1.
Drugs.com
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Drugs. com is an online pharmaceutical encyclopedia which provides drug information for consumers and healthcare professionals primarily in the USA. The domain Drugs. com was registered by Bonnie Neubeck in 1994. In 1999 at the height of the boom, Eric MacIver purchased an option to buy the domain from Neubeck. com. Venture Frogs sold the drugs. com domain name to an investor in June 2001. The Drugs. com website is owned and operated by the Drugsite Trust, the Drugsite Trust is a privately held Trust administered by two New Zealand pharmacists, Karen Ann and Phillip James Thornton The Drugs. com website was officially launched in September 2001. Stedmans, AHFS, Harvard Health Publications, Mayoclinic, North American Compendiums, in March 2008, Drugs. com announced the release of Mednotes —an online personal medication record application which connected to Google Health. In May 2010, U. S. FDA announced a collaboration with Drugs. com to distribute consumer health updates on the Drugs. com website, Drugs. com is certified by the TRUSTe online privacy certification program and the HONcode Health on the Net Foundation
2.
Tablet (pharmacy)
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A tablet is a pharmaceutical dosage form. Tablets may be defined as the solid unit dosage form of medicament or medicaments with or without suitable excipients and it comprises a mixture of active substances and excipients, usually in powder form, pressed or compacted from a powder into a solid dose. The compressed tablet is the most popular form in use today. About two-thirds of all prescriptions are dispensed as solid dosage forms, a tablet can be formulated to deliver an accurate dosage to a specific site, it is usually taken orally, but can be administered sublingually, buccally, rectally or intravaginally. The tablet is just one of the forms that an oral drug can take such as syrups, elixirs, suspensions. Medicinal tablets were made in the shape of a disk of whatever color their components determined. Tablets are often stamped with symbols, letters, and numbers, sizes of tablets to be swallowed range from a few millimeters to about a centimeter. Pills are thought to date back to around 1500 BC, earlier medical recipes, such as those from 4000 BC, were for liquid preparations rather than solids. The first references to pills were found on papyruses in ancient Egypt, medicinal ingredients, such as plant powders or spices, were mixed in and formed by hand to make little balls, or pills. In ancient Greece, such medicines were known as katapotia, and the Roman scholar Pliny, Pills have always been difficult to swallow and efforts long have been made to make them go down easier. In medieval times, people coated pills with slippery plant substances, another approach, used as recently as the 19th century, was to gild them in gold and silver, although this often meant that they would pass through the digestive tract with no effect. In the 1800s sugar-coating and gelatin-coating was invented, as were gelatin capsules, in 1843, the British painter and inventor William Brockedon was granted a patent for a machine capable of Shaping Pills, Lozenges and Black Lead by Pressure in Dies. The device was capable of compressing powder into a tablet without use of an adhesive, today, pills include tablets, capsules, and variants thereof like caplets—essentially anything with medication that can be digested, minus the liquid forms, colloquially falls into the pill category. A caplet is a smooth, coated, oval-shaped medicinal tablet in the shape of a capsule. Many caplets have a running down the middle so they may be split in half easier. An orally disintegrating tablet or orodispersible tablet, is a dosage form available for a limited range of over-the-counter. In the tablet-pressing process, it is important that all ingredients be fairly dry, powdered or granular, somewhat uniform in particle size, content uniformity ensures that the same API dose is delivered with each tablet. Some APIs may be tableted as pure substances, but this is rarely the case, normally, a pharmacologically inactive ingredient termed a binder is added to help hold the tablet together and give it strength
3.
Solution
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In chemistry, a solution is a homogeneous mixture composed of two or more substances. In such a mixture, a solute is a substance dissolved in another substance, the mixing process of a solution happens at a scale where the effects of chemical polarity are involved, resulting in interactions that are specific to solvation. The solution assumes the characteristics of the solvent when the solvent is the fraction of the mixture. The concentration of a solute in a solution is the mass of that solute expressed as a percentage of the mass of the whole solution, a solution is a homogeneous mixture of two or more substances. The particles of solute in a solution cannot be seen by the naked eye, a solution does not allow beams of light to scatter. The solute from a solution cannot be separated by filtration and it is composed of only one phase. Homogeneous means that the components of the form a single phase. Heterogeneous means that the components of the mixture are of different phase, the properties of the mixture can be uniformly distributed through the volume but only in absence of diffusion phenomena or after their completion. Usually, the present in the greatest amount is considered the solvent. Solvents can be gases, liquids or solids, one or more components present in the solution other than the solvent are called solutes. The solution has the physical state as the solvent. If the solvent is a gas, only gases are dissolved under a set of conditions. An example of a solution is air. Since interactions between molecules play almost no role, dilute gases form rather trivial solutions, in part of the literature, they are not even classified as solutions, but addressed as mixtures. If the solvent is a liquid, then almost all gases, liquids, here are some examples, Gas in liquid, Oxygen in water Carbon dioxide in water – a less simple example, because the solution is accompanied by a chemical reaction. Liquid in liquid, The mixing of two or more substances of the same chemistry but different concentrations to form a constant, alcoholic beverages are basically solutions of ethanol in water. Solid in liquid, Sucrose in water Sodium chloride or any other salt in water, solutions in water are especially common. Counterexamples are provided by liquid mixtures that are not homogeneous, colloids, body fluids are examples for complex liquid solutions, containing many solutes
4.
Regulation of therapeutic goods
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The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the level by a single agency. In other jurisdictions they are regulated at the level, or at both state and national levels by various bodies, as is the case in Australia. The role of therapeutic goods regulation is designed mainly to protect the health, regulation is aimed at ensuring the safety, quality, and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered before they are allowed to be marketed, there is usually some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Therapeutic goods in Australia are regulated by the Therapeutic Goods Administration, there are 5 main categories, Normal Medicines - Cough, cold and fever medicines, antiseptics, vitamins and others. Sold freely in pharmacies and some large supermarkets, red Stripe Medicines - These medicines are sold only with medical prescription. Antibiotics, Anti allergenics, Anti inflammatories, and other medicines, in Brazil, governmental control is loose on this type, it is not uncommon to buy this type of prescription medicine over the counter without a prescription. Red Stripe Psychoactive Medicines - These medicines are only with a Special Control white medical prescription with carbon copy. The original must be retained by the pharmacist after the sale, Drugs include anti-depressants, anti-convulsants, some sleep aids, anti-psychotics and other non-habit-inducing controlled medicines. Though some consider them habit inducing, anabolic steroids are also regulated under this category, black Stripe Medicines - These medicines are sold only with the Blue B Form medical prescription, which is valid for 30 days and must be retained by the pharmacist after the sale. Includes sedatives, some anorexic inducers and other habit-inducing controlled medicines, includes amphetamines and other stimulants, opioids and other strong habit-forming controlled medicines. In Canada, regulation of goods are governed by the Food and Drug Act. In addition, the Controlled Drugs and Substances Act requires additional regulatory requirements for controlled drugs, the regulation of drugs in Burma is governed by the Food and Drug Administration and Food and Drug Board of Authority. The regulation of drugs in China is governed by the China Food, Medicines for Human Use in the United Kingdom are regulated by the Medicines and Healthcare products Regulatory Agency. The availability of drugs is regulated by classification by the MHRA as part of marketing authorisation of a product, Medicines in the Republic of Ireland are regulated according to the Misuse of Drugs Regulations 1988. Controlled drugs are divided into five categories based on their potential for misuse, cD1, cannabis, lysergamide, coca leaf, etc. Use prohibited except in limited circumstances where a license has been granted, CD2, amphetamine, methadone, morphine, fentanyl, oxycodone, tapentadol, etc
5.
Prescription drug
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A prescription drug is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription, the reason for this difference in substance control is the potential scope of misuse, from drug abuse to practicing medicine without a license and without sufficient education. Different jurisdictions have different definitions of what constitutes a prescription drug, rx is often used as a short form for prescription drug in North America- a contraction of the Latin word recipe meaning take. Prescription drugs are often dispensed together with a monograph that gives detailed information about the drug, the use of prescription drugs has been increasing since the 1960s. In the U. S. 88% of older adults use at least 1 prescription drug, who is able to prescribe the drug. When purchasing a drug under the PBS the maximum price a consumer pays is the patient co-payment contribution and those covered by government entitlements and those covered under the Repatriation Pharmaceutical Benefits Scheme have a reduced co-payment, which is $6.00 in 2014. The table below indicates the changes in co-payments over the years and these co-payments are compulsory and cannot be discounted by pharmacies under any circumstances. Private prescriptions are issued for medicines not covered on the PBS, or being used off-label, the patient pays the pharmacy for medicines privately prescribed. In the United Kingdom the Medicines Act 1968 and Prescription Only Medicines Order 1997 contain regulations that cover the supply of sale, use, prescribing is also covered by this legislation. A patient visits a medical practitioner or dentist authorised to prescribe drugs and certain other medical items, also, suitably qualified and experienced nurses and pharmacists may be independent prescribers. Both can prescribe all POMs but pharmacists are not allowed to prescribe schedule 1 controlled drugs, once issued, a prescription is taken by the patient to a pharmacy, which dispenses the medicine. Most prescriptions in the UK are NHS prescriptions, subject to a standard charge unrelated to what is dispensed, the NHS prescription fee was increased to £8. The pharmacy charges the NHS the actual cost of the medicine, a patient can consolidate prescription charges using a prescription payment certificate, effectively capping costs at £29.10 per quarter or £104.00 per year. Outside the NHS, private prescriptions are issued by private medical practitioners, NHS supply beyond three months worth is not covered, and must be purchased privately. A patient pays the pharmacy the normal price for medicine prescribed outside the NHS, in the United States, the Federal Food, Drug, and Cosmetic Act defines what substances require a prescription in order to be dispensed by a pharmacy. The Controlled Substances Act was enacted into law by the Congress of the United States in 1970, the CSA is the federal U. S. drug law under which the manufacture, importation, possession, use and distribution of certain substances is regulated. The legislation created five schedules with varying qualifications for a substance to be included in each, the safety and effectiveness of prescription drugs in the US is regulated by the federal Prescription Drug Marketing Act of 1987. The Food and Drug Administration is charged with implementing this law, misuse or abuse of prescription drugs can lead to adverse drug events, including those due to dangerous drug interactions
6.
Pharmacokinetics
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Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as, pharmaceutical drugs, pesticides, food additives, cosmetic ingredients, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, both together influence dosing, benefit, and adverse effects, as seen in PK/PD models. Pharmacokinetic properties of chemicals are affected by the route of administration and these may affect the absorption rate. Models have been developed to simplify conceptualization of the processes that take place in the interaction between an organism and a chemical substance. The various compartments that the model is divided into are commonly referred to as the ADME scheme, absorption - the process of a substance entering the blood circulation. Distribution - the dispersion or dissemination of substances throughout the fluids, metabolism – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites. Excretion - the removal of the substances from the body, in rare cases, some drugs irreversibly accumulate in body tissue. The two phases of metabolism and excretion can also be grouped together under the title elimination, the study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. All these concepts can be represented through mathematical formulas that have a graphical representation. The model outputs for a drug can be used in industry or in the application of pharmacokinetic concepts. Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals, in practice, it is generally considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph, compartmental methods estimate the concentration-time graph using kinetic models. Noncompartmental methods are more versatile in that they do not assume any specific compartmental model. The final outcome of the transformations that a drug undergoes in an organism, a number of functional models have been developed in order to simplify the study of pharmacokinetics. These models are based on a consideration of an organism as a number of related compartments, the simplest idea is to think of an organism as only one homogenous compartment. However, these models do not always reflect the real situation within an organism
7.
Bioavailability
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By definition, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes, its bioavailability generally decreases or may vary from patient to patient, Bioavailability is one of the essential tools in pharmacokinetics, as bioavailability must be considered when calculating dosages for non-intravenous routes of administration. Bioavailability is defined differently for drugs as opposed to dietary supplements primarily due to the method of administration and Food. Bioaccessibility is a related to bioavailability in the context of biodegradation. A molecule is said to be bioaccessible when is available to cross a cellular membrane from the environment. In pharmacology, bioavailability is a measurement of the rate and extent to which a drug reaches at the site of action and it is denoted by the letter f. Therefore, bioavailability for dietary supplements can be defined as the proportion of the administered substance capable of being absorbed, in both pharmacology and nutrition sciences, bioavailability is measured by calculating the area under curve of the drug concentration time profile. Bioavailability is commonly a factor in the production of crops. Toxic materials in soil, such as lead from paint may be rendered unavailable to animals ingesting contaminated soil by supplying phosphorus fertilizers in excess and it is the fraction of the drug absorbed through non-intravenous administration compared with the corresponding intravenous administration of the same drug. The comparison must be normalized, consequently, the amount absorbed is corrected by dividing the corresponding dose administered. The absolute bioavailability is the area under curve non-intravenous divided by AUC intravenous. For example, the formula for calculating F for a drug administered by the route is given below. If we compare the two different dosage forms having same active ingredients and compare the two drug bioavailability is called comparative bioavailability, although knowing the true extent of systemic absorption is clearly useful, in practice it is not determined as frequently as one may think. The reason for this is that its assessment requires a reference, that is. These limitations may be overcome, however, by administering a low dose of an isotopically labelled drug concomitantly with a therapeutic non-labelled oral dose. This technique eliminates pharmacokinetic issues on non-equivalent clearance as well as enabling the intravenous dose to be administered with a minimum of toxicology, the technique was first applied using stable-isotopes such as 13C and mass-spectrometry to distinguish the isotopes by mass difference. More recently, 14C labelled drugs are administered intravenously and accelerator mass spectrometry used to measure the isotopically labelled drug along with mass spectrometry for the unlabelled drug, in all such cases, to conduct an absolute bioavailability study requires that the drug be given intravenously. Intravenous administration of a drug can provide valuable information on the fundamental pharmacokinetic parameters of volume of distribution
8.
Drug metabolism
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Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. These pathways are a form of biotransformation present in all groups of organisms. These reactions often act to detoxify poisonous compounds, the study of drug metabolism is called pharmacokinetics. The metabolism of drugs is an important aspect of pharmacology. For example, the rate of metabolism determines the duration and intensity of a drugs pharmacologic action, the enzymes of xenobiotic metabolism, particularly the glutathione S-transferases are also important in agriculture, since they may produce resistance to pesticides and herbicides. Drug metabolism is divided into three phases, in phase I, enzymes such as cytochrome P450 oxidases introduce reactive or polar groups into xenobiotics. These modified compounds are conjugated to polar compounds in phase II reactions. These reactions are catalysed by enzymes such as glutathione S-transferases. Finally, in phase III, the conjugated xenobiotics may be processed, before being recognised by efflux transporters. Drug metabolism often converts lipophilic compounds into hydrophilic products that are readily excreted. The exact compounds an organism is exposed to will be unpredictable, and may differ widely over time. The solution that has evolved to address this problem is an elegant combination of physical barriers, all organisms use cell membranes as hydrophobic permeability barriers to control access to their internal environment. This selective uptake means that most hydrophilic molecules cannot enter cells, in contrast, the diffusion of hydrophobic compounds across these barriers cannot be controlled, and organisms, therefore, cannot exclude lipid-soluble xenobiotics using membrane barriers. However, the existence of a permeability barrier means that organisms were able to evolve detoxification systems that exploit the hydrophobicity common to membrane-permeable xenobiotics and these systems therefore solve the specificity problem by possessing such broad substrate specificities that they metabolise almost any non-polar compound. Useful metabolites are excluded since they are polar, and in general one or more charged groups. However, since these compounds are few in number, specific enzymes can recognize, the metabolism of xenobiotics is often divided into three phases, - modification, conjugation, and excretion. These reactions act in concert to detoxify xenobiotics and remove them from cells, in phase I, a variety of enzymes act to introduce reactive and polar groups into their substrates. One of the most common modifications is hydroxylation catalysed by the cytochrome P-450-dependent mixed-function oxidase system and these enzyme complexes act to incorporate an atom of oxygen into nonactivated hydrocarbons, which can result in either the introduction of hydroxyl groups or N-, O- and S-dealkylation of substrates
9.
Excretion
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Excretion is the process by which metabolic wastes and other non-useful materials are eliminated from an organism. In vertebrates this is carried out by the lungs, kidneys. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell, excretion is an essential process in all forms of life. For example, in urine is expelled through the urethra. In unicellular organisms, waste products are discharged directly through the surface of the cell, green plants produce carbon dioxide and water as respiratory products. In green plants, the carbon dioxide released during respiration gets utilized during photosynthesis, oxygen is a by product generated during photosynthesis, and exits through stomata, root cell walls, and other routes. Plants can get rid of water by transpiration and guttation. These latter processes do not need added energy, they act passively, however, during the pre-abscission phase, the metabolic levels of a leaf are high. Plants also excrete some waste substances into the soil around them, in animals, the main excretory products are carbon dioxide, ammonia, urea, uric acid, guanine and creatine. The liver and kidneys clear many substances from the blood, aquatic animals usually excrete ammonia directly into the external environment, as this compound has high solubility and there is ample water available for dilution. In terrestrial animals ammonia-like compounds are converted into other materials as there is less water in the environment. Birds excrete their nitrogenous wastes as uric acid in the form of a paste and this is metabolically more expensive, but allows more efficient water retention and it can be stored more easily in the egg. Many avian species, especially seabirds, can also excrete salt via specialized nasal salt glands, in insects, a system involving Malpighian tubules is utilized to excrete metabolic waste. Metabolic waste diffuses or is actively transported into the tubule, which transports the wastes to the intestines, the metabolic waste is then released from the body along with fecal matter. The excreted material may be called dejecta or ejecta, in pathology the word ejecta is more commonly used. UAlberta. ca, Animation of excretion Brian J Ford on leaf fall in Nature
10.
PubChem
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PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information, a component of the National Library of Medicine, PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be downloaded via FTP. PubChem contains substance descriptions and small molecules with fewer than 1000 atoms and 1000 bonds, more than 80 database vendors contribute to the growing PubChem database. PubChem consists of three dynamically growing primary databases, as of 28 January 2016, Compounds,82.6 million entries, contains pure and characterized chemical compounds. Substances,198 million entries, contains also mixtures, extracts, complexes, bioAssay, bioactivity results from 1.1 million high-throughput screening programs with several million values. PubChem contains its own online molecule editor with SMILES/SMARTS and InChI support that allows the import and export of all common chemical file formats to search for structures and fragments. In the text search form the database fields can be searched by adding the name in square brackets to the search term. A numeric range is represented by two separated by a colon. The search terms and field names are case-insensitive, parentheses and the logical operators AND, OR, and NOT can be used. AND is assumed if no operator is used, example,0,5000,50,10 -5,5 PubChem was released in 2004. The American Chemical Society has raised concerns about the publicly supported PubChem database and they have a strong interest in the issue since the Chemical Abstracts Service generates a large percentage of the societys revenue. To advocate their position against the PubChem database, ACS has actively lobbied the US Congress, soon after PubChems creation, the American Chemical Society lobbied U. S. Congress to restrict the operation of PubChem, which they asserted competes with their Chemical Abstracts Service
11.
DrugBank
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The DrugBank database is a comprehensive, freely accessible, online database containing information on drugs and drug targets. As both a bioinformatics and a resource, DrugBank combines detailed drug data with comprehensive drug target information. Because of its scope, comprehensive referencing and unusually detailed data descriptions. As a result, links to DrugBank are maintained for nearly all drugs listed in Wikipedia, DrugBank is widely used by the drug industry, medicinal chemists, pharmacists, physicians, students and the general public. Its extensive drug and drug-target data has enabled the discovery and repurposing of a number of existing drugs to treat rare, the latest release of the database contains 8227 drug entries including 2003 FDA-approved small molecule drugs,221 FDA-approved biotech drugs,93 nutraceuticals and over 6000 experimental drugs. Additionally,4270 non-redundant protein sequences are linked to these drug entries, each DrugCard entry contains more than 200 data fields with half of the information being devoted to drug/chemical data and the other half devoted to drug target or protein data. Four additional databases, HMDB, T3DB, SMPDB and FooDB are also part of a suite of metabolomic/cheminformatic databases. The first version of DrugBank was released in 2006 and this early release contained relatively modest information about 841 FDA-approved small molecule drugs and 113 biotech drugs. It also included information on 2133 drug targets, the second version of DrugBank was released in 2009. This greatly expanded and improved version of the database included 1344 approved small molecule drugs and 123 biotech drugs as well as 3037 unique drug targets. Version 2.0 also included, for the first time, withdrawn drugs and illicit drugs, version 3.0 was released in 2011. This version contained 1424 approved small molecule drugs and 132 biotech drugs as well as >4000 unique drug targets, version 3.0 also included drug transporter data, drug pathway data, drug pricing, patent and manufacturing data as well as data on >5000 experimental drugs. Version 4.0 was released in 2014 and this version included 1558 FDA-approved small molecule drugs,155 biotech drugs and 4200 unique drug targets. Version 4.0 also incorporated information on drug metabolites, drug taxonomy, drug spectra, drug binding constants. Table 1 provides a complete statistical summary of the history of DrugBank’s development. All data in DrugBank is non-proprietary or is derived from a non-proprietary source and it is freely accessible and available to anyone. In addition, nearly every item is fully traceable and explicitly referenced to the original source. DrugBank data is available through a web interface and downloads
12.
ChemSpider
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ChemSpider is a database of chemicals. ChemSpider is owned by the Royal Society of Chemistry, the database contains information on more than 50 million molecules from over 500 data sources including, Each chemical is given a unique identifier, which forms part of a corresponding URL. This is an approach to develop an online chemistry database. The search can be used to widen or restrict already found results, structure searching on mobile devices can be done using free apps for iOS and for the Android. The ChemSpider database has been used in combination with text mining as the basis of document markup. The result is a system between chemistry documents and information look-up via ChemSpider into over 150 data sources. ChemSpider was acquired by the Royal Society of Chemistry in May,2009, prior to the acquisition by RSC, ChemSpider was controlled by a private corporation, ChemZoo Inc. The system was first launched in March 2007 in a release form. ChemSpider has expanded the generic support of a database to include support of the Wikipedia chemical structure collection via their WiChempedia implementation. A number of services are available online. SyntheticPages is an interactive database of synthetic chemistry procedures operated by the Royal Society of Chemistry. Users submit synthetic procedures which they have conducted themselves for publication on the site and these procedures may be original works, but they are more often based on literature reactions. Citations to the published procedure are made where appropriate. They are checked by an editor before posting. The pages do not undergo formal peer-review like a journal article. The comments are moderated by scientific editors. The intention is to collect practical experience of how to conduct useful chemical synthesis in the lab, while experimental methods published in an ordinary academic journal are listed formally and concisely, the procedures in ChemSpider SyntheticPages are given with more practical detail. Comments by submitters are included as well, other publications with comparable amounts of detail include Organic Syntheses and Inorganic Syntheses
13.
ChEMBL
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ChEMBL or ChEMBLdb is a manually curated chemical database of bioactive molecules with drug-like properties. It is maintained by the European Bioinformatics Institute, of the European Molecular Biology Laboratory, based at the Wellcome Trust Genome Campus, Hinxton, the database, originally known as StARlite, was developed by a biotechnology company called Inpharmatica Ltd. later acquired by Galapagos NV. The data was acquired for EMBL in 2008 with an award from The Wellcome Trust, resulting in the creation of the ChEMBL chemogenomics group at EMBL-EBI, the ChEMBL database contains compound bioactivity data against drug targets. Bioactivity is reported in Ki, Kd, IC50, and EC50, data can be filtered and analyzed to develop compound screening libraries for lead identification during drug discovery. ChEMBL version 2 was launched in January 2010, including 2.4 million bioassay measurements covering 622,824 compounds and this was obtained from curating over 34,000 publications across twelve medicinal chemistry journals. ChEMBLs coverage of available bioactivity data has grown to become the most comprehensive ever seen in a public database, in October 2010 ChEMBL version 8 was launched, with over 2.97 million bioassay measurements covering 636,269 compounds. ChEMBL_10 saw the addition of the PubChem confirmatory assays, in order to integrate data that is comparable to the type, ChEMBLdb can be accessed via a web interface or downloaded by File Transfer Protocol. It is formatted in a manner amenable to computerized data mining, ChEMBL is also integrated into other large-scale chemistry resources, including PubChem and the ChemSpider system of the Royal Society of Chemistry. In addition to the database, the ChEMBL group have developed tools and these include Kinase SARfari, an integrated chemogenomics workbench focussed on kinases. The system incorporates and links sequence, structure, compounds and screening data, the primary purpose of ChEMBL-NTD is to provide a freely accessible and permanent archive and distribution centre for deposited data. July 2012 saw the release of a new data service, sponsored by the Medicines for Malaria Venture. The data in this service includes compounds from the Malaria Box screening set, myChEMBL, the ChEMBL virtual machine, was released in October 2013 to allow users to access a complete and free, easy-to-install cheminformatics infrastructure. In December 2013, the operations of the SureChem patent informatics database were transferred to EMBL-EBI, in a portmanteau, SureChem was renamed SureChEMBL. 2014 saw the introduction of the new resource ADME SARfari - a tool for predicting and comparing cross-species ADME targets
14.
European Chemicals Agency
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ECHA is the driving force among regulatory authorities in implementing the EUs chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and it is located in Helsinki, Finland. The Agency, headed by Executive Director Geert Dancet, started working on 1 June 2007, the REACH Regulation requires companies to provide information on the hazards, risks 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 commonly used substances have been registered, the information is technical but gives detail on the impact of each chemical on people and the environment. This also gives European consumers the right to ask whether the goods they buy contain dangerous substances. The Classification, Labelling 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, companies need to notify ECHA of the classification and labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100000 substances, the information is freely available on their website. Consumers can check chemicals in the products they use, Biocidal products include, for example, insect repellents and disinfectants used in hospitals. The Biocidal Products Regulation ensures that there is 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 export and import of hazardous chemicals. Through this mechanism, countries due to hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have effects on human health and the environment are identified as Substances of Very High Concern 1. These are mainly substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment, other substances considered as SVHCs include, for example, endocrine disrupting chemicals. Companies manufacturing or importing articles containing these substances in a concentration above 0 and 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 officially identified in the EU as being of very 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 then move to another list
15.
Chemical formula
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These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of only the simplest of molecules and chemical substances, the simplest types of chemical formulas are called empirical formulas, which use letters and numbers indicating the numerical proportions of atoms of each type. Molecular formulas indicate the numbers of each type of atom in a molecule. For example, the formula for glucose is CH2O, while its molecular formula is C6H12O6. This is possible if the relevant bonding is easy to show in one dimension, an example is the condensed molecular/chemical formula for ethanol, which is CH3-CH2-OH or CH3CH2OH. For reasons of structural complexity, there is no condensed chemical formula that specifies glucose, chemical formulas may be used in chemical equations to describe chemical reactions and other chemical transformations, such as the dissolving of ionic compounds into solution. A chemical formula identifies each constituent element by its chemical symbol, in empirical formulas, these proportions begin with a key element and then assign numbers of atoms of the other elements in the compound, as ratios to the key element. For molecular compounds, these numbers can all be expressed as whole numbers. For example, the formula of ethanol may be written C2H6O because the molecules of ethanol all contain two carbon atoms, six hydrogen atoms, and one oxygen atom. Some types of compounds, however, cannot be written with entirely whole-number empirical formulas. An example is boron carbide, whose formula of CBn is a variable non-whole number ratio with n ranging from over 4 to more than 6.5. When the chemical compound of the consists of simple molecules. These types of formulas are known as molecular formulas and condensed formulas. A molecular formula enumerates the number of atoms to reflect those in the molecule, so that the formula for glucose is C6H12O6 rather than the glucose empirical formula. However, except for very simple substances, molecular chemical formulas lack needed structural information, for simple molecules, a condensed formula is a type of chemical formula that may fully imply a correct structural formula. For example, ethanol may be represented by the chemical formula CH3CH2OH
16.
Jmol
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Jmol is computer software for molecular modelling chemical structures in 3-dimensions. Jmol returns a 3D representation of a molecule that may be used as a teaching tool and it is written in the programming language Java, so it can run on the operating systems Windows, macOS, Linux, and Unix, if Java is installed. It is free and open-source software released under a GNU Lesser General Public License version 2.0, a standalone application and a software development kit exist that can be integrated into other Java applications, such as Bioclipse and Taverna. A popular feature is an applet that can be integrated into web pages to display molecules in a variety of ways, for example, molecules can be displayed as ball-and-stick models, space-filling models, ribbon diagrams, etc. Jmol supports a range of chemical file formats, including Protein Data Bank, Crystallographic Information File, MDL Molfile. There is also a JavaScript-only version, JSmol, that can be used on computers with no Java, the Jmol applet, among other abilities, offers an alternative to the Chime plug-in, which is no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS9. Jmol requires Java installation and operates on a variety of platforms. For example, Jmol is fully functional in Mozilla Firefox, Internet Explorer, Opera, Google Chrome, fast and Scriptable Molecular Graphics in Web Browsers without Java3D
17.
Chirality (chemistry)
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Chirality /kaɪˈrælɪti/ is a geometric property of some molecules and ions. A chiral molecule/ion is non-superposable on its mirror image, the presence of an asymmetric carbon center is one of several structural features that induce chirality in organic and inorganic molecules. The term chirality is derived from the Greek word for hand, the mirror images of a chiral molecule/ion are called enantiomers or optical isomers. Individual enantiomers are often designated as either right- or left-handed, Chirality is an essential consideration when discussing the stereochemistry in organic and inorganic chemistry. The concept is of practical importance because most biomolecules and pharmaceuticals are chiral. Chirality is based on molecular symmetry elements, specifically, a chiral compound can contain no improper axis of rotation, which includes planes of symmetry and inversion center. Chiral molecules are always dissymmetric but not always asymmetric, in general, chiral molecules have point chirality at a single stereogenic atom, which has four different substituents. The two enantiomers of such compounds are said to have different absolute configurations at this center, the stereogenic atom is usually carbon, as in many biological molecules. However chirality can exist in any atom, including metals, phosphorus, Chiral nitrogen is equally possible, although the effects of nitrogen inversion can make many of these compounds impossible to isolate. While the presence of a stereogenic atom describes the great majority of cases, for instance it is not necessary for the chiral substance to have a stereogenic atom. Examples include 1-bromo-1-chloro-1-fluoroadamantane, methylethylphenyltetrahedrane, certain calixarenes and fullerenes, which have inherent chirality, the C2-symmetric species 1, 1-bi-2-naphthol,1, 3-dichloro-allene have axial chirality. -cyclooctene and many ferrocenes have planar chirality, when the optical rotation for an enantiomer is too low for practical measurement, the species is said to exhibit cryptochirality. Even isotopic differences must be considered when examining chirality, illustrative is the derivative of benzyl alcohol PhCHDOH is chiral. The S enantiomer has D = +0. 715°, many biologically active molecules are chiral, including the naturally occurring amino acids and sugars. In biological systems, most of these compounds are of the chirality, most amino acids are levorotatory. Typical naturally occurring proteins, made of L amino acids, are known as left-handed proteins, d-amino acids are very rare in nature and have only been found in small peptides attached to bacteria cell walls. The origin of this homochirality in biology is the subject of much debate, however, there is some suggestion that early amino acids could have formed in comet dust. Enzymes, which are chiral, often distinguish between the two enantiomers of a chiral substrate, one could imagine an enzyme as having a glove-like cavity that binds a substrate
18.
Simplified molecular-input line-entry system
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The simplified molecular-input line-entry system is a specification in form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules, the original SMILES specification was initiated in the 1980s. It has since modified and extended. In 2007, a standard called OpenSMILES was developed in the open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. The Environmental Protection Agency funded the project to develop SMILES. It has since modified and extended by others, most notably by Daylight Chemical Information Systems. In 2007, a standard called OpenSMILES was developed by the Blue Obelisk open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, in July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is generally considered to have the advantage of being slightly more human-readable than InChI, the term SMILES refers to a line notation for encoding molecular structures and specific instances should strictly be called SMILES strings. However, the term SMILES is also used to refer to both a single SMILES string and a number of SMILES strings, the exact meaning is usually apparent from the context. The terms canonical and isomeric can lead to confusion when applied to SMILES. The terms describe different attributes of SMILES strings and are not mutually exclusive, typically, a number of equally valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol, algorithms have been developed to generate the same SMILES string for a given molecule, of the many possible strings, these algorithms choose only one of them. This SMILES is unique for each structure, although dependent on the algorithm used to generate it. These algorithms first convert the SMILES to a representation of the molecular structure. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database, there is currently no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, and these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES
19.
International Chemical Identifier
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Initially developed by IUPAC and NIST from 2000 to 2005, the format and algorithms are non-proprietary. The continuing development of the standard has supported since 2010 by the not-for-profit InChI Trust. The current version is 1.04 and was released in September 2011, prior to 1.04, the software was freely available under the open source LGPL license, but it now uses a custom license called IUPAC-InChI Trust License. Not all layers have to be provided, for instance, the layer can be omitted if that type of information is not relevant to the particular application. InChIs can thus be seen as akin to a general and extremely formalized version of IUPAC names and they can express more information than the simpler SMILES notation and differ in that every structure has a unique InChI string, which is important in database applications. Information about the 3-dimensional coordinates of atoms is not represented in InChI, the InChI algorithm converts input structural information into a unique InChI identifier in a three-step process, normalization, canonicalization, and serialization. The InChIKey, sometimes referred to as a hashed InChI, is a fixed length condensed digital representation of the InChI that is not human-understandable. The InChIKey specification was released in September 2007 in order to facilitate web searches for chemical compounds and it should be noted that, unlike the InChI, the InChIKey is not unique, though collisions can be calculated to be very rare, they happen. In January 2009 the final 1.02 version of the InChI software was released and this provided a means to generate so called standard InChI, which does not allow for user selectable options in dealing with the stereochemistry and tautomeric layers of the InChI string. The standard InChIKey is then the hashed version of the standard InChI string, the standard InChI will simplify comparison of InChI strings and keys generated by different groups, and subsequently accessed via diverse sources such as databases and web resources. Every InChI starts with the string InChI= followed by the version number and this is followed by the letter S for standard InChIs. The remaining information is structured as a sequence of layers and sub-layers, the layers and sub-layers are separated by the delimiter / and start with a characteristic prefix letter. The six layers with important sublayers are, Main layer Chemical formula and this is the only sublayer that must occur in every InChI. The atoms in the formula are numbered in sequence, this sublayer describes which atoms are connected by bonds to which other ones. Describes how many hydrogen atoms are connected to each of the other atoms, the condensed,27 character standard InChIKey is a hashed version of the full standard InChI, designed to allow for easy web searches of chemical compounds. Most chemical structures on the Web up to 2007 have been represented as GIF files, the full InChI turned out to be too lengthy for easy searching, and therefore the InChIKey was developed. With all databases currently having below 50 million structures, such duplication appears unlikely at present, a recent study more extensively studies the collision rate finding that the experimental collision rate is in agreement with the theoretical expectations. Example, Morphine has the structure shown on the right, as the InChI cannot be reconstructed from the InChIKey, an InChIKey always needs to be linked to the original InChI to get back to the original structure
20.
Sympathomimetic drug
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Sympathomimetic drugs are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. The primary endogenous agonists of the nervous system are the catecholamines. Sympathomimetic drugs are used to treat cardiac arrest and low pressure, or even delay premature labor. If the amine is primary or secondary, it will have direct action, also, if the amine has bulky substituents, then it will have greater beta adrenergic receptor activity, but if the substituent is not bulky, then it will favor the alpha adrenergic receptors. Direct stimulation of the α- and β-adrenergic receptors can produce sympathomimetic effects, salbutamol is a widely used direct-acting β2-agonist. Other examples include phenylephrine, isoproterenol, and dobutamine, stimulation of the D1 receptor by dopaminergic agonists such as fenoldopam is used intravenously to treat hypertensive crisis. Dopaminergic stimulants such as amphetamine, ephedrine, and propylhexedrine work by causing the release of dopamine and norepinephrine, a primary or secondary aliphatic amine separated by 2 carbons from a substituted benzene ring is minimally required for high agonist activity. The pKa of the amine is approximately 8. 5-10, the presence of hydroxy group in the benzene ring at 3rd and 4th position shows maximum alpha- and beta-adrenergic activity. Substances such as cocaine also affect dopamine, and some such as MDMA affect serotonin. Norepinephrine is synthesized by the body from the amino acid tyrosine, and is used in the synthesis of epinephrine, thus, all sympathomimetic amines fall into the larger group of stimulants. Physical withdrawal from some sedatives can be lethal, for instance benzodiazepine withdrawal syndrome. Parasympatholytic and sympathomimetic have similar effects, but through different pathways. For example, both cause mydriasis, but parasympatholytics reduce accommodation while sympathomimetics do not
21.
Amine
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In organic chemistry, amines are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group, important amines include amino acids, biogenic amines, trimethylamine, and aniline, see Category, Amines for a list of amines. Inorganic derivatives of ammonia are also called amines, such as chloramine, see Category, compounds with a nitrogen atom attached to a carbonyl group, thus having the structure R–CO–NR′R″, are called amides and have different chemical properties from amines. An aliphatic amine has no aromatic ring attached directly to the nitrogen atom, aromatic amines have the nitrogen atom connected to an aromatic ring as in the various anilines. The aromatic ring decreases the alkalinity of the amine, depending on its substituents, the presence of an amine group strongly increases the reactivity of the aromatic ring, due to an electron-donating effect. Amines are organized into four subcategories, Primary amines — Primary amines arise when one of three atoms in ammonia is replaced by an alkyl or aromatic. Important primary alkyl amines include, methylamine, most amino acids, Secondary amines — Secondary amines have two organic substituents bound to the nitrogen together with one hydrogen. Important representatives include dimethylamine, while an example of an aromatic amine would be diphenylamine, tertiary amines — In tertiary amines, nitrogen has three organic substituents. Examples include trimethylamine, which has a fishy smell. Cyclic amines — Cyclic amines are either secondary or tertiary amines, examples of cyclic amines include the 3-membered ring aziridine and the six-membered ring piperidine. N-methylpiperidine and N-phenylpiperidine are examples of tertiary amines. It is also possible to have four organic substituents on the nitrogen and these species are not amines but are quaternary ammonium cations and have a charged nitrogen center. Quaternary ammonium salts exist with many kinds of anions, Amines are named in several ways. Typically, the compound is given the prefix amino- or the suffix, the prefix N- shows substitution on the nitrogen atom. An organic compound with multiple amino groups is called a diamine, triamine, tetraamine, systematic names for some common amines, Hydrogen bonding significantly influences the properties of primary and secondary amines. Thus the melting point and boiling point of amines is higher than those of the corresponding phosphines, for example, methyl and ethyl amines are gases under standard conditions, whereas the corresponding methyl and ethyl alcohols are liquids. Amines possess a characteristic smell, liquid amines have a distinctive fishy smell. The nitrogen atom features a lone pair that can bind H+ to form an ammonium ion R3NH+
22.
Bronchodilator
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Bronchodilator, A bronchodilator is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lungs. Bronchodilators may be endogenous, or they may be administered for the treatment of breathing difficulties. They are most useful in obstructive lung diseases, of which asthma, although this remains somewhat controversial, they might be useful in bronchiolitis and Bronchiectasis. They are often prescribed but of significance in restrictive lung diseases. Bronchodilators are either short-acting or long-acting, short-acting medications provide quick or rescue relief from acute bronchoconstriction. Long-acting bronchodilators help to control and prevent symptoms, the three types of prescription bronchodilating drugs are β2-agonists, anticholinergics, and theophylline. These are quick-relief or rescue medications that provide quick, temporary relief from asthma symptoms or flare-ups and these medications usually take effect within 20 minutes or less, and can last from four to six hours. These inhaled medications are best for treating sudden and severe or new asthma symptoms, taken 15 to 20 minutes ahead of time, these medications can also prevent asthma symptoms triggered by exercise or exposure to cold air. Some short-acting β-agonists are specific to the lungs, they are called β2-agonists, patients who regularly or frequently need to take short-acting β-agonists should consult their doctor, as such usage indicates uncontrolled asthma, and their routine medications may need adjustment. These are long-term medications taken routinely in order to control and prevent bronchoconstriction and they are not intended for fast relief. These medications may take longer to begin working, but relieve airway constriction for up to 12 hours, commonly taken twice a day with an anti-inflammatory medication, they maintain open airways and prevent asthma symptoms, particularly at night. Salmeterol and formoterol are examples of these, some examples of anticholinergics are tiotropium and ipratropium bromide. Tiotropium is a long-acting, 24-hour, anticholinergic bronchodilator used in the management of chronic pulmonary disease. Only available as an inhalant, ipratropium bromide is used in the treatment of asthma and it relieves acute or new asthma symptoms. It will not stop an asthma attack already in progress, because it has no effect on asthma symptoms when used alone, it is most often paired with a short-acting β2-agonist. While it is considered a relief or rescue medication, it can take an hour to begin working. For this reason, it plays a role in asthma treatment. Dry throat is the most common side effect, if the medication gets in contact with the eyes, it may cause blurred vision for a brief time
23.
Salt (chemistry)
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In chemistry, a salt is an ionic compound that results from the neutralization reaction of an acid and a base. Salts are composed of related numbers of cations and anions so that the product is electrically neutral and these component ions can be inorganic, such as chloride, or organic, such as acetate, and can be monatomic, such as fluoride, or polyatomic, such as sulfate. There are several varieties of salts, salts that hydrolyze to produce hydroxide ions when dissolved in water are alkali salts, whilst those that hydrolyze to produce hydronium ions in water are acidic salts. Neutral salts are those salts that are neither acidic nor basic, zwitterions contain an anionic centre and a cationic centre in the same molecule, but are not considered to be salts. Examples of zwitterions include amino acids, many metabolites, peptides, usually, non-dissolved salts at standard conditions for temperature and pressure are solid, but there are exceptions. Molten salts and solutions containing dissolved salts are called electrolytes, as they are able to conduct electricity. As observed in the cytoplasm of cells, in blood, urine, plant saps and mineral waters, therefore, their salt content is given for the respective ions. Salts can appear to be clear and transparent, opaque, and even metallic, in many cases, the apparent opacity or transparency are only related to the difference in size of the individual monocrystals. Since light reflects from the boundaries, larger crystals tend to be transparent. The color of the salt is due to the electronic structure in the d-orbitals of transition elements or in the conjugated organic dye framework. Different salts can elicit all five basic tastes, e. g. salty, sweet, sour, bitter, and umami or savory. Salts of strong acids and strong bases are non-volatile and odorless and that slow, partial decomposition is usually accelerated by the presence of water, since hydrolysis is the other half of the reversible reaction equation of formation of weak salts. Many ionic compounds can be dissolved in water or other similar solvents, the exact combination of ions involved makes each compound have a unique solubility in any solvent. The solubility is dependent on how well each ion interacts with the solvent, for example, all salts of sodium, potassium and ammonium are soluble in water, as are all nitrates and many sulfates – barium sulfate, calcium sulfate and lead sulfate are examples of exceptions. However, ions that bind tightly to each other and form highly stable lattices are less soluble, for example, most carbonate salts are not soluble in water, such as lead carbonate and barium carbonate. Some soluble carbonate salts are, sodium carbonate, potassium carbonate, solid salts do not conduct electricity. Moreover, solutions of salts also conduct electricity, the name of a salt starts with the name of the cation followed by the name of the anion. Salts are often referred to only by the name of the cation or by the name of the anion. g
24.
Epinephrine
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Epinephrine, also known as adrenalin or adrenaline, is a hormone, neurotransmitter and medication. Epinephrine is normally produced by both the adrenal glands and certain neurons and it plays an important role in the fight-or-flight response by increasing blood flow to muscles, output of the heart, pupil dilation, and blood sugar. It does this by binding to alpha and beta receptors and it is found in many animals and some one cell organisms. Jokichi Takamine first isolated epinephrine in 1901, as a medication it is used to treat a number of conditions, including anaphylaxis, cardiac arrest, and superficial bleeding. Inhaled epinephrine may be used to improve the symptoms of croup and it may also be used for asthma when other treatments are not effective. It is given intravenously, by injection into a muscle, by inhalation, common side effects include shakiness, anxiety, and sweating. A fast heart rate and high pressure may occur. Occasionally it may result in a heart rhythm. While the safety of its use during pregnancy and breastfeeding is unclear, the adrenal medulla is a minor contributor to total circulating catecholamines, though it contributes over 90% of circulating epinephrine. Little epinephrine is found in tissues, mostly in scattered chromaffin cells. Following adrenalectomy, epinephrine disappears below the limit in the blood stream. The adrenals contribute about 7% of circulating norepinephrine, most of which is a spill over from neurotransmission with little activity as a hormone, pharmacological doses of epinephrine stimulate α1, α2, β1, β2, and β3 adrenoceptors of the sympathetic nervous system. Sympathetic nerve receptors are classified as adrenergic, based on their responsiveness to adrenaline, the term adrenergic is often misinterpreted in that the main sympathetic neurotransmitter is norepinephrine, rather than epinephrine, as discovered by Ulf von Euler in 1946. Epinephrine does have a β2 adrenoceptor-mediated effect on metabolism and the airway, the concept of the adrenal medulla and the sympathetic nervous system being involved in the flight, fight and fright response was originally proposed by Cannon. But the adrenal medulla, in contrast to the cortex, is not required for survival. In adrenalectomized patients hemodynamic and metabolic responses to such as hypoglycemia. One physiological stimulus to epinephrine secretion is exercise and this was first demonstrated using the denervated pupil of a cat as an assay, later confirmed using a biological assay on urine samples. Biochemical methods for measuring catecholamines in plasma were published from 1950 onwards, the development of extraction methods and enzyme-isotope derivate radio-enzymatic assays transformed the analysis down to a sensitivity of 1 pg for epinephrine
25.
Salbutamol
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Salbutamol, also known as albuterol and marketed as Ventolin among other names, is a medication that opens up the medium and large airways in the lungs. It is used to treat asthma, exercise-induced bronchoconstriction, and chronic pulmonary disease. It may also be used to high blood potassium levels. It is usually used by inhaler or nebulizer but is available as a pill. Onset of action of the version is typically within 15 minutes. Common side effects include shakiness, headache, fast heart rate, dizziness, serious side effects may include worsening bronchospasm, irregular heartbeat, and low blood potassium levels. It can be used during pregnancy and breastfeeding, but safety is not entirely clear, salbutamol is a short-acting β2 adrenergic receptor agonist which works by causing airway smooth muscles to relax. Salbutamol was first made in 1967 in Britain and it was approved for medical use in the United States in 1982. It is on the World Health Organizations List of Essential Medicines and it is available as a generic medication. The wholesale cost in the world of an inhaler which contains 200 doses is between $1.12 and $2.64 as of 2014. In the United States it is between $25 and $50 for a month supply. Salbutamol is typically used to treat bronchospasm, as well as chronic obstructive pulmonary disease, as a β2 agonist, salbutamol also finds use in obstetrics. Intravenous salbutamol can be used as a tocolytic to relax the smooth muscle to delay premature labor. Salbutamol has been used to treat acute hyperkalemia, as it stimulates potassium flow into cells thus lowering the level in the blood, the most common side effects are fine tremor, anxiety, headache, muscle cramps, dry mouth, and palpitation. Other symptoms may include tachycardia, arrhythmia, flushing, myocardial ischemia, rarely occurring, but of importance, are allergic reactions of paradoxical bronchospasm, urticaria, angioedema, hypotension, and collapse. High doses or prolonged use may cause hypokalaemia, which is of concern especially in patients with renal failure and this drug is sold as a racemic mixture. With regard to structure-activity relationships, the tertiary butyl group in salbutamol makes it selective for β2 receptors. Salbutamol may be quantified in blood or plasma, practical needs for this include to confirm a diagnosis of poisoning in hospitalized patients, or to aid in a forensic investigation
26.
Aerobic exercise
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Aerobic exercise is physical exercise of low to high intensity that depends primarily on the aerobic energy-generating process. Aerobic literally means relating to, involving, or requiring free oxygen, generally, light-to-moderate intensity activities that are sufficiently supported by aerobic metabolism can be performed for extended periods of time. S. Air Force personnel by Dr. Kenneth H. Cooper, Kenneth Cooper was the first person to introduce the concept of aerobic exercise. In the 1960s, Cooper started research into preventive medicine and he became intrigued by the belief that exercise can preserve ones health. In 1970 he created his own institute for research and education devoted to preventive medicine. He sparked millions into becoming active and is now known as the father of aerobics, aerobic exercise and fitness can be contrasted with anaerobic exercise, of which strength training and short-distance running are the most salient examples. The two types of exercise differ by the duration and intensity of muscular contractions involved, as well as by how energy is generated within the muscle, myokine secretion in turn is dependent on the amount of muscle contracted, and the duration and intensity of contraction. As such, both types of exercise produce endocrine benefits, if there is a shortage of oxygen, carbohydrate is consumed more rapidly because the pyruvate ferments into lactate. As glycogen levels in the begin to fall, glucose is released into the bloodstream by the liver. Aerobic exercise may be fueled by glycogen reserves, fat reserves, prolonged moderate-level aerobic exercise at 65% VO2 max results in the maximum contribution of fat to the total energy expenditure. At this level, fat may contribute 40% to 60% of total, vigorous exercise above 75% VO2max primarily burns glycogen. Major muscles in a rested, untrained human typically contain enough energy for about 2 hours of vigorous exercise, exhaustion of glycogen is a major cause of what marathon runners call hitting the wall. Training, lower intensity levels, and carbohydrate loading may allow postponement of the onset of exhaustion beyond 4 hours, in general, it is performed at a moderate level of intensity over a relatively long period of time. For example, running a distance at a moderate pace is an aerobic exercise. Some sports are thus inherently aerobic, while other aerobic exercises, such as training or aerobic dance classes, are designed specifically to improve aerobic capacity. It is most common for aerobic exercises to involve the leg muscles, for example, rowing to distances of 2,000 m or more is an aerobic sport that exercises several major muscle groups, including those of the legs, abdominals, chest, and arms. Common kettlebell exercises combine aerobic and anaerobic aspects, one meta-analysis has shown, from multiple conducted studies, that aerobic exercise does help lower Hb A1Clevels for type 2 diabetics. As a result, aerobic exercise can reduce the risk of death due to cardiovascular problems, in addition, high-impact aerobic activities can stimulate bone growth, as well as reduce the risk of osteoporosis for both men and women
27.
Oxygen
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Oxygen is a chemical element with symbol O and atomic number 8. It is a member of the group on the periodic table and is a highly reactive nonmetal. By mass, oxygen is the third-most abundant element in the universe, after hydrogen, at standard temperature and pressure, two atoms of the element bind to form dioxygen, a colorless and odorless diatomic gas with the formula O2. This is an important part of the atmosphere and diatomic oxygen gas constitutes 20. 8% of the Earths atmosphere, additionally, as oxides the element makes up almost half of the Earths crust. Most of the mass of living organisms is oxygen as a component of water, conversely, oxygen is continuously replenished by photosynthesis, which uses the energy of sunlight to produce oxygen from water and carbon dioxide. Oxygen is too reactive to remain a free element in air without being continuously replenished by the photosynthetic action of living organisms. Another form of oxygen, ozone, strongly absorbs ultraviolet UVB radiation, but ozone is a pollutant near the surface where it is a by-product of smog. At low earth orbit altitudes, sufficient atomic oxygen is present to cause corrosion of spacecraft, the name oxygen was coined in 1777 by Antoine Lavoisier, whose experiments with oxygen helped to discredit the then-popular phlogiston theory of combustion and corrosion. One of the first known experiments on the relationship between combustion and air was conducted by the 2nd century BCE Greek writer on mechanics, Philo of Byzantium. In his work Pneumatica, Philo observed that inverting a vessel over a burning candle, Philo incorrectly surmised that parts of the air in the vessel were converted into the classical element fire and thus were able to escape through pores in the glass. Many centuries later Leonardo da Vinci built on Philos work by observing that a portion of air is consumed during combustion and respiration, Oxygen was discovered by the Polish alchemist Sendivogius, who considered it the philosophers stone. In the late 17th century, Robert Boyle proved that air is necessary for combustion, English chemist John Mayow refined this work by showing that fire requires only a part of air that he called spiritus nitroaereus. From this he surmised that nitroaereus is consumed in both respiration and combustion, Mayow observed that antimony increased in weight when heated, and inferred that the nitroaereus must have combined with it. Accounts of these and other experiments and ideas were published in 1668 in his work Tractatus duo in the tract De respiratione. Robert Hooke, Ole Borch, Mikhail Lomonosov, and Pierre Bayen all produced oxygen in experiments in the 17th and the 18th century but none of them recognized it as a chemical element. This may have been in part due to the prevalence of the philosophy of combustion and corrosion called the phlogiston theory, which was then the favored explanation of those processes. Established in 1667 by the German alchemist J. J. Becher, one part, called phlogiston, was given off when the substance containing it was burned, while the dephlogisticated part was thought to be its true form, or calx. The fact that a substance like wood gains overall weight in burning was hidden by the buoyancy of the combustion products
28.
Basal metabolic rate
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Basal metabolic rate is the minimal rate of energy expenditure per unit time by endothermic animals at rest. It is reported in units per unit time ranging from watt to ml O2/min or joule per hour per kg body mass J/). Proper measurement requires a set of criteria be met. These criteria include being in a physically and psychologically undisturbed state, in a neutral environment. In bradymetabolic animals, such as fish and reptiles, the equivalent term standard metabolic rate is used and it follows the same criteria as BMR, but requires the documentation of the temperature at which the metabolic rate was measured. This makes BMR a variant of standard metabolic rate measurement that excludes the temperature data, Metabolism comprises the processes that the body needs to function. Basal metabolic rate is the amount of energy expressed in calories that a person needs to keep the body functioning at rest, some of those processes are breathing, blood circulation, controlling body temperature, cell growth, brain and nerve function, and contraction of muscles. Basal metabolic rate affects the rate that a person burns calories and ultimately whether that individual maintains, gains, the basal metabolic rate accounts for about 60 to 75% of the daily calorie expenditure by individuals. It is influenced by several factors, BMR typically declines by 1–2% per decade after age 20, mostly due to loss of fat-free mass, although the variability between individuals is high. The bodys generation of heat is known as thermogenesis and it can be measured to determine the amount of energy expended, BMR generally decreases with age and with the decrease in lean body mass. Increasing muscle mass has the effect of increasing BMR, but anaerobic exercise does increase resting energy consumption. Illness, previously consumed food and beverages, environmental temperature, BMR is measured under very restrictive circumstances when a person is awake. An accurate BMR measurement requires that the sympathetic nervous system not be stimulated. A more common measurement, which uses less strict criteria, is resting metabolic rate, BMR may be measured by gas analysis through either direct or indirect calorimetry, though a rough estimation can be acquired through an equation using age, sex, height, and weight. Basal metabolism is usually by far the largest component of total caloric expenditure, Exercise physiology textbooks have tables to show the conversion of height and body surface area as they relate to weight and basal metabolic values. The primary organ responsible for regulating metabolism is the hypothalamus, the hypothalamus is located on the diencephalon and forms the floor and part of the lateral walls of the third ventricle of the cerebrum. Through the ANS, the hypothalamus is the regulator of visceral activities, such as heart rate, movement of food through the gastrointestinal tract. When sufficient food or substrates have received and leptin is high, then the satiety center is stimulated
29.
Smooth muscle
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Smooth muscle is an involuntary non-striated muscle. It is divided into two subgroups, the single-unit and multiunit smooth muscle, within single-unit cells, the whole bundle or sheet contracts as a syncytium. Single unit smooth muscle, however, is most common and lines blood vessels, the tract. Smooth muscle is different from skeletal muscle and cardiac muscle in terms of structure, function, regulation of contraction. Smooth muscle cells known as myocytes, have a shape and, like striated muscle, can tense. However, smooth muscle tissue tends to demonstrate greater elasticity and function within a larger length-tension curve than striated muscle and this ability to stretch and still maintain contractility is important in organs like the intestines and urinary bladder. In the relaxed state, each cell is spindle-shaped, 20-500 micrometers in length, the smooth muscle is the only type of muscle without the ability to be voluntarily controlled in stressful situations. Myosin is primarily class II in smooth muscle, myosin II contains two heavy chains which constitute the head and tail domains. Each of these heavy chains contains the N-terminal head domain, while the C-terminal tails take on a coiled-coil morphology, thus, myosin II has two heads. In smooth muscle, there is a gene that codes for the heavy chains myosin II. Also, smooth muscle may contain MHC that is not involved in contraction, myosin II also contains 4 light chains, resulting in 2 per head, weighing 20 and 17 kDa. These bind the chains in the neck region between the head and tail. The MLC20 is also known as the light chain and actively participates in muscle contraction. Two MLC20 isoforms are found in muscle, and they are encoded by different genes. The MLC17 is also known as the light chain. Its exact function is unclear, but its believed that it contributes to the stability of the myosin head along with MLC20. Two variants of MLC17 exist as a result of alternate splicing at the MLC17 gene, in the uterus, a shift in myosin expression has been hypothesized to avail for changes in the directions of uterine contractions that are seen during the menstrual cycle. The thin filaments that form part of the machinery are predominantly composed of α-
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