Zopiclone (brand name Zimovane and Imovane) is a nonbenzodiazepine hypnotic agent used in the treatment of insomnia. Zopiclone is molecularly different from the benzodiazepine drug and is classified as cyclopyrrolone. However, zopiclone improves the normal transmission of gamma-aminobutyric acid neurotransmitters in the central nervous system, through the modulation of benzodiazepine receptors in the same way as benzodiazepine drugs do.
Because zopiclone is soothing, it is marketed as a sleeping pill. It works by causing depression or tranquilizing the central nervous system. After long-term use, the body may become accustomed to the effects of zopiclone. When the dose is reduced or the drug is stopped suddenly, withdrawal symptoms may occur. This may include a variety of symptoms similar to the withdrawal of benzodiazepines. Although withdrawal from therapeutic doses of zopiclone and its isomers (ie eszopiclone) are usually not accompanied by seizures and are therefore not considered life-threatening, patients may experience significant agitation or anxiety so that they seek emergency medical attention.
In the United States, zopiclone is not commercially available, although its active stereoisomer, eszopiclone, is sold under the Lunesta name. Zopiclone is a controlled substance in the United States, Japan, Brazil, and some European countries, and may be illegal to have without a prescription. However, it is available in other countries where it is marketed under the brand name Imovane, and not controlled substances in oral tablet formulations available at 7.5 mg, 5 mg, and 3.75 mg.
Zopiclone is known colloquially as "Z-drug". Other Z-drugs include zaleplon (Sonata) and zolpidem (Ambien and AmbienCR) and are initially considered less addictive or habitual formers than benzodiazepines. However, this assessment has shifted somewhat in recent years as cases of addiction and habituation have been presented. Zopiclone is recommended to be taken in the short term, usually a week or less. Daily or continuous drug use is usually not recommended, and caution should be taken when these compounds are used in conjunction with antidepressants, sedatives or other drugs that affect the central nervous system.
Video Zopiclone
Medical use
Zopiclone is indicated for the treatment of short-term insomnia in which sleep initiation or sleep maintenance is a prominent symptom. Long-term use is not recommended, because tolerance, addiction, and addiction can occur with long-term use. One low-quality study found that zopiclone was not effective in improving sleep quality or increasing sleep time in shift workers - more research in this field has been recommended.
Elderly
Zopiclone, similar to benzodiazepines and other nonbenzodiazepine hypnotic drugs, causes impaired body balance and stands upright in individuals who wake up at night or the next morning. Falling and hip fractures are often reported. Combination with alcohol consumption increases this disorder. Partial, but incomplete tolerance develops into this disorder.
An extensive review of the medical literature on the management of insomnia and parents found that sufficient evidence of the effectiveness and lasting benefits of nondrug treatment for insomnia exist. Compared with benzodiazepines, nonbenzodiazepine hypnotic tranquilizers, such as zopiclone, offer little if any benefit in the efficacy or tolerability of the elderly. New agents such as melatonin receptor agonists may be more suitable and effective for the management of chronic insomnia in the elderly. The use of long-term hypnotic sedatives for insomnia has no evidence base and is not recommended for reasons that include concerns about adverse drug effects such as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and water plunge. In addition, the effectiveness and safety of long-term use of nonbenzodiazepine hypnotic drugs remains to be determined.
Maps Zopiclone
Adverse reactions
The British National Formulary states the following adverse reactions: "nausea, vomiting, dizziness, drowsiness, dry mouth, headache, rare amnesia, confusion, depression, hallucinations, nightmares, very rarely dizziness, incoordination, paradoxical effects [.] and sleep-walking are also reported ".
Contraindications
Zopiclone causes impaired driving skills similar to benzodiazepines. Long-term users of hypnotic medications for sleep disorders only develop partial tolerance for adverse effects on driving with hypnotic drug users even after 1 year of use still show an increase in motor vehicle accident rates. Patients riding in motor vehicles should not use zopiclone unless they stop driving due to a significant increase in the risk of accidents on zopiclone users. Zopiclone induces impaired psychomotor function. Driving or operating the machine should be avoided after taking zopiclone as the effect can be carried over to the next day, including impaired hand eye coordination.
Custom precautions
Alcohol should be avoided when using zopiclone, because alcohol and zopiclone increase the effects of each other and the risk of dependence may increase.
Patients with liver disease eliminate zopiclone much more slowly than normal patients and in addition to experiencing excessive pharmacological effects of the drug.
Zopiclone improves postural swing and increases the number of falls in the elderly, as well as cognitive side effects. Waterfalls are a significant cause of death in the elderly.
Patients who suffer from muscle weakness due to myasthenia gravis or have poor respiratory reserve due to severe chronic bronchitis, emphysema, or other lung disease, or have sleep apnea can not safely take zopiclone, nor can patients with disorders of the thyroid gland that are not treated.
EEG and sleep
Similarly for other hypnotic sedative drugs, zopiclone causes a decrease in core body temperature and is effective in reducing sleep latency. This led to similar changes in EEG readings and sleep architecture as benzodiazepines and caused disruption in sleep architecture in withdrawal as part of its reflective effect. Zopiclone reduces both delta waves and the number of high amplitude delta waves while increasing the low amplitude waves. Zopiclone reduces the total amount of time spent in REM sleep and delayed its onset. Cognitive behavioral therapy has been found to be superior to zopiclone in the treatment of insomnia and has been found to have long-term effects on sleep quality at least one year after therapy.
Pharmacology
The therapeutic pharmacological properties of zopiclone include hypnotic, anxiolytic, anticonvulsant, and myorelaxant properties. Zopiclone and benzodiazepines bind to the same site on receptors containing GABA A , causing increased GABA action to produce therapeutic effects and the detrimental effects of zopiclone. The zopiclone metabolite called desmethylzopiclone is also pharmacologically active, although it has the dominant anxiolytic properties. One study found little selectivity for zopiclone in subunit 1 and? 5, although it is considered not selective in binding to benzodiazepine receptors? 1,? 2,? 3, and? 5 GABA A complex. Desmethylzopiclone has been found to have partial agonist properties, unlike the parent drug zopiclone, which is a full agonist. The mechanism of action of zopiclone is similar to benzodiazepines, with the same effect on locomotor activity and on dopamine and serotonin turnover. A meta-analysis of randomized controlled trials comparing benzodiazepines with zopiclone or other Z drugs such as zolpidem and zaleplon has found some clear and consistent differences between zopiclone and benzodiazepines in sleep onset latency, total sleep duration, amount of awakening, sleep quality, side, tolerance, rebound insomnia, and daytime alertness. Zopiclone in the cyclopyrrolone drug family. Other cycloprrolone drugs include suriclone. Zopiclone, though molecularly different from benzodiazepines, has a pharmacological profile similar to that of benzodiazepines, including anxiolytic properties. The mechanism of action is to bind to the benzodiazepine site and act as a full agonist, which in turn positively modulates the benzodiazepine-sensitive GABA A benzodiazepine receptors and increases the binding of GABA on GABA A receptor to produce pharmacological properties of zoplastik. In addition to the pharmacological properties of zoplorozin, it also has several properties such as barbiturates.
In the EEG study, zopiclone significantly increased the beta frequency band energy and showed the characteristics of slow high-voltage waves, desynchronization of theta hippocampal waves, and increased energy from the delta frequency band. Zopiclone improves both stage 2 and slow-wave sleep (SWS), while zolpidem, the 1-selective compound, only increases SWS and does not cause any effect in stage 2 sleep. Zopiclone is less selective for site 1 and has a higher affinity to site 2 than zaleplon. Therefore, zopiclone is very similar to pharmacological for benzodiazepines.
Pharmacokinetics
After oral administration, zopiclone is absorbed rapidly, with bioavailability of about 75-80%. The time for peak plasma concentration is 1-2 hours. High-fat foods before administration of zopiclone do not alter absorption (as measured by AUC), but reduce plasma peak levels and delay its appearance, thus delaying therapeutic effects.
The binding of zopiclone plasma proteins has been reported to be weak, between 45 and 80% (mean 52-59%). It's fast and widely distributed to body tissues, including the brain, and excreted in urine, saliva, and breast milk. Zopiclone is partly metabolized extensively in the liver to form derivative derivatives active N ( N -desmethylzopiclone) and inactive zopiclone- N -oxide. Hepatic enzymes play the most important role in zopiclone metabolism are CYP3A4 and CYP2E1. In addition, about 50% of the doses administered are decarboxylated and are removed through the lungs. In urine, metabolites N -demethyl and N -oxide accounted for 30% of the initial dose. Between 7 and 10% of zopiclone are taken from the urine, indicating extensive metabolism of the drug before excretion. The removal of the zopiclone halfway terminal ranges from 3.5 to 6.5 hours (average 5 hours).
Zopiclone pharmacokinetics in humans is stereoselective. After oral administration of the racemic mixture, C max (time for maximum plasma concentration), the area under the plasma concentration time curve (AUC) and the elimination of the higher half-life terminals for the dextrorotatory enstrane, due to greater total looseness slow and smaller distribution volumes (corrected by bioavailability), compared with levorotatory enantiomers. In urine, the concentration of dextrorotatory enastomers from metabolite N -demethyl and N -oxide is higher than the associated antipodes.
Pharmacokinetics zopiclone is altered by aging and is affected by kidney and liver function. In severe chronic renal failure, the area under the curve value for zopiclone is greater and the half-life associated with elimination rates is longer, but these changes are not considered clinically significant. Genders and races have not been found to interact with zopiclone pharmacokinetics.
Interactions
Zopiclone also interacts with trimipramine and caffeine. Alcohol has additional effects when combined with zopiclone, increasing adverse effects including significant zarlon potential. Erythromycin appears to increase the rate of absorption of zopiclone and prolong the elimination half-life, leading to elevated plasma levels and a clearer effect. Itraconazole has the same effect on the pharmacokinetics of zopiclone as erythromycin. Parents may be very sensitive to the interaction of erythromycin and itraconazole drugs with zopiclone. Temporary dose reduction during joint therapy may be necessary, especially in the elderly. Rifampicin causes a very important decline in the zopiclone beak and peak plasma levels, which results in a substantial reduction in the zopiclone hypnotic effect. Phenytoin and carbamazepine can also provoke similar interactions. Ketoconazole and sulfaphenazole interfere with zopiclone metabolism. Nefazodone destroys zopiclone metabolism leading to elevated levels of zopiclone and marks sedation the next day.
History
Zopiclone was developed and first introduced in 1986 by RhÃÆ'Â'ne-Poulenc S.A., now part of Sanofi-Aventis, the world's major producer. Initially, it was promoted as an improvement in benzodiazepines, but recent meta-analyzes found it was no better than benzodiazepines in one of the assessed aspects. On April 4, 2005, the US Drug Enforcement Administration registered zopiclone on schedule IV, due to evidence that the drug had an addictive properties similar to benzodiazepines.
Zopiclone, traditionally sold worldwide, is a racemic mixture of two stereoisomers, only one active. In 2005, pharmaceutical company Sepracor of Marlborough, Massachusetts began marketing an active stereoisomer eszopiclone under the name Lunesta in the United States. This has the consequence of putting generic drugs in most of the world under the control of patents in the United States. Although it is expected to be available in generic form by 2010, there is no generic available there at the moment. However, zopiclone is currently available outside patents in a number of European countries, as well as Brazil, Canada, and Hong Kong. The difference in eszopiclone/zopiclone in the strongest eszopiclone dose doses contains 3 mg of therapeutic stereoisomers, whereas the highest dose of zopiclone (7.5 mg) contains 3.75 mg of active stereoisomers. Both agents have not been studied in a head-to-head clinical trial to determine potential clinical differences (efficacy, side effects, drug dependence, safety, etc.).
Use of recreation
Zopiclone has the potential for abuse and dose escalation, drug abuse, and drug dependence. It is abused verbally and sometimes intravenously, and is often combined with alcohol to achieve a combined sedative hypnotic euphoria. Patients who abuse these drugs are also at risk of dependency. Withdrawal symptoms can be seen after long-term use of normal doses even after a gradual decrease regimen. The Compendium of Pharmaceuticals and Specialties recommends zopiclone recipes not to exceed 7 to 10 days, due to an addiction, tolerance, and physical dependency concern. Two types of drug abuse may occur: recreational abuse, in which the drug is taken to achieve a high, or when the drug is continued long-term on medical advice. Zopiclone may be more addictive than benzodiazepines. Those with a history of substance abuse or mental health disorder may be at higher risk of high-dose zopiclone abuse. Abuse of high doses of zopiclone and increase in popularity among drug users who have been prescribed with zopiclone. Symptoms of zopiclone dependence can include depression, dysphoria, discouragement, slow thoughts, social isolation, worrying, sexual anhedonia, and anxiety.
Zopiclone and other sedative hypnotic drugs are often detected in the case of people suspected of driving under the influence of drugs. Other drugs, including benzodiazepines and zolpidem, are also found in large numbers suspected as an anesthetized driver. Many drivers have blood levels far exceeding therapeutic dose ranges and often combined with alcohol, illegal, or other prescription drugs, indicating a high potential for abuse of benzodiazepines, zolpidem, and zopiclone. Zopiclone, which at prescribed doses caused moderate damage the following day, has been estimated to increase the risk of vehicle accidents by 50%, leading to an increase of 503 over accidents per 100,000 people. Zaleplon or other non-active sleep aids are recommended to be used instead of zopiclone to reduce traffic accidents. Zopiclone like other hypnosis medicines is sometimes abused to commit criminal acts such as sexual assault.
Zopiclone has crosstolerance with barbiturates and is able to suppress signs of barbiturate withdrawal. This is often given intravenously in studies on monkeys, indicating a high potential risk of abuse.
Zopiclone is in the top ten drugs obtained by using fake recipes in France.
Overdose
Zopiclone is sometimes used as a method of suicide. It has a fatality index similar to benzodiazepine drugs, in addition to temazepam, which is highly toxic in overdose. Death occurs from an overdose of zopiclone, alone or in combination with other drugs. Overdose of zopiclone may present with excessive sedation and depressed respiratory function that may develop into coma and possibly death. Zopiclone combined with alcohol, opiates, or other central nervous system depressants may be more likely to cause a fatal overdose. Overdose Zopiclone can be treated with benzodiazepine receptor flumazenil antagonist, which replaces zopiclone from its binding site on the benzodiazepine receptor, thus rapidly reversing its effect. Serious cardiac effects can also occur from overdose of zopiclone when combined with piperazine.
The death certificate shows the number of deaths associated with zopiclone continues to rise. When taken alone, it is usually not fatal, but when mixed with alcohol or other drugs such as opioids, or in patients with respiratory disorders, or liver disorders, the risk of serious and fatal overdose increases.
Detection in biological fluid
Zopiclone can be measured in blood, plasma, or urine by chromatography. Plasma concentrations are usually less than 100 μg/l during therapeutic use, but often exceed 100 μg/l in automotive vehicle operators who are caught due to impaired driving ability and may exceed 1000 Âμg/l in patients with acute poisoning. Post mortem blood concentrations are usually in the range of 0.4-3.9 mg/l in fatal acute overdose victims.
See also
- Pazinaclone
References
External links
- Detailed pharmacological information
- Scheduling recommendations (PDF files)
- Details about scheduling
- Erowid zopiclone vault
- Support for addiction/addiction zopiclone
Source of the article : Wikipedia
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