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Benzodiazepine

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Benzodiazepine drugs are substituted 1,4-benzodiazepines, although the chemical term can refer to many other compounds that do not have useful pharmacological properties. Different benzodiazepine drugs have different side groups attached to this central structure.

The different side groups affect the binding of the molecule to the GABA A receptor and so modulate the pharmacological properties. Nonbenzodiazepines also bind to the benzodiazepine binding site on the GABA A receptor and possess similar pharmacological properties.

While the nonbenzodiazepines are by definition structurally unrelated to the benzodiazepines, both classes of drugs possess a common pharmacophore see figure to the lower-right , which explains their binding to a common receptor site. The first benzodiazepine, chlordiazepoxide Librium , was synthesized in by Leo Sternbach while working at Hoffmann—La Roche on the development of tranquilizers.

The pharmacological properties of the compounds prepared initially were disappointing, and Sternbach abandoned the project. Two years later, in April , co-worker Earl Reeder noticed a "nicely crystalline" compound left over from the discontinued project while spring-cleaning in the lab.

This compound, later named chlordiazepoxide, had not been tested in because of Sternbach's focus on other issues. Expecting pharmacology results to be negative, and hoping to publish the chemistry-related findings, researchers submitted it for a standard battery of animal tests.

However, the compound showed very strong sedative , anticonvulsant , and muscle relaxant effects. These impressive clinical findings led to its speedy introduction throughout the world in under the brand name Librium. The introduction of benzodiazepines led to a decrease in the prescription of barbiturates , and by the s they had largely replaced the older drugs for sedative and hypnotic uses. The new group of drugs was initially greeted with optimism by the medical profession, but gradually concerns arose; in particular, the risk of dependence became evident in the s.

Benzodiazepines have a unique history in that they were responsible for the largest-ever class-action lawsuit against drug manufacturers in the United Kingdom, involving 14, patients and 1, law firms that alleged the manufacturers knew of the dependence potential but intentionally withheld this information from doctors.

At the same time, general practitioners and 50 health authorities were sued by patients to recover damages for the harmful effects of dependence and withdrawal. This led some doctors to require a signed consent form from their patients and to recommend that all patients be adequately warned of the risks of dependence and withdrawal before starting treatment with benzodiazepines.

This litigation led to changes in the British law , making class action lawsuits more difficult. Although antidepressants with anxiolytic properties have been introduced, and there is increasing awareness of the adverse effects of benzodiazepines, prescriptions for short-term anxiety relief have not significantly dropped. In the United States, benzodiazepines are Schedule IV drugs under the Federal Controlled Substances Act , even when not on the market for example, nitrazepam and bromazepam.

Flunitrazepam is subject to more stringent regulations in certain states and temazepam prescriptions require specially coded pads in certain states. In Canada, possession of benzodiazepines is legal for personal use. College of Physicians and Surgeons of British Columbia. In the United Kingdom, the benzodiazepines are Class C controlled drugs, carrying the maximum penalty of 7 years imprisonment, an unlimited fine or both for possession and a maximum penalty of 14 years imprisonment an unlimited fine or both for supplying benzodiazepines to others.

A prescription is needed for possession of all benzodiazepines. In East Asia and Southeast Asia, temazepam and nimetazepam are often heavily controlled and restricted. In certain countries, triazolam , flunitrazepam , flutoprazepam and midazolam are also restricted or controlled to certain degrees. Internationally, benzodiazepines are categorized as Schedule IV controlled drugs, apart from flunitrazepam, which is a Schedule III drug under the Convention on Psychotropic Substances.

Benzodiazepines are considered major drugs of abuse. British law requires that temazepam but not midazolam be stored in safe custody. Safe custody requirements ensures that pharmacists and doctors holding stock of temazepam must store it in securely fixed double-locked steel safety cabinets and maintain a written register, which must be bound and contain separate entries for temazepam and must be written in ink with no use of correction fluid although a written register is not required for temazepam in the United Kingdom.

Disposal of expired stock must be witnessed by a designated inspector either a local drug-enforcement police officer or official from health authority. Benzodiazepines are used recreationally and by problematic drug misusers. Mortality is higher among poly-drug misusers that also use benzodiazepines. Heavy alcohol use also increases mortality among poly-drug users. Long-term use has the potential to cause both physical and psychological dependence and severe withdrawal symptoms such as depression, anxiety often to the point of panic attacks , and agoraphobia.

Sharing syringes and needles for this purpose also brings up the possibility of transmission of hepatitis , HIV, and other diseases. Benzodiazepines are also misused intranasally , which may have additional health consequences.

Once benzodiazepine dependence has been established, a clinician usually converts the patient to an equivalent dose of diazepam before beginning a gradual reduction program. A — Australian police survey of detainees reported preliminary findings that self-reported users of benzodiazepines were less likely than non-user detainees to work full-time and more likely to receive government benefits, use methamphetamine or heroin, and be arrested or imprisoned.

Overall, anecdotal evidence suggests that temazepam may be the most psychologically habit-forming addictive benzodiazepine. Temazepam abuse reached epidemic proportions in some parts of the world, in particular, in Europe and Australia, and is a major drug of abuse in many Southeast Asian countries. This led authorities of various countries to place temazepam under a more restrictive legal status.

Some countries, such as Sweden, banned the drug outright. Benzodiazepines are used in veterinary practice in the treatment of various disorders and conditions.

As in humans, they are used in the first-line management of seizures , status epilepticus , and tetanus , and as maintenance therapy in epilepsy in particular, in cats.

From Wikipedia, the free encyclopedia. For the derivative drug of benzofuran , see Benzofury. The core structure of benzodiazepines. Effects of benzodiazepines on newborns. Benzodiazepine dependence , Benzodiazepine withdrawal syndrome , and post-acute withdrawal syndrome. This section needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the section and add the appropriate references if you can.

Unsourced or poorly sourced material may be challenged and removed. Benzodiazepine drug misuse and Drug-related crime. A Historical Dictionary of Psychiatry. Drugs Across the Spectrum. Integrated Pharmacology 2nd ed. In Schüttler J, Schwilden H. Handbook of Experimental Pharmacology. A Review of the Literature". Current Opinion in Psychiatry. Adverse Syndromes and Psychiatric Drugs: Oxford Handbook of Psychiatry 1st ed. Journal of the American Geriatrics Society.

Clinical management guidelines for obstetrician-gynecologists number 92, April replaces practice bulletin number 87, November Use of psychiatric medications during pregnancy and lactation".

Retrieved 1 September Pharmacoepidemiology and Drug Safety. The Journal of Clinical Psychiatry. Reviews in Neurological Diseases. The American Journal of Emergency Medicine. The frequent use of benzodiazepines for the treatment of anxiety is likely a reflection of their effectiveness, rapid onset of anxiolytic effect, and tolerability. National Collaborating Centre for Primary Care. The World Journal of Biological Psychiatry.

Retrieved July 12, National Institute for Health and Clinical Excellence. Management of anxiety disorders". Guidance on the use of zaleplon, zolpidem and zopiclone for the short-term management of insomnia" PDF. National Institute for Clinical Excellence.

Archived from the original PDF on Perspectives, Practices, and Research. Agency for Healthcare Research and Quality.

Food and Drug Administration. Clinical Guidelines and Evidence Review for the Epilepsies: Royal College of General Practitioners. The Cochrane Database of Systematic Reviews. Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie. Compendium of Continuing Education in Dentistry. Clinics in Podiatric Medicine and Surgery. Current Medical Research and Opinion. Oxford Handbook of Accident and Emergency Medicine 2nd ed. Journal of Affective Disorders. Cochrane Database of Systematic Reviews.

A review of the literature on sleep related disorders and abnormal sexual behaviors and experiences". Opinion of Brazilian experts]. Arquivos de Neuro-Psiquiatria in Portuguese. The Journal of ECT. Meyler's Side Effects of Drugs: Medicines and Healthcare products Regulatory Agency. Handbook of Drug Interactions: Introductory Clinical Pharmacology 8th ed. Clinics in Geriatric Medicine. The American Journal of Geriatric Pharmacotherapy.

Use of benzodiazepines among elderly patients" PDF. Prescribing for Elderly Patients. A literature review of epidemiological studies". Current Neurology and Neuroscience Reports.

Benzodiazepines—side effects, abuse risk and alternatives". Handbook of Psychiatric Drugs. Cambridge Handbook of Psychology, Health and Medicine 2nd ed. Journal of Consulting and Clinical Psychology. Behaviour Research and Therapy. Resident and Staff Physician. Journal of Psychiatric Research. Psychiatry and Clinical Neurosciences. Diagnostic and statistical manual of mental disorders: Shorter Oxford Textbook of Psychiatry 5th ed.

Oxford Handbook of Clinical Specialties. Journal of Substance Abuse Treatment. Desk Reference for Clinical Pharmacology 2nd ed. Journal of Clinical Sleep Medicine. A meta-analysis of observational studies". International Journal of Cancer. Additional progress was made with AV1 and the Open Media Alliance to achieve a video codec that performs better than existing solutions. Pocket currently has more than 10 million active monthly registered users and is integrated into hundreds of leading apps.

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The benefits of benzodiazepines are least and the risks are greatest in the elderly.

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Some of the other impairments reported were decreased IQ, visiomotor coordination, information processing, verbal learning and concentration. In terms of experimental basic science evidence, an analysis of carcinogenetic and genotoxicity data for various benzodiazepines has suggested a small possibility of carcinogenesis for a small number of benzodiazepines.

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