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
The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1
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
Roussel Uclaf S. A. was one of several predecessor companies of today's Sanofi. It was the second largest French pharmaceutical company before it was acquired by Hoechst AG of Frankfurt, Germany in 1997, with pharmaceutical operations combined into the Hoechst Marion Roussel division in the United States. Roussel Uclaf's agrochemical operations had been transferred to Hoechst Schering AgrEvo GmbH in 1994. HMR subsequently merged in 1999 with Rhône-Poulenc to form Aventis, which merged in 2004 with Sanofi-Synthélabo to form Sanofi-Aventis, since renamed Sanofi. Hoechst Schering AgrEvo merged in 1999 with Rhône-Poulenc's agrochemical division to form Aventis CropScience, acquired by Bayer AG in 2002 and combined with Bayer's agrochemical division to form Bayer CropScience. In April 1980, as part of a formal research project at Roussel-Uclaf for the development of glucocorticoid receptor antagonists, chemist Georges Teutsch synthesized mifepristone. In October 1981, endocrinologist Étienne-Émile Baulieu, a consultant to Roussel-Uclaf, arranged tests of its use for medical abortion in eleven women in Switzerland by gynecologist Walter Herrmann at the University of Geneva's Cantonal Hospital, with successful results announced on April 19, 1982.
On October 9, 1987, following worldwide clinical trials in 20,000 women of mifepristone with a prostaglandin analogue for medical abortion, Roussel-Uclaf sought approval in France for their use for medical abortion, with approval announced on September 23, 1988. On October 21, 1988, in response to antiabortion protests and concerns of majority owner Hoechst AG of Germany, Roussel-Uclaf’s executives and board of directors voted 16 to 4 to stop distribution of mifepristone, which they announced on October 26, 1988. Two days the French government ordered Roussel-Uclaf to distribute mifepristone in the interests of public health. French Health Minister Claude Évin explained that: "I could not permit the abortion debate to deprive women of a product that represents medical progress. From the moment Government approval for the drug was granted, RU-486 became the moral property of women, not just the property of a drug company." Following use by 34,000 women in France from April 1988 to February 1990 of mifepristone distributed free of charge, Roussel-Uclaf began selling Mifegyne to hospitals in France in February 1990 at a price of $48 per 600 mg dose.
Mifegyne was subsequently approved in Great Britain on July 1, 1991, in Sweden in September 1992, but until his retirement in late April 1994, Hoechst AG chairman Wolfgang Hilger, a devout Roman Catholic, blocked any further expansion in availability. On May 16, 1994, Roussel-Uclaf announced that it was donating without remuneration all rights for medical uses of mifepristone in the U. S. to the Population Council, which subsequently licensed mifepristone to Danco Laboratories, a new single-product company immune to antiabortion boycotts, which won FDA approval as Mifeprex on September 28, 2000. On April 8, 1997, after buying the remaining 43.5% of Roussel-Uclaf stock in early 1997, Hoechst AG announced the end of its manufacture and sale of Mifegyne and the transfer of all rights for medical uses of mifepristone outside of the U. S. to Exelgyn S. A. a new single-product company immune to antiabortion boycotts, whose CEO was former Roussel-Uclaf CEO Édouard Sakiz. In 1999, Exelgyn won approval of Mifegyne in 11 additional countries, in 28 more countries over the following decade...
"Roussel takes off". Chemical Week. Pp. 60, 62. Cornwell, Rupert. "France: the mask of modernity". In Rowley, Anthony; the barons of European industry. London: Croom Helm. Pp. 5–22. ISBN 0-85664-105-7... "Roussel Uclaf". In Derdak, Thomas. International directory of company histories, Volume 1. Chicago: St. James Press. Pp. 669–670. ISBN 0-912289-10-4. Taggart, James. "The European pharmaceutical industry". The world pharmaceutical industry. London: Routledge. Pp. 316–370. ISBN 0-415-02500-1. Dougal, April S.. "Roussel Uclaf". In Kepos, Paula. International directory of company histories, Volume 8. Detroit: St. James Press. Pp. 451–453. ISBN 1-55862-323-X... "Hoechst Marion Roussel". The pharmaceutical industry: a history & calendar. West Lafayette: Bioanalytical Systems, Inc. Furio, Antoine. "Gaston Roussel to Sanofi-Aventis: nearly a century of Romainville pharmaceutical history and heritage". Heritage in Seine-Saint-Denis, No. 15. Bobigny: General Council of Seine-Saint-Denis... "History of Roussel laboratories". Paris: Society for the History of Pharmacy...
"Some dates". Romainville: Biocitech. Archived from the original on 2010-03-29. Kugener, André. "Opotherapie". Museum of Medical History. Luxembourg: Kugener.com. Rossignol, Sylvain. Notre usine est un roman. Paris: La Découverte. ISBN 2-7071-5462-8... "Photo gallery - Our factory is a novel". Paris: notreusineestunroman.com
A carbamate is an organic compound derived from carbamic acid. A carbamate group, carbamate ester, carbamic acids are functional groups that are inter-related structurally and are interconverted chemically. Carbamate esters are called urethanes. Carbamic acids are unstable. For example, ammonium carbamate is generated by treatment of ammonia with carbon dioxide 2 NH3 + CO2 → NH4Carbamates arise via alcoholysis of chloroformamides: R2NCCl + R'OH → R2NCO2R' + HClAlternatively, cabamates can be formed from chloroformates and amines: R'OCCl + R2NH → R2NCO2R' + HClCarbamates may be formed from the Curtius rearrangement, where isocyanates formed are reacted with an alcohol. RCON3 → RNCO + N2 RNCO + R′OH → RNHCO2R′ Although most of this article concerns organic carbamates, the inorganic salt ammonium carbamate is produced on a large scale as an intermediate in the production of the commodity chemical urea from ammonia and carbon dioxide; the N-terminal amino groups of valine residues in the α- and β-chains of deoxyhemoglobin exist as carbamates.
They help to stabilise the protein, when it becomes deoxyhemoglobin and increases the likelihood of the release of remaining oxygen molecules bound to the protein. This stabilizing effect should not be confused with the Bohr effect; the ε-amino groups of the lysine residues in urease and phosphotriesterase feature carbamate. The carbamate derived from aminoimidazole is an intermediate in the biosynthesis of inosine. Carbamoyl phosphate is generated from carboxyphosphate rather than CO2; the most important carbamate is the one involved in the capture of CO2 by plants since this process is necessary for their growth. The enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase fixes a molecule of carbon dioxide as phosphoglycerate in the Calvin cycle. At the active site of the enzyme, a Mg2+ ion is bound to glutamate and aspartate residues as well as a lysine carbamate; the carbamate is formed when an uncharged lysine side chain near the ion reacts with a carbon dioxide molecule from the air, which renders it charged, therefore, able to bind the Mg2+ ion.
Some of the most common amine protecting groups, such as BOC, FMOC, Cbz and troc are carbamates. The so-called carbamate insecticides feature the carbamate ester functional group. Included in this group are aldicarb, carbaryl, fenobucarb and methomyl; these insecticides kill insects by reversibly inactivating the enzyme acetylcholinesterase. The organophosphate pesticides inhibit this enzyme, although irreversibly, cause a more severe form of cholinergic poisoning. Fenoxycarb has a carbamate group but acts as a juvenile hormone mimic, rather than inactivating acetylcholinesterase; the insect repellent icaridin is a substituted carbamate. Carbamate nerve agentsWhile the carbamate acetylcholinesterase inhibitors are referred to as "carbamate insecticides" due to their high selectivity for insect acetylcholinesterase enzymes over the mammalian versions, the most potent compounds such as aldicarb and carbofuran are still capable of inhibiting mammalian acetylcholinesterase enzymes at low enough concentrations that they pose a significant risk of poisoning to humans when used in large amounts for agricultural applications.
Other carbamate based acetylcholinesterase inhibitors are known with higher toxicity to humans, some such as T-1123 and EA-3990 were investigated for potential military use as nerve agents. However, since all compounds of this type have a quaternary ammonium group with a permanent positive charge, they have poor blood-brain barrier penetration, are only stable as crystalline salts or aqueous solutions, so were not considered to have suitable properties for weaponisation. Polyurethanes contain multiple carbamate groups as part of their structure; the "urethane" in the name "polyurethane" refers to these carbamate groups. In contrast, the substance called "urethane", ethyl carbamate, is neither a component of polyurethanes, nor is it used in their manufacture. Urethanes are formed by reaction of an alcohol with an isocyanate. Urethanes made by a non-isocyanate route are called carbamates. Polyurethane polymers have a wide range of properties and are commercially available as foams and solids. Polyurethane polymers are made by combining diisocyanates, e.g. toluene diisocyanate, diols, where the carbamate groups are formed by reaction of the alcohols with the isocyanates: RN=C=O + R′OH → RNHCOR′ Iodopropynyl butylcarbamate is a wood and paint preservative and used in cosmetics.
Urethane was once produced commercially in the United States as a chemotherapy agent and for other medicinal purposes. It was found to be toxic and ineffective, it is used as a veterinary medicine. In addition, some carbamates are used in human pharmacotherapy, for example, the acetylcholinesterase inhibitors neostigmine and rivastigmine, whose chemical structure is based on the natural alkaloid physostigmine. Other examples are meprobamate and its derivatives like carisoprodol, felbamate and tybamate, a class of anxiolytic and muscle relaxant drugs used in the 1960s before the rise of benzodiazepines, still used nowadays in some cases. Carbachol is used for various ophthalmic purposes; the protease inhibitor darunavir for HIV treatment contains a carbamate functional group. Carbamate insecticides target human melatonin receptors, along with inhibiting acetylcholi
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.
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