Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the 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 been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open 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 considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of 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; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is 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, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
Route of administration
A route of administration in pharmacology and toxicology is the path by which a drug, poison, or other substance is taken into the body. Routes of administration are classified by the location at which the substance is applied. Common examples include intravenous administration. Routes can be classified based on where the target of action is. Action may be enteral, or parenteral. Route of administration and dosage form are aspects of drug delivery. Routes of administration are classified by application location; the route or course the active substance takes from application location to the location where it has its target effect is rather a matter of pharmacokinetics. Exceptions include the transdermal or transmucosal routes, which are still referred to as routes of administration; the location of the target effect of active substances are rather a matter of pharmacodynamics. An exception is topical administration, which means that both the application location and the effect thereof is local. Topical administration is sometimes defined as both a local application location and local pharmacodynamic effect, sometimes as a local application location regardless of location of the effects.
Administration through the gastrointestinal tract is sometimes termed enteral or enteric administration. Enteral/enteric administration includes oral and rectal administration, in the sense that these are taken up by the intestines. However, uptake of drugs administered orally may occur in the stomach, as such gastrointestinal may be a more fitting term for this route of administration. Furthermore, some application locations classified as enteral, such as sublingual and sublabial or buccal, are taken up in the proximal part of the gastrointestinal tract without reaching the intestines. Enteral administration can be used for systemic administration, as well as local, such as in a contrast enema, whereby contrast media is infused into the intestines for imaging. However, for the purposes of classification based on location of effects, the term enteral is reserved for substances with systemic effects. Many drugs as tablets, capsules, or drops are taken orally. Administration methods directly into the stomach include those by gastric feeding tube or gastrostomy.
Substances may be placed into the small intestines, as with a duodenal feeding tube and enteral nutrition. Enteric coated tablets are designed to dissolve in the intestine, not the stomach, because the drug present in the tablet causes irritation in the stomach; the rectal route is an effective route of administration for many medications those used at the end of life. The walls of the rectum absorb many medications and effectively. Medications delivered to the distal one-third of the rectum at least avoid the "first pass effect" through the liver, which allows for greater bio-availability of many medications than that of the oral route. Rectal mucosa is vascularized tissue that allows for rapid and effective absorption of medications. A suppository is a solid dosage form. In hospice care, a specialized rectal catheter, designed to provide comfortable and discreet administration of ongoing medications provides a practical way to deliver and retain liquid formulations in the distal rectum, giving health practitioners a way to leverage the established benefits of rectal administration.
The parenteral route is any route, not enteral. Parenteral administration can be performed by injection, that is, using a needle and a syringe, or by the insertion of an indwelling catheter. Locations of application of parenteral administration include: central nervous systemepidural, e.g. epidural anesthesia intracerebral direct injection into the brain. Used in experimental research of chemicals and as a treatment for malignancies of the brain; the intracerebral route can interrupt the blood brain barrier from holding up against subsequent routes. Intracerebroventricular administration into the ventricular system of the brain. One use is as a last line of opioid treatment for terminal cancer patients with intractable cancer pain. Epicutaneous, it can be used both for local effect as in allergy testing and typical local anesthesia, as well as systemic effects when the active substance diffuses through skin in a transdermal route. Sublingual and buccal medication administration is a way of giving someone medicine orally.
Sublingual administration is. The word "sublingual" means "under the tongue." Buccal administration involves placement of the drug between the cheek. These medications can come in the form of films, or sprays. Many drugs are designed for sublingual administration, including cardiovascular drugs, barbiturates, opioid analgesics with poor gastrointestinal bioavailability and vitamins and minerals. Extra-amniotic administration, between the endometrium and fetal membranes nasal administration (th
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determine the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, food additives, 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, whereas pharmacodynamics is the study of how the drug affects the organism. Both together influence dosing and adverse effects, as seen in PK/PD models. Pharmacokinetics describes how the body affects a specific xenobiotic/chemical after administration through the mechanisms of absorption and distribution, as well as the metabolic changes of the substance in the body, the effects and routes of excretion of the metabolites of the drug. Pharmacokinetic properties of chemicals are affected by the route of administration and the dose of administered drug.
These may affect the absorption rate. Models have been developed to simplify conceptualization of the many processes that take place in the interaction between an organism and a chemical substance. One of these, the multi-compartmental model, is the most used approximations to reality; the various compartments that the model is divided into are referred to as the ADME scheme: Liberation – the process of release of a drug from the pharmaceutical formulation. See IVIVC. Absorption – the process of a substance entering the blood circulation. Distribution – the dispersion or dissemination of substances throughout the fluids and tissues of the body. 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 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. For this reason in order to comprehend the kinetics of a drug it is necessary to have detailed knowledge of a number of factors such as: the properties of the substances that act as excipients, the characteristics of the appropriate biological membranes and the way that substances can cross them, or the characteristics of the enzyme reactions that inactivate the drug. All these concepts can be represented through mathematical formulas that have a corresponding graphical representation; the use of these models allows an understanding of the characteristics of a molecule, as well as how a particular drug will behave given information regarding some of its basic characteristics such as its acid dissociation constant and solubility, absorption capacity and distribution in the organism. The model outputs for a drug can be used in industry or in the clinical application of pharmacokinetic concepts.
Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals and in veterinary medicine. The following are the most measured pharmacokinetic metrics: In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is in dynamic equilibrium with its elimination. In practice, it is 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; the following graph depicts a typical time course of drug plasma concentration and illustrates main pharmacokinetic metrics: Pharmacokinetic modelling is performed by noncompartmental or compartmental methods. 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 and produce accurate results acceptable for bioequivalence studies.
The final outcome of the transformations that a drug undergoes in an organism and the rules that determine this fate depend on a number of interrelated factors. 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; this monocompartmental model presupposes that blood plasma concentrations of the drug are a true reflection of the drug's concentration in other fluids or tissues and that the elimination of the drug is directly proportional to the drug's concentration in the organism. However, these models do not always reflect the real situation within an organism. For example, not all body tissues have the same blood supply, so the distribution of the drug will be slower in these tissues than in others with a better blood supply. In addition, there are some tissues (s
A drug is any substance that, when inhaled, smoked, absorbed via a patch on the skin, or dissolved under the tongue causes a physiological change in the body. In pharmacology, a drug is a chemical substance of known structure, other than a nutrient of an essential dietary ingredient, when administered to a living organism, produces a biological effect. A pharmaceutical drug called a medication or medicine, is a chemical substance used to treat, prevent, or diagnose a disease or to promote well-being. Traditionally drugs were obtained through extraction from medicinal plants, but more also by organic synthesis. Pharmaceutical drugs may be used for a limited duration, or on a regular basis for chronic disorders. Pharmaceutical drugs are classified into drug classes—groups of related drugs that have similar chemical structures, the same mechanism of action, a related mode of action, that are used to treat the same disease; the Anatomical Therapeutic Chemical Classification System, the most used drug classification system, assigns drugs a unique ATC code, an alphanumeric code that assigns it to specific drug classes within the ATC system.
Another major classification system is the Biopharmaceutics Classification System. This classifies drugs according to their permeability or absorption properties. Psychoactive drugs are chemical substances that affect the function of the central nervous system, altering perception, mood or consciousness, they include alcohol, a depressant, the stimulants nicotine and caffeine. These three are the most consumed psychoactive drugs worldwide and are considered recreational drugs since they are used for pleasure rather than medicinal purposes. Other recreational drugs include hallucinogens and amphetamines and some of these are used in spiritual or religious settings; some drugs can cause addiction and all drugs can have side effects. Excessive use of stimulants can promote stimulant psychosis. Many recreational drugs are illicit and international treaties such as the Single Convention on Narcotic Drugs exist for the purpose of their prohibition. In English, the noun "drug" is thought to originate from Old French "drogue" deriving into "droge-vate" from Middle Dutch meaning "dry barrels", referring to medicinal plants preserved in them.
The transitive verb "to drug" arose and invokes the psychoactive rather than medicinal properties of a substance. A medication or medicine is a drug taken to cure or ameliorate any symptoms of an illness or medical condition; the use may be as preventive medicine that has future benefits but does not treat any existing or pre-existing diseases or symptoms. Dispensing of medication is regulated by governments into three categories—over-the-counter medications, which are available in pharmacies and supermarkets without special restrictions. In the United Kingdom, behind-the-counter medicines are called pharmacy medicines which can only be sold in registered pharmacies, by or under the supervision of a pharmacist; these medications are designated by the letter P on the label. The range of medicines available without a prescription varies from country to country. Medications are produced by pharmaceutical companies and are patented to give the developer exclusive rights to produce them; those that are not patented are called generic drugs since they can be produced by other companies without restrictions or licenses from the patent holder.
Pharmaceutical drugs are categorised into drug classes. A group of drugs will share a similar chemical structure, or have the same mechanism of action, the same related mode of action or target the same illness or related illnesses; the Anatomical Therapeutic Chemical Classification System, the most used drug classification system, assigns drugs a unique ATC code, an alphanumeric code that assigns it to specific drug classes within the ATC system. Another major classification system is the Biopharmaceutics Classification System; this groups drugs according to their permeability or absorption properties. Some religions ethnic religions are based on the use of certain drugs, known as entheogens, which are hallucinogens,—psychedelics, dissociatives, or deliriants; some drugs used as entheogens include kava which can act as a stimulant, a sedative, a euphoriant and an anesthetic. The roots of the kava plant are used to produce a drink, consumed throughout the cultures of the Pacific Ocean; some shamans from different cultures use entheogens, defined as "generating the divine within" to achieve religious ecstasy.
Amazonian shamans use ayahuasca a hallucinogenic brew for this purpose. Mazatec shamans have a long and continuous tradition of religious use of Salvia divinorum a psychoactive plant, its use is to facilitate visionary states of consciousness during spiritual healing sessions. Silene undulata is used as an entheogen, its root is traditionally used to induce vivid lucid dreams during the initiation process of shamans, classifying it a occurring oneirogen similar to the more well-known dream herb Calea ternifolia. Peyote a small spineless cactus has been a
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A potent drug evokes a given response at low concentrations, while a drug of lower potency evokes the same response only at higher concentrations. Higher potency does not mean more side effects; the IUPHAR has stated that'potency' is "an imprecise term that should always be further defined", for instance as EC 50, IC 50, ED50, LD50 and so on. Harris, Robert. "Formulating High Potency Drugs". Contract Pharma. Retrieved 2013-11-13. Walker MG, Page CP, Hoffman BF, Curtis M. Integrated Pharmacology. St. Louis: Mosby. ISBN 978-0-323-04080-8
China the People's Republic of China, is a country in East Asia and the world's most populous country, with a population of around 1.404 billion. Covering 9,600,000 square kilometers, it is the third- or fourth-largest country by total area. Governed by the Communist Party of China, the state exercises jurisdiction over 22 provinces, five autonomous regions, four direct-controlled municipalities, the special administrative regions of Hong Kong and Macau. China emerged as one of the world's earliest civilizations, in the fertile basin of the Yellow River in the North China Plain. For millennia, China's political system was based on hereditary monarchies, or dynasties, beginning with the semi-legendary Xia dynasty in 21st century BCE. Since China has expanded, re-unified numerous times. In the 3rd century BCE, the Qin established the first Chinese empire; the succeeding Han dynasty, which ruled from 206 BC until 220 AD, saw some of the most advanced technology at that time, including papermaking and the compass, along with agricultural and medical improvements.
The invention of gunpowder and movable type in the Tang dynasty and Northern Song completed the Four Great Inventions. Tang culture spread in Asia, as the new Silk Route brought traders to as far as Mesopotamia and Horn of Africa. Dynastic rule ended in 1912 with the Xinhai Revolution; the Chinese Civil War resulted in a division of territory in 1949, when the Communist Party of China established the People's Republic of China, a unitary one-party sovereign state on Mainland China, while the Kuomintang-led government retreated to the island of Taiwan. The political status of Taiwan remains disputed. Since the introduction of economic reforms in 1978, China's economy has been one of the world's fastest-growing with annual growth rates above 6 percent. According to the World Bank, China's GDP grew from $150 billion in 1978 to $12.24 trillion by 2017. Since 2010, China has been the world's second-largest economy by nominal GDP and since 2014, the largest economy in the world by purchasing power parity.
China is the world's largest exporter and second-largest importer of goods. China is a recognized nuclear weapons state and has the world's largest standing army and second-largest defense budget; the PRC is a permanent member of the United Nations Security Council as it replaced the ROC in 1971, as well as an active global partner of ASEAN Plus mechanism. China is a leading member of numerous formal and informal multilateral organizations, including the Shanghai Cooperation Organization, WTO, APEC, BRICS, the BCIM, the G20. In recent times, scholars have argued that it will soon be a world superpower, rivaling the United States; the word "China" has been used in English since the 16th century. It is not a word used by the Chinese themselves, it has been traced through Portuguese and Persian back to the Sanskrit word Cīna, used in ancient India."China" appears in Richard Eden's 1555 translation of the 1516 journal of the Portuguese explorer Duarte Barbosa. Barbosa's usage was derived from Persian Chīn, in turn derived from Sanskrit Cīna.
Cīna was first used including the Mahābhārata and the Laws of Manu. In 1655, Martino Martini suggested that the word China is derived from the name of the Qin dynasty. Although this derivation is still given in various sources, it is complicated by the fact that the Sanskrit word appears in pre-Qin literature; the word may have referred to a state such as Yelang. The meaning transferred to China as a whole; the origin of the Sanskrit word is still a matter of debate, according to the Oxford English Dictionary. The official name of the modern state is the "People's Republic of China"; the shorter form is "China" Zhōngguó, from zhōng and guó, a term which developed under the Western Zhou dynasty in reference to its royal demesne. It was applied to the area around Luoyi during the Eastern Zhou and to China's Central Plain before being used as an occasional synonym for the state under the Qing, it was used as a cultural concept to distinguish the Huaxia people from perceived "barbarians". The name Zhongguo is translated as "Middle Kingdom" in English.
Archaeological evidence suggests that early hominids inhabited China between 2.24 million and 250,000 years ago. The hominid fossils of Peking Man, a Homo erectus who used fire, were discovered in a cave at Zhoukoudian near Beijing; the fossilized teeth of Homo sapiens have been discovered in Fuyan Cave in Hunan. Chinese proto-writing existed in Jiahu around 7000 BCE, Damaidi around 6000 BCE, Dadiwan from 5800–5400 BCE, Banpo dating from the 5th millennium BCE; some scholars have suggested. According to Chinese tradition, the first dynasty was the Xia, which emerged around 2100 BCE; the dynasty was considered mythical by historians until scientific excavations found early Bronze Age sites at Erlitou, Henan in 1959. It remains unclear whether these sites are the remains of the Xia dynasty or of another culture from the same period; the succeeding Shang dynasty is the earliest to be confirmed by contemporary records. The Shang ruled the plain of the Yellow River in eastern China from the 17th to the 11th century BCE.
Their oracle bone script
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