Hypnotic or soporific drugs known as sleeping pills, are a class of psychoactive drugs whose primary function is to induce sleep and to be used in the treatment of insomnia, or for surgical anesthesia. This group is related to sedatives. Whereas the term sedative describes drugs that serve to calm or relieve anxiety, the term hypnotic describes drugs whose main purpose is to initiate, sustain, or lengthen sleep; because these two functions overlap, because drugs in this class produce dose-dependent effects they are referred to collectively as sedative-hypnotic drugs. Hypnotic drugs are prescribed for insomnia and other sleep disorders, with over 95% of insomnia patients being prescribed hypnotics in some countries. Many hypnotic drugs are habit-forming and, due to a large number of factors known to disturb the human sleep pattern, a physician may instead recommend changes in the environment before and during sleep, better sleep hygiene, the avoidance of caffeine or other stimulating substances, or behavioral interventions such as cognitive behavioral therapy for insomnia before prescribing medication for sleep.
When prescribed, hypnotic medication should be used for the shortest period of time necessary. Among individuals with sleep disorders, 13.7% are taking or prescribed nonbenzodiazepines, while 10.8% are taking benzodiazepines, as of 2010. Early classes of drugs, such as barbiturates, have fallen out of use in most practices but are still prescribed for some patients. In children, prescribing hypnotics is not yet acceptable unless used to treat night terrors or somnambulism. Elderly people are more sensitive to potential side effects of daytime fatigue and cognitive impairments, a meta-analysis found that the risks outweigh any marginal benefits of hypnotics in the elderly. A review of the literature regarding benzodiazepine hypnotics and Z-drugs concluded that these drugs can have adverse effects, such as dependence and accidents, that optimal treatment uses the lowest effective dose for the shortest therapeutic time period, with gradual discontinuation in order to improve health without worsening of sleep.
Falling outside the above-mentioned categories, the neuro-hormone melatonin has a hypnotic function. Hypnotica was a class of somniferous drugs and substances tested in medicine of the 1890s and including: Urethan, Methylal, paraldehyde, Hypnon and Ohloralamid or Chloralimid. Research about using medications to treat insomnia evolved throughout the last half of the 20th century. Treatment for insomnia in psychiatry dates back to 1869 when chloral hydrate was first used as a soporific. Barbiturates emerged as the first class of drugs that emerged in the early 1900s, after which chemical substitution allowed derivative compounds. Although the best drug family at the time they were dangerous in overdose and tended to cause physical and psychological dependence. During the 1970s, quinazolinones and benzodiazepines were introduced as safer alternatives to replace barbiturates. Benzodiazepines are not without their drawbacks. Questions have been raised as to. Nonbenzodiazepines are the most recent development.
Although it's clear that they are less toxic than their predecessors, comparative efficacy over benzodiazepines have not been established. Without longitudinal studies, it is hard to determine. Other sleep remedies that may be considered "sedative-hypnotics" exist. Examples of these include mirtazapine, clonidine and the over-the-counter sleep aid diphenhydramine. Off-label sleep remedies are useful when first-line treatment is unsuccessful or deemed unsafe. Barbiturates are drugs that act as central nervous system depressants, can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia, they are effective as anxiolytics and anticonvulsalgesic effects. They have dependence liability, both psychological. Barbiturates have now been replaced by benzodiazepines in routine medical practice – for example, in the treatment of anxiety and insomnia – because benzodiazepines are less dangerous in overdose. However, barbiturates are still used in general anesthesia, for epilepsy, assisted suicide.
Barbiturates are derivatives of barbituric acid. The principal mechanism of action of barbiturates is believed to be positive allosteric modulation of GABAA receptors. Examples include amobarbital, phenobarbital and sodium thiopental. Quinazolinones are a class of drugs which function as hypnotic/sedatives that contain a 4-quinazolinone core, their use has been proposed in the treatment of cancer. Examples of quinazolinones include cloroqualone, etaqualone, mebroqualone and methaqualone. Benzodiaz
Bayer AG is a German multinational pharmaceutical and life sciences company and one of the largest pharmaceutical companies in the world. Headquartered in Leverkusen, where its illuminated corporate logo, the Bayer cross, is a landmark, Bayer's areas of business include human and veterinary pharmaceuticals; the company is a component of the Euro Stoxx 50 stock market index. Werner Baumann has been CEO since 2016. Founded in Barmen in 1863 as a dyestuffs factory, Bayer's first and best-known product was aspirin. In 1898 Bayer trademarked the name heroin for the drug diacetylmorphine and marketed it as a cough suppressant and non-addictive substitute for morphine until 1910. Bayer introduced phenobarbital. In 1925 Bayer was one of six chemical companies that merged to form IG Farben, the world's largest chemical and pharmaceutical company; the Allied Control Council seized IG Farben after World War II, because of its role in the Nazi war effort and involvement in the Holocaust, which included using slave labour from concentration camps.
It was split into its six constituent companies in 1951 split again into three: BASF, Bayer and Hoechst. Bayer played a key role in the Wirtschaftswunder in post-war West Germany regaining its position as one of the world's largest chemical and pharmaceutical corporations. In 2006 the company acquired Schering, in 2014 it acquired Merck & Co.'s consumer business, with brands such as Claritin, Coppertone and Dr. Scholl's, in 2018 it acquired Monsanto, a leading producer of genetically engineered crops, for $63 billion. Bayer CropScience develops genetically modified pesticides. Bayer AG was founded as a dyestuffs factory in 1863 in Barmen, Germany, by Friedrich Bayer and his partner, Johann Friedrich Weskott, a master dyer. Bayer was responsible for the commercial tasks. Fuchsine and aniline became; the headquarters and most production facilities moved from Barmen to a larger area in Elberfeld in 1866. Friedrich Bayer, son of the company's founder, was a chemist and joined the company in 1873. After the death of his father in 1880, the company became a joint-stock company, Farbenfabriken vorm.
Friedr. Bayern & Co known as Elberfelder Farbenfabriken. A further expansion in Elberfeld was impossible, so the company moved to the village Wiesdorf at Rhein and settled in the area of the alizarin producer Leverkus and Sons. A new city, was founded there in 1930 and became home to Bayer AG's headquarters; the company's corporate logo, the Bayer cross, was introduced in 1904, consisting of the word BAYER written vertically and horizontally, sharing the Y and enclosed in a circle. An illuminated version of the logo is a landmark in Leverkusen. Bayer's first major product was acetylsalicylic acid—first described by French chemist Charles Frederic Gerhardt in 1853—a modification of salicylic acid or salicin, a folk remedy found in the bark of the willow plant. By 1899 Bayer's trademark Aspirin was registered worldwide for Bayer's brand of acetylsalicylic acid, but it lost its trademark status in the United States and the United Kingdom after the confiscation of Bayer's US assets and trademarks during World War I by the United States, because of the subsequent widespread usage of the word.
The term aspirin continued to be used in the US, UK and France for all brands of the drug, but it is still a registered trademark of Bayer in over 80 countries, including Canada, Mexico and Switzerland. As of 2011 40,000 tons of aspirin were produced each year and 10–20 billion tablets consumed in the United States alone for prevention of cardiovascular events, it is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. There is an unresolved controversy over the roles played by Bayer scientists in the development of aspirin. Arthur Eichengrün, a Bayer chemist, said he was the first to discover an aspirin formulation that did not have the unpleasant side effects of nausea and gastric pain, he said he had invented the name aspirin and was the first person to use the new formulation to test its safety and efficacy. Bayer contends. Various sources support the conflicting claims. Most mainstream historians attribute the invention of aspirin to Hoffmann and/or Eichengrün.
Heroin, now illegal as an addictive drug, was introduced as a non-addictive substitute for morphine, trademarked and marketed by Bayer from 1898 to 1910 as a cough suppressant and over-the-counter treatment for other common ailments, including pneumonia and tuberculosis. Bayer scientists were not the first to make heroin, but the company led the way in commercializing it. Heroin was a Bayer trademark until after World War I. In 1903 Bayer licensed the patent for the hypnotic drug diethylbarbituric acid from its inventors Emil Fischer and Joseph von Mering, it was marketed under the trade name Veronal as a sleep aid beginning in 1904. Systematic investigations of the effect of structural changes on potency and duration of action at Bayer led to the discovery of phenobarbital in 1911 and the discovery of its potent anti-epileptic activity in 1912. Phenobarbital was among the most used drugs for the treatment of epilepsy through the 1970s, as of 2014 it remains on the World Health Organization's list of essential medications.
During World War I, Bayer's assets, including the rights to
Quebracho blanco, called kebrako or white quebracho, is a South American tree species, native to Brazil, N Argentina, Bolivia and Uruguay. It must not be confused with other species known as quebracho, but belonging to the genus Schinopsis. Quebracho blanco wood is uniformly yellow-ochre, without differences between sapwood, it is quite heavy and hard, responds well to bending and shock. Upon drying it tends to collapse, producing deformations and cracks, so the drying process is slow, it has many uses in carpentry. Preserved with creosote it can be used outdoors. In some places it is used as coal, since it does not produce sparks or large amounts of ash, it burns strong and slowly. Quebrachitol is a cyclic polyol found in the bark of A. quebracho. Quebrachine is a chemical synonym for yohimbine since it was first isolated from the bark of A. quebracho-blanco.'Pendula' - with weeping branches
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.
The United States of America known as the United States or America, is a country composed of 50 states, a federal district, five major self-governing territories, various possessions. At 3.8 million square miles, the United States is the world's third or fourth largest country by total area and is smaller than the entire continent of Europe's 3.9 million square miles. With a population of over 327 million people, the U. S. is the third most populous country. The capital is Washington, D. C. and the largest city by population is New York City. Forty-eight states and the capital's federal district are contiguous in North America between Canada and Mexico; the State of Alaska is in the northwest corner of North America, bordered by Canada to the east and across the Bering Strait from Russia to the west. The State of Hawaii is an archipelago in the mid-Pacific Ocean; the U. S. territories are scattered about the Pacific Ocean and the Caribbean Sea, stretching across nine official time zones. The diverse geography and wildlife of the United States make it one of the world's 17 megadiverse countries.
Paleo-Indians migrated from Siberia to the North American mainland at least 12,000 years ago. European colonization began in the 16th century; the United States emerged from the thirteen British colonies established along the East Coast. Numerous disputes between Great Britain and the colonies following the French and Indian War led to the American Revolution, which began in 1775, the subsequent Declaration of Independence in 1776; the war ended in 1783 with the United States becoming the first country to gain independence from a European power. The current constitution was adopted in 1788, with the first ten amendments, collectively named the Bill of Rights, being ratified in 1791 to guarantee many fundamental civil liberties; the United States embarked on a vigorous expansion across North America throughout the 19th century, acquiring new territories, displacing Native American tribes, admitting new states until it spanned the continent by 1848. During the second half of the 19th century, the Civil War led to the abolition of slavery.
By the end of the century, the United States had extended into the Pacific Ocean, its economy, driven in large part by the Industrial Revolution, began to soar. The Spanish–American War and World War I confirmed the country's status as a global military power; the United States emerged from World War II as a global superpower, the first country to develop nuclear weapons, the only country to use them in warfare, a permanent member of the United Nations Security Council. Sweeping civil rights legislation, notably the Civil Rights Act of 1964, the Voting Rights Act of 1965 and the Fair Housing Act of 1968, outlawed discrimination based on race or color. During the Cold War, the United States and the Soviet Union competed in the Space Race, culminating with the 1969 U. S. Moon landing; the end of the Cold War and the collapse of the Soviet Union in 1991 left the United States as the world's sole superpower. The United States is the world's oldest surviving federation, it is a representative democracy.
The United States is a founding member of the United Nations, World Bank, International Monetary Fund, Organization of American States, other international organizations. The United States is a developed country, with the world's largest economy by nominal GDP and second-largest economy by PPP, accounting for a quarter of global GDP; the U. S. economy is post-industrial, characterized by the dominance of services and knowledge-based activities, although the manufacturing sector remains the second-largest in the world. The United States is the world's largest importer and the second largest exporter of goods, by value. Although its population is only 4.3% of the world total, the U. S. holds 31% of the total wealth in the world, the largest share of global wealth concentrated in a single country. Despite wide income and wealth disparities, the United States continues to rank high in measures of socioeconomic performance, including average wage, human development, per capita GDP, worker productivity.
The United States is the foremost military power in the world, making up a third of global military spending, is a leading political and scientific force internationally. In 1507, the German cartographer Martin Waldseemüller produced a world map on which he named the lands of the Western Hemisphere America in honor of the Italian explorer and cartographer Amerigo Vespucci; the first documentary evidence of the phrase "United States of America" is from a letter dated January 2, 1776, written by Stephen Moylan, Esq. to George Washington's aide-de-camp and Muster-Master General of the Continental Army, Lt. Col. Joseph Reed. Moylan expressed his wish to go "with full and ample powers from the United States of America to Spain" to seek assistance in the revolutionary war effort; the first known publication of the phrase "United States of America" was in an anonymous essay in The Virginia Gazette newspaper in Williamsburg, Virginia, on April 6, 1776. The second draft of the Articles of Confederation, prepared by John Dickinson and completed by June 17, 1776, at the latest, declared "The name of this Confederation shall be the'United States of America'".
The final version of the Articles sent to the states for ratification in late 1777 contains the sentence "The Stile of this Confederacy shall be'The United States of America'". In June 1776, Thomas Jefferson wrote the phrase "UNITED STATES OF AMERICA" in all capitalized letters in the headline of his "original Rough draught" of the Declaration of Independence; this draft of the document did not surface unti
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
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