Temazepam (brand name Restoril and Normison , among others) is medium-sized 3-hydroxy hypnotics of the benzodiazepine psychoactive drug class. This is the analogy of 3-hydroxy diazepam, and one of the main active metabolites of diazepam. In the US, temazepam is approved for the treatment of short-term insomnia. In addition, temazepam has anxiolytic (antianxiety), anticonvulsions, and skeletal muscle relaxation properties.
Temazepam was patented in 1965 and went on sale in the United States in 1981.
Video Temazepam
Medical use
In a sleep laboratory study, temazepam significantly reduces the amount awakened at night, but has the disadvantage of distorting normal sleep patterns. This is officially indicated for severe insomnia and other severe or paralyzing sleep disorders. Prescribing guidelines in the UK limit hypnosis to two to four weeks due to concerns of tolerance and dependence.
The United States Air Force uses temazepam as one of the hypnotists approved as a "travel ban" to help pilots and sleep specialists to support mission preparedness. "Land test" is required before the necessary authorization is issued to use the drug in operational situation, and a 12 hour restriction is imposed on the next flight operation. Other hypnotics used as "non-go pills" are zaleplon and zolpidem, which have shorter mandatory recovery periods.
Maps Temazepam
Contraindications
The use of temazepam should be avoided, if possible, in individuals with this condition:
- Ataxia (lack of coordination of muscle movement)
- Severe hypoventilation
- Acute narrow angle glaucoma
- Severe hepatic deficiency (hepatitis and liver cirrhosis decreases elimination by a factor of two)
- Severe renal deficiency (eg patients with dialysis)
- Sleep apnea
- Severe depression, especially if accompanied by suicidal tendencies
- acute intoxication with alcohol, narcotics, or other psychoactive substances
- Myasthenia gravis (an autoimmune disorder that causes muscle weakness)
- Hypersensitivity or allergy to any drug in the benzodiazepine class
Special caution is required
Temazepam should not be used in pregnancy, as it can cause damage to the fetus. The safety and effectiveness of temazepam has not been established in children; Therefore, temazepam should not generally be given to individuals under 18 years of age, and should not be used at all in children under six months of age. Benzodiazepines also require special attention when used in older people, alcohol-dependent individuals or drugs, and individuals with comorbid psychiatric disorders.
Temazepam, similar to benzodiazepines and other nonbenzodiazepine hypnotic drugs, causes disturbances in the balance of the body and stands upright in individuals who wake up at night or the next morning. Falling and hip fractures are often reported. Combination with alcohol increases this disorder. Partial but incomplete tolerance develops into this disorder. The smallest effective dose possible may be used in elderly or very sick patients, as the risk of apnea and/or cardiac arrest is present. This risk increases when temazepam is given in conjunction with other drugs that suppress the central nervous system (CNS).
People at high risk for abuse and dependency
Because benzodiazepines can be abused and cause dependence, their use should be avoided in people in certain high-risk groups. These groups include people with a history of alcohol or drug addiction, people are significantly struggling with their moods or people with long-term mental health difficulties. If temazepam should be prescribed for people in these groups, they should be closely monitored for signs of abuse and the development of dependence.
Adverse effects
General
The typical side effects of hypnotic benzodiazepines are associated with CNS depression, and include somnolence, sedation, drunkenness, dizziness, fatigue, ataxia, headache, lethargy, memory and learning disorders, longer reaction time and impaired motor function (including coordination problems ), slurred speech, decreased physical performance, numbing emotions, diminished alertness, muscle weakness, blurred vision (in higher doses), and lack of attention. Euphoria is rarely reported with its use. According to the US Food and Drug Administration, temazepam has a 1.5% euphoria incidence, much less commonly reported than headache and diarrhea. Anterograde amnesia can also occur, such as respiratory depression at higher doses.
Less common
Hyperhidrosis, hypotension, burning eyes, increased appetite, changes in libido, hallucinations, fainting, nystagmus, vomiting, pruritus, gastrointestinal disorders, nightmares, palpitations and paradoxical reactions including anxiety, aggression, violence, overstimulation and agitation have been reported,. (less than 0.5%).
Before taking temazepam, one should make sure at least 8 hours to sleep. Failure to do so may increase drug side effects.
Like all benzodiazepines, the use of this drug in combination with alcohol potentiates side effects, and can lead to toxicity and death.
Although rare, the effects of residual "hangover" after temazepam at night sometimes occur. These include drowsiness, psychomotor disorders and cognitive functioning that may progress to the next day, impaired users' ability to safely drive, and a possible increased risk of falling and hip fractures, especially in the elderly.
Tolerance
Chronic or excessive use of temazepam can lead to drug tolerance, which can develop rapidly, so this drug is not recommended for long-term use. In 1979, the Institute of Medicine (USA) and the National Institute on Drug Abuse stated that most hypnotics lose their sleep-inducing properties after about three to 14 days. In the use of more than one to two weeks, tolerance will progress quickly toward the ability of temazepam to maintain sleep, resulting in loss of effectiveness. Several studies have observed tolerance to temazepam after as little as one week of use. Another study investigated the short-term effects of temazepam accumulation for seven days in elderly inpatients, and found little tolerance developed during drug accumulation. Other studies examined the use of temazepam for six days and saw no evidence of tolerance. A study of 11 young male subjects showed significant tolerance for the effects of themazepam thermoregulation and the inducing properties of sleep after one week of 30-mg temazepam use. Body temperature correlates well with drugs that stimulate sleep or insomnia.
In one study, the sensitivity of drug people who had used temazepam for one to 20 years was no different from controls. An additional study, in which at least one of the authors was employed by several drug companies, examined the effectiveness of temazepam treatment in chronic insomnia for three months, and did not see drug tolerance, with the authors even suggesting the drug might be more effective than time.
Setting ongoing efficacy beyond a few weeks can be complicated by difficulties in distinguishing between the return of genuine insomnia complaints and withdrawal or rebound related insomnia. EEG sleep studies on hypnotic benzodiazepines show tolerance tends to occur completely after one to four weeks with EEG sleeping back to pre-treatment levels. The paper concludes, because of concerns about long-term use of both toxicity and tolerance and dependence, as well as controversy over long-term success, a wise planner should limit benzodiazepines for several weeks and avoid prescriptions that are sustainable for months or years. A literature review finding nonfarmacological treatment options is a more effective treatment option for insomnia because of their continuous improvement in sleep quality.
Physical dependency
Temazepam, like other benzodiazepine drugs, can cause physical dependence and addiction. Withdrawal from temazepam or other benzodiazepines after regular use often leads to benzodiazepine withdrawal syndrome, which resembles symptoms 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 also occur from standard doses and after short-term use. The sudden withdrawal of therapeutic doses of temazepam after prolonged use may lead to severe benzodiazepine withdrawal syndrome. Gradual and careful dosing reductions, preferably with long-acting benzodiazepines with long-acting active metabolites, such as chlordiazepoxide or diazepam, are recommended to prevent severe withdrawal syndrome developing. Other hypnotic benzodiazepines are not recommended. A study in mice found temazepam was cross-tolerant with barbiturates and was able to effectively replace barbiturates and suppress barbiturate withdrawal signs. Cases that are rarely reported in the medical literature of psychotic countries develop after the sudden withdrawal of benzodiazepines, even from therapeutic doses. Antipsychotics increase the severity of the effects of benzodiazepine withdrawal by increasing the intensity and severity of seizures. Patients admitted to the hospital with temazepam or nitrazepam continue to take this after leaving the hospital. The use of hypnotics in hospitals is recommended to be restricted to use only for five nights, to avoid the development of withdrawal symptoms such as insomnia.
Interactions
As with other benzodiazepines, temazepam produces a CNS-depressant additive effect when used with other drugs that also produce CNS depression, such as barbiturates, alcohols, opiates, tricyclic antidepressants, non-selective MAO inhibitors, phenothiazines and other antipsychotics, skeletal muscle relaxants, antihistamines, and anesthesia. Theophylline or aminophylline has been shown to reduce the sedative effects of temazepam and other benzodiazepines.
Unlike many benzodiazepines, pharmacokinetic interactions involving the P450 system have not been observed with temazepam. Temazepam showed no significant interaction with CYP3A4 inhibitors (eg iraconazole, erythromycin). Oral contraceptives can decrease the effectiveness of temazepam and accelerate the elimination half-life.
Overdose
Overdose of temazepam results in increased CNS effects, including:
- Somnolen (difficulty staying awake)
- Mind confusion
- Respiratory depression
- Hypotension
- Impaired motor function
- Impaired or absent reflexes
- Disrupted coordination
- Residual interruption
- Dizziness, Sedation
- Comes
- Off
Temazepam had the highest levels of drug poisoning, including overdose, among benzodiazepines common in cases with and without combination with alcohol in the 1985 study. Temazepam and nitrazepam were the two most frequently detected benzodiazepines in overdose-related deaths in the study of drug death in Australia. A 1993 study in the UK found temazepam had the highest number of deaths per million prescriptions among drugs prescribed in 1980 (11.9, versus 5.9 for benzodiazepines as a whole, taken with or without alcohol).
An Australian study in 1995 of hospitalized patients after benzodiazepine overdose confirmed this result, and found temazepam overdose was far more likely to cause coma than other benzodiazepines (odds ratio 1.86). The authors noted several factors, such as potential differences, receptor affinity, and rates of absorption between benzodiazepines, may explain this higher toxicity. Although benzodiazepines have a high therapeutic index, temazepam is one of the more dangerous classes of these drugs. The combination of alcohol and temazepam makes deaths due to alcohol poisoning more likely.
Pharmacology
Temazepam is a white crystalline substance, very little soluble in water, and slightly soluble in alcohol. The main pharmacological action is to increase the effects of gamma-aminobutyric acid neurotransmitter (GABA) on GABA receptors A . This results in sedation, motor damage, ataxia, ansiolysis, anticonvulsant effects, muscle relaxation, and reinforcement effects. As a drug before surgery, temazepam lowers cortisol in elderly patients. In mice, it triggers the release of vasopressin into the paraventricular nucleus of the hypothalamus and decreases ACTH release under pressure.
Pharmacokinetics
Oral administration of 15 to 45 mg of temazepam in humans results in rapid absorption with significant blood levels achieved in less than 30 minutes and peak levels at two to three hours. In the absorption study, the distribution, metabolism, and single and multiple excretion (ADME), using tritium-labeled drugs, temazepam is well absorbed and found to have minimal first-pass drug metabolism (8%). No active metabolite is formed and the only metabolite present in the blood is O-conjugate. Unchanged drug is 96% bound to plasma proteins. Decreased blood levels of biphasic parent drugs, with short half-lives ranging from 0.4 to 0.6 hours and terminal half-life from 3.5 to 18.4 hours (average 8.8 hours), depending on the study population and method determination.
Temazepam has excellent bioavailability, with almost 100% absorbed from the intestine. The drug is metabolized through conjugation and demetilation prior to excretion. Most drugs are excreted in the urine, with about 20% appearing in faeces. The main metabolite is O-conjugate of temazepam (90%); O-conjugate of N-desmethyl temazepam is a minor metabolite (7%).
History
Temazepam was synthesized in 1964, but it began to be used in 1981 when its ability to fight insomnia was manifested. In the late 1980s, temazepam was one of the most popular and widely prescribed hypnotics on the market and it became one of the most widely prescribed drugs.
Society and culture
Use of recreation
Temazepam is a drug with high potential for abuse.
Benzodiazepines have been abused either orally or intravenously. Different benzodiazepines have different potential abuses; the faster the plasma level increases after consumption, the greater the intoxicating effect and the more open to drug abuse. The rate of onset of a particular benzodiazepine action correlates well with the 'popularity' of the drug because of its misuse. The two most common reasons for preference are that benzodiazepine is 'strong' and it gives a good 'high'.
A study in 1995 found that temazepam was more rapidly absorbed and oxytocin was slower absorbed than most other benzodiazepines.
A 1985 study found that temazepam and triazolam maintained a much higher rate of self-injection than other benzodiazepines. This study examined and compared the responsibility for the misuse of temazepam, triazolam, diazepam, lorazepam, oxazepam, flurazepam, alprazolam, chlordiazepoxide, clonazepam, nitrazepam, flunitrazepam, bromazepam, and clorazepate. This study tested the level of self-injection in human subjects, baboons, and mice. All test subjects consistently demonstrated a strong preference for temazepam and triazolam over all residual benzodiazepines included in the study.
North America
In North America, temazepam misuse is not widespread. Other benzodiazepines are more commonly prescribed for insomnia. In the United States, temazepam is the fifth most prescribed benzodiazepine prescription. Individuals who abuse benzodiazepines get the drug by getting prescriptions from some doctors, prescription forgings, or buying pharmaceutical products that are diverted on the black market. North America has never had a serious problem with temazepam abuse, but is becoming increasingly vulnerable to the temazepam black trade.
Australia
Temazepam accounts for most of the benzodiazepines sought by prescription counterfeiting and through pharmaceutical theft in Victoria. Due to the widespread intravenous abuse, the Australian government decided to place it under a more stringent schedule than before, and since March 2004 temazepam capsules have been withdrawn from the Australian market, leaving only 10 mg of available tablets. Benzodiazepines are generally detected by Customs at ports and airports, arriving by post, also found occasionally in the trunk of air passengers, mostly small or medium (up to 200-300 tablets) for personal use. From 2003 to 2006, customs detected about 500 illegal imports of benzodiazepines per year, most often diazepam. The amount varies from one tablet to 2,000 tablets.
United Kingdom
In 1987, temazepam was the most abused legal prescription drug in the UK. The use of benzodiazepines by drug abusers is part of the pattern of polydrug abuse, but many of those who enter treatment facilities state that temazepam as their main abuse drug. Temazepam is the most commonly used benzodiazepine in a study published in 1994, injecting drug users in seven cities, and has been injected from the preparation of capsules, tablets and syrups. Increased use of heroin, often mixed with other drugs, most commonly including temazepam, diazepam, and alcohol, was a major factor in increased drug-related deaths in Glasgow and Edinburgh in 1990-1992. The use of Temazepam was primarily linked to violent or irregular behavior and contact with police in a 1997 study of young homeless people in Scotland. The BBC series Panorama features an episode titled "Temazepam Wars", dealing with the epidemic of temazepam abuse and related crime directly in Paisley, Scotland.
Medical research issues
The Journal of Clinical Sleep Medicine published a paper expressing concerns about benzodiazepine receptor agonist drugs, benzodiazepines and Z-drugs used as hypnotics in humans. This paper cites a systematic review of the medical literature on insomnia medications and states almost all experiments of sleep disorders and pharmaceutical drugs sponsored by the pharmaceutical industry, while this does not occur in general medicine or psychiatry. This cites another study that "found that odds ratios to find favorable outcomes for industry in industry-sponsored trials were 3.6 times higher than in non-sponsored industry studies". Issues discussed in industry-sponsored studies include: the ratio of drugs to placebo, but not to alternative treatments; unpublished studies with poor results; and trials held around the baseline placebo followed by drug therapy, but not matched by controlled parallel-placebo studies. Citing a 1979 report that too little research on hypnotics is independent of drug manufacturers, the authors conclude, "communities desperately need the same assessment of the benefits and risks of hypnosis" and NIH and VA should provide leadership for that purpose.
Street term
The street term for temazepam includes king kong pills (formerly called barbiturates, now more commonly referred to as temazepam), jelly, jelly, Edinburgh eccies, tams, terms, mazzies, temazies, tammies, temmies, nuts, eggs, green eggs, Knockouts, robbers, terminators, red and blue, no-gos, num num, blackout, green devils, drunken pills, brainwashing, mind wipe, neurotrashers , tem-tem's (combined with buprenorphine), great mother aide, vitamin T, large T, TZ, Resties (North America) and others. In Northeast England "The Mazepam" has become popular with the word for temazepam in recent months.
Availability
Temazepam is available in English-speaking countries with the following brand names:
- Euhypnos
- Normison
- Norkotral
- Nortem
- Remestant
- Restoril
- Temaze
- Temtab
- Tenox
In Spain, the drug is sold as a 'temzpem'. In Hungary, the drug is sold as Signopam.
Legal status
In Austria, temazepam is listed on UN71 Schedule III under the 1997 Psychotropic Regulations. This drug is considered to have high potential for abuse and addiction, but has received medical use for the treatment of severe insomnia.
In Australia, temazepam is Schedule 4 - Prescription Drugs Only. It is mainly used for the treatment of insomnia, and is also seen as a pre-anesthetic drug.
In Canada, temazepam is a substance administered in Schedule IV that requires a registered prescription.
In Denmark, temazepam was listed as Class D substance under Executive Order 698 of 1993 on Euphoric Substance which means it has high potential for abuse, but is used for medical and scientific purposes.
In Finland, temazepam is more tightly controlled than other benzodiazepines. Normison temazepam products are pulled out of the shelf and prohibited because the fluid inside the gelatin capsule has led to a major increase in the use of intravenous temazepam. Other temazepam products, Tenox, are not affected and remain as prescription drugs. The intravenous use of Temazepam has not declined to levels before Normison came to market.
In France, temazepam is prescribed by a doctor, it is registered under Medical Psychotropics UN71 Schedule III, which is determined only when other drugs will not be made, prescriptions can not be updated (new doctors visit each time), and are only available in seven pills, at theory one week, packing.
In Hong Kong, temazepam is set out under Schedule 1 of Chapter 134 of the Hong Kong Drug Abuse Ordinance. Temazepam can only be used legally by health professionals and for university research purposes. Substance can be given by the pharmacist under the prescription. Anyone who supplies non-prescription materials can be fined HKD $ 10,000. Penalties for trading or manufacturing of substance are a fine of $ 5,000,000 and life imprisonment. Substance holdings for unlicensed consumption from the Ministry of Health are illegal with $ 1,000,000-fines and/or seven years in prison.
In Ireland, temazepam is a Schedule 3 controlled substance with strict restrictions.
In the Netherlands, temazepam is available for prescription as tablets and capsules of 10 or 20 mg. A temazepam formulation containing less than 20 mg is included in List 2 of the Opium Act, whereas formulations containing 20 mg or more of the drug (together with gel-capsule) are the 1st substance of Opium Law, resulting in more strict regulation. In addition to being used for insomnia, it is sometimes also used as a preanesthetic medicine.
In Norway, temazepam is not available as a prescription drug. It is set as a Class A substance under the Norwegian Narcotics Act.
In Portugal, temazepam is a drug administered under Schedule IV under Decree-Law 15/93.
In Singapore, temazepam is a Class A controlled drug (Schedule I), making it illegal to own and requiring a personal recipe from a licensed physician to distribute.
In Slovenia, it is organized as Group II (Schedule 2) of substances controlled under Production and Commerce in the Dark Drug Act.
In South Africa, temazepam is a drug Schedule 5, requiring special prescriptions, and is limited to 10 to 30 mg doses.
In Sweden, temazepam is classified as a "narcotic" drug listed as either List II (Schedule II) which suggests it is a drug with limited drug use and high addiction risk, and is also listed as List V (Schedule V). ) substances indicating drugs were banned in Sweden under the Narcotics Drug Act (1968). Temazepam is banned in Sweden and ownership and distribution even in small amounts can be punished by imprisonment and fines.
In Switzerland, temazepam is a Class B controlled substance, like all other benzodiazepines. This means it is the only prescribed medication.
In Thailand, temazepam is a drug regulated under Schedule II under the Psychotropic Substance Act. Drug ownership and distribution is illegal.
In the United Kingdom, temazepam is a Class C controlled drug under Drug Abuse Act 1971 (Schedule 3 under Drug Abuse 2001). If prescribed personally (not on NHS), temazepam is only available with a prescribed form of a prescription drug (FP10PCD) and the pharmacy is required to follow specific procedures for storage and expenditure. In addition, all manufacturers in the UK have replaced gel capsules with solid tablets. Temazepam requires safe guarding and until June 2015 is released from the CD prescription requirements.
In the United States, Temazepam is currently a drug Schedule IV under the International Convention on Psychotropic Substances in 1971 and is only available on prescription. Specific coded recipes may be required in certain countries.
Synthesis
Active metabolite pharmacology diazepam, q.v.
N-oxides are susceptible to undergoing Polonovski rearrangement when treated with acetic anhydride, and this is illustrated by oxazepam synthesis. Not surprisingly, the N-methyl analog ( 1 ) also undergoes this process, and the hydrolysis of acetate yields temazepam ( 2 ). Care must be ensured with conditions, or inactive reordering ( 3 ) results.
References
External links
- Temazepam | Rx List
- Temazepam | Inchem
- Temazepam | Medline Plus
- Active Ingredients Information | DrugLib
- Benzodiazepine Addiction, Withdrawal & amp; Recovery | benzo.org.uk
Source of the article : Wikipedia
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