Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process can occur with all post-pregnancy female mammals. In humans the process of feeding milk is called breastfeeding or nursing. Newborn infants produce some milk from their own breast tissue, known colloquially as witch's milk. In most species, milk comes out of the mother's nipples. In only one species of mammal, the Dayak fruit bat from Southeast Asia, is milk production a normal male function. Galactopoiesis is the maintenance of milk production; this stage requires prolactin. Oxytocin is critical for the milk let-down reflex in response to suckling. Galactorrhea is milk production unrelated to nursing, it can occur in males and females of many mammal species as result of hormonal imbalances such as hyperprolactinaemia. The chief function of a lactation is to provide nutrition and immune protection to the young after birth. In all mammals, lactation induces a period of infertility, which serves to provide the optimal birth spacing for survival of the offspring.
From the eighteenth week of pregnancy, a woman's body produces hormones that stimulate the growth of the milk duct system in the breasts: Progesterone influences the growth in size of alveoli and lobes. Progesterone levels drop after birth. Estrogen stimulates the milk duct system to differentiate. Like progesterone, high levels of estrogen inhibit lactation. Estrogen levels drop at delivery and remain low for the first several months of breastfeeding. Breastfeeding mothers should avoid estrogen-based birth control methods, as a spike in estrogen levels may reduce a mother's milk supply. Prolactin contributes to the increased growth and differentiation of the alveoli, influences differentiation of ductal structures. High levels of prolactin during pregnancy and breastfeeding increase insulin resistance, increase growth factor levels and modify lipid metabolism in preparation for breastfeeding. During lactation, prolactin is the main factor maintaining tight junctions of the ductal epithelium and regulating milk production through osmotic balance.
Human placental lactogen – from the second month of pregnancy, the placenta releases large amounts of HPL. This hormone is associated with prolactin and appears to be instrumental in breast and areola growth before birth. Follicle stimulating hormone, luteinizing hormone, human chorionic gonadotropin, through control of estrogen and progesterone production, by extension and growth hormone production, are essential. Growth hormone is structurally similar to prolactin and independently contributes to its galactopoiesis. Adrenocorticotropic hormone and glucocorticoids such as cortisol have an important lactation inducing function in several animal species, including humans. Glucocorticoids play a complex regulating role in the maintenance of tight junctions. Thyroid-stimulating hormone and thyrotropin-releasing hormone are important galactopoietic hormones whose levels are increased during pregnancy. Oxytocin contracts the smooth muscle of the uterus during and after birth, during orgasm. After birth, oxytocin contracts the smooth muscle layer of band-like cells surrounding the alveoli to squeeze the newly produced milk into the duct system.
Oxytocin is necessary for the milk ejection reflex, or let-down, in response to occur. It is possible to induce lactation without pregnancy. Protocols for inducing lactation are called the Goldfarb protocols. Using birth control pills to mimic the hormone levels of pregnancy discontinuing the birth control, followed by use of a double electric breast pump for 15 minute sessions at regular 2-3 hour intervals _ helps induce milk production. During the latter part of pregnancy, the woman's breasts enter into the Secretory Differentiation stage; this is when the breasts make a thick, sometimes yellowish fluid. At this stage, high levels of progesterone inhibit most milk production, it is not a medical concern if a pregnant woman leaks any colostrum before her baby's birth, nor is it an indication of future milk production. At birth, prolactin levels remain high, while the delivery of the placenta results in a sudden drop in progesterone, HPL levels; this abrupt withdrawal of progesterone in the presence of high prolactin levels stimulates the copious milk production of Secretory Activation.
When the breast is stimulated, prolactin levels in the blood rise, peak in about 45 minutes, return to the pre-breastfeeding state about three hours later. The release of prolactin triggers the cells in the alveoli to make milk. Prolactin transfers to the breast milk; some research indicates that prolactin in milk is greater at times of higher milk production, lower when breasts are fuller, that the highest levels tend to occur between 2 a.m. and 6 a.m. Other hormones—notably insulin and cortisol—are involved, but their roles are not yet well understood. Although biochemical markers indicate that Secretory Activation begins about 30–40 hours after birth, mothers do not begin feeling increased breast fullness until 50–73 hours after birth. Colostrum is the first milk, it contains higher amounts of white blood cells and antibodies than matur
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
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
A prescription drug is a pharmaceutical drug that 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. "Rx" is used as a short form for prescription drug in North America - a contraction of the Latin word "recipe" meaning "take". Prescription drugs are 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, while 36% take at least 5 prescription medicines concurrently. In Australia, the Standard for the Uniform Scheduling of Medicines and Poisons governs the manufacture and supply of drugs with several categories: Schedule 1 – Defunct Schedule 2 – Pharmacy Medicine Schedule 3 – Pharmacist-Only Medicine Schedule 4 – Prescription-Only Medicine/Prescription Animal Remedy Schedule 5 – Caution Schedule 6 – Poison Schedule 7 – Dangerous Poison Schedule 8 – Controlled Drug Schedule 9 – Prohibited Substance Unscheduled SubstancesLike in the UK, the patient visits a health practitioner, who may prescribe the drug.
Many prescriptions issued by health practitioners in Australia are covered by the Pharmaceutical Benefits Scheme, a scheme that provides subsidised prescription drugs to residents of Australia to ensure that all Australians have affordable and reliable access to a wide range of necessary medicines. When purchasing a drug under the PBS, the consumer pays no more than the patient co-payment contribution, which, as of January 1, 2018, is A$39.50 for general patients. Those covered by government entitlements and or under the Repatriation Pharmaceutical Benefits Scheme have a reduced co-payment, $6.40 in 2018. The co-payments are compulsory and can be discounted by pharmacies up to a maximum of A$1.00 at cost to the pharmacy. In the United Kingdom, the Medicines Act 1968 and the Prescription Only Medicines Order 1997 contain regulations that cover the supply of sale, use and production of medicines. There are three categories of medicine: Prescription-only medicines, which may be dispensed by a pharmacist if they are prescribed by a prescriber Pharmacy medicines, which may be sold by a pharmacist without a prescription General sales list medicines, which may be sold without a prescription in any shopThe possession of a prescription-only medicine without a prescription is legal unless it is covered by the Misuse of Drugs Act 1971.
A patient visits a medical practitioner or dentist, who may prescribe drugs and certain other medical items, such as blood glucose-testing equipment for diabetics. Qualified and experienced nurses and pharmacists may be independent prescribers. Both may prescribe all POMs, but may not prescribe Schedule 1 controlled drugs, 3 listed controlled drugs for the treatment of addiction. Schedule 1 drugs have little or no medical benefit, hence their limitations on prescribing. District nurses and health visitors have had limited prescribing rights since the mid-1990s. Once issued, a prescription is taken by the patient to a pharmacy. Most prescriptions are NHS prescriptions, subject to a standard charge, unrelated to what is dispensed; the NHS prescription fee was increased to £8.80 per item in England on 1 April 2018. The pharmacy charges the NHS the actual cost of the medicine, which may vary from a few pence to hundreds of pounds. A patient can consolidate prescription charges by using a prescription payment certificate capping costs at £29.10 per quarter or £104.00 per year.
Outside the NHS, private prescriptions are issued by private medical practitioner and sometimes under the NHS for medicines that are not covered by the NHS. A patient pays the pharmacy the normal price for medicine prescribed outside the NHS. Survey results published by Ipsos MORI in 2008 found that around 800,000 people in England were not collecting prescriptions or getting them dispensed because of the cost, the same as in 2001. In the United States, the Federal Food and Cosmetic Act defines what substances require a prescription for them to be dispensed by a pharmacy; the federal government authorizes physicians, physician assistants, nurse practitioners and other advanced practice nurses, veterinarians and optometrists to prescribe any controlled substance. They are issued unique Drug Enforcement Act numbers.
The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1
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
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.