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
Kiev or Kyiv is the capital and most populous city of Ukraine, located in the north-central part of the country on the Dnieper. The population in July 2015 was 2,887,974. Kiev is an important industrial, scientific and cultural center of Eastern Europe, it is home to many high-tech industries, higher education institutions, world-famous historical landmarks. The city has an extensive infrastructure and developed system of public transport, including the Kiev Metro; the city's name is said to derive from the name of one of its four legendary founders. During its history, one of the oldest cities in Eastern Europe, passed through several stages of great prominence and relative obscurity; the city existed as a commercial centre as early as the 5th century. A Slavic settlement on the great trade route between Scandinavia and Constantinople, Kiev was a tributary of the Khazars, until its capture by the Varangians in the mid-9th century. Under Varangian rule, the city became a capital of the first East Slavic state.
Destroyed during the Mongol invasions in 1240, the city lost most of its influence for the centuries to come. It was a provincial capital of marginal importance in the outskirts of the territories controlled by its powerful neighbours; the city prospered again during the Russian Empire's Industrial Revolution in the late 19th century. In 1917, after the Ukrainian National Republic declared independence from the Russian Empire, Kiev became its capital. From 1921 onwards Kiev was a city of the Ukrainian Soviet Socialist Republic, proclaimed by the Red Army, from 1934, Kiev was its capital. During World War II, the city again suffered significant damage, but recovered in the post-war years, remaining the third largest city of the Soviet Union. Following the collapse of the Soviet Union and Ukrainian independence in 1991, Kiev remained the capital of Ukraine and experienced a steady migration influx of ethnic Ukrainians from other regions of the country. During the country's transformation to a market economy and electoral democracy, Kiev has continued to be Ukraine's largest and richest city.
Kiev's armament-dependent industrial output fell after the Soviet collapse, adversely affecting science and technology. But new sectors of the economy such as services and finance facilitated Kiev's growth in salaries and investment, as well as providing continuous funding for the development of housing and urban infrastructure. Kiev emerged as the most pro-Western region of Ukraine where parties advocating tighter integration with the European Union dominate during elections. Kiev is the traditional and most used English name for the city; the Ukrainian government however uses Kyiv as the mandatory romanization where legislative and official acts are translated into English. As a prominent city with a long history, its English name was subject to gradual evolution; the early English spelling was derived from Old East Slavic form Kyjevŭ. The name is associated with that of the legendary eponymous founder of the city. Early English sources use various names, including Kiou, Kiew, Kiovia. On one of the oldest English maps of the region, Moscoviae et Tartariae published by Ortelius the name of the city is spelled Kiou.
On the 1650 map by Guillaume de Beauplan, the name of the city is Kiiow, the region was named Kÿowia. In the book Travels, by Joseph Marshall, the city is referred to as Kiovia; the form Kiev is based on Russian orthography and pronunciation, during a time when Kiev was in the Russian Empire. In English, Kiev was used in print as early as in 1804 in the John Cary's "New map of Europe, from the latest authorities" in "Cary's new universal atlas" published in London; the English travelogue titled New Russia: Journey from Riga to the Crimea by way of Kiev, by Mary Holderness was published in 1823. By 1883, the Oxford English Dictionary included Kiev in a quotation. Kyiv is the romanized version of the name of the city used in modern Ukrainian. Following independence in 1991, the Ukrainian government introduced the national rules for transliteration of geographic names from Ukrainian into English. According to the rules, the Ukrainian Київ transliterates into Kyiv; this has established the use of the spelling Kyiv in all official documents issued by the governmental authorities since October 1995.
The spelling is used by the United Nations, European Union, all English-speaking foreign diplomatic missions, several international organizations, Encarta encyclopedia, by some media in Ukraine. In October 2006, the United States Board on Geographic Names unanimously voted to change its standard transliteration to Kyiv, effective for the entire U. S. government, although'Kiev' remains the BGN conventional name for this city. The alternate romanizations Kyyiv and Kyjiv are in use in English-language atlases. Many major English-language news sources like the BBC, The New York Times continue to prefer Kiev, but others have adopted Kyiv in their style guides, including The Economist and The Guardian. Kiev, one of the oldest cities of Eastern Europe, played a pivotal role in the development of the medieval East Slavic civilization as well as in the modern Ukrainian nation. Scholars debate as to period of the foundation of the city: some date the founding to the late 9th century, other historians
Cytochromes P450 are proteins of the superfamily containing heme as a cofactor and, are hemeproteins. CYPs use a variety of large molecules as substrates in enzymatic reactions, they are, in general, the terminal oxidase enzymes in electron transfer chains, broadly categorized as P450-containing systems. The term "P450" is derived from the spectrophotometric peak at the wavelength of the absorption maximum of the enzyme when it is in the reduced state and complexed with carbon monoxide. CYP enzymes have been identified in all kingdoms of life: animals, fungi, bacteria, in viruses. However, they are not omnipresent. More than 50,000 distinct CYP proteins are known. Most CYPs require a protein partner to deliver one or more electrons to reduce the iron. Based on the nature of the electron transfer proteins, CYPs can be classified into several groups: Microsomal P450 systems, in which electrons are transferred from NADPH via cytochrome P450 reductase. Cytochrome b5 can contribute reducing power to this system after being reduced by cytochrome b5 reductase.
Mitochondrial P450 systems, which employ adrenodoxin reductase and adrenodoxin to transfer electrons from NADPH to P450. Bacterial P450 systems, which employ a ferredoxin reductase and a ferredoxin to transfer electrons to P450. CYB5R/cyb5/P450 systems, in which both electrons required by the CYP come from cytochrome b5. FMN/Fd/P450 systems found in Rhodococcus species, in which a FMN-domain-containing reductase is fused to the CYP. P450 only systems, which do not require external reducing power. Notable ones include thromboxane synthase, prostacyclin synthase, CYP74A; the most common reaction catalyzed by cytochromes P450 is a monooxygenase reaction, e.g. insertion of one atom of oxygen into the aliphatic position of an organic substrate while the other oxygen atom is reduced to water: RH + O2 + NADPH + H+ → ROH + H2O + NADP+ Many hydroxylation reactions use CYP enzymes. Genes encoding CYP enzymes, the enzymes themselves, are designated with the root symbol CYP for the superfamily, followed by a number indicating the gene family, a capital letter indicating the subfamily, another numeral for the individual gene.
The convention is to italicise the name. For example, CYP2E1 is the gene that encodes the enzyme CYP2E1—one of the enzymes involved in paracetamol metabolism; the CYP nomenclature is the official naming convention, although CYP450 or CYP450 is used synonymously. However, some gene or enzyme names for CYPs may differ from this nomenclature, denoting the catalytic activity and the name of the compound used as substrate. Examples include CYP5A1, thromboxane A2 synthase, abbreviated to TBXAS1, CYP51A1, lanosterol 14-α-demethylase, sometimes unofficially abbreviated to LDM according to its substrate and activity; the current nomenclature guidelines suggest that members of new CYP families share at least 40% amino acid identity, while members of subfamilies must share at least 55% amino acid identity. There are nomenclature committees that track both base gene names and allele names; the active site of cytochrome P450 contains a heme-iron center. The iron is tethered to the protein via a cysteine thiolate ligand.
This cysteine and several flanking residues are conserved in known CYPs and have the formal PROSITE signature consensus pattern - - x - - - - - C - -. Because of the vast variety of reactions catalyzed by CYPs, the activities and properties of the many CYPs differ in many aspects. In general, the P450 catalytic cycle proceeds as follows: Substrate binds in proximity to the heme group, on the side opposite to the axial thiolate. Substrate binding induces a change in the conformation of the active site displacing a water molecule from the distal axial coordination position of the heme iron, changing the state of the heme iron from low-spin to high-spin. Substrate binding induces electron transfer from NADH via cytochrome P450 reductase or another associated reductase. Molecular oxygen binds to the resulting ferrous heme center at the distal axial coordination position giving a dioxygen adduct not unlike oxy-myoglobin. A second electron is transferred, from either cytochrome P450 reductase, ferredoxins, or cytochrome b5, reducing the Fe-O2 adduct to give a short-lived peroxo state.
The peroxo group formed in step 4 is protonated twice, releasing one molecule of water and forming the reactive species referred to as P450 Compound 1. This reactive intermediate was isolated in 2010, P450 Compound 1 is an iron oxo species with an additional oxidizing equivalent delocalized over the porphyrin and thiolate ligands. Evidence for the alternative perferryl iron-oxo is lacking. Depending on the substrate and enzyme involved, P450 enzymes can catalyze any of a wide variety of reactions. A hypothetical hydroxylation is shown in this illustration. After the product has been released from the active site, the enzyme returns to its original state, with a water molecule returning to occupy the distal coordination position of the iron nucleus. An alternative route for mono-oxygenation is via the "peroxide shunt"; this pathway entails oxidation of the ferric-substrate complex with oxygen-atom donors such as peroxides and hypochlorites. A hypothetical peroxide "XOOH" is shown in the di
In chemistry, an alcohol is any organic compound in which the hydroxyl functional group is bound to a carbon. The term alcohol referred to the primary alcohol ethanol, used as a drug and is the main alcohol present in alcoholic beverages. An important class of alcohols, of which methanol and ethanol are the simplest members, includes all compounds for which the general formula is CnH2n+1OH, it is these simple monoalcohols. The suffix -ol appears in the IUPAC chemical name of all substances where the hydroxyl group is the functional group with the highest priority; when a higher priority group is present in the compound, the prefix hydroxy- is used in its IUPAC name. The suffix -ol in non-IUPAC names typically indicates that the substance is an alcohol. However, many substances that contain hydroxyl functional groups have names which include neither the suffix -ol, nor the prefix hydroxy-. Alcohol distillation originated in India. During 2000 BCE, people of India used. Alcohol distillation was known to Islamic chemists as early as the eighth century.
The Arab chemist, al-Kindi, unambiguously described the distillation of wine in a treatise titled as "The Book of the chemistry of Perfume and Distillations". The Persian physician, alchemist and philosopher Rhazes is credited with the discovery of ethanol; the word "alcohol" is from a powder used as an eyeliner. Al- is the Arabic definite article, equivalent to the in English. Alcohol was used for the fine powder produced by the sublimation of the natural mineral stibnite to form antimony trisulfide Sb2S3, it was considered to be the essence or "spirit" of this mineral. It was used as an antiseptic and cosmetic; the meaning of alcohol was extended to distilled substances in general, narrowed to ethanol, when "spirits" was a synonym for hard liquor. Bartholomew Traheron, in his 1543 translation of John of Vigo, introduces the word as a term used by "barbarous" authors for "fine powder." Vigo wrote: "the barbarous auctours use alcohol, or alcofoll, for moost fine poudre."The 1657 Lexicon Chymicum, by William Johnson glosses the word as "antimonium sive stibium."
By extension, the word came to refer to any fluid obtained by distillation, including "alcohol of wine," the distilled essence of wine. Libavius in Alchymia refers to "vini alcohol vel vinum alcalisatum". Johnson glosses alcohol vini as "quando omnis superfluitas vini a vino separatur, ita ut accensum ardeat donec totum consumatur, nihilque fæcum aut phlegmatis in fundo remaneat." The word's meaning became restricted to "spirit of wine" in the 18th century and was extended to the class of substances so-called as "alcohols" in modern chemistry after 1850. The term ethanol was invented 1892, combining the word ethane with the "-ol" ending of "alcohol". IUPAC nomenclature is used in scientific publications and where precise identification of the substance is important in cases where the relative complexity of the molecule does not make such a systematic name unwieldy. In naming simple alcohols, the name of the alkane chain loses the terminal e and adds the suffix -ol, e.g. as in "ethanol" from the alkane chain name "ethane".
When necessary, the position of the hydroxyl group is indicated by a number between the alkane name and the -ol: propan-1-ol for CH3CH2CH2OH, propan-2-ol for CH3CHCH3. If a higher priority group is present the prefix hydroxy-is used, e.g. as in 1-hydroxy-2-propanone. In cases where the OH functional group is bonded to an sp2 carbon on an aromatic ring the molecule is known as a phenol, is named using the IUPAC rules for naming phenols. In other less formal contexts, an alcohol is called with the name of the corresponding alkyl group followed by the word "alcohol", e.g. methyl alcohol, ethyl alcohol. Propyl alcohol may be n-propyl alcohol or isopropyl alcohol, depending on whether the hydroxyl group is bonded to the end or middle carbon on the straight propane chain; as described under systematic naming, if another group on the molecule takes priority, the alcohol moiety is indicated using the "hydroxy-" prefix. Alcohols are classified into primary and tertiary, based upon the number of carbon atoms connected to the carbon atom that bears the hydroxyl functional group.
The primary alcohols have general formulas RCH2OH. The simplest primary alcohol is methanol, for which R=H, the next is ethanol, for which R=CH3, the methyl group. Secondary alcohols are those of the form RR'CHOH, the simplest of, 2-propanol. For the tertiary alcohols the general form is RR'R"COH; the simplest example is tert-butanol, for which each of R, R', R" is CH3. In these shorthands, R, R', R" represent substituents, alkyl or other attached organic groups. In archaic nomenclature, alcohols can be named as derivatives of methanol using "-carbinol" as the ending. For instance, 3COH can be named trimethylcarbinol. Alcohols have a long history of myriad uses. For simple mono-alcohols, the focus on this article, the following are most important industrial alcohols: methanol for the production of formaldehyde and as a fuel additive ethanol for alcoholic beverages, fuel additive, solvent 1-propanol, 1-butanol, isobutyl alcohol for use as a solvent a
Activated carbon called activated charcoal, is a form of carbon processed to have small, low-volume pores that increase the surface area available for adsorption or chemical reactions. Activated is sometimes substituted with active. Due to its high degree of microporosity, one gram of activated carbon has a surface area in excess of 3,000 m2 as determined by gas adsorption. An activation level sufficient for useful application may be obtained from high surface area. Further chemical treatment enhances adsorption properties. Activated carbon is derived from charcoal and is sometimes used as biochar; when derived from coal or corn it is referred to as activated coal. Activated coke is derived from coke. Activated carbon is used in methane and hydrogen storage, air purification, gold purification, metal extraction, water purification, sewage treatment, air filters in gas masks and respirators, filters in compressed air, teeth whitening, many other applications. One major industrial application involves use of activated carbon in metal finishing for purification of electroplating solutions.
For example, it is the main purification technique for removing organic impurities from bright nickel plating solutions. A variety of organic chemicals are added to plating solutions for improving their deposit qualities and for enhancing properties like brightness, ductility, etc. Due to passage of direct current and electrolytic reactions of anodic oxidation and cathodic reduction, organic additives generate unwanted breakdown products in solution, their excessive build up can adversely affect plating quality and physical properties of deposited metal. Activated carbon treatment removes such impurities and restores plating performance to the desired level. Activated carbon is used to treat overdoses following oral ingestion. Tablets or capsules of activated carbon are used in many countries as an over-the-counter drug to treat diarrhea and flatulence. However, activated charcoal shows no effect of intestinal gas and diarrhea, is, medically ineffective if poisoning resulted from ingestion of corrosive agents such as alkalis and strong acids, boric acid, petroleum products, or alcohol.
Activated carbon will not prevent these chemicals from being absorbed into the human body. It is ineffective against poisonings of strong acids or alkali, iron, arsenic, ethanol or ethylene glycol. Incorrect application results in pulmonary aspiration, which can sometimes be fatal if immediate medical treatment is not initiated. Activated carbon, in 50% w/w combination with celite, is used as stationary phase in low-pressure chromatographic separation of carbohydrates using ethanol solutions as mobile phase in analytical or preparative protocols. Carbon adsorption has numerous applications in removing pollutants from air or water streams both in the field and in industrial processes such as: Spill cleanup Groundwater remediation Drinking water filtration Air purification Volatile organic compounds capture from painting, dry cleaning, gasoline dispensing operations, other processes. During early implementation of the 1974 Safe Drinking Water Act in the US, EPA officials developed a rule that proposed requiring drinking water treatment systems to use granular activated carbon.
Because of its high cost, the so-called GAC rule encountered strong opposition across the country from the water supply industry, including the largest water utilities in California. Hence, the agency set aside the rule. Activated carbon filtration is an effective water treatment method due to its multi-functional nature. There are specific types of activated carbon filtration methods and equipment that are indicated – depending upon the contaminants involved. Activated carbon is used for the measurement of radon concentration in air. Activated carbon is an allowed substance used by organic farmers in both livestock production and wine making. In livestock production it is used as a pesticide, animal feed additive, processing aid, nonagricultural ingredient and disinfectant. In organic winemaking, activated carbon is allowed for use as a processing agent to adsorb brown color pigments from white grape concentrates. Activated carbon filters can be used to filter vodka and whiskey of organic impurities which can affect color and odor.
Passing an organically impure vodka through an activated carbon filter at the proper flow rate will result in vodka with an identical alcohol content and increased organic purity, as judged by odor and taste. Research is being done testing various activated carbons' ability to store natural gas and hydrogen gas; the porous material acts like a sponge for different types of gases. The gas is attracted to the carbon material via Van der Waals forces; some carbons have been able to achieve bonding energies of 5–10 kJ per mol. The gas may be desorbed when subjected to higher temperatures and either combusted to do work or in the case of hydrogen gas extracted for use in a hydrogen fuel cell. Gas storage in activated carbons is an appealing gas storage method because the gas can be stored in a low pressure, low mass, low volume environment that would be much more feasible than bulky on-board pressure tanks in vehicles; the United States Department of Energy has specified certain goals to be achieved in the area of research and development of nano-porous carbon materials.
All of the goals are yet to be satisfied but numerous institutions, including the ALL-CRAFT program, are continuing to conduct work in this promising field. Filters with activated carbon are used in compressed air and gas purification to remove oil vapors, o
Corvalol is a tranquilizer based on the herb valerian root and the barbiturate phenobarbital, popular in Eastern Europe and the former Soviet Union as a heart medication. It is available as a transparent liquid with a characteristic strong aroma, as white bi-concave scored tablets. While not available for sale in the Western countries, Corvalol is sometimes brought over from Eastern Europe for self-administration to other countries of residence. Corvalol contains documented amounts of psychoactive chemicals, may interact with other prescription medications that a person is taking. Corvalol was developed in the USSR in 1960 as an analogue of the German drug - Valocordin, therefore it is copied in composition and action. Corvalol is labeled by the manufacturer for use in Neuroses with heightened irritability Insomnia As a part of complex treatment of hypertension Non-acute spasm of coronary vessels Tachycardia Gastrointestinal cramping Valerian extract, a component of corvalol, has been used in herbal medicine for insomnia and conditions associated with anxiety.
Phenobarbital is a barbiturate anticonvulsant used in epilepsy. There is no evidence to support the use of phenobarbital in cardiovascular or bronchospastic disease states. Due to lack of scientific evidence supported by randomized clinical trials in humans and its components should be used with caution in patients with serious cardiovascular conditions, such as hypertension, angina, or respiratory conditions such as asthma. Prescription medications that have been scientifically proved to be effective in these disease states should be preferred due to evidence supporting their clinical use. According to the American Geriatrics Society, phenobarbital should not be used in the elderly population due to high rate of physical dependence, tolerance to sleep benefits, the risk of overdose at low dosages. According to the manufacturer, overdose is possible due to accumulation of the ingredients when Corvalol is used and in large doses. Symptoms of overdose include central nervous system depression, dizziness and somnolence.
In serious cases overdose may result in breathing depression, arrhythmia, cardiovascular collapse, coma. Phenobarbital is a strong inducer of several hepatic cytochrome P450 enzymes, including CYP1A2, CYP2C9, CYP3A4 and others. One of the functions of these enzymes is to change the molecular structure of medications and other substances taken in by the human body. Taking phenobarbital-containing products, such as Corvalol, while taking other medications may reduce their effectiveness; some of the medications that may have decreased effectiveness when used with Corvalol are apixaban, clozapine, nifedipine and many others. Corvalol may increase CNS depressant effect of other hypnotics. Corvalol valerianate component of the preparation is purported to offer mild spasmolytic effects on the vasculature. Phenobarbital is a central nervous system depressant. According to the Farmak product label of Colvalol oral solution, the composition per 1 mL is as follows: Ethyl ester of α-bromoisovaleric acid — 20 mg Phenobarbital — 18.26 mg Peppermint oil — 1.42 mgInactive ingredients: stabilizer, ethanol 96%, purified water.
According to the Farmak product label, the composition of 1 tablet is as follows: Ethyl ester of α-bromoisovaleric acid — 12.42 mg Phenobarbital — 11.34 mg Peppermint oil — 0.88 mgInactive ingredients: lactose monohydrate, magnesium stearate, β-cyclodextrin, acesulfame potassium. Phenobarbital, one of the principal ingredients in Corvalol, is a DEA Schedule IV substance in the United States. Schedule IV substances have a low potential for abuse relative to substances in Schedules I–III. Examples of Schedule IV substances are alprazolam, clonazepam and others, it is illegal to import Corvalol into United States. In some countries of Eastern Europe, Corvalol is believed to be safe enough to use in recommended doses without prescription, it is used to treat elevated blood pressure and as a general-purpose tranquilizer/sedative. Despite the -lol suffix, the drug is not a beta-blocker. Corvalol is so common in Eastern Europe that, in 1996, the Ministry of Health of the Russian Federation included it in the list of mandatory items in all Russian passenger vehicle first aid kits, alongside such drugs as aspirin, metamizole sodium and activated charcoal.
The prototype of Corvalol, the original medicine Valokardin, is produced by Krewel Meuselbach GmbH in Germany as a sedative. Corvalol was produced by Kiev Chemical and Pharmaceutical Plant in Kiev, Ukraine in 1960-1991, by its successor, the Joint Stock Company "Farmak", from 1991 onward. Farmak owns the exclusive trade mark to the drug name in Ukraine and a number of countries of Eastern Europe and the former Soviet Union, but not in Russia, where Corvalol is available from a number of different drug companies; the manufacturer Farmak produces another similar product, similar in composition to Corvalol, but contains 0.2 mg hops oil per 1mL on tincture
Ukraine, sometimes called the Ukraine, is a country in Eastern Europe. Excluding Crimea, Ukraine has a population of about 42.5 million, making it the 32nd most populous country in the world. Its capital and largest city is Kiev. Ukrainian is the official language and its alphabet is Cyrillic; the dominant religions in the country are Greek Catholicism. Ukraine is in a territorial dispute with Russia over the Crimean Peninsula, which Russia annexed in 2014. Including Crimea, Ukraine has an area of 603,628 km2, making it the largest country within Europe and the 46th largest country in the world; the territory of modern Ukraine has been inhabited since 32,000 BC. During the Middle Ages, the area was a key centre of East Slavic culture, with the powerful state of Kievan Rus' forming the basis of Ukrainian identity. Following its fragmentation in the 13th century, the territory was contested and divided by a variety of powers, including Lithuania, Austria-Hungary, the Ottoman Empire and Russia. A Cossack republic emerged and prospered during the 17th and 18th centuries, but its territory was split between Poland and the Russian Empire, merged into the Russian-dominated Soviet Union in the late 1940s as the Ukrainian Soviet Socialist Republic.
In 1991 Ukraine gained its independence from the Soviet Union in the aftermath of its dissolution at the end of the Cold War. Before its independence, Ukraine was referred to in English as "The Ukraine", but most sources have since moved to drop "the" from the name of Ukraine in all uses. Following its independence, Ukraine declared itself a neutral state. In 2013, after the government of President Viktor Yanukovych had decided to suspend the Ukraine-European Union Association Agreement and seek closer economic ties with Russia, a several-months-long wave of demonstrations and protests known as the Euromaidan began, which escalated into the 2014 Ukrainian revolution that led to the overthrow of Yanukovych and the establishment of a new government; these events formed the background for the annexation of Crimea by Russia in March 2014, the War in Donbass in April 2014. On 1 January 2016, Ukraine applied the economic component of the Deep and Comprehensive Free Trade Area with the European Union.
Ukraine is ranks 88th on the Human Development Index. As of 2018, Ukraine has the second lowest GDP per capita in Europe. At US$40, it has the lowest median wealth per adult in the world, it suffers from a high poverty rate and severe corruption. However, because of its extensive fertile farmlands, Ukraine is one of the world's largest grain exporters. Ukraine maintains the second-largest military in Europe after that of Russia; the country is home to a multi-ethnic population, 77.8 percent of whom are Ukrainians, followed by a large Russian minority, as well as Georgians, Belarusians, Crimean Tatars, Jews and Hungarians. Ukraine is a unitary republic under a semi-presidential system with separate powers: legislative and judicial branches; the country is a member of the United Nations, the Council of Europe, the OSCE, the GUAM organization, one of the founding states of the Commonwealth of Independent States. There are different hypotheses as to the etymology of the name Ukraine. According to the older widespread hypothesis, it means "borderland", while some more recent linguistic studies claim a different meaning: "homeland" or "region, country"."The Ukraine" used to be the usual form in English, but since the Declaration of Independence of Ukraine, "the Ukraine" has become less common in the English-speaking world, style-guides recommend not using the definite article.
"The Ukraine" now implies disregard for the country's sovereignty, according to U. S. ambassador William Taylor. The Ukrainian position is that the usage of "'The Ukraine' is incorrect both grammatically and politically." Neanderthal settlement in Ukraine is seen in the Molodova archaeological sites which include a mammoth bone dwelling. The territory is considered to be the location for the human domestication of the horse. Modern human settlement in Ukraine and its vicinity dates back to 32,000 BC, with evidence of the Gravettian culture in the Crimean Mountains. By 4,500 BC, the Neolithic Cucuteni–Trypillia culture flourished in wide areas of modern Ukraine including Trypillia and the entire Dnieper-Dniester region. During the Iron Age, the land was inhabited by Cimmerians and Sarmatians. Between 700 BC and 200 BC it was Scythia. Beginning in the sixth century BC, colonies of Ancient Greece, Ancient Rome and the Byzantine Empire, such as Tyras and Chersonesus, were founded on the northeastern shore of the Black Sea.
These colonies thrived well into the 6th century AD. The Goths stayed in the area but came under the sway of the Huns from the 370s AD. In the 7th century AD, the territory of eastern Ukraine was the centre of Old Great Bulgaria. At the end of the century, the majority of Bulgar tribes migrated in different directions, the Khazars took over much of the land. In the 5th and 6th centuries, the Antes were located in the territory of; the Antes were the ancestors of Ukrainians: White Croats, Polans, Dulebes and Tiverians. Migrations from Ukraine throughout the Balkans established many Southern Slavic nations. Northern migrations, reaching to the Ilmen l