycin with linezolid for nosocomial pneumonia with conflicting results. This review compares both substances regarding pharmacodynamics, resistance, safety and clinical efficacy and discusses preliminary data of the ZEPHyR study. This study compared linezolid versus vancomycin in patients with proven MRSA pneumonia and was the largest trial ever conducted in this population.

  11. Principles of safety pharmacology.

    Science.gov (United States)

    Pugsley, M K; Authier, S; Curtis, M J

    2008-08-01

    Safety Pharmacology is a rapidly developing discipline that uses the basic principles of pharmacology in a regulatory-driven process to generate data to inform risk/benefit assessment. The aim of Safety Pharmacology is to characterize the pharmacodynamic/pharmacokinetic (PK/PD) relationship of a drug's adverse effects using continuously evolving methodology. Unlike toxicology, Safety Pharmacology includes within its remit a regulatory requirement to predict the risk of rare lethal events. This gives Safety Pharmacology its unique character. The key issues for Safety Pharmacology are detection of an adverse effect liability, projection of the data into safety margin calculation and finally clinical safety monitoring. This article sets out to explain the drivers for Safety Pharmacology so that the wider pharmacology community is better placed to understand the discipline. It concludes with a summary of principles that may help inform future resolution of unmet needs (especially establishing model validation for accurate risk assessment). Subsequent articles in this issue of the journal address specific aspects of Safety Pharmacology to explore the issues of model choice, the burden of proof and to highlight areas of intensive activity (such as testing for drug-induced rare event liability, and the challenge of testing the safety of so-called biologics (antibodies, gene therapy and so on.).

  12. Exploring pharmacological significance of chalcone scaffold: a review.

    Science.gov (United States)

    Sahu, N K; Balbhadra, S S; Choudhary, J; Kohli, D V

    2012-01-01

    Chalcones (1,3-diaryl-2-propen-1-ones) and their heterocyclic analogues, belong to the flavonoid family, which possess a number of interesting biological properties such as antioxidant, cytotoxic, anticancer, antimicrobial, antiprotozoal, antiulcer, antihistaminic and anti-inflammatory activities. Several pure chalcones have been approved for clinical use or tested in humans. Clinical trials have shown that these compounds reached reasonable plasma concentration and are well-tolerated. For this reason they are an object of continuously growing interest amongst the scientists. However, much of the pharmacological potential of chalcones is still not utilized. The purpose of this review is to provide an overview of the pharmacological activity of naturally occurring and synthetic chalcones. This review highlights more recent pharmacological screening of these compounds, their mechanisms of action and relevant structure-activity relationships.

  13. Epoetin zeta in the management of anemia associated with chronic kidney disease, differential pharmacology and clinical utility

    Directory of Open Access Journals (Sweden)

    Davis-Ajami ML

    2014-04-01

    Full Text Available Mary Lynn Davis-Ajami,1 Jun Wu,2 Katherine Downton,3 Emilie Ludeman,3 Virginia Noxon4 1Organizational Systems and Adult Health, University of Maryland School of Nursing, Baltimore, MD, USA; 2South Carolina College of Pharmacy, University of South Carolina, Greenville, SC, USA; 3Health Sciences and Human Services Library, University of Maryland, Baltimore, MD, USA; 4Department of Clinical Pharmacy and Outcomes Science, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA Abstract: Epoetin zeta was granted marketing authorization in October 2007 by the European Medicines Agency as a recombinant human erythropoietin erythropoiesis-stimulating agent to treat symptomatic anemia of renal origin in adult and pediatric patients on hemodialysis and adults on peritoneal dialysis, as well as for symptomatic renal anemia in adult patients with renal insufficiency not yet on dialysis. Currently, epoetin zeta can be administered either subcutaneously or intravenously to correct for hemoglobin concentrations ≤10 g/dL (6.2 mmol/L or with dose adjustment to maintain hemoglobin levels at desired levels not in excess of 12 g/dL (7.5 mmol/L. This review article focuses on epoetin zeta indications in chronic kidney disease, its use in managing anemia of renal origin, and discusses its pharmacology and clinical utility. Keywords: biosimilar, chronic kidney disease, epoetin alfa, erythropoiesis, renal anemia, Retacrit®

  14. 苯达莫司汀的药理与临床研究%Pharmacological and clinical studies of bendamustine

    Institute of Scientific and Technical Information of China (English)

    陈祥峰; 马俊杰

    2011-01-01

    As a new generation of anti-cancer drugs, bendamustine has an obvious effect on a wide range of cancers. The clinical practice indicated that its monotherapy or combination therapy has a curative effect on nonHodgkin's lymphoma, multiple myeloma, chronic lymphocytic leukemia and breast carcinoma. Besides, bendamustine significantly reduces the relapse rate and mortality with lower adverse reactions. It is safe and worthy of a wide use for cancer patients. This article summarized its pharmacology and the clinical research.%盐酸苯达莫司汀作为新一代抗癌药物,对多种癌症具有明显的治疗作用.临床应用表明,本品单独治疗或联合用药治疗非霍奇金淋巴瘤、多发性骨髓瘤、慢性淋巴细胞白血病和乳腺癌等,疗效确切,明显降低复发率与死亡率,而且不良反应小,安全性高,值得推广应用.文中对其药理作用、临床研究及安全性进行综述.

  15. Trends in Qualifying Biomarkers in Drug Safety. Consensus of the 2011 Meeting of the Spanish Society of Clinical Pharmacology

    Science.gov (United States)

    Agúndez, José A. G.; del Barrio, Jaime; Padró, Teresa; Stephens, Camilla; Farré, Magí; Andrade, Raúl J.; Badimon, Lina; García-Martín, Elena; Vilahur, Gemma; Lucena, M. Isabel

    2012-01-01

    In this paper we discuss the consensus view on the use of qualifying biomarkers in drug safety, raised within the frame of the XXIV meeting of the Spanish Society of Clinical Pharmacology held in Málaga (Spain) in October, 2011. The widespread use of biomarkers as surrogate endpoints is a goal that scientists have long been pursuing. Thirty years ago, when molecular pharmacogenomics evolved, we anticipated that these genetic biomarkers would soon obviate the routine use of drug therapies in a way that patients should adapt to the therapy rather than the opposite. This expected revolution in routine clinical practice never took place as quickly nor with the intensity as initially expected. The concerted action of operating multicenter networks holds great promise for future studies to identify biomarkers related to drug toxicity and to provide better insight into the underlying pathogenesis. Today some pharmacogenomic advances are already widely accepted, but pharmacogenomics still needs further development to elaborate more precise algorithms and many barriers to implementing individualized medicine exist. We briefly discuss our view about these barriers and we provide suggestions and areas of focus to advance in the field. PMID:22294980

  16. Menaquinone-7 as a novel pharmacological therapy in the treatment of rheumatoid arthritis: A clinical study.

    Science.gov (United States)

    Abdel-Rahman, Mahran S; Alkady, Eman A M; Ahmed, Sameh

    2015-08-15

    Menaquinones (MKs) have been reported to induce apoptosis in rheumatoid arthritis (RA) synovial cells. Recently, menaquinone-4 (MK-4) was proven as a new potential agent for the treatment of RA. However, menaquinone-7 (MK-7) has greater bioavailability and efficacy than MK-4 after oral administration. Yet, the therapeutic benefits of MK-7 in the management of patients with RA have never been addressed. This study was designed to clarify the therapeutic role of MK-7 added to normal therapeutic regimen of RA in patients with different stages of the disease with a clinical follow up through a randomized clinical trial. In a cross sectional study, 84 RA patients (24 male, 60 female) (average age=47.2 years) were enrolled in this study. The patients were divided into MK-7 treated group (n=42) and MK-7 naïve group (n=42). MK-7 capsules were administered in a dose of 100µg/day for three months in the first group without changing in other medications. The clinical and biochemical markers on RA patients treated with MK-7 and naïve group were assessed. In MK-7 treated group, serum concentrations of MK-7 were monitored before and after three months of MK-7 administration. In the cross sectional study, a significant decrease in MK-7 treated group for the levels of undercarboxylated osteocalcin (ucOC), erythrocyte sedimentation rate (ESR), disease activity score assessing 28 joints with ESR (DAS28-ESR), C-reactive protein (CRP) and matrix metalloproteinase (MMP-3) was found. In MK-7 treated group, a marked decrease in RA clinical and biochemical markers for moderate and good response compared to non-responders was observed in ucOC, ESR and DAS28-ESR. A marked increase in the levels of MK-7 for the moderate and good responders compared to non-responders was observed. The results suggest that MK-7 improves disease activity in RA patients. Therefore, MK-7 represents a new promising agent for RA in combination therapy with other disease modifying antirheumatic drugs.

  17. Incretin-based therapies– review of the physiology, pharmacology and emerging clinical experience

    DEFF Research Database (Denmark)

    Martin, JH; Deacon, Carolyn F.; Gorrell, MD

    2011-01-01

    primarily in response to oral nutrient ingestion. They have various effects, but those most relevant to metabolic dysfunction include stimulation of insulin and suppression of glucagon secretion, with resultant reduction in fasting and postprandial glucose. Incretin secretion and/or action is impaired......-resistant peptides that bind to and activate the glucagon-like peptide-1 receptor. In this review, we address aspects of incretin biology and pharmacotherapy with a view to highlighting potentially clinically relevant issues and areas of basic research that may impinge on these....

  18. Expert committee to formulate policy and guidelines for approval of new drugs, clinical trials and banning of drugs-comments.

    Science.gov (United States)

    Ghooi, Ravindra B

    2014-07-01

    All is not well with the clinical research industry. Instances of scientific misconduct by investigators, cutting corners by sponsors, irregularities by regulators, have brought a bad name to the industry. These however form a small part of the clinical research done in this country. The US FDA has conducted over 40 audits, and not made any major observations, suggesting that the clinical research in India is by and large above board. Regulators have amended trial rules recently which have cost the industry dear. A committee appointed to formulate the policy and guidelines for approval of new drugs, clinical trials and banning of the drugs has made 25 recommendations of which most are either superfluous or not likely produce the desired effect. Clubbing banning of the drugs with approval of new drugs and clinical trials also does not make sense, since the mechanisms involved are totally different. Barring a few, most recommendations are counterproductive and should be rejected outright. It is time we learnt that appointment of a committee is not the best way to solve a problem.

  19. Paroxysmal Sympathetic Hyperactivity in Pediatric Rehabilitation: Clinical Factors and Acute Pharmacological Management.

    Science.gov (United States)

    Pozzi, Marco; Conti, Valentino; Locatelli, Federica; Galbiati, Sara; Radice, Sonia; Citerio, Giuseppe; Clementi, Emilio; Strazzer, Sandra

    2015-01-01

    Paroxysmal sympathetic hyperactivity (PSH) is widely described as occurring during intensive care, but in a number of patients it may last longer into the rehabilitation phase. Furthermore, drug therapy has been based on isolated observations. In this study, our aims are to describe a group of 26 pediatric rehabilitation patients with PSH and to quantify the effect of several drugs used to suppress PSH episodes. Neurorehabilitation unit of IRCCS Eugenio Medea, Bosisio Parini (LC), Italy. A total of 407 pediatric patients with postacute acquired brain injury, 26 of which had PSH. Retrospective cohort study. Descriptive demographic and clinical data. Odds ratios quantification of the efficacy of drug therapies administered acutely to suppress PSH episodes. PSH was associated with a longer duration of coma and a greater incidence of death. When administered acutely to suppress PSH episodes, the best drugs were clonazepam, hydroxyzine, and delorazepam, while analgesic drugs showed little efficacy. PSH, whether causative or not, is associated with a worse long-term course in rehabilitation. Clinical management of PSH may be helped by a number of acutely administered drug therapies.

  20. Pediatric Clinical Pharmacology of Voriconazole: Role of Pharmacokinetic/Pharmacodynamic Modeling in Pharmacotherapy.

    Science.gov (United States)

    Kadam, Rajendra S; Van Den Anker, Johannes N

    2016-09-01

    Voriconazole is a potent antifungal agent used for the treatment of invasive fungal infections caused by Aspergillus and Candida species in adult and pediatric patients. Voriconazole has a narrow therapeutic index and a large intra- and inter-individual pharmacokinetics (PK) variability. Several factors including non-linear PK, age, body weight, cytochrome P450 2C19 genotype, concomitant drugs, liver function, and food are responsible for the large variability in voriconazole PK. A combination of a narrow therapeutic index with a large PK variability results in treatment failure in many patients at clinically recommended doses. There is an urgent need to establish an optimal dosing regimen for pediatric patients 60 %) treatment failure rates. Therapeutic drug monitoring is commonly used in clinical practice to optimize the voriconazole dosing regimens in pediatric patients, but it is associated with several practical limitations. Implementation of a PK model-guided individualized dose selection will help in reducing the PK variability and will improve therapeutic outcomes. In this review, we have summarized the covariates influencing the PK of voriconazole in adult and pediatric patients, emphasizing that the clearance of voriconazole is significantly different between adult and pediatric patients owing to developmental changes in the major clearance pathways. Moreover, we have provided the limitations of the current dosing regimens and have proposed a new dosing method using a PK model-guided dose individualization of voriconazole in pediatric patients.

  1. Clinical Pharmacology Research Internships at the Interface between Academia and Industry: Students' Perceptions and Scientific Output.

    Science.gov (United States)

    Goulooze, Sebastiaan C; Franson, Kari L; Cohen, Adam F; Rissmann, Robert

    2017-01-08

    The Centre for Human Drug Research (CHDR) is a non-profit clinical research institute at the interface between academia and the pharmaceutical industry. CHDR hosts a research internship programme for undergraduate (bio)medical students. The aim of this study was (i) to investigate the student perceptions of the undergraduate research internship and (ii) to quantify the scientific output related to these internships. We surveyed former interns at the CHDR from the year 2007 to 2014 and quantified their scientific output with a PubMed search. There was a response rate to the survey of 61%, with a good overall rating of the internships. Many students considered their internship at CHDR to be (much) more broad (55%) and with a (much) stricter planning (48%), compared to previous internships at academic research groups. In turn, there were many aspects reported to be similar to academic research internships such as focus on research methodology and 'outcome-drivenness'. Twenty-four per cent of the internships resulted in a co-authorship on papers published in peer-reviewed journals with an average impact factor of 3.3. In conclusion, with appropriate management and supervision, effective research electives are possible in the more commercial environment of a clinical research organization.

  2. The clinical pharmacology of single doses of otilonium bromide in healthy volunteers.

    Science.gov (United States)

    Sutton, J A; Kilminster, S G; Mould, G P

    1997-01-01

    Otilonium is a smooth muscle spasmolytic with greater affinity for receptors in the smooth muscle of distal than proximal gut in rats. This study was the first to compare distal and proximal GI transit effects in human subjects. Using an increasing dose design for the safe exploration of clinical and supraclinical single dose levels, two groups of eight volunteers received either 40, 120 and 200 mg or 80, 160 and 240 mg otilonium. Gastric emptying of 400 ml 10% glucose solution was assessed by epigastric impedance (EI), orocaecal transit time (OCTT) by the lactulose breath-hydrogen method and whole gut transit time (WGTT) by the method of Hinton et al. [1]. Potential anticholinergic effects were assessed via visual accommodation using the RAF rule and saliva flow in response to sucking a sweet. Median WGTT after 120 mg significantly increased by 4.1 h relative to placebo, but at higher doses median changes relative to placebo were not significant due to wide increases in group variance. The EI t50% was delayed by 1.4 min when results from the two highest doses were combined and compared with placebo; this small difference was statistically significant but seems unlikely to achieve physiological or clinical significance. OCTT, visual accommodation and saliva flow were unaltered. Otilonium bromide was well tolerated at all doses, due mainly to low systemic absorption.

  3. Thuja occidentalis (Arbor vitae: A Review of its Pharmaceutical, Pharmacological and Clinical Properties

    Directory of Open Access Journals (Sweden)

    Belal Naser

    2005-01-01

    Full Text Available Arbor vitae (Thuja occidentalis L. is a native European tree widely used in homeopathy and evidence-based phytotherapy. Many reviews and monographs have been published on the herbal substance's description, mode of action and clinical use. However, no comprehensive evidence-based review is available. Therefore, our aim was to search MEDLINE databases and survey manufacturers for further details or unpublished data. This review presents the botany, ethnobotany and phytochemistry, especially the different contents of essential oil (Thujone in relation to different extraction procedures of this medicinal plant. Thuja's antiviral action and immunopharmacological potential, such as stimulatory and co-stimulatory effects on cytokine and antibody production and activation of macrophages and other immunocompetent cells, have been evaluated in numerous in vitro and in vivo investigations. Although no controlled trials have been conducted on Thuja occ alone, many clinical studies have been performed with a herbal medicinal product containing a special extract of Thuja occ and other immunostimulants, demonstrating its therapeutic efficacy and safety in respiratory tract infections.

  4. Effective use of real-life events as tools for teaching-learning clinical pharmacology in a problem-based learning curriculum

    Directory of Open Access Journals (Sweden)

    Henry James

    2015-01-01

    Full Text Available Aim: This paper describes how in a problem-based learning (PBL medical curriculum, having identified the learning outcomes, problems can be developed from real-life events for teaching-learning clinical pharmacology topics for which PBL cases might be inadequate. Such problems can be very interesting and educational. Methodology: Using the story of the development and withdrawal of rofecoxib (Vioxx ® , we developed a problem for undergraduate medical students to address important issues related to clinical pharmacology and therapeutics such as new drug development, preclinical testing, clinical trials, adverse drug reactions, professionalism, and critical appraisal of literature. These topics would otherwise be difficult to address in patient-based problems. Results: The evaluation of the problem based on pooled feedback from 57 tutorial groups, each comprising 8-10 students, collected over 5 years, supported the effectiveness of the problem. Conclusion: A systematic approach described in this paper can be used for the development and validation of educational material for introducing focal topics of pharmacology/clinical pharmacology integrated with other disciplines in innovative medical (and other health profession curricula.

  5. Overview on Pharmacological and Clinical Study of Earthworm%地龙的药理与临床研究概况

    Institute of Scientific and Technical Information of China (English)

    孙姹; 张长林

    2011-01-01

    This article summarizes the pharmacological effect and clinical application of earthworm, in order to provide the reference for the further research and development of earthworm.%为进一步研究和开发地龙,本文对地龙的药理作用及临床研究的进展做一综述.

  6. The matching quality of experimental and control interventions in blinded pharmacological randomised clinical trials

    DEFF Research Database (Denmark)

    Bello, Segun; Wei, Maoling; Hilden, Jørgen

    2016-01-01

    Background: Blinding is a pivotal method to avoid bias in randomised clinical trials. In blinded drug trials, experimental and control interventions are often designed to be matched, i.e. to appear indistinguishable. It is unknown how often matching procedures are inadequate, so we decided...... published before 1977. The studies differed considerably with regard to design, methodology and analysis. Sixteen of the 36 studies (44 %) concluded inadequate matching. When we adapted high or low thresholds for inadequate matching, the number of trials with inadequate matching was reduced to 12 (33...... to systematically identify and analyse studies of matching quality in drug trials. Our primary objective was to assess the proportion of studies that concluded that the matching was inadequate; our secondary objective was to describe mechanisms for inadequate matching. Methods: Systematic review. We searched Pub...

  7. Clinical pharmacology review of opicapone for the treatment of Parkinson's disease.

    Science.gov (United States)

    Fabbri, Margherita; Rosa, Mario M; Ferreira, Joaquim J

    2016-10-01

    Two catechol-O-methyl transferase inhibitors are currently used as add-on therapy to levodopa for the amelioration of end-of-dose motor fluctuations in Parkinson's disease patients: entacapone, which has moderate efficacy and requires multiple dosing, and tolcapone, which has a poor safety profile. Opicapone (OPC) is a novel, long-acting, peripherally selective, once daily, third-generation catechol-O-methyl transferase inhibitor. Two Phase III clinical trials demonstrated OPC efficacy in reducing OFF-time by an average of about 60 min daily compared with placebo, without increasing ON-time with troublesome dyskinesias, with a good drug safety profile. In June 2016, the European Commission granted a marketing authorization valid throughout the European Union for OPC, indicated as adjunctive of levodopa decarboxylase inhibitors in adult patients with Parkinson's disease and end-of-dose motor fluctuations.

  8. Chronic neuropathic facial pain after intense pulsed light hair removal. Clinical features and pharmacological management

    Science.gov (United States)

    Párraga-Manzol, Gabriela; Sánchez-Torres, Alba; Moreno-Arias, Gerardo

    2015-01-01

    Intense Pulsed Light (IPL) photodepilation is usually performed as a hair removal method. The treatment is recommended to be indicated by a physician, depending on each patient and on its characteristics. However, the use of laser devices by medical laypersons is frequent and it can suppose a risk of damage for the patients. Most side effects associated to IPL photodepilation are transient, minimal and disappear without sequelae. However, permanent side effects can occur. Some of the complications are laser related but many of them are caused by an operator error or mismanagement. In this work, we report a clinical case of a patient that developed a chronic neuropathic facial pain following IPL hair removal for unwanted hair in the upper lip. The specific diagnosis was painful post-traumatic trigeminal neuropathy, reference 13.1.2.3 according to the International Headache Society (IHS). Key words:Neuropathic facial pain, photodepilation, intense pulse light. PMID:26535105

  9. Pharmacology and clinical potential of oblimersen sodium in the treatment of chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    O'Brien S

    2012-08-01

    Full Text Available Gautam Borthakur, Susan O'BrienDepartment of Leukemia, MD Anderson Cancer Center, Houston, TX, USAAbstract: Targeted inhibition of the Bcl-2 family of antiapoptotic proteins is expected to improve outcomes in chronic lymphocytic leukemia. Antisense oligonucleotides and small molecule inhibitors (BH3 mimetics are two approaches that have been used to target Bcl-2 proteins. In this review, we summarize the experience with oblimersen sodium, an 18-base oligonucleotide targeting the first six codons of Bcl-2 mRNA, with particular focus on chronic lymphocytic leukemia. Despite evidence of improved outcomes in randomized trials of combination with chemoimmunotherapy, further development of this antisense approach has been slow, likely because of the clinical development of small molecule inhibitors.Keywords: oblimersen, Bcl-2, antisense, chronic lymphocytic leukemia

  10. International Union of Basic and Clinical Pharmacology. XCVI. Pattern recognition receptors in health and disease.

    Science.gov (United States)

    Bryant, Clare E; Orr, Selinda; Ferguson, Brian; Symmons, Martyn F; Boyle, Joseph P; Monie, Tom P

    2015-01-01

    Since the discovery of Toll, in the fruit fly Drosophila melanogaster, as the first described pattern recognition receptor (PRR) in 1996, many families of these receptors have been discovered and characterized. PRRs play critically important roles in pathogen recognition to initiate innate immune responses that ultimately link to the generation of adaptive immunity. Activation of PRRs leads to the induction of immune and inflammatory genes, including proinflammatory cytokines and chemokines. It is increasingly clear that many PRRs are linked to a range of inflammatory, infectious, immune, and chronic degenerative diseases. Several drugs to modulate PRR activity are already in clinical trials and many more are likely to appear in the near future. Here, we review the different families of mammalian PRRs, the ligands they recognize, the mechanisms of activation, their role in disease, and the potential of targeting these proteins to develop the anti-inflammatory therapeutics of the future.

  11. Pharmacology and clinical potential of vortioxetine in the treatment of major depressive disorder

    Directory of Open Access Journals (Sweden)

    Alvarez E

    2014-07-01

    Full Text Available Enric Alvarez,1,2 Victor Perez,4,2 Francesc Artigas3,2 1Department of Psychiatry, Hospital de Sant Pau, Universitat Autonoma de Barcelona, Institut de Recerca Biomedica Sant Pau, Barcelona, Spain; 2Ministry of Science and Innovation, CIBERSAM, Madrid, Spain; 3Institut d’Investigacions Biomediques de Barcelona, CSIC, Barcelona, Spain; 4Institut de Neuropsiquiatria I Adiccions, Universitat Autonoma de Barcelona, Hospital del Mar, Barcelona, Spain Abstract: Vortioxetine is a new multimodal action antidepressant with two types of action: serotonin transporter (SERT blockade and a strong affinity for several serotoninergic receptors. It is an antagonist of the 5-HT3 and 5-HT7 receptors, a partial agonist of 5-HT1B, and an agonist of 5-HT1A. Its combined action on SERT and four subtypes of serotoninergic receptors increases the extracellular concentration of serotonin, dopamine, and noradrenaline. Twelve ­clinical trials have been carried out, nine of which had positive results versus placebo. When active comparators were included in the study design, no significant differences were found except in one study in which the efficacy of vortioxetine was superior to the comparator (agomelatine in depression resistant to selective serotonin reuptake inhibitors (SSRI/serotonin–norepinephrine reuptake inhibitors (SNRI treatment. Tolerability studies indicate that the drug does not cause any important problems on blood tests, vital signs, or on electrocardiography. The lack of weight gain and induction of metabolic syndrome and the lack of significant changes in the QTc are especially important. The incidence rate of sexual dysfunction is low and similar to placebo in various trials. Similarly, cognitive function remains intact with vortioxetine. Keywords: depression, clinical trial, efficacy

  12. Development of innovative teaching materials: clinical pharmacology problem-solving (CPPS) units: comparison with patient-oriented problem-solving units and problem-based learning--a 10-year review.

    Science.gov (United States)

    Lathers, Claire M; Smith, Cedric M

    2002-05-01

    The First Teaching Clinic in Clinical Pharmacology, sponsored by the American College of Clinical Pharmacology in September 1992, was designed for the preparation and development of new clinical pharmacology problem-solving (CPPS) units. CPPS units are case histories that illustrate pertinent principles in clinical pharmacology. Each unit consists of the following sections: introduction, learning objectives, pretest, four clinical pharmacology scenarios, posttest, answers to pre- and posttest questions, and selected references. The clinical pharmacology content of the CPPS units place greater emphasis on clinical information, drug selection, and risk/benefit analyses, and thus they complement the basic pharmacology presented in the patient-oriented problem-solving (POPS) units. In general, the CPPS units are intended for use by students more advanced in clinical pharmacology than first- and second-year medical students. The CPPS unit "Clinical Pharmacology of Antiepileptic Drug Use: Clinical Pearls about the Perils of Patty" was developed for use by third- and fourth-year medical students doing rotations in neurology or clinical pharmacology; advanced pharmacy students; residents in neurology, pediatrics, internal medicine, and family practice; fellows in clinical pharmacology, and those taking the board examination in clinical pharmacology. The CPPS unit titled "Geriatric Clinical Psychopharmacology" was written for third- and fourth-year medical students; residents in psychiatry, family practice, and internal medicine;fellows in clinical pharmacology; and those studying for boards in clinical pharmacology. The CPPS unit "Anisocoria and Glaucoma" was written for more advanced students of clinical pharmacology. The CPPS unit titled "Antiepileptic Drugs" was intended for second-year medical students. The second teaching clinic was held in November 1993 and focused on the development and editing of the CPPS units and their evaluations by faculty and students from

  13. Differential pharmacology and clinical utility of sonidegib in advanced basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Wahid M

    2017-01-01

    Full Text Available Mohd Wahid, Arshad Jawed, Sajad Ahmad Dar, Raju K Mandal, Shafiul Haque Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Kingdom of Saudi Arabia Abstract: Patients suffering from advanced basal cell carcinoma (BCC have very limited treatment options. Sonidegib selectively inhibits the growth of Hedgehog pathway-dependent tumors and can treat locally advanced BCC patients who are not candidates for surgery or radiation therapy. The BOLT clinical trials were conducted to evaluate the efficacy/potency of sonidegib in the treatment of advanced BCC or metastatic BCC. The patients were randomized in 1:2 ratios to receive 200 or 800 mg oral sonidegib daily, stratified by disease, histological subtype and geographical region. The primary efficacy analyses showed that 18 patients in the 200 mg group and 35 patients in the 800 mg group show an objective response (Central Review Committee that corresponds to 43% (95% confidence interval [CI]: 28–59 and 38% (95% CI: 28–48 in their respective categories. Disease control was found in 93% (39 patients and 80% (74 patients of the patients administered 200 and 800 mg sonidegib, respectively. The adverse events were assessed by the Central Review Committee as well as the investigator review team as per the guidelines of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. The most frequently found adverse events reported in BOLT trials were muscle spasms, alopecia, dysgeusia (taste disturbance, nausea, elevated blood creatine kinase and fatigue. Comparatively, the patients administered 200 mg sonidegib showed fewer adverse events than those in the 800 mg sonidegib category. Thus, the benefit of using the 200 mg dose of sonidegib outweighs the associated risks and it can be inferred that it would be judicious to choose doses of lesser strength. Keywords: locally advanced basal cell carcinoma, metastatic basal

  14. A HUMANIZED CLINICALLY CALIBRATED QUANTITATIVE SYSTEMS PHARMACOLOGY MODEL FOR HYPOKINETIC MOTOR SYMPTOMS IN PARKINSON’S DISEASE

    Directory of Open Access Journals (Sweden)

    Hugo eGeerts

    2016-02-01

    Full Text Available The current treatment of Parkinson’s disease with dopamine-centric approaches such as L-DOPA and dopamine agonists, although very succesfull, is in need of alternative treatment strategies, both in terms of disease modification and symptom management. Various non-dopaminergic treatment approaches did not result in a clear clinical benefit, despite showing a clear effect in preclinical animal models. In addition, polypharmacy is common, sometimes leading to unintended effects on non-motor symptoms such as in cognitive and psychiatric domains. To explore novel targets for symptomatic treatment and possible synergistic pharmacodynamic effects between different drugs, we developed a Quantitative Systems Pharmacology (QSP platform of the closed cortico-striatal-thalamic-cortical basal ganglia loop of the dorsal motor circuit. This mechanism-based simulation platform is based on the known neuro-anatomy and neurophysiology of the basal ganglia and explicitly incorporates domain expertise in a formalized way. The calculated beta/gamma power ratio of the local field potential in the subthalamic nucleus correlates well (R2=0.71 with clinically observed extra-pyramidal symptoms triggered by antipsychotics during schizophrenia treatment (43 drug-dose combinations. When incorporating Parkinsonian (PD pathology and reported compensatory changes, the computer model suggests a major increase in b/g ratio (corresponding to bradykinesia and rigidity from a dopamine depletion of 70% onwards. The correlation between the outcome of the QSP model and the reported changes in UPDRS III Motor Part for 22 placebo-normalized drug-dose combinations is R2=0.84. The model also correctly recapitulates the lack of clinical benefit for perampanel, MK-0567 and flupirtine and offers a hypothesis for the translational disconnect. Finally, using human PET imaging studies with placebo response, the computer model predicts well the placebo response for chronic treatment, but not

  15. Pharmacology, toxicology, clinical efficacy, and adverse effects of calcium polycarbophil, an enteral hydrosorptive agent.

    Science.gov (United States)

    Danhof, I E

    1982-01-01

    Calcium polycarbophil is the calcium salt of polyacrylic acid crosslinked with divinyl glycol. It is chemically and physiologically inert. In dilute alkali it possesses marked hydrophilic capacity (60 to 100 times its weight), which is the basis for its therapeutic use. In daily dosages of 4 to 5 g in adults, it appears to be quite safe, is non-toxic, does not interfere with digestion or absorption, and does not cause gastrointestinal irritation. It appears to be effective in the treatment of both constipation and diarrhea due to functional or organic causes. Several days of continuous use are necessary before effectiveness becomes apparent. Clinical studies, of which there are relatively few, range from uncontrolled, unblinded evaluations of an almost anecdotal nature to well controlled, double-blind, crossover studies. Additional carefully controlled studies on dietary influences, exercise, and patient compliance would be helpful. Adverse effects, which are minimal, include epigastric fullness or heaviness, abdominal distention and bloating, and flatulence. As with all bulk-forming agents, calcium polycarbophil should not be used by persons who have stenotic lesions of the gastrointestinal tract.

  16. Risperidone use in a teaching hospital during its first year after market approval: economic and clinical implications.

    Science.gov (United States)

    Carter, C S; Mulsant, B H; Sweet, R A; Maxwell, R A; Coley, K; Ganguli, R; Branch, R

    1995-01-01

    Risperidone, a new antipsychotic drug, was recently approved by the Food and Drug Administration (FDA) on the basis of its having comparable efficacy and less toxicity than haloperidol. In a preliminary study to evaluate the therapeutic efficiency of this drug, we conducted a survey of resperidone utilization, cost, and safety during its first year of availability at an academic psychiatric hospital. Data were obtained from a computerized, centralized medical record system, from an adverse drug reaction monitoring system, and from pharmacy purchasing records. In its first year of availability, risperidone became the second most widely used antipsychotic agent at our institution. Most of this use extended beyond the adult schizophrenia population, for whom pre-marketing safety and efficacy data are available. The direct institutional cost of risperidone treatment exceeded the entire budget for antipsychotic drugs during the year before its release. Results from the adverse drug reaction reporting system did not indicate a strong advantage of risperidone over more established antipsychotic agents with respect to extrapyramidal side effects. Furthermore, the mean dose of risperidone associated with extrapyramidal symptoms was 3.5 mg/day, considerably lower than that suggested by pre-marketing studies in a more select patient group. These results confirm that new pharmacological agents are generally used in much broader patient populations than those for which efficacy and safety have been established prior to FDA approval. This study also raises questions about the therapeutic efficiency of risperidone compared with other antipsychotic drugs. We conclude that systematic studies of outcome, safety, and cost of new pharmaceuticals in naturalistic settings are needed to provide the data necessary to establish local standards of cost-effective care.

  17. Human primary osteoclasts: in vitro generation and applications as pharmacological and clinical assay

    Directory of Open Access Journals (Sweden)

    Zamurovic Natasa

    2004-03-01

    Full Text Available Abstract Osteoclasts are cells of hematopoietic origin with a unique property of dissolving bone; their inhibition is a principle for treatment of diseases of bone loss. Protocols for generation of human osteoclasts in vitro have been described, but they often result in cells of low activity, raising questions on cell phenotype and suitability of such assays for screening of bone resorption inhibitors. Here we describe an optimized protocol for the production of stable amounts of highly active human osteoclasts. Mononuclear cells were isolated from human peripheral blood by density centrifugation, seeded at 600,000 cells per 96-well and cultured for 17 days in α-MEM medium, supplemented with 10% of selected fetal calf serum, 1 μM dexamethasone and a mix of macrophage-colony stimulating factor (M-CSF, 25 ng/ml, receptor activator of NFκB ligand (RANKL, 50 ng/ml, and transforming growth factor-β1 (TGF-β1, 5 ng/ml. Thus, in addition to widely recognized osteoclast-generating factors M-CSF and RANKL, other medium supplements and lengthy culture times were necessary. This assay reliably detected inhibition of osteoclast formation (multinucleated cells positive for tartrate-resistant acid phosphatase and activity (resorbed area and collagen fragments released from bone slices in dose response curves with several classes of bone resorption inhibitors. Therefore, this assay can be applied for monitoring bone-resorbing activity of novel drugs and as an clinical test for determining the capacity of blood cells to generate bone-resorbing osteoclasts. Isolation of large quantities of active human osteoclast mRNA and protein is also made possible by this assay.

  18. Differential pharmacology and clinical utility of sonidegib in advanced basal cell carcinoma

    Science.gov (United States)

    Wahid, Mohd; Jawed, Arshad; Dar, Sajad Ahmad; Mandal, Raju K; Haque, Shafiul

    2017-01-01

    Patients suffering from advanced basal cell carcinoma (BCC) have very limited treatment options. Sonidegib selectively inhibits the growth of Hedgehog pathway-dependent tumors and can treat locally advanced BCC patients who are not candidates for surgery or radiation therapy. The BOLT clinical trials were conducted to evaluate the efficacy/potency of sonidegib in the treatment of advanced BCC or metastatic BCC. The patients were randomized in 1:2 ratios to receive 200 or 800 mg oral sonidegib daily, stratified by disease, histological subtype and geographical region. The primary efficacy analyses showed that 18 patients in the 200 mg group and 35 patients in the 800 mg group show an objective response (Central Review Committee) that corresponds to 43% (95% confidence interval [CI]: 28–59) and 38% (95% CI: 28–48) in their respective categories. Disease control was found in 93% (39 patients) and 80% (74 patients) of the patients administered 200 and 800 mg sonidegib, respectively. The adverse events were assessed by the Central Review Committee as well as the investigator review team as per the guidelines of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. The most frequently found adverse events reported in BOLT trials were muscle spasms, alopecia, dysgeusia (taste disturbance), nausea, elevated blood creatine kinase and fatigue. Comparatively, the patients administered 200 mg sonidegib showed fewer adverse events than those in the 800 mg sonidegib category. Thus, the benefit of using the 200 mg dose of sonidegib outweighs the associated risks and it can be inferred that it would be judicious to choose doses of lesser strength. PMID:28182134

  19. Approval procedures for clinical trials in the field of radiation oncology; Genehmigungsverfahren klinischer Studien im Bereich der Radioonkologie

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Monique; Buettner, Daniel [Deutsches Konsortium fuer Translationale Krebsforschung (DKTK), Dresden (Germany); Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany); Medizinische Fakultaet und Universitaetsklinikum Carl Gustav Carus, Technische Universitaet Dresden, Klinik fuer Strahlentherapie und Radioonkologie und OncoRay - Nationales Zentrum fuer Strahlenforschung in der Onkologie, Dresden (Germany); Habeck, Matthias; Habeck, Uta; Brix, Gunnar [Bundesamt fuer Strahlenschutz (BfS), Fachbereich Strahlenschutz und Gesundheit, Neuherberg (Germany); Krause, Mechthild; Baumann, Michael [Deutsches Konsortium fuer Translationale Krebsforschung (DKTK), Dresden (Germany); Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany); Medizinische Fakultaet und Universitaetsklinikum Carl Gustav Carus, Technische Universitaet Dresden, Klinik fuer Strahlentherapie und Radioonkologie und OncoRay - Nationales Zentrum fuer Strahlenforschung in der Onkologie, Dresden (Germany); Helmholtz-Zentrum Dresden - Rossendorf, Institut fuer Radioonkologie und OncoRay - Nationales Zentrum fuer Strahlenforschung in der Onkologie, Dresden (Germany); Willich, Normann [Universitaetsklinikum Muenster, Klinik fuer Strahlentherapie - Radioonkologie, Muenster (Germany); Wenz, Frederik [Universitaetsmedizin Mannheim, Medizinische Fakultaet Mannheim, Universitaet Heidelberg, Klinik fuer Strahlentherapie und Radioonkologie, Mannheim (Germany); Schmidberger, Heinz [Universitaetsmedizin Mainz, Klinik fuer Radioonkologie und Strahlentherapie, Mainz (Germany); Debus, Juergen [Universitaetsklinikum Heidelberg, Klinik fuer Radioonkologie und Strahlentherapie, Heidelberg (Germany); Noelling, Torsten

    2015-12-15

    Application of ionizing radiation for the purpose of medical research in Germany needs to be approved by the national authority for radiation protection (Bundesamt fuer Strahlenschutz, BfS). For studies in the field of radiation oncology, differentiation between use of radiation for ''medical care (Heilkunde)'' versus ''medical research'' frequently leads to contradictions. The aim of this article is to provide principle investigators, individuals, and institutions involved in the process, as well as institutional review or ethics committees, with the necessary information for this assessment. Information on the legal frame and the approval procedures are also provided. A workshop was co-organized by the German Society for Radiation Oncology (DEGRO), the Working Party for Radiation Oncology (ARO) of the German Cancer Society (DKG), the German Society for Medical Physics (DGMP), and the German Cancer Consortium (DKTK) in October 2013. This paper summarizes the results of the workshop and the follow-up discussions between the organizers and the BfS. Differentiating between ''Heilkunde'' which does not need to be approved by the BfS and ''medical research'' is whether the specific application of radiation (beam quality, dose, schedule, target volume, etc.) is a clinically established and recognized procedure. This must be answered by the qualified physician(s) (''fachkundiger Arzt'' according to German radiation protection law) in charge of the study and the treatments of the patients within the study, taking into consideration of the best available evidence from clinical studies, guidelines and consensus papers. Among the important parameters for assessment are indication, total dose, and fractionation. Radiation treatments applied outside clinical trials do not require approval by the BfS, even if they are applied within a randomized or nonrandomized clinical trial

  20. Systems Pharmacology in Small Molecular Drug Discovery.

    Science.gov (United States)

    Zhou, Wei; Wang, Yonghua; Lu, Aiping; Zhang, Ge

    2016-02-18

    Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity), target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.

  1. Systems Pharmacology in Small Molecular Drug Discovery

    Science.gov (United States)

    Zhou, Wei; Wang, Yonghua; Lu, Aiping; Zhang, Ge

    2016-01-01

    Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity), target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level. PMID:26901192

  2. Systems Pharmacology in Small Molecular Drug Discovery

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    2016-02-01

    Full Text Available Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity, target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.

  3. Progress on pharmacology and clinical research of eribulin mesylate%eribulin mesylate的药理与临床研究

    Institute of Scientific and Technical Information of China (English)

    倪倩; 封宇飞; 傅得兴; 孙春华

    2012-01-01

    By literature review, pharmacology, pharmacokinetics, clinical study, and safety of eribulin mesylate in the treatment of metastatic breast cancer ( MBC) were evaluated in the paper. As a microtuhule inhibitor, eribulin mesylate has a good effect on multiple drug resistance of chemotherapy medicines in patients with MBC. The main adverse drug reaction is neutropenia. Eribulin mesylate could extend overall survival in patients with MBC. However, further studies should be conducted.%通过文献回顾,评价eribulin mesylate治疗转移性乳腺癌中的药理作用、药动学、临床研究和安全性.本品作为微管抑制剂,临床试验结果显示,对化疗药物产生多重耐药性的转移性乳腺癌具有很好的疗效,主要的不良反应为中性粒细胞减少症.本品可延长转移性乳腺癌患者的总存活时间,更多的研究有待进一步的评价.

  4. Amphotericin B and its new formulations: pharmacologic characteristics, clinical efficacy, and tolerability.

    Science.gov (United States)

    Tiphine, M; Letscher-Bru, V; Herbrecht, R

    1999-12-01

    candidiasis. Several comparative studies have confirmed that this formulation has similar or superior efficacy relative to amB in various fungal infections and also in the empirical treatment of febrile neutropenia. Renal and general tolerability is excellent. The optimal dosing remains unclear but is generally between 3 and 5 mg/kg/day. A double-blind trial comparing the tolerance of liposomal amB and ABLC demonstrated that both infusion-related events and nephrotoxicity were significantly lower for liposomal amB. In sum, the new lipid formulations of amB are effective in various invasive fungal infections. The three formulations exhibit reduced nephrotoxicity compared with conventional amB. Large-scale comparative clinical trials may clarify issues of relative efficacy in various forms of mycotic infections.

  5. Three newly approved drugs for chronic lymphocytic leukemia: incorporating ibrutinib, idelalisib, and obinutuzumab into clinical practice.

    Science.gov (United States)

    Sanford, David S; Wierda, William G; Burger, Jan A; Keating, Michael J; O'Brien, Susan M

    2015-07-01

    Three agents have received Food and Drug Administration (FDA) approval for treatment of chronic lymphocytic leukemia (CLL) within the past year. Ibrutinib and idelalisib block B-cell receptor signaling through inhibition of Bruton tyrosine kinase and phosphatidylinositol 3-kinase δ molecules respectively, interfering with several pathways required for leukemia cell survival. Idelalisib has shown efficacy in the relapsed setting and is currently approved by the FDA for use in combination with rituximab. Ibrutinib has been studied in patients with relapsed CLL and as frontline therapy. In the relapsed setting, these agents produce durable remissions, and might be preferable to re-treatment with chemoimmunotherapy for many patients. Ibrutinib is also effective treatment for patients with deletion 17p and is approved by the FDA as frontline therapy in this patient group, although it does not appear to completely abrogate this adverse prognostic factor. These agents have a unique side effect profile and longer follow-up is required to further understand tolerability and rare adverse effects. Obinutuzumab is a type-2 monoclonal anti-CD20 antibody which results in direct and antibody-dependent cell-mediated cytotoxicity of leukemia cells. It is approved by the FDA for use in combination with chlorambucil, and has shown efficacy in the frontline setting in patients unfit for more intensive chemoimmunotherapy. It produces increased response rates and minimal residual disease negativity compared with chlorambucil/rituximab and is associated with an advantage in progression-free survival but not yet overall survival. These agents underscore our advancement in the understanding of the biology of CLL and will improve outcomes for many patients with CLL.

  6. Assessing the potential clinical impact of reciprocal drug approval legislation on access to novel therapeutics in the USA: a cohort study

    Science.gov (United States)

    Larochelle, Matthieu; Downing, Nicholas S; Ross, Joseph S; David, Frank S

    2017-01-01

    Objective To quantify the potential effect of reciprocal approval legislation on access to clinically impactful therapeutics in the USA. Design A cohort study. Setting New therapeutics approved by the Food and Drug Administration (FDA), European Medicines Agency (EMA) and/or Health Canada between 2000 and 2010. Main outcome measures Characteristics of new therapeutics approved by the EMA and/or Health Canada before the FDA, including mechanistic novelty, likely clinical impact, size of the affected population and FDA review outcome. Results From 2001 to 2010, 282 drugs were approved in the USA, Europe or Canada, including 172 (61%) first approved in the USA, 24 (9%) never approved in the USA, and 86 (30%) approved in the USA after Europe and/or Canada. Of the 110 new drugs approved in Europe and/or Canada before the USA, 37 (34%) had a novel mechanisms of action compared with drugs already approved by the FDA, but only 10 (9%) were for conditions lacking alternate available therapies in the USA at the time of ex-US approval—of which the majority (9/10; 90%) were indicated for rare diseases. 12 of the 37 agents with novel mechanisms of action approved first in Europe and/or Canada (32%) had their initial FDA submissions rejected for safety reasons—including 2 drugs that were ultimately withdrawn from the market in Europe due to safety concerns. Conclusions If enacted, reciprocal approval legislation would most likely benefit only a small number of US patients receiving treatment for rare diseases, and the benefit may be somewhat mitigated by an increased exposure to harms. PMID:28179418

  7. In vitro and in vivo clinical pharmacology of dimethyl benzoylphenylurea, a novel oral tubulin-interactive agent.

    Science.gov (United States)

    Rudek, Michelle A; Zhao, Ming; Smith, Nicola F; Robey, Robert W; He, Ping; Hallur, Gurulingappa; Khan, Saeed; Hidalgo, Manuel; Jimeno, Antonio; Colevas, A Dimitrios; Messersmith, Wells A; Wolff, Antonio C; Baker, Sharyn D

    2005-12-01

    Dimethyl benzoylphenylurea (BPU) is a novel tubulin-interactive agent with poor and highly variable oral bioavailability. In a phase I clinical trial of BPU, higher plasma exposure to BPU and metabolites was observed in patients who experienced dose-limiting toxicity. The elucidation of the clinical pharmacology of BPU was sought. BPU, monomethylBPU, and aminoBPU were metabolized by human liver microsomes. Studies with cDNA-expressed human cytochrome P450 enzymes revealed that BPU was metabolized predominantly by CYP3A4 and CYP1A1 but was also a substrate for CYP2C8, CYP2D6, CYP3A5, and CYP3A7. BPU was not a substrate for the efflux transporter ABCG2. Using simultaneous high-performance liquid chromatography/diode array and tandem mass spectrometry detection, we identified six metabolites in human liver microsomes, plasma, or urine: monomethylBPU, aminoBPU, G280, G308, G322, and G373. In patient urine, aminoBPU, G280, G308, and G322 collectively represented BPU dose. G280, G308, G322, and G373 showed minimal cytotoxicity. When BPU was given p.o. to mice in the presence and absence of the CYP3A and ABCG2 inhibitor, ritonavir, there was an increase in BPU plasma exposure and decrease in metabolite exposure but no overall change in cumulative exposure to BPU and the cytotoxic metabolites. Thus, we conclude that (a) CYP3A4 and CYP1A1 are the predominant cytochrome P450 enzymes that catalyze BPU metabolism, (b) BPU is metabolized to two cytotoxic and four noncytotoxic metabolites, and (c) ritonavir inhibits BPU metabolism to improve the systemic exposure to BPU without altering cumulative exposure to BPU and the cytotoxic metabolites.

  8. Pharmacologic Approaches to Weight Management: Recent Gains and Shortfalls in Combating Obesity.

    Science.gov (United States)

    Saunders, Katherine H; Kumar, Rekha B; Igel, Leon I; Aronne, Louis J

    2016-07-01

    Obesity is a growing epidemic in the USA with over one third of adults presently classified as obese. Obesity-related comorbidities include many leading causes of preventable death such as heart disease, stroke, type 2 diabetes, and certain types of cancer. Modest weight loss of 5-10 % of body weight is sufficient to produce clinically relevant improvements in cardiovascular disease risk factors among patients with overweight and obesity. Until recently, there were limited pharmacologic options approved by the Food and Drug Administration to treat obesity. Phentermine/topiramate ER and lorcaserin were approved in 2012, and naltrexone SR/bupropion SR and liraglutide 3.0 mg were approved in 2014. This article reviews recent literature in the field of Obesity Medicine and highlights important findings from clinical trials. Future directions in the pharmacologic management of obesity are presented along with new diabetes medications that promote weight loss and reduce cardiovascular mortality.

  9. Interns' knowledge of clinical pharmacology and therapeutics after undergraduate and on-going internship training in Nigeria: a pilot study

    Science.gov (United States)

    Oshikoya, Kazeem A; Senbanjo, Idowu O; Amole, Olufemi O

    2009-01-01

    Background A sound knowledge of pathophysiology of a disease and clinical pharmacology and therapeutics (CPT) of a drug is required for safe and rational prescribing. The aim of this study was therefore to assess how adequately the undergraduate CPT teaching had prepared interns in Nigeria for safe and rational prescribing and retrospectively, to know how they wanted the undergraduate curriculum to be modified so as to improve appropriate prescribing. The effect of internship training on the prescribing ability of the interns was also sought. Methods A total of 100 interns were randomly selected from the Lagos State University Teaching Hospital (LASUTH), Ikeja; Lagos University Teaching Hospital (LUTH), Idiaraba; General Hospital Lagos (GHL); the EKO Hospital, Ikeja; and Havana Specialist Hospital, Surulere. A structured questionnaire was the instrument of study. The questionnaire sought information about the demographics of the interns, their undergraduate CPT teaching, experience of adverse drug reactions (ADRs) and drug interactions since starting work, confidence in drug usage and, in retrospect; any perceived deficiencies in their undergraduate CPT teaching. Results The response rate was 81%. All the respondents graduated from universities in Nigeria. The ability of the interns to prescribe rationally (66, 81.4%) and safely (47, 58%) was provided by undergraduate CPT teaching. Forty two (51.8%) respondents had problems with prescription writing. The interns would likely prescribe antibiotics (71, 87.6%), nonsteroidal analgesics (66, 81.4%), diuretics (55, 67.9%), sedatives (52, 62.9%), and insulin and oral hypoglycaemics (43, 53%) with confidence and unsupervised. The higher the numbers of clinical rotations done, the more confident were the respondents to prescribe unsupervised (χ2 = 19.98, P < 0.001). Similarly, respondents who had rotated through the four major clinical rotations and at least a special posting (χ2 = 11.57, P < 0.001) or four major

  10. Pharmacological Effects of Mangiferin

    Institute of Scientific and Technical Information of China (English)

    WEI Zhi-quan; DENG Jia-gang; YAN Li

    2011-01-01

    Mango leaves have been widely used in the clinical practice for thousands of years in traditional Chinese medicine.Mangiferin,an effective constituent in the mango leaves,has multiple pharmacological actions involved in some basic pathological processes,such as inflammation,oxidative injury,tumor growth,micro-organism infections,metabolic regulations,and immunological regulations.The pharmacological effects of mangiferin from some published data are reviewed in this article.

  11. Pre-Clinical Studies with D-Penicillamine as a Novel Pharmacological Strategy to Treat Alcoholism: Updated Evidences

    Science.gov (United States)

    Orrico, Alejandro; Martí-Prats, Lucía; Cano-Cebrián, María J.; Granero, Luis; Polache, Ana; Zornoza, Teodoro

    2017-01-01

    Ethanol, as other drugs of abuse, is able to activate the ventral tegmental area dopamine (VTA-DA) neurons leading to positively motivational alcohol-seeking behavior and use, and, ultimately to ethanol addiction. In the last decades, the involvement of brain-derived acetaldehyde (ACD) in the ethanol actions in the mesolimbic pathway has been widely demonstrated. Consistent published results have provided a mechanistic support to the use of ACD inactivating agents to block the motivational and reinforcing properties of ethanol. Hence, in the last years, several pre-clinical studies have been performed in order to analyze the effects of the sequestering ACD agents in the prevention of ethanol relapse-like drinking behavior as well as in chronic alcohol consumption. In this sense, one of the most explored interventions has been the administration of D-Penicillamine (DP). These pre-clinical studies, that we critically summarize in this article, are considered a critical step for the potential development of a novel pharmacotherapeutic strategy for alcohol addiction treatment that could improve the outcomes of current ones. Thus, on one hand, several experimental findings provide the rationale for using DP as a novel therapeutic intervention alone and/or in combination to prevent relapse into alcohol seeking and consumption. On the other hand, its effectiveness in reducing voluntary ethanol consumption in long-term experienced animals still remains unclear. Finally, this drug offers the additional advantage that has already been approved for use in humans, hence it could be easily implemented as a new therapeutic intervention for relapse prevention in alcoholism. PMID:28326026

  12. Pre-Clinical Studies with D-Penicillamine as a Novel Pharmacological Strategy to Treat Alcoholism: Updated Evidences.

    Science.gov (United States)

    Orrico, Alejandro; Martí-Prats, Lucía; Cano-Cebrián, María J; Granero, Luis; Polache, Ana; Zornoza, Teodoro

    2017-01-01

    Ethanol, as other drugs of abuse, is able to activate the ventral tegmental area dopamine (VTA-DA) neurons leading to positively motivational alcohol-seeking behavior and use, and, ultimately to ethanol addiction. In the last decades, the involvement of brain-derived acetaldehyde (ACD) in the ethanol actions in the mesolimbic pathway has been widely demonstrated. Consistent published results have provided a mechanistic support to the use of ACD inactivating agents to block the motivational and reinforcing properties of ethanol. Hence, in the last years, several pre-clinical studies have been performed in order to analyze the effects of the sequestering ACD agents in the prevention of ethanol relapse-like drinking behavior as well as in chronic alcohol consumption. In this sense, one of the most explored interventions has been the administration of D-Penicillamine (DP). These pre-clinical studies, that we critically summarize in this article, are considered a critical step for the potential development of a novel pharmacotherapeutic strategy for alcohol addiction treatment that could improve the outcomes of current ones. Thus, on one hand, several experimental findings provide the rationale for using DP as a novel therapeutic intervention alone and/or in combination to prevent relapse into alcohol seeking and consumption. On the other hand, its effectiveness in reducing voluntary ethanol consumption in long-term experienced animals still remains unclear. Finally, this drug offers the additional advantage that has already been approved for use in humans, hence it could be easily implemented as a new therapeutic intervention for relapse prevention in alcoholism.

  13. Flupirtine : Clinical pharmacology

    Directory of Open Access Journals (Sweden)

    S Harish

    2012-01-01

    Full Text Available Flupirtine is neither an opioid nor a non steroidal anti-inflammatory drug (NSAID producing its analgesic action through blockade of glutamate N-methyl-D-aspartate receptor. It is devoid of adverse effects of routinely used analgesic drugs, but is equally efficacious in reducing pain sensation. It has a distinctive mechanism of action, exerting a dual therapeutic effect with both analgesic and muscle relaxant properties that has utility in the treatment of pain, including that associated with muscle tension.

  14. Clinical pharmacology of levosimendan.

    Science.gov (United States)

    Antila, Saila; Sundberg, Stig; Lehtonen, Lasse A

    2007-01-01

    Levosimendan has been developed for the treatment of decompensated heart failure and is used intravenously when patients with heart failure require immediate initiation of drug therapy. It increases cardiac contractility and induces vasodilatation. The pharmacokinetics of levosimendan are linear at the therapeutic dose range of 0.05-0.2 microg/kg/minute. The short half-life (about 1 hour) of the parent drug, levosimendan, enables fast onset of drug action, although the effects are long-lasting due to the active metabolite OR-1896, which has an elimination half-life of 70-80 hours in patients with heart failure (New York Heart Association functional class III-IV). Although levosimendan is administered intravenously, it is excreted into the small intestine and reduced by intestinal bacteria to an amino phenolpyridazinone metabolite (OR-1855). This metabolite is further metabolised by acetylation to N-acetylated conjugate (OR-1896). The circulating metabolites OR-1855 and OR-1896 are formed slowly, and their maximum concentrations are seen on average 2 days after stopping a 24-hour infusion. The haemodynamic effects after levosimendan seem to be similar between fast and slow acetylators despite the fact that the enzyme N-acetyltransferase-2, which is responsible for the metabolism of OR-1855 to OR-1896, is polymorphically distributed in the population. Levosimendan reduces peripheral vascular resistance and has direct contractility-enhancing effects on the failing left ventricle. It also improves indices of diastolic function and seems to improve the function of stunned myocardium. Despite an improvement in ventricular function, levosimendan does not increase myocardial oxygen uptake significantly. An increase in coronary blood flow and a reduction in coronary vascular resistance have been observed. Levosimendan reduces plasma brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels substantially, and a decrease in plasma endothelin-1 has been observed. Levosimendan also exerts beneficial effects on proinflammatory cytokines and apoptosis mediators. The effects of a 24-hour levosimendan infusion on filling pressure, ventricular function and BNP, as well as NT-proBNP, last for at least 7 days.

  15. Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

    Science.gov (United States)

    Driver, Vickie R; Gould, Lisa J; Dotson, Peggy; Gibbons, Gary W; Li, William W; Ennis, William J; Kirsner, Robert S; Eaglstein, William H; Bolton, Laura L; Carter, Marissa J

    2017-05-01

    Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory

  16. Nonclinical pharmacology and toxicology of the first biosimilar insulin glargine drug product (BASAGLAR(®)/ABASAGLAR(®)) approved in the European Union.

    Science.gov (United States)

    Byrd, Richard A; Owens, Rebecca A; Blackbourne, Jamie L; Coutant, David E; Farmen, Mark W; Michael, M Dodson; Moyers, Julie S; Schultze, A Eric; Sievert, Michael K; Tripathi, Niraj K; Vahle, John L

    2017-08-01

    Basaglar(®)/Abasaglar(®) (Lilly insulin glargine [LY IGlar]) is a long-acting human insulin analogue drug product granted marketing authorisation as a biosimilar to Lantus(®) (Sanofi insulin glargine [SA IGlar]) by the European Medicines Agency. We assessed the similarity of LY IGlar to the reference drug product, European Union-sourced SA IGlar (EU-SA IGlar), using nonclinical in vitro and in vivo studies. No biologically relevant differences were observed for receptor binding affinity at either the insulin or insulin-like growth factor-1 (IGF-1) receptors, or in assays of functional or de novo lipogenic activity. The mitogenic potential of LY IGlar and EU-SA IGlar was similar when tested in both insulin- and IGF-1 receptor dominant cell systems. Repeated subcutaneous daily dosing of rats for 4 weeks with 0, 0.3, 1.0, or 2.0 mg/kg LY IGlar and EU-SA IGlar produced mortalities and clinical signs consistent with severe hypoglycaemia. Glucodynamic profiles of LY IGlar and EU-SA IGlar in satellite animals showed comparable dose-related hypoglycaemia. Severe hypoglycaemia was associated with axonal degeneration of the sciatic nerve; the incidence and severity were low and did not differ between LY IGlar and EU-SA IGlar. These results demonstrated no biologically relevant differences in toxicity between LY IGlar and EU-SA IGlar. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The Methodology of Clinical Studies Used by the FDA for Approval of High-Risk Orthopaedic Devices.

    Science.gov (United States)

    Barker, Jordan P; Simon, Stephen D; Dubin, Jonathan

    2017-05-03

    The purpose of this investigation was to examine the methodology of clinical trials used by the U.S. Food and Drug Administration (FDA) to determine the safety and effectiveness of high-risk orthopaedic devices approved between 2001 and 2015. Utilizing the FDA's online public database, this systematic review audited study design and methodological variables intended to minimize bias and confounding. An additional analysis of blinding as well as the Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR NPT) was applied to the randomized controlled trials (RCTs). Of the 49 studies, 46 (94%) were prospective and 37 (76%) were randomized. Forty-seven (96%) of the studies were controlled in some form. Of 35 studies that reported it, blinding was utilized in 21 (60%), of which 8 (38%) were reported as single-blinded and 13 (62%) were reported as double-blinded. Of the 37 RCTs, outcome assessors were clearly blinded in 6 (16%), whereas 15 (41%) were deemed impossible to blind as implants could be readily discerned on imaging. When the CLEAR NPT was applied to the 37 RCTs, >70% of studies were deemed "unclear" in describing generation of allocation sequences, treatment allocation concealment, and adequate blinding of participants and outcome assessors. This study manifests the highly variable reporting and strength of clinical research methodology accepted by the FDA to approve high-risk orthopaedic devices.

  18. Intern’s knowledge of clinical pharmacology and therapeutics at Puducherry: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Nitya S

    2013-10-01

    Full Text Available Background: Internship is the intermediate period between under-graduation and general practice. The dexterity of health professional relies upon prescribing practices. Clinical pharmacology and therapeutics (CPT is a crucial discipline for interns to acquire safe and rational prescription of drugs. Cultivating sound knowledge about CPT during under graduation is, henceforth, mandatory. Aims and objectives: 1.To assess whether the undergraduate CPT teaching and internship training had prepared interns adequately for safe and rational prescription. 2.To assess the awareness and reporting of adverse drug reaction (ADR. Methods: 110 interns were enrolled after obtaining informed written consent. A structured questionnaire was given to them including basic demographic information, undergraduate CPT teaching, experience of ADR and any deficiency in the under-graduate CPT teaching. Results: Response rate was 91 % in which 53 were males and 47 females. 81 considered themselves aware of CPT. 56% & 57% interns were able to prescribe drug safely and rationally respectively. Without supervision, they were confident to prescribe antacids (93%, vitamins and minerals (90%, NSAIDS (85%, antihistamines (82%, antibiotics (75%, antiemetics (62% and antiasthmatics (52%. Only 22% had reported ADR and opined that it could lead to hospitalization (51%, prolonged hospital stay (33%, morbidity (16% and death (21%. According to interns, the topics where more emphasis needed were ADR, dosage calculation, pediatric and emergency medicine and therapeutic drug monitoring during undergraduate CPT teaching. Conclusion: CPT teaching should be improved at undergraduate level for safe and rational prescribing including ADR monitoring, ADR reporting and dosage calculation. [Int J Basic Clin Pharmacol 2013; 2(5.000: 622-628

  19. Interns' knowledge of clinical pharmacology and therapeutics after undergraduate and on-going internship training in Nigeria: a pilot study

    Directory of Open Access Journals (Sweden)

    Senbanjo Idowu O

    2009-07-01

    Full Text Available Abstract Background A sound knowledge of pathophysiology of a disease and clinical pharmacology and therapeutics (CPT of a drug is required for safe and rational prescribing. The aim of this study was therefore to assess how adequately the undergraduate CPT teaching had prepared interns in Nigeria for safe and rational prescribing and retrospectively, to know how they wanted the undergraduate curriculum to be modified so as to improve appropriate prescribing. The effect of internship training on the prescribing ability of the interns was also sought. Methods A total of 100 interns were randomly selected from the Lagos State University Teaching Hospital (LASUTH, Ikeja; Lagos University Teaching Hospital (LUTH, Idiaraba; General Hospital Lagos (GHL; the EKO Hospital, Ikeja; and Havana Specialist Hospital, Surulere. A structured questionnaire was the instrument of study. The questionnaire sought information about the demographics of the interns, their undergraduate CPT teaching, experience of adverse drug reactions (ADRs and drug interactions since starting work, confidence in drug usage and, in retrospect; any perceived deficiencies in their undergraduate CPT teaching. Results The response rate was 81%. All the respondents graduated from universities in Nigeria. The ability of the interns to prescribe rationally (66, 81.4% and safely (47, 58% was provided by undergraduate CPT teaching. Forty two (51.8% respondents had problems with prescription writing. The interns would likely prescribe antibiotics (71, 87.6%, nonsteroidal analgesics (66, 81.4%, diuretics (55, 67.9%, sedatives (52, 62.9%, and insulin and oral hypoglycaemics (43, 53% with confidence and unsupervised. The higher the numbers of clinical rotations done, the more confident were the respondents to prescribe unsupervised (χ2 = 19.98, P 2 = 11.57, P 2 = 11.25, P Conclusion Undergraduate CPT teaching in Nigeria appears to be deficient. Principles of rational prescribing, drug dose

  20. The pharmacology of neuroplasticity induced by non-invasive brain stimulation: building models for the clinical use of CNS active drugs.

    Science.gov (United States)

    Nitsche, Michael A; Müller-Dahlhaus, Florian; Paulus, Walter; Ziemann, Ulf

    2012-10-01

    The term neuroplasticity encompasses structural and functional modifications of neuronal connectivity. Abnormal neuroplasticity is involved in various neuropsychiatric diseases, such as dystonia, epilepsy, migraine, Alzheimer's disease, fronto-temporal degeneration, schizophrenia, and post cerebral stroke. Drugs affecting neuroplasticity are increasingly used as therapeutics in these conditions. Neuroplasticity was first discovered and explored in animal experimentation. However, non-invasive brain stimulation (NIBS) has enabled researchers recently to induce and study similar processes in the intact human brain. Plasticity induced by NIBS can be modulated by pharmacological interventions, targeting ion channels, or neurotransmitters. Importantly, abnormalities of plasticity as studied by NIBS are directly related to clinical symptoms in neuropsychiatric diseases. Therefore, a core theme of this review is the hypothesis that NIBS-induced plasticity can explore and potentially predict the therapeutic efficacy of CNS-acting drugs in neuropsychiatric diseases. We will (a) review the basics of neuroplasticity, as explored in animal experimentation, and relate these to our knowledge about neuroplasticity induced in humans by NIBS techniques. We will then (b) discuss pharmacological modulation of plasticity in animals and humans. Finally, we will (c) review abnormalities of plasticity in neuropsychiatric diseases, and discuss how the combination of NIBS with pharmacological intervention may improve our understanding of the pathophysiology of abnormal plasticity in these diseases and their purposeful pharmacological treatment.

  1. Clinical Application and Pharmacological Actions of Ligustrazine Chuanxiong%川芎的药理作用及临床应用

    Institute of Scientific and Technical Information of China (English)

    张文海

    2015-01-01

    目的:研究川芎的药理作用及临床应用。方法收集关于川穹药理作用及临床应用的相关文献,对文献进行总结分析。结果川芎具有活血化瘀、镇静镇痛、抑制氧自由基释放等方面的药理作用。结论川芎在治疗呼吸系统疾病、冠心病、心绞痛、肾病综合征等方面具备比较好的临床疗效。%ObjectiveTo study the pharmacological action and clinical application of Ligusticum chuanxiong. Methods colected the relevant literatures on the pharmacological effects and clinical application of Ligusticum chuanxiong dome, to summarize the literature.Results Ligusticum chuanxiong with pharmacological effects of Huoxue Huayu, sedation and analgesia, inhibit the release of oxygen free radicals.Conclusion Ligusticum chuanxiong in the treatment of respiratory system disease, coronary heart disease, angina pectoris, nephrotic syndrome has better clinical efficacy.

  2. Lifestyle-oriented non-pharmacological treatments for fibromyalgia: a clinical overview and applications with home-based technologies

    Science.gov (United States)

    Friedberg, Fred; Williams, David A; Collinge, William

    2012-01-01

    Fibromyalgia (FM) is a persistent and disabling widespread pain condition often accompanied by chronic fatigue, cognitive problems, sleep disturbance, depression, anxiety, and headache. To date, the most thoroughly studied non-pharmacological approaches to managing FM are those with a focus on changing patient activities and beliefs that affect the illness. These interventions are intended to facilitate enduring improvement in pain and functional status. Lifestyle-oriented treatments include patient education, aerobic or other physical exercise, and cognitive-behavioral therapy (CBT). These interventions in FM can be delivered in medical or behavioral health care settings by trained professionals, through patient-oriented treatment manuals, or via remote-access technologies. Non-pharmacological treatments, in particular exercise and CBT, have yielded effect sizes and cost–benefit ratios comparable to medications. This paper describes lifestyle-oriented non-pharmacological treatments for FM and highlights selected literature reviews of these interventions. In addition, behavioral and practical issues are addressed that may affect these non-pharmacological treatments, including patient expectations, participant burden, and treatment availability. Recommendations are made to facilitate these interventions and potentially improve outcomes. In particular, the increasing availability of convenient home-based mobile technologies to deliver these non-pharmacological treatments is described. PMID:23166446

  3. Sumatriptan transdermal iontophoretic patch (NP101-Zelrix™: review of pharmacology, clinical efficacy, and safety in the acute treatment of migraine

    Directory of Open Access Journals (Sweden)

    Vikelis M

    2012-09-01

    Full Text Available Michail Vikelis,1 Dimos D Mitsikostas,2 Alan M Rapoport31Glyfada Headache Center, Glyfada, Greece; 2Neurology Department, Athens Naval Hospital, Athens, Greece; 3The David Geffen School of Medicine at UCLA, Los Angeles, CA, USAAbstract: Migraine is a chronic, painful, and often disabling primary headache disorder, typically presenting with recurrent attacks that may be accompanied by a variety of neurological, gastrointestinal, and autonomic symptoms. Gastrointestinal symptoms in association with migraine including, nausea, vomiting, and gastroparesis, affect a large proportion of migraine sufferers. These symptoms may result in delays or inconsistencies in the absorption of oral treatments. Hence, the necessity for an innovative, non-invasive, parenteral delivery formulation for quick and effective treatment of migraine attacks is evident. Iontophoresis utilizes minimal amounts of electrical potential to support the fast transfer of ionized medication transdermally and into the general circulation. Two pharmacokinetic clinical trials have shown that iontophoretic delivery of sumatriptan through the skin produces quick and reproducible therapeutic plasma concentrations. A randomized, double-blind, multicenter, phase III study demonstrated superior efficacy versus placebo and excellent tolerability, with no triptan-related adverse events. The proportion of patients that were pain-free at 2 h post-treatment was 18% for the sumatriptan patch vs 9% for placebo (P = 0.0092; number needed to treat = 11.1. Upon approval from the Food and Drug Administration and other regulatory authorities, the iontophoretic transdermal delivery of sumatriptan will be a good choice for patients experiencing poor absorption of oral medication often associated with migraine and/or for those with intolerable triptan-related adverse events.Keywords: iontophoretic patch, migraine, migraine treatment, sumatriptan, transdermal patch

  4. Application of a Static Fluorescence-based Cytometer (the CellScan in Basic Cytometric Studies, Clinical Pharmacology, Oncology and Clinical Immunology

    Directory of Open Access Journals (Sweden)

    Michal Harel

    2005-01-01

    Full Text Available The CellScan apparatus is a laser scanning cytometer enabling repetitive fluorescence intensity (FI and polarization (FP measurements in living cells, as a means of monitoring lymphocyte activation. The CellScan may serve as a tool for diagnosis of rheumatoid arthritis (RA and systemic lupus erythematosus (SLE as well as other autoimmune diseases by monitoring FP changes in peripheral blood lymphocytes (PBLs following exposure to autoantigenic stimuli. Changes in FI and FP in atherosclerotic patients' PBLs following exposure to various stimuli have established the role of the immune system in atherosclerotic disease. The CellScan has been evaluated as a diagnostic tool for drug-allergy, based on FP reduction in PBLs following incubation with allergenic drugs. FI and FP changes in cancer cells have been found to be well correlated with the cytotoxic effect of anti-neoplastic drugs. In conclusion, the CellScan has a variety of applications in cell biology, immunology, cancer research and clinical pharmacology.

  5. Healthspan Pharmacology.

    Science.gov (United States)

    Jafari, Mahtab

    2015-12-01

    The main goal of this paper is to present the case for shifting the focus of research on aging and anti-aging from lifespan pharmacology to what I like to call healthspan pharmacology, in which the desired outcome is the extension of healthy years of life rather than lifespan alone. Lifespan could be influenced by both genetic and epigenetic factors, but a long lifespan may not be a good indicator of an optimal healthspan. Without improving healthspan, prolonging longevity would have enormous negative socioeconomic outcomes for humans. Therefore, the goal of aging and anti-aging research should be to add healthy years to life and not merely to increase the chronological age. This article summarizes and compares two categories of pharmacologically induced lifespan extension studies in animal model systems from the last two decades-those reporting the effects of pharmacological interventions on lifespan extension alone versus others that include their effects on both lifespan and healthspan in the analysis. The conclusion is that the extrapolation of pharmacological results from animal studies to humans is likely to be more relevant when both lifespan and healthspan extension properties of pharmacological intervention are taken into account.

  6. Case studies on clinical evaluation of biosimilar monoclonal antibody: scientific considerations for regulatory approval.

    Science.gov (United States)

    Kudrin, Alex; Knezevic, Ivana; Joung, Jeewon; Kang, Hye-Na

    2015-01-01

    The objective of this paper is to provide considerations based on comprehensive case studies important for regulatory evaluation of monoclonal antibodies as similar biotherapeutic products (SBPs) with a special emphasis on clinical aspects. Scientific principles from WHO Guidelines on SBPs were used as a basis for the exercise. Working groups consisted of regulators, manufacturers and academia. The following topics were discussed by the working groups: clinical criteria for biosimilarity, extrapolation approach and the overall regulatory decision making process. In order to determine typical pitfalls in the design of a SBP clinical programme and evaluate the gap of knowledge, amongst different industry and regulatory stakeholders on the appraisal of the data arising from SBP clinical studies, we have presented two fictional but realistic clinical case studies. The first case consists of the fictional development programme for an infliximab SBP candidate. The second case describes clinical studies proposed for a fictional rituximab SBP candidate. In the first scenario a highly similar quality profile has been taken forward into clinical studies whereas there was an important residual difference in functional attributes for the rituximab SBP candidate. These case studies were presented at the WHO implementation workshop for the WHO guidelines on evaluation of similar biotherapeutic products held in Seoul, Republic of Korea, in May 2014. The goal was to illustrate the interpretation of the clinical data arising from studies with SBP candidates and elicit knowledge gaps in clinical assessment. This paper reflects the outcome of the exercise and discussions held in Seoul and offers an analysis of the case studies as a learning opportunity on clinical development and evaluation of SBPs.

  7. Lifestyle-oriented non-pharmacological treatments for fibromyalgia: a clinical overview and applications with home-based technologies

    Directory of Open Access Journals (Sweden)

    Friedberg F

    2012-10-01

    Full Text Available Fred Friedberg,1 David A Williams,2 William Collinge31Department of Psychiatry and Behavioral Science, Stony Brook University, Stony Brook, New York; 2Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, 3Collinge and Associates, Kittery, Maine, USAAbstract: Fibromyalgia (FM is a persistent and disabling widespread pain condition often accompanied by chronic fatigue, cognitive problems, sleep disturbance, depression, anxiety, and headache. To date, the most thoroughly studied non-pharmacological approaches to managing FM are those with a focus on changing patient activities and beliefs that affect the illness. These interventions are intended to facilitate enduring improvement in pain and functional status. Lifestyle-oriented treatments include patient education, aerobic or other physical exercise, and cognitive-behavioral therapy (CBT. These interventions in FM can be delivered in medical or behavioral health care settings by trained professionals, through patient-oriented treatment manuals, or via remote-access technologies. Non-pharmacological treatments, in particular exercise and CBT, have yielded effect sizes and cost–benefit ratios comparable to medications. This paper describes lifestyle-oriented non-pharmacological treatments for FM and highlights selected literature reviews of these interventions. In addition, behavioral and practical issues are addressed that may affect these non-pharmacological treatments, including patient expectations, participant burden, and treatment availability. Recommendations are made to facilitate these interventions and potentially improve outcomes. In particular, the increasing availability of convenient home-based mobile technologies to deliver these non-pharmacological treatments is described.Keywords: cognitive-behavior therapy, exercise, education, mobile technology

  8. ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials.

    Science.gov (United States)

    Schwartz, Lisa M; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A

    2016-09-20

    Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on Drugs@FDA. ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews). 100 parallel-group, randomized trials for new drug approvals (January 2013 to July 2014) with results posted on ClinicalTrials.gov (15 March 2015). 2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths. Most trials were phase 3 (90%), double-blind (92%), and placebo-controlled (73%) and involved 32 drugs from 24 companies. Of 137 primary outcomes identified from ClinicalTrials.gov, 134 (98%) had corresponding data at Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results. Most differences were nominal (that is, relative difference gov, Drugs@FDA mentioned 1061 (55%) and included results data for 367 (19%). Of 96 trials with 1 or more serious adverse events in either source, 14 could be compared and 7 had discordant numbers of persons experiencing the adverse events. Of 62 trials with 1 or more deaths in either source, 25 could be compared and 17 were discordant. Unknown generalizability to uncontrolled or crossover trial results. Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half the secondary outcomes, as well as serious events and deaths, could not be validated because Drugs@FDA includes only "key outcomes" for regulatory decision making and frequently includes only adverse event results aggregated across multiple trials. National Library of Medicine.

  9. Improving data transparency in clinical trials using blockchain smart contracts [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Timothy Nugent

    2016-10-01

    Full Text Available The scientific credibility of findings from clinical trials can be undermined by a range of problems including missing data, endpoint switching, data dredging, and selective publication. Together, these issues have contributed to systematically distorted perceptions regarding the benefits and risks of treatments. While these issues have been well documented and widely discussed within the profession, legislative intervention has seen limited success. Recently, a method was described for using a blockchain to prove the existence of documents describing pre-specified endpoints in clinical trials. Here, we extend the idea by using smart contracts - code, and data, that resides at a specific address in a blockchain, and whose execution is cryptographically validated by the network - to demonstrate how trust in clinical trials can be enforced and data manipulation eliminated. We show that blockchain smart contracts provide a novel technological solution to the data manipulation problem, by acting as trusted administrators and providing an immutable record of trial history.

  10. Pharmacology and clinical evaluation of the new antidepressant drug vilazodone%新型抗抑郁药维拉唑酮的药理与临床评价

    Institute of Scientific and Technical Information of China (English)

    王来海; 张瑞岭; 李焕芬

    2011-01-01

    Vilazodone, a new type of antidepressant, possesses dual mechanism of action. It was approved for the treatment of major depressive disorder by FDA in January 21, 2011. It is a selective serotonin (5-HT) re-uptake inhibitor and a partial 5-HT1A receptor agonist. The most common adverse reactions of vilazodone are diarrhea, nausea, vomiting and insomnia. The pharmacology, pharmacokinetics, clinical evaluation, safety and drug interactions of vilazodone were reviewed in this paper.%维拉唑酮为一种双重作用机制的新型抗抑郁药,即选择性5-羟色胺(5-HT)再摄取抑制剂和5-HT1A受体部分激动剂,2011年1月21日获得美国食品药品管理局(FDA)批准,用于成人重症抑郁症(major depressive disorder,MDD)的治疗.其常见不良反应包括腹泻、恶心、呕吐和失眠.文中对维拉唑酮的药理作用、药动学、临床评价、安全性以及药物相互作用等进行了综述.

  11. Pharmacology and clinical evaluation of anti-allergic drug:rupatadine fumarate%抗变态反应药物富马酸卢帕他定的药理及临床评价

    Institute of Scientific and Technical Information of China (English)

    杨婧芝; 熊玉卿

    2011-01-01

    Rupatadine fumarate is a long-acting dual antagonist for both histamine receptor 1 and platelet-acting factor ( PAF) receptors. It was approved in Spain in 2003 , and has been indicated for the treatment of allergic rhinitis and chronic urticaria. Here, the pharmacology, pharmacokinetics and clinical evaluations were re-, viewed.%富马酸卢帕他定是一种长效血小板活化因子受体及H1受体双重拮抗剂,它通过特异性阻断上述受体而抑制过敏反应,于2003年3月首次在西班牙上市,目前已广泛用于治疗过敏性鼻炎和慢性荨麻疹等过敏性疾病,获得良好的临床疗效.文中就其药理作用、药动学及其临床研究等作一综述.

  12. Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012

    OpenAIRE

    Miller, Jennifer E.; Korn, David; Ross, Joseph S

    2015-01-01

    Objective: To evaluate clinical trial registration, reporting and publication rates for new drugs by: (1) legal requirements and (2) the ethical standard that all human subjects research should be publicly accessible to contribute to generalisable knowledge. Design: Cross-sectional analysis of all clinical trials submitted to the Food and Drug Administration (FDA) for drugs approved in 2012, sponsored by large biopharmaceutical companies. Data sources Information from Drugs@FDA, ClinicalTrial...

  13. Efforts and success world-wide in the field of clinical pharmacology. A personal review on the occasion of Folke Sjöqvist's 80th birthday.

    Science.gov (United States)

    Orme, Michael

    2013-05-01

    In this personal review I describe my early expectations and experiences when I first came to work with Prof. Folke Sjöqvist as a training fellow in the early 1970s. At that time Prof. Sjöqvist and his unit had already earned an international reputation, and in the following decades this success has been magnified many times. Although a description of the research performed by Prof. Sjöqvist during his long career is not the main objective of this article, it is clear that the research carried out in his unit has been instrumental in the development of his international reputation. Over an 18-year period from 1994 onwards, some 272 papers bearing the name of Folke Sjöqvist have been cited over 13,000 times, with an average of over 50 citations per paper. In terms of training clinical pharmacologists from around the world, at the last count 112 individuals from 37 different countries have received a substantial part of their training in his unit. As another measure of his world-wide success, 33 individuals from 18 different countries who received a substantial part of their training in his unit between 1968 and 1996 have gone on to become professors of clinical pharmacology. Prof. Sjöqvist has been requested to consult on various aspects of clinical pharmacology in 15 different countries, from Russia to Spain and from Egypt to Latvia. Here I describe the long-term involvement that Prof. Sjöqvist has had with IUPHAR (now the International Union of Basic and Clinical Pharmacology) and with institutions such as the World Health Organisation (WHO). In particular, I recount his role in the long-term saga involved in updating the original WHO manifesto on clinical pharmacology published in 1970 up to the eventual success of the new manifesto published by WHO in 2012. Finally, I briefly describe the international honours that have been bestowed on Prof. Sjöqvist, including various prizes, designated lectureships and honorary Doctorates (5). Taken together, these

  14. Educational issues in clinical pharmacology: who are our audiences and what are their specialized needs? One specialized need: "understanding the role of veterinary medicine in public health".

    Science.gov (United States)

    Lathers, Claire M

    2002-07-01

    When considering educational issues and the need to update the curriculum for clinical pharmacologists for the new millennium, a number of questions must be raised. Who are our audiences? What are the specialized needs? This educational article identifies the audience, which includes those with diverse degrees such as MDs, PhDs, PharmDs, RNs, DVMs, and other non-MD prescribers working in academia, industry, clinical research organizations, and government in multifaceted disciplines requiring a knowledge base of physiology, pharmacology, biochemistry, anatomy, microbiology, pathology, medicine, and the drug development process of preclinical and clinical studies complete with protocols, pharmacokinetics, and statistics. One specialized current educational issue for clinical pharmacologists to understand is the impact of animal therapeutic and subtherapeutic use of antimicrobials on antibiotic use in human medicine.

  15. Clinical Analysis the Pharmacologic Action of Alprostadil%前列地尔的药理作用临床分析

    Institute of Scientific and Technical Information of China (English)

    赵娟

    2016-01-01

    Alprostadil the common drugs in treatment of chronic disease, there has speciifc function of elderly patient clinical therapy, which is continuously extending the clinial appplication range, has higher value of clinical application. At present, the clinical application study increase gradually about the pharmacologic action of alprostadil. This article analysis the research progress, pharmacologic, application status of alprostadil, aim at provide some reference in alprostadil clinical application.%前列地尔是治疗较多慢性疾病的常用药,其在老年疾病的临床治疗中有特殊的作用,临床应用范围也不断扩大,有较高的临床应用价值。当前,关于前列地尔药理作用及临床应用研究逐渐增多,本文对前列地尔应用现状、药理作用及研究进展进行分析,以期为前列地尔临床应用提供借鉴。

  16. Are erlotinib and gefitinib interchangeable, opposite or complementary for non-small cell lung cancer treatment? Biological, pharmacological and clinical aspects.

    Science.gov (United States)

    Bronte, Giuseppe; Rolfo, Christian; Giovannetti, Elisa; Cicero, Giuseppe; Pauwels, Patrick; Passiglia, Francesco; Castiglia, Marta; Rizzo, Sergio; Vullo, Francesca Lo; Fiorentino, Eugenio; Van Meerbeeck, Jan; Russo, Antonio

    2014-02-01

    Gefitinib and erlotinib are the two anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) approved for treatment of advanced NSCLC patients. These drugs target one of the most important pathways in lung carcinogenesis and are able to exploit the phenomenon of 'oncogene addiction', with different efficacy according to EGFR gene mutational status in tumor samples. Gefitinib has been approved only for EGFR mutation bearing patients regardless the line of treatment, while erlotinib is also indicated in patients without EGFR mutation who undergo second- or third-line treatment. Some studies evaluated the main differences between these drugs both for direct comparison and to improve their sequential use. In particular, toxicity profile resulted partially different, and these observations may be explained by several molecular and pharmacokinetic features. Therefore, this review integrates preclinical data with clinical evidences of TKIs to guide the optimization of currently available treatments in advanced NSCLC patients.

  17. 化瘀通闭丸的药理作用及临床应用%Pharmacological Action and Clinical Application of Huayu Tongbi Pill

    Institute of Scientific and Technical Information of China (English)

    郭国富

    2012-01-01

    目的:探讨化疼通闭丸的药理作用和临床应用.方法:结合科研及实际,对化瘀通用丸的药理作用及临床应用进行归纳和总结.结果:化瘀通闭丸具有抗炎消炎、抑菌杀菌、镇痛、提高免疫力等作用,临床用于治疗泌尿系统及生殖系统炎症.结论:化瘀通闭丸治疗泌尿系统及生殖系统炎症疗效确切、安全可靠.%Objective;To investigate the pharmacological effects of huayu tongbi pill in clinical application. Methods:Pharmacological function and clinical application of huayu tongbi pill are summarized combined with scientific research and practice. Results; Huayu tongbi pill has anti - inflammatory, antibacterial sterilization .analgesia and immunity function improvement, the clinic for the treatment of urinary system and reproductive system inflammation. Conclusion;The curative effect of huayu tongbi pill in the treatment of urinary system and reproductive system inflammation is accurate,safe and reliable.

  18. Adapting drug approval pathways for bacteriophage-based therapeutics

    Directory of Open Access Journals (Sweden)

    Callum Cooper

    2016-08-01

    Full Text Available The global rise of multi-drug resistant bacteria has resulted in the notion that an antibiotic apocalypse is fast approaching. This has led to a number of well publicized calls for global funding initiatives to develop new antibacterial agents. The long clinical history of phage therapy in Eastern Europe, combined with more recent in vitro and in vivo success, demonstrates the potential for whole phage or phage based antibacterial agents. To date, no whole phage or phage derived products are approved for human therapeutic use in the EU or USA. There are at least three reasons for this: (i phages possess different biological, physical and pharmacological properties compared to conventional antibiotics. Phages need to replicate in order to achieve a viable antibacterial effect, resulting in complex pharmacodynamics / pharmacokinetics. (ii The specificity of individual phages requires multiple phages to treat single species infections, often as part of complex cocktails. (iii The current approval process for antibacterial agents has evolved with the development of chemically based drugs at its core, and is not suitable for phages. Due to similarities with conventional antibiotics, phage derived products such as endolysins are suitable for approval under current processes as biological therapeutic proteins. These criteria render the approval of phages for clinical use theoretically possible but not economically viable. In this review, pitfalls of the current approval process will be discussed for whole phage and phage derived products, in addition to the utilization of alternative approval pathways including adaptive licensing and Right to try legislation.

  19. Pharmacological management of sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, J.R.

    1985-01-01

    Systemic sepsis continues to be the most-difficult management problem in caring for the combat casualty. The complications of sepsis pervade all areas of injury to soldiers in the field, whether it is mechanical (missiles), thermal (burns), chemical, biological, or radiation injury. With the advent of tactical nuclear weapons, the problem of sepsis will be much higher in future wars than has previously been experienced through the world. The purpose of this chapter is a) to review the data suggesting pharmacological agents that may benefit the septic patient, and b) to emphasize the adjunctive therapies that should be explored in clinical trials. The pharmacological management of sepsis remains controversial. Most of the drugs utilized clinically treat the symptoms of the disease and are not necessarily directed at fundamental mechanisms that are known to be present in sepsis. A broad data base is emerging, indicating that NSAID should be used in human clinical trials. Prostaglandins are sensitive indicators of cellular injury and may be mediators for a number of vasoactive chemicals. Opiate antagonists and calcium channel blockers require more in-depth data; however, recent studies generate excitement for their potential use in the critically ill patient. Pharmacological effects of antibiotics, in concert with other drugs, suggest an entirely new approach to pharmacological treatment in sepsis. There is no doubt that new treatment modalities or adjunctive therapies must be utilized to alter the poor prognosis of severe sepsis that we have observed in the past 4 decades.

  20. Genomic variant annotation workflow for clinical applications [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Thomas Thurnherr

    2016-10-01

    Full Text Available Annotation and interpretation of DNA aberrations identified through next-generation sequencing is becoming an increasingly important task. Even more so in the context of data analysis pipelines for medical applications, where genomic aberrations are associated with phenotypic and clinical features. Here we describe a workflow to identify potential gene targets in aberrated genes or pathways and their corresponding drugs. To this end, we provide the R/Bioconductor package rDGIdb, an R wrapper to query the drug-gene interaction database (DGIdb. DGIdb accumulates drug-gene interaction data from 15 different resources and allows filtering on different levels. The rDGIdb package makes these resources and tools available to R users. Moreover, rDGIdb queries can be automated through incorporation of the rDGIdb package into NGS sequencing pipelines.

  1. Oncology drug clinical development and approval in Japan: the role of the pharmaceuticals and medical devices evaluation center (PMDEC).

    Science.gov (United States)

    Fujiwara, Yasuhiro; Kobayashi, Ken

    2002-05-01

    In 1996 the Japanese Diet amended the Pharmaceutical Affairs Law (PAL) and its related laws based on 1996 report of the ad-hoc Committee for Drug Safety Ensuring Measures. Between 1996 and 2000, the drug approval system in Japan underwent a series of radical reforms. We describe in this paper the current system for drug approval, discuss the post-approval reexamination and reevaluation system, conditions under which development and review may be expedited, and mechanisms for approval of off-label usage. Finally, we discuss the impact of the International Conference on Harmonization (ICH) agreement on drug development and review in Japan.

  2. A review on dronedarone:Pharmacological, pharmacodynamic and pharmacokinetic profile

    Institute of Scientific and Technical Information of China (English)

    Farah Iram; Sadaf Ali; Aftab Ahmad; Shah Alam Khan; Asif Husain

    2016-01-01

    Dronedarone, a benzofuran containing chemical compound, is a derivative of amiodarone which is classified as a Class III antiarrhythmic agent. It is prescribed to the cardiovas-cular patients who have paroxysmal or persistent atrial fibrillation to lower the chances of hospitalization. Amiodarone, sotalol, procainamide dofetilide, quinidine, ibutilide, fle-cainide, and propafenone are the other useful medicinal products used to treat atrial fibrillation or cardiac arrhythmia. Dronedarone was approved for clinical use in atrial fibrillation by the Food and Drug Administration in 2009. The generic name for drone-darone is Multaq (Sanofi Aventis). This article briefly highlights the important pharma-cological, pharmacodynamic and pharmacokinetic properties of dronedarone.

  3. Vascular dementia: Pharmacological treatment approaches and perspectives

    Directory of Open Access Journals (Sweden)

    Andrius Baskys

    2007-10-01

    Full Text Available Andrius Baskys1,3, Anthony C Hou21Department of Psychiatry and Human Behavior; 2Program in Geriatrics, University of California at Irvine, Irvine, California; 3Memory Disorders Program, VA Health Care System Long Beach, Long Beach, California, USAAbstract: Vascular dementia is a common condition for which there are no effective approved pharmacological treatments available. Absence of effective treatments creates a difficult situation for those suffering from the disease, their caregivers, and healthcare providers. This review will address our current understanding of the mechanisms of nerve cell damage due to ischemia and summarize available clinical trial data on several commonly used compounds including memantine, donepezil, galantamine, rivastigmine, nimodipine, hydergine, nicergoline, CDPcholine, folic acid, as well as such nonpharmacological approaches as validation therapy.Keywords: vascular dementia, excitotoxicity, treatment, NMDA, memantine, donepezil, galantamine, rivastigmine, nimodipine, hydergine, nicergoline, CDP-choline, folic acid

  4. Phytochemical and pharmacological properties of essential oils from Cedrus species.

    Science.gov (United States)

    Saab, Antoine M; Gambari, Roberto; Sacchetti, Gianni; Guerrini, Alessandra; Lampronti, Ilaria; Tacchini, Massimo; El Samrani, Antoine; Medawar, Samir; Makhlouf, Hassane; Tannoury, Mona; Abboud, Jihad; Diab-Assaf, Mona; Kijjoa, Anake; Tundis, Rosa; Aoun, Jawad; Efferth, Thomas

    2017-07-03

    Natural products frequently exert pharmacological activities. The present review gives an overview of the ethnobotany, phytochemistry and pharmacology of the Cedrus genus, e.g. cytotoxic, spasmolytic immunomodulatory, antiallergic, anti-inflammatory and analgesic activities. Cancer patients frequently seek remedies from traditional medicinal plants that are believed to exert less side effects than conventional therapy with synthetic drugs. A long-lasting goal of anti-cancer and anti-microbial therapy research is to find compounds with reduced side effects compared to currently approved drugs. In this respect, Cedrus species might be of interest. The essential oil isolated from Cedrus libani leaves may bear potential for drug development due to its high concentrations of germacrene D and β-caryophyllene. The essential oils from Cedrus species also show bioactivity against bacteria and viruses. More preclinical analyses (e.g. in vivo experiments) as well as clinical trials are required to evaluate the potential of essential oils from Cedrus species for drug development.

  5. 丹参的药理分析及临床应用研究%Pharmacological Analysis of and Study on Clinical Application of Salvia Miltiorrhiza

    Institute of Scientific and Technical Information of China (English)

    高波

    2016-01-01

    丹参是一味临床常用药材,在我国医疗上应用历史悠久,随着对丹参药理作用的深入研究以及临床应用,该种药材具有祛瘀止痛、活血通经、清心除烦等诸多疗效,在肝硬化、恶性肿瘤、冠心病、消化性溃疡等疾病的临床治疗中具有显著的应用效果,并且其药用价值已经得到了医学界和患者的广泛认可,并且在临床上的应用也越来越广泛。本文主要对丹参的药理作用进行简要分析,并就其在临床上的应用进行研究。%Salvia miltiorrhiza is an ordinary medication ingredient in clinical treatment with a long history. With a deep pharmacological analysis on salvia miltiorrhiza and its clinical application, salvia miltiorrhiza has extraordinary effects on getting rid of bruise, relieving pain, activating blood circulation and dispeling upset and irritation. Besides, salvia miltiorrhiza is quite efficiency in clinical treatment of liver cirrhosis, malignant tumor, coronary heart disease, peptic ulcer and other diseases. Its medication value has been recognized widely by medical experts and patients and it has been applied clinicaly more and more widespread. This paper mainly makes a brief analysis on pharmacological function and a study on clinical application of salvia miltiorrhiza.

  6. Cross-sectional analysis of the reporting of continuous outcome measures and clinical significance of results in randomized trials of non-pharmacological interventions.

    Science.gov (United States)

    Hoffmann, Tammy C; Thomas, Sarah T; Shin, Paul Ng Hung; Glasziou, Paul P

    2014-09-17

    Reporting the scoring details of continuous outcome measures in randomized trials allows readers to interpret the size of any effect of the intervention. This study aimed to determine, in a sample of randomized trials: 1) the completeness of reporting of scoring details for continuous outcome measures, and 2) whether trial authors comment on the clinical significance of statistically significant trial results. A descriptive analysis of randomized trials of non-pharmacological interventions published during 2009 in the six leading general medical journals (n = 138), and which used at least one continuous outcome measure (n = 85). From each trial report, two authors independently extracted the following information about each continuous outcome measure: the reporting of its scoring details, presentation of its results, and the reporting and justification of the clinical significance of the results. Across the 84 trials, we identified 336 continuous outcome measures. A total of 146 (44%) were published measures, 12 (4%) were adapted from published measures, 5 (1%) were developed for the trial, and 173 (51%) were 'conventional measures' for which scoring details are not necessary (such as weight). For 57 (35%) of the 163 non-conventional outcome measures no scoring details or reference to the outcome measure were provided in the trial report. Of the 159 outcome measures with a statistically significant result, clinical significance was not mentioned for 81 (51%) and was reported without any elaboration or justification for 39 (25%) of them. Scoring details of continuous outcome measures used in this sample of randomized trials of non-pharmacological interventions were incompletely reported, which hampers interpretation of a trial's results. Complete reporting of scoring details is important when considering the clinical significance of the results. When deciding about an intervention, having this information may help clinicians in their conversations with patients

  7. 2013 Pharmacology Risk SRP Status Review Comments to Chief Scientist. The Risk of Clinically Relevant Unpredicted Effects of Medication

    Science.gov (United States)

    2014-01-01

    On December 5, 2013, the Pharmacology Risk SRP, participants from the JSC, HQ, the NSBRI, and NRESS participated in a WebEx/teleconference. The purpose of the call (as stated in the Statement of Task) was to allow the SRP members to: 1. Receive an update by the HRP Chief Scientist or Deputy Chief Scientist on the status of NASA's current and future exploration plans and the impact these will have on the HRP. 2. Receive an update on any changes within the HRP since the 2012 SRP meeting. 3. Receive an update by the Element or Project Scientist(s) on progress since the 2012 SRP meeting. 4. Participate in a discussion with the HRP Chief Scientist, Deputy Chief Scientist, and the Element regarding possible topics to be addressed at the next SRP meeting.

  8. CFTR pharmacology.

    Science.gov (United States)

    Zegarra-Moran, Olga; Galietta, Luis J V

    2017-01-01

    CFTR protein is an ion channel regulated by cAMP-dependent phosphorylation and expressed in many types of epithelial cells. CFTR-mediated chloride and bicarbonate secretion play an important role in the respiratory and gastrointestinal systems. Pharmacological modulators of CFTR represent promising drugs for a variety of diseases. In particular, correctors and potentiators may restore the activity of CFTR in cystic fibrosis patients. Potentiators are also potentially useful to improve mucociliary clearance in patients with chronic obstructive pulmonary disease. On the other hand, CFTR inhibitors may be useful to block fluid and electrolyte loss in secretory diarrhea and slow down the progression of polycystic kidney disease.

  9. FDG PET in non-pharmacological therapy in Alzheimer's disease; cerebral metabolic increase correlates with clinical improvement after cognitive therapy

    Energy Technology Data Exchange (ETDEWEB)

    Na, Hae Ri; Kim, Yu Kyeong; Park, Seong Min; Lee, Seung Hyun; Park, Eun Kyung; Lee, Jung Seok; Kim, Sang Yun; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    In management of AD, pharmacological treatment alone using acetylcholinesterase inhibitor (AChEI) is general consensus, and provides beneficial effect to prolong their progression. Combined non-pharmacological therapy, especially cognitive therapy is recently having attention with expectation of improvement in cognitive ability. This study examined the effect of combined cognitive therapy in AD patients who were maintaining AChEI using FDG PET. Four patients (689 yrs) who diagnosed as probable Alzheimer's disease based on the NINCDS-ADRDA criteria participated in this study. 12-week cognitive therapy comprised seven fields to enhance orientation, memory, recall, visuo-motor organization, categorization and behavior modification/sequencing. They received 45-minute sessions twice per week with maintaining their previous medication. Clinical improvement was assessed by comprehensive neuropsychological tests. Two FDG PET studies were performed before cognitive therapy and in the middle of the therapy, and compared to evaluate the effect of cognitive therapy to cerebral metabolism. Two of 4 patients whose initial cognitive impairment was milder had clinical improvement after 12 weeks, the rest who were more severely impaired failed to have clinical improvement. Regional cerebral hypometabolism on initial PET was correlated with their functional status. Follow up PET of two responders demonstrated the increases in regional metabolism in the temporal and/or frontal cortex, which was associated their functional improvement. Cerebral metabolism in poor responders were minimally increased or no changed. This preliminary data suggests that cognitive therapy is potentially useful to stabilize or improve cognitive and functional performance in AD patients with relatively mild cognitive dysfunction. And FDG PET could demonstrate possible candidates for cognitive therapy and the effect of the therapy.

  10. Social pharmacology: expanding horizons

    OpenAIRE

    Rituparna Maiti; José Luis Alloza

    2014-01-01

    In the current modern and global society, social changes are in constant evolution due to scientific progress (technology, culture, customs, and hygiene) and produce the freedom in individuals to take decisions by themselves or with their doctors toward drug consumption. In the arena of marketed drug products which includes society, individual, administration, and pharmaceutical industry, the young discipline emerged is social pharmacology or sociopharmacology. This science arises from clinic...

  11. Social pharmacology: expanding horizons.

    Science.gov (United States)

    Maiti, Rituparna; Alloza, José Luis

    2014-01-01

    In the current modern and global society, social changes are in constant evolution due to scientific progress (technology, culture, customs, and hygiene) and produce the freedom in individuals to take decisions by themselves or with their doctors toward drug consumption. In the arena of marketed drug products which includes society, individual, administration, and pharmaceutical industry, the young discipline emerged is social pharmacology or sociopharmacology. This science arises from clinical pharmacology, and deals with different parameters, which are important in creating knowledge on marketed drugs. However, the scope of "social pharmacology" is not covered by the so-called "Phase IV" alone, but it is the science that handles the postmarketing knowledge of drugs. The social pharmacology studies the "life cycle" of any marketed pharmaceutical product in the social terrain, and evaluates the effects of the real environment under circumstances totally different in the drug development process. Therefore, there are far-reaching horizons, plural, and shared predictions among health professionals and other, for beneficial use of a drug, toward maximizing the benefits of therapy, while minimizing negative social consequences.

  12. Social Pharmacology: Expanding horizons

    Directory of Open Access Journals (Sweden)

    Rituparna Maiti

    2014-01-01

    Full Text Available In the current modern and global society, social changes are in constant evolution due to scientific progress (technology, culture, customs, and hygiene and produce the freedom in individuals to take decisions by themselves or with their doctors toward drug consumption. In the arena of marketed drug products which includes society, individual, administration, and pharmaceutical industry, the young discipline emerged is social pharmacology or sociopharmacology. This science arises from clinical pharmacology, and deals with different parameters, which are important in creating knowledge on marketed drugs. However, the scope of "social pharmacology" is not covered by the so-called "Phase IV" alone, but it is the science that handles the postmarketing knowledge of drugs. The social pharmacology studies the "life cycle" of any marketed pharmaceutical product in the social terrain, and evaluates the effects of the real environment under circumstances totally different in the drug development process. Therefore, there are far-reaching horizons, plural, and shared predictions among health professionals and other, for beneficial use of a drug, toward maximizing the benefits of therapy, while minimizing negative social consequences.

  13. Pharmacological and clinical differences among transmucosal fentanyl formulations for the treatment of breakthrough cancer pain: a review article.

    Science.gov (United States)

    Corli, O; Roberto, A

    2014-10-01

    Breakthrough pain (BTP) is highly prevalent (59.2%) in chronic cancer patients and normally needs rescue treatments' with opioids when pain flares up. Transmucosal oral/nasal fentanyl formulations are commonly used in clinical practice. The different methods of release influence the pharmacokinetics and clinical properties of these formulations. The aim of this review was to assess and weigh these differences. Clinical trials comparing one transmucosal fentanyl with placebo or another active drug were included. We searched Medline for the last ten years and analyzed 13 studies, totaling 1447 patients. Clinical data on efficacy and safety were compared. In parallel, we report the differences in delivery systems, bioavailability, maximum plasma concentration (Cmax), plasma half-life, and time to reach Cmax (tmax). Considerable variability emerged between formulations. This suggests some considerations on the choice of the fentanyl formulation in the light of the BTP features in each clinical case.

  14. Pharmacometrics in early clinical drug development

    NARCIS (Netherlands)

    Keizer, R.J.

    2010-01-01

    Pharmacometrics, the science of quantitative clinical pharmacology, has been recognized as one of the main research fields able to improve efficiency in drug development, and to reduce attrition rates on the route from drug discovery to approval. This field of drug research, which builds heavily on

  15. Pharmacometrics in early clinical drug development

    NARCIS (Netherlands)

    Keizer, R.J.

    2010-01-01

    Pharmacometrics, the science of quantitative clinical pharmacology, has been recognized as one of the main research fields able to improve efficiency in drug development, and to reduce attrition rates on the route from drug discovery to approval. This field of drug research, which builds heavily on

  16. 聚卡波非钙的药理及临床研究%Progress on pharmacology and clinical research of calcium polycarbophil

    Institute of Scientific and Technical Information of China (English)

    韩振杰; 袁耀宗

    2012-01-01

    通过文献回顾,评价聚卡波非钙治疗肠易激综合征及其他原因所致便秘的药理作用、药动学、临床研究和安全性.本品为高分子聚合物,临床试验显示其对肠易激综合症及其他原因引起的便秘具有很好的疗效,主要的不良反应为消化道症状.%By literature review, pharmacology, pharmacokinetics, clinical study, and safety of calcium polycarbophil in the treatment of constipation in irritable bowel syndrome and others were evaluated in the paper. As a polymer, calcium polycarbophil has a positive effect on IBS and other constipation. The main adverse drug reaction is the digestive system symptoms.

  17. The pharmacology of regenerative medicine.

    Science.gov (United States)

    Christ, George J; Saul, Justin M; Furth, Mark E; Andersson, Karl-Erik

    2013-07-01

    Regenerative medicine is a rapidly evolving multidisciplinary, translational research enterprise whose explicit purpose is to advance technologies for the repair and replacement of damaged cells, tissues, and organs. Scientific progress in the field has been steady and expectations for its robust clinical application continue to rise. The major thesis of this review is that the pharmacological sciences will contribute critically to the accelerated translational progress and clinical utility of regenerative medicine technologies. In 2007, we coined the phrase "regenerative pharmacology" to describe the enormous possibilities that could occur at the interface between pharmacology, regenerative medicine, and tissue engineering. The operational definition of regenerative pharmacology is "the application of pharmacological sciences to accelerate, optimize, and characterize (either in vitro or in vivo) the development, maturation, and function of bioengineered and regenerating tissues." As such, regenerative pharmacology seeks to cure disease through restoration of tissue/organ function. This strategy is distinct from standard pharmacotherapy, which is often limited to the amelioration of symptoms. Our goal here is to get pharmacologists more involved in this field of research by exposing them to the tools, opportunities, challenges, and interdisciplinary expertise that will be required to ensure awareness and galvanize involvement. To this end, we illustrate ways in which the pharmacological sciences can drive future innovations in regenerative medicine and tissue engineering and thus help to revolutionize the discovery of curative therapeutics. Hopefully, the broad foundational knowledge provided herein will spark sustained conversations among experts in diverse fields of scientific research to the benefit of all.

  18. Effect of vitamin B/sub 6/ on the neurotoxicity and pharmacology of desmethylmisonidazole and misonidazole: clinical and laboratory studies

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, C.N.; Hirst, V.K.; Brown, D.M.; Halsey, J.

    1984-08-01

    The clinical usefulness of misonidazole (MISO) and desmethylmisonidazole (DMM) is severely limited by neurotoxicity. Based on theoretical considerations and on laboratory data suggesting that pyridoxine (PN) decreased MISO toxicity in mice. The authors attempted to ameliorate the clinical neuropathy of DMM using oral PN. Pharmacokinetic analysis suggested interaction of PN and DMM but no protection against neuropathy was observed. Serial experiments with C3H and BALB/c mice were done using various forms of vitamin B/sub 6/ (PN, pyridoxal, pyridoxal phosphate) administered orally and i.p. No consistent protection was observed. Dexamethasone did not alter MISO toxicity in mice, contrary to the clinical findings. They conclude that vitamin B/sub 6/ is not useful in preventing clinical neurotoxicity of MISO or DMM.

  19. Study on the pharmacological action and clinical application SanQi%三七的药理作用及其临床应用研究

    Institute of Scientific and Technical Information of China (English)

    钟晓凤

    2015-01-01

    Objective: To discuss the pharmacological action and clinical application of three seven. Methods: Thechemical constituents of three seven analysis, pharmacological action and summarize three seven in chemical composition in clinical application effect. Results:Sanqi can affect the central nervous system, circulatory system, digestive system, urinary system, reproductive system and the immune system and other systems, but also has anti-aging, antitumor and anti-inflammatory effects. Conclusion:as a kind of natural plant medicine,three seven and its extract medicinal extensive effect, less side effect, is worth paying attention to anddeveloped a taste of traditional Chinese medicine.%目的:讨论三七的药理作用及临床应用。方法:对三七的化学成分进行分析,总结三七的药理作用及其在化学成分在临床的应用效果。结果:三七能够对中枢神经系统、循环系统、消化系统、泌尿系统、生殖系统以及免疫系统等系统产生影响,还具有抗衰老、抗肿瘤和抗炎的作用。结论:作为一种天然的植物药,三七及其提取物药用作用广泛,副作用少,是一味值得重视和开发的中药。

  20. Molecular pharmacology of the mineralocorticoid receptor: prospects for novel therapeutics.

    Science.gov (United States)

    Kolkhof, Peter; Borden, Steffen A

    2012-03-24

    The blockade of mineralocorticoid receptors (MR) has been shown to be an invaluable therapy in heart failure and hypertension. To date, only two steroidal antimineralocorticoids, spironolactone (and its active metabolite canrenone) and eplerenone, have been approved, whereas novel non-steroidal compounds are in preclinical and early development. The careful investigation of the efficacy and tolerance of spironolactone in essential hypertension initially supported the idea that a more selective second generation of MR antagonists is desired for chronic treatment of cardiovascular diseases. More than 40 years went by between the approval of the first MR antagonist spironolactone and the market introduction of its sole successor, eplerenone. The molecular pharmacology of MR antagonists may be addressed at different levels. Available preclinical and clinical data of the two approved steroidal antimineralocorticoids allow a good comparison of potency and selectivity of MR antagonists and their pharmacokinetic properties. The search for novel generations of MR antagonists with the ultimate goal of a more tissue selective mode of action may require novel compounds that are differentiated with respect to the binding mode to the MR. Other factors that may contribute to tissue selectivity as e.g. the physicochemical properties of a drug and how they influence the resulting pharmacology in the context of tissue selective co-factor expression are even less well understood. In the following we will review these aspects and demonstrate that the molecular pharmacology of current MR antagonists is on the one hand far from well understood and, on the other hand, still offers room for improvements.

  1. Adult attention-deficit/hyperactivity disorder: Associations between subtype and lifetime substance use – a clinical study. [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Michael Liebrenz

    2015-07-01

    Full Text Available ADHD is the one of the most prevalent childhood disorders and has been associated with impairments persisting into adulthood. Specifically, childhood ADHD is an independent clinical risk factor for the development of later substance use disorders (SUD. Moreover, adults who meet diagnostic criteria for ADHD have shown high rates of comorbid SUDs. Few studies, however, have reported on the relationship between ADHD subtypes and SUD in adult samples. The purpose of this study was to characterize a clinical sample of adults with ADHD and to identify possible associations between ADHD subtypes, lifetime substance use, and if ADHD subtypes may be preferentially associated with specific substances of abuse. We recruited 413 adult ADHD patients, performed an evaluation of their ADHD and conducted an interview on their use of psychotropic substances. Complete data was obtained for 349 patients. Lifetime substance abuse or dependence was 26% and occasional use was 57% in this sample. The inattentive subtype was significantly less likely to abuse or be dependent on cocaine than the combined subtype. Our findings underscore the high rate of comorbidity between substance use and ADHD in adults. The more frequent abuse/dependence of cocaine by adult patients with hyperactive-impulsive symptoms should be kept in mind when treating this patient group.

  2. Adult attention-deficit/hyperactivity disorder: Associations between subtype and lifetime substance use – a clinical study [version 2; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Michael Liebrenz

    2016-10-01

    Full Text Available ADHD is the one of the most prevalent childhood disorders and has been associated with impairments persisting into adulthood. Specifically, childhood ADHD is an independent clinical risk factor for the development of later substance use disorders (SUD. Moreover, adults who meet diagnostic criteria for ADHD have shown high rates of comorbid SUDs. Few studies, however, have reported on the relationship between ADHD subtypes and SUD in adult samples. The purpose of this study was to characterize a clinical sample of adults with ADHD and to identify possible associations between ADHD subtypes, lifetime substance use, and if ADHD subtypes may be preferentially associated with specific substances of abuse. We recruited 413 adult ADHD patients, performed an evaluation of their ADHD and conducted an interview on their use of psychotropic substances. Complete data was obtained for 349 patients. Lifetime substance abuse or dependence was 26% and occasional use was 57% in this sample. The inattentive subtype was significantly less likely to abuse or be dependent on cocaine than the combined subtype. Our findings underscore the high rate of comorbidity between substance use and ADHD in adults. The more frequent abuse/dependence of cocaine by adult patients with hyperactive-impulsive symptoms should be kept in mind when treating this patient group.

  3. Preclinical pharmacology, efficacy, and safety of varenicline in smoking cessation and clinical utility in high risk patients

    Directory of Open Access Journals (Sweden)

    Zheng-Xiong Xi

    2010-04-01

    Full Text Available Zheng-Xiong XiNational Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, USAAbstract: Smoking is still the most prominent cause of preventable premature death in the United States and an increasing cause of morbidity and mortality throughout the world. Although the current treatments such as nicotine replacement therapy (NRT and bupropion are effective, long-term abstinence rates are low. Mechanism studies suggest that the pleasurable effects of smoking are mediated predominantly by nicotine, which activates the brain reward system by activation of brain α4β2 nicotinic acetylcholine receptors (nAChRs. Varenicline is a novel α4β2 nAChR partial agonist and has been found to be even more effective than NRT or bupropion in attenuating smoking satisfaction and in relieving craving and withdrawal symptoms after abstinence. Thus, varenicline has been recently approved to be a first-line medication for smoking cessation in the United States and European countries. Varenicline is generally well tolerated in healthy adult smokers, with the most commonly reported adverse effects being nausea, insomnia, and headache. However, growing postmarketing data has linked varenicline to an increase in neuropsychiatric symptoms such as seizures, suicidal attempts, depression, and psychosis as well as serious injuries potentially relating to unconsciousness, dizziness, visual disturbances, or movement disorders. Therefore, new safety warnings are issued to certain high risk populations, such as patients with mental illness and operators of commercial vehicles and heavy machinery. In particular, pilots, air traffic controllers, truck and bus drivers have been banned from taking varenicline.Keywords: nicotine, varenicline, α4β2 nicotinic acetylcholine receptor, nAChRs, partial agonist, smoking cessation

  4. A New Level A Type IVIVC for the Rational Design of Clinical Trials Toward Regulatory Approval of Generic Polymeric Long-Acting Injectables.

    Science.gov (United States)

    Somayaji, Mahadevabharath R; Das, Debarun; Przekwas, Andrzej

    2016-10-01

    Chronic neuropsychiatric disorders and diabetes mellitus affect millions of patients and require long-term supervision and expensive medical care. Although repeated drug administration can help manage these diseases, relapses and re-hospitalization owing to patient non-adherence and reduced therapeutic efficacy remain challenging. In response, long-acting injectables, which provide sustained drug release over longer periods at concentrations close to therapeutic ranges, have been proposed. Recent advancements include polymeric long-acting injectables (pLAIs), in which the active pharmaceutical ingredient (API) is encapsulated within U.S. Food and Drug Administration (FDA)-approved biocompatible polymers, such as poly(lactic-co-glycolic acid), or PLGA. Despite significant progress and development in the global pLAI market, FDA guidance for the approval of complex drug products, such as generic pLAIs, is not clearly defined. Although in vitro to in vivo correlation (IVIVC) can facilitate the identification of critical quality attributes (CQAs), drug formulations, and in vitro test platforms for evaluating drug performance in vivo, the application of IVIVC in order to shortlist time- and resource-intensive clinical trials for generic pLAIs has not been reported. Here, we propose a new Level A Type IVIVC that directly correlates the in vitro outcomes, such as drug dissolution, of candidate generic formulations with the clinical characteristics, such as drug absorption, of a reference listed drug (RLD), to help identify the specific generic pLAI formulations with clinical absorptions that are likely to be similar to that of the RLD, thereby reducing the number of clinical trials required for evaluation of clinical bioequivalence (BE). Therefore, the scope of the proposed method is intended only for the rational design of clinical trials, i.e., to shortlist the specific pLAI generic formulations for clinical BE evaluation, and not necessarily to analyze drug performances

  5. Case Report: A case report highlighting bilateral EDB wasting as a clinical marker for lumbar canal stenosis [version 1; referees: 2 approved, 1 approved with reservations

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    Bijoy Mohan Kumar

    2015-08-01

    Full Text Available Herein we discuss a case of a 55 year old male presenting with history suggestive of sciatica on the left leg. Straight leg raising (SLR test was positive at 45 degrees on the left side. His ankle reflex was absent and the power of extensor hallusus longus (EHL was 4/5 on the same side. MRI lumbosacral spine revealed left paramedian disc prolapsed on L4/L5 level with spinal canal diameter of 9mm.However since his bilateral extensor digitorm brevis (EDB were wasted, we suspected associated lumbar canal stenosis and thereby opted for laminectomy and discectomy in this case. Intraoperatively dural wasting, hypertrophied facets and narrow canal were confirmed. Laminectomy, medial facectectomy and discectomy were carried out. The patient recovered uneventfully with resolution of his sciatica-like pain. Bilateral EDB wasting thereby provides a clinical clue to the underlying lumbar canal stenosis and can help in making correct therapeutic decisions.

  6. The prevalence and clinical significance of anemia in patients hospitalized with acute heart failure [version 2; referees: 2 approved, 1 not approved

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    Attila Frigy

    2017-08-01

    Full Text Available Abstract: In a cohort of patients hospitalized with acute heart failure (AHF the prevalence of anemia and the existence of a correlation between anemia and the severity of the clinical picture were assessed. Methods: 50 consecutive patients (34 men, 16 women, mean age 67.5 years hospitalized with AHF were enrolled.  Statistical analysis was performed for studying correlations between anemia and the presence/levels of diverse parameters (clinical, laboratory, echocardiographic, treatment related  reflecting the severity and prognosis of AHF (α=0.05. Results: 21 patients (14 men, 7 women, mean age 69.6 years, representing 42%, had anemia  at admission. Comparing patients with and without anemia there were no significant differences regarding age,  gender,  presence of atrial fibrillation (p=0.75, diabetes (p=1, ischemic heart disease (p=0.9, left ventricular ejection fraction (EF (p=1, hypotension (p=0.34 and tachycardia>100 b/min at admission (p=0.75, level of eGFR (p=0.72, and need of high dose (>80 mg/day  loop diuretic (p=0.23. However, EF showed a significant positive correlation with eGFR only in AHF patients with anemia (r=0,65, p=0.001. In a multiple regression model, EF had a significant effect on the eGFR quartiles (p=0,004. Conclusions: Anemia is a frequent finding in patients hospitalized with AHF. The presence of anemia was not correlated with other factors related to AHF severity and prognosis. However, a low EF associated with low eGFR was characteristic for patients with anemia, suggesting that the decrease of renal perfusion by low cardiac output further aggravates anemia on the background of chronic kidney disease.

  7. Vernakalant (RSD1235) in the management of atrial fibrillation: a review of pharmacological properties, clinical efficacy and safety

    DEFF Research Database (Denmark)

    Weeke, Peter; Andersson, Charlotte; Brendorp, Bente;

    2008-01-01

    Vernakalant (RSD1235) is a novel antiarrhythmic agent for conversion of rapid onset atrial fibrillation (AF). It is an atria-selective multichannel ion blocker (blocks I(Kur), I(Na), I(Ca, L), I(to) and I(Kr)), with a small effect on ventricular repolarization. In clinical Phase II and III studie...

  8. Systematic Review of Randomized Clinical Trials on Safety and Efficacy of Pharmacological and Nonpharmacological Treatments for Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Marta Sacchetti

    2015-01-01

    Full Text Available Aims. Several treatments have been proposed to slow down progression of Retinitis pigmentosa (RP, a hereditary retinal degenerative condition leading to severe visual impairment. The aim of this study is to systematically review data from randomized clinical trials (RCTs evaluating safety and efficacy of medical interventions for the treatment of RP. Methods. Randomized clinical trials on medical treatments for syndromic and nonsyndromic RP published up to December 2014 were included in the review. Visual acuity, visual field, electroretinogram, and adverse events were used as outcome measures. Results. The 19 RCTs included in this systematic review included trials on hyperbaric oxygen delivery, topical brimonidine tartrate, vitamins, docosahexaenoic acid, gangliosides, lutein, oral nilvadipine, ciliary neurotrophic factor, and valproic acid. All treatments proved safe but did not show significant benefit on visual function. Long term supplementation with vitamin A showed a significantly slower decline rate in electroretinogram amplitude. Conclusions. Although all medical treatments for RP appear safe, evidence emerging from RCTs is limited since they do not present comparable results suitable for quantitative statistical analysis. The limited number of RCTs, the poor clinical results, and the heterogeneity among studies negatively influence the strength of recommendations for the long term management of RP patients.

  9. UNDERGRADUATE MBBS AND BDS STUDENTS’ OPINION BASED SURVEY ON CURRENT TEACHING PRACTICES IN PHARMACOLOGY AND CHANGES RECOMMENDED FOR BETTERMENT OF THE SAME

    Directory of Open Access Journals (Sweden)

    Mohammed Waseem

    2014-12-01

    Full Text Available CONTEXT: Pharmacology is one of the most fundamental subjects in the field of medicine and a good grasp of this subject is vital for any clinical practitioner. The teaching of pharmacology in medical and dental colleges of India has evolved from mere didactic lectures to audio-visual aid based lectures and computer based learning. Evolution of teaching methods is an on-going process and a docent needs proper feedback from the pupils regarding their opinion on what is satisfactory and what needs improvement. AIMS: By way of this survey-based study we aim to grasp the MBBS and BDS students’ opinion regarding the teaching practices in pharmacology and changes recommended for the betterment of the same. METHODS AND MATERIALS: After obtaining due approval of the Institutional Ethics Committee, the study was conducted amongst 2nd year exam going MBBS and BDS students of M R Medical College and S Nijalingappa Dental College, Gulbarga, Karnataka in the Department of Pharmacology M R Medical College. An exhaustive questionnaire based survey was prepared of 17 questions with choices ranging from 3-8 different options. RESULTS AND CONCLUSION: The result of our study favours the need for pharmacology as a subject to be more clinically oriented as well as being technologically sound. The students overall have a positive outlook of pharmacology (53% and consider lectures as the most appropriate and helpful teaching method (62%. Introduction of group discussion is one change that is warranted by students overwhelmingly (41%, followed by introduction of clinical pharmacology exercises (31%. A vast majority of the students (70% found the lectures in pharmacology to be interesting and want them to be more clinically oriented. The importance of pharmacology in clinical decision making is well understood by the majority of students and they aim to act in that behest. Also, we find that computer based learning is a new and important tool coming up in the arsenal

  10. Experimental strategy of animal trial for the approval of anti-diabetic agents prior to their use in pre-human clinical trials

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    Vivek K. Bajpai

    2016-03-01

    Full Text Available Although several naturally available drugs have been historically used for the treatment of diabetes mellitus throughout the world, few of them have been validated by scientific criteria. Before approval of any drug developed it should pass through animal trial prior to clinical human trial, which should followed by some standard ethical rules. Recently, a large diversity of animal models have been developed to better understand the pathogenesis of diabetes mellitus, and new drugs have been introduced in the market to treat this autoimmune disease. In the present article, we demonstrated some standard handling procedure of animal trial for the approval of anti-diabetic drug, which could be helpful for both academics and industrial scientific community to conduct the animal experiments. This research also contributes in the field of ethnopharmacology to design new strategies for the development of novel drugs to treat this serious condition of diabetes mellitus that constitutes a global public health.

  11. Non-pharmacological treatment of hypertension in primary health care: A comparative clinical trial of two education strategies in health and nutrition

    Directory of Open Access Journals (Sweden)

    Ribeiro Andréia Q

    2011-08-01

    Full Text Available Abstract Background Poor adherence to non-pharmacological treatment of hypertension represents a serious challenge for public health policies in several countries. This study was conducted to compare two intervention strategies regarding the adherence of adult women to dietary changes recommended for the treatment of hypertension in a community covered by Primary Health Care Unit. Methods This study is a randomized controlled trial of a sample composed of 28 women with hypertension enrolled in the Primary Health Care Unit located in the urban area of southeastern Brazil. The participants were already undergoing treatment for hypertension but devoid of nutritional care; and were divided into two groups, each composed of 14 individuals, who received interventions that consisted of two different strategies of nutritional guidance: monthly health education workshops alone (Group 1 and combined with family orientation through home visits (Group 2. Adherence to nutritional guidelines was evaluated by dietary, anthropometric, clinical and serum biochemical parameters, measured before and after the interventions. Knowledge on control and risk of hypertension was also investigated. The study lasted five months. Results Mean age was 55.6 (± 2.8 and 50.7 (± 6.5 in the groups 1 and 2, respectively. The home orientation strategy promoted greater adherence to dietary changes, leading to a statistically significant improvement in the clinical, anthropometric, biochemical and dietary parameters. The group 2 reduced the consumption of risk foods (p = 0.01, oil (p = 0.002 and sugar (p = 0.02, and decreased body mass index (-0.7 kg/m2; p = 0.01; waist circumference (-4.2 cm; p = 0.001, systolic blood pressure (-13 mm HG; p = 0.004 and glycemia (-18.9 mg/dl; p = 0. 01. In group 1 only waist circumference (-2 cm; p = 0.01 changed significantly. Conclusion Nutritional orientations at the household level were more effective with regard to the adherence of

  12. 酸枣仁的药理作用及现代临床应用研究%Pharmacological effects and modern clinical application research of Suanzao Ren

    Institute of Scientific and Technical Information of China (English)

    胡明亚

    2012-01-01

      According to the TCM Suanzao Ren flat sweet and sour, Bugan, Ning Xin, Lianhan, Shengjin as its main active ingredient Jujuboside, Suanzao Ren flavonoids, Suanzao Ren oil, and some experimental results to explore Suanzao Ren has a sedative and hypnotic, anticonvulsant, anti-arrhythmic, anti-ischemic, blood pressure, cholesterol, and so enhance the immune pharmacological effects, as well as in modern clinical applications, and for further research to explore Suanzao Ren clinical applications providing valuable materials.%  根据中药酸枣仁性平味甘酸,具有补肝、宁心、敛汗、生津之功,其主要有效成分为酸枣仁皂苷、酸枣仁黄酮、酸枣仁油等,并根据一些实验结果探讨酸枣仁具有镇静催眠、抗惊厥、抗心律失常、抗心肌缺血、降压、降血脂等,增强免疫等药理作用,以及在现代临床上的应用,并为进一步研究探索酸枣仁的临床应用提供了有价值的材料。

  13. Characteristics of Clinical Studies Conducted Over the Total Product Life Cycle of High-Risk Therapeutic Medical Devices Receiving FDA Premarket Approval in 2010 and 2011.

    Science.gov (United States)

    Rathi, Vinay K; Krumholz, Harlan M; Masoudi, Frederick A; Ross, Joseph S

    2015-08-11

    The US Food and Drug Administration (FDA) approves high-risk medical devices, those that support or sustain human life or present potential unreasonable risk to patients, via the Premarket Approval (PMA) pathway. The generation of clinical evidence to understand device safety and effectiveness is shifting from predominantly premarket to continual study throughout the total product life cycle. To characterize the clinical evidence generated for high-risk therapeutic devices over the total product life cycle. All clinical studies of high-risk therapeutic devices receiving initial market approval via the PMA pathway in 2010 and 2011 identified through ClinicalTrials.gov and publicly available FDA documents as of October 2014. Studies were characterized by type (pivotal, studies that served as the basis of FDA approval; FDA-required postapproval studies [PAS]; or manufacturer/investigator-initiated); premarket or postmarket; status (completed, ongoing, or terminated/unknown); and design features, including enrollment, comparator, and longest duration of primary effectiveness end point follow-up. In 2010 and 2011, 28 high-risk therapeutic devices received initial marketing approval via the PMA pathway. We identified 286 clinical studies of these devices: 82 (28.7%) premarket and 204 (71.3%) postmarket, among which there were 52 (18.2%) nonpivotal premarket studies, 30 (10.5%) pivotal premarket studies, 33 (11.5%) FDA-required PAS, and 171 (59.8%) manufacturer/investigator-initiated postmarket studies. Six of 33 (18.2%) PAS and 20 of 171 (11.7%) manufacturer/investigator-initiated postmarket studies were reported as completed. No postmarket studies were identified for 5 (17.9%) devices; 3 or fewer were identified for 13 (46.4%) devices overall. Median enrollment was 65 patients (interquartile range [IQR], 25-111), 241 patients (IQR, 147-415), 222 patients (IQR, 119-640), and 250 patients (IQR, 60-800) for nonpivotal premarket, pivotal, FDA-required PAS, and manufacturer

  14. Aliskiren – an orally active renin inhibitor. Review of pharmacology, pharmacodynamics, kinetics, and clinical potential in the treatment of hypertension

    Directory of Open Access Journals (Sweden)

    Kristina Allikmets

    2008-01-01

    Full Text Available Kristina AllikmetsDepartment of Drug Development and Medical Affairs, Nycomed Group, Roskilde, DenmarkAbstract: The importance of renin-angiotensin-aldosterone system (RAAS in diseases such as hypertension, congestive heart failure and chronic renal failure has long ago been recognized. It has also been established that inhibition of RAAS, using inhibitors of the angiotensin-converting enzyme (ACE or angiotensin II receptor blockers (ARB, is an effective way to intervene with the pathogenesis of these disorders. Renin inhibitors block the RAAS at the highest level, at its origin, and might thus offer a new exciting approach for pharmacotherapy of arterial hypertension. Aliskiren is the first in a new class of orally active, non-peptide, low molecular weight renin inhibitors, and so far the only renin inhibitor that has progressed to phase III clinical trials. This review summarizes the available data on the pharmacokinetic and pharmacodynamic properties of aliskiren and its clinical development for treatment of arterial hypertension.Keywords: aliskiren, hypertension, renin-angiotensin-aldosterone system, renin inhibition, essential hypertension

  15. Social Pharmacology: Expanding horizons

    Science.gov (United States)

    Maiti, Rituparna; Alloza, José Luis

    2014-01-01

    In the current modern and global society, social changes are in constant evolution due to scientific progress (technology, culture, customs, and hygiene) and produce the freedom in individuals to take decisions by themselves or with their doctors toward drug consumption. In the arena of marketed drug products which includes society, individual, administration, and pharmaceutical industry, the young discipline emerged is social pharmacology or sociopharmacology. This science arises from clinical pharmacology, and deals with different parameters, which are important in creating knowledge on marketed drugs. However, the scope of “social pharmacology” is not covered by the so-called “Phase IV” alone, but it is the science that handles the postmarketing knowledge of drugs. The social pharmacology studies the “life cycle” of any marketed pharmaceutical product in the social terrain, and evaluates the effects of the real environment under circumstances totally different in the drug development process. Therefore, there are far-reaching horizons, plural, and shared predictions among health professionals and other, for beneficial use of a drug, toward maximizing the benefits of therapy, while minimizing negative social consequences. PMID:24987168

  16. Pharmacological interactions of vasoconstrictors.

    Science.gov (United States)

    Gómez-Moreno, Gerardo; Guardia, Javier; Cutando, Antonio; Calvo-Guirado, José Luis

    2009-01-01

    This article is the first of a series on pharmacological interactions involving medicaments commonly prescribed and/or used in odontology: vasoconstrictors in local anaesthetics and anti-inflammatory and anti-microbial analgesics. The necessity for the odontologist to be aware of adverse reactions as a result of the pharmacological interactions is due to the increase in medicament consumption by the general population. There is a demographic change with greater life expectancy and patients have increased chronic health problems and therefore have increased medicament intake. The presence of adrenaline (epinephrine) and other vasoconstrictors in local odontological anaesthetics is beneficial in relation to the duration and depth of anaesthesia and reduces bleeding and systemic toxicity of the local anaesthetic. However, it might produce pharmacological interactions between the injected vasoconstrictors and the local anaesthetic and adrenergic medicament administered exogenically which the odontologist should be aware of, especially because of the risk of consequent adverse reactions. Therefore the importance of conducting a detailed clinical history of the general state of health and include all medicaments, legal as well as illegal, taken by the patient.

  17. Differential pharmacology and clinical utility of emerging combination treatments in the management of COPD – role of umeclidinium/vilanterol

    Directory of Open Access Journals (Sweden)

    Malerba M

    2014-06-01

    Full Text Available Mario Malerba,1 Jaymin Bhagwanji Morjaria,2 Alessandro Radaeli3 1Department of Internal Medicine, University of Brescia, Brescia, Italy; 2Department of Academic Respiratory Medicine, Hull York Medical School, University of Hull, Castle Hill Hospital, Cottingham, United Kingdom; 3Department of Emergency, Spedali Civili di Brescia, Brescia, Italy Abstract: Chronic obstructive pulmonary disease (COPD is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. Bronchodilator therapy is the cornerstone in COPD treatment. Bronchodilation in COPD is mainly achieved via administration of long- and ultralong-acting β2-agonists and with long-acting muscarinic antagonists. New combinations of bronchodilators with dual-acting muscarinic antagonist and β2-agonist properties have been licensed, and others are currently being developed with the aim of achieving once-daily dosing, and therefore may improve the likelihood of treatment compliance. These combination bronchodilators include glycopyrronium bromide/indacaterol maleate, umeclidinium (UMEC bromide/vilanterol trifenatate (VI, aclidinium bromide/formoterol and tiotropium bromide/olodaterol (Boehringer Ingelheim, Germany. This review will focus mainly on studies and clinical trials involving the novel fixed-dose combination of UMEC/VI at doses of 125/25 µg and 62.5/25 µg in patients with COPD. Data from large clinical trials involving more than 4,500 COPD patients indicate that UMEC/VI is an effective once-daily treatment in COPD with improved pulmonary function. Future studies assessing the impact of this combination on exacerbations, delay in disease progression, and health status in patients with COPD are warranted. Keywords: COPD treatment, umeclidinium, vilanterol, bronchodilators combination, long acting beta2-agonists, long acting muscarinic receptor antagonists

  18. Late-onset ankylosing spondylitis and spondylarthritis: an update on clinical manifestations, differential diagnosis and pharmacological therapies.

    Science.gov (United States)

    Toussirot, Eric

    2010-07-01

    Ankylosing spondylitis (AS) and spondylarthritis (SpA) are generally observed in young male patients but can be diagnosed in the elderly. These cases correspond to late-onset or late-diagnosed AS or SpA. The clinical presentation may be either typical axial disease with a more severe illness compared with young-onset disease, or peripheral oligoarthritis of the lower limbs with pitting oedema (late-onset peripheral spondylarthropathy). New criteria for axial SpA including MRI-determined modifications of the sacroiliac joints may help the clinician with diagnosis. The treatment options for late-onset/-diagnosed AS include the same drugs as those taken by patients with young-onset AS, i.e. NSAIDs, sulfasalazine and anti-tumour necrosis factor (TNF)-alpha agents. Anti-TNFalpha agents are very effective drugs in young-onset AS and SpA. However, the effectiveness and safety of this drug class has not been specifically evaluated in elderly AS/SpA patients, and caution is therefore required with use of these drugs in elderly patients with co-morbidities and/or polypharmacy. In particular, careful evaluation for the risk of infection and cardiovascular events is recommended before initiating anti-TNFalpha agents in this age category. However, safety data from elderly patients with rheumatoid arthritis seem reassuring. With the increasing life expectancy and the new diagnostic modalities for axial (and peripheral) SpA, it is likely that the number of patients (diagnosed) with late-onset AS/SpA will increase. Thus, the clinician must be familiar with the clinical characteristics and particularities of this group of inflammatory rheumatic diseases.

  19. Modern Pharmacology Theory Research and Clinical New-application of Aconitum Carmichaeli Debx%附子的现代药理研究与临床新用

    Institute of Scientific and Technical Information of China (English)

    丁涛

    2012-01-01

    目的:总结附子的药用原理,扩展其临床应用范围.方法:总结、归纳近年来的相关文献,用现代药理理论研究附子的医用价值与临床新用手段.结果:附子回阳救逆、补阳助火的功效,用现代医学的理论来说,与强心、抗心律失常、扩张血管、增强肾上腺皮质系统的作用直接相关;而散寒作用可以理解为与增强免疫系统、镇痛、增加血氧等作用相关.附子的药效主要体现在其化合物对神经膜蛋白和激素受体的作用,由于二者的作用机理复杂,交互环节很多,难以用单一化合物的药理来解释附子的作用.结论:附子的药理作用复杂,单一成分的作用还有待进一步研究.%Objective:To summarize the officinal principle of Aconitum Caraiichaeli Debx and extend its clinical application range. Methods : Related literatures in recent years were summarized and concluded, modern pharmacology theory was used to research the medical value and clinical new-application method of Aconitum Garmichaeli Debx. Results: Aconitum Carmichaeli Debx had the effects of regenerating yang and rescue cold limbs, tonifying yang and adding fire, in terms of modern medical theory, the effects had direct relation with stronging heart % resisting arrhythmia, dilating vessel % enhancing function of adrenal cortex system; dispersing cold effects of Aconitum Carmichaeli Debx could be interpreted as had relationship with stringing immune system, easing pain, increasing blood oxygen. Pesticide effect of Aconitum Garmichaeli Debx was mainly embodied in its compound had effects on neurilemma protein and hormone receptor, and the two objects had complex functional mechanism and multiple interactive links, thus, the effects of Aconitum Carmichaeli Debx could not be explained by single compound. Conclusion; Aconitum Carmichaeli Debx has complex pharmacology function, effect of its single component needs to be further studied.

  20. A clinical pharmacological study of the potential beneficial effects of a propolis food product as an adjuvant in asthmatic patients.

    Science.gov (United States)

    Khayyal, M T; el-Ghazaly, M A; el-Khatib, A S; Hatem, A M; de Vries, P J F; el-Shafei, S; Khattab, M M

    2003-02-01

    The aqueous extract of propolis has been formulated as a nutritional food product and administered, as an adjuvant to therapy, to patients with mild to moderate asthma daily for 2 months in the framework of a comparative clinical study in parallel with a placebo preparation. The diagnosis of asthma was made according to the criteria of patient classification of the National Institutes of Health and Global Initiative for Asthma Management. At inclusion, the pulmonary forced expiratory volume in the first second (FEV1) as a percentage of the forced vital capacity (FVC) was more than 80% in mild persistent cases, and between 60 and 80% in moderate persistent cases, showing an increase in the degree of reversibility of > 15% in FEV1. All patients were on oral theophylline as controller therapy, none was receiving oral or inhaled corticosteroids, none had other comorbidities necessitating medical treatment, and all were from a middle-class community and had suffered from asthma for the last 2-5 years. Twenty-four patients received the placebo, with one drop-out during the study, while 22 received the propolis extract, with no drop-outs. The age range of the patients was 19-52 years; 36 were male and 10 female. The number of nocturnal attacks was recorded on a weekly basis, while pulmonary function tests were performed on all patients at the beginning of the trial, 1 month later and at the termination of the trial. Immunological parameters, including various cytokines and eicosanoids known to play a role in asthma, were measured in all patients at the beginning of the trial and 2 months later. Analysis of the results at the end of the clinical study revealed that patients receiving propolis showed a marked reduction in the incidence and severity of nocturnal attacks and improvement of ventilatory functions. The number of nocturnal attacks dropped from an average of 2.5 attacks per week to only 1. The improvement in pulmonary functions was manifested as a nearly 19

  1. [Physicochemical and pharmacological characteristic and clinical efficacy of an anti-irritable bowel syndrome agent, polycarbophil calcium (Polyful)].

    Science.gov (United States)

    Iwanaga, Yuji

    2002-03-01

    Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain or discomfort and abnormal defecation. Polycarbophil calcium, a water-absorbing polymer, is expected to improve stool consistency. Polycarbophil calcium decalcified under the acidic condition and then absorbed 70 times its weight of water under the neutral condition. In in situ experiments using rat jejunum and colon, polycarbophil decreased water absorption by the intestine without affecting water secretion. Polycarbophil inhibited prostaglandin E2-, 5-hydroxy-L-tryptophan- and castor oil-induced diarrhea in mice or rats. Polycarbophil calcium also inhibited sennoside-induced diarrhea in dogs. Polycarbophil increased the weight of feces in naive or low-fiber diet feeding rats. In naive dogs, polycarbophil calcium increased stool frequency, stool weight and moisture. Polycarbophil was not absorbed from the gastrointestine, not metabolized and eliminated into feces in rats and dogs. Polycarbophil calcium did not affect the absorption of coadministered drugs in dogs. In the dose-finding clinical study for IBS, polycarbophil calcium was effective both in diarrhea and constipation. In the Phase III study, polycarbophil calcium was superior to trimebutine maleate in efficacy and equal in safety. Emesis/vomiting and thirst were observed, but episodes of diarrhea or constipation by excessive action were few. Polycarbophil calcium seems promising as an anti-IBS agent.

  2. Beyond the era of NPH insulin--long-acting insulin analogs: chemistry, comparative pharmacology, and clinical application.

    Science.gov (United States)

    Owens, D R; Bolli, G B

    2008-10-01

    The new rDNA and DNA-derived "basal" insulin analogs, glargine and detemir, represent significant advancement in the treatment of diabetes compared with conventional NPH insulin. This review describes blood glucose homeostasis by insulin in people without diabetes and outlines the physiological application of exogenous insulin in patients with type 1 and type 2 diabetes. The requirements for optimal basal insulin treatment are discussed and the methods used in the evaluation of basal insulins are presented. An essential criterion in the development of an "ideal" basal insulin preparation is that the molecular modifications made to the human insulin molecule do not compromise safety. It is also necessary to obtain a clear understanding of the pharmacokinetic and pharmacodynamic characteristics of the two currently available basal insulin analogs. When comparing glargine and detemir, the different molar concentration ratios of the two insulin formulations should be considered along with the nonspecificity of assay systems used to determine insulin concentrations. However, euglycemic clamp studies in crossover study design provide a good basis for comparing the pharmacodynamic responses. When the latter is analyzed by results of intervention clinical trials, it is concluded that both glargine and detemir are superior to NPH in type 1 and type 2 diabetes. However, there is sufficient evidence to demonstrate that these two long-acting insulin analogs are different in both their pharmacokinetic and pharmacodynamic profiles. These differences should be taken into consideration when the individual analogs are introduced to provide basal insulin supplementation to optimize blood glucose control in patients with type 1 and type 2 diabetes as well. PubMed-Medline was searched for articles relating to pharmacokinetics and pharmacodynamics of glargine and detemir. Articles retrieved were reviewed and selected for inclusion if (1) the euglycemic clamp method was used with a

  3. The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledgebase of drug targets and their ligands

    Science.gov (United States)

    Pawson, Adam J.; Sharman, Joanna L.; Benson, Helen E.; Faccenda, Elena; Alexander, Stephen P.H.; Buneman, O. Peter; Davenport, Anthony P.; McGrath, John C.; Peters, John A.; Southan, Christopher; Spedding, Michael; Yu, Wenyuan; Harmar, Anthony J.

    2014-01-01

    The International Union of Basic and Clinical Pharmacology/British Pharmacological Society (IUPHAR/BPS) Guide to PHARMACOLOGY (http://www.guidetopharmacology.org) is a new open access resource providing pharmacological, chemical, genetic, functional and pathophysiological data on the targets of approved and experimental drugs. Created under the auspices of the IUPHAR and the BPS, the portal provides concise, peer-reviewed overviews of the key properties of a wide range of established and potential drug targets, with in-depth information for a subset of important targets. The resource is the result of curation and integration of data from the IUPHAR Database (IUPHAR-DB) and the published BPS ‘Guide to Receptors and Channels’ (GRAC) compendium. The data are derived from a global network of expert contributors, and the information is extensively linked to relevant databases, including ChEMBL, DrugBank, Ensembl, PubChem, UniProt and PubMed. Each of the ∼6000 small molecule and peptide ligands is annotated with manually curated 2D chemical structures or amino acid sequences, nomenclature and database links. Future expansion of the resource will complete the coverage of all the targets of currently approved drugs and future candidate targets, alongside educational resources to guide scientists and students in pharmacological principles and techniques. PMID:24234439

  4. A Pharmacological Primer of Biased Agonism

    OpenAIRE

    Andresen, Bradley T.

    2011-01-01

    Biased agonism is one of the fastest growing topics in G protein-coupled receptor pharmacology; moreover, biased agonists are used in the clinic today: carvedilol (Coreg®) is a biased agonist of beta-adrenergic receptors. However, there is a general lack of understanding of biased agonism when compared to traditional pharmacological terminology. Therefore, this review is designed to provide a basic introduction to classical pharmacology as well as G protein-coupled receptor signal transductio...

  5. Research on Using PASS System in Clinical Pharmacology Teaching%PASS系统在临床药理学教学中的应用探索

    Institute of Scientific and Technical Information of China (English)

    雷力力; 王凤芝; 季方茹; 荆洪英; 李艳翠

    2011-01-01

    目的 探索临床药理学教学新的方法和形式.方法 在循环系统、消化系统、呼吸系统用药为主,理论课教学中对部分学生引进并应用PASS系统软件,同时以同年级的其它学生为对照.结果 实验班较对照班的成绩平均高出7分,实验班的合格率高出对照班2倍之多.PASS系统的应用有助于培养学生和提高在自学、分析问题和解决问题等多方面能力,为学生将来进入临床合理用药奠定了基础.结论 临床药理学的教学引进PASS系统软件可行,值得推广使用.%Objective To find a better method and style of clinical pharm acology teaching . Methods In theory course teachig of circulatory system ,digestive system and respiratory system ,the teaching method of applying PASS softw are system was used to teach apart of students and compared with the students those who without applying PASS softw are system in the same grade . Results The average score of experim ental class was seven points more than comparative class. The pass rate of experimental class was 2 times higher than comparative class. T he method of applying PASS softw are system contributes to improve student's self-educated ability, analyzing and abilities of solving problem . Conclusion It is feasible to apply PASS system in clinical pharmacology teaching .

  6. Tinnitus: Network pathophysiology-network pharmacology

    Directory of Open Access Journals (Sweden)

    Ana Belen eElgoyhen

    2012-01-01

    Full Text Available Tinnitus, the phantom perception of sound, is a prevalent disorder. One in 10 adults has clinically significant subjective tinnitus, and for 1 in 100, tinnitus severely affects their quality of life. Despite the significant unmet clinical need for a safe and effective drug targeting tinnitus relief, there is currently not a single FDA-approved drug on the market. The search for drugs that target tinnitus is hampered by the lack of a deep knowledge of the underlying neural substrates of this pathology. Recent studies are increasingly demonstrating that, as described for other central nervous system disorders, tinnitus is a pathology of brain networks. The application of graph theoretical analysis to brain networks has recently provided new information concerning their topology, their robustness and their vulnerability to attacks. Moreover, the philosophy behind drug design and pharmacotherapy in central nervous system pathologies is changing from that of magic bullets that target individual chemoreceptors or disease-causing genes into that of magic shotguns, promiscuous or dirty drugs that target disease-causing networks, also known as network pharmacology. In the present work we provide some insight into how this knowledge could be applied to tinnitus pathophysiology and pharmacotherapy.

  7. Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants.

    Science.gov (United States)

    Ma, Julian K-C; Drossard, Jürgen; Lewis, David; Altmann, Friedrich; Boyle, Julia; Christou, Paul; Cole, Tom; Dale, Philip; van Dolleweerd, Craig J; Isitt, Valerie; Katinger, Dietmar; Lobedan, Martin; Mertens, Hubert; Paul, Mathew J; Rademacher, Thomas; Sack, Markus; Hundleby, Penelope A C; Stiegler, Gabriela; Stoger, Eva; Twyman, Richard M; Vcelar, Brigitta; Fischer, Rainer

    2015-10-01

    Although plant biotechnology has been widely investigated for the production of clinical-grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma-Planta project, the HIV-neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco (Nicotiana tabacum). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant-derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant-derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first-in-human, double-blind, placebo-controlled, randomized, dose-escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant-derived pharmaceutical proteins. © 2015 Society for Experimental Biology, Association of

  8. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

    Bang, Ulrich-Christian; Semb, Synne; Nojgaard, Camilla

    2008-01-01

    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may...

  9. Available therapies and current management of fibromyalgia: focusing on pharmacological agents.

    Science.gov (United States)

    Han, C; Lee, S-J; Lee, S-Y; Seo, H-J; Wang, S-M; Park, M-H; Patkar, A A; Koh, J; Masand, P S; Pae, C-U

    2011-07-01

    Fibromyalgia (FM) is a chronic medical condition characterized by physical, psychiatric and psychological symptoms. Widespread pain, fatigue, sleep disturbances, heightened sensitivity, morning stiffness, decreased volition, depressed mood and a history of early abuse are frequently reported by patients with FM. Treatment of fibromyalgia is multidisciplinary, with an emphasis on active patient participation, medications, cognitive-behavioral therapy and physical modalities. No single medication has yet been found to sufficiently control all the symptoms of FM; currently available medication classes include antidepressants, nonsteroidal anti-inflammatory drugs, opioids, sedatives, muscle relaxants, analgesics, hypnotic agents and anticonvulsants. Hence, treatment for patients with FM, including pharmacological and non-pharmacological approaches, should be individualized based on each patient's clinical history, target symptoms and functional impairments. Although nonpharmacological modalities are also frequently used, recent research has focused on identifying more effective pharmacological treatments, particularly antidepressants and anticonvulsants. Furthermore, several new pharmacological agents have been now officially approved for the treatment of patients with FM. Thus, the purpose of this review is to help healthcare professionals make informed decisions about the appropriate use of a number of pharmacological treatments for patients with FM.

  10. Phase I Clinical Pharmacology Studies

    Science.gov (United States)

    1993-09-28

    Organ Cultures el Humnan BEGCUE. SARA SPANGE.NB.RGER. BARBARA A. ReISpnfiy Elowhie’n. £ ARAUDA’. C CRUMP S MARLIN. V`JRUWE LS AND GEORGES PETER Bmw...SUMHARY T.O. #10 JR 6026, an 8-aminoquinoline similar to primaquine, may be a useful agent to treat visceral leishmaniasis and may hold an advantage over

  11. Bleomycin clinical pharmacology by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Hall, S.W.; Strong, J.E.; Broughton, A.; Frazier, M.L.; Benjamin, R.S.

    1982-01-01

    Bleomycin pharmacokinetics were studied by radioimmunoassay in 11 patients who received 7-30 U intravenously (IV) and eight patients who received 4-30 U subcutaneously (SC). For patients who received IV bleomycin plasma disappearance was biphasic, with a mean initial half-life of 0.26 h and a terminal half-life of 2.3 h. Mean plasma drug clearance was 67.8 ml/min/m/sup 2/ and the volume of distribution was 13.2 l/m/sup 2/. Urinary excretion accounted for 63.9% of the drug in 24 h. After SC administration peak plasma levels occurred in 1.1 h, with a mean elimination half-life of 4.3 h. Mean plasma drug clearance was 60.5 ml/min/m/sup 2/ and the volume of distribution was 19.2 l/m/sup 2/. Bleomycin plasma clearance correlated well with serum creatinine (r/sup 2/=0.72). Bleomycin has a rapid plasma elimination and urinary excretion. Bleomycin bioavailability after SC administration appears comparable to that seen after IV administration as determined by the areas under the plasma disappearance curves. Prolonged plasma levels are seen after SC injection, suggesting this route of administration can produce plasma concentrations comparable to those attained with continuous IV infusions.

  12. Aspirin: Pharmacology and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Enma V. Paez Espinosa

    2012-01-01

    Full Text Available Antiplatelet therapy has been documented to reduce risks of cardiovascular disease after acute myocardial infarction, coronary artery bypass graft, and in chronic atrial fibrillation patients, amongst other risk factors. Conventional management of thrombosis-based disorders includes the use of heparin, oral anticoagulants, and the preferred antiplatelet agent aspirin. Interestingly, aspirin was not intended to be used as an antiplatelet agent; rather, after being repurposed, it has become one of the most widely prescribed antithrombotic drugs. To this end, there have been several milestones in the development of antiplatelet agents in the last few decades, such as adenosine diphosphate receptor inhibitors, phosphodiesterase inhibitors, and GPIIb/IIIa inhibitors. However, given some of the limitations of these therapies, aspirin continues to play a major role in the management of thrombotic and cardiovascular disorders and is expected to do so for years to come.

  13. Atorvastatin pharmacological effect and clinical application%阿托伐他汀药理作用以及临床应用

    Institute of Scientific and Technical Information of China (English)

    杨天忠

    2013-01-01

    Objective To explore the pharmacological action and clinical application of atorvastatin. Methods The hospital treated 52 cases of familial hypercholesterolemia patients were given oral atorvastatin treatment, compared before and after treatment of high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), triglyceride (TG three), total cholesterol (TC), C reactive protein (CRP) and other indicators.Results After treatment than before treatment in patients with HDL-C increased, while LDL-C, TC, TG and CRP were decreased signiifcantly, the treatment, there was statistically signiifcant (P<0.05). Treatment of patients with only 3 patients had mild appetite decrease adverse reactions (without treatment improved), all the patients had no serious adverse events occurred. Conclusion Atorvastatin has good clinical efifcacy in treatment of familial hypercholesterolemia, good safety, no serious adverse reactions, it is worthy of clinical use.%目的:探讨阿托伐他汀的药理作用及临床应用。方法2011年7月至2013年6月我院共收治52例家族性高胆固醇血症(FH)患者,治疗方案为口服阿托伐他汀,分别于治疗前后检测高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、三酰甘油(TG)、总胆固醇(TC)、C反应蛋白(CRP)指标并进行比较。结果治疗后患者的HDL-C均比治疗前升高,而LDL-C、TC、TG以及CRP均比治疗降低,差异明显,有统计学意义(P<0.05)。治疗期间,有3例患者出现便秘、腹胀、消化不良等可耐受的不良反应,所有患者均未出现的严重不良反应。结论应用阿托伐他汀治疗FH,临床效果显著,而且不良反应发生率低,安全可靠,可在临床应用。

  14. Clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy": the influence of gender and genetics (CYP2D6, COMT, 5-HTT.

    Directory of Open Access Journals (Sweden)

    Ricardo Pardo-Lozano

    Full Text Available The synthetic psychostimulant MDMA (± 3,4-methylenedioxymethamphetamine, ecstasy acts as an indirect serotonin, dopamine, and norepinephrine agonist and as a mechanism-based inhibitor of the cytochrome P-450 2D6 (CYP2D6. It has been suggested that women are more sensitive to MDMA effects than men but no clinical experimental studies have satisfactorily evaluated the factors contributing to such observations. There are no studies evaluating the influence of genetic polymorphism on the pharmacokinetics (CYP2D6; catechol-O-methyltransferase, COMT and pharmacological effects of MDMA (serotonin transporter, 5-HTT; COMT. This clinical study was designed to evaluate the pharmacokinetics and physiological and subjective effects of MDMA considering gender and the genetic polymorphisms of CYP2D6, COMT, and 5-HTT. A total of 27 (12 women healthy, recreational users of ecstasy were included (all extensive metabolizers for CYP2D6. A single oral weight-adjusted dose of MDMA was administered (1.4 mg/kg, range 75-100 mg which was similar to recreational doses. None of the women were taking oral contraceptives and the experimental session was performed during the early follicular phase of their menstrual cycle. Principal findings show that subjects reached similar MDMA plasma concentrations, and experienced similar positive effects, irrespective of gender or CYP2D6 (not taking into consideration poor or ultra-rapid metabolizers or COMT genotypes. However, HMMA plasma concentrations were linked to CYP2D6 genotype (higher with two functional alleles. Female subjects displayed more intense physiological (heart rate, and oral temperature and negative effects (dizziness, sedation, depression, and psychotic symptoms. Genotypes of COMT val158met or 5-HTTLPR with high functionality (val/val or l/* determined greater cardiovascular effects, and with low functionality (met/* or s/s negative subjective effects (dizziness, anxiety, sedation. In conclusion, the contribution

  15. Phosphodiesterase inhibitors: history of pharmacology.

    Science.gov (United States)

    Schudt, Christian; Hatzelmann, Armin; Beume, Rolf; Tenor, Hermann

    2011-01-01

    The first pharmacological investigations of phosphodiesterase (PDE) inhibitors were developed with the clinical efficacies of drugs isolated from coffee, cacao and tea but only later their relevant ingredients were identified as xanthines that act as PDE. With its diuretic, inotropic and bronchodilating clinical efficacy, use of theophylline anticipated the clinical goals, which were later approached with the first-generation of weakly selective PDE inhibitors in the period from 1980 to 1990. Pharmacological and clinical research with these early compounds provided a vast pool of information regarding desired and adverse actions - although most of these new drugs had to be discontinued due to severe adverse effects. The pharmacological models for cardiac, vascular and respiratory indications were analysed for their PDE isoenzyme profiles, and when biochemical and molecular biological approaches expanded our knowledge of the PDE superfamily, the purified isoenzymes that were now available opened the door for more systematic studies of inhibitors and for generation of highly selective isoenzyme-specific drugs. The development of simple screening models and clinically relevant indication models reflecting the growing knowledge about pathomechanisms of disease are summarised here for today's successful application of highly selective PDE3, PDE4 and PDE5 inhibitors. The interplay of serendipitous discoveries, the establishment of intelligent pharmacological models and the knowledge gain by research results with new substances is reviewed. The broad efficacies of new substances in vitro, the enormous biodiversity of the PDE isoenzyme family and the sophisticated biochemical pharmacology enabled Viagra to be the first success story in the field of PDE inhibitor drug development, but probably more success stories will follow.

  16. Comparison of FDA Approved Kinase Targets to Clinical Trial Ones: Insights from Their System Profiles and Drug-Target Interaction Networks

    Directory of Open Access Journals (Sweden)

    Jingyu Xu

    2016-01-01

    Full Text Available Kinase is one of the most productive classes of established targets, but the majority of approved drugs against kinase were developed only for cancer. Intensive efforts were therefore exerted for releasing its therapeutic potential by discovering new therapeutic area. Kinases in clinical trial could provide great opportunities for treating various diseases. However, no systematic comparison between system profiles of established targets and those of clinical trial ones was conducted. The reveal of probable difference or shift of trend would help to identify key factors defining druggability of established targets. In this study, a comparative analysis of system profiles of both types of targets was conducted. Consequently, the systems profiles of the majority of clinical trial kinases were identified to be very similar to those of established ones, but percentages of established targets obeying the system profiles appeared to be slightly but consistently higher than those of clinical trial targets. Moreover, a shift of trend in the system profiles from the clinical trial to the established targets was identified, and popular kinase targets were discovered. In sum, this comparative study may help to facilitate the identification of the druggability of established drug targets by their system profiles and drug-target interaction networks.

  17. Is the large simple trial design used for comparative, post-approval safety research? A review of a clinical trials registry and the published literature.

    Science.gov (United States)

    Reynolds, Robert F; Lem, Joanna A; Gatto, Nicolle M; Eng, Sybil M

    2011-10-01

    Post-approval, observational drug safety studies face well known difficulties in controlling for confounding, particularly confounding by indication for drug use. A study design that addresses confounding by indication is the large simple trial (LST). LSTs are characterized by large sample sizes, often in the thousands; broad entry criteria consistent with the approved medication label; randomization based on equipoise, i.e. neither physician nor patient believes that one treatment option is superior; minimal, streamlined data collection requirements; objectively-measured endpoints (e.g. death, hospitalization); and follow-up that minimizes interventions or interference with normal clinical practice. In theory then, the LST is a preferred study design for drug and vaccine safety research because it controls for biases inherent to observational research while still providing results that are generalizable to 'real-world' use. To evaluate whether LSTs are used for comparative safety evaluation and if the design is, in fact, advantageous compared with other designs, we conducted a review of the published literature (1949 through 31 December 2010) and the ClinicalTrials.gov registry (2000 through 31 December 2010). Thirteen ongoing or completed safety LSTs were identified. The design has rarely been used in comparative drug safety research, which is due to the operational, financial and scientific hurdles of implementing the design. The studies that have been completed addressed important clinical questions and, in some cases, led to re-evaluation of medical practice. We conclude the design has demonstrated utility for comparative safety research of medicines and vaccines if the necessary scientific and operational conditions for its use are met.

  18. Reward Learning as a Potential Target for Pharmacological Augmentation of Cognitive Remediation for Schizophrenia: A Roadmap for Preclinical Development

    Directory of Open Access Journals (Sweden)

    Dean T Acheson

    2013-06-01

    Full Text Available Rationale: Impaired cognitive abilities are a key characteristic of schizophrenia. Although currently approved pharmacological treatments have demonstrated efficacy for positive symptoms, to date no pharmacological treatments successfully reverse cognitive dysfunction in these patients. Cognitively-based interventions such as cognitive remediation (CR and other psychosocial interventions however, may improve some of the cognitive and functional deficits of schizophrenia. Given that these treatments are time-consuming and labor-intensive, maximizing their effectiveness is a priority. Augmenting psychosocial interventions with pharmacological treatments may be a viable strategy for reducing the impact of cognitive deficits in patients with schizophrenia. Objective: We propose a strategy to develop pharmacological treatments that can enhance the reward-related learning processes underlying successful skill-learning in psychosocial interventions. Specifically, we review clinical and preclinical evidence and paradigms that can be utilized to develop these pharmacological augmentation strategies. Prototypes for this approach include dopamine D1 receptor and α7 nicotinic acetylcholine receptor agonists as attractive targets to specifically enhance reward-related learning during CR. Conclusion: The approach outlined here could be used broadly to develop pharmacological augmentation strategies across a number of cognitive domains underlying successful psychosocial treatment.

  19. The Pharmacology of Regenerative Medicine

    Science.gov (United States)

    Saul, Justin M.; Furth, Mark E.; Andersson, Karl-Erik

    2013-01-01

    Regenerative medicine is a rapidly evolving multidisciplinary, translational research enterprise whose explicit purpose is to advance technologies for the repair and replacement of damaged cells, tissues, and organs. Scientific progress in the field has been steady and expectations for its robust clinical application continue to rise. The major thesis of this review is that the pharmacological sciences will contribute critically to the accelerated translational progress and clinical utility of regenerative medicine technologies. In 2007, we coined the phrase “regenerative pharmacology” to describe the enormous possibilities that could occur at the interface between pharmacology, regenerative medicine, and tissue engineering. The operational definition of regenerative pharmacology is “the application of pharmacological sciences to accelerate, optimize, and characterize (either in vitro or in vivo) the development, maturation, and function of bioengineered and regenerating tissues.” As such, regenerative pharmacology seeks to cure disease through restoration of tissue/organ function. This strategy is distinct from standard pharmacotherapy, which is often limited to the amelioration of symptoms. Our goal here is to get pharmacologists more involved in this field of research by exposing them to the tools, opportunities, challenges, and interdisciplinary expertise that will be required to ensure awareness and galvanize involvement. To this end, we illustrate ways in which the pharmacological sciences can drive future innovations in regenerative medicine and tissue engineering and thus help to revolutionize the discovery of curative therapeutics. Hopefully, the broad foundational knowledge provided herein will spark sustained conversations among experts in diverse fields of scientific research to the benefit of all. PMID:23818131

  20. Pomalidomide: first global approval.

    Science.gov (United States)

    Elkinson, Shelley; McCormack, Paul L

    2013-05-01

    Pomalidomide (Pomalyst(®)) is a small molecule analogue of thalidomide under development with Celgene Corporation for the oral treatment of haematological and connective tissue diseases. Pomalidomide has been approved in the USA and is awaiting approval in the EU for use with low-dose dexamethasone for the treatment of relapsed and refractory multiple myeloma that has progressed following at least two prior therapies, including lenalidomide and bortezomib. The efficacy and safety of pomalidomide as monotherapy in patients with relapsed and refractory multiple myeloma has also been evaluated in a phase III trial. The agent is in phase III clinical development for the treatment of myelofibrosis and in phase II development for systemic sclerosis. Pomalidomide is also being investigated in patients with amyloidosis, prostate cancer, small cell lung cancer, pancreatic cancer, graft-versus-host disease, and Waldenstrom's macroglobulinaemia. This article summarizes the milestones in the development of pomalidomide leading to this first global approval for relapsed and refractory multiple myeloma.

  1. The pharmacological management of erectile dysfunction

    African Journals Online (AJOL)

    Senior Lecturer and Clinical Pharmacologist. Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Pretoria. Corresponding ... dyslipidaemia and obesity, should be advocated. Psychotherapy alone, or in ...

  2. [Pharmacological treatment of schizophrenia].

    Science.gov (United States)

    Thomas, Pierre

    2013-03-01

    Decades of practice in psychiatriy and hundreds of clinical trials have demonstrated the efficacy of antipsychotics on symptoms of schizophrenia. Recently, the knowledge acquired from non-interventional studies have supplemented the information needed in daily practice by raising the issue of efficiency by incorporating not only the effectiveness and safety of treatment but also its acceptability by the patient. Adherence to antipsychotic treatment has become the key issue of the prognosis. The pharmacological management of patients with an acute episode of schizophrenia requires rapid therapeutic decisions to treat a patient who is likely to be sometimes unhelpful and agitated. The choice of treatment will have a significant impact on the prevention of psychotic relapses, on the overall prognosis and on the quality of life of the patient. In many countries of the recommendations and treatment algorithms for the management of acute psychosis were distributed, considering factors specific to the patient and his environment, his mental characteristics and local care setting.

  3. Pharmacogenomics of alcohol addiction: Personalizing pharmacologic treatment of alcohol dependence

    Directory of Open Access Journals (Sweden)

    Ragia Georgia

    2014-01-01

    Full Text Available Alcohol dependence is a serious psychiatric disorder with harmful physical, mental and social consequences, and a high probability of a chronic relapsing course. The field of pharmacologic treatment of alcohol dependence and craving is expanding rapidly; the drugs that have been found to reduce relapse rates or drinking in alcohol-dependent patients and are approved for treatment of alcohol dependence are naltrexone, acamprosate and disulfiram, whereas also topiramate appears as a promising therapy. For many patients, however, these treatments are not effective. Evidence from a number of different studies suggests that genetic variation is a significant contributor to interindividual variation of clinical presentation of alcohol problems and response to a given treatment. The aim of the present review is to summarize and discuss the findings on the association between gene polymorphisms and the response to alcohol dependence treatment medications. It is anticipated that future implementation of pharmacogenomics in clinical practice will help personalize alcohol dependence drug treatment, and development personalized hospital pharmacology.

  4. Pharmacological treatment of depression in older people

    OpenAIRE

    Curran, Stephen; Byrne, Andrew; Wattis, John

    2006-01-01

    In the light of recent National Institute for Clinical Excellence (NICE) and Committee for the Safety of Medicines (CSM) guidance we discuss the importance of the diagnosis of depression in old age and review pharmacological interventions. An introductory section is followed by sections on each of the main antidepressant groups. This briefly describes their pharmacology and reviews research done specifically relevant to older people. Finally practical clinical applications are discussed.

  5. Exploratory safety pharmacology: a new safety paradigm to de-risk drug candidates prior to selection for regulatory science investigations.

    Science.gov (United States)

    Cavero, Icilio

    2009-11-01

    The primary objective of Safety Pharmacology is to ensure the safety of medicines on physiological functions in order to protect humans against adverse drug reactions. Safety Pharmacology became a major non-clinical discipline in 2000 when the International Conference on Harmonization approved the S7A guideline. This regulatory document requires pharmaceutical companies to undertake Safety Pharmacology assessment under Good Laboratory Practice (GLP) in order to guarantee the absence of unmanageable risks on vital organ function for compounds to be tested on humans. These regulatory studies often reveal liabilities impacting on the smooth transition of drug candidates from the discovery phase into the clinical arena. However, if these safety issues were uncovered prior to regulatory science assessment, the chemistry of poorly safe molecules could be modified during the lead optimisation phase for preventing later occurring attrition accidents. This article proposes the establishment of a spin-off specialty of Regulatory Safety Pharmacology, for which the name 'Exploratory Safety Pharmacology' is proposed. The objective of this discipline would be to conduct early safety investigations on potential drug candidates by applying, outside the constraints of GLP, in silico, in vitro, ex vivo and in vivo platforms translating clinical liabilities into simple, fast and cost-effective screening assays. This approach should result in early hazard detection with rapid turnaround of the data, enabling medicinal chemists to mitigate the safety liabilities of new compounds in an iterative manner. Hence, the ultimate aim of Exploratory Safety Pharmacology activities is to transform Regulatory Safety Pharmacology investigations into risk-known exercises.

  6. Quantitative systems pharmacology: a promising approach for translational pharmacology.

    Science.gov (United States)

    Gadkar, K; Kirouac, D; Parrott, N; Ramanujan, S

    Biopharmaceutical companies have increasingly been exploring Quantitative Systems Pharmacology (QSP) as a potential avenue to address current challenges in drug development. In this paper, we discuss the application of QSP modeling approaches to address challenges in the translational of preclinical findings to the clinic, a high risk area of drug development. Three cases have been highlighted with QSP models utilized to inform different questions in translational pharmacology. In the first, a mechanism based asthma model is used to evaluate efficacy and inform biomarker strategy for a novel bispecific antibody. In the second case study, a mitogen-activated protein kinase (MAPK) pathway signaling model is used to make translational predictions on clinical response and evaluate novel combination therapies. In the third case study, a physiologically based pharmacokinetic (PBPK) model it used to guide administration of oseltamivir in pediatric patients.

  7. Training in psychodiagnostic testing in APA-approved PsyD and PhD clinical psychology programs.

    Science.gov (United States)

    Piotrowski, C; Zalewski, C

    1993-10-01

    Fifty-one percent (N = 80) of directors of doctoral PhD and PsyD programs in clinical psychology, accredited by the American Psychological Association (APA), responded to a survey on assessment training. The study was a replication of an earlier survey by Piotrowski and Keller (1984b) on instruction, practices, and attitudes on testing. Our findings indicated that training emphasis in assessment coursework has changed very little over the past decade. Intelligence testing was emphasized in most programs, followed by objective and projective personality assessment. However, training in behavioral assessment techniques was required in only half of the responding programs. There were no significant differences between PhD and PsyD programs concerning required coursework in assessment. Factors that influence the perennial importance of testing in the clinical core curriculum are discussed.

  8. A randomized, placebo-controlled double-blinded comparative clinical study of five over-the-counter non-pharmacological topical analgesics for myofascial pain: single session findings

    Directory of Open Access Journals (Sweden)

    Avrahami Daniel

    2012-03-01

    Full Text Available Abstract Objectives To investigate the effects of topical agents for the treatment of Myofascial Pain Syndrome (MPS and Myofascial Trigger Point (MTRP. Methods Subjects with an identifiable trigger point in the trapezius muscle, age 18-80 were recruited for a single-session randomized, placebo-blinded clinical study. Baseline measurements of trapezius muscle pressure pain threshold (PPT: by pressure algometer along with right and left cervical lateral flexion (rangiometer were obtained by a blinded examiner. An assessor blinded to the outcomes assessments applied one of 6 topical formulations which had been placed in identical plastic containers. Five of these topicals were proposed active formulations; the control group was given a non-active formulation (PLA. Five minutes after the application of the formula the outcome measures were re-tested. Data were analyzed with a 5-way ANOVA and Holms-adjusted t-tests with an alpha level of 0.05. Results 120 subjects were entered into the study (63 females; ages 16-82; 20 subjects randomly allocated into each group. The pre- and post-treatment results for pressure threshold did show significant intra-group increases for the Ben-Gay Ultra Strength Muscle Pain Ointment (BG, the Professional Therapy MuscleCare Roll-on (PTMC roll-on and Motion Medicine Cream (MM with an increased threshold of 0.5 kg/cm2 (+/-0.15, 0.72 kg/cm2 (+/-0.17 and 0.47 Kg/cm2 (+/-0.19 respectively. With respect to the inter-group comparisons, PTMC roll-on showed significant increases in pressure threshold compared with Placebo (PLA (p = 0.002 and Icy Hot Extra Strength Cream (IH (p = 0.006. In addition, BG demonstrated significant increases in pressure threshold compared with PLA (p = 0.0003. Conclusions With regards to pressure threshold, PTMC roll-on, BG and MM showed significant increases in pain threshold tolerance after a short-term application on a trigger points located in the trapezius muscle. PTMC roll-on and BG were both

  9. Linaclotide: first global approval.

    Science.gov (United States)

    McWilliams, Vanessa; Whiteside, Glenn; McKeage, Kate

    2012-11-12

    Linaclotide is a once-daily, orally administered, first-in-class agonist of guanylate cyclase-C that is minimally absorbed. It is being developed to treat gastrointestinal disorders by Ironwood Pharmaceuticals and its partners, Forest Laboratories (North America), Almirall (Europe) and Astellas Pharma (Asia-Pacific). Linaclotide has received its first global approval in the US for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation (CIC), and a marketing submission has been filed in the EU for IBS-C. This article summarizes the milestones in the development of linaclotide leading to this first approval for IBS-C and CIC. This profile has been extracted and modified from the Adis R&D Insight drug pipeline database. Adis R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.

  10. Neuropathic pain and pharmacological treatment.

    Science.gov (United States)

    Jongen, Joost L M; Hans, Guy; Benzon, Honorio T; Huygen, Frank; Hartrick, Craig T

    2014-03-01

    Neuropathic pain is a serious chronic condition strongly affecting quality of life, which can be relieved but cannot be cured. Apart from symptomatic management, treatment should focus on the underlying disorder. The estimated prevalence is at least 1% to 5% of the general population. Neuropathic pain is characterized both by spontaneous and evoked pain. A diagnosis of neuropathic pain can usually be established based solely on history and neurological examination. Ancillary investigations may include EMG and computerized tomography/magnetic resonance imaging scans, depending on the localization of the suspected lesion. A limited number of agents, primarily directed at symptom control, are currently approved for use in neuropathic pain. A mechanism-based approach to pharmacological intervention supports the use of polypharmacy in neuropathic pain.

  11. Ipilimumab: first global approval.

    Science.gov (United States)

    Cameron, Fiona; Whiteside, Glenn; Perry, Caroline

    2011-05-28

    Ipilimumab (Yervoy®) is an anti-cytotoxic T-lymphocyte antigen (CTLA)-4 monoclonal antibody that has been approved in the US for the first- or second-line treatment of patients with malignant melanoma. In the EU, it is awaiting approval as second-line therapy for melanoma. Ipilimumab blocks the effects of the negative T-cell regulator CTLA-4, which may in turn augment T-cell responses to tumour cells. Preclinical studies have indicated that antibody blocking of CTLA-4 can lead to potent immune responses. Ipilimumab is also in development as first- and second-line therapy for prostate cancer where it has progressed to phase III clinical trials worldwide, and it is in phase II development for non-small cell lung cancer. Ipilimumab was originated by the University of California, Berkeley, in the US and subsequently licensed to Medarex, which was later acquired by Bristol-Myers Squibb. This article summarizes the milestones in the development of intravenous ipilimumab leading to this first approval. This profile has been extracted from Wolters Kluwer's R&D Insight drug pipeline database. R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.

  12. Advances in the understanding and clinical management of mastocytosis and clonal mast cell activation syndromes [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    David González-de-Olano

    2016-11-01

    Full Text Available Clonal mast cell activation syndromes and indolent systemic mastocytosis without skin involvement are two emerging entities that sometimes might be clinically difficult to distinguish, and they involve a great challenge for the physician from both a diagnostic and a therapeutic point of view. Furthermore, final diagnosis of both entities requires a bone marrow study; it is recommended that this be done in reference centers. In this article, we address the current consensus and guidelines for the suspicion, diagnosis, classification, treatment, and management of these two entities.

  13. Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer.

    Science.gov (United States)

    Du, Juan; Cieslak, John A; Welsh, Jessemae L; Sibenaller, Zita A; Allen, Bryan G; Wagner, Brett A; Kalen, Amanda L; Doskey, Claire M; Strother, Robert K; Button, Anna M; Mott, Sarah L; Smith, Brian; Tsai, Susan; Mezhir, James; Goswami, Prabhat C; Spitz, Douglas R; Buettner, Garry R; Cullen, Joseph J

    2015-08-15

    The toxicity of pharmacologic ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Because pancreatic cancer cells are sensitive to H2O2 generated by ascorbate, they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacologic ascorbate enhances the cytotoxic effects of ionizing radiation as seen by decreased cell viability and clonogenic survival in all pancreatic cancer cell lines examined, but not in nontumorigenic pancreatic ductal epithelial cells. Ascorbate radiosensitization was associated with an increase in oxidative stress-induced DNA damage, which was reversed by catalase. In mice with established heterotopic and orthotopic pancreatic tumor xenografts, pharmacologic ascorbate combined with ionizing radiation decreased tumor growth and increased survival, without damaging the gastrointestinal tract or increasing systemic changes in parameters indicative of oxidative stress. Our results demonstrate the potential clinical utility of pharmacologic ascorbate as a radiosensitizer in the treatment of pancreatic cancer.

  14. Unwarranted claims of drug efficacy in pharmaceutical sales visits: are drugs approved on the basis of surrogate outcomes promoted appropriately?

    Science.gov (United States)

    Habibi, Roojin; Lexchin, Joel; Mintzes, Barbara; Holbrook, Anne

    2017-06-29

    This study compares physicians' recall of the claims of benefits on cardiovascular disease and diabetes made by pharmaceutical sales representatives for drugs approved on the basis of a surrogate outcome, i.e., an off-label claim, compared with those approved on the basis of a serious morbidity or mortality (clinical) outcome. Physicians in primary care practices in Montreal, Vancouver, Sacramento and Toulouse, who saw sales representatives as part of their usual practice and served a non-referral population, were contacted in blocks of 25 from a randomized list of all physicians practising in the relevant metropolitan area. We compared how frequently physicians reported that sales reps made claims of serious morbidity or mortality (clinically meaningful) benefits for drugs approved on the basis of surrogate outcomes vs. drugs approved on the basis of clinical outcomes. There were 448 promotions for 58 unique brand name cardiovascular and diabetes drugs. Claims of clinically meaningful benefit were reported in 156 (45%) of the 347 promotions for surrogate outcome drugs, constituting unwarranted efficacy claims, i.e., off-label promotion. Claims of clinical benefit were reported in 72 of the 101 promotions (71%) for drugs approved on the basis of clinical outcomes, adjusted OR = 0.3 (95% CI 0.2, 0.6), P sales visit promotions for drugs approved only on the basis of surrogate outcomes extended beyond the regulator-approved efficacy information for the product in almost half of promotions. Unapproved claims of drug efficacy constitute a form of off-label promotion and merit greater attention from regulators. © 2017 The British Pharmacological Society.

  15. Non-Pharmacological Treatments of Allergic Rhinitis (Neglected Treatments).

    Science.gov (United States)

    Zohalinezhad, Mohammad Ebrahim; Zarshenas, Mohammad M

    2016-05-01

    Allergic rhinitis is the most common diseases affecting people in industrialized society. However, this is not a new disease and it was clinically described and treated for the first time by Rhazes (865-925 CE). The disease was also mentioned in "The Canon of Medicine" by Avicenna (980-1037). We searched in Scopus, Web of Science, and PubMed for "allergic rhinitis", "interactions", "non-prescription", "prescription", and in electronic copies of ITM sources the "canon" and "Al-Havi". Both Persian pioneers of Medicine recommended non-pharmacologic management as an important phase of the therapy. Their recommendations consisted of avoiding overeating and polydipsia, massage of the lower extremities, adjusting the duration and time of sleep, sleeping in the supine position, avoiding exposure of the head to cold air and taking a shower early in the morning. Although some aspects of their recommendations, such as massage of the lower extremities, avoiding of overeating and adjusting of sleep pattern were approved, but further cross-sectional and prospective studies are needed to confirm other non-pharmacological treatments.

  16. Comparison of the cancer gene targeting and biochemical selectivities of all targeted kinase inhibitors approved for clinical use.

    Directory of Open Access Journals (Sweden)

    Joost C M Uitdehaag

    Full Text Available The anti-proliferative activities of all twenty-five targeted kinase inhibitor drugs that are in clinical use were measured in two large assay panels: (1 a panel of proliferation assays of forty-four human cancer cell lines from diverse tumour tissue origins; and (2 a panel of more than 300 kinase enzyme activity assays. This study provides a head-on comparison of all kinase inhibitor drugs in use (status Nov. 2013, and for six of these drugs, the first kinome profiling data in the public domain. Correlation of drug activities with cancer gene mutations revealed novel drug sensitivity markers, suggesting that cancers dependent on mutant CTNNB1 will respond to trametinib and other MEK inhibitors, and cancers dependent on SMAD4 to small molecule EGFR inhibitor drugs. Comparison of cellular targeting efficacies reveals the most targeted inhibitors for EGFR, ABL1 and BRAF(V600E-driven cell growth, and demonstrates that the best targeted agents combine high biochemical potency with good selectivity. For ABL1 inhibitors, we computationally deduce optimized kinase profiles for use in a next generation of drugs. Our study shows the power of combining biochemical and cellular profiling data in the evaluation of kinase inhibitor drug action.

  17. Case Report: Myelodysplastic syndrome- associated myeloid sarcoma: an unusual clinical presentation of a rare disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Emoke Horvath

    2016-02-01

    Full Text Available Myeloid sarcoma results from the extramedullary homing and proliferation of immature myeloid precursors. We present the timeline, events and diagnostic pitfalls related to a 66 year-old male patient’s case, admitted to the Hematology Clinic for pancytopenia, fever, weight loss and fatigue. The severe cytopenia and the few blasts observed in his blood smear indicated a bone marrow biopsy. The bone marrow showed hypercellularity and multilineage dysplasia with the presence of 15% myeloblasts. After the biopsy, he promptly developed paraplegia and nuclear magnetic resonance revealed an epidural tumour which was then resected.In the epidural tumour mass blast-like, round cells were observed with a complex immunophenotype, characterized by myeloperoxidase, CD117, CD15, CD99, leucocyte common antigen positivity and a high Ki-67 proliferation index. Considering the main differential diagnostic issues, the final diagnosis was stated as myelodysplastic syndrome-associated myeloid sarcoma. The prognosis was unfavourable, the bone marrow was quickly invaded by proliferating blast cells, and despite chemotherapy attempts, the patient died.

  18. 药物性白细胞减少和粒细胞缺乏症临床分析%Clinical analysis of pharmacologic leukopenia and agranulocytosis

    Institute of Scientific and Technical Information of China (English)

    蔡成才

    2012-01-01

    目的 分析一组临床常用药物致白细胞减少和粒细胞缺乏的临床表现,提高对药物所致血液系统损害的认识,促进合理用药,提高临床用药安全性.方法 收集1990年1月至2010年12月经我院血液科诊治的66例药物性白细胞减少和粒细胞缺乏患者的临床资料进行回顾性分析.结果 66例药物性白细胞减少和粒细胞缺乏患者中,抗甲状腺功能亢进药所致者16例,占24.2%,抗菌药物9例,占13.6%;抗精神病药物9例,占13.6%;抗癫痫病药物9例,占13.6%;抗类风湿性关节炎药物6例,占9.1%;抗痛风药物4例,占6.1%;降糖药物3例,占4.5%;治疗系统性红斑狼疮皮肤损害的药物3例,占4.5%;治疗胃、十二指肠球部溃疡的药物2例,占3.0%;解热镇痛药物2例,占3.0%;预防乳腺癌根治术后复发的抗雌激素药物2例,占3.0%;口腔科治疗牙痛的中成药制剂1例,占1.5%.临床表现有:白细胞下降(54例,81.8%),粒细胞缺乏(12例,18.2%),骨髓造血功能停滞(3例,4.5%),高热(23例,34.8%),皮肤损害(10例,15.1%),继发各种感染(58例,89%),重症感染(10例,15.1%),感染性休克(3例,4.5%),真菌性败血症(2例,3%),肝功能衰竭(1例,1.5%),肾功能衰竭(1例,1.5%),死亡(3例,4.5%).结论 临床部分常用药物可致白细胞减少、粒细胞缺乏而继发各种感染,可导致病情急剧变化,甚至危及生命,所以要高度重视药物使用的安全性.%Objective By describing the clinical manifestation of a group of commonly used medicines causing pharmacologic leukopenia and agranulocytosis,obtain a better understanding of damage to the blood system by medicines,call attention to rational medication and increase the pharmic safety.Methods Retrospectively analyze the clinical data of the 66 patients of the Department of Hematology in my working hospital from January 1990 to December 2010.Results Among the 66 patients,ADR of 16(24.2

  19. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

    Bang, U.C.; Semb, S.; Nøjgaard, Camilla

    2008-01-01

    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may...... be useful as prophylaxis against post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The protease inhibitor gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL...

  20. Highlights From the American Association of Pharmaceutical Scientists/ International Transporter Consortium Joint Workshop on Drug Transporters in Absorption, Distribution, Metabolism, and Excretion: From the Bench to the Bedside - Clinical Pharmacology Considerations.

    Science.gov (United States)

    Ronaldson, P T; Bauer, B; El-Kattan, A F; Shen, H; Salphati, L; Louie, S W

    2016-11-01

    The American Association of Pharmaceutical Scientists/International Transporter Consortium Joint Workshop on Drug Transporters in absorption, distribution, metabolism, and excretion was held with the objective of discussing innovative advances in transporter pharmacology. Specific topics included (i) transporters at the blood-brain barrier (BBB); (ii) emerging transport proteins; (iii) recent advances in achieving hepatoselectivity and optimizing clearance for organic anion-transporting polypeptide (OATP) substrates; (iv) utility of animal models for transporter studies; and (v) clinical correlation of transporter polymorphisms. Here, we present state-of-the-art highlights from this workshop in these key areas of focus.

  1. Pharmacology for the Psychotherapist.

    Science.gov (United States)

    Goldenberg, Myron Michael

    This book covers those areas of pharmacology that are of importance and interest to the psychotherapist. The 1st chapter introduces the various types of drugs. The 2nd chapter presents an overview of pharmacology and its principles. The 3rd chapter reviews aspects of the human body of importance to understanding the workings of psychotropic drugs.…

  2. Implementation of quality control performance criteria and approved guidelines for upgrading of clinical chemistry laboratory procedures in Alexandria University hospitals.

    Science.gov (United States)

    Rizk, Mohamed Moustafa M; el-Badawi, Nashwa A; Moez, Pacint E; Khattab, Azza A

    2009-03-01

    The aim of the present work was to assess the quality of work in Clinical Pathology Department, Alexandria Main University Hospital, Egypt; as regards the pre-analytical and analytical phases of testing; for later accreditation. This evaluation was performed using inspection sheets that were designed according to the CAP 2006 recommendations. All checklist questions that could not be answered "yes" were considered deficiencies and had to be corrected before being accredited. The questions were classified into ten groups; each group contained a number of questions concerning one of the pre-analytical and analytical assessment activities. We ranked our results into 4 categories according to the degree of fulfillment. The total number of questions that were answered "no" at the start and the end of the study accounted for 64/101 (63.4%) and 34/101 (33.7%) questions respectively. Most of the deficiencies were detected in the pre-analytical phase of the testing process; the first two checklists were used for the evaluation of this phase. At the start of the study, the degree of requirements fulfillment in checklist I and II were 0% and 21.1% respectively. By the end of the study the degree of fulfillment became, 85.7% and 63.2% respectively. Average number of sample rejection due to different causes was evaluated before and after implementing CAP recommendations; these causes include haemolysis, clotted serum, quantity not sufficient, and lost samples; the percentage of rejected samples before implementing CAP recommendations was 15.8%, 1.81%, 0.70%, and 0.51% respectively, while after implementing CAP recommendations it was 7%, 0.77%, 0.08%, and 0.05%, respectively. We concluded that the presence of standardized protocol for the pre-analytical activities had improved the quality of samples received by the lab, and we also concluded that accreditation allows laboratories to evaluate their performance, their compliance with the requirements of the accrediting association

  3. Fisiología y farmacología clínica de los opioides epidurales e intratecales Physiology and clinical pharmacology of epidural and intrathecal opioids

    Directory of Open Access Journals (Sweden)

    B. Mugabure

    2005-02-01

    intradural. La metadona es otro fármaco al que se le ha observado una selectividad medular moderada tras su administración epidural. Sin embargo, su prolongada vida media puede resultar en su acumulación plasmática y presencia de efectos supraespinales a lo largo del tiempo. La administración epidural de fentanilo ofrece muy pocas ventajas sobre su utilización intravenosa, salvo en obstetricia donde parece producir una analgesia selectiva medular de grado moderado. Finalmente, la administración epidural de sufentanilo o alfentanilo parece producir analgesia por recaptación sistémica y redistribución hacia los receptores opioides cerebrales.The history of intrathecal and epidural anaesthesia is in parallel with the development of general anaesthesia. The first published report on opioids for intrathecal anaesthesia belongs to a Romanian surgeon, who presented his experience at Paris in 1901. It was almost a century before the opioids were used for epidural analgesia. Epidural and intrathecal opioids are today part of a routine regimen for intra and postoperative analgesia. Over the last 30 years, the use of epidural opioids has became a standard for analgesia in labor and delivery, and for the management of acute and chronic pain. It has been widely asumed that any opioid placed in the epidural or intrathecal spaces will produce highly selective spinally mediated analgesia that is superior to that produced by other analgesic techniques. Unfortunately, this is simply not true. In fact, multiples opioids are currently employed for spinal use despite the fact that clinical evidence has shown that spinal administration does not produce analgesia with a selective spinal mechanism or the analgesia produced is not superior to that produced by intravenous administration. Appropriate use of spinal opioids necessitates under-standing the physiology and clinical pharmacology of these drugs and which opioids produce selective spinal analgesia and which do not. In short, spinal

  4. Pharmacological research in neonatology.

    Science.gov (United States)

    Dotta, Andrea; Braguglia, Annabella; Salvatori, Guglielmo

    2011-10-01

    In neonatology unit 40 to 80% of the drugs are used as off-label or unlicensed, particularly in Neonatal Intensive Care Unit (NICU), where it has been described that in a single patient up to 60 parenteral drugs can be administered. The course of a drug inside the organism can be defined in 4 different phases: absorption, distribution, metabolism, elimination; for each of these phases the newborn infant has different characteristics than child and adult. In the last years much more attention has been put in pharmacological research specific for the neonatal age and a good trial design should take into account the following points: (1) to define the pediatric disease in terms of natural history, prevalence, severity, treatment and impact of the new drug; (2) to avoid the "try and error" method based on the adult dose corrected for weight or age; (3) to use adapted methodologies (pharmacokinetics); (4) to avoid small clinical trials (limited number of patients), the use of Randomized Controlled Trials rather than observational studies; (5) to consider ethics providing clear information and reducing pain and stress to the baby and its family.

  5. Pharmacological Treatment Effects on Eye Movement Control

    Science.gov (United States)

    Reilly, James L.; Lencer, Rebekka; Bishop, Jeffrey R.; Keedy, Sarah; Sweeney, John A.

    2008-01-01

    The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to…

  6. Antidiabetic herbal drugs officially approved in China.

    Science.gov (United States)

    Jia, Wei; Gao, Wenyuan; Tang, Lida

    2003-12-01

    Over the centuries, Chinese herbal drugs have served as a major source of medicines for the prevention and treatment of diseases including diabetes mellitus (known as 'Xiao-ke'). It is estimated that more than 200 species of plants exhibit hypoglycaemic properties, including many common plants, such as pumpkin, wheat, celery, wax guard, lotus root and bitter melon. To date, hundreds of herbs and traditional Chinese medicine formulas have been reported to have been used for the treatment of diabetes mellitus. This paper provides a brief review of the antidiabetic drugs of plant origin that have been approved by the Chinese health regulatory agency for commercial use in China. It was believed, through pharmacological studies, that medicinal herbs were meticulously organized in these antidiabetic drug formulas such that polysaccharide containing herbs restore the functions of pancreatic tissues and cause an increase in insulin output by the functional beta cells, while other ingredients enhance the microcirculation, increase the availability of insulin and facilitate the metabolism in insulin-dependent processes. Pharmacological and clinical evaluations indicated that these drugs had a mild, but significant, blood glucose lowering effect and that the long-term use of these agents may be advantageous over chemical drugs in alleviating some of the chronic diseases and complications caused by diabetes. Additionally, the use of these natural agents in conjunction with conventional drug treatments, such as a chemical agent or insulin, permits the use of lower doses of the drug and/or decreased frequency of administration which decreases the side effects most commonly observed. Copyright 2003 John Wiley & Sons, Ltd.

  7. Pharmacology of Periodontal Disease.

    Science.gov (United States)

    2014-09-26

    k 7RD-A157 116 PHARMRCOLOGY’ OF PERIODONTAL DISEASE(U) UNIVERSITY OF i/ I HEALTH SCIENCES/CHICAGO MEDICAL SCHOOL DEPT OF I PHARMACOLOGY S F HOFF 24...Region Bethesda, MD 20814-5044 • .RE: Annual Letter Report , ONR Contract #N00014-84-K-0562 "Pharmacology of Periodontal Disease" Dear Capt. Hancock...Annual Letter Report ONR Contract #N00014-84-K-0562 1,! t "Pharmacology of Periodontal Disease" f Steven F. Hoff, Ph.D. (Principal Investigator) A

  8. Pharmacological studies of rolapitant and its clinical application%新型化疗止吐药罗拉匹坦的药理研究及临床应用

    Institute of Scientific and Technical Information of China (English)

    任月英

    2016-01-01

    化疗所致恶心呕吐(CINV)是影响肿瘤患者治疗依从性的关键因素.新型神经激肽-1(NK-1)受体拮抗剂罗拉匹坦与其他已批准上市的NK-1拮抗剂不同,可联合其他止吐药用于延迟性CINV,并能避免药物间相互作用.本文简要综述罗拉匹坦的药理作用及其在CINV治疗中的应用进展.%Nausea and vomiting are the major side effects of chemotherapy and the key reason for non-compliance with cancer treatment.Rolapitant,which is new type of neurokinin-1(NK-1) receptor antagonist,is unlike other approved agents in this class,it can be in combination with other antiemetic agents for the prevention from delayed chemotherapy-induced nausea and vomiting (CINV).Rolapitant may be beneficial for some patients where drug-drug interaction should ideally be avoided.This review describes the pharmacological action and application status of rolapitant in CINV treatment.

  9. Drugs Approved for Melanoma

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Melanoma This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Melanoma Aldesleukin Cobimetinib Cotellic (Cobimetinib) Dabrafenib Dacarbazine DTIC-Dome ( ...

  10. The pharmacology of psilocybin.

    Science.gov (United States)

    Passie, Torsten; Seifert, Juergen; Schneider, Udo; Emrich, Hinderk M

    2002-10-01

    Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the major psychoactive alkaloid of some species of mushrooms distributed worldwide. These mushrooms represent a growing problem regarding hallucinogenic drug abuse. Despite its experimental medical use in the 1960s, only very few pharmacological data about psilocybin were known until recently. Because of its still growing capacity for abuse and the widely dispersed data this review presents all the available pharmacological data about psilocybin.

  11. Safety and pharmacodynamic effects of a pharmacological chaperone on α-galactosidase A activity and globotriaosylceramide clearance in Fabry disease: report from two phase 2 clinical studies

    Directory of Open Access Journals (Sweden)

    Germain Dominique P

    2012-11-01

    Full Text Available Abstract Background Fabry disease (FD is a genetic disorder resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A, which leads to globotriaosylceramide (GL-3 accumulation in multiple tissues. We report on the safety and pharmacodynamics of migalastat hydrochloride, an investigational pharmacological chaperone given orally at 150 mg every-other-day. Methods Two open-label uncontrolled phase 2 studies of 12 and 24 weeks (NCT00283959 and NCT00283933 in 9 males with FD were combined. At multiple time points, α-Gal A activity and GL-3 levels were quantified in blood cells, kidney and skin. GL-3 levels were also evaluated through skin and renal histology. Results Compared to baseline, increased α-Gal A activity of at least 50% was demonstrated in blood, skin and kidney in 6 of 9 patients. Patients’ increased α-Gal A activities paralleled the α-Gal A increases observed in vitro in HEK-293 cells transfected with the corresponding mutant form of the enzyme. The same 6 patients who demonstrated increases of α-Gal A activity also had GL-3 reduction in skin, urine and/or kidney, and had α-Gal A mutations that responded in transfected cells incubated with the drug. The 3 patients who did not show a consistent response in vivo had α-Gal A mutations that did not respond to migalastat HCl in transfected cells. Migalastat HCl was well tolerated. Conclusions Migalastat HCl is a candidate pharmacological chaperone that provides a novel genotype-specific treatment for FD. It enhanced α-Gal A activity and resulted in GL-3 substrate decrease in patients with responsive GLA mutations. Phase 3 studies are ongoing. Trial registration Clinicaltrial.gov: NCT00283959 and NCT00283933

  12. Pharmacologic Treatments for Binge-Eating Disorder.

    Science.gov (United States)

    McElroy, Susan L

    2017-01-01

    Binge-eating disorder (BED) is the most common eating disorder and is associated with poor physical and mental health outcomes. Psychological and behavioral interventions have been a mainstay of treatment for BED, but as understanding of this disorder has grown, pharmacologic agents have become promising treatment options for some patients. At this time, only one drug-the stimulant prodrug lisdexamfetamine-is approved for the treatment of BED. Numerous classes of medications including antidepressants, anticonvulsants, and antiobesity drugs have been explored as off-label treatments for BED with variable success. Although not all patients with BED may be suitable candidates for pharmacotherapy, all patients should be considered for and educated about pharmacologic treatment options. © Copyright 2017 Physicians Postgraduate Press, Inc.

  13. 参附注射液的药理作用研究与临床应用进展%The research of the Pharmacological Effects and the progress of Clinical Applications of Shenfu injection

    Institute of Scientific and Technical Information of China (English)

    隋玉玲

    2015-01-01

    目的:探讨参附注射液的临床应用研究和临床应用进展。方法选取国内外2005至2015年药理作用研究进行总结,对国内临床应用多个、多中心、随机对照研究进行总结。结果参附注射液药理作用确凿,能有效地治疗疾病;应用于临床,临床应用对照试验研究有显著差异,临床症状改善明显。结论参附注射液药理作用科学可靠,临床用于循环系统,呼吸系统,免疫系统,血液病,消化系统,神经系统等多个方面均有疗效明显,具有良好的应用前景。%Objective To investigate the research of the pharmacological effects and the progress of clinical applications of Shenfu injection.Methods Selected the research of the pharmacological effects during 2005 ~2015 at home and abroad for summary,summaried many randomizing controlled studys managed by many research centres in our country.Results The pharmacological effects of Shenfu injection is scientific and reliable,it has manifest effects when being used into circulatory system ,respiratory system ,immune system,blood disease,digestive system,nervous system and so on,as well as good application prospect.

  14. Pharmacology of novel psychoactive substances

    OpenAIRE

    Rickli, Anna

    2016-01-01

    This PhD work consists of an in vitro and in vivo part. In the in vivo part, we investigated the role of dopamine in the acute clinical effects of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) in healthy human subjects. The role of dopamine in the addictive effects of drug of abuse is well established, but whether it contributes to the acute psychotropic effects of MDMA is unclear. In this pharmacological interaction study, we used the dopamine and weak norepinephrine transporter in...

  15. Pharmacological approach to acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Ulrich Christian Bang; Synne Semb; Camilla Nφjgaard; Flemming Bendtsen

    2008-01-01

    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP)based on experimental animal models and clinical trials.Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against Post Endoscopic retrograde cholangiopancreatography Pancreatitis (PEP). The protease inhibitor Gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL) is a nitrogen oxide (NO) donor, which relaxes the sphincter of Oddi.Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results.Antibodies against tumor necrosis factor-alpha (TNF-α)have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics betalactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.

  16. Orofacial Pain: Pharmacologic Paradigms for Therapeutic Intervention.

    Science.gov (United States)

    Halpern, Leslie; Willis, Porchia

    2016-04-01

    Pain is a universal experience with profound effects on the physiology, psychology, and sociology of the population. Orofacial pain (OFP) conditions are especially prevalent and can be severely debilitating to a patient's health-related quality of life. Evidence-based clinical trials suggest that pharmacologic therapy may significantly improve patient outcomes either alone or when used as part of a comprehensive treatment plan for OFP. The aim of this article is to provide therapeutic options from a pharmacologic perspective to treat a broad spectrum of OFP. Clinical-based systemic and topical applied pharmaceutical approaches are presented to treat the most common OFP syndromes. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Biosimilars approval process.

    Science.gov (United States)

    Zuñiga, Leyre; Calvo, Begoña

    2010-04-01

    For similar biological medicinal products, the so-called biosimilars, clinical trials are required rather than just the bioequivalence studies required to support the registration of a generic small molecule drug product. The EU Directive 2001/83/EC, as amended, stated that where a biological medicinal product which is similar to a reference biological product, does not meet the conditions in the definition of generic medicinal products the results of appropriate pre-clinical tests or clinical trials relating to these conditions must be provided. The challenge is to determine the exact nature of the non-clinical and clinical programme required to gain regulatory approval. The applicant is encouraged to provide a detailed description of the strategy used to demonstrate the biosimilar and the reference product have similar profiles in terms of quality, safety and efficacy. The extent to which comparability can be proven will have quite an impact on how many non-clinical and clinical studies the biosimilar applicant will be required to conduct. The dossier submitted by the applicant to the EMEA should cover all aspects of the comparability assessment and must include data on possible unwanted immune reactions to the therapeutic protein. Post-marketing pharmacovigilance plans are also expected to be included in the biosimilar dossier.

  18. Pharmacologic agents for mucus clearance in bronchiectasis.

    Science.gov (United States)

    Nair, Girish B; Ilowite, Jonathan S

    2012-06-01

    There are no approved pharmacologic agents to enhance mucus clearance in non-cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a mucolytic in other lung diseases. Dornase α is beneficial to patients with CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents such as β-agonists have the potential to improve mucociliary clearance in normals and many disease states, but have not been adequately studied in patients with bronchiectasis.

  19. Ethnobotany, phytochemistry, and pharmacology of the genus Litsea: An update.

    Science.gov (United States)

    Wang, Yun-Song; Wen, Zheng-Qi; Li, Bi-Tao; Zhang, Hong-Bin; Yang, Jing-Hua

    2016-04-02

    modern pharmacology research. Deep and systematic phytochemical investigation of the genus Litsea and the pharmacological properties, especially its mechanism of action and toxicology, to illustrate its ethnomedicinal use, explore the therapeutic potential and support further health-care product development will undoubtedly be the focus of further research. Therefore, detailed and extensive studies and clinical evaluation of Litsea species should be carried out in future for the safety approval of therapeutic applications. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Where are we heading to in pharmacological IBD therapy?

    Science.gov (United States)

    Rogler, Gerhard

    2015-10-01

    After a relatively long time of failed developments and negative clinical trials in pharmacological inflammatory bowel disease (IBD) therapy we now phase a time of a great number of successful studies and new therapy principles that will most likely make it into clinical practice. This will change the landscape of IBD therapy in future markedly. Many new therapeutic principles have been developed and old ones that seemed to have failed such as anti-sense technology suddenly now provide promising results. Some initially promising therapies will need further development or have failed such as Trichuris suis ova therapy (but not helminth therapy in general), CCR9 targeted therapies or recombinant IL-10. In contrast anti-leukocate trafficking therapies appear to be quite promising. Vedolizumab is the first in class anti-integrin antibody that was approved for the therapy of CD and UC recently. Other anti-integrin antibodies and small molecule adhesion inhibitors will most likely be approved in the next years for IBD therapy. Tofacitinib, a small molecule JAK inhibitor, is a promising candidate for the treatment of UC. Phosphatidylcholine may be a future option for patients with 5-ASA refractory UC or 5-ASA intolerance. The preliminary data for Mongersen, a Smad7 antisense oligonucleotide, are promising despite some concerns about long term effect of TGFβ induction. Anti IL6 strategies will hopefully be further evaluated keeping in mind the caveat of a lack of CRP induction in anti-IL6 treated patients. Stem cell transplantation will become an option for patients that have experienced failure of established medications. Fecal microbiota transplantation and also perhaps combined probiotic therapy is a field that will be evaluated in more detail in the near future especially for UC patients. Based on these new developments treatment algorithms need to be updated. This review will reflect these current developments and give a perspective for future IBD therapy. Copyright

  1. Medical curriculum and pharmacology: An appraisal.

    Science.gov (United States)

    Haranath, P S R K

    2016-10-01

    Pharmacology was introduced with Western Medical Education in India in 1900s. RN Chopra was the first Professor of Pharmacology along with patient care in School of Tropical Medicine Calcutta. Now Pharmacologists do not have clinical care nor give laboratory services to hospitals. Medical Education advanced in the West in 1960s with more emphasis on Integrated Teaching and Student Self-study and less on didactic lectures. System Based Learning and Problem Based Learning reduced importance of individual subjects. Medical Council of India (MCI) has mandatory regulations with no major changes in the last 5 decades. Universities and Medical institutions have no freedom in teaching programs. In Pharmacology didactic lectures dominate teaching. Practicals started with Dispensing Pharmacy were later replaced with Experimental Pharmacology. At present after restrictions on animals for study practicals are converted to Theoretical Exercises on Prescription writing and Incompatibilities. Students study mostly before examinations with little influence of yearlong teaching. Suggestions in line with Western Countries: Reduce the course of Pharmacology to 6 months. Examinations should be completely Internal with frequent tests by Internal Examiners. MD (Therapeutics) course may be introduced to teach Pharmacology in first semester. MCI rules to be only advisory and not mandatory. Teaching Institutions should form an independent Association and have freedom in teaching programs. A Nonofficial National Board of Medical Examination has to be formed to conduct an Entrance Test for admissions to Medical College and a National test for each graduate before registration.

  2. Methodological innovations expand the safety pharmacology horizon.

    Science.gov (United States)

    Pugsley, M K; Curtis, M J

    2012-09-01

    Almost uniquely in pharmacology, drug safety assessment is driven by the need for elaboration and validation of methods for detecting drug actions. This is the 9th consecutive year that the Journal of Pharmacological and Toxicological Methods (JPTM) has published themed issues arising from the annual meeting of the Safety Pharmacology Society (SPS). The SPS is now past its 10th year as a distinct (from pharmacology to toxicology) discipline that integrates safety pharmacologists from industry with those in academia and the various global regulatory authorities. The themes of the 2011 meeting were (i) the bridging of safety assessment of a new chemical entity (NCE) between all the parties involved, (ii) applied technologies and (iii) translation. This issue of JPTM reflects these themes. The content is informed by the regulatory guidance documents (S7A and S7B) that apply prior to first in human (FIH) studies, which emphasize the importance of seeking model validation. The manuscripts encompass a broad spectrum of safety pharmacology topics including application of state-of-the-art techniques for study conduct and data processing and evaluation. This includes some exciting novel integrated core battery study designs, refinements in hemodynamic assessment, arrhythmia analysis algorithms, and additionally an overview of safety immunopharmacology, and a brief survey discussing similarities and differences in business models that pharmaceutical companies employ in safety pharmacology, together with SPS recommendations on 'best practice' for the conduct of a non-clinical cardiovascular assessment of a NCE.

  3. Mitochondrial biogenesis: pharmacological approaches.

    Science.gov (United States)

    Valero, Teresa

    2014-01-01

    Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and divide to give rise to two identical daughter cells. Mitochondrial biogenesis occurs by growth and division of pre-existing organelles and is temporally coordinated with cell cycle events [1]. However, mitochondrial biogenesis is not only produced in association with cell division. It can be produced in response to an oxidative stimulus, to an increase in the energy requirements of the cells, to exercise training, to electrical stimulation, to hormones, during development, in certain mitochondrial diseases, etc. [2]. Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass [3]. Recent discoveries have raised attention to mitochondrial biogenesis as a potential target to treat diseases which up to date do not have an efficient cure. Mitochondria, as the major ROS producer and the major antioxidant producer exert a crucial role within the cell mediating processes such as apoptosis, detoxification, Ca2+ buffering, etc. This pivotal role makes mitochondria a potential target to treat a great variety of diseases. Mitochondrial biogenesis can be pharmacologically manipulated. This issue tries to cover a number of approaches to treat several diseases through triggering mitochondrial biogenesis. It contains recent discoveries in this novel field, focusing on advanced mitochondrial therapies to chronic and degenerative diseases, mitochondrial diseases, lifespan extension, mitohormesis, intracellular signaling, new pharmacological targets and natural therapies. It contributes to the field by covering and gathering the scarcely reported pharmacological approaches in the novel and promising field of mitochondrial biogenesis. There are several diseases that have a mitochondrial origin such as chronic progressive external ophthalmoplegia (CPEO) and the Kearns- Sayre syndrome (KSS

  4. Quality management of pharmacology and safety pharmacology studies

    DEFF Research Database (Denmark)

    Spindler, Per; Seiler, Jürg P

    2002-01-01

    Pharmacology has traditionally been excluded from the mandatory application of good laboratory practice (GLP) principles. Consensus has been reached through the process of the International Conference on Harmonisation (ICH, Topic S7A) with regard to the definitions of the different types...... to encourage a positive attitude among researchers and academics towards these lines, whenever possible. GLP principles applied to the management of non-clinical safety studies are appropriate quality standards when studies are used in the context of protecting public health, and these quality standards...... be prepared to exercise flexibility in their requirement for GLP compliance, however, if non-clinical studies used in human safety assessment are not formally in compliance with the principles of GLP, regulatory acceptance may not be guaranteed. Historically, the application of formal GLP standards in safety...

  5. Analysis on the Pattern for the Teaching Team Construction of Traditional Chinese Pharmacology in Clinical Teaching Hospital%临床教学医院中药学教师队伍建设模式的分析

    Institute of Scientific and Technical Information of China (English)

    常馨予; 郭桂明; 范峥

    2015-01-01

    临床教学是高等医学教育过程中不可或缺的重要组成部分,临床教学质量与教师的教学技能、学术水平、医德医风等息息相关,建立一支高水平、高素质、能力强、与时俱进的药师教师队伍是提高教学质量的关键,也是临床教学医院开展教学工作的坚实基础。文章从建设适应新形势要求的临床教学医院师资队伍出发,探讨临床中药学教师队伍建设的重要意义,提出了从教师基本技能培训、教师队伍建设、医德医风建设、设置特色教学课程及奖励与竞争机制等五方面来加强大学附属医院临床中药学教师队伍建设的建议。%Clinical teaching is the indispensable and important component in the advanced medical education. The clinical teaching quality is closely related to teachers'teaching skill,academic level,medical ethics,etc. Building a pharmacist teaching team of high quality and strong capacity is the key for the improve-ment of teaching quality and is the solid foundation for the clinical teaching hospital to develop teaching pro-gram. In the paper,concerning to the construction of teaching team in clinical teaching hospital for adaption to the requirement of new situation,the importance was discussed on the construction of clinical teaching team of traditional Chinese pharmacology in five aspects,named basic skill training,teaching team construction,medi-cal ethics construction,setting up characteristic teaching program and award and competitive mechanism. As a result,the clinical teaching team of traditional Chinese pharmacology could be strengthened in the affiliated hospital of university.

  6. Renin inhibitor in hypertension treatment: from pharmacological point of view

    Directory of Open Access Journals (Sweden)

    Johannes Hudyono

    2011-08-01

    Full Text Available The use of drugs that inhibit the renin-angiotensin system is one of the effective way to intervene in the pathogenesis of cardiovascular and renal disorders, especially in hypertension treatment. The idea of blocking the renin system at its origin by renin inhibitor has existed for more than 30 years. Renin inhibitor supresses the covension of angiotensinogen into angiotensin, and further deacreases the generation of the active peptide angiotensin II. The first generation (enalkiren and second generation (remikiren of orally active renin inhibitors were never used clinically because of low bioavailability and weak blood pressure-lowering activity. At present, aliskiren is the first non-peptide orally active renin inhibitor of the third generation to progress to phase III clinical trials and was approved by U.S. Food and Drug Administration (FDA in March 2007. Aliskiren becomes the first renin inhibitor with indications for the treatment of hypertension in Indonesia, a compounds with improved oral bioavailability, specificity and efficacy. This review summarises the development of oral renin inhibitors, pharmacological aspects, with a focus on aliskiren. (Med J Indones 2011; 20:232-7Keywords: aliskiren, hypertension, renin inhibitor, renin-angiotensin

  7. 抗感染新药非达霉素的药理作用与临床评价%Pharmacology and clinical evaluation of the new anti-infective drug fidaxomicin

    Institute of Scientific and Technical Information of China (English)

    姜春梅; 刘洋; 王京晶; 张清; 康博欣

    2011-01-01

    Fidaxomicin (edarbi) is the antibiotic with a novel structure of macrolides for the treatment of clostridium difficile-associated diarrhea ( CDAD). Literature was searched from FDA database with the key word edarbi. The pharmacology, pharmacokinetics, clinical evaluation, safety evaluation and drug interactions of fidaxomicin were reviewed.%非达霉素( fidaxomicin)是一种新型的大环内酯类抗生素,适用于艰难梭菌相关性腹泻(clostridium difficile-associated diarrhea,CDAD)的治疗.本文参考美国FDA的相关资料,对非达霉素的药理作用、药动学、临床评价、安全性评价及药物相互作用等进行综述.

  8. 依托咪酯的药理特点及临床应用%Pharmacological Features and Clinical Application of Etomidate

    Institute of Scientific and Technical Information of China (English)

    胡红专

    2013-01-01

    Etomidate is a kind of hypnotic intravenous anesthetics. The pharmacological features include short half time of both elimination and instant infusion, rapidly going through the blood-brain barrier, strong hypnotic effect, rapid onset of action , wide safety margin , fast recovery from unconsciousness , little influence on respiratory and circulatory systems and so on. Etomidate is the only drug that does not interfere with the cardiovascular stability in the intravenous anesthetics, and it can also reduce the intracranial pressure and maintain cerebral perfusion. It is especially suitable for the patients of old age, or with coronary heart disease, high blood pressure and shock. Myoclonus, nausea and vomiting, inhibition of adrenocortical function and other side effects may be observed after the application of etonidate.%依托咪酯是一种催眠性静脉麻醉药,其消除半衰期及即时输注半衰期均较短,能迅速通过血-脑脊液屏障,催眠作用强,具有起效快、安全界限大、清醒迅速、对呼吸循环影响小等特点.在静脉麻醉药中,依托咪酯是唯一不干扰心血管稳定性的药物,还可以降低颅内压和维持脑灌注,尤其适用于老年、冠状动脉粥样硬化性心脏病、高血压及休克患者.应用后可能出现肌阵挛、恶心、呕吐、抑制肾上腺皮质功能等不良反应.

  9. Toxicological evidence in forensic pharmacology.

    Science.gov (United States)

    Ferner, R E

    2012-01-01

    Laboratory evidence of the presence and concentration of a drug in a person who has come to harm is often helpful in forensic pharmacology, and may be crucial. However, its value depends on two critical interpretations by the expert. First, the expert must make a careful analysis of the relationship between the results as measured in the sample and the drug in the patient at the time that harm occurred. That is especially difficult with post-mortem samples. Secondly, the expert must syntheses the laboratory information with the available clinical history and clinical or pathological findings. Even in the most favourable circumstances, when the sample is correctly obtained, identified, and analyzed, it can be hard to say that beyond reasonable doubt a given concentration had a given effect.

  10. The genus Carpesium: a review of its ethnopharmacology, phytochemistry and pharmacology.

    Science.gov (United States)

    Zhang, Jian-Ping; Wang, Guo-Wei; Tian, Xin-Hui; Yang, Yong-Xun; Liu, Qing-Xin; Chen, Li-Ping; Li, Hui-Liang; Zhang, Wei-Dong

    2015-04-02

    during the treatment of cancer, inflammatory, parasitosis, etc. However, apart from those bioactive molecules, a considerable part of compounds, including a lot of sesquiterpenes, and several other type of compounds that have been previously isolated but have not been tested biologically need to be further tested. Therefore, more pharmacological experiments should be focused on these untested chemical constituents. Additionally, another issue concerns that most pharmacological studies were only performed in vitro-based experiments, so additional in vivo tests in animal models are required to estimate their side effects for the safety approval of therapeutic applications. Finally, further studies through well controlled, double-blind clinical trials are required to re-evaluate their efficacious and possible side effects, and more pharmacological mechanisms on main active compounds will also be needed for illuminating correlations between ehnopharmacology and pharmacology in future. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Developmental paediatric anaesthetic pharmacology

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing

    2015-01-01

    Safe and effective drug therapy in neonates, infants and children require detailed knowledge about the ontogeny of drug disposition and action as well how these interact with genetics and co-morbidity of children. Recent advances in developmental pharmacology in children follow the increased...

  12. Pharmacology Isotoma Longiflorum

    OpenAIRE

    Cruz Sánchez, César Guillermo; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    We have studied the pharmacology of Isotoma longiflorum plant campanuláceas the family, native to Peru. Was extracted from this plant a crystalline active ingredient. Se ha estudiado la farmacología de la Isotoma longiflorum planta de la familia de las campanuláceas, nativas del Perú. Se extrajo de esta planta un principio activo cristalino.

  13. An Integrated Approach to Instruction in Pharmacology and Therapeutics

    Science.gov (United States)

    Talbert, Robert L.; Walton, Charles A.

    1976-01-01

    The impact of the clinical faculty on the content of the pharmacology course is described in a discussion of trends in pharmacology instruction. Interfaculty communication and development of course objectives are reviewed, and descriptions of two baccalaureate courses at the University of Texas College of Pharmacy are appended. (LBH)

  14. Cardiac Safety Research Consortium: can the thorough QT/QTc study be replaced by early QT assessment in routine clinical pharmacology studies? Scientific update and a research proposal for a path forward.

    Science.gov (United States)

    Darpo, Borje; Garnett, Christine; Benson, Charles T; Keirns, James; Leishman, Derek; Malik, Marek; Mehrotra, Nitin; Prasad, Krishna; Riley, Steve; Rodriguez, Ignacio; Sager, Philip; Sarapa, Nenad; Wallis, Robert

    2014-09-01

    The International Conference on Harmonization E14 guidance for the clinical evaluation of QT/QTc interval prolongation requires almost all new drugs to undergo a dedicated clinical study, primarily in healthy volunteers, the so-called TQT study. Since 2005, when the E14 guidance was implemented in United States and Europe, close to 400 TQT studies have been conducted. In February 2012, the Cardiac Safety Research Consortium held a think tank meeting at Food and Drug Administration's White Oak campus to discuss whether "QT assessment" can be performed as part of routine phase 1 studies. Based on these discussions, a group of experts convened to discuss how to improve the confidence in QT data from early clinical studies, for example, the First-Time-in-Human trial, through collection of serial electrocardiograms and pharmacokinetic samples and the use of exposure response analysis. Recommendations are given on how to design such "early electrocardiogram assessment," and the limitation of not having a pharmacologic-positive control in these studies is discussed. A research path is identified toward collecting evidence to replace or provide an alternative to the dedicated TQT study.

  15. Are pharmacological randomised controlled clinical trials relevant to real-life asthma populations? A protocol for an UNLOCK study from the IPCRG

    NARCIS (Netherlands)

    Lisspers, Karin; Teixeira, Pedro; Blom, Coert; Kocks, Janwillem; Stallberg, Bjorn; Price, David; Chavannes, Niels

    2016-01-01

    Asthma has a high prevalence worldwide with a high incidence in primary care settings in many countries.1 It is by definition a variable disease with a broad spectrum of clinical phenotypes, in which management and treatment can be difficult.2–8 The aim of asthma treatment is optimal control of the

  16. Serum levels of brain-derived neurotrophic factor in major depressive disorder : state-trait issues, clinical features and pharmacological treatment

    NARCIS (Netherlands)

    Molendijk, M. L.; Bus, B. A. A.; Spinhoven, Ph; Penninx, B. W. J. H.; Kenis, G.; Prickaerts, J.; Voshaar, R. C. Oude; Elzinga, B. M.

    2011-01-01

    Recent evidence supports 'the neurotrophin hypothesis of depression' in its prediction that brain-derived neurotrophic factor (BDNF) is involved in depression. However, some key questions remain unanswered, including whether abnormalities in BDNF persist beyond the clinical state of depression, whet

  17. Postmarketing Safety Events Relating to New Drugs Approved in Brazil Between 2003 and 2013: A Retrospective Cohort Study.

    Science.gov (United States)

    Botelho, Stephanie Ferreira; Martins, Maria Auxiliadora Parreiras; Vieira, Liliana Batista; Reis, Adriano Max Moreira

    2017-04-01

    This study investigated postmarketing safety events (PMSEs) for new drugs approved in Brazil and evaluated whether a range of drug characteristics influenced the time between approval and the first PMSE. This retrospective study included new drugs registered between 2003 and 2013 by the National Health Surveillance Agency (ANVISA), which is responsible for medicines approval in Brazil. PMSEs were defined as any drug safety alert or drug withdrawal from the market. The existence of risk evaluation and mitigation strategies (REMS) by the US Food and Drug Administration (FDA) and Brazil were recorded. A Kaplan-Meier survival curve of the period between the date of ANVISA registration and the PMSE was calculated. We found a statistically significant difference between the time to PMSE for drugs with an FDA REMS compared with those without a REMS, with a log rank value (Mantel Cox) of 0.002. There was no association between the time to PMSE and the other drug characteristics investigated. This study demonstrated that the frequency of PMSEs for new drugs approved by ANVISA was statistically associated with the existence of an FDA REMS. The time between approval and first PMSE was shorter for drugs with an FDA REMS, and this finding may contribute to improved awareness of the risk/benefit balance required to ensure continued safe and effective use of new drugs. © 2016, The American College of Clinical Pharmacology.

  18. A SURVEY ON METHODS OF UNDERGRADUATE PHARMACOLOGY TEACHING

    Directory of Open Access Journals (Sweden)

    MOHANBABU AMBERKAR, LALIT MOHAN, MEENA KUMARI, BAIRY K.L

    2013-09-01

    Full Text Available Knowledge of pharmacology to choose and prescribe drugs is a major challenge encountered by medical practitioners. A number of initiatives have been carried out to improve the teaching of pharmacology and applied therapeutics.Material & methods-A survey was conducted on medical students,pursuing pharmacology at Kasturba Medical College,Manipal,during the month of August 2010,to obtain information regarding students attitude towards Pharmacology. Result-Two hundred and fourteen students participated.The total median score was 56 (maximum score 80.Majority of them suggested to have more problem based learning than didactic lectures and to have integrated teaching with other clinical subjects. Suggestions to improve pharmacology teaching were noted.Conclusion-The findings of the study would be of interest to medical educators in modifying undergraduate pharmacology teaching programme

  19. Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”): The Influence of Gender and Genetics (CYP2D6, COMT, 5-HTT)

    OpenAIRE

    Ricardo Pardo-Lozano; Magí Farré; Samanta Yubero-Lahoz; Brian O'Mathúna; Marta Torrens; Cristina Mustata; Clara Pérez-Mañá; Klaus Langohr; Elisabet Cuyàs; Marcel lí Carbó; Rafael de la Torre

    2012-01-01

    The synthetic psychostimulant MDMA (±3,4-methylenedioxymethamphetamine, ecstasy) acts as an indirect serotonin, dopamine, and norepinephrine agonist and as a mechanism-based inhibitor of the cytochrome P-450 2D6 (CYP2D6). It has been suggested that women are more sensitive to MDMA effects than men but no clinical experimental studies have satisfactorily evaluated the factors contributing to such observations. There are no studies evaluating the influence of genetic polymorphism on the pharmac...

  20. Post-Approval Studies

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a...

  1. Investigational pharmacology for low back pain.

    Science.gov (United States)

    Bhandary, Avinash K; Chimes, Gary P; Malanga, Gerard A

    2010-09-06

    Review and reinterpretation of existing literature. This review article summarizes the anatomy and pathogenesis of disease processes that contribute to low back pain, and discusses key issues in existing therapies for chronic low back pain. The article also explains the scientific rationale for investigational pharmacology and highlights emerging compounds in late development. While the diverse and complex nature of chronic low back pain continues to challenge clinicians, a growing understanding of chronic low back pain on a cellular level has refined our approach to managing chronic low back pain with pharmacology. Many emerging therapies with improved safety profiles are currently in the research pipeline and will contribute to a multimodal therapeutic algorithm in the near future. With the heterogeneity of the patient population suffering from chronic low back pain, the clinical challenge will be accurately stratifying the optimal pharmacologic approach for each patient.

  2. Analysis of pharmacological characteristics and clinical application of cephalosporins antibiotics%头孢菌素类抗生素的药理特性及临床应用分析

    Institute of Scientific and Technical Information of China (English)

    康庆

    2016-01-01

    ObjectiveTo analyze pharmacological characteristics and clinical application of cephalosporins antibiotics.MethodsClinical data of 110 patients with antibiotics-related adverse reactions were retrospectively analyzed. Observation was made on adverse reactions and involved regions by cephalosporins antibiotics.ResultsThere were 45 cases with adverse reactions by cephalosporins antibiotics among 110 patients, accounting for 40.9%. Main involved regions included digestive system, nervous system, skin and appendages of skin.ConclusionCephalosporins antibiotics-induced adverse reactions mainly involve digestive system, nervous system, skin and appendages of skin. Therefore, understanding pharmacological characteristics and closely observing clinical symptom and vital signs can reduce incidence of adverse reactions and improve curative effects for patients.%目的:探索分析头孢菌素类抗生素的药理特性及临床应用。方法回顾性分析110例抗生素相关不良反应患者的临床资料,观察本组患者中由于头孢菌素类抗生素的应用而出现的不良反应的发生情况、累及部位等。结果110例患者中由于应用头孢菌素类抗生素出现不良反应者45例,占总体的40.9%,累及的部位主要包括消化系统、神经系统、皮肤、皮肤附件等。结论应用头孢菌素类抗生素后,患者出现的不良反应主要涉及消化系统、神经系统、皮肤、皮肤附件等部位,因此在临床用药时,需要掌握药理特性,严密观察患者的临床症状和体征情况,以降低不良反应发生率,提高患者的治疗效果。

  3. Lack of proportionality. Seven specifications of public interest that override post-approval commercial interests on limited access to clinical data

    Directory of Open Access Journals (Sweden)

    Strech Daniel

    2012-07-01

    Full Text Available Abstract For the protection of commercial interests, licensing bodies such as the EMA and health technology assessment institutions such as NICE restrict full access to unpublished evidence. Their respective policies on data transparency, however, lack a systematic account of (1 what kinds of commercial interests remain relevant after market approval has been granted, (2 what the specific types of public interest are that may override these commercial interests post approval, and, most importantly, (3 what criteria guide the trade-off between public interest and legitimate measures for the protection of commercial interest. Comparing potential commercial interests with seven specifications of relevant public interest reveals the lack of proportionality inherent in the current practices of EMA and NICE.

  4. Pharmacological approaches to the management of binge eating disorder.

    Science.gov (United States)

    Brownley, Kimberly A; Peat, Christine M; La Via, Maria; Bulik, Cynthia M

    2015-01-01

    In the USA, binge eating disorder (BED) is the most common eating disorder, with a lifetime prevalence of ~3.5 % in adult women, 2.0 % in adult men, and 1.6 % in adolescents. BED is characterized by frequent episodes of binge eating that are accompanied by a sense of loss of control over eating and result in marked psychological distress. BED is highly co-morbid with obesity and with depression and other psychiatric conditions, and it is associated with substantial role impairment. Currently, there are no US FDA-approved pharmacological treatments for BED. Animal and human studies implicate underlying dysregulation in dopamine, opioid, acetylcholine, and serotonin neurocircuitry within brain reward regions in the pathogenesis and maintenance of BED. To date, the efficacy of various agents that target these and other neurotransmitter systems involved in motivated feeding behavior, mood regulation, and impulse control have been investigated in the treatment of BED. Several antidepressant and anticonvulsant agents have demonstrated efficacy in reducing binge eating frequency, but only in limited cases have these effects resulted in patients achieving abstinence, which is the primary goal of treatment; they also range from less (fluvoxamine) to more (topiramate) effective in achieving weight loss that is both clinically meaningful and significantly greater than placebo. Collectively, the literature on pharmacological treatment approaches to BED is limited in that very few agents have been studied in multiple, confirmatory trials with adequate follow up, and almost none have been evaluated in large patient samples that are diverse with respect to age, sex, and ethnicity. In addition, prior trials have not adequately addressed, through study design, the high placebo response commonly observed in this patient population. Several novel agents are in various phases of testing, and recent animal studies focusing on glutamate-signaling circuits linking the amygdala to the

  5. Progress in pharmacological and clinical studies of miriplatin on interventional therapy of hepatocellular carcinoma%肝癌介入治疗新药米铂的药理与临床研究

    Institute of Scientific and Technical Information of China (English)

    赵俊; 马俊杰

    2012-01-01

    米铂是第三代铂类抗肿瘤药物,其与碘化油亲和性高,且肝动脉内给药后滞留于肿瘤部位,混悬液中的铂成分可长时间缓慢释放进入血液或组织中.其与DNA结合,通过阻止DNA合成而产生细胞毒效应.临床研究结果表明,米铂治疗肝细胞癌具有良好的疗效和安全性.现对其药理学、药动学、临床研究及安全性评价等作一综述.%Miriplatin is a third-generation platinum compound developed to treat hepatocellular carcinoma (HCC). It is administered via the hepatic artery using the carrier lipiodol that consists of ethyl esters of iodized poppy seed oil. Miriplatin has a high affinity for lipiodol and it is anticipated to exert antitumor effects with prolonged retention along with local lipiodol at the tumor site. Therefore, it is suggested that the active compound released from miriplatin/lipiodol can bind to DNA and produce a cytotoxic effect. The clinical research shows that miriplatin has beneficial curative effect and safety in the treatment of hepatocellular carcinoma. This article will summarize its pharmacology, pharmacokinetics, clinical research, and safety evaluation.

  6. Clinical pharmacology of single- and multiple-ascending doses of ACT-178882, a new direct renin inhibitor, and its pharmacokinetic interaction with food and midazolam.

    Science.gov (United States)

    Dingemanse, Jasper; Nicolas, Laurent; Binkert, Christoph

    2013-12-01

    This study investigated the tolerability, safety, pharmacokinetics, and pharmacodynamics of ACT-178882, a new direct renin inhibitor, as well as its interaction with food and midazolam. Healthy male subjects received either single (10-1000 mg) or multiple doses (30-600 mg) administered once daily for 14 days of ACT-178882, placebo, or 20 mg enalapril in the fasted state. Following a 2-week washout, the single dose of 30 mg ACT-178882 was also administered in the fed state. In the multiple-ascending-dose part, subjects were dosed with midazolam on days -2, 2, and 12 to investigate interactions with CYP3A4. Dizziness and headache were the most frequently reported adverse events. No clinically relevant changes occurred for body weight, vital signs, clinical laboratory variables, and ECG although both enalapril and ACT-178882 tended to decrease systolic blood pressure. Following single doses of ACT-178882, t1/2 and tmax varied from 18.7 to 24.7 h and from 3 to 5 h, respectively, and food had no significant effect. Steady-state conditions were achieved after 4-6 days of dosing and accumulation was minimal. ACT-178882 pharmacokinetics were dose proportional. ACT-178882 but not enalapril dose-dependently increased Cmax and area under the concentration-time curve of midazolam. Single and multiple doses of ACT-178882 dose-dependently increased active renin and decreased plasma renin activity, whereas enalapril increased both variables. No effects on urinary excretion of creatinine, potassium, and the 6β-hydroxycortisol/cortisol ratio were observed, whereas sodium and aldosterone excretion was decreased by both ACT-178882 and enalapril. The current results with ACT-178882 warrant further clinical investigation of this renin inhibitor in hypertensive patients.

  7. Pharmacology and drug distribution

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, L.R.; Weatherall, T.J.

    1979-08-01

    An overview of the pharmacology of drugs in the treatment of cancer is presented. The discussion begins with the simplest relationship of drugs and particles to one another then proceeds to demonstrate the interrelationship in a biologic system to produce a chemobiodynamic response. The basic principles of pharmacokinetics are reviewed and their correlation with investigational and standard drug therapies is discussed. Voids in the consideration of interactions between chemotherapy and radiotherapy are discussed.

  8. Overview of safety pharmacology.

    Science.gov (United States)

    Goineau, Sonia; Lemaire, Martine; Froget, Guillaume

    2013-12-02

    Safety pharmacology entails the assessment of the potential risks of novel pharmaceuticals for human use. As detailed in the ICH S7A guidelines, safety pharmacology for drug discovery involves a core battery of studies on three vital systems: central nervous (CNS), cardiovascular (CV), and respiratory. Primary CNS studies are aimed at defining compound effects on general behavior, locomotion, neuromuscular coordination, seizure threshold, and vigilance. The primary CV test battery includes an evaluation of proarrhythmic risk using in vitro tests (hERG channel and Purkinje fiber assays) and in vivo measurements in conscious animals via telemetry. Comprehensive cardiac risk assessment also includes full hemodynamic evaluation in a large, anesthetized animal. Basic respiratory function can be examined in conscious animals using whole-body plethysmography. This allows for an assessment of whether the sensitivity to respiratory-depressant effects can be enhanced by exposure to increased CO2 . Other safety pharmacology topics detailed in this unit are the timing of such studies, ethical and animal welfare issues, and statistical evaluation.

  9. Pharmacological Treatment of Obesity in Children and Adolescents: Present and Future

    Directory of Open Access Journals (Sweden)

    Lorenzo Iughetti

    2011-01-01

    Full Text Available The prevalence of overweight and obesity is increasing in children and adolescents worldwide raising the question on the approach to this condition because of the potential morbidity, mortality, and economic tolls. Dietetic and behavioral treatments alone have only limited success; consequently, discussion on strategies for treating childhood and adolescent obesity has been promoted. Considering that our knowledge on the physiological systems regulating food intake and body weight is considerably increased, many studies have underlined the scientific and clinical relevance of potential treatments based on management of peripheral or central neuropeptides signals by drugs. In this paper, we analyze the data on the currently approved obesity pharmacological treatment suggesting the new potential drugs.

  10. Pharmacological Treatment of Cannabis-Related Disorders: A Narrative Review.

    Science.gov (United States)

    Gorelick, David A

    2016-01-01

    Cannabis is the most widely used illicit psychoactive substance world-wide, yet no medication is approved for the treatment of intoxication, withdrawal, or cannabis use disorder (CUD). To comprehensively review the current state of knowledge. Search of the PubMed electronic data base and review of reference lists of relevant articles to identify controlled clinical trials of pharmacological treatment. The search identified 4 trials for specific intoxication symptoms (none for global intoxication), 7 trials for withdrawal, and 12 phase II trials for CUD. One or two trials each suggest that propranolol is effective for some intoxication symptoms, antipsychotics for cannabis-induced psychosis, and dronabinol (synthetic THC) and gabapentin for cannabis withdrawal. Of 10 medications and one medication combination studied in 12 trials for CUD, only two medications were effective (in single trials): gabapentin and Nacetylcysteine (in adolescents). Not effective were dronabinol and several antidepressants, anticonvulsants, and antianxiety medications. Three trials of antidepressants for CUD with comorbid depression gave inconsistent results. A trial of atomoxetine for CUD with comorbid ADHD showed no efficacy. Five trials of second-generation antipsychotics for CUD with comorbid schizophrenia showed none better than any other. Further research is needed to confirm the efficacy of gabapentin for withdrawal and gabapentin and N-acetylcysteine for CUD and to develop new medications for all 3 cannabis-related disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Pharmacological treatment of depression in women with breast cancer

    DEFF Research Database (Denmark)

    Toftegård Andersen, Lærke; Voigt Hansen, Melissa; Rosenberg, Jacob

    2013-01-01

    that escitalopram and the norepinephrine reuptake inhibitor, reboxetine, significantly improved depression and QOL compared with baseline values. In conclusion, depression is a clinical problem in patients with breast cancer. Pharmacological treatment with antidepressants may improve depression and QOL. However...

  12. Cluster headache: conventional pharmacological management.

    Science.gov (United States)

    Becker, Werner J

    2013-01-01

    Cluster headache pain is very intense, usually increases in intensity very rapidly from onset, and attacks are often frequent. These clinical features result in significant therapeutic challenges. The most effective pharmacological treatment options for acute cluster attack include subcutaneous sumatriptan, 100% oxygen, and intranasal zolmitriptan. Subcutaneous or intramuscular dihydroergotamine and intranasal sumatriptan are additional options. Transitional therapy is applicable mainly for patients with high-frequency (>2 attacks per day) episodic cluster headache, and options include short courses of high-dose oral corticosteroids, dihydroergotamine, and occipital nerve blocks with local anesthetic and steroids. Prophylactic therapy is important both for episodic and chronic cluster headache, and the main options are verapamil and lithium. Verapamil is drug of first choice but may cause cardiac arrhythmias, and periodic electrocardiograms (EKGs) during dose escalation are important. Many other drugs are also in current use, but there is an insufficient evidence base to recommend them.

  13. Pharmacological treatment of schizophrenia and co-occurring substance use disorders.

    Science.gov (United States)

    Smelson, David A; Dixon, Lisa; Craig, Thomas; Remolina, Stephen; Batki, Steven L; Niv, Noosha; Owen, Richard

    2008-01-01

    Substance abuse among individuals with schizophrenia is common and is often associated with poor clinical outcomes. Comprehensive, integrated pharmacological and psychosocial treatments have been shown to improve these outcomes. While a growing number of studies suggest that second-generation antipsychotic medications may have beneficial effects on the treatment of co-occurring substance use disorders, this review suggests that the literature is still in its infancy. Few existing well controlled trials support greater efficacy of second-generation antipsychotics compared with first-generation antipsychotics or any particular second-generation antipsychotic. This article focuses on and reviews studies involving US FDA-approved medications for co-occurring substance abuse problems among individuals with schizophrenia.Comprehensive treatment for individuals with schizophrenia and co-occurring substance use disorders must include specialized, integrated psychosocial intervention. Most approaches use some combination of cognitive-behavioural therapy, motivational enhancement therapy and assertive case management. The research on antipsychotic and other pharmacological treatments is also reviewed, as well as psychosocial treatments for individuals with schizophrenia and co-occurring substance use disorders, and clinical recommendations to optimize care for this population are offered.

  14. Practical considerations in the pharmacological treatment of postherpetic neuralgia for the primary care provider

    Directory of Open Access Journals (Sweden)

    Massengill JS

    2014-03-01

    Full Text Available Jamie S Massengill,1 John L Kittredge2 1JSM Medical, Edmond, OK, USA; 2Michiana Spine, Sports and Occupational Rehab, PC, Mishawaka, IN, USA Abstract: An estimated one million individuals in the US are diagnosed with herpes zoster (HZ; shingles each year. Approximately 20% of these patients will develop postherpetic neuralgia (PHN, a complex HZ complication characterized by neuropathic pain isolated to the dermatome that was affected by the HZ virus. PHN is debilitating, altering physical function and quality of life, and commonly affects vulnerable populations, including the elderly and the immunocompromised. Despite the availability of an immunization for HZ prevention and several approved HZ treatments, the incidence of PHN is increasing. Furthermore, management of the neuropathic pain associated with PHN is often suboptimal, and the use of available therapeutics may be complicated by adverse effects and complex, burdensome treatment regimens, as well as by patients' comorbidities and polypharmacy, which may lead to drug–drug interactions. Informed and comprehensive assessments of currently available pharmacological treatment options to achieve effective pain control in the primary care setting are needed. In this article, we discuss the situation in clinical practice, review currently recommended prevention and treatment options for PHN, and outline practical considerations for the management of this neuropathic pain syndrome, with a focus on optimal, individual-based treatment plans for use in the primary care setting. Keywords: herpes zoster, postherpetic neuralgia, primary care, clinical practice, pharmacological treatment, practical guidelines

  15. Pharmacology exercise for undergraduate: MLNMC model

    Directory of Open Access Journals (Sweden)

    Rakesh C. Chaurasia

    2013-08-01

    Full Text Available Pharmacology is the backbone of clinical discipline of medical science. In the computer era of advancement, paraclinical teachings become more technical and clinical oriented. Regarding to undergraduate practical’s the animal experimentation and dispensing pharmacy are only exercises. But these are matter of critics due to their non-utility in future. Student’s apathy and non-interest are hidden factor to perform such boring experiments. Meanwhile the old-dated exercises have no potential to tone-up adequate clinical skills in future study instead of wastage of time and money. Killing of innocent animals is crucial and should be socially discouraged. Thus Pharmacology practical are matter of debate in current scenario. Being attachment with past sentiment of traditional dispensing pharmacy and animal experimentations, they are difficult to delete completely. The present article highlights some of our efforts in undergraduate exercises. [Int J Basic Clin Pharmacol 2013; 2(4.000: 495-497

  16. FDA-approved small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Nielsen, Thomas E.; Clausen, Mads Hartvig

    2015-01-01

    Kinases have emerged as one of the most intensivelypursued targets in current pharmacological research,especially for cancer, due to their critical roles in cellularsignaling. To date, the US FDA has approved 28 smallmoleculekinase inhibitors, half of which were approvedin the past 3 years. While...

  17. High on treatment platelet reactivity against aspirin by non-steroidal anti-inflammatory drugs--pharmacological mechanisms and clinical relevance.

    Science.gov (United States)

    Hohlfeld, T; Saxena, A; Schrör, K

    2013-05-01

    Inhibition of platelet function by aspirin results from irreversible inhibition of platelet cyclooxygenase (COX)-1. While sufficient inhibition is obtained at antiplatelet doses (75-325 mg/day) in most (≥95%) treated patients, the antiplatelet effect of aspirin and subsequent cardiovascular risk reduction is much less in clinical settings and disease-dependent. Several reasons for this "high on treatment platelet reactivity" are known. This paper reviews the evidence for an interaction between aspirin and other COX inhibitors, namely non-steroidal anti-inflammatory drugs (NSAIDs). Numerous experimental studies demonstrated a pharmacodynamic interaction between aspirin and NSAIDs. This likely occurs within the hydrophobic substrate channel of platelet COX-1 and might be explained by molecular competition between inhibitor drugs and substrate (arachidonic acid) at overlapping binding sites. This interaction is found with some compounds, notably ibuprofen and dipyrone (metamizole), but not with others, such as diclofenac and acetaminophen (paracetamol). Hence, this interaction is not a class effect of NSAIDs and/or non-steroidal analgesics but rather due to specific structural requirements which still remain to be defined. In vivo studies on healthy subjects and patients tend to confirm this type of interaction as well as large differences between NSAIDs and non-steroidal analgesics, respectively. These interactions may be clinically relevant and may increase the cardiovascular risk in long-term treatment for primary and secondary cardiovascular prevention in patients with chronic inflammation, such as rheumatoid arthritis. These patients have an elevated risk for myocardial infarctions and may require chronic antiplatelet treatment by aspirin in addition to treatment of inflammatory pain.

  18. Pharmacologic Treatment of Hypertension in Adults Aged 60 Years or Older to Higher Versus Lower Blood Pressure Targets: A Clinical Practice Guideline From the American College of Physicians and the American Academy of Family Physicians.

    Science.gov (United States)

    Qaseem, Amir; Wilt, Timothy J; Rich, Robert; Humphrey, Linda L; Frost, Jennifer; Forciea, Mary Ann

    2017-03-21

    The American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) jointly developed this guideline to present the evidence and provide clinical recommendations based on the benefits and harms of higher versus lower blood pressure targets for the treatment of hypertension in adults aged 60 years or older. This guideline is based on a systematic review of published randomized, controlled trials for primary outcomes and observational studies for harms only (identified through EMBASE, the Cochrane Database of Systematic Reviews, MEDLINE, and ClinicalTrials.gov), from database inception through January 2015. The MEDLINE search was updated through September 2016. Evaluated outcomes included all-cause mortality, morbidity and mortality related to stroke, major cardiac events (fatal and nonfatal myocardial infarction and sudden cardiac death), and harms. This guideline grades the evidence and recommendations using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method. The target audience for this guideline includes all clinicians, and the target patient population includes all adults aged 60 years or older with hypertension. ACP and AAFP recommend that clinicians initiate treatment in adults aged 60 years or older with systolic blood pressure persistently at or above 150 mm Hg to achieve a target systolic blood pressure of less than 150 mm Hg to reduce the risk for mortality, stroke, and cardiac events. (Grade: strong recommendation, high-quality evidence). ACP and AAFP recommend that clinicians select the treatment goals for adults aged 60 years or older based on a periodic discussion of the benefits and harms of specific blood pressure targets with the patient. ACP and AAFP recommend that clinicians consider initiating or intensifying pharmacologic treatment in adults aged 60 years or older with a history of stroke or transient ischemic attack to achieve a target systolic blood pressure of less than 140 mm Hg to

  19. Safety and secondary pharmacology: successes, threats, challenges and opportunities.

    Science.gov (United States)

    Valentin, Jean-Pierre; Hammond, Tim

    2008-01-01

    This review summarises the lecture of Dr Tim Hammond, recipient of the Distinguished Service Award of the Safety Pharmacology Society, given on 20 September 2007 in Edinburgh. The lecture discussed the rationale behind the need for optimal non-clinical Safety and Secondary Pharmacology testing; the evolution of Safety and Secondary Pharmacology over the last decade; its impact on drug discovery and development; the value of adopting an integrated risk assessment approach; the translation of non-clinical findings to humans and finally the future challenges and opportunities facing these disciplines.

  20. Pharmacological interventions for phantom limb pain

    Institute of Scientific and Technical Information of China (English)

    FANG Jun; LIAN Yan-hong; XIE Kang-jie; CAI Shu-nü

    2013-01-01

    Objective To review the mechanisms and current clinical application of pharmacological interventions for phantom limb pain.Data sources Both Chinese and English language literatures were searched using MEDLINE (1982-2011),Pubmed (1982-2011) and the Index of Chinese Language Literature (1982-2011).Study selection Data from published articles about pharmacological management of phantom limb pain in recent domestic and foreign literature were selected.Data extraction Data were mainly extracted from 96 articles which are listed in the reference section of this review.Results By reviewing the mechanisms and current clinical application of pharmacological interventions for phantom limb pain,including anticonvulsants,antidepressants,local anaesthetics,N-methyl-D-aspartate receptor antagonists,non-steroidal anti-inflammatory drugs,tramadol,opioids,calcitonin,capsaicin,beta-adrenergic blockers,clonidine,muscle relaxants,and emerging drugs,we examined the efficacy and safety of these medications,outlined the limitations and future directions.Conclusions Although there is lack of evidence-based consensus guidelines for the pharmacological management of phantom limb pain,we recommend tricyclic antidepressants,gabapentin,tramadol,opioids,local anaesthetics and N-methyl-D-aspartate receptor antagonists as the rational options for the treatment of phantom limb pain.

  1. An update on the clinical pharmacology of the dipeptidyl peptidase 4 inhibitor alogliptin used for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Chen, Xiao-Wu; He, Zhi-Xu; Zhou, Zhi-Wei; Yang, Tianxin; Zhang, Xueji; Yang, Yin-Xue; Duan, Wei; Zhou, Shu-Feng

    2015-12-01

    Alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor that is a class of relatively new oral hypoglycaemic drugs used in patients with type 2 diabetes (T2DM), can be used as monotherapy or in combination with other anti-diabetic agents, including metformin, pioglitazone, sulfonylureas and insulin with a considerable therapeutic effect. Alogliptin exhibits favorable pharmacokinetic and pharmacodynamic profiles in humans. Alogliptin is mainly metabolized by cytochrome P450 (CYP2D6) and CYP3A4. Dose reduction is recommended for patients with moderate or worse renal impairment. Side effects of alogliptin include nasopharyngitis, upper-respiratory tract infections and headache. Hypoglycaemia is seen in about 1.5% of the T2DM patients. Rare but severe adverse reactions such as acute pancreatitis, serious hypersensitivity including anaphylaxis, angioedema and severe cutaneous reactions such as Stevens-Johnson syndrome have been reported from post-marketing monitoring. Pharmacokinetic interactions have not been observed between alogliptin and other drugs including glyburide, metformin, pioglitazone, insulin and warfarin. The present review aimed to update the clinical information on pharmacodynamics, pharmacokinetics, adverse effects and drug interactions, and to discuss the future directions of alogliptin.

  2. Perioperative pharmacology in morbid obesity.

    Science.gov (United States)

    Lemmens, Hendrikus J m

    2010-08-01

    Morbid obesity alters drug dose requirement and time course of drug response. In addition, morbid obesity's impact on many organ systems decreases the margin of safety of anesthetic drugs. Consequently, incorrect dosing will increase the rate of perioperative complications. In this review, we will discuss factors that affect the pharmacokinetics and pharmacodynamics of anesthetic agents in the obese population, we specify certain dosing scalars, and we relate our current knowledge of obesity's effects on the clinical pharmacology of anesthetic drugs. A morbidly obese individual's increased cardiac output requires administration of higher drug doses than would be required for a standard-size person to attain the same peak-plasma concentration. Lean body weight (LBW) is highly correlated with the increased cardiac output, more so than fat mass or other variables. For most drugs, clearance increases nonlinearly with total body weight but linearly with LBW. Morbid obesity has no clinically significant impact on the uptake of the inhalation anesthetics isoflurane, sevoflurane, and desflurane when used in routine clinical practice. Total body weight dosing of neuromuscular blocking agents will result in a prolonged effect. For the induction dose of hypnotics and the initial dose of other drugs that have a fast onset of effect, cardiac output or LBW are relevant dosing scalars. For maintenance dosing, LBW seems to be a more appropriate dosing scalar than total body weight.

  3. Nelfinavir: fourth protease inhibitor approved.

    Science.gov (United States)

    1997-01-01

    The Food and Drug Administration (FDA) has granted accelerated approval to nelfinavir in both adult and pediatric formulations. Agouron, the manufacturer, used innovative computerized drug design techniques to discover, design, and refine the nelfinavir molecule. Nelfinavir is marketed under the trade name Viracept, and costs $5,000 per year. Early clinical trials find it to be as powerful as the other protease inhibitors, but with a different resistance profile. The drug has relatively few drug indications; however, several compounds have been contraindicated.

  4. Evaluation of hepatic impairment dosing recommendations in FDA-approved product labels.

    Science.gov (United States)

    Chang, Yang; Burckart, Gilbert J; Lesko, Lawrence J; Dowling, Thomas C

    2013-09-01

    Pharmacokinetic (PK) studies in patients with liver disease are an important clinical pharmacology component of drug development. In 2003, FDA released the guidance for industry on "Pharmacokinetics in Patients with Impaired Hepatic Function," which provides recommendations to sponsors on study design, data analysis, and impact on dosing and labeling. We evaluated the quality and consistency of hepatic dosing recommendations, and compared contemporary clinical practice of dosing in patients with impaired hepatic function with product labels. All new molecular entities (NME) and labels approved by the FDA during the period of January 2004 to December 2011 were reviewed. The fraction of the dose hepatically eliminated, quality of hepatic impairment PK studies reported, and any dose recommendations provided in the label and in a tertiary clinical reference (Micromedex) were reviewed. Out of 157 NMEs, 67 met the criteria for evaluation of dosing in hepatic disease. Problem areas were identified related to the lack of specific hepatic metabolism information in 90% of FDA-approved labels, inconsistent terminology, and "use with caution in liver disease" in 27% of NME. Updating the FDA guidance on PK studies in patients with impaired hepatic function could provide a standardized approach to improve the clinical usefulness of this dosing information for practitioners.

  5. Systems Pharmacology Links GPCRs with Retinal Degenerative Disorders

    Science.gov (United States)

    Chen, Yu; Palczewski, Krzysztof

    2015-01-01

    In most biological systems, second messengers and their key regulatory and effector proteins form links between multiple cellular signaling pathways. Such signaling nodes can integrate the deleterious effects of genetic aberrations, environmental stressors, or both in complex diseases, leading to cell death by various mechanisms. Here we present a systems (network) pharmacology approach that, together with transcriptomics analyses, was used to identify different G protein–coupled receptors that experimentally protected against cellular stress and death caused by linked signaling mechanisms. We describe the application of this concept to degenerative and diabetic retinopathies in appropriate mouse models as an example. Systems pharmacology also provides an attractive framework for devising strategies to combat complex diseases by using (repurposing) US Food and Drug Administration–approved pharmacological agents. PMID:25839098

  6. Pharmacological treatment of schizophrenia.

    Science.gov (United States)

    Leucht, S; Heres, S; Kissling, W; Davis, J M

    2013-05-01

    We present the pharmacological treatment of schizophrenia based on a simple algorithm that starts with the most important decisions starting from the choice of an antipsychotic drug for an acutely ill patient and ends with maintenance treatment. It represents experts opinions, a formal guideline development process was not followed. Concerning acute treatment we present recommendations for the choice of drug in acutely patients, the treatment of agitated patients, persistent depression, negative symptoms and treatment resistance. Concerning maintenance treatment with antipsychotics we discuss indication, choice of drug, continuous versus intermittent treatment, duration of relapse prevention and dose.

  7. The pharmacology game.

    Science.gov (United States)

    Batscha, Catherine

    2002-09-01

    This article gives instructions for designing a visually attractive, entertaining, faculty-led computer game for pharmacology review in a nursing education program. The game uses Microsoft PowerPoint, a presentation program that is inexpensive, easy to master, and widely available. Instructions for using Visual Basic for Applications to customize the game are included to allow tracking questions asked and the score of groups playing the game. The game can be easily adapted to material by specific nursing programs with access to PowerPoint.

  8. Pharmacological Profile of Quinoxalinone

    Directory of Open Access Journals (Sweden)

    Youssef Ramli

    2014-01-01

    Full Text Available Quinoxalinone and its derivatives are used in organic synthesis for building natural and designed synthetic compounds and they have been frequently utilized as suitable skeletons for the design of biologically active compound. This review covers updated information on the most active quinoxalinone derivatives that have been reported to show considerable pharmacological actions such as antimicrobial, anti-inflammatory, antidiabetic, antiviral, antitumor, and antitubercular activity. It can act as an important tool for chemists to develop newer quinoxalinone derivatives that may prove to be better agents in terms of efficacy and safety.

  9. Analytical pharmacology: the impact of numbers on pharmacology.

    Science.gov (United States)

    Kenakin, Terry; Christopoulos, Arthur

    2011-04-01

    Analytical pharmacology strives to compare pharmacological data to detailed quantitative models. The most famous tool in this regard is the Black/Leff operational model, which can be used to quantify agonism in a test system and predict it in any other system. Here we give examples of how and where analytical pharmacology has been used to classify drugs and predict mechanism of action in pharmacology. We argue for the importance of analytical pharmacology in drug classification and in prediction of drug mechanisms of action. Although some of the specifics of Black's models have been updated to account for new developments, the principles of analytical pharmacology should shape drug discovery for many years to come.

  10. Pharmacological Treatments in Pathological Gambling

    DEFF Research Database (Denmark)

    Grant, Jon E; Odlaug, Brian Lawrence; Schreiber, Liana R N

    2012-01-01

    demonstrated mixed results in controlled clinical trials. Although limited information is available, opioid antagonists and glutamatergic agents have demonstrated efficacious outcomes, especially for individuals with PG suffering from intense urges to engage in the behavior. CONCLUSIONS: Given that several......AIMS: Pathological gambling (PG) is a relatively common and often disabling psychiatric condition characterized by intrusive urges to engage in deleterious gambling behavior. Although common and financially devastating to individuals and families, there currently exist no formally approved...... pharmacotherapeutic interventions for this disorder. This review seeks to examine the history of medication treatments for PG. METHODS: A systematic review of the 18 double-blind, placebo-controlled pharmacotherapy studies conducted for the treatment of pathological gambling was conducted. Study outcome and the mean...

  11. Pharmacological characteristics and clinical application of trans-dermal fentanyl in cancer pain management%芬太尼透皮贴剂治疗癌痛的药理特点及其临床应用

    Institute of Scientific and Technical Information of China (English)

    程志祥(综述); 王科明(审校)

    2013-01-01

    Cancer pain seriously affects the quality of life of patients and could disturb normal cancer treatment. Therefore, ap-propriate drugs should be chosen to control the pain. Transdermal fentanyl is a type of potent opioid that is widely used in controlling moderate and severe cancer pains. This paper reviews the pharmacological characteristics of transdermal fentanyl and its clinical appli-cation in cancer pain management.%癌痛严重影响患者的生存质量,有时影响正常的肿瘤治疗,因而选择合适的药物控制癌痛至关重要。芬太尼透皮贴剂是一种强阿片类药物,临床上广泛应用于中重度癌痛的治疗,尤其适合一些特别的人群,本文对芬太尼透皮贴剂在癌痛治疗中的药理特点及临床应用进行综述。

  12. Pharmacological Attenuation of Myocardial Reperfusion Injury in a Closed-Chest Porcine Model

    DEFF Research Database (Denmark)

    Ekeløf, Sarah; Rosenberg, Jacob; Jensen, Jan Skov;

    2014-01-01

    Myocardial ischemia-reperfusion injury is a clinical challenge in interventional cardiology, and at the moment, no pharmacological agent is universally accepted in the prevention. In order to prevent inappropriate clinical trials, a potential pharmacological agent should be proved reproducibly...... effective in clinically relevant experimental studies before initiation of human studies. The closed-chest porcine model is a promising experimental model of ischemia-reperfusion injury. The purpose of this systematic review was to describe the pharmacological treatments evaluated in the closed...

  13. Pharmacologic prevention of microvascular and macrovascular complications in diabetes mellitus: implications of the results of recent clinical trials in type 2 diabetes.

    Science.gov (United States)

    Tandon, Nikhil; Ali, Mohammed K; Narayan, K M Venkat

    2012-02-01

    -CoA reductase inhibitors (statins) on vascular outcomes in patients with diabetes. However, data from earlier studies, and also from the subgroup analysis of ACCORD, indicate a probable benefit of adding treatment with fibric acid derivatives to individuals with persistently elevated triglyceride levels despite statin therapy. The most compelling evidence comes from studies assessing the impact of multiple risk factors - glucose, BP, and cholesterol. Studies like the Steno study unequivocally demonstrate the benefit of aggressive control of all three parameters on vascular outcomes in patients with diabetes. In conclusion, attempts to achieve euglycemia in older patients with type 2 diabetes with co-morbidities are not associated with any survival benefit, but may reduce the occurrence of non-fatal CV events. There is a significant risk of major hypoglycemia with this approach, thereby probably limiting its utility to younger patients with new-onset disease. Similarly, lowering systolic BP below 120 mmHg in high CV risk people with diabetes is associated with significant excess adverse events, limiting the utility of such an intervention. However, a clear benefit, which is also cost effective, is observed with strategies for multiple risk-factor control, which should be universally adopted in clinical practice.

  14. Epigenetics and pharmacology

    Science.gov (United States)

    Stefanska, Barbara; MacEwan, David J

    2015-01-01

    Recent advances in the understanding of gene regulation have shown there to be much more regulation of the genome than first thought, through epigenetic mechanisms. These epigenetic mechanisms are systems that have evolved to either switch off gene activity altogether, or fine-tune any existing genetic activation. Such systems are present in all genes and include chromatin modifications and remodelling, DNA methylation (such as CpG island methylation rates) and histone covalent modifications (e.g. acetylation, methylation), RNA interference by short interfering RNAs (siRNAs) and long non-coding RNAs (ncRNAs). These systems regulate genomic activity ‘beyond’ simple transcriptional factor inducer or repressor function of genes to generate mRNA. Epigenetic regulation of gene activity has been shown to be important in maintaining normal phenotypic activity of cells, as well as having a role in development and diseases such as cancer and neurodegenerative disorders such as Alzheimer's. Newer classes of drugs regulate epigenetic mechanisms to counteract disease states in humans. The reports in this issue describe some advances in epigenetic understanding that relate to human disease, and our ability to control these mechanisms by pharmacological means. Increasingly the importance of epigenetics is being uncovered – it is pharmacology that will have to keep pace. PMID:25966315

  15. [Pharmacological treatment of hyperinflation].

    Science.gov (United States)

    Devillier, P; Roche, N

    2009-06-01

    Introduction Lung hyperinflation leads to breathlessness, limitation in exercise capacity and tolerance, and impaired quality of life. Thus, it is important to target this key and characteristic feature of COPD. Current knowledge Available pharmacological approaches rely mainly on bronchodilators, in particular beta2 agonists and anticholinergic agents. These treatments act through the reduction of expiratory airflow limitation. However, changes in classical indices of airflow obstruction do not accurately predict effects on hyperinflation and symptoms. The decrease in operating lung volumes (as reflected by inspiratory capacity or functional residual capacity) at rest and during exercise is one of the mechanisms by which these treatments improve quality of life and maybe also decrease the impact of exacerbations. The effect of beta2 agonists on hyperinflation might be amplified by concurrent treatment with inhaled corticosteroids. Perspectives The effect of new treatments targeting airways inflammation on hyperinflation remains to be explored. Conclusions Measuring the reduction in the degree of lung hyperinflation allows a better understanding of the symptomatic effect of COPD pharmacological treatments.

  16. Prevention of cardiovascular disease guided by total risk estimations - challenges and opportunities for practical implementation: highlights of a CardioVascular Clinical Trialists (CVCT) Workshop of the ESC Working Group on CardioVascular Pharmacology and Drug Therapy.

    LENUS (Irish Health Repository)

    Zannad, Faiez

    2011-11-03

    This paper presents a summary of the potential practical and economic barriers to implementation of primary prevention of cardiovascular disease guided by total cardiovascular risk estimations in the general population. It also reviews various possible solutions to overcome these barriers. The report is based on discussion among experts in the area at a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy that took place in September 2009. It includes a review of the evidence in favour of the \\'treat-to-target\\' paradigm, as well as potential difficulties with this approach, including the multiple pathological processes present in high-risk patients that may not be adequately addressed by this strategy. The risk-guided therapy approach requires careful definitions of cardiovascular risk and consideration of clinical endpoints as well as the differences between trial and \\'real-world\\' populations. Cost-effectiveness presents another issue in scenarios of finite healthcare resources, as does the difficulty of documenting guideline uptake and effectiveness in the primary care setting, where early modification of risk factors may be more beneficial than later attempts to manage established disease. The key to guideline implementation is to improve the quality of risk assessment and demonstrate the association between risk factors, intervention, and reduced event rates. In the future, this may be made possible by means of automated data entry and various other measures. In conclusion, opportunities exist to increase guideline implementation in the primary care setting, with potential benefits for both the general population and healthcare resources.

  17. 丹红注射液治疗老年病的临床应用及药理作用研究进展%Research progress of Danhong injection treatment for geriatric diseases in clinic and pharmacological activity

    Institute of Scientific and Technical Information of China (English)

    吕海洋; 莫颖宁

    2016-01-01

    Danhong injection, a Chinese medicine injection, is made of effective components extracted from Salviae miltiorrhizae Bge. (Lamiaceae) and Carthamus tinctorius L. (Composite) using modern preparation technologies based on the guide of the theory of traditional Chinese medicine. It is characterized by activating blood circulation and resolving stasis and used for treating cardiovascular and cerebrovascular diseases such as coronary heart disease and ischemic encephalopathy in clinic. In recent years, the application scope is expanding with the deepening of the research on Danhong injection. In the present study, literatures from CNKI and Pubmed were adopted, in order to review the application of Danhong injection on geriatric diseases prevention and treatment as well as the research of pharmacological actions in the recent ten years. It will provide references for the clinical application of Danhong injection.%丹红注射液是以中医理论为指导,采用现代制剂工艺从丹参和红花中提取有效成分制成的中药注射剂。具有活血化瘀作用,临床上常用于治疗心脑血管疾病,如冠心病和缺血性脑病。近年来,随着对丹红注射液研究的深入,其应用范围不断扩展。主要采纳中国知网(CNKI)和 Pubmed 中收录的文献,旨在综述近10年丹红注射液用于防治老年病的临床应用及其药理作用研究进展,为丹红注射液的临床应用提供参考。

  18. Alcohol use disorder: pathophysiology, effects, and pharmacologic options for treatment

    Directory of Open Access Journals (Sweden)

    Wackernah RC

    2014-01-01

    Full Text Available Robin C Wackernah,1 Matthew J Minnick,1 Peter Clapp2 1Department of Pharmacy Practice, 2Department of Pharmaceutical Sciences, School of Pharmacy, Rueckert-Hartman College for Health Professions, Regis University, Denver, CO, USA Abstract: Alcohol use disorders (AUD continue to be a concerning health issue worldwide. Harmful alcohol use leads to 2.5 million deaths annually worldwide. Multiple options exist for the management of dependence on alcohol, not all of which are approved by drug-regulating agencies. Current practice in treating AUD does not reflect the diversity of pharmacologic options that have potential to provide benefit, and guidance for clinicians is limited. Few medications are approved for treatment of AUD, and these have exhibited small and/or inconsistent effects in broad patient populations with diverse drinking patterns. The need for continued research into the treatment of this disease is evident in order to provide patients with more specific and effective options. This review describes the neurobiological mechanisms of AUD that are amenable to treatment and drug therapies that target pathophysiological conditions of AUD to reduce drinking. In addition, current literature on pharmacologic (both approved and non-approved treatment options for AUD offered in the United States and elsewhere are reviewed. The aim is to inform clinicians regarding the options for alcohol abuse treatment, keeping in mind that not all treatments are completely successful in reducing craving or heavy drinking or increasing abstinence. Keywords: abuse, alcohol, alcoholism, craving, dependence, relapse

  19. Pharmacological management of hypertension in pregnancy.

    Science.gov (United States)

    Easterling, Thomas R

    2014-12-01

    Hypertension in pregnancy remains a significant public health problem. Pharmacological management of blood pressure in pregnancy is impacted by changes in maternal drug disposition and by the pharmacodynamic effects of specific agents. This article will review the impact of pregnancy on pathways of drug elimination and the associated clinical implications, the pharmacodynamic effects of specific drugs and classes of drugs in pregnancy, and the data to date on the impact of antihypertensive therapy on mothers and their fetuses.

  20. Network pharmacology of cancer: From understanding of complex interactomes to the design of multi-target specific therapeutics from nature.

    Science.gov (United States)

    Poornima, Paramasivan; Kumar, Jothi Dinesh; Zhao, Qiaoli; Blunder, Martina; Efferth, Thomas

    2016-09-01

    Despite massive investments in drug research and development, the significant decline in the number of new drugs approved or translated to clinical use raises the question, whether single targeted drug discovery is the right approach. To combat complex systemic diseases that harbour robust biological networks such as cancer, single target intervention is proved to be ineffective. In such cases, network pharmacology approaches are highly useful, because they differ from conventional drug discovery by addressing the ability of drugs to target numerous proteins or networks involved in a disease. Pleiotropic natural products are one of the promising strategies due to their multi-targeting and due to lower side effects. In this review, we discuss the application of network pharmacology for cancer drug discovery. We provide an overview of the current state of knowledge on network pharmacology, focus on different technical approaches and implications for cancer therapy (e.g. polypharmacology and synthetic lethality), and illustrate the therapeutic potential with selected examples green tea polyphenolics, Eleutherococcus senticosus, Rhodiola rosea, and Schisandra chinensis). Finally, we present future perspectives on their plausible applications for diagnosis and therapy of cancer.

  1. The Clinical Curative Effect of Cefmetazole Treatment of Aspiration Pneumonia and Pharmacological Analysis%头孢美唑治疗吸入性肺炎的临床疗效与药理分析

    Institute of Scientific and Technical Information of China (English)

    孙桂华

    2014-01-01

    目的:探讨头孢美唑治疗吸入性肺炎的药理机制及临床治疗疗效。方法回顾性分析了2010年1月---2012年12月我院收治的240例吸入性肺炎患者的临床资料,随机分为治疗组和对照组,两组均常规治疗,治疗组在此基础上给于头孢美唑治疗,比较两组治疗效果。结果治疗组治疗总有效率为88.33%,对照组治疗总有效率为63.33%,治疗组总有效率明显高于对照组,差异有统计学意义(P<0.05)。治疗组不良反应发生率为2.5%,对照组不良反应发生率为3.3%,治疗组不良反应发生率低于对照组,但差异无统计学意义(P >0.05)。结论头孢美唑治疗吸入性肺炎的临床疗效较好,安全,不良反应少,值得临床推广。%Objective To study the pharmacologic mechanism of cefmetazole in treatment of aspiration pneumonia and clinical therapeutic effect .Methods A retro-spective analysis of 2010 January-2012 December in our hospital treated 240 cases of aspiration pneumonia in patients with clinical data,were randomly divided into treatment group and control group,two groups were treated with conventional treatment,the treatment group based on the given Cefmetazole treatment,treatment effects were compared between the two groups.Results Treatment group total effective rate was 88.33%,control group total effective rate was 63.33%,total effective treatment group was obviously higher than that of control group,and the difference was statistically significant(P0.05).Conclusion cefmetazole treatment of aspiration pneumonia has good clinical curative effect,safety,less adverse reactions,worthy of clinical promotion.

  2. Investigational pharmacology for low back pain

    Directory of Open Access Journals (Sweden)

    Avinash K Bhandary

    2010-09-01

    Full Text Available Avinash K Bhandary1 , Gary P Chimes2, Gerard A Malanga3 1Department of Physical Medicine and Rehabilitation, 2Department of Physical Medicine and Rehabilitation, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 3New Jersey Sports Medicine Institute; Overlook Hospital; Mountainside Hospital; Rehabilitation Medicine and Electrodiagnosis, St Michael’s Medical Center; Horizon Healthcare Worker’s Compensation Services, Blue Cross and Blue Shield Worker’s Compensation, Summit, NJ, USAStudy design: Review and reinterpretation of existing literature.Objective: This review article summarizes the anatomy and pathogenesis of disease processes that contribute to low back pain, and discusses key issues in existing therapies for chronic low back pain. The article also explains the scientific rationale for investigational pharmacology and highlights emerging compounds in late development.Results/conclusion: While the diverse and complex nature of chronic low back pain continues to challenge clinicians, a growing understanding of chronic low back pain on a cellular level has refined our approach to managing chronic low back pain with pharmacology. Many emerging therapies with improved safety profiles are currently in the research pipeline and will contribute to a multimodal therapeutic algorithm in the near future. With the heterogeneity of the patient population suffering from chronic low back pain, the clinical challenge will be accurately stratifying the optimal pharmacologic approach for each patient.Keywords: low back pain, investigational, pharmacology, drugs

  3. Uncertainty sources in radiopharmaceuticals clinical studies; Fontes de incertezas em estudos clinicos com radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Degenhardt, Aemilie Louize; Oliveira, Silvia Maria Velasques de, E-mail: silvia@cnen.gov.br, E-mail: amilie@bolsista.ird.gov.br [Instituto de Radioprotecao e Dosimetria, (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2014-07-01

    The radiopharmaceuticals should be approved for consumption by evaluating their quality, safety and efficacy. Clinical studies are designed to verify the pharmacodynamics, pharmacological and clinical effects in humans and are required for assuring safety and efficacy. The Bayesian analysis has been used for clinical studies effectiveness evaluation. This work aims to identify uncertainties associated with the process of production of the radionuclide and radiopharmaceutical labelling as well as the radiopharmaceutical administration and scintigraphy images acquisition and processing. For the development of clinical studies in the country, the metrological chain shall assure the traceability of the surveys performed in all phases. (author)

  4. Pharmacological Curriculum Reform of Vocational Clinical Major Based on the Working Process%基于工作过程的高职临床医学专业药理课程改革

    Institute of Scientific and Technical Information of China (English)

    楚丽雅; 田维忠; 邵红英; 莫莉

    2013-01-01

    Objective: To investigate the pharmacology curriculum reform effect of vocational clinical major based on the work process and improve the quality of teaching. Methods:To conduct comparison study of two classes with the same teacher. To use traditional teaching methods in control classes; conduct work process-based curriculum reform in experimental class, and design course content in accordance with the patient's diagnosis and treatment process and the drug process, and build five learning contexts, 13 learning units, 56 project tasks, and integrate the teaching content of each unit with a comprehensive training project. After class to investigate the students in experimental class and the teachers about clinical training and internship with education and compare the summative assessment results of two classes. Results:The theoretical results and training assessment scores of experimental class is significantly higher than the control class (P<0.01);98.00%of the students in experimental class think that their self-learning ability is improved, 100%of the teachers think that they create a student-centered learning atmosphere. Conclusion: The pharmacology curriculum reform of vocational clinical major based on the working process adapts to the requirements of higher vocational education reform, and it pays more attention to high-end skilled expertise, and can improve the comprehensive professional abilities of the students.%  目的:探讨基于工作过程的高职临床医学专业药理课程改革效果,提高教学质量。方法:选择同一教师授课的两个班级进行对照研究。对照班采用传统授课方式;实验班实施基于工作过程的课程改革,按照病人的诊疗流程和用药过程设计课程内容,构建5个学习情境、13个学习单元、56个项目任务,每个单元用一个综合实训项目将教学内容串联在一起。授课后用自制调查问卷对实验班学生、临床见习和实习带教教

  5. Prediction of pharmacological and xenobiotic responses to drugs based on time course gene expression profiles.

    Directory of Open Access Journals (Sweden)

    Tao Huang

    Full Text Available More and more people are concerned by the risk of unexpected side effects observed in the later steps of the development of new drugs, either in late clinical development or after marketing approval. In order to reduce the risk of the side effects, it is important to look out for the possible xenobiotic responses at an early stage. We attempt such an effort through a prediction by assuming that similarities in microarray profiles indicate shared mechanisms of action and/or toxicological responses among the chemicals being compared. A large time course microarray database derived from livers of compound-treated rats with thirty-four distinct pharmacological and toxicological responses were studied. The mRMR (Minimum-Redundancy-Maximum-Relevance method and IFS (Incremental Feature Selection were used to select a compact feature set (141 features for the reduction of feature dimension and improvement of prediction performance. With these 141 features, the Leave-one-out cross-validation prediction accuracy of first order response using NNA (Nearest Neighbor Algorithm was 63.9%. Our method can be used for pharmacological and xenobiotic responses prediction of new compounds and accelerate drug development.

  6. Pharmacology of fenofibrate.

    Science.gov (United States)

    Chapman, M J

    1987-11-27

    This discussion outlines the major aspects of the human pharmacology of fenofibrate, a hypolipidemic agent. In view of its short half-life, efficient absorption, and elimination, fenofibrate would not appear to accumulate in either plasma or tissues. It is extensively absorbed only in the presence of food and is transported through the bloodstream by albumin. Fenofibrate is taken up by both the liver and kidney. Except for a small percentage (about 5 percent) reduced at the ketone moiety before conjugation, most drug is excreted as a conjugate in the urine. Less than 20 percent is excreted through the bile. In normal persons, at steady state with usual doses of 100 mg three times daily, the plasma half-life approximates 30 hours. Because fenofibrate is not dialyzable, it has a markedly prolonged half life in patients with renal failure and should not be used.

  7. Pharmacology of antiplatelet agents.

    Science.gov (United States)

    Kalra, Kiran; Franzese, Christopher J; Gesheff, Martin G; Lev, Eli I; Pandya, Shachi; Bliden, Kevin P; Tantry, Udaya S; Gurbel, Paul A

    2013-12-01

    Pharmacotherapies with agents that inhibit platelet function have proven to be effective in the treatment of acute coronary syndromes, and in the prevention of complications during and after percutaneous coronary intervention. Because of multiple synergetic pathways of platelet activation and their close interplay with coagulation, current treatment strategies are based not only on platelet inhibition, but also on the attenuation of procoagulant activity, inhibition of thrombin generation, and enhancement of clot dissolution. Current strategies can be broadly categorized as anticoagulants, antiplatelet agents, and fibrinolytics. This review focuses on the pharmacology of current antiplatelet therapy primarily targeting the inhibition of the enzyme cyclooxygenase 1, the P2Y12 receptor, the glycoprotein IIb/IIIa receptor, and protease-activated receptor 1.

  8. 28 CFR 549.51 - Approval procedures.

    Science.gov (United States)

    2010-07-01

    ... SERVICES Plastic Surgery § 549.51 Approval procedures. The Clinical Director shall consider individually any request from an inmate or a BOP medical consultant. (a) In circumstances where plastic surgery is... the Clinical Director recommends plastic surgery for the good order and security of the...

  9. Radiological Medical Device Innovation: Approvals via the Premarket Approval Pathway From 2000 to 2015.

    Science.gov (United States)

    Ghobadi, Comeron W; Hayman, Emily L; Finkle, Joshua H; Walter, Jessica R; Xu, Shuai

    2017-01-01

    The aim of this study was to critically assess the clinical evidence leading to radiologic medical device approvals via the premarket approval pathway from 2000 to 2015. This study used the publically available FDA premarket database for radiologic device approvals over the past 15 years (September 1, 2000, to August 31, 2015). Approval characteristics were collected for each device, and statistical analysis was performed on the data for each pivotal trial. Additionally, methodological quality of the pivotal trial was determined using the Quality Assessment of Diagnostic Accuracy Studies tool. Twenty-three class III radiologic device approvals were identified, with breast imaging accounting for 16 (70%) and computer-aided detection software accounting for 9 (39%) approvals. The median premarket approval time was 475 days (range, 180-1,116). Twenty-one devices were approved on the basis of multireader, multicenter studies, one on the basis of a randomized controlled trial, and one on the basis of a preclinical technical equivalence trial. The median number of patients per pivotal trial was 201 (range, 25-3,946). Twenty-six of the 34 pivotal trials (76%) had at least one methodologic bias. Breast imaging devices had a greater number of patients per pivotal trial (P = .009) and more prospective studies. With regard to all modalities, increased time to device approval correlated with weaker trial quality (r = 0.600, P < .001). Radiologic devices are largely approved by multireader, multicenter studies, the recommended standard for assessing diagnostic technologies. Given that radiologic devices play a key role in modern medicine, further efforts should be made to increase transparency of clinical data leading to approval. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  10. Neurotransmitters, Pharmacologic Synergy, and Clinical Strategies

    National Research Council Canada - National Science Library

    Stark, Martha

    2006-01-01

    ... of neurotransmitters and their receptor sites, more ingenious methods of drug administration, and more creative combinations of the various drugs, more than half our patients have psychiatric sympto...

  11. Fluoxetine: clinical pharmacology and physiologic disposition

    Energy Technology Data Exchange (ETDEWEB)

    Lemberger, L.; Bergstrom, R.F.; Wolen, R.L.; Farid, N.A.; Enas, G.G.; Aronoff, G.R.

    1985-03-01

    Fluoxetine (30 mg), administered for 7 days to normal volunteers, produced a 66% inhibition of tritiated serotonin uptake into platelets. Plasma concentrations of fluoxetine correlated positively with inhibition of serotonin uptake. Fluoxetine is well absorbed after oral administration in both the fed and fasted states and demonstrates dose proportionality. Fluoxetine disappears from plasma with a half-life of 1-3 days; its metabolite norfluoxetine has a plasma half-life of 7-15 days. After administration of /sup 14/C-fluoxetine, approximately 65% of the administered dose of radioactivity is recovered in urine and about 15% in feces. Fluoxetine, given as a single dose or in multiple doses over 8 days, did not produce significant effects on the plasma disappearance of warfarin, diazepam, tolbutamide, or chlorothiazide. Coadministration of fluoxetine and ethanol did not result in an increase from control values in the blood ethanol levels, nor did it produce significant changes in physiologic, psychometric, or psychomotor activity. Pharmacokinetics of fluoxetine in the elderly and normal volunteers appear to be similar. In addition, pharmacokinetic analyses in patients with varying degrees of renal impairment did not show significant differences from healthy subjects.

  12. [The clinical pharmacological profile of pinaverium bromide].

    Science.gov (United States)

    Guslandi, M

    1994-04-01

    Pinaverium bromide is a locally acting spasmolytic agent of the digestive tract. Its mechanism of action relies upon inhibition of calcium ion entrance into smooth muscle cells (calcium-antagonist effect). In humans pinaverium facilitates gastric emptying and decreases intestinal transit time in patients with constipation. Pinaverium is very effective in improving symptoms of irritable bowel syndrome (abdominal pain, gas, diarrhea or constipation). In this respect the drug proved to be significantly superior to placebo, at least as effective as trimebutine and on the whole more active than otilonium and prifinium bromide, being always extremely well tolerated.

  13. Pharmacological fMRI; a clinical exploration

    OpenAIRE

    Goekoop, R.

    2006-01-01

    Dit proefschrift beschrijft de resultaten van een verkennend onderzoek naar een nieuwe techniek die gebruikt kan worden om de effecten van geneesmiddelen op hersenaktiviteit af te beelden: pharmacologische functionele magnetic resonance imaging (farmacologische fMRI of phMRI). Met behulp van deze techniek werden de effecten onderzocht van drie verschillende medicijnen (de bètablokker propranolol, de selectieve oestrogeen-receptor modulator (SERM) raloxifene en de cholinesteraseremmer galantam...

  14. Clinical pharmacology of ifosfamide and metabolites

    NARCIS (Netherlands)

    Kerbusch, T.

    2001-01-01

    Introduction Ifosfamide is an alkylating agent, which is used in the treatment of various types of malignant diseases in adults and childeren. Its use, however, can be accompanied by severe haematological, neuro- and nephrotoxicities. Since its development in the middle of the 1960’s, most of its ex

  15. Clinical pharmacology of tiamulin in ruminants.

    Science.gov (United States)

    Ziv, G; Levisohn, S L; Bar-Moshe, B; Bor, A; Soback, S

    1983-03-01

    Median values for the minimum inhibitory concentrations (MIC) of tiamulin for Mycoplasma and Acholeplasma isolated from ruminants were 0.05 micrograms/ml and 0.025 micrograms/ml, respectively. These values were close to the MIC values of tylosin and considerably lower than the respective values for spectinomycin, Spiramycin and oxytetracycline. The serum concentration--time profile of tiamulin after intramuscular (i.m.) injection to goats, ewes, cows and calves, and after oral administration to preruminant calves was characterized by a rapid absorption phase (absorption t1/2 of less than 30 min.), a short plateau phase, an elimination t1/2 ranging between 3 and 6 h, and low peak serum drug levels. The serum elimination t1/2 of the drug after intravenous (i.v.) injection was 25 min. It appears that tiamulin is extensively metabolized in ruminants and is well distributed throughout the body. Drug concentrations in the lungs, liver, and the kidneys 1 h after i.v. injection were four to seven times higher than in blood. The drug penetrated very rapidly into the milk after i.m. administration; mean peak drug concentrations in normal milk and in milk secreted from inflamed glands of cows were 7.5 times and 1.2 times higher respectively, than the mean peak serum drug concentrations. Concentrations of tiamulin of potential therapeutic value in the treatment of mycoplasmal infections can be maintained in the lungs for at least 12 h after i.m. injection at 10 mg/kg, and in preruminant calves after an oral dose of 20 mg/kg. However, tiamulin possesses several very serious side-effects and the i.v. route of administration is definitely contraindicated.

  16. Pharmacologic and non-pharmacologic treatments for chronic pain in individuals with HIV: a systematic review.

    Science.gov (United States)

    Merlin, Jessica S; Bulls, Hailey W; Vucovich, Lee A; Edelman, E Jennifer; Starrels, Joanna L

    2016-12-01

    Chronic pain occurs in as many as 85% of individuals with HIV and is associated with substantial functional impairment. Little guidance is available for HIV providers seeking to address their patients' chronic pain. We conducted a systematic review to identify clinical trials and observational studies that examined the impact of pharmacologic or non-pharmacologic interventions on pain and/or functional outcomes among HIV-infected individuals with chronic pain in high-development countries. Eleven studies met inclusion criteria and were mostly low or very low quality. Seven examined pharmacologic interventions (gabapentin, pregabalin, capsaicin, analgesics including opioids) and four examined non-pharmacologic interventions (cognitive behavioral therapy, self-hypnosis, smoked cannabis). The only controlled studies with positive results were of capsaicin and cannabis, and had short-term follow-up (≤12 weeks). Among the seven studies of pharmacologic interventions, five had substantial pharmaceutical industry sponsorship. These findings highlight several important gaps in the HIV/chronic pain literature that require further research.

  17. Molecular pharmacology of G protein-coupled receptors.

    Science.gov (United States)

    Summers, R J

    2016-10-01

    This themed issue of the British Journal of Pharmacology stems from the eighth in the series of meetings on the Molecular Pharmacology of G protein coupled receptors (MPGPCR) held as part of a joint meeting with the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) in Melbourne Australia from 7 to 11 December 2014. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc.

  18. [Integrative pharmacology: new paradigm of modernization of Chinese medicine].

    Science.gov (United States)

    Xu, Hai-Yu; Yang, Hong-Jun

    2014-02-01

    Chinese medicinal formulae( CMF) were often used in the clinics of traditional Chinese medicine (TCM) which were critical for modernization of Chinese medicine to shed light on the interaction between CMF and biological organisms. In current studies, correlation between system and part, macroscopic actions and microcosmic mechanism, ADME process and pharmacologic actions were often neglected. Thus, we put forward integrative pharmacology, which could integrate the correlation between CMF and biological organisms from multi-levels and multi-dimensional views. Integrative pharmacology would reveal the molecular mechanism of CMF for ailments treatment and screen out effective material systematically, which would be the new paradigm of TCM research.

  19. Non-pharmacological approaches to alleviate distress in dementia care.

    Science.gov (United States)

    Mitchell, Gary; Agnelli, Joanne

    2015-11-25

    Distress is one of the most common clinical manifestations associated with dementia. Pharmacological intervention may be appropriate in managing distress in some people. However, best practice guidelines advocate non-pharmacological interventions as the preferred first-line treatment. The use of non-pharmacological interventions encourages healthcare professionals to be more person-centred in their approach, while considering the causes of distress. This article provides healthcare professionals with an overview of some of the non-pharmacological approaches that can assist in alleviating distress for people living with dementia including: reminiscence therapy, reality orientation, validation therapy, music therapy, horticultural therapy, doll therapy and pet therapy. It provides a summary of their use in clinical practice and links to the relevant literature.

  20. Novel pharmacologic treatment in acute binge eating disorder – role of lisdexamfetamine

    Directory of Open Access Journals (Sweden)

    Guerdjikova AI

    2016-04-01

    Full Text Available Anna I Guerdjikova,1,2 Nicole Mori,1,2 Leah S Casuto,1,2 Susan L McElroy1,2 1Lindner Center of HOPE, Mason, OH, USA; 2Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA Abstract: Binge eating disorder (BED is the most common eating disorder and an important public health problem. It is characterized by recurrent episodes of excessive food consumption accompanied by a sense of loss of control over the binge eating behavior without the inappropriate compensatory weight loss behaviors of bulimia nervosa. BED affects both sexes and all age groups and is associated with medical and psychiatric comorbidities. Until recently, self-help and psychotherapy were the primary treatment options for patients with BED. In early 2015, lisdexamfetamine dimesylate, a prodrug stimulant marketed for attention deficit hyperactive disorder, was the first pharmacologic agent to be approved by the US Food and Drug Administration for the treatment of moderate or severe BED in adults. This article summarizes BED clinical presentation, and discusses the pharmacokinetic profile, efficacy, and safety of lisdexamfetamine dimesylate in the treatment of BED in adults. Keywords: binging, overeating, Vyvanse, stimulant, approved medication