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Paramorphine

Paramorphine

A minor constituent of opium, thebaine or paramorphine (C₁₉ H₂₁ N O₃) is chemically similar to both morphine and codeine, but produces stimulatory rather than depressant effects. Thebaine is not used therapeutically, but is converted into a variety of compounds including codeine, hydrocodone, hydromorphone, oxycodone, oxymorphone, nalbuphine, naloxone, naltrexone, buprenorphine and etorphine. It is controlled in Schedule II of the Controlled Substances Act as well as under international law. Thebaine is listed as a Class A drug under the Misuse of Drugs Act 1971 in the United Kingdom. Category:Alkaloids Category:Ethers Category:Natural opium alkaloids Category:Opioids Category:Schedule II controlled substances th:ทีบาอีน

Opium

Opium is a narcotic analgesic drug which is obtained from the unripe seed pods of the opium poppy (Papaver somniferum L. or the synonym paeoniflorum). opium poppy

Harvesting opium

To harvest opium, the skin of the ripening pods is scored by a sharp blade. The slashes exude a white, milky latex, which dries to a sticky brown resin that is scraped off the pods as raw opium. latex Opium has powerful narcotic properties, and is used as a painkiller in extreme circumstances, such as in terminal stages of cancer. Therefore, a small amount of legal production is discreetly conducted under strict supervision by law enforcement. The leading legal producers of opium are France and Australia. The French company Francopia produces 20% to 25% of the world's total, with total sales of approximately 60 million € (1 Euro (EUR) = 1.19380 USD).

Opium preparation

Raw opium must be processed and refined (called "cooking") before it is suitable for smoking. The raw opium is first dissolved in water and simmered over a low heat. The brown solution is then filtered to remove the insoluble vegetable waxes and then evaporated over a low heat. The result is a smokable form of opium with a considerably higher morphine content percentage-wise than the raw latex. This is then pressed into bricks and either transported to heroin laboratories or used as is. Although opium is used in the form of paregoric to treat diarrhea, most opium imported into the United States is broken down into its alkaloid constituents. These alkaloids are divided into two distinct chemical classes, phenanthrenes and isoquinolines. The principal phenanthrenes are morphine, codeine, and thebaine, while the isoquinolines have no significant central nervous system effects and are not regulated under the Controlled Substances Act. Opium is also processed into heroin, and most current drug use occurs with processed derivatives rather than with raw opium.

Seed Capsules

The seed capsules also contain morphine, codeine, and other alkaloids. These pods can be boiled in water to produce a bitter tea that induces a long-lasting intoxication. Addiction to poppy tea is rare, but does occur.

Chemical properties and physiological effects

Opium resin contains two groups of alkaloids: phenanthrenes (including morphine and codeine) and benzylisoquinolines (including papaverine). Morphine is by far the most prevalent and important alkaloid in opium, consisting of 10%-16% of the total. It binds to and activates μ-opioid receptors in the brain, spinal cord, stomach and intestine. Regular use, even for a few days, invariably leads to physical tolerance and dependence. Various degrees of psychological addiction can occur, though this is relatively rare when opioids are properly used -- for treatment of pain, rather than for euphoric effects. These mechanisms result from changes in nervous system receptors in response to the drug. In response to the drug, the brain creates new receptors for opiates. These receptors are "pseudo" receptors and do not work. When the opiates are out of the body, the brain has more receptors than before the use of the drug, but only the same amount of endogenous opiate (endorphins) to fill these receptors.

History of opium

endorphin]] The image of the poppy capsule was an attribute of deities, long before opium was extracted from its milky latex. At the Metropolitan Museum's Assyrian relief gallery, a winged deity in a bas-relief from the palace of Ashurnasirpal II at Nimrud, dedicated in 879 BC, bears a bouquet of poppy capsules on long stems, described by the museum as "pomegranates". Hailed as the gift of the gods, Babylonians enjoyed opium, and even made cakes out of it. At this time in history, smoking opium had not been developed yet. Over the following centuries, opium use spread across the known world. In the 19th century, smoking opium became possible, enhancing its effects. In the 19th century, the smuggling of opium to China from India, particularly by the British, was the cause of the Opium Wars. It led to Britain seizing Hong Kong and to what the Chinese term the "century of shame". This illegal trade became one of the world's most valuable single commodity trades and was described by the eminent Harvard University historian John K. Fairbank as "the most long continued and systematic international crime of modern times." Opium can be smoked, sometimes in combination with tobacco. Opium smoking was often associated with immigrant Chinese communities around the world, with "opium dens" becoming notorious fixtures of many Chinatowns. There were no legal restrictions on the importation or use of opium in the United States until the Harrison Narcotics Tax Act of 1914. Medicines often contained opium without any warning label. U.S president William Henry Harrison was treated with opium in 1841. Today, there are numerous national and international laws governing the production and distribution of narcotic substances. In particular, Article 23 of the Single Convention on Narcotic Drugs requires opium-producing nations to designate a government agency to take physical possession of licit opium crops as soon as possible after harvest and conduct all wholesaling and exporting through that agency. Opium's pharmaceutical use is strictly controlled worldwide and non-pharmaceutical uses are generally prohibited.

Medicinal uses

Opium has been a major item of trade for centuries, and has long been used as a painkiller and sedative. It was well known to the ancient Greeks, who named it opion ("poppy juice"), from which the present name—a Latinisation—is derived. Many patent medicines of the 19th century were based around laudanum (known as "tincture of opium", a solution of opium in ethyl alcohol). Tincture of opium is prescribed in modern times, among other reasons, for ongoing, severe diarrhea caused, for example, by the creation of an ileostomy. A 10% tincture of opium solution (10% opium, 90% ethyl alcohol) taken 30 minutes prior to meals will significantly slow intestinal motility, giving the intestines greater time to absorb fluid in the stool.

Other meanings

"Opium" is the name of a perfume by Yves Saint Laurent. A poster advertising campaign for the perfume caused great controversy in October and November 2000. The posters showed a voluptuous model, Sophie Dahl, photographed (by Stephen Meisel) lying on her back wearing only a pair of stiletto heels [http://www.sophie-dahl.com/images/full-size/opium.jpg]. The Advertising Standards Authority received hundreds of complaints from the public, and ordered the posters to be withdrawn on the grounds that they were too sexually suggestive and likely to cause "serious or widespread offence". [http://www.guardian.co.uk/uk_news/story/0,3604,413209,00.html] "Opium" is the best-known song of the Portuguese Goth metal band Moonspell, released in 1996 on the album Irreligious.

External links

- [http://www.erowid.org/chemicals/opiates/opiates.shtml Erowid Opium Vault]
- [http://montages.blogspot.com/2004/12/new-opium-war.html A New Opium War]
- [http://www.geopium.org Geopium: Geopolitics of Illicit Drugs in Asia]
- [http://www.taima.org/en/opium.htm Opium in Japan]
- [http://www.goldentrianglepark.org/ Hall of Opium]
- [http://www.victorianlondon.org/entertainment/opiumsmokingdens.htm Opium Dens of Victorian London]
- [http://www.poppies.org Opium Poppies]
- [http://www.cia.gov/cia/publications/heroin/flowers_to_heroin.htm From Flowers to Heroin], CIA publication
- [http://www.wesjones.com/pollan1.htm Opium Made Easy] by Michael Pollan (originally appeared in Harper's.)
- [http://opioids.com/timeline/ A Brief History of Opium]

References

- Fairbank, JK. (1978) The Cambridge History of China: volume 10 part I, Cambridge, CUP
- Franck Daninos, L'opium légal produit en France, La Recherche, May 2005

Photos

- [http://www.geopium.org/Photos/Pavots_Poppies/pavotspoppies.htm Photos of opium poppies on www.geopium.org] Category:Herbal & fungal drugs/medicines Category:Opioids Category:Schedule II controlled substances ko:아편 ja:アヘン

Carbon

:Alternative meaning: Carbon (API) :For the portable music player, see Rio Carbon Carbon is a chemical element in the periodic table that has the symbol C and atomic number 6. An abundant nonmetallic, tetravalent element, carbon has several allotropic forms:
- Diamond (hardest known natural mineral). Structure: each atom is bonded tetrahedrally to four others, making a 3-dimensional network of puckered six-membered rings of atoms.
- Graphite (one of the softest substances). Structure: each atom is bonded trigonally to three other atoms, making a 2-dimensional network of flat six-membered rings; the flat sheets are loosely bonded.
- Fullerenes. Structure: comparatively large molecules formed completely of carbon bonded trigonally, forming spheroids (of which the best-known and simplest is the buckminsterfullerene or buckyball).
- Chaoite A mineral supposedly formed in meteorite impacts.
- Lonsdaleite (a corruption of diamond). Structure: similar to diamond, but forming a hexagonal crystal lattice.
- Amorphous carbon (a glassy substance). Structure: an assortment of carbon molecules in a non-crystalline, irregular, glassy state.
- Carbon nanofoam (an extremely light magnetic web). Structure: a low-density web of graphite-like clusters, in which the atoms are bonded trigonally in six- and seven-membered rings.
- Carbon nanotubes (tiny tubes). Structure: each atom is bonded trigonally in a curved sheet that forms a hollow cylinder.
- Aggregated diamond nanorods, the most recently discovered allotrope. Lamp black consists of small graphitic areas. These areas are randomly distributed, so the whole structure is isotropic. 'Glassy carbon' is isotropic and contains a high proportion of closed porosity. Unlike normal graphite, the graphitic layers are not stacked like pages in a book, but have a more random arrangement. Carbon fibers are similar to glassy carbon. Under special treatment (stretching of organic fibers and carbonization) it is possible to arrange the carbon planes in direction of the fiber. Perpendicular to the fiber axis there is no orientation of the carbon planes. The result are fibers with a higher specific strength than steel. Carbon occurs in all organic life and is the basis of organic chemistry. This nonmetal also has the interesting chemical property of being able to bond with itself and a wide variety of other elements, forming nearly 10 million known compounds. When united with oxygen it forms carbon dioxide which is absolutely vital to plant growth. When united with hydrogen, it forms various compounds called hydrocarbons which are essential to industry in the form of fossil fuels. When combined with both oxygen and hydrogen it can form many groups of compounds including fatty acids, which are essential to life, and esters, which give flavor to many fruits. The isotope carbon-14 is commonly used in radioactive dating.

Notable characteristics

Carbon is a remarkable element for many reasons. Its different forms include one of the softest (graphite) and one of the hardest (diamond) substances known to humankind. Moreover, it has a great affinity for bonding with other small atoms, including other carbon atoms, and its small size makes it capable of forming multiple bonds. Because of these properties, carbon is known to form nearly ten million different compounds, the large majority of all chemical compounds. Carbon compounds form the basis of all life on Earth and the carbon-nitrogen cycle provides some of the energy produced by the sun and other stars. Moreover, carbon has the highest melting/sublimation point of all elements. At atmospheric pressure it has no actual melting point as its triple point is at 10 MPa (100 bar) so it sublimates above 4000 K. Thus it remains solid at higher temperatures than the highest melting point metals like tungsten or rhenium, regardless of its allotropic form. Carbon was not created in the Big Bang due to the fact that it needs a triple collision of alpha particles (helium nuclei) to be produced. The universe initially expanded and cooled too fast for that to be possible. It is produced, however, in the interior of stars in the horizontal branch, where stars transform a helium core into carbon by means of the triple-alpha process. It was also created in a multi atomic state.

Applications

Carbon is a vital component of all known living systems, and without it life as we know it could not exist (see alternative biochemistry). The major economic use of carbon is in the form of hydrocarbons, most notably the fossil fuels methane gas and crude oil (petroleum). Crude oil is used by the petrochemical industry to produce, amongst others, gasoline and kerosene, through a distillation process, in refineries. Crude oil forms the raw material for many synthetic substances, many of which are collectively called plastics.

Other uses

- The isotope Carbon-14 was discovered in February 27 1940 and is used in radiocarbon dating.
- Some smoke detectors use tiny amounts of a radioactive isotope of carbon as source of ionizing radiation. (Most smoke detectors of this type use an isotope of americium.)
- Graphite is combined with clays to form the 'lead' used in pencils.
- Diamond is used for decorative purposes, and also as drill bits and other applications making use of its hardness.
- Carbon is added to iron to make steel.
- Carbon is used as a neutron moderator in nuclear reactors.
- Graphite carbon in a powdered, caked form is used as charcoal for cooking, artwork and other uses.
- Activated charcoal is used in medicine (as powder or compounded in tablets or capsules) to absorb toxins or poisons from the digestive system. The chemical and structural properties of fullerenes, in the form of carbon nanotubes, has promising potential uses in the nascent field of nanotechnology. Nanoparticles might however be toxic.

History and Etymology

Carbon was discovered in prehistory and was known to the ancients, who manufactured it by burning organic material in insufficient oxygen (making charcoal). Diamonds have long been considered rare and beautiful. One of the last-known allotropes of carbon, fullerenes, were discovered as byproducts of molecular beam experiments in the 1980s. The name comes from French charbone, which in turn came from Latin carbo, meaning charcoal. In German and Dutch, the names for carbon are Kohlenstoff and koolstof respectively, both literally meaning "coal-stuff".

Allotropes

The allotropes of carbon are the different molecular configurations (allotropes) that pure carbon can take. The three relatively well-known allotropes of carbon are amorphous carbon, graphite, and diamond. Several exotic allotropes have also been synthesized or discovered, including fullerenes, carbon nanotubes, lonsdaleite and aggregated diamond nanorods. In its amorphous form, carbon is essentially graphite but not held in a crystalline macrostructure. It is, rather, present as a powder which is the main constituent of substances such as charcoal, lamp black (soot) and activated carbon. activated carbon, so that two phases can coexist. ]] At normal pressures carbon takes the form of graphite, in which each atom is bonded to three others in a plane composed of fused hexagonal rings, just like those in aromatic hydrocarbons. The two known forms of graphite, alpha (hexagonal) and beta (rhombohedral), both have identical physical properties, except for their crystal structure. Graphites that naturally occur have been found to contain up to 30% of the beta form, when synthetically-produced graphite only contains the alpha form. The alpha form can be converted to the beta form through mechanical treatment and the beta form reverts back to the alpha form when it is heated above 1000 °C. Because of the delocalization of the pi-cloud, graphite conducts electricity. The material is soft and the sheets, frequently separated by other atoms, are held together only by van der Waals forces, so easily slip past one another. At very high pressures carbon forms an allotrope called diamond, in which each atom is bonded to four others. Diamond has the same cubic structure as silicon and germanium and, thanks to the strength of the carbon-carbon bonds, is together with the isoelectronic boron nitride (BN) the hardest substance in terms of resistance to scratching. The transition to graphite at room temperature is so slow as to be unnoticeable. Under some conditions, carbon crystallizes as Lonsdaleite, a form similar to diamond but hexagonal. Fullerenes have a graphite-like structure, but instead of purely hexagonal packing, also contain pentagons (or possibly heptagons) of carbon atoms, which bend the sheet into spheres, ellipses or cylinders. The properties of fullerenes (also called "buckyballs" and "buckytubes") have not yet been fully analyzed. All the names of fullerenes are after Buckminster Fuller, developer of the geodesic dome, which mimics the structure of "buckyballs". A nanofoam allotrope has been discovered which is ferromagnetic. Carbon allotropes include:
- Amorphous carbon
- Carbon nanofoam (discovered in 1997)
- Carbon nanotube
- Diamond
- Fullerene
- Graphite
- Lonsdaleite
- Aggregated diamond nanorods (synthesised in 2005) The system of carbon allotropes spans a range of extremes. Between diamond and graphite:
- Graphite is soft and is used in pencils
- Diamond is the hardest mineral known to man (although aggregated diamond nanorods are now believed to be even harder), but graphite is one of the softest.
- Diamond is the ultimate abrasive, but graphite is a very good lubricant.
- Diamond is an excellent electrical insulator, but graphite is a conductor of electricity.
- Diamond is usually transparent, but graphite is opaque.
- Diamond crystallizes in the cubic system but graphite crystallizes in the hexagonal system. Between amorphous carbon and nanotubes:
- Amorphous carbon is among the easiest materials to synthesize, but carbon nanotubes are extremely expensive to make.
- Amorphous carbon is completely isotropic, but carbon nanotubes are among the most anisotropic materials ever produced.

Occurrence

There are nearly ten million carbon compounds known to science. Many thousands of these are vital to life processes. They are also many organic-based reactions of economic importance. Carbon is abundant in the sun, stars, comets, and in the atmospheres of most planets. Some meteorites contain microscopic diamonds that were formed when the solar system was still a protoplanetary disk. In combination with other elements, carbon is found the earth's atmosphere and dissolved in all water bodies. With smaller amounts of calcium, magnesium, and iron, it is a major component of very large masses carbonate rock (limestone, dolomite, marble etc.). When combined with hydrogen, carbon forms coal, petroleum, and natural gas which are called hydrocarbons. Graphite is found in large quantities in New York and Texas, the United States; Russia; Mexico; Greenland and India. Natural diamonds occur in the mineral kimberlite found in ancient volcanic "necks," or "pipes". Most diamond deposits are in Africa, notably in South Africa, Namibia, Botswana, the Republic of the Congo and Sierra Leone. There are also deposits in Arkansas, Canada, the Russian Arctic, Brazil and in Northern and Western Australia.

Organic compounds

The most prominent oxide of carbon is carbon dioxide, CO₂. This is a minor component of the Earth's atmosphere, produced and used by living things, and a common volatile elsewhere. In water it forms trace amounts of methanoic acid, HCO₂H, but as most compounds with multiple single-bonded oxygens on a single carbon it is unstable. Through this intermediate, though, resonance-stabilized carbonate ions are produced. Some important minerals are carbonates, notably calcite. Carbon disulfide, CS₂, is similar. The other oxides are carbon monoxide, CO, and the uncommon carbon suboxide, C₃O₂. Carbon monoxide is formed by incomplete combustion, and is a colorless, odorless gas. The molecules each contain a triple bond and are fairly polar, resulting in a tendency to bind permanently to haemoglobin molecules, so that the gas is highly poisonous. Cyanide, CN-, has a similar structure and behaves a lot like a halide ion; the nitride cyanogen, (CN)₂, is related. With reactive metals, such as tungsten, carbon forms either carbides, C^-, or acetylides, C₂^2- to form alloys with very high melting points. These anions are also associated with methane and acetylene, both very weak acids. All in all, with an electronegativity of 2.5, carbon prefers to form covalent bonds. A few carbides are covalent lattices, like carborundum, SiC, which resembles diamond.

Carbon chains

Carbon has the ability to form long chains with interconnecting C-C bonds. This property is called Catenation. Carbon-Carbon bonds are fairly strong, and abnormaly stable. This property is important as it allows carbon to form a huge number of compounds; if fact, there are more known carbon-containing compounds than all the other compounds of the chemical elements combined! The simplest form of an organic molecule is the hydrocarbon - a large family of organic molecules that, by definition, are composed of hydrogen atoms bonded to a chain of carbon atoms. Chain length, side chains and functional groups all affect the properties of organic molecules.

Carbon cycle

Under terrestrial conditions, conversion of one isotope to another is very rare. Therefore, for practical purposes, the amount of carbon on Earth is constant. Thus processes that use carbon must obtain it from somewhere, and dispose of it somewhere. The paths that carbon follows in the environment are called the carbon cycle. For example, plants draw carbon dioxide out of the environments and use it to build biomass. Some of this biomass is eaten by animals, where some of it is exhaled as carbon dioxide. The carbon cycle is considerably more complicated than this short loop; for example, some carbon dioxide is dissolved in the oceans; dead plant or animal matter may become sedimentary rock, and so forth.

Isotopes

Carbon has two stable, naturally-occurring isotopes: carbon-12, or ¹²C, (98.89%) and carbon-13, or ¹³C, (1.11%), and one unstable, naturally-occurring, radioisotope; carbon-14 or ¹⁴C. There are 15 known isotopes of carbon and the shortest-lived of these is ⁸C which decays through proton emission and alpha decay. It has a half-life of 1.98739x10^-21 s. In 1961 the International Union of Pure and Applied Chemistry adopted the isotope carbon-12 as the basis for atomic weights. Carbon-14 has a half-life of 5730 y and has been used extensively for radiocarbon dating carbonaceous materials.

Precautions

Carbon is relatively safe. Inhalation of fine soot in large quantities can be dangerous. Carbon may catch fire at very high temperatures and burn vigorously (as in the Windscale fire). There are a tremendous number of carbon compounds; some are lethally poisonous (cyanide, CN^-), and some are essential to life (dextrose).

References

- [http://lbruno.home.cern.ch/lbruno/documents/Bibliography/LHC_Note_78.pdf On Graphite Transformations at High Temperature and Pressure Induced by Absorption of the LHC Beam], J.M. Zazula, 1997
- WebElements.com and EnvironmentalChemistry.com per the guidelines at [http://en.wikipedia.org/wiki/Wikipedia:WikiProject_Elements Wikipedia's WikiProject Elements]

External links

- [http://periodic.lanl.gov/elements/6.html Los Alamos National Laboratory – Carbon]
- [http://www.webelements.com/webelements/elements/text/C/index.html WebElements.com – Carbon]
- [http://education.jlab.org/itselemental/ele006.html It's Elemental – Carbon]
- [http://www.vincentherr.com/cf/ – Carbon Fullerene and other Allotropes] models by Vincent Herr
- [http://invsee.asu.edu/nmodules/Carbonmod/everywhere.html Extensive Carbon page at asu.edu]
- [http://electrochem.cwru.edu/ed/encycl/art-c01-carbon.htm Electrochemical uses of carbon]
- [http://www.compchemwiki.org/index.php?title=Carbon Computational Chemistry Wiki] Category:Chemical elements Category:Nonmetals Category:Materials ko:탄소 ms:Karbon ja:炭素 simple:Carbon th:คาร์บอน

Nitrogen

Nitrogen is the chemical element in the periodic table that has the symbol N and atomic number 7. Commonly a colorless, odorless, tasteless and mostly inert diatomic non-metal gas, nitrogen constitutes 78 percent of Earth's atmosphere and is a constituent of all living tissues. Nitrogen forms many important compounds such as amino acids, ammonia, nitric acid, and cyanides.

Notable characteristics

Nitrogen is a non-metal, with an electronegativity of 3.0. It has five electrons in its outer shell, so is trivalent in most compounds. Pure nitrogen is an unreactive colorless diatomic gas at room temperature, and comprises about 78.08% of the Earth's atmosphere. It condenses at 77 K at atmospheric pressure and freezes at 63 K. Liquid nitrogen is a common cryogen.

Applications

Nitrogen Compounds

Molecular nitrogen in the atmosphere is relatively non-reactive, but in nature it is slowly converted into biologically (and industrially) useful compounds by some living organisms, notably certain bacteria (see Biological role below). The ability to combine or fix nitrogen is a key feature of modern industrial chemistry, where nitrogen (along with natural gas) is converted into ammonia (via the Haber process). Ammonia, in turn, can be used directly (primarily as a fertilizer), or as a precursor of many other important materials including explosives, largely via the production of nitric acid by the Ostwald process. The salts of nitric acid include important compounds like potassium nitrate (or saltpeter, important historically for its use in gunpowder) and ammonium nitrate, an important fertilizer. Various other nitrated organic compounds, such as nitroglycerin and trinitrotoluene, are used as explosives. Nitric acid is used as an oxidizer in liquid fueled rockets. Hydrazine and hydrazine derivatives find use as rocket fuels.

Molecular nitrogen (gas and liquid)

Nitrogen gas is readily produced by allowing liquid nitrogen (see below) to warm up and evaporate. It has a wide variety of applications, including serving as a more inert replacement for air where oxidation is undesirable;
- to preserve the freshness of packaged or bulk foods (by delaying rancidity and other forms of oxidative damage)
- on top of liquid explosives for safety It is also used in:
- the production of electronic parts such as transistors, diodes, and integrated circuits
- the manufacture of stainless steel
- filling automotive tires due to its inertness and lack of moisture or oxidative qualities, as opposed to air. A further example of its versitility is its use (as a preferred alternative to carbon dioxide) to pressurize kegs of some beers, particularly thicker stouts and Scottish and English ales, due to the smaller bubbles it produces, which make the dispensed beer smoother and headier. A modern application of a pressure sensitive nitrogen capsule known commonly as a "widget" now allows nitrogen charged beers to be packaged in cans and bottles. A very popular example of this is Guinness Draught. Liquid nitrogen is produced industrially in large quantities by distillation from liquid air and is often referred to by the quasi-formula LN₂. It is a cryogenic (extremely cold) fluid which can cause instant frostbite on direct contact with living tissue. When appropriately insulated from ambient heat it serves as a compact and readily transported source of nitrogen gas without pressurization. Further, its ability to maintain an unearthly temperature as it evaporates (77 K, -196 °C or -320 °F) makes it extremely useful in a wide range of applications as an open-cycle refrigerant, including;
- the immersion freezing and transportation of food products
- the preservation of bodies, reproductive cells (sperm and egg), and biological samples and materials
- in the study of cryogenics
- for demonstrations in science education
- in dermatology for removing unsightly or potentially malignant skin lesions,e.g., warts, actinic keratosis, etc.

History

Nitrogen (Latin nitrum, Greek Nitron meaning "native soda", "genes", "forming") is formally considered to have been discovered by Daniel Rutherford in 1772, who called it noxious air or fixed air. That there was a fraction of air that did not support combustion was well known to the late 18th century chemist. Nitrogen was also studied at about the same time by Carl Wilhelm Scheele, Henry Cavendish, and Joseph Priestley, who referred to it as burnt air or phlogisticated air. Nitrogen gas was inert enough that Antoine Lavoisier referred to it as azote, which stands for without life; this term has become the French word for "nitrogen" and later spread out to many other languages. Compounds of nitrogen were known in the Middle Ages. The alchemists knew nitric acid as aqua fortis. The mixture of nitric and hydrochloric acids was known as aqua regia, celebrated for its ability to dissolve gold. The earliest industrial and agricultural applications of nitrogen compounds used it in the form of saltpeter (sodium- or potassium nitrate), notably in gunpowder, and much later, as fertilizer, and later still, as a chemical feedstock.

Occurrence

Nitrogen is the largest single component of the Earth's atmosphere (78.084% by volume, 75.5% by weight) and is acquired for industrial purposes by the fractional distillation of liquid air or by mechanical means of gaseous air (i.e. pressurised reverse osmosis membrane or PSA (Pressure Swing Adsorption). Compounds that contain this element have been observed in outer space. Nitrogen-14 is created as part of the fusion processes in stars. Nitrogen is a large component of animal waste (for example, guano), usually in the form of urea, uric acid, and compounds of these nitrogenous products. Molecular nitrogen has been known to occur in Titan's atmosphere for some time, and has now been detected in interstellar space by David Knauth and coworkers using the Far Ultraviolet Spectroscopic Explorer.

Compounds

The main hydride of nitrogen is ammonia (NH₃) although hydrazine (N₂H₄) is also well known. Ammonia is somewhat more basic than water, and in solution forms ammonium ions (NH₄⁺). Liquid ammonia is in fact slightly amphiprotic and forms ammonium and amide ions (NH₂^-); both amides and nitride (N^3-) salts are known, but decompose in water. Singly and doubly substituted compounds of ammonia are called amines. Larger chains, rings and structures of nitrogen hydrides are also known but virtually unstable. Other classes of nitrogen anions are azides (N₃^-), which are linear and isoelectronic to carbon dioxide. Another molecule of the same structure is dinitrogen monoxide (N₂O), or laughing gas. This is one of a variety of oxides, the most prominent of which are nitrogen monoxide (NO) and nitrogen dioxide (NO₂), which both contain an unpaired electron. The latter shows some tendency to dimerize and is an important component of smog. The more standard oxides, dinitrogen trioxide (N₂O₃) and dinitrogen pentoxide (N₂O₅), are actually fairly unstable and explosive. The corresponding acids are nitrous (HNO₂) and nitric acid (HNO₃), with the corresponding salts called nitrites and nitrates. Nitric acid is one of the few acids stronger than hydronium.

Biological role

Nitrogen is an essential part of amino and nucleic acids which makes nitrogen vital to all life. Legumes like the soybean plant, can recover nitrogen directly from the atmosphere because their roots have nodules harboring microbes that do the actual conversion to ammonia in a process known as nitrogen fixation. The legume subsequently converts ammonia to nitrogen oxides and amino acids to form proteins.

Isotopes

There are two stable isotopes: N-14 and N-15. By far the most common is N-14 (99.634%), which is produced in the CNO cycle in stars. The rest is N-15. Of the ten isotopes produced synthetically, one has a half life of nine minutes and the remaining isotopes have half lives on the order of seconds or less. Biologically-mediated reactions (e.g., assimilation, nitrification, and denitrification) strongly control nitrogen dynamics in the soil. These reactions almost always result in N-15 enrichment of the substrate and depletion of the product. Although precipitation often contains subequal quantities of ammonium and nitrate, because ammonium is preferentially retained by the canopy relative to atmospheric nitrate, most of the atmospheric nitrogen that reaches the soil surface is in the form of nitrate. Soil nitrate is preferentially assimilated by tree roots relative to soil ammonium.

Precautions

Nitrate fertilizer washoff is a major source of ground water and river pollution. Cyano (-CN) containing compounds form extremely poisonous salts and are deadly to many animals and all mammals.

References

- [http://periodic.lanl.gov/elements/7.html Los Alamos National Laboratory – Nitrogen]

External links

- [http://www.webelements.com/webelements/elements/text/N/index.html WebElements.com – Nitrogen]
- [http://education.jlab.org/itselemental/ele007.html It's Elemental – Nitrogen]
- [http://www.sunysccc.edu/academic/mst/ptable/n.html Schenectady County Community College – Nitrogen]
- [http://www.uigi.com/nitrogen.html Nitrogen N2 Properties, Uses, Applications]
- [http://box27.bluehost.com/~edsanvil/wiki/index.php?title=Nitrogen_gas Computational Chemistry Wiki] Category:Nonmetals Category:Pnictogens Category:Nitrogen metabolism ko:질소 ja:窒素 simple:Nitrogen th:ไนโตรเจน

Morphine

Morphine (INN), the principal active agent in opium, is a powerful opioid analgesic drug. Like other opiates, morphine acts directly on the central nervous system (CNS) to relieve pain, and at synapses of the arcuate nucleus, in particular. Side effects include impairment of mental performance, euphoria, drowsiness, lethargy, and blurred vision. It also decreases hunger, inhibits the cough reflex, and produces constipation. Morphine is usually highly addictive, and tolerance and physical and psychological dependence develop quickly. Patients on morphine often report insomnia and nightmares. The word derives from Morpheus, the god of sleep in Greek mythology.

Medical use

Administration

Morphine may be given parenterally as subcutaneous, intravenous, or epidural injections. The military sometimes issues morphine loaded in an autoinjector. Morphine can also be administered through a slow-release transdermal patch. Orally, it comes as an elixir, concentrated solution, powder (for compounding) or in tablet form. Morphine is rarely supplied in suppository form. Due to its poor oral bioavailability, oral morphine is only one-sixth to one-third of the potency of parenteral morphine. Morphine is available in extended-release capsules for chronic administration, as well as immediate-release formulations.

Uses

Morphine is used legally —
- in the relief of acute, severe pain
- pain after surgery
- pain associated with trauma
- in the relief of moderate to severe chronic pain
- cancer pain
- tooth extraction
- as an adjunct to general anesthesia
- in epidural anesthesia
- for palliative care (i.e. to alleviate pain without curing the underlying reason for it)
- as an antitussive for severe cough
- as an antidiarrheal in chronic conditions (e.g., for diarrhea associated with AIDS)

Contraindications

- Acute pancreatitis (this may be a result of morphine use as well)
- Renal failure (due to accumulation of the metabolite morphine-6-glucuronide)

Legal classification

In the United Kingdom, morphine is listed as a Class A drug under the Misuse of Drugs Act 1971. In the United States, morphine is classified as a Schedule II drug under the Controlled Substances Act. Internationally, morphine is a Schedule I drug under the Single Convention on Narcotic Drugs[http://www.incb.org/pdf/e/list/yellow.pdf].

History

Morphine was first isolated in 1803 by the German pharmacist Friedrich Wilhelm Adam Serturner, who named it "morphium" after Morpheus, the Greek god of dreams. But it was not until the development of the hypodermic needle (1853) that its use spread. It was used for pain relief and, ironically, as a "cure" for opium or alcohol addiction. Its extensive use during the American Civil War resulted in over 400,000 sufferers from the "soldier's disease" (addiction). Heroin (diacetylmorphine) was derived from morphine in 1874. Along with other drugs, its possession without a prescription was criminalised in the US by the Harrison Narcotics Tax Act of 1914.

External links

- [http://wired.com/news/medtech/0,1286,65053,00.html?tw=wn_tophead_4 Morphine Apparently in Your Head] -- Wired Magazine article about endogenous production of morphine
- [http://www.emsb.qc.ca/laurenhill/science/morphine.html Morphine], [http://www.chm.bris.ac.uk/motm/motm.htm Molecule of the Month]. Category:Alkaloids Category:Analgesics Category:Ethers Category:Mu-opioid agonists Category:Natural opium alkaloids Category:Opioids Category:Phenols ms:Morfina ja:モルヒネ th:มอร์ฟีน

Codeine

:For the rock band of this name see Codeine (band). Codeine (INN) is an opioid used for its analgesic, antitussive and antidiarrheal properties. It is marketed as the salts codeine sulfate and codeine phosphate. Codeine is an alkaloid found in opium in concentrations ranging from 0.7 to 2.5 percent. While codeine can be extracted from opium, most codeine used in the United States is synthesized from morphine through the process of O-methylation.

Indications

Approved indications for codeine include:
- Cough, though its efficacy has been disputed (Schroeder & Fahey, 2001)
- Diarrhea
- Mild to moderate pain Codeine is sometimes marketed in combination preparations with paracetamol (co-codamol), aspirin (co-codaprin) or ibuprofen. These combinations provide greater pain relief than either agent used singly (q.v. Drug Synergy).

Controlled substance

In the United States, codeine is regulated by the Controlled Substances Act. It is a Schedule II controlled substance for pain-relief products containing codeine alone. In combination with aspirin or acetaminophen (paracetamol) it is listed as Schedule III. Codeine is also available outside the United States over-the-counter_substance (Schedule V) in liquid cough-relief formulations. Internationally, codeine is a Schedule II drug under the Single Convention on Narcotic Drugs.[http://www.incb.org/pdf/e/list/yellow.pdf] In the United Kingdom, codeine is regulated by the Misuse of Drugs Act 1971; it is a Class B Drug. In Australia and Canada, codeine is regulated, however it is available without prescription in combination preparations from licensed pharmacists in doses up to 12.5 mg/tablet.

Pharmacokinetics

Codeine is considered a prodrug, since it is metabolised in vivo to the principal active analgesic agent morphine. It is, however, less potent than morphine since only about 10% of the codeine is converted. It also has a correspondingly lower dependence-liability than morphine. Theoretically, a dose of approximately 200 mg (oral) of codeine must be administered to give equivalent analgesia to 30 mg (oral) of morphine (Rossi, 2004). It is not used, however, in single doses of greater than 60mg (and no more than 240 mg in 24 hours) since there is a ceiling effect. The conversion of codeine to morphine occurs in the liver and is catalysed by the cytochrome P450 enzyme CYP2D6. Approximately 6–10% of the Caucasian population have poorly functional CYP2D6 and codeine is virtually ineffective for analgesia in these patients (Rossi, 2004). Many of the adverse effects, however, are still experienced. Also, some medications are CYP2D6 inhibitors and reduce or even completely eliminate the efficacy of codeine. The most notorious of these are the selective serotonin reuptake inhibitors, such as fluoxetine (Prozac) and citalopram (Celexa).

Pharmacology

Codeine itself has weak affinity for the μ-opioid receptor. Its principal analgesic actions are mediated by the affinity of morphine for the μ-opioid receptor, though other therapeutic and adverse effects are produced by activation of other opioid receptors.

Adverse effects

Common adverse drug reactions (ADRs) associated with the use of codeine include: Itching, nausea, vomiting, drowsiness, dry mouth, miosis, orthostatic hypotension, urinary retention and constipation. (Rossi, 2004) Tolerance to many of the effects of codeine develop with prolonged use, including therapeutic effects. The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance. A potentially serious ADR, as with other opioids, is respiratory depression. This depression is dose-related and is the mechanism for the potentially fatal consequences of overdose.

Recreational use

Codeine is often used as a recreational drug. This may be due to its easy availability over-the-counter or on prescription in combination products (which, in the certain countries, are scheduled lower than codeine as a single-agent). People use it in order to obtain the euphoric effects associated with use of opioids.
- In certain areas of the United States; more specifically Texas, codeine syrup form is called Lean. It is commonly mixed with alcohol, or a blunt and smoked. It has been said this is done because it makes you "lean".
- In some countries, cough syrups and tablets containing codeine are available without prescription; people will frequently purchase it from multiple pharmacies so as not to incur suspicions. It is reported that in France, 95% of the consumption of Néo-codion cough preparation, containing codeine, cannot be attributed to medical use, but is rather used as a substitute for heroin. A heroin addict may use paracetamol to ward off the effects of a withdrawal [http://www.cedro-uva.org/lib/boekhout.heroine.fr.7.html]
- In the United Kingdom, people purchase tablets which combine codeine and paracetamol (acetaminophen), and consume these at higher-than-recommended doses, without apparent concern of the hepatotoxicity associated with large doses of paracetamol. Some may try to extract the codeine from the paracetamol through various methods, the most common and simplest being the cold water extraction.
- While the combination of codeine with paracetamol, at higher-than-recommended doses, can possibly cause hepatotoxicity (liver damage), combination with ibuprofen can result in kidney problems/failure and additional stomach pain and nausea and combination with aspirin can lead to internal hemorrhaging, particularly gastrointestinal hemorrhage. Certain codeine products are encountered on the illicit market, frequently in combination with carisoprodol. Combinations of codeine and glutethimide (Doriden) used to be fairly commonplace, but are almost unheard of today, due to the withdrawal of glutethimide products from the marketplace in the US and almost all other countries.

References

- Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.
- Schroeder K & Fahey T (2004). Over-the-counter medications for acute cough in children and adults in ambulatory settings. The Cochrane Database of Systematic Reviews 2004 (4), DOI:10.1002/14651858.CD001831.pub2.

Hydrocodone

Hydrocodone or dihydrocodeinone (marketed as Vicodin, Anexsia, Dicodid, Hycodan, Hycomine, Lorcet, Lortab, Norco, Tussionex, Vicoprofen) is an opioid derived from either of the naturally occurring opiates codeine or thebaine. Hydrocodone is an orally active narcotic analgesic and antitussive. The typical therapeutic dose of 5 to 10 mg is pharmacologically equivalent to 30 to 60 mg of oral codeine. Sales and production of this drug have increased significantly in recent years, as have diversion and illicit use. Hydrocodone is commonly available in tablet, capsule, and syrup form. As a narcotic, hydrocodone relieves pain by binding to opioid receptors in the brain and spinal cord. It may be taken with or without food, but should never be combined with alcohol. It may interact with monoamine oxidase inhibitors, as well as other drugs that cause drowsiness. It is in FDA pregnancy category C: its effect on an unborn embryo or fetus is not clearly known and pregnant women should consult their physicians before taking it. Common side effects include dizziness, lightheadedness, nausea, drowsiness, euphoria, vomiting, and constipation. Some less common side effects are allergic reaction, blood disorders, changes in mood, mental fogginess, anxiety, lethargy, difficulty urinating, spasm of the ureter, irregular or depressed respiration, and rash. Hydrocodone can be habit-forming, and can lead to physical and psychological addiction. In the U.S., pure hydrocodone and forms containing more than 15 mg per dosage unit are considered Schedule II drugs. Those containing less than 15 mg per dosage unit are Schedule III drugs. Hydrocodone is typically found in combination with other drugs such as Paracetamol (acetaminophen), Aspirin and homatropine methylbromide. In the UK it is listed as a Class A drug under the Misuse of Drugs Act 1971. The presence of acetaminophen in hydrocodone-containing products deters many drug users from taking excessive amounts. However, some users will get around this by extracting a portion of the acetaminophen using hot/cold water, taking advantage of the water-soluble element of the drug. It is not uncommon for addicts to have liver problems from taking excessive amounts of acetaminophen over a long period of time--taking 10–15 grams of acetaminophen in a period of 24 hours typically results in severe hepatotoxicity. It is this factor that leads many addicts to use only pure forms of opiates such as OxyContin. Symptoms of hydrocodone overdosage include respiratory depression, extreme somnolence, coma, stupor, cold/clammy skin, sometimes bradycardia, and hypotension. A severe overdose may involve circulatory collapse, cardiac arrest and/or death.

Notes

# Tarascon Pocket Pharmacopoeia.

External links

- [http://forum.opiophile.org/forumdisplay.php?f=9 Opiophile's Hydrocodone Forum] Category:Analgesics Category:Antitussives Category:Class A drugs Category:Opioids Category:Schedule II controlled substances Category:Schedule III controlled substances Category:Semisynthetic opioids

Hydromorphone

Overview

Hydromorphone is a drug used to relieve moderate to severe pain. Hydromorphone is known by the trade names Dilaudid® and Palladone®. It belongs to a category of drugs known as opioid agonists. It is commonly given to patients who have recently undergone surgery or who have suffered serious injury, and it is given intravenously, intramuscularly, rectally, or orally.

Details

Hydromorphone, a semi-synthetic μ-opioid agonist, is a hydrogenated ketone of morphine and shares the pharmacologic properties typical of opioid analgesics. Hydromorphone and related opioids produce their major effects on the central nervous system and gastrointestinal tract. These include analgesia, drowsiness, mental clouding, changes in mood, euphoria or dysphoria, respiratory depression, cough suppression, decreased gastrointestinal motility, nausea, vomiting, increased cerebrospinal fluid pressure, increased biliary pressure, pinpoint constriction of the pupils, increased parasympathetic activity and transient hyperglycemia. CNS depressants, such as other opioids, anesthetics, sedatives, hypnotics, barbiturates, phenothiazines, chloral hydrate and glutethimide may enhance the depressant effects of hydromorphone. MAO inhibitors (including procarbazine), first-generation antihistamines (brompheniramine, diphenhydramine, chlorpheniramine), beta-blockers and alcohol may also enhance the depressant effect of hydromorphone. When combined therapy is contemplated, the dose of one or both agents should be reduced.

Side Effects

Adverse effects of hydromorphone are similar to those of other opioid analgesics, and represent an extension of pharmacological effects of the drug class. The major hazards of hydromorphone include respiratory and CNS depression. To a lesser degree, circulatory depression, respiratory arrest, shock and cardiac arrest have occurred. The most frequently observed adverse effects are sedation, nausea, vomiting, constipation, lightheadedness, dizziness and sweating.

References

- [http://www.drugs.com/MTM/hydromorphone.html Hydromorphone Consumer Drug Information] Drugs.com.

Notes

# Vallner JJ, Stewart JT, Kotzan JA, Kirsten EB, Honigberg IL. "Pharmacokinetics and bioavailability of hydromorphone following intravenous and oral administration to human subjects." Journal of Clinical Pharmacology. 1981 Apr;21(4):152-6. PMID 6165742 [http://jcp.sagepub.com/cgi/reprint/21/4/152 Fulltext] Category:Analgesics Category:Semisynthetic opioids Category:Mu-opioid agonists

Oxymorphone

Oxymorphone is a powerful synthetic narcotic analgesic drug that is similar to morphine. Clinically, it is administered either via injection or suppository, typically in dosages of 1mg (injected) to 5mg (suppository). As a narcotic, oxymorphone can be habit forming, leading to addiction. __TOC__

Chemical Structure

The chemical structure of Oxymorphone could be also described as 14-Hydroxydihydromorphinone.

Usage

In some cases, it is used during pregnancy. Some veterinarians use the drug during animal operations, such as spaying/neutering or declawing. A semi-synthetic phenanthrene narcotic agonist, oxymorphone HCL occurs as odorless white crystals or white to off-white powder. It will darken in color with prolonged exposure to light. One gram of oxymorphone is soluble in 4ml of water and it is sparingly[?] in alcohol and ether. The commercially available injection has a pH of 2.7-4.5.

Legal Status

Oxymorphone is a C-II controlled substance.

Medicaments

Injectable opioid sedative/restraining agent, analgesic and preanesthetic DuPont markets oxymorphone under the trade name Numorphan.

References

Category:Opioids Category:Semisynthetic opioids

Naloxone

Naloxone is a drug used to counter the effects of overdosing on opioids such as heroin and morphine. Specifically, naloxone is used in opioid overdoses for countering life-threatening depression of the central nervous system and respiratory system. It is marketed under trade names including Narcan, Nalone, and Narcanti. The drug is derived from thebaine and has an extremely high affinity for μ-opioid receptors in the central nervous system. Naltrexone can be described as a substituted oxymorphone—here the tertiary amine methyl substituent is replaced with but-2-enyl. Naloxone is a μ-opioid receptor competitive antagonist, and its rapid blockade of those receptors often produces rapid onset of withdrawal symptoms. Naloxone also has an antagonist action, though with a lower affinity, at κ- and δ-opioid receptors. Naloxone is injected, usually initially intravenously for fastest action. The drug acts after about two minutes, and its effects may last about 45 minutes. Naloxone has been distributed as part of emergency kits to heroin addicts, and has been shown to reduce death rates. The drug also blocks the action of pain-lowering endorphins which the body produces naturally. The likely reason for this is that these endorphins operate on the same opioid receptors. In one experiment, women treated with naloxone reported higher pain levels during childbirth than women not so treated; in another experiment, the pain lowering effect of placebos was blocked if the placebos were administered along with naloxone. While naloxone is still often used in emergency treatments for opioid overdose, its clinical use in the long-term treatment of opioid addiction is being increasingly superseded by naltrexone. Naltrexone is structurally similar but has a slightly increased affinity for κ-opioid receptors over naloxone, can be administered orally and has a longer duration of action. The patent for Naloxone has expired and it is manufactured by various companies. The CAS number of naloxone is 465-65-6; the anhydrous hydrochloride salt has CAS 357-08-4 and the hydrochloride salt with 2 molecules of water has CAS 51481-60-8. Naloxone has sometimes been mistakenly called "naltrexate." Enteral naloxone has been successfully used in the reduction of gastritis and oesophagitis associated with opioid therapy in mechanically-ventilated acute care patients. (Meissner et al., 2004)

References

- Meissner W, Hartmann M, Kahler G, Brauer M (2004). Der Einfluss von enteralem Naloxon auf die Inzidenz von Gastritis und Ösophagitis bei opioidbehandelten Intensivpatienten: Doppelblinde plazebokontrollierte Studie. Anasthesiol Intensivmed Notfallmed Schmerzther 39 (9), 538-41. PMID 15334330

External link

- [http://www.inchem.org/documents/antidote/antidote/ant01.htm Report on Naloxone and other opiate antidotes], by the International Programme on Chemical Safety Category:Antidotes Category:Opioids Category:Opioid antagonists

Buprenorphine

Buprenorphine, also colloquially referred to as bupe, is an opioid drug with partial agonist and antagonist actions. Buprenorphine hydrochloride was first marketed in the 1980s by Reckitt & Colman (now Reckitt Benckiser) as an analgesic, yet is now primarily used for the treatment of opioid addiction. It is a Schedule III drug under the Convention on Psychotropic Substances[http://www.incb.org/pdf/e/list/green.pdf].

Commercial preparations

Britsh firm Reckitt & Colman (now Reckitt Benckiser) first marketed buprenorphine under the trade names Temgesic (sublingual/parenteral preparations, no active additives) and Buprenex (parenteral, no active additives). Two more recent formulations from Reckitt Benckiser have been approved for opioid addiction treatment in the U.S.: Subutex (lemon-lime flavored sublingual, no active additives; in 2mg, 4mg, and 8mg dosages) and Suboxone (orange-tang flavored sublingual, one part naloxone for every four parts buprenorphine; hexagon shaped tablet in 2mg, 4mg, and 8mg dosages). Suboxone contains the opioid antidote naloxone to deter illicit intravenous preparation of the tablet, and will seriously (though only temporarily) debilitate a user if injected.

Pharmacology and pharmacokinetics

Buprenorphine is a thebaine derivative, and its analgesic effect is due to partial agonist activity at μ-opioid receptors. Buprenorphine is also a κ-opioid receptor antagonist. The partial agonist activity means that opioid receptor antagonists (e.g., an antidote such as naloxone) only partially reverse the effects of buprenorphine. Buprenorphine hydrochloride is administered by intramuscular injection or intravenous infusion or as a sublingual tablet. It is not administered orally, due to very high first-pass metabolism. Buprenorphine is metabolised by the liver, via the CYP3A4 isozyme of the cytochrome p450 enzyme system, into norbuprenorphine (by N-dealkylation) and other metabolites. The metabolites are further conjugated with glucuronic acid and eliminated mainly through excretion into the bile. The elimination half-life of buprenorphine is 20.4–72.9 hours (mean 34.6).

Clinical use

Buprenorphine is indicated for the treatment of moderate to severe pain, peri-operative analgesia, and opioid dependence. It has a longer duration of action than morphine, and sublingual tablets offer an analgesic effect for 6 to 8 hours. (Joint Formulary Committee, 2004) Australian guidelines recommend against the use of buprenorphine as an analgesic because: its effect is not reversed by naloxone, it may precipitate withdrawal symptoms in people dependent on other opioids, and it may cause dependence itself and has potential for misuse. (Rossi, 2005) When used for opioid dependence, buprenorphine remains effective in the body for up to 48 hours, curbing withdrawal symptoms and counteracting other opioids that may be administered to the patient (licitly or illicitly).

Adverse effects

Common adverse drug reactions associated with the use of buprenorphine are similar to those of other opioids and include: nausea and vomiting, drowsiness, dizziness, headache, itch, dry mouth, miosis, orthostatic hypotension, urinary retention, and constipation. (Rossi, 2005) Hepatic necrosis and hepatitis with jaundice have been reported with the use of buprenorphine, and hepatic function is commonly monitored during buprenorphine therapy. The most severe and serious adverse reaction associated with opioid use in general is respiratory depression, the mechanism behind fatal overdose. This is particularly problematic with buprenorphine owing to the lack of an effective antagonist (antidote). As with other opioids, buprenorphine can produce both physical and psychological dependence. However, unlike other opioids, users of buprenorphine rarely develop a tolerance to the drug. Maintenance dosages can remain at the same moderate level indefinitely, and in many cases even lowered, without discomfort. Due to buprenorphine's unique chemistry[http://buprenorphine.samhsa.gov/about.html], raising the dosage will not result in a stronger analgesic effect after a certain point (around 16–32mg), beyond which the drug will actually have a reduced analgesic effect. The partial agonist/antagonist activity of buprenorphine means that it may precipitate opioid withdrawal symptoms when an opioid-dependent patient is commenced on the drug soon after the use of another opioid drug.

Dependence treatment

Buprenorphine sublingual preparations are often used in the management of opioid dependence (that is, dependence on heroin, oxycodone, hydrocodone, morphine, or other opioids). The Suboxone and Subutex preparations were approved for this indication by the United States FDA in October 2002. The use of opioid-replacement therapy in the management of opioid dependence is highly regulated, owing to the sometimes controversial nature of this aspect of harm reduction policy. In the United States, each approved prescriber is only allowed to manage 30 patients on buprenorphine. Similar restrictions are placed on prescribers in many other jurisdictions outside the U.S.

Buprenorphine vs. methadone

Buprenorphine and methadone are both used for short-term and long-term opioid maintenance therapy. Each agent has its relative advantages, and several are cited for buprenorphine. Buprenorphine sublingual tablets (Suboxone and Subutex) have a long duration of action which may allow dosing every two days, compared with the daily dosing required with methadone. In the United States, following initial management, a patient may be prescribed one month supply for self-administration on the condition that the patient receive other dependence therapy. Buprenorphine may have a lower dependence-liability than methadone. Buprenorphine treatment typically lasts several months (though sometimes for only a few weeks or up to two or three years), as opposed to an indefinite, often life-long methadone regimen. Buprenorphine itself appears to have less-severe withdrawal effects than methadone, and thus it is easier to discontinue use. Buprenorphine, as a partial μ-opioid receptor agonist, also has a reduced euphoric effect compared to the full agonist methadone, resulting in less illicit diversion of the drug. The Suboxone preparation contains the μ-opioid receptor antagonist naloxone which reverses the effect of common opioid drugs of abuse the patient may take, such as heroin, morphine or oxycodone. Since these drugs have little or no effect in patients being treated with Suboxone, risk of addiction relapse is greatly reduced provided the patient is compliant with medication.

Inpatient rehabilitation

The practice of using buprenorphine (Subutex or Suboxone) in an inpatient rehabilitation setting is increasing rapidly. These rehabilitation programs consist of "detox" and "treatment" phases. The detoxification ("detox") phase consists of medically-supervised withdrawal from the drug of dependency, sometimes aided by the use of medications such as buprenorphine and oxazepam. The treatment phase begins once the patient receives medical clearance and has completed the initial acute detoxification process. This portion of treatment is comprised of multiple therapy sessions, which include both group and individual counseling with various chemical dependency counselors, psychologists, psychiatrists, social workers, and other professionals. Additionally, many of these treatment centers strongly base their treatment models on 12-step fellowship traditions and principles, such as those practised by Alcoholics Anonymous and Narcotics Anonymous. Patients who enter rehabilitation voluntarily, as opposed to those who are court-ordered, can often choose a facility with the option of only staying for detox, or they can enter treatment facilities that provide the option to complete both detox and rehab. Completing both portions of the treatment increases the probability of success. Rehabilitation programs typically average about 28 days for primary care, but some may extend anywhere from 90 days to 6 months in an extended care unit. Buprenorphine is used only during the detox protocol with the purpose of reducing the patient's use of mood-altering substances. It considerably reduces opioid withdrawal symptoms that are normally experienced by opioid-dependent patients on cessation of those opioids, including diarrhea, vomiting, fever, chills, cold sweats, muscle and bone aches, muscle cramps and spasms, restless legs, agitation, gooseflesh, insomnia, nausea, watery eyes, runny nose and post-nasal drip, nightmares, etc. The buprenorphine detox protocol usually lasts about 7-10 days, provided that the patient does not need to be detoxed from any additional substances such as barbituates, benzodiazepines, or alcohol. During this time, Suboxone or Subutex will be administered by a nurse or doctor. Generally, the patient receives a single dose each day (despite the fact that a single dose lasts for up to 48 hours, medical professionals in many treatment facilities administer a dose every 24 hours to ensure a consistent active level of the medication remains in the patient's central nervous system). Typically, the initial daily dose totals around 8-16mg (of either Suboxone or Subutex). The dosage is slowly tapered each day and the medication is usually stopped 36-48 hours prior to the end of the detox program, with the patient's vitals monitored up until discharge from the detox program.

References

- Joint Formulary Committee (2004). British National Formulary (47th ed.). London: British Medical Association and Royal Pharmaceutical Society of Great Britain. ISBN 0-85369-584-9
- Rossi S (Ed.) (2005). Australian Medicines Handbook 2005. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-9-3

External links

- [http://www.wired.com/wired/archive/13.04/bupe.html The Bitter Pill], WIRED article on buprenorphine
- [http://www.wired.com/wired/archive/13.01/detox.html Instant Detox], earlier WIRED article on rapid detoxification, related to but not including buprenorphine
- [http://buprenorphine.samhsa.gov/ SAMHSA], federal U.S. buprenorphine program
- [http://buprenorphine.samhsa.gov/bwns_locator/index.html Government-run physician locator], listing of U.S. doctors who can prescribe buprenorphine
- [http://www.suboxone-directory.com/ Non-government physician locator], another listing of U.S. doctors who can prescribe buprenorphine
- [http://www.naabt.org/ National Alliance of Advocates for Buprenorphine Treatment, NAABT.org], non-profit educational site
- [http://www.suboxone.com Suboxone website], run by Reckitt Benckiser Category:Analgesics Category:Opioids Category:Oripavines Category:Schedule V controlled substances

Controlled Substances Act

The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. It can be found in amended form at 21 U.S.C. § 801 et. seq. (Chapter 13). This statute is the legal basis by which the manufacture, importation, possession, and distribution of certain drugs are regulated by the federal government of the United States. The Act also served as national implementing legislation for the Single Convention on Narcotic Drugs. The legislation created five Schedules (classifications), with varying qualifications for a drug to be included in each. Two federal departments, the Department of Justice and the Department of Health and Human Services (which includes the Food and Drug Administration) determine which drugs are added or removed from the various schedules; though the statute passed by Congress created the initial listing. Classification decisions are required to be made on the criteria of potential for abuse, accepted medical use in the United States, and potential for addiction. The Department of Justice is also the executive agency in charge of federal law enforcement (i.e. it is the federal police force). State governments also regulate certain drugs.

Enforcement authority

Proceedings to add, delete, or change the schedule of a drug or other substance may be initiated by the Drug Enforcement Administration (DEA), the Department of Health and Human Services (HHS), or by petition from any interested party, including the manufacturer of a drug, a medical society or association, a pharmacy association, a public interest group concerned with drug abuse, a state or local government agency, or an individual citizen. When a petition is received by the DEA, the agency begins its own investigation of the drug. The DEA also may begin an investigation of a drug at any time based upon information received from law enforcement laboratories, state and local law enforcement and regulatory agencies, or other sources of information. Once the DEA has collected the necessary data, the DEA Administrator, by authority of the Attorney General, requests from the HHS a scientific and medical evaluation and recommendation as to whether the drug or other substance should be controlled or removed from control. This request is sent to the Assistant Secretary of Health of the HHS. Then, the HHS solicits information from the Commissioner of the Food and Drug Administration and evaluations and recommendations from the National Institute on Drug Abuse, and on occasion, from the scientific and medical community at large. The Assistant Secretary, by authority of the Secretary, compiles the information and transmits back to the DEA a medical and scientific evaluation regarding the drug or other substance, a recommendation as to whether the drug should be controlled, and in what schedule it should be placed. The medical and scientific evaluations are binding to the DEA with respect to scientific and medical matters. The recommendation on scheduling is binding only to the extent that if HHS recommends that the substance not be controlled, the DEA may not control the substance. Once the DEA has received the scientific and medical evaluation from HHS, the Administrator will evaluate all available data and make a final decision whether to propose that a drug or other substance be controlled and into which schedule it should be placed. Under certain circumstances, the Government may temporarily schedule a drug without following the normal procedure. An example is when international treaties require control of a substance. In addition, 21 U.S.C. § 811(h) allows the Attorney General to temporarily place a substance in Schedule I "to avoid an imminent hazard to the public safety". Thirty days' notice is required before the order can be issued, and the scheduling expires after a year; however, the period may be extended six months if rulemaking proceedings to permanently schedule the drug are in progress. In any case, once these proceedings are complete, the temporary order is automatically vacated. The CSA also creates a closed system of distribution for those authorized to handle controlled substances. The cornerstone of this system is the registration of all those authorized by the DEA to handle controlled substances. All individuals and firms that are registered are required to maintain complete and accurate inventories and records of all transactions involving controlled substances, as well as security for the storage of controlled substances.

History

Since its enactment in 1970, the Act has been amended several times:
- The Psychotropic Substances Act of 1978 added provisions implementing the Convention on Psychotropic Substances.
- The Chemical Diversion and Trafficking Act of 1988 added provisions implementing the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.
- The Domestic Chemical Diversion and Control Act of 1993.
- The Federal Analog Act.

International law

The Congressional findings in 21 U.S.C. § 801(7), 21 U.S.C. § 801(a)(2), and 21 U.S.C. § 801(a)(3) state that a major purpose of the CSA is to "enable the United States to meet all of its obligations" under international treaties - specifically, the 1961 Single Convention on Narcotic Drugs and the 1971 Convention on Psychotropic Substances[http://www.usdoj.gov/dea/agency/csa.htm]. The CSA bears many resemblances to these Conventions. Both the CSA and the treaties set out a system for classifying controlled substances in several Schedules in accordance with the binding scientific and medical findings of a public health authority. Under [http://www.usdoj.gov/dea/pubs/csa/811.htm 21 U.S.C. § 811] of the CSA, that authority is the Secretary of Health and Human Services (HHS). Under [http://www.incb.org/e/conv/1961/articles.htm#3 Article 3] of the Single Convention and [http://www.incb.org/e/conv/1971/articles.htm#2 Article 2] of the Convention on Psychotropic Substances, the World Health Organization is that authority. 21 U.S.C. § 811(d) provides for automatic compliance with treaty obligations and establishes mechanisms for amending international drug control regulations to correspond with HHS findings on scientific and medical issues. If control of a substance is mandated by the Single Convention, the Attorney General is required to "issue an order controlling such drug under the schedule he deems most appropriate to carry out such obligations," without regard to the normal scheduling procedure or the findings of the HHS Secretary. However, the Secretary has great influence over any drug scheduling proposal under the Single Convention, because 21 USC § 811(d)(2)(B) requires the Secretary the power to "evaluate the proposal and furnish a recommendation to the Secretary of State which shall be binding on the representative of the United States in discussions and negotiations relating to the proposal." Similarly, if the UN Commission on Narcotic Drugs adds or transfers a substance to a Schedule established by the Convention on Psychotropic Substances, so that current U.S. regulations on the drug do not meet the treaty's requirements, the Secretary is required to issue a recommendation on how the substance should be scheduled under the CSA. If the Secretary agrees with the Commission's scheduling decision, he can recommend that the Attorney General initiate proceedings to reschedule the drug accordingly. If the HHS Secretary disagrees with the UN controls, however, the Attorney General must temporarily place the drug in Schedule IV or V (whichever meets the minimum requirements of the treaty) and exclude the substance from any regulations not mandated by the treaty, while the Secretary is required to request that the Secretary of State take action, through the Commission or the UN Economic and Social Council, to remove the drug from international control or transfer it to a different Schedule under the Convention. The temporary scheduling expires as soon as control is no longer needed to meet international treaty obligations. This provision was invoked in 1984 to place rohypnol in Schedule IV. The drug did not then meet the Controlled Substances Act's criteria for scheduling; however, control was required by the Convention on Psychotropic Substances. In 1999, an FDA official explained to Congress[http://www.hhs.gov/asl/testify/t990311b.html]: :Rohypnol is not approved or available for medical use in the United States, but it is temporarily controlled in Schedule IV pursuant to a treaty obligation under the 1971 Convention on Psychotropic Substances. At the time flunitrazepam was placed temporarily in Schedule IV (November 5, 1984), there was no evidence of abuse or trafficking of the drug in the United States. The Cato Institute's Handbook for Congress calls for repealing the CSA, an action that would likely bring the U.S. into conflict with international law[http://www.cato.org/pubs/handbook/hb108/hb108-17.pdf]. The exception would be if the U.S. were to claim that the treaty obligations violate the United States Constitution. Many articles in these treaties - such as [http://www.incb.org/e/conv/1961/articles_II.htm?#35 Article 35] and [http://www.incb.org/e/conv/1961/articles_II.htm?#36 Article 36] of the Single Convention - are prefaced with phrases such as "Having due regard to their constitutional, legal and administrative systems, the Parties shall . . ." or "Subject to its constitutional limitations, each Party shall . . ." According to former United Nations Drug Control Programme Chief of Demand Reduction Cindy Fazey, "This has been used by the USA not to implement part of article 3 of the 1988 Convention, which prevents inciting others to use narcotic or psychotropic drugs, on the basis that this would be in contravention of their constitutional amendment guaranteeing freedom of speech"[http://www.fuoriluogo.it/arretrati/2003/apr_17_en.htm].

Constitutional issues

Most of the Congressional findings and declarations in 21 U.S.C. § 801 are devoted to establishing the statute's constitutionality. Using similar language to Article I, Section 8 of the U.S. Constitution, the CSA cites the impact of intrastate drug offences on "interstate commerce" and the "general welfare" of the American people. However, David Boaz, executive director of the Cato Institute, claims that "The Tenth Amendment reserves to the states or the people all powers not granted to the federal government. At least the advocates of alcohol Prohibition had enough respect for the Constitution to seek a constitutional amendment to impose Prohibition, but Congress never asked the American people for the constitutional power to impose drug prohibition"[http://www.cato.org/dailys/3-03-97.html]. In 2003, the United States Court of Appeals for the Ninth Circuit ruled the CSA illegal as it applied to the use of medical marijuana in the case Raich v. Ashcroft, 352 F.3d 1222 (9th Cir. 2003). However, the case was appealed to the Supreme Court by the federal government, and in 2005, the Supreme Court ruled in favor of the federal government.

Drug Schedules

The below lists are incomplete. Cons

Paramorphine

Opium

Harvesting opium

Opium preparation

Seed Capsules

Chemical properties and physiological effects

History of opium

Medicinal uses

Other meanings

See also

External links

References

Photos

Carbon

Notable characteristics

Applications

Other uses

History and Etymology

Allotropes

Occurrence

Organic compounds

Carbon chains

Carbon cycle

Isotopes

Precautions

References

See also

External links

Nitrogen

Notable characteristics

Applications

Nitrogen Compounds

Molecular nitrogen (gas and liquid)

History

Occurrence

Compounds

Biological role

Isotopes

Precautions

See also

References

External links

Morphine

Medical use

Administration

Uses

Contraindications

Legal classification

History

External links

Codeine

Indications

Controlled substance

Pharmacokinetics

Pharmacology

Adverse effects

Recreational use

References

See also

Hydrocodone

Notes

External links

Hydromorphone

Overview

Details

Side Effects

References

Notes

Oxymorphone

Chemical Structure

Usage

Legal Status

Medicaments

References

Naloxone

References

External link

Buprenorphine

Commercial preparations

Pharmacology and pharmacokinetics