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Task shifting involves the rational redistribution of tasks among health workforce teams discount 25 mg endep mastercard symptoms gestational diabetes. With this approach discount endep 10 mg without a prescription medicine head, specifc tasks are reassigned buy discount endep 25mg symptoms 9f anxiety, where appropriate, from highly qualifed health workers to health workers with shorter training and fewer complementary qualifcations to more effciently and effectively use the available human resources. Task shifting should be implemented alongside other strategies designed to increase the total numbers and capacity of all types of health workers. Rationale and supporting evidence The systematic review identifed three randomized trials and six observational studies addressing task shifting. The quality of care in these studies was ensured by (1) providing training, mentoring, supervision and support for nurses, non-physician clinicians and community health workers; (2) ensuring clear indications for patient referral; (3) implementing referral systems and (4) implementing monitoring and evaluation systems. Patient education could help people and their families understand that care provided by nurses and community health workers is not of lower quality than that provided by physicians (106–108,111,113,114,119–121). To ensure that testing services are accurate and reliable, relevant quality assurance systems need to be developed and strengthened. Since an increasing number of new diagnostic tests and point-of-care systems is entering the market, the use of only high-quality diagnostics and equipment needs to be ensured. Strategic planning for properly placing and harmonizing testing platforms should be carried out to ensure appropriate use and cost–effectiveness. The guidelines should include training requirements for specifc tests and the process for certifcation and recertifcation. All health workers assigned to perform point- of-care tests must be trained and profcient on the testing procedure, specimen collection and quality assurance before implementing these services. The quality management system should: be implemented within the laboratory network and all remote testing sites; be incorporated into the routine testing procedures and monitored; ensure that testing sites undertake quality control, as appropriate; ensure that testing sites are enrolled in an external quality assessment scheme (profciency testing programme); ensure the use of standard operating procedures for all processes, including specimen collection and processing, test methods, interpreting results and reporting; ensure the use of standardized logbooks or electronic data management and reporting, including identifying errors and potential misclassifcation; and ensure that equipment and facilities are maintained, both preventive and corrective. This can be achieved only if the procurement and supply management system is strengthened at all levels of the health system. This requires a more effcient and dynamic supply management system to prevent waste and shortages. Since a single health facility may not carry out the dispensing of all needed pharmaceuticals, in some settings clients would need to be able to access services through a referral system. It includes a variety of activities at all levels of the health care delivery system: from the national programme level down to where medicines are dispensed and diagnostics are used. The main activities include managing the information system, ensuring timely information flow between stakeholders at different levels and securing financial and other resources, including the medicines and diagnostics needed for the programme. The following provides broad guidance on key activities at each stages of the supply management cycle. Countries may consider removing less preferred products and aligning paediatric formulations with those of adults, where possible. Health workers need to be trained at different levels in managing pharmaceuticals and diagnostics, including forecasting, procurement and distribution and ensuring adequate supervision throughout the supply system. Procurement should be based on appropriate selection of products and need-based forecasting, considering consumption, expanding services, phasing in and phasing out formulations and implementing new recommendations. Transparent procedures should be adopted to achieve best-value procurement and a quality assurance system implemented to procure, store and distribute high-quality pharmaceuticals, diagnostics and other health products (124,126). Product integrity and quality need to be maintained during storage and distribution (125,132), and waste from spoilage and expired products should be minimized. Integrated supply systems should be promoted when planning for decentralization, building on what exists and strengthening capacity where required. Facilities should have adequate storage space, trained personnel and the tools to manage supplies effectively. The number of storage levels should be rationalized to reduce the supply pipeline. Accurate inventory records should be maintained and a system created to track products that enter and leave the supply system. A routine consumption-based reordering cycle at service delivery sites should be established. Monitoring procurement and supply management through the effective use of early warning indicators prevents stock-outs and overstocks leading to expiry (126). National stakeholders face several important choices on how to optimally translate these recommendations into national practice. For example, although evidence of clinical efficacy supports the uptake of interventions, issues such as cost and cost– effectiveness, ethical and human rights considerations, the perceptions of various stakeholders and the legal and regulatory environment must also be taken into account (1). First, convening a broad, inclusive and transparent consultative process can help to define what programme changes are relevant and necessary, such as revising national protocols, guidelines and regulations. Second, in parallel, it is necessary to secure the financial resources and political support required to implement the proposed changes. Third, systems are required to ensure broad accountability for implementation from all partners at all levels and adequately document performance to inform programming decisions and maintain political support. Lastly, implementation and operations research should be supported so that innovative approaches can be assessed and taken to scale. Human rights and ethical principles should guide the revision of national treatment policies to ensure that they are equitable and meet the specific needs of all beneficiaries. Although national programme managers should oversee the decision-making process, it should also be broadly representative. The composition of the working group may vary over time and depend on the specific recommendations under discussion. In some countries, these data may be available from regular monitoring and evaluation activities or from recent programme assessments. Quantitative and qualitative data should, whenever possible, be disaggregated by gender, age, subnational administrative categories (such as regions and districts) and other relevant stratifications, including key populations, to ensure that new policies address inequities in access and increase the coverage of interventions. The consolidation of health information systems, including patient record registries, into electronic databases is critical to facilitate the management of increasing amounts of data and improve their robustness and availability for programme decision-making (see section 11. Data on adherence, retention and viral load suppression are key to assess the quality of the services provided. Relevance: Do stakeholders affected by these decisions agree that the rationale rests on relevant reasons, principles and evidence? Revisability and appeals: Can decisions be revised and/or appealed in light of new evidence and arguments? Enforcement: Are all stakeholders aware of the means to ensure that these conditions (publicity, relevance and revisability) are met? Can all stakeholders participate effectively, be heard and infuence decision- making? Is information accessible to all key stakeholders in written and understandable language? Is the process organized to ensure the meaningful participation of all relevant stakeholders? Have the potential social, cultural, and legal barriers that deter the meaningful participation of historically marginalized stakeholders been identifed and addressed? Transparency regarding the grounds for decisions Are the decision-making criteria transparent and is the rationale stated explicitly with reference to: Scientific evidence, including effectiveness and risk? Alignment between evidence and recommendations Are the recommendations appropriate for the epidemiological setting in which they will be implemented? Are the recommendations aligned with and do they support the implementation of the programme’s overarching vision, goals and objectives?

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Henriques Institute for Molecular Bioscience The University of Queensland purchase genuine endep line medications 5113, Brisbane discount endep 10 mg fast delivery medications 123, Queensland buy cheap endep 25 mg on-line medications in mexico, Australia David J. Craik Institute for Molecular Bioscience The University of Queensland, Brisbane, Queensland, Australia 6. All organisms screen their environment and produce compounds that provide them with an evolutionary advan- tage [1, 2]. Thus, natural compounds are often the starting point for the design of drugs with high selectivity and potency [1–4]. Peptides are expressed in all living species and display a large diversity of structures and biological effects. Therefore it is not surprising that natural occurring peptides are attractive drug leads and are mak- ing their way into clinical applications [5–15]. A vast number of active peptides have been isolated and characterized from a broad variety of biological sources. Peptides involved in host defense and prey capture are among the best drug candidates, due to their fast-acting protection/capture mechanism. Organisms that produce host-defense peptides with potential applications in drug development include prokaryotes, plants, and animals, and we begin this article with brief descriptions of a few examples. Bacteria are a rich source of peptides with potential pharmaceutical appli- cations. Both Gram-negative and Gram-positive bacteria produce antimicrobial Peptide Chemistry and Drug Design, First Edition. Bacteriocins are attractive candidates both as antimicrobial agents for the treatment of human and animal infections, and as food preservatives [16–18]. Nisin also has promising applications for the treatment of Helicobacter infections, ulcers [20] and intestinal colonization by Enterococci [21] and more recently has been suggested to have potential therapeutic anti-tumorigenic properties [22]. The emergence of vancomycin-resistant Entero- cocci has led to the need for alternative therapies to traditional antibiotics, and nisin has entered preclinical trials [23]. Other bacteriocins have attracted attention for the treatment of diarrheagenic bacterial contamination [24] and as spermicidal agents [25]. Plants also produce peptides to defend themselves against pathogen attack [26–28]. We focus here on a group of plant peptides that, as well as having defense properties [29, 30], have topological properties that make them particularly stable and hence suitable as framework in drug design [31–34]. These peptides have a head-to-tail cyclised peptidic backbone and are referred to as cyclotides [35]. Cyclotide-containing plants were frst used for medicinal purposes in the Congo region of Africa [36, 37]. It was later determined that they incorporate a unique knotted macrocyclic structure that confers them with great stability relative to conventional linear proteins [35]. Overall, cyclotides are fascinating peptides that have the chemical constitution of proteins but the stability properties of organic chemicals, thus making them useful drug leads. Cyclotides will be explored in more detail later in this chapter, revealing what plants have to offer to the drug design feld. Venomous organisms are spread throughout the animal kingdom and include rep- tiles, fshes, amphibians, mammals, mollusks, arachnids, and insects. In any niche there is a competition for resources, and the use of venom for prey capturing, or as a defense mechanism, represents a successful adaptative trait [42]. Venoms are typically produced as deadly cocktails, comprising mixtures of peptides adapted by natural selection. These toxins disrupt cardiovascular and neuromuscular systems by disturbing the activity of critical enzymes, receptors, and ion channels. Venom tox- ins have a high degree of target specifcity and they have been used increasingly as pharmacological tools and leads in drug development [42–45]. Amphibians secrete peptides with antimicrobial properties from their skin as part of their defense system [46–48]. The magainins are of particular interest as they have potent antimicrobial activity, with little or no hemolytic activity [49], and they represent early examples of peptides that were considered to have great potential as drugs due to their specifcity and broad antibacterial spectrum. Nevertheless, the interest in magainin stimulated searches for other antibiotics, and peptides with a range of antimicrobial [46, 52, 53], anticancer [54], and antiviral activities [55–57] have now been isolated from amphibian skin. Peptides with potential therapeutic applications have been found in the venom of a range of other animals, including cone snails, spiders, scorpions, and snakes [58]. Such peptides are particularly abundant in cone snails and due to their small size and suitability for synthesis these peptides, called conotoxins, are valuable drug leads [45, 58]. The genus Conus is a large group of carnivorous predators found in tropical marine habitats, and although each Conus species is a highly specialized predator, collectively, cone snails have a remarkably broad spectrum of prey. All members of this genus use their venom, which contains numerous (100–1000) toxic peptides, for prey capture [59]. They bind to a diverse range of sodium, calcium and potassium channels, membrane receptors and transporters, leading to effcient immobilization of the prey [60, 61]. Conotoxins have great diversity and specifcity, and each peptide targets a spe- cifc receptor protein. With their ability to discriminate between different isoforms of the same receptor, these peptides are valuable pharmacological probes as well as potential leads in drug design [62]. In fact, a conotoxin extracted from Conus magus, is an example of the development of a toxin into an approved drug. This is a relatively rare example of a peptide used without further modifca- tion. Several other conotoxins are currently being evaluated in clinical and preclinical trials (e. Overall, cone snail venoms contain a huge reservoir of compounds that can be regarded as a combinatorial library of drug leads. Having introduced a few examples of peptide drug leads, we briefy overview the drug development process before examining particular classes of peptides in more detail. There are a number of key steps in the development of a drug, as shown in Figure 6. The frst consideration is to satisfy an unmet medical need [3] and so selection of a drug target is usually the starting point for drug development [67]. Other steps include the choice of natural sources containing promising active compounds; the screening of large numbers of compounds [68]; identifcation and isolation of the most active peptides; characterization of primary structure using sequencing tech- niques or genomics for gene determination; and three-dimensional (3D) structure determination [9]. Knowledge obtained from peptide structure characterization allows leads to be optimized via medicinal chemistry. Substitution analysis and chemical modifcation are used to improve stability and activity. Cost of production, stability, selectivity, delivery, and mechanism of action need to be considered [58]. Peptides are particu- larly amenable to modifcations to confer improved selectivity, potency, and stability [51], while maintaining bioactivity [69].

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Is digoxin a ciplinary study identifes digoxin as a possible drug for designer oestrogen? Rate control and sinus rhythm maintenance A new buy endep 25mg lowest price treatment improvement protocol, high-throughput high-performance liquid in atrial fbrillation: national trends in medication chromatographic/mass spectrometric assay for thera- use purchase endep 50mg online medicine 4h2, 1980–1996 purchase 50mg endep mastercard treatment trichomonas. Is digitalis a therapy for breast carci- Wang Z, Zheng M, Li Z, Li R, Jia L, Xiong X et al. High- performance liquid chromatography-ionspray mass spectrometry for the specifc determination of digoxin and some related cardiac glycosides in human plasma. Other agents evaluated included the drugs primidone, sulfasalazine, pentosan polysulfate sodium, and triamterene, and five herbal products (or their components): Aloe vera whole leaf extract, goldenseal root powder, Ginkgo biloba leaf extract, kava extract, and pulegone. In view of the limited agent-specific information available from epidemiological studies, assessments of these agents relied mainly on carcinogenicity bioassays to reach conclusions as to the carcinogenic hazard to exposed humans. No part of this ebook may be reproduced in any form, by photostat, microfilm, xerography, or any other means, or incorporated into any information retrieval system, electronic or mechanical, without the written permission of the publisher. The Invention of a New Specialized Laboratory Procedure Brings About Rapid Conquests in New Fields of Science and Technology. Von Cholnoky This page intentionally left blank Preface to the Second Edition Modern Pharmaceutical Drug Analysis essentially involves as a necessary integral component even greater horizons than the actual prevalent critical analysis of not only the active pharmaceutical substances but also the secondary pharmaceutical product(s) i. The fundamental reasons for this sudden legitimate surge in the newer evolving methodologies in the ‘analysis of drug substances’ are perhaps due to the tremendous growth in the progress of ‘medicinal chemistry’ towards achieving one ultimate objective which is to obtain ‘better drugs for a better world’. Keeping in view the above astronomical growth in the design of complicated, specific and highly active drug molecules an equally viable, rigorous, accurate and precise analytical methods have been evolved with the passage of time which have now occupied pivotal and vital positions in most of the Official Compendia viz. The present revised textbook on‘Pharmaceutical Drug Analysis’ caters for the much needed handbook and reference book, which is absolutely current with regard to the esteemed philosophy of analytical chemistry, an obvious solid support towards drug discovery, development, stability stud- ies, bioavailability and pharmacokinetic studies, and above all the quality assurance of pure drugs together with their respective dosage forms. The thirty-two different chapters meticulously divided into six parts invariably covers up analytical techniques being used in most of the Official Compendia. Each chapter categorically and explicitly deals with the introduction, theoretical aspect(s), instrumentation, typical examples of pharmaceutical analysis and cognate assays. The textbook on ‘Pharmaceutical Drug Analysis’ would enormously serve the undergradu- ates, postgraduates, researchers, analytical chemists working in the Quality Assurance Laborato- ries, new drug development, production and control, teaching, or regulatory authorities. All these salient features of a ‘drug’ help a researcher not only in planning a precise experimental design but also in the interpretation of data in a logical and scientific manner. Pharmaceutical scientists ought to have a good command over the wide-spectrum of chemical analysis so as to achieve completeness in their scientific pursuit of knowledge. Unfortunately, such information is either found scattered in various available literatures or appears as an extremely specific work on a rather scanty and limited subject area. The main objective of ‘Pharmaceutical Drug Analysis’ is to offer not only a ready reference handy textbook but also an intermediate level of coverage for the convenient analysis of pure pharmaceutical substances and their respective dosage forms wherever applicable. The present copious textual compilation of information is solely intended to narrow down the apparently wide gap existing between the available basic texts and the extremely specific research papers from various scientific journals. The contents of this textbook have been meticulously designed to provide fundamentals of various disciplines embodying pharmaceutical drug analysis specifically for the under-graduate students. It will also be useful to the graduate students studying modern methods of pharmaceutical analysis to a great extent. Particular emphasis has been laid on the pharmaceutical substances that are specially found in theOfficial Compendia. It will also cater to scientists and investigators, working in other fields of pharmaceutical sciences who wish to update their personal wealth of knowledge and understanding of the intricacies of modern methods of Pharmaceutical Drug Analysis. Enough literature have been cited at the end of each chapter under ‘Recommended Readings’ so as to enable the reader to follow up a particular topic with ease. Part—I has three chapters that exclusively deal with ‘General Aspects’ of pharmaceutical analysis. Chapter 1 focuses on the pharmaceutical chemicals and their respective purity and management. Critical information with regard to description of the finished product, sampling procedures, bioavailability, identification tests, physical constants and miscellaneous characteristics, such as : ash values, loss on drying, clarity and color of solution, specific tests, limit tests of metallic and non-metallic impurities, limits of moisture content, volatile and non-volatile matter and lastly residue on ignition have also been dealt with. Each section provides adequate procedural details supported by ample typical examples from the Official Compendia. Chapter 2 embraces the theory and technique of quantitative analysis with specific emphasis on volumetric analysis, volumetric apparatus, their specifications, standardization and utility. It also includes biomedical analytical chemistry, colorimetric assays, theory and assay of biochemicals, such as : urea, bilirubin, cholesterol; and enzymatic assays, such as alkaline phosphatase, lactate dehydrogenase, salient features of radioimmunoassay and automated methods of chemical analysis. Chapter 3 provides special emphasis on errors in pharmaceutical analysis and their statistical validation. The first aspect is related to errors in pharmaceutical analysis and embodies classification of errors, accuracy, precision and makes ( x ) an attempt at minimizing systematic errors. The second aspect is mainly devoted to statistical validation and comprises of statistical treatment of finite samples, distribution of random errors, significant errors, comparison of results, method of least squares and criteria for rejection of an observation. Each chapter has its unique style of presentation that essentially comprises of the following vital features, namely : brief introduction, theory with necessary details and relevant reactions, instrumentation, assay methods—with typical appropriate examples invariably selected from the Official Compendia including brief theoretical treatment of individual pharmaceutical substance and dosage form, materials required, procedures, calculations wherever applicable, cognate assays and lastly citation of relevant literature under ‘Recommended Readings’. Section— A deals on treatment by ‘titrimetric methods’ based on acidimetry and alkalimetry. The first arm of this section deliberates on aqueous titrations (Chapter 4), while the second on non-aqueous titrations (Chapter 5). Section—B relates to ‘redox methods’ with specific reference to permanganate, dichromate and ceric sulphate titration methods (Chapter 6); and also the iodimetric and iodometric titrations (Chapter 7). Section—C concerns with the ‘precipitation methods’ and focuses on argentometric methods (Chapter 8). Particular stress has been laid on the effect of pH on complexation, stability of complexes, usage of pM indicators and masking and demasking agents (Chapter 9). The topic has been treated with respect to Law of Mass Action, reversible reactions, principle of solubility of product and common-ion effect. Typical examples have been included of pharmaceutical substances assayed after conversion to free acid, or free base, or free compound and lastly to derivatives or substitution products (Chapter 10). Section—G particularly embodies the ‘miscellaneous methods’ which do not fall into the regimen of Section—A through Section—F. It deals with diazotization (Chapter 12), estimation of phenols and related compounds (Chapter 13) using bromine or potassium bromate, potassium iodate solutions; Karl Fischer method for determination of water (Chapter 14); and lastly tetrazolium assay of steroids (Chapter 15). Two important methods, namely; potentiometric methods (Chapter 16) deal with various types of reference electrodes and indicator electrodes, automatic titrator; besides typical examples of nitrazepam, allopurinol and clonidine hydrochloride. Amperometric methods (Chapter 17) comprise of titrations involving dropping-mercury electrode, rotating—platinum electrode and twin-polarized microelectrodes (i. Polarimetry (Chapter 19) describes optical rotation and specific optical rotation of important pharmaceutical substances. Nephelometry and turbidimetry (Chapter 20) have been treated with sufficient detail with typical examples of chloroetracyclin, sulphate and phosphate ions. Ultraviolet and absorption spectrophotometry (Chapter 21) have been discussed with adequate depth and with regard to various vital theoretical considerations, single-beam and double-beam spectrophotometers; besides typical examples amoxycillin trihydrate, folic acid, glyceryl trinitrate tablets and stilbosterol.