Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules; the original SMILES specification was initiated in the 1980s. It has since been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open standard called "OpenSMILES" was developed by the Blue Obelisk open-source chemistry community. Other'linear' notations include the Wiswesser Line Notation, ROSDAL and SLN. In July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol. Algorithms have been developed to generate the same SMILES string for a given molecule; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
Valerian is a perennial flowering plant native to Europe and Asia. In the summer when the mature plant may have a height of 1.5 metres, it bears sweetly scented pink or white flowers that attract many fly species hoverflies of the genus Eristalis. It is consumed as food including the grey pug. Crude extract of valerian root may have sedative and anxiolytic effects, is sold in dietary supplement capsules to promote sleep. Valerian has been used as a medicinal herb since at least the time of ancient Rome. Hippocrates described its properties, Galen prescribed it as a remedy for insomnia. In medieval Sweden, it was sometimes placed in the wedding clothes of the groom to ward off the "envy" of the elves. In the 16th century, the Anabaptist reformer Pilgram Marpeck prescribed valerian tea for a sick woman. John Gerard's Herball states that his contemporaries found Valerian "excellent for those burdened and for such as be troubled with croup and other like convulsions, for those that are bruised with falls."
He says that the dried root was valued as a medicine by the poor in the north of England and the south of Scotland, so that "no broth or pottage or physicall meats be worth anything if Setewale be not there."The seventeenth century astrological botanist Nicholas Culpeper thought the plant was "under the influence of Mercury, therefore hath a warming faculty." He recommended both herb and root, said that "the root boiled with liquorice and aniseed is good for those troubled with cough. It is of special value against the plague, the decoction thereof being drunk and the root smelled; the green herb being bruised and applied to the head taketh away pain and pricking thereof." The name of the herb is derived from the Latin verb valere. Other names used for this plant include garden valerian, garden heliotrope and all-heal. Red valerian grown in gardens, is sometimes referred to as "valerian", but is a different species, from the same family but not closely related. Known compounds detected in valerian that may contribute to its method of action are: Alkaloids: actinidine, shyanthine and valerine Isovaleramide may be created in the extraction process.
Gamma-aminobutyric acid Isovaleric acid Iridoids, including valepotriates: isovaltrate and valtrate Sesquiterpenes: valerenic acid, hydroxyvalerenic acid and acetoxyvalerenic acid Flavanones: hesperidin, 6-methylapigenin, linarin Because of valerian's historical use as a sedative, anticonvulsant, migraine treatment, pain reliever, most basic science research has been directed at the interaction of valerian constituents with the GABA receptor. Many studies remain all require clinical validation; the mechanism of action of valerian in general, as a mild sedative in particular, has not been elucidated. However, some of the GABA-analogs valerenic acids as components of the essential oil along with other semivolatile sesquiterpenoids are believed to have some affinity for the GABAA receptor, a class of receptors on which benzodiazepines are known to act. Valeric acid, responsible for the typical odor of older valerian roots, does not have any sedative properties. Valeric acid is related to valproic acid, a prescribed anticonvulsant.
Valerian contains isovaltrate, shown to be an inverse agonist for adenosine A1 receptor sites. This action does not contribute to the herb's possible sedative effects, which would be expected from an agonist, rather than an inverse agonist, at this particular binding site. Hydrophilic extractions of the herb sold over the counter, however do not contain significant amounts of isovaltrate. Valerenic acid in valerian stimulates serotonin receptors as a partial agonist, including 5-HT5A, implicated in the sleep-wake cycle; the chief constituent of valerian is a yellowish-green to brownish-yellow oil present in the dried root, varying in content from 0.5 to 2.0%. This variation in quantity may be determined by location; the volatile oils that form the active ingredient are pungent, somewhat reminiscent of well-matured cheese. Though some people remain partial to the earthy scent, some find it unpleasant, comparing the odor to that of unwashed feet. Although valerian is a common traditional medicine used for treating insomnia, there is no good evidence it is effective for this purpose.
Valerian is not helpful in treating anxiety. There is insufficient evidence for safety of valerian for anxiety disorders; the European Medicines Agency approved the health claim that valerian can be used as a traditional herbal medicine to relieve mild nervous tension and to aid sleep. In the United States, valerian extracts are sold as a nutritional supplement under the Dietary Supplement Health and Education Act of 1994. Oral forms are available in both unstandardized forms. Standardized products may be preferable considering the wide variation of the chemicals in the dried root, as noted above; when standardized, it is done so as a percentage of valeric acid. Because th
Oxazepam is a short-to-intermediate-acting benzodiazepine. Oxazepam is used for the treatment of anxiety and insomnia and in the control of symptoms of alcohol withdrawal syndrome, it is a metabolite of diazepam and temazepam, has moderate amnesic, anticonvulsant, hypnotic and skeletal muscle relaxant properties compared to other benzodiazepines. It was patented in 1962 and approved for medical use in 1964, it is an intermediate-acting benzodiazepine with a slow onset of action, so it is prescribed to individuals who have trouble staying asleep, rather than falling asleep. It is prescribed for anxiety disorders with associated tension and agitation, it is prescribed for drug and alcohol withdrawal, for anxiety associated with depression. Physicians may use oxazepam outside its approved indications to treat social phobia, post-traumatic stress disorder, premenstrual syndrome, other conditions; the side effects of oxazepam are similar to those of other benzodiazepines, may include dizziness, headache, memory impairment, paradoxical excitement, anterograde amnesia, but does not affect transient global amnesia.
Side effects due to rapid decrease in dose or abrupt withdrawal from oxazepam may include abdominal and muscle cramps, depression, inability to fall asleep or stay asleep, tremors, or vomiting. Oxazepam, as with other benzodiazepine drugs, can cause tolerance, physical dependence and benzodiazepine withdrawal syndrome. Withdrawal from oxazepam or other benzodiazepines leads to withdrawal symptoms which are similar to those seen during alcohol and barbiturate withdrawal; the higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can occur, though, at standard dosages and after short-term use. Benzodiazepine treatment should be discontinued as soon as possible by a slow and gradual dose reduction regimen. Oxazepam is contraindicated in myasthenia gravis, chronic obstructive pulmonary disease, limited pulmonary reserve, as well as severe hepatic disease. Benzodiazepines require special precautions if used in the elderly, during pregnancy, in children, alcohol- or drug-dependent individuals, individuals with comorbid psychiatric disorders.
Benzodiazepines including oxazepam are lipophilic drugs and penetrate membranes, so crosses over into the placenta with significant uptake of the drug. Use of benzodiazepines in late pregnancy high doses, may result in floppy infant syndrome. Oxazepam when taken during late in pregnancy, the third trimester, causes a definite risk to the neonate including a severe benzodiazepine withdrawal syndrome including hypotonia, reluctance to suck, to apnoeic spells and impaired metabolic responses to cold stress. Floppy infant syndrome and sedation in the newborn may occur. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth; as oxazepam is an active metabolite of diazepam, an overlap in possible interactions is with other drugs or food, with exception of the pharmacokinetic CYP450 interactions. Precautions and following the prescription are required when taking oxazepam in combinations with antidepressant medication, potent painkillers.
Concurrent use of these medicines can interact in a way, difficult to predict. Drinking alcohol when taking oxazepam is not recommended. Concomitant use of oxazepam and alcohol can lead to increased sedation, severe problems with coordination, decreased muscle tone, in severe cases or in predisposed patients to life-threatening intoxications with respiratory depression and collapse. Oxazepam is less toxic in overdose than other benzodiazepines. Important factors which affect the severity of a benzodiazepine overdose include the dose ingested, the age of the patient, health status prior to overdose. Benzodiazepine overdoses can be much more dangerous if a coingestion of other CNS depressants such as opiates or alcohol has occurred. Symptoms of an oxazepam overdose include: Respiratory depression Excessive somnolence Altered consciousness Central nervous system depression Occasionally cardiovascular and pulmonary toxicity Rarely, deep coma Oxazepam is an intermediate-acting benzodiazepine of the 3-hydroxy family.
The half-life of oxazepam is four to 15 hours. It has been shown to suppress cortisol levels. Oxazepam is the most absorbed and has the slowest onset of action of all the common benzodiazepines according to one British study. Oxazepam is an active metabolite formed during the breakdown of diazepam and certain similar drugs, it may be safer than many other benzodiazepines in patients with impaired liver function because it does not require hepatic oxidation, but rather, it is metabolized by glucuronidation, so oxazepam is less to accumulate and cause adverse reactions in the elderly or people with liver disease. Oxazepam is similar to lorazepam in this respect. Preferential storage of oxazepam occurs in some organs, including the heart of the neonate. Absorption by any administered route and the risk of accumulation is increased in the neonate, withdrawal of oxazepam during pregnancy and breast feedin
A drug is any substance that, when inhaled, smoked, absorbed via a patch on the skin, or dissolved under the tongue causes a physiological change in the body. In pharmacology, a drug is a chemical substance of known structure, other than a nutrient of an essential dietary ingredient, when administered to a living organism, produces a biological effect. A pharmaceutical drug called a medication or medicine, is a chemical substance used to treat, prevent, or diagnose a disease or to promote well-being. Traditionally drugs were obtained through extraction from medicinal plants, but more also by organic synthesis. Pharmaceutical drugs may be used for a limited duration, or on a regular basis for chronic disorders. Pharmaceutical drugs are classified into drug classes—groups of related drugs that have similar chemical structures, the same mechanism of action, a related mode of action, that are used to treat the same disease; the Anatomical Therapeutic Chemical Classification System, the most used drug classification system, assigns drugs a unique ATC code, an alphanumeric code that assigns it to specific drug classes within the ATC system.
Another major classification system is the Biopharmaceutics Classification System. This classifies drugs according to their permeability or absorption properties. Psychoactive drugs are chemical substances that affect the function of the central nervous system, altering perception, mood or consciousness, they include alcohol, a depressant, the stimulants nicotine and caffeine. These three are the most consumed psychoactive drugs worldwide and are considered recreational drugs since they are used for pleasure rather than medicinal purposes. Other recreational drugs include hallucinogens and amphetamines and some of these are used in spiritual or religious settings; some drugs can cause addiction and all drugs can have side effects. Excessive use of stimulants can promote stimulant psychosis. Many recreational drugs are illicit and international treaties such as the Single Convention on Narcotic Drugs exist for the purpose of their prohibition. In English, the noun "drug" is thought to originate from Old French "drogue" deriving into "droge-vate" from Middle Dutch meaning "dry barrels", referring to medicinal plants preserved in them.
The transitive verb "to drug" arose and invokes the psychoactive rather than medicinal properties of a substance. A medication or medicine is a drug taken to cure or ameliorate any symptoms of an illness or medical condition; the use may be as preventive medicine that has future benefits but does not treat any existing or pre-existing diseases or symptoms. Dispensing of medication is regulated by governments into three categories—over-the-counter medications, which are available in pharmacies and supermarkets without special restrictions. In the United Kingdom, behind-the-counter medicines are called pharmacy medicines which can only be sold in registered pharmacies, by or under the supervision of a pharmacist; these medications are designated by the letter P on the label. The range of medicines available without a prescription varies from country to country. Medications are produced by pharmaceutical companies and are patented to give the developer exclusive rights to produce them; those that are not patented are called generic drugs since they can be produced by other companies without restrictions or licenses from the patent holder.
Pharmaceutical drugs are categorised into drug classes. A group of drugs will share a similar chemical structure, or have the same mechanism of action, the same related mode of action or target the same illness or related illnesses; the Anatomical Therapeutic Chemical Classification System, the most used drug classification system, assigns drugs a unique ATC code, an alphanumeric code that assigns it to specific drug classes within the ATC system. Another major classification system is the Biopharmaceutics Classification System; this groups drugs according to their permeability or absorption properties. Some religions ethnic religions are based on the use of certain drugs, known as entheogens, which are hallucinogens,—psychedelics, dissociatives, or deliriants; some drugs used as entheogens include kava which can act as a stimulant, a sedative, a euphoriant and an anesthetic. The roots of the kava plant are used to produce a drink, consumed throughout the cultures of the Pacific Ocean; some shamans from different cultures use entheogens, defined as "generating the divine within" to achieve religious ecstasy.
Amazonian shamans use ayahuasca a hallucinogenic brew for this purpose. Mazatec shamans have a long and continuous tradition of religious use of Salvia divinorum a psychoactive plant, its use is to facilitate visionary states of consciousness during spiritual healing sessions. Silene undulata is used as an entheogen, its root is traditionally used to induce vivid lucid dreams during the initiation process of shamans, classifying it a occurring oneirogen similar to the more well-known dream herb Calea ternifolia. Peyote a small spineless cactus has been a
The scientific method is an empirical method of acquiring knowledge that has characterized the development of science since at least the 17th century. It involves careful observation, applying rigorous skepticism about what is observed, given that cognitive assumptions can distort how one interprets the observation, it involves formulating hypotheses, via induction, based on such observations. These are principles of the scientific method, as distinguished from a definitive series of steps applicable to all scientific enterprises. Though diverse models for the scientific method are available, there is in general a continuous process that includes observations about the natural world. People are inquisitive, so they come up with questions about things they see or hear, they develop ideas or hypotheses about why things are the way they are; the best hypotheses lead to predictions. The most conclusive testing of hypotheses comes from reasoning based on controlled experimental data. Depending on how well additional tests match the predictions, the original hypothesis may require refinement, expansion or rejection.
If a particular hypothesis becomes well supported, a general theory may be developed. Although procedures vary from one field of inquiry to another, they are the same from one to another; the process of the scientific method involves making conjectures, deriving predictions from them as logical consequences, carrying out experiments or empirical observations based on those predictions. A hypothesis is a conjecture, based on knowledge obtained while seeking answers to the question; the hypothesis might be specific, or it might be broad. Scientists test hypotheses by conducting experiments or studies. A scientific hypothesis must be falsifiable, implying that it is possible to identify a possible outcome of an experiment or observation that conflicts with predictions deduced from the hypothesis; the purpose of an experiment is to determine whether observations agree with or conflict with the predictions derived from a hypothesis. Experiments can take place anywhere from a garage to CERN's Large Hadron Collider.
There are difficulties in a formulaic statement of method, however. Though the scientific method is presented as a fixed sequence of steps, it represents rather a set of general principles. Not all steps take place in every scientific inquiry, they are not always in the same order; some philosophers and scientists have argued. Robert Nola and Howard Sankey remark that "For some, the whole idea of a theory of scientific method is yester-year's debate, the continuation of which can be summed up as yet more of the proverbial deceased equine castigation. We beg to differ." Important debates in the history of science concern rationalism as advocated by René Descartes. The term "scientific method" emerged in the 19th century, when a significant institutional development of science was taking place and terminologies establishing clear boundaries between science and non-science, such as "scientist" and "pseudoscience", appeared. Throughout the 1830s and 1850s, by which time Baconianism was popular, naturalists like William Whewell, John Herschel, John Stuart Mill engaged in debates over "induction" and "facts" and were focused on how to generate knowledge.
In the late 19th and early 20th centuries, a debate over realism vs. antirealism was conducted as powerful scientific theories extended beyond the realm of the observable. The term "scientific method" came into popular use in the twentieth century, popping up in dictionaries and science textbooks, although there was little scientific consensus over its meaning. Although there was a growth through the middle of the twentieth century, by the end of that century numerous influential philosophers of science like Thomas Kuhn and Paul Feyerabend had questioned the universality of the "scientific method" and in doing so replaced the notion of science as a homogeneous and universal method with that of it being a heterogeneous and local practice. In particular, Paul Feyerabend argued against there being any universal rules of science. Historian of science Daniel Thurs maintains that the scientific method is a myth or, at best, an idealization; the scientific method is the process. As in other areas of inquiry, science can build on previous knowledge and develop a more sophisticated understanding of its topics of study over time.
This model can be seen to underlie the scientific revolution. The ubiquitous element in the model of the scientific method is empiricism, or more epistemologic sensualism; this is in opposition to stringent forms of rationalism: the scientific method embodies that reason alone cannot solve a particular scientific problem. A strong formulation of the scientific method is not always aligned with a form of empiricism in which the empirical data is put forward in the form of experience or other abstracted forms of knowledge; the scientific method is of necessity als
Kava or kava kava or Piper methysticum is a crop of the Pacific Islands. The name kava is from Tongan and Marquesan, meaning "bitter". Kava is consumed throughout the Pacific Ocean cultures of Polynesia, including Hawaii and Vanuatu, Melanesia and some parts of Micronesia for its sedating effects; the root of the plant is used to produce a drink with sedative and euphoriant properties. Its active ingredients are called kavalactones. A Cochrane systematic review concluded it was to be more effective than placebo at treating short-term anxiety. Moderate consumption of kava has been deemed as presenting an "acceptably low level of health risk" by the World Health Organization. However, consumption of kava extracts produced with organic solvents or excessive amounts of poor quality kava products may be linked to an increased risk of adverse health outcomes. Kava is believed to have been domesticated in either Vanuatu by Papuans, it is believed to be a domesticated variety of Piper subbullatum, native to New Guinea and the Philippines.
It was spread by the Austronesian Lapita culture after contact eastward into the rest of Polynesia. It is not found in other Austronesian groups. Kava reached Hawaii. Consumption of kava is believed to be the reason why betel chewing, ubiquitous elsewhere, was lost for Austronesians in Oceania. According to Lynch, the reconstructed Proto-Polynesian term for the plant, *kava, was derived from the Proto-Oceanic term *kawaRi in the sense of a "bitter root" or "potent root ", it referred to Zingiber zerumbet, used to make a similar mildly psychoactive bitter drink in Austronesian rituals. Cognates for *kava include Pohnpeian sa-kau. In some languages, most notably Māori kawa, the cognates have come to mean "bitter", "sour", or "acrid" to the taste. In the Cook Islands, the reduplicated forms of kawakawa or kavakava are applied to the unrelated members of the genus Pittosporum, and in other languages like in Futunan, compound terms like kavakava atua refer to other species belonging to the genus Piper.
The reduplication of the base form is indicative of falsehood or likeness, in the sense of "false kava". In Aotearoa, it was applied to the kawakawa, endemic to Aotearoa and nearby Norfolk Island, Lord Howe Island, the Rangitāhua Islands, it was exploited by the Māori based on previous knowledge of the kava, as the latter could not survive in the colder climates of Aotearoa. The Māori name for the plant, reduplicated, it is a sacred tree among the Māori people. It is seen as a symbol of death, corresponding to the rangiora, the symbol of life. However, kawakawa has no psychoactive properties, its connection to kava is limited purely on similarity in appearance. Kava was grown only in the Pacific islands of Hawaii, Federated States of Micronesia, Fiji, the Samoas and Tonga. An inventory of P. methysticum distribution showed it was cultivated on numerous islands of Micronesia, Melanesia and Hawaii, whereas specimens of P. wichmannii were all from Papua New Guinea, the Solomon Islands, Vanuatu. The kava shrub thrives in well-drained soils where plenty of air reaches the roots.
It grows where rainfall is plentiful. Ideal growing conditions are 70–95 °F and 70–100% relative humidity. Too much sunlight is harmful in early growth, so kava is an understory crop. Kava cannot reproduce sexually. Female flowers are rare and do not produce fruit when hand-pollinated, its cultivation is by propagation from stem cuttings. Traditionally, plants are harvested around four years of age, as older plants have higher concentrations of kavalactones. After reaching about 2 m height, plants grow a wider stalk and additional stalks, but not much taller; the roots can reach a depth of 60 cm. Kava consists of sterile cultivars cloned from Piper wichmanii. Today it comprises hundreds of different cultivars grown across the Pacific; each cultivar has not only different requirements for successful cultivation, but displays unique characteristics both in terms of its appearance, in terms of its psychoactive properties. Scholars make a distinction between the so-called "noble" and non-noble kava; the latter category comprises medicinal kavas and wild kava.
Traditionally, only noble kavas have been used for regular consumption due to their more favourable composition of kavalactones and other compounds that produce more pleasant effects and have lower potential for causing negative side-effects, such as nausea or "kava hangover". The perceived benefits of noble cultivars explain why only these cultivars were spread around the Pacific by Polynesian and Melanesian migrants, with presence of non-noble cultivars limited to the islands of Vanuatu from which they originated. More it has been suggested that the widespread use of tudei cultivars in the manufacturing of several kava products might have been the key factor contributing to the rare reports of adverse reactions to kava observed among the consumers of kava-based products in Europe. Tudei v
Benzodiazepines, sometimes called "benzos", are a class of psychoactive drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. The first such drug, was discovered accidentally by Leo Sternbach in 1955, made available in 1960 by Hoffmann–La Roche, since 1963, has marketed the benzodiazepine diazepam. In 1977 benzodiazepines were globally the most prescribed medications, they are in the family of drugs known as minor tranquilizers. Benzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid at the GABAA receptor, resulting in sedative, anxiolytic and muscle relaxant properties. High doses of many shorter-acting benzodiazepines may cause anterograde amnesia and dissociation; these properties make benzodiazepines useful in treating anxiety, agitation, muscle spasms, alcohol withdrawal and as a premedication for medical or dental procedures. Benzodiazepines are categorized as either intermediary, or long-acting. Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia.
Benzodiazepines are viewed as safe and effective for short-term use, although cognitive impairment and paradoxical effects such as aggression or behavioral disinhibition occur. A minority of people can have paradoxical reactions such as worsened panic. Benzodiazepines are associated with increased risk of suicide. Long-term use is controversial because of concerns about decreasing effectiveness, physical dependence, an increased risk of dementia. Stopping benzodiazepines leads to improved physical and mental health; the elderly are at an increased risk of both short- and long-term adverse effects, as a result, all benzodiazepines are listed in the Beers List of inappropriate medications for older adults. There is controversy concerning the safety of benzodiazepines in pregnancy. While they are not major teratogens, uncertainty remains as to whether they cause cleft palate in a small number of babies and whether neurobehavioural effects occur as a result of prenatal exposure. Benzodiazepines can cause dangerous deep unconsciousness.
However, they are less toxic than their predecessors, the barbiturates, death results when a benzodiazepine is the only drug taken. When combined with other central nervous system depressants such as alcoholic drinks and opioids, the potential for toxicity and fatal overdose increases. Benzodiazepines are misused and taken in combination with other drugs of abuse. Benzodiazepines possess psycholeptic, hypnotic, anticonvulsant, muscle relaxant, amnesic actions, which are useful in a variety of indications such as alcohol dependence, anxiety disorders, panic and insomnia. Most are administered orally. In general, benzodiazepines are well-tolerated and are safe and effective drugs in the short term for a wide range of conditions. Tolerance can develop to their effects and there is a risk of dependence, upon discontinuation a withdrawal syndrome may occur; these factors, combined with other possible secondary effects after prolonged use such as psychomotor, cognitive, or memory impairments, limit their long-term applicability.
The effects of long-term use or misuse include the tendency to cause or worsen cognitive deficits and anxiety. The College of Physicians and Surgeons of British Columbia recommends discontinuing the usage of benzodiazepines in those on opioids and those who have used them long term. Benzodiazepines can have serious adverse health outcomes, these findings support clinical and regulatory efforts to reduce usage in combination with non-benzodiazepine receptor agonists; because of their effectiveness and rapid onset of anxiolytic action, benzodiazepines are used for the treatment of anxiety associated with panic disorder. However, there is disagreement among expert bodies regarding the long-term use of benzodiazepines for panic disorder; the views range from those that hold that benzodiazepines are not effective long-term and that they should be reserved for treatment-resistant cases to those that hold that they are as effective in the long term as selective serotonin reuptake inhibitors. The American Psychiatric Association guidelines note that, in general, benzodiazepines are well tolerated, their use for the initial treatment for panic disorder is supported by numerous controlled trials.
APA states that there is insufficient evidence to recommend any of the established panic disorder treatments over another. The choice of treatment between benzodiazepines, SSRIs, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, psychotherapy should be based on the patient's history and other individual characteristics. Selective serotonin reuptake inhibitors are to be the best choice of pharmacotherapy for many patients with panic disorder, but benzodiazepines are often used, some studies suggest that these medications are still used with greater frequency than the SSRIs. One advantage of benzodiazepines is that they alleviate the anxiety symptoms much faster than antidepressants, therefore may be preferred in patients for whom rapid symptom control is critical. However, this advantage is offset by the possibility of developing benzodiazepine dependence. APA does not recommend benzodiazepines for persons with depressive