United States Adopted Name
United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, co-sponsored by the American Medical Association, the United States Pharmacopeial Convention, the American Pharmacists Association; the USAN Program states that its goal is to select simple and unique nonproprietary names for drugs by establishing logical nomenclature classifications based on pharmacological or chemical relationships. In addition to drugs, the USAN Council names agents for gene therapy and cell therapy, contact lens polymers, surgical materials, diagnostics and substances used as an excipient; the USAN Council works in conjunction with the World Health Organization International Nonproprietary Name Expert Committee and national nomenclature groups to standardize drug nomenclature and establish rules governing the classification of new substances. The USAN Council began in June 1961 after the AMA and the USP jointly formed the AMA-USP Nomenclature Committee.
The American Pharmacists Association became the third sponsoring organization in 1964, at which point the name of the committee was changed to the USAN Council, United States Adopted Name became the official term to describe any nonproprietary name negotiated and formally adopted by the Council. In 1967, a liaison representative from the Food and Drug Administration was appointed to serve on the USAN Council; the FDA announced in 1984 that it would discontinue adding drug names to its official list and use the USAN as the established name for labeling and advertising new single-entity drugs marketed in the United States. The AMA Council on Drugs no longer exists as a separate entity. FDA now has a representative on the USAN Council, which has moved away from chemically derived names; the USAN Council has five members, one from each sponsoring organization, one from the FDA, a member-at-large. One member is nominated to the USAN Council annually by each sponsoring organization; the member-at-large is selected by the sponsoring organizations from a list of candidates proposed by the AMA, APhA, the USP.
The five nominees to the Council must be approved annually by the board of trustees of the three sponsoring organizations. Judith Jones Thomas P. Reinders David Lewis Peter Rheinstein, Chair Armen Melikian By definition, nonproprietary names are not subject to proprietary trademark rights but are in the public domain; this distinguishes them from the trademarked names. Assignment of a USAN takes into account practical considerations, such as the existence of trademarks, international harmonization of drug nomenclature, the development of new classes of drugs, the fact that the intended uses of substances for which names are being selected may change. USANs assigned today reflect both present nomenclature practices and older methods used to name drug entities. Early drug nomenclature was based on the chemical structure; as newer drugs became chemically more complex and numerous, nonproprietary names based on chemistry became long and difficult to spell, pronounce, or remember. Additionally, chemically derived names provided little useful information to non-chemist health practitioners.
Considering the needs of health professionals led to a system in which USANs reflect relationships between new entities and older drugs, avoid names that might suggest non-existent relationships. Current nomenclature practices involve the adoption of standardized syllables called "stems" that relate new chemical entities to existing drug families. Stems may be suffixes, or infixes in the nonproprietary name; each stem can emphasize a specific chemical structure type, a pharmacologic property, or a combination of these attributes. The recommended list of USAN stems is updated to keep pace to accommodate drugs with new chemical and pharmacologic properties; as a general rule, the application for a USAN should be forwarded to the USAN Council after the Investigational New Drug is active and clinical trials have begun. Many drug manufacturers seeking a USAN are multinational companies with subsidiaries in various parts of the world or contractual agreements with drug firms outside the United States.
Therefore, it is desirable to the pharmaceutical company, the various nomenclature committees, the medical community in general that a global name be established for each new single-entity compound introduced. Assigning a USAN and standardizing names internationally can take anywhere from several months to a few years. Examples of drugs for which the USAN differs from the INN include: British Approved Name International Nonproprietary Name Nomenclature of monoclonal antibodies United States Pharmacopeia US Adopted Names Program
The scientific method is an empirical method of acquiring knowledge that has characterized the development of science since at least the 17th century. It involves careful observation, applying rigorous skepticism about what is observed, given that cognitive assumptions can distort how one interprets the observation, it involves formulating hypotheses, via induction, based on such observations. These are principles of the scientific method, as distinguished from a definitive series of steps applicable to all scientific enterprises. Though diverse models for the scientific method are available, there is in general a continuous process that includes observations about the natural world. People are inquisitive, so they come up with questions about things they see or hear, they develop ideas or hypotheses about why things are the way they are; the best hypotheses lead to predictions. The most conclusive testing of hypotheses comes from reasoning based on controlled experimental data. Depending on how well additional tests match the predictions, the original hypothesis may require refinement, expansion or rejection.
If a particular hypothesis becomes well supported, a general theory may be developed. Although procedures vary from one field of inquiry to another, they are the same from one to another; the process of the scientific method involves making conjectures, deriving predictions from them as logical consequences, carrying out experiments or empirical observations based on those predictions. A hypothesis is a conjecture, based on knowledge obtained while seeking answers to the question; the hypothesis might be specific, or it might be broad. Scientists test hypotheses by conducting experiments or studies. A scientific hypothesis must be falsifiable, implying that it is possible to identify a possible outcome of an experiment or observation that conflicts with predictions deduced from the hypothesis; the purpose of an experiment is to determine whether observations agree with or conflict with the predictions derived from a hypothesis. Experiments can take place anywhere from a garage to CERN's Large Hadron Collider.
There are difficulties in a formulaic statement of method, however. Though the scientific method is presented as a fixed sequence of steps, it represents rather a set of general principles. Not all steps take place in every scientific inquiry, they are not always in the same order; some philosophers and scientists have argued. Robert Nola and Howard Sankey remark that "For some, the whole idea of a theory of scientific method is yester-year's debate, the continuation of which can be summed up as yet more of the proverbial deceased equine castigation. We beg to differ." Important debates in the history of science concern rationalism as advocated by René Descartes. The term "scientific method" emerged in the 19th century, when a significant institutional development of science was taking place and terminologies establishing clear boundaries between science and non-science, such as "scientist" and "pseudoscience", appeared. Throughout the 1830s and 1850s, by which time Baconianism was popular, naturalists like William Whewell, John Herschel, John Stuart Mill engaged in debates over "induction" and "facts" and were focused on how to generate knowledge.
In the late 19th and early 20th centuries, a debate over realism vs. antirealism was conducted as powerful scientific theories extended beyond the realm of the observable. The term "scientific method" came into popular use in the twentieth century, popping up in dictionaries and science textbooks, although there was little scientific consensus over its meaning. Although there was a growth through the middle of the twentieth century, by the end of that century numerous influential philosophers of science like Thomas Kuhn and Paul Feyerabend had questioned the universality of the "scientific method" and in doing so replaced the notion of science as a homogeneous and universal method with that of it being a heterogeneous and local practice. In particular, Paul Feyerabend argued against there being any universal rules of science. Historian of science Daniel Thurs maintains that the scientific method is a myth or, at best, an idealization; the scientific method is the process. As in other areas of inquiry, science can build on previous knowledge and develop a more sophisticated understanding of its topics of study over time.
This model can be seen to underlie the scientific revolution. The ubiquitous element in the model of the scientific method is empiricism, or more epistemologic sensualism; this is in opposition to stringent forms of rationalism: the scientific method embodies that reason alone cannot solve a particular scientific problem. A strong formulation of the scientific method is not always aligned with a form of empiricism in which the empirical data is put forward in the form of experience or other abstracted forms of knowledge; the scientific method is of necessity als
5-hydroxytryptamine receptors or 5-HT receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both inhibitory neurotransmission; the serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand. The serotonin receptors modulate the release of many neurotransmitters, including glutamate, GABA, epinephrine / norepinephrine, acetylcholine, as well as many hormones, including oxytocin, vasopressin, cortisol and substance P, among others; the serotonin receptors influence various biological and neurological processes such as aggression, appetite, learning, mood, nausea and thermoregulation. The serotonin receptors are the target of a variety of pharmaceutical and recreational drugs, including many antidepressants, anorectics, gastroprokinetic agents, antimigraine agents and entactogens. Serotonin receptors are found in all animals and are known to regulate longevity and behavioral aging in the primitive nematode, Caenorhabditis elegans.
5-hydroxytryptamine receptors or 5-HT receptors, or serotonin receptors are found in the central and peripheral nervous systems. They can be divided into 7 families of G protein-coupled receptors except for the 5-HT3 receptor, a ligand-gated ion channel, which activate an intracellular second messenger cascade to produce an excitatory or inhibitory response. In 2014, a novel 5-HT receptor was isolated from the small white butterfly, Pieris rapae, named pr5-HT8, it does not occur in mammals and shares low similarity to the known 5-HT receptor classes. The 7 general serotonin receptor classes include a total of 14 known serotonin receptors; the specific types have been characterized as follows: Note that there is no 5-HT1C receptor since, after the receptor was cloned and further characterized, it was found to have more in common with the 5-HT2 family of receptors and was redesignated as the 5-HT2C receptor. Nonselective agonists of 5-HT receptor subtypes include ergotamine, which activates 5-HT1A, 5-HT1D, 5-HT1B, D2 and norepinephrine receptors.
LSD is a 5-HT2A, 5-HT2C, 5-HT5A, 5-HT5, 5-HT6 agonist. The genes coding for serotonin receptors are expressed across the mammalian brain. Genes coding for different receptors types follow different developmental curves. There is a developmental increase of HTR5A expression in several subregions of the human cortex, paralleled by a decreased expression of HTR1A from the embryonic period to the post-natal one. A number of receptors were classed as "5-HT1-like" - by 1998 it was being argued that, since these receptors were "a heterogeneous population of 5-HT1B, 5-HT1D and 5-HT7" receptors the classification was redundant. Serotonin+Receptors at the US National Library of Medicine Medical Subject Headings "5-Hydroxytryptamine Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Rubenstein LA, Lanzara RG. "Activation of G protein-coupled receptors entails cysteine modulation of agonist binding". Cogprints. Retrieved 2008-04-11. Paterson LM, Kornum BR, Nutt DJ, Pike VW, Knudsen GM.
"5-HT radioligands for human brain imaging with PET and SPECT". Med Res Rev. 33: 54–111. Doi:10.1002/med.20245. PMC 4188513. PMID 21674551
The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1
A clinic is a healthcare facility, focused on the care of outpatients. Clinics can be operated or publicly managed and funded, they cover the primary healthcare needs of populations in local communities, in contrast to larger hospitals which offer specialised treatments and admit inpatients for overnight stays. Most the English word clinic refers to a general medical practice, run by one or more general practitioners, but it can mean a specialist clinic; some clinics retain the name "clinic" while growing into institutions as large as major hospitals or becoming associated with a hospital or medical school. Clinics are associated with a general medical practice run by one or several general practitioners. Other types of clinics are run by the type of specialist associated with that type: physical therapy clinics by physiotherapists and psychology clinics by clinical psychologists, so on for each health profession; some clinics are operated in-house by employers, government organizations, or hospitals, some clinical services are outsourced to private corporations which specialize in providing health services.
In China, for example, owners of such clinics do not have formal medical education. There were 659,596 village clinics in China in 2011. Health care in India, China and Africa is provided to those countries' vast rural areas by mobile health clinics or roadside dispensaries, some of which integrate traditional medicine. In India these traditional clinics provide unani herbal medical practice. In each of these countries, traditional medicine tends to be a hereditary practice; the word clinic derives from Ancient Greek κλίνειν klinein meaning to lean or recline. Hence κλίνη klinē is a couch or bed and κλινικός klinikos is a physician who visits his patients in their beds. In Latin, this became clīnicus. An early use of the word clinic was "one who receives baptism on a sick bed"; the function of clinics differs from country to country. For instance, a local general practice run by a single general practitioner provides primary health care and is run as a for-profit business by the owner, whereas a government-run specialist clinic may provide subsidised or specialised health care.
Some clinics function as a place for people with injuries or illnesses to come and be seen by a triage nurse or other health worker. In these clinics, the injury or illness may not be serious enough to require a visit to an emergency room, but the person can be transferred to one if needed. Treatment at these clinics is less expensive than it would be at a casualty department. Unlike an ER these clinics are not open on a 24 × 7 x 365 basis, they sometimes have access to diagnostic equipment such as X-ray machines if the clinic is part of a larger facility. Doctors at such clinics can refer patients to specialists if the need arises. Large outpatient clinics can be as large as hospitals. Typical large outpatient clinics house general medical practitioners such as doctors and nurses to provide ambulatory care and some acute care services but lack the major surgical and pre- and post-operative care facilities associated with hospitals. Besides GPs, if a clinic is a polyclinic, it can house outpatient departments of some medical specialties, such as gynecology, ophthalmology, neurology, pulmonology and endocrinology.
In some university cities, polyclinics contain outpatient departments for the entire teaching hospital in one building. Large outpatient clinics are a common type of healthcare facility in many countries, including France, Germany and most of the countries of Central and Eastern Europe, as well as in former Soviet republics such as Russia and Ukraine. Recent Russian governments have attempted to replace the polyclinic model introduced during Soviet times with a more western model. However, this has failed. India has set up huge numbers of polyclinics for former defence personnel; the network envisages 426 polyclinics in 343 districts of the country which will benefit about 33 lakh ex-servicemen residing in remote and far-flung areas. Polyclinics are the backbone of Cuba's primary care system and have been credited with a role in improving that nation's health indicators. There are many different types of clinics providing outpatient services; such clinics may be private medical practices. A CLSC are in Quebec.
A retail-based clinic is housed in supermarkets and similar retail outlets providing walk-in health care, which may be staffed by nurse practitioners. A general out-patient clinic offers general treatments without an overnight stay. A polyclinic provides a range of healthcare services without need of an overnight stay A specialist clinic provides advanced diagnostic or treatment services for specific diseases or parts of the body; this type contrasts with general out-patient clinics. A sexual health clinic deals with sexual health related problems, such as prevention and treatment of sexually transmitted infections. A fertility clinic aims to help couples to become pregnant. An abortion clinic is a medical facility providing aborti
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. They are sometimes called blockers. In pharmacology, antagonists have affinity but no efficacy for their cognate receptors, binding will disrupt the interaction and inhibit the function of an agonist or inverse agonist at receptors. Antagonists mediate their effects by binding to the active site or to the allosteric site on a receptor, or they may interact at unique binding sites not involved in the biological regulation of the receptor's activity. Antagonist activity may be reversible or irreversible depending on the longevity of the antagonist–receptor complex, which, in turn, depends on the nature of antagonist–receptor binding; the majority of drug antagonists achieve their potency by competing with endogenous ligands or substrates at structurally defined binding sites on receptors. The English word antagonist in pharmaceutical terms comes from the Greek ἀνταγωνιστής – antagonistēs, "opponent, villain, rival", derived from anti- and agonizesthai.
Biochemical receptors are large protein molecules that can be activated by the binding of a ligand such as a hormone or a drug. Receptors can be membrane-bound, as cell surface receptors, or inside the cell as intracellular receptors, such as nuclear receptors including those of the mitochondrion. Binding occurs as a result of non-covalent interactions between the receptor and its ligand, at locations called the binding site on the receptor. A receptor may contain one or more binding sites for different ligands. Binding to the active site on the receptor regulates receptor activation directly; the activity of receptors can be regulated by the binding of a ligand to other sites on the receptor, as in allosteric binding sites. Antagonists mediate their effects through receptor interactions by preventing agonist-induced responses; this may be accomplished by binding to the allosteric site. In addition, antagonists may interact at unique binding sites not involved in the biological regulation of the receptor's activity to exert their effects.
The term antagonist was coined to describe different profiles of drug effects. The biochemical definition of a receptor antagonist was introduced by Ariens and Stephenson in the 1950s; the current accepted definition of receptor antagonist is based on the receptor occupancy model. It narrows the definition of antagonism to consider only those compounds with opposing activities at a single receptor. Agonists were thought to turn "on" a single cellular response by binding to the receptor, thus initiating a biochemical mechanism for change within a cell. Antagonists were thought to turn "off" that response by'blocking' the receptor from the agonist; this definition remains in use for physiological antagonists, substances that have opposing physiological actions, but act at different receptors. For example, histamine lowers arterial pressure through vasodilation at the histamine H1 receptor, while adrenaline raises arterial pressure through vasoconstriction mediated by alpha-adrenergic receptor activation.
Our understanding of the mechanism of drug-induced receptor activation and receptor theory and the biochemical definition of a receptor antagonist continues to evolve. The two-state model of receptor activation has given way to multistate models with intermediate conformational states; the discovery of functional selectivity and that ligand-specific receptor conformations occur and can affect interaction of receptors with different second messenger systems may mean that drugs can be designed to activate some of the downstream functions of a receptor but not others. This means efficacy may depend on where that receptor is expressed, altering the view that efficacy at a receptor is receptor-independent property of a drug. By definition, antagonists display no efficacy to activate the receptors they bind. Antagonists do not maintain the ability to activate a receptor. Once bound, antagonists inhibit the function of agonists, inverse agonists, partial agonists. In functional antagonist assays, a dose-response curve measures the effect of the ability of a range of concentrations of antagonists to reverse the activity of an agonist.
The potency of an antagonist is defined by its half maximal inhibitory concentration. This can be calculated for a given antagonist by determining the concentration of antagonist needed to elicit half inhibition of the maximum biological response of an agonist. Elucidating an IC50 value is useful for comparing the potency of drugs with similar efficacies, however the dose-response curves produced by both drug antagonists must be similar; the lower the IC50 the greater the potency of the antagonist, the lower the concentration of drug, required to inhibit the maximum biological response. Lower concentrations of drugs may be associated with fewer side-effects; the affinity of an antagonist for its binding site, i.e. its ability to bind to a receptor, will determine the duration of inhibition of agonist activity. The affinity of an antagonist can be determined experimentally using Schild regression or for competitive antagonists in radioligand binding studies using the Cheng-Prusoff equation. Schild regression can be used to determine the nature of antagonism as beginning either competitive or non-competitive and Ki determination is independent of the affinity, efficacy or concentration of the agonist used.
However, it is important. The effects of receptor desensitization on reaching equilibrium must als
European Chemicals Agency
The European Chemicals Agency is an agency of the European Union which manages the technical and administrative aspects of the implementation of the European Union regulation called Registration, Evaluation and Restriction of Chemicals. ECHA is the driving force among regulatory authorities in implementing the EU's chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and addresses chemicals of concern, it is located in Finland. The agency headed by Executive Director Bjorn Hansen, started working on 1 June 2007; the REACH Regulation requires companies to provide information on the hazards and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most used substances have been registered; the information is technical but gives detail on the impact of each chemical on people and the environment.
This gives European consumers the right to ask retailers whether the goods they buy contain dangerous substances. The Classification and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU; this worldwide system makes it easier for workers and consumers to know the effects of chemicals and how to use products safely because the labels on products are now the same throughout the world. Companies need to notify ECHA of the labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100 000 substances; the information is available on their website. Consumers can check chemicals in the products. Biocidal products include, for example, insect disinfectants used in hospitals; the Biocidal Products Regulation ensures that there is enough information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation; the law on Prior Informed Consent sets guidelines for the import of hazardous chemicals.
Through this mechanism, countries due to receive hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have serious effects on human health and the environment are identified as Substances of Very High Concern 1; these are substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment and do not break down. Other substances considered. Companies manufacturing or importing articles containing these substances in a concentration above 0,1% weight of the article, have legal obligations, they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy. Once a substance has been identified in the EU as being of high concern, it will be added to a list; this list is available on ECHA's website and shows consumers and industry which chemicals are identified as SVHCs.
Substances placed on the Candidate List can move to another list. This means that, after a given date, companies will not be allowed to place the substance on the market or to use it, unless they have been given prior authorisation to do so by ECHA. One of the main aims of this listing process is to phase out SVHCs where possible. In its 2018 substance evaluation progress report, ECHA said chemical companies failed to provide “important safety information” in nearly three quarters of cases checked that year. "The numbers show a similar picture to previous years" the report said. The agency noted that member states need to develop risk management measures to control unsafe commercial use of chemicals in 71% of the substances checked. Executive Director Bjorn Hansen called non-compliance with REACH a "worry". Industry group CEFIC acknowledged the problem; the European Environmental Bureau called for faster enforcement to minimise chemical exposure. European Chemicals Bureau Official website