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
Adamantane is a colorless, crystalline chemical compound with a camphor-like odor. With a formula C10H16, it is a cycloalkane and the simplest diamondoid. Adamantane molecules consists of three connected cyclohexane rings arranged in the "armchair" configuration, it is unique in that it is both rigid and stress-free. Adamantane is the most stable among all the isomers with formula C10H16, which include the somewhat similar twistane; the spatial arrangement of carbon atoms in the adamantane molecule is the same as in the diamond crystal. This motivates the name adamantane, derived from the Greek adamantinos; the discovery of adamantane in petroleum in 1933 launched a new field of chemistry dedicated to studying the synthesis and properties of polyhedral organic compounds. Adamantane derivatives have found practical application as drugs, polymeric materials, thermally stable lubricants; the possibility of the existence of a hydrocarbon with the C10H16 formula and diamond-like structure of the molecule was suggested by H. Decker at a conference in 1924.
Decker was surprised that it had not been synthesized yet. The first attempted laboratory synthesis was made in 1924 by German chemist Hans Meerwein using the reaction of formaldehyde with diethyl malonate in the presence of piperidine. Instead of adamantane, Meerwein obtained 1,3,5,7-tetracarbomethoxybicyclononane-2,6-dione: this compound was named Meerwein's ester and used in the synthesis of adamantane and its derivatives. Another German chemist D. Bottger tried to obtain adamantane using Meerwein's ester as precursor. However, the product, tricyclo- decane ring system, was again an adamantane derivative. Other researchers attempted to synthesize adamantane using phloroglucinol and derivatives of cyclohexanone, but failed. Adamantane was first synthesized by Vladimir Prelog in 1941 from Meerwein's ester; the process was impractical, as it contained five stages and had a yield of about 0.16%. However, it was sometimes used to synthesize certain derivatives of adamantane. Prelog's method was refined in 1956.
The decarboxylation yield was increased by the addition of the Heinsdecker pathway and the Hoffman reaction that raised the total yield to 6.5%. The process was still too complex, a more convenient method was found in 1957 by Paul von Ragué Schleyer: dicyclopentadiene was first hydrogenated in the presence of a catalyst and transformed into adamantane using a Lewis acid as another catalyst; this method provided an affordable source of adamantane. The adamantane synthesis yield was increased to 60% and 98% by ultrasound and super acid catalysts. Today, adamantane is an affordable chemical compound with a cost of about $1 a gram. All the above methods yield adamantane as a polycrystalline powder. Using this powder, single crystals can be grown from the melt, vapor phase. Melt growth results in the worst crystalline quality with a mosaic spread in the X-ray reflection of about 1°; the best crystals are obtained from the liquid phase, but the growth is impracticably slow – several months for a 5–10 mm crystal.
Growth from the vapor phase is a reasonable compromise in terms of quality. Adamantane is sublimed in a quartz tube placed in a furnace, equipped with several heaters maintaining a certain temperature gradient along the tube. Crystallization starts at one end of the tube, kept near the freezing point of adamantane. Slow cooling of the tube, while maintaining the temperature gradient shifts the melting zone producing a single-crystal boule. Before adamantane was synthesized, it was isolated from petroleum by the Czech chemists S. Landa, V. Machacek and M. Mzourek in 1932, they used fractional distillation, which separates the organic molecule components of petroleum based on their boiling points. Landa et al. could produce only a few milligrams of adamantane, but noticed its high boiling and melting points. Because of the similarity of its structure to that of diamond, the new compound was named adamantane. Petroleum remains the only natural source of adamantane. Beside adamantane, petroleum contains more than thirty of its derivatives.
Their isolation from a complex mixture of hydrocarbons is possible due to their high melting point and the ability to distill with water vapor and form stable adducts with thiourea. Pure adamantane is a colorless, crystalline solid with a characteristic camphor smell, it is insoluble in water, but soluble in nonpolar organic solvents. Adamantane has an unusually high melting point for a hydrocarbon. At 270 °C, its melting point is much higher than other hydrocarbons with the same molecular weight, such as camphene, ocimene, terpinene or twistane, or than a linear C10H22 hydrocarbon decane. However, adamantane sublimes at room temperature. Adamantane can be distilled with water vapor; the adamantane molecule consists of three condensed cyclohexane rings fused in the armchair conformation. The molecular parameters were deduced by electron X-ray crystallography; the carbon–carbon bond length is 1.54 Å identical to that of diamond, the carbon–hydrogen distance is 1.112 Å. At ambient conditions, adamantane crystallizes in a face-centered cubic structur
Regulation of therapeutic goods
The regulation of therapeutic goods, drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the national level by a single agency. In other jurisdictions they are regulated at the state 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 to protect the health and safety of the population. Regulation is aimed at ensuring the safety and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered. There is some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Modern drug regulation has historical roots in the response to the proliferation of universal antidotes which appeared in the wake of Mithridates' death. Mithridates had brought together physicians and shamans to concoct a potion that would make him immune to poisons.
Following his death, the Romans became keen on further developing the Mithridates potion's recipe. Mithridatium re-entered western society through multiple means; the first was through the Leechbook of the Bald, written somewhere between 900 and 950, which contained a formula for various remedies, including for a theriac. Additionally, theriac became a commercial good traded throughout Europe based on the works of Greek and Roman physicians; the resulting proliferation of various recipes needed to be curtailed in order to ensure that people were not passing off fake antidotes, which led to the development of government involvement and regulation. Additionally, the creation of these concoctions took on ritualistic form and were created in public and the process was observed and recorded, it was believed that if the concoction proved unsuccessful, it was due to the apothecaries’ process of making them and they could be held accountable because of the public nature of the creation. In the 9th century, many Muslim countries established an office of the hisba, which in addition to regulating compliance to Islamic principles and values took on the role of regulating other aspects of social and economic life, including the regulation of medicines.
Inspectors were appointed to employ oversight on those who were involved in the process of medicine creation and were given a lot of leigh weigh to ensure compliance and punishments were stringent. The first official'act', the'Apothecary Wares and Stuffs' Act was passed in 1540 by Henry VIII and set the foundation for others. Through this act, he encouraged physicians in his College of Physicians to appoint four people dedicated to inspecting what was being sold in apothecary shops. In conjunction with this first piece of legislation, there was an emergence of standard formulas for the creation of certain ‘drugs’ and ‘antidotes’ through Pharmacopoeias which first appeared in the form of a decree from Frederick II of Sicily in 1240 to use consistent and standard formulas; the first modern pharmacopoeias were the Florence Pharmacopoeia published in 1498, the Spanish Pharmacopoeia published in 1581 and the London Pharmacopoeia published in 1618. In the United States, regulation of drugs was a state right, as opposed to federal right.
But with the increase in fraudulent practices due to private incentives to maximize profits and poor enforcement of state laws, increased the need for stronger federal regulation. President Roosevelt signed the Federal Food and Drug Act in 1906 which established stricter standards. A 1911 Supreme Court decision, United States vs. Johnson, established that misleading statements were not covered under the FFDA; this directly led to Congress passing the Sherley Amendment which established a clearer definition of ‘misbranded’. Another key catalyst for advances in drug regulation were certain catastrophes that served as calls to the government to step in and impose regulations that would prevent repeats of those instances. One such instance occurred in 1937 when more than a hundred people died from using sulfanilamide elixir which had not gone through any safety testing; this directly led to the passing of the Federal, Food and Cosmetic Act in 1938. One other major catastrophe occurred in the late 1950s when Thalidomide, sold in Germany and sold around the world, led to 100,000 babies being born with various deformities.
The UK's Chief Medical Officer had established a group to look into safety of drugs on the market in 1959 prior to the crisis and was moving in the direction of address the problem of unregulated drugs entering the market. The crisis created a greater sense of emergency to establish safety and efficacy standards around the world; the UK started a temporary Committee on Safety of Drugs while they attempted to pass more comprehensive legislation. Though compliance and submission of drugs to the Committee on Safety of Drugs was not mandatory after, the pharmaceutical industry larger complied due to the thalidomide situation; the European Economic Commission passed a directive in 1965 in order to impose greater efficacy standards before marketing a drug. The United States congress passed the Drug Amendments Act of 1962 The Drug Amendments Act required the FDA to ensure that new drugs being introduced to the market had passed certain tests and standards. Both the EU and US acts introduced the requirements to ensure efficacy.
Of note, increased regulations and standards for testing led to greater innovation in pharm
Rauvolfia is a genus of evergreen trees and shrubs known as devil peppers, in the dogbane family, Apocynaceae. The genus is named to honor Leonhard Rauwolf; the genus can be found in tropical regions of Africa, Latin America, various oceanic islands. The International Code of Nomenclature for algae and plants stipulates that the genus name was established by Carl Linnaeus in his 1753 book Species Plantarum, which cites his earlier description which states in Botanical Latin that the name is dedicated "to Leonhard Rauwolf": "Leon. Rauvolfio". Although some subsequent authors hypercorrected the Classical Latin letter "v" to a modern "w", this is not accepted by the code of nomenclature. Rauvolfia serpentina known as or Indian Snakeroot or Sarpagandha, contains many indole alkaloids. Reserpine is an alkaloid first isolated from R. serpentina and was used as an antihypertensive drug. It had drastic psychological side effects and has been replaced as a first-line antihypertensive drug by other compounds that lack such adverse effects, although combination drugs that include it are still available in some countries as second-line antihypertensive drugs.
Other plants of this genus are used medicinally, both in conventional western medicine and in Ayurveda and folk medicine. Women who are pregnant, may be pregnant, or plan pregnancy in the near future should not ingest Rauvolfia plants or preparations made from them, they may be harmful for people with any chronic disease of the gastrointestinal tract, such as stomach or duodenal ulcers, gastroesophageal reflux disease, ulcerative colitis, irritable bowel syndrome, diverticulosis. No "safe" dosage has been established. Rauvolfia serpentina is declining in the wild due to collection for its medicinal uses, it is listed in CITES Appendix II. Rauvolfia vomitoria is a invasive species in Hawaiʻi, is capable of establishing dense monotypic stands. Species include: includedRauvolfia celastrifolia Baker = Stephanostegia hildebrandtii Baill. Rauvolfia dentata Tafalla ex D. Don = Citharexylum dentatum D. Don Rauvolfia flexuosa Ruiz & Pav. = Citharexylum flexuosum D. Don Rauvolfia glabra Cav. = Vallesia glabra Link Rauvolfia laevigata Willd.
Ex Roem. & Schult. = Tabernaemontana amygdalifolia Jacq. Rauvolfia longifolia A. DC. = Alstonia longifolia Pichon Rauvolfia macrophylla Ruiz & Pav. 1799 not Stapf 1894 = Citharexylum flexuosum D. Don Rauvolfia oppositifolia Spreng. 1822 not Sessé & Moc. 1888 = Tabernaemontana oppositifolia Urb. Rauvolfia pubescens Willd. Ex Roem. & Schult. = Citharexylum quitense Spreng. Rauvolfia spinosa Cav. = Citharexylum flexuosum D. Don Rauvolfia stenophylla Donn. Sm. = Alstonia longifolia Pichon Rauvolfia strempelioides Griseb. = Strempeliopsis strempelioides Benth. Ex B. D. Jacks. Rauvolfia striata Poir. = Ochrosia borbonica J. F. Gmel. McNeill, J.. R.. R.. L.. S.. F.. F.. H.. J.. International Code of Nomenclature for algae and plants adopted by the Eighteenth International Botanical Congress Melbourne, July 2011. Regnum Vegetabile 154. A. R. G. Gantner Verlag KG. ISBN 978-3-87429-425-6
In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may be considered ligands which display both agonistic and antagonistic effects—when both a full agonist and partial agonist are present, the partial agonist acts as a competitive antagonist, competing with the full agonist for receptor occupancy and producing a net decrease in the receptor activation observed with the full agonist alone. Clinically, partial agonists can be used to activate receptors to give a desired submaximal response when inadequate amounts of the endogenous ligand are present, or they can reduce the overstimulation of receptors when excess amounts of the endogenous ligand are present; some common drugs that have been classed as partial agonists at particular receptors include buspirone, buprenorphine and norclozapine. Examples of ligands activating peroxisome proliferator-activated receptor gamma as partial agonists are honokiol and falcarindiol.
Delta 9-tetrahydrocannabivarin is a partial agonist at CB2 receptors and this activity might be implicated in ∆9-THCV-mediated anti-inflammatory effects. Competitive antagonist Intrinsic sympathomimetic activity of beta blockers Inverse agonist Mixed agonist/antagonist
The adenosine receptors are a class of purinergic G protein-coupled receptors with adenosine as endogenous ligand. There are four known types of adenosine receptors in humans: A1, A2A, A2B and A3; the adenosine receptors are known for their antagonists caffeine and theophylline, whose action on the receptors produces the stimulating effects of coffee and chocolate. Each type of adenosine receptor has different functions. For instance, both A1 receptors and A2A play roles in the heart, regulating myocardial oxygen consumption and coronary blood flow, while the A2A receptor has broader anti-inflammatory effects throughout the body; these two receptors have important roles in the brain, regulating the release of other neurotransmitters such as dopamine and glutamate, while the A2B and A3 receptors are located peripherally and are involved in processes such as inflammation and immune responses. Most older compounds acting on adenosine receptors are nonselective, with the endogenous agonist adenosine being used in hospitals as treatment for severe tachycardia, acting directly to slow the heart through action on all four adenosine receptors in heart tissue, as well as producing a sedative effect through action on A1 and A2A receptors in the brain.
Xanthine derivatives such as caffeine and theophylline act as non-selective antagonists at A1 and A2A receptors in both heart and brain and so have the opposite effect to adenosine, producing a stimulant effect and rapid heart rate. These compounds act as phosphodiesterase inhibitors, which produces additional anti-inflammatory effects, makes them medically useful for the treatment of conditions such as asthma, but less suitable for use in scientific research. Newer adenosine receptor agonists and antagonists are much more potent and subtype-selective, have allowed extensive research into the effects of blocking or stimulating the individual adenosine receptor subtypes, now resulting in a new generation of more selective drugs with many potential medical uses; some of these compounds are still derived from adenosine or from the xanthine family, but researchers in this area have discovered many selective adenosine receptor ligands that are structurally distinct, giving a wide range of possible directions for future research.
The adenosine A1 receptor has been found to be ubiquitous throughout the entire body. This receptor has an inhibitory function on most of the tissues. In the brain, it slows metabolic activity by a combination of actions. Presynaptically, it reduces synaptic vesicle release while post synaptically it has been found to stabilize the magnesium on the NMDA receptor. Specific A1 antagonists include 8-Cyclopentyl-1,3-dipropylxanthine, Cyclopentyltheophylline or 8-cyclopentyl-1,3-dipropylxanthine, while specific agonists include 2-chloro-N-cyclopentyladenosine. Tecadenoson is an effective A1 adenosine agonist; the A1, together with A2A receptors of endogenous adenosine play a role in regulating myocardial oxygen consumption and coronary blood flow. Stimulation of the A1 receptor has a myocardial depressant effect by decreasing the conduction of electrical impulses and suppressing pacemaker cell function, resulting in a decrease in heart rate; this makes adenosine a useful medication for treating and diagnosing tachyarrhythmias, or excessively fast heart rates.
This effect on the A1 receptor explains why there is a brief moment of cardiac standstill when adenosine is administered as a rapid IV push during cardiac resuscitation. The rapid infusion causes a momentary myocardial stunning effect. In normal physiological states, this serves as a protective mechanism. However, in altered cardiac function, such as hypoperfusion caused by hypotension, heart attack or cardiac arrest caused by nonperfusing bradycardias, adenosine has a negative effect on physiological functioning by preventing necessary compensatory increases in heart rate and blood pressure that attempt to maintain cerebral perfusion. Adenosine antagonists are used in neonatal medicine. Theophylline and caffeine are nonselective adenosine antagonists that are used to stimulate respiration in premature infants. Adenosine receptors play a key role in the homeostasis of bone; the A1 receptor has been shown to stimulate osteoclast function. Studies have found that blockade of the A1 Receptor suppresses the osteoclast function, leading to increased bone density.
As with the A1, the A2A receptors are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow. The activity of A2A adenosine receptor, a G-protein coupled receptor family member, is mediated by G proteins that activate adenylyl cyclase, it is abundant in basal ganglia and platelets and it is a major target of caffeine. The A2A receptor is responsible for regulating myocardial blood flow by vasodilating the coronary arteries, which increases blood flow to the myocardium, but may lead to hypotension. Just as in A1 receptors, this serves as a protective mechanism, but may be destructive in altered cardiac function. Specific antagonists include istradefylline and SCH-58261, while specific agonists include CGS-21680 and ATL-146e; the role of A2A receptor opposes that of A1 in that it inhibits osteoclast differentiation and activates osteoblasts. Studies have shown it to be effective in decreasing inflammatory osteolysis in inflamed bone; this role could potentiate new therapeutic treatment in
In animal anatomy, the mouth known as the oral cavity, buccal cavity, or in Latin cavum oris, is the opening through which many animals take in food and issue vocal sounds. It is the cavity lying at the upper end of the alimentary canal, bounded on the outside by the lips and inside by the pharynx and containing in higher vertebrates the tongue and teeth; this cavity is known as the buccal cavity, from the Latin bucca. Some animal phyla, including vertebrates, have a complete digestive system, with a mouth at one end and an anus at the other. Which end forms first in ontogeny is a criterion used to classify animals into protostomes and deuterostomes. In the first multicellular animals, there was no mouth or gut and food particles were engulfed by the cells on the exterior surface by a process known as endocytosis; the particles became enclosed in vacuoles into which enzymes were secreted and digestion took place intracellularly. The digestive products were diffused into other cells; this form of digestion is used nowadays by simple organisms such as Amoeba and Paramecium and by sponges which, despite their large size, have no mouth or gut and capture their food by endocytosis.
The vast majority of other multicellular organisms have a mouth and a gut, the lining of, continuous with the epithelial cells on the surface of the body. A few animals which live parasitically had guts but have secondarily lost these structures; the original gut of multicellular organisms consisted of a simple sac with a single opening, the mouth. Many modern invertebrates have such a system, food being ingested through the mouth broken down by enzymes secreted in the gut, the resulting particles engulfed by the other cells in the gut lining. Indigestible waste is ejected through the mouth. In animals at least as complex as an earthworm, the embryo forms a dent on one side, the blastopore, which deepens to become the archenteron, the first phase in the formation of the gut. In deuterostomes, the blastopore becomes the anus while the gut tunnels through to make another opening, which forms the mouth. In the protostomes, it used to be thought that the blastopore formed the mouth while the anus formed as an opening made by the other end of the gut.
More recent research, shows that in protostomes the edges of the slit-like blastopore close up in the middle, leaving openings at both ends that become the mouth and anus. Apart from sponges and placozoans all animals have an internal gut cavity, lined with gastrodermal cells. In less advanced invertebrates such as the sea anemone, the mouth acts as an anus. Circular muscles around the mouth are able to contract in order to open or close it. A fringe of tentacles thrusts food into the cavity and it can gape enough to accommodate large prey items. Food passes first into a pharynx and digestion occurs extracellularly in the gastrovascular cavity. Annelids have simple tube-like gets and the possession of an anus allows them to separate the digestion of their foodstuffs from the absorption of the nutrients. Many molluscs have a radula, used to scrape microscopic particles off surfaces. In invertebrates with hard exoskeletons, various mouthparts may be involved in feeding behaviour. Insects have a range of mouthparts suited to their mode of feeding.
These include mandibles and labium and can be modified into suitable appendages for chewing, piercing and sucking. Decapods have six pairs of mouth appendages, one pair of mandibles, two pairs of maxillae and three of maxillipeds. Sea urchins have a set of five sharp calcareous plates which are used as jaws and are known as Aristotle's lantern. In vertebrates, the first part of the digestive system is the buccal cavity known as the mouth; the buccal cavity of a fish is separated from the opercular cavity by the gills. Water flows in through passes over the gills and exits via the operculum or gill slits. Nearly all fish have jaws and may seize food with them but most feed by opening their jaws, expanding their pharynx and sucking in food items; the food may be held or chewed by teeth located in the jaws, on the roof of the mouth, on the pharynx or on the gill arches. Nearly all amphibians are carnivorous as adults. Many catch their prey by flicking out an elongated tongue with a sticky tip and drawing it back into the mouth where they hold the prey with their jaws.
They swallow their food whole without much chewing. They have many small hinged pedicellate teeth, the bases of which are attached to the jaws while the crowns break off at intervals and are replaced. Most amphibians have one or two rows of teeth in both jaws but some frogs lack teeth in the lower jaw. In many amphibians there are vomerine teeth attached to the bone in the roof of the mouth; the mouths of reptiles are similar to those of mammals. The crocodilians are the only reptiles to have teeth anchored in sockets in their jaws, they are able to replace each of their 80 teeth up to 50 times during their lives. Most reptiles are either carnivorous or insectivorous but turtles are herbivorous. Lacking teeth that are suitable for efficiently chewing of their food, turtles have gastroliths in their stomach to further grind the plant material. Snakes have a flexible lower jaw, the two halves of which are not rigidly attached, numerous other joints in their skull; these modifications allow them to open their mouths wide enough to swallow their prey whole if it is wider than they are.
Birds do not have teeth, macerating their food. Their beaks have a range of sizes and shapes according to their diet and are compose