Benzodiazepines are a pharmaceutical drug and a narcotic drug. Benzodiazepine: mechanism of action and occurrence of dependence Is there a diagnosis of dependence on benzodiazepines?

Abuse that occurs with regular use of drugs from the benzodiazepine group leads to drug addiction. These psychoactive substances share a similar structural chemical structure.

Each drug in this class of medications exhibits the following effects to varying degrees:

• sedative (calming, tranquilizing);
• hypnotic;
• anxiolytic (eliminating anxiety);
• muscle relaxant (removing excessive muscle tension, both striated and smooth muscles);
• anticonvulsant.

When they are consumed, a peculiar mental state arises, akin to alcoholic or intoxication.. This is the reason why a person who takes benzodiazepines unnecessarily tries to achieve these sensations again and again. If medications are not taken as prescribed by a doctor and without control, then when a certain therapeutic time interval is exceeded, a mental and physical craving for the medicine occurs.

note: emerging addiction (lack of the expected effect from the usual doses) leads to taking an increased amount of benzodiazepines.

General information about benzodiazepines

The classification of drugs in this series is quite extensive, but our task is somewhat different - to consider the development of painful abuse of these drugs. Let us only note that There are three types of benzodiazepines: short-acting, intermediate-acting and long-acting.

The history of the first benzodiazepine - Chlordiazepoxide (Librium) begins in 1955 based on the experimental work of L. Sternbach. After 4 years, the following drug was synthesized - Diazepam. Due to its positive effect, a new group of substances has become actively used in many areas of medicine. But by the 80s of the 20th century, doctors were seriously faced with the massive development of benzodiazepine abuse. It became clear that the drugs require special monitoring when prescribed. Despite ongoing work to find new types of drugs in this group that will not cause addiction, the problem remains at the same level.

The list of benzodiazepines and standard dosage are given in the table:

The narcotic effect of benzodiazepines is based on changing the quality of gamma-aminobutyric acid (GABA), enhancing its effect on neurons, leading to anti-anxiety and calming effects.

When benzodiazepines are used, features of effects

Drugs are prescribed for the treatment of mental disorders in the context of chronic alcoholism, for prevention and mitigation, in treatment practice. These medications are especially effective for eliminating anxiety and sleep disorders.

It should be remembered that during pregnancy, breastfeeding and in old age, benzodiazepines give unwanted effects much more often than in other categories of people.

Paradoxical reactions and side effects

In some cases, while taking it, instead of the expected result, the following may occur:

• increased frequency and intensification of convulsive manifestations;
• attacks of aggression, malice, impulsiveness;
• suicidal forms of behavior, severe;
• sexual dysfunction;
• , thinking;
• speech defects;
• pathological changes in the intestines, loss of appetite, toxic liver damage.

Development of dependence due to benzodiazepine abuse

Constant, uncontrolled abuse of drugs leads to the gradual development of addiction. The effect of therapy decreases. This forces patients to increase the dose and frequency of medications. Continuous use of benzodiazepines creates mental cravings and physical dependence.

note: To avoid mental complications, you should periodically stop taking medications, replacing them with others, or taking nothing at all.

Patients should be aware that this group of substances can only eliminate the manifestations of ailments, but not cure them. To get rid of a disease, you must eradicate its cause. Therefore, it is very important to carry out the main “etiotropic” treatment while benzodiazepines are in effect.

Therapeutic periods of administration should not exceed 2-3 months. If during this time it is not possible to eliminate the causes that caused the main manifestations of the disease, then after stopping the drugs, patients will develop a withdrawal syndrome (return of fears, anxiety, etc.), and possibly in a stronger form - rebound syndrome.

In untreated cases, patients quickly return to the main drug. Manifestations of addiction are gradually increasing.

In some cases, with the help of benzodiazepines, people taking drugs are trying to escape their influence and mitigate drug withdrawal. Most often, this ends in the formation of a new type of polydrug addiction, and after a while - the development of severe benzodiazepine dependence.

How does benzodiazepine abuse manifest?

The effects of drugs in this series are characterized by:

• a feeling of complete calm, drowsiness, lack of coordination and slowness of movements;
• the onset of a feeling of relaxation in the body;
• improved mood (but mood swings are possible);
• periodic development of motor and non-purposeful activity;
• difficulty perceiving external stimuli, slowness of attention switching;
• decrease in the overall speed of mental reactions.

note: the manifestation of benzodiazepine intoxication by most of the symptoms resembles that of barbiturates and alcohol.

When examining a patient, the doctor pays attention to:

The phenomena gradually increase, the patient falls asleep after a few hours. After awakening, severe weakness and emotional “dullness” remain. Gradually the manifestations go away.

Constant use of medications forms an addiction to the drug, tolerance grows (low sensitivity to usual doses). The absence of the usual sensations forces patients to constantly increase the dose. Mental changes come first in intoxication, and problems of incoordination are reduced. Doses for people dependent on benzodiazepines can be many times higher than single and daily doses.

Withdrawal syndrome, benzodiazepine withdrawal

During abstinence, painful sensations increase, requiring another dose. That is, the withdrawal syndrome is becoming more and more obvious. The patient increasingly begins to look for reasons and opportunities to take medications.

The addict has:

• severe pallor, lethargy, depression;
• irritability with capriciousness and tearfulness, even in men;
• the heart rate increases sharply, blood pressure decreases, the patient sweats profusely;
• fingers
• pupils dilate sharply;
• expressed;
• sleep disturbances with nightmares, frequently interrupted dreams;

In more severe cases, seizures may occur, with hallucinatory experiences, and behavior. Some patients develop depersonalization.

Note: abstinence can last about 2-3 weeks or more, depending on individual characteristics.

Over time, the course of benzodiazepine abuse is complicated by psychopathology and personality disorders. Patients experience severe pain, intellectual capabilities are impaired, emotional coloring becomes depleted, and the face becomes mask-like. A person’s egocentrism and moral distortions progress (the whole world owes him something). Character traits include rudeness and boorishness, indifference to others, and cruelty. Mental stress is difficult. The ability to do physical work is reduced.

Overdose due to benzodiazepine abuse

Overdoses of benzodiazepines occur in rare cases. The toxic effect of these drugs is more common when used in combination with alcohol, opiate drugs, and tricyclic antidepressants.

Overdose manifests itself:

• pronounced, turning into stupor and coma;
• dysfunction of the eyeballs with nystagmus (pendulum-like movement);
• speech problems;
• sphincter disorders;
• arrest of breathing and cardiac activity.

Treatment of benzodiazepine abuse

Treatment of benzodiazepine addiction has a number of features. If the patient’s condition allows, it can be performed on an outpatient basis. Severe cases, especially combined addiction, require hospital conditions.

The issue of discontinuing treatment is considered on an individual basis. For the right approach, many factors must be taken into account. The optimal solution would be to immediately, completely stop using the drug. Although some narcologists also use stepwise dose reduction. Practice shows that an abrupt “break” of intake gives more effective results, even with high doses of benzodiazepines.

Most patients develop very severe depression, fear of death, weight loss, and asthenia during withdrawal.

In this case, an experienced narcologist selects the necessary one. In recent years, the drug Trittico has proven itself very well.. With its help, withdrawal symptoms are mitigated and pass almost painlessly. Usually, several months are enough to eliminate all the negative manifestations of withdrawal. Trittico acts very gently and does not contain strict contraindications.

After quitting antidepressants, you will have to eliminate the effects of asthenia for a long time. They are most suitable for this purpose. They should be selected depending on the dominant residual phenomena. Sometimes nootropics with a stimulating effect are required, sometimes, on the contrary, with a calming effect. Taking this group of medications may take quite a long time, since after benzodiazepine addiction there remains significant damage to the patient’s mnestic functions.

It is important to support the activity of the heart (most optimally) and liver. Long-term use of benzodiazepines puts a significant strain on liver cells. Therefore, the use of hepatoprotectors in a short time eliminates the toxic effect. Of the modern liver medications that protect and detoxify, special attention can be paid to Gepadif, both in injection and capsule form.

Psychotherapy plays an important role. Techniques of suggestion and persuasion, which are the main form of influence of this method of treatment, are used both individually and in group options.

Hypnotherapy helps reinforce motivational goals based on benzodiazepine abstinence.

After completing treatment with psychiatrists and narcologists, psychologists take over the baton of psychotherapy. The duration of remission depends on their ability to stabilize mental processes in a recovering patient.

Lotin Alexander, medical columnist

Current recommendations indicate the need to treat with benzodiazepines for a short period of time, without extending their use over a long period of time. However, in reality, doctors and patients do not always follow the recommendations. Long-term use of benzodiazepines leads to addiction. In such cases, stopping benzodiazepines becomes difficult.

To prevent withdrawal symptoms, a gradual dose reduction is usually recommended. Sometimes slow tapering takes months or even years, although there is no evidence that this slow tapering off of benzodiazepines is any better than a faster taper.

Withdrawal symptoms often resemble those of the conditions for which benzodiazepines were prescribed. Moreover, symptoms may return in a more severe form.

Added to this is the development of tolerance to benzodiazepines, which are taken to improve sleep and reduce anxiety. Over time, patients must increase the dose to obtain the desired effect.

There is currently no scientific consensus on how to pharmacologically facilitate benzodiazepine cessation. A drug or set of drugs is required that will solve several problems: remove the physical symptoms of withdrawal syndrome (tremor, tachycardia), improve the patient’s psychological state, reduce anxiety and normalize sleep.

The review included 38 randomized controlled trials (RCTs) with a total number of participants exceeding 2500. All of them took benzodiazepines for more than two months in a row and some were diagnosed with benzodiazepine dependence. The average age of participants was 50 years, and the majority of RCTs were female.

The studies reviewed by the review authors indicated potential beneficial effects of some drugs. First, valproic acid and tricyclic antidepressants helped stop benzodiazepines. Secondly, a number of drugs alleviated withdrawal symptoms: pregabalin, captodiam, paroxetine, tricyclic antidepressants and flumanesil. Third, several drugs reduced anxiety: carbamazepine, pregabalin, captodiam, paroxetine, and flumanesil. However, flumanesil could, on the contrary, increase the withdrawal syndrome. One study had to be stopped prematurely because flumanesil worsened symptoms of panic disorder.

A drug has been found that works the worst when withdrawing benzodiazepines, and also increases the withdrawal syndrome. This is alpidem, and, according to the authors of the review, further study of its role in benzodazepine withdrawal is not worthwhile. Almost as useless in this context is magnesium aspartate.

The effectiveness of individual drugs in solving this problem has already been tested. In 2006, a review of studies on the use of carbamazepine in benzodiazepine withdrawal was published. The conclusions of that review were that there is a positive effect, but more RCTs are needed.

Also in 2006, data were published that imipramine helps get rid of benzodiazepine addiction. The Cochrane review also noted the potential benefits of tricyclic antidepressants.

The final conclusion is that not a single pharmacological method of treating benzodiazepine dependence with proven effectiveness has yet been identified. For all drugs tested, the level of evidence was assessed by the review authors as low or very low. This is mainly due to the small scale of the RCTs and the conflict of interest that arose due to the fact that the RCTs were funded by pharmaceutical companies.

Thus, the question of effective pharmacological assistance to patients accustomed to taking benzodiazepines remains open.

The material was prepared with the support of the Doctor SAN clinic, a leading private psychiatric clinic and one of the best drug treatment hospitals in the North-West region.

Prepared by: Filippov D.S.

Source: Baandrup L, Ebdrup BH, Rasmussen JØ, Lindschou J, Gluud C, Glenthøj BY. Pharmacological interventions for benzodiazepine discontinuation in chronic benzodiazepine users. Cochrane Database of Systematic Reviews 2018, Issue 3. Art. No.: CD011481

Benzodiazepine abuse is a growing problem and poses a serious threat to health and society.
Benzodiazepines are widely used by polydependent drug addicts, alcoholics, and sometimes as a primary drug.
Individuals who abuse benzodiazepines often take very large doses orally, by injection, or by smoking.
The use of benzodiazepines leads to dependence and withdrawal symptoms, which may include seizures and psychosis.
The main source of illicit use of benzodiazepines is through medical prescriptions.
There are two main populations of benzodiazepine users: users taking low doses of benzodiazepines as prescribed by a doctor; users taking large doses not prescribed by a doctor. This article concerns the second group, as well as a small intermediate group of users taking high doses as prescribed by doctors, some of whom have become addicted. While the prevalence of benzodiazepine prescriptions by physicians has been declining, illicit use has increased sharply since 1980 and now represents a major public health problem.
An increasing number of drug abusers are taking benzodiazepines. True prevalence figures are not known, but benzodiazepines are commonly part of the substance abuse pattern, with 44 percent of 100 injection drug users in recovery also using benzodiazepines. Opiate, amphetamine and cocaine addicts around the world have been using benzodiazepines for about 20 years, which are now making their way into teenage users of MDMA (ecstasy) and LSD. Various drug and benzodiazepine combinations such as Tem-Tems (buprenorphine and temazepam) are popular, particularly in the north of England and Scotland. In fact, benzodiazepines are the most commonly used drug in Scotland. A modern craze among young people in Glasgow is riding buses all day while under the influence of cannabis-enhanced temazepam. Some of these young people began using benzodiazepines at the age of 13-14, along with alcohol and smoking. The age range of benzodiazepine abusers surveyed at various UK drug treatment clinics was 19–31 years, and the male to female ratio ranged from 2.8:1 to 2.1:1.
Benzodiazepine abuse is also common among alcoholics. About 30-50 percent of alcoholics also take benzodiazepines.
Additionally, some people (again an unknown number) take benzodiazepines as their primary drug of choice, which usually results in taking the drug in large doses.
The use of benzodiazepines is said to have little or no consequences for the vast number of people to whom they are prescribed. However, their dose may gradually increase and go beyond the legal limits. It is important to remember that substance abuse can occur at any age. Case 1: Peter was the youngest of nine brothers and sisters. His mother was an alcoholic, his father is unknown. He was taken into care at the age of 2 and raised in an orphanage. He was said to be a quiet and sensitive child who was always afraid of violence. When he was about 13, after an incident with one of the teachers at his boarding school, Peter discovered that he was gay. When he was 20 years old, Peter was involved in a traffic accident as a passenger on a motorcycle. He suffered serious injuries, including fractures to his arm, collarbone and leg. He spent several months in the orthopedic ward and suffered a number of complications, including infections, a broken leg that did not heal, pain from the inserted pins and plates, etc. In the hospital, he experienced severe attacks of panic and fear. He received no psychological treatment but was prescribed temazepam and dihydrocodeine. Initially, the dosage of temazepam was 20 mg to improve sleep, but in the hospital it was increased to 60 mg. After discharge, he continued to receive temazepam from his GP for panic attacks and insomnia, and over the course of a year the dosage was increased until he was taking 80 mg temazepam every night and 40–80 mg during the day. He felt he had to take temazepam, otherwise he would experience panic attacks, stomach pain and insomnia. After taking temazepam, he felt good and calm for a while, but then the panic and fear returned. At the age of 30, when it was discovered that he had forged a prescription for temazepam, he was transferred to another doctor, but continued to receive more prescriptions for temazepam and dihydrocodeine, often making up stories that his prescription had been lost or stolen. He also attempted to obtain temazepam from the hospital pharmacy, sometimes wearing a white coat and badge, making it appear that he was a clinic employee. When he could no longer meet his needs, Peter began buying temazepam illegally, taking large and irregular doses. His behavior became erratic and he was sent to prison twice for credit card fraud. In prison he was terrified and made strange statements about his health: that he was on hemodialysis, that he had HIV, that he expected to have his leg amputated due to illness. While in prison, he received temazepam from other prisoners. After his release at the age of 34, Peter agreed to undergo treatment and apparently made a real effort to stop taking temazepam. Initially he made significant progress. Temazepam was replaced by a reduced dose of diazepam. He was taking no other medications, as confirmed by weekly urine tests, and very little alcohol. He has never injected drugs. Unfortunately, when he was down to only 4 mg of diazepam daily, he broke his contract and purchased temazepam on the street. This resulted in immediate discharge from the center and cessation of further medical follow-up. When last heard from, Peter was again seen illegally purchasing temazepam and was involved in a court case for obtaining money under false pretenses. If benzodiazepines are not initially controlled, this can lead to dosage escalation and dependence in vulnerable individuals. Strict contract terms are not always suitable for benzodiazepine-dependent patients. If Peter had been given another chance at a drug treatment center, he might have gotten rid of his addiction.
The most common reason for using benzodiazepines is that they increase and often prolong the period of euphoria obtained through other drugs, including heroin, other opiates, cocaine and amphetamine. Benzodiazepines are mostly taken together with a primary drug, but are sometimes used alone as an alternative or in situations of deficiency. Second, benzodiazepines provide relief from anxiety and insomnia when other medications are limited. Users of stimulants, including cocaine, amphetamine and ecstasy, also take benzodiazepines to cope with their effects and combat the effects of a hangover. Alcoholics take benzodiazepines partly to relieve anxiety associated with chronic alcohol consumption, but also because the combination of alcohol and benzodiazepines produces an enhanced effect. Finally, benzodiazepines, taken by themselves in large doses, can also have a narcotic effect. Diazepam, alprazolam, lorazepam, and triazolam can all be used off-label. A dose of 1 mg alprazolam is comparable to 10 mg D-amphetamine.
Those benzodiazepines that have a quick effect (such as diazepam) are more popular than those that are absorbed more slowly (such as oxazepam). However, drug preferences vary across countries and over time depending on their availability. In the UK, temazepam has replaced diazepam, nitrazepam and flurazepam in line with the increase in temazepam prescriptions and possibly due to the availability (until recently) of an easily administered injectable capsule form of temazepam. Flunitrazepam tablets have become popular in the United States, partly due to cargo leakage across the Mexican border. Potent benzodiazepines such as triazolam (no longer available in the UK), alprazolam (widely prescribed in the US) and lorazepam are also popular among benzodiazepine abusers.
Benzodiazepines can be taken orally, smoked like tobacco, or injected. The most common practice is oral administration, but other forms of administration have recently been used. Inhalation of flunitrazepam powder is common, and this method can be used for other benzodiazepines and related medications such as buprenorphine. However, the main alternative to oral administration is intravenous injection, particularly for flurazepam, and is increasingly being used in the UK. Diazepam and other benzodiazepines have been popular, but temazepam is now primarily used.
A survey of subjects attending drug clinics was conducted in seven British cities. Of the 208 patients, 186 used benzodiazepines and 103 used intravenous benzodiazepines. Temazepam is the most commonly used drug and is available in the form of capsules, tablets and syrup. Other common benzodiazepines include diazepam, lorazepam, triazolam, nitrazepam, and chlordiazepoxide.
Attempts to discourage injection of temazepam by replacing the liquid with gel capsules and tablets and elixir appear to be unsuccessful, since the gel can be heated to a liquid consistency, the tablets can be dissolved in warm water and the elixir diluted to an injectable solution. The dosages used in this case, as a rule, far exceed the dosages recommended for therapeutic purposes.
The main source of prescriptions is general practitioners. Some users visit multiple doctors under false names, others obtain drugs from friends or from patients (often elderly) who exaggerate their needs at their doctors' appointments and sell the excess.
Benzodiazepines are generally considered safe in overdose, but deaths after poisoning do occur even when the drugs are taken alone, and overdose deaths are most likely associated with flurazepam and temazepam. Benzodiazepines also increase respiratory depression caused by other drugs: in Glasgow alone, combining temazepam with other opiates (eg buprenorphine) causes around 100 deaths a year. The use of benzodiazepines increases the risk of motor vehicle accidents, especially at higher doses. Psychiatric disorders caused by benzodiazepine use include loss of consciousness, memory loss, aggression, violence and erratic behavior associated with paranoia. Loss of judgment and amnesia caused by benzodiazepines may also be associated with risky sexual behavior, including casual sex and unprotected sexual activity. Cognitive impairment, including attention and memory deficits, also occurs in many cases and may persist after stopping benzodiazepines. Their use during pregnancy may result in fetal developmental abnormalities. Regular use of benzodiazepines, especially in large doses, usually leads to physical dependence, as evidenced by the onset of withdrawal symptoms when the drugs are suddenly stopped. The use of temazepam, especially when associated with the practice of sharing injection equipment, increases the risk of contracting HIV infection and hepatitis. In addition, benzodiazepines, especially temazepam (whether it comes in capsule, tablet, or elixir form), are a strong irritant and can cause damage to body tissue. When it becomes impossible to inject into veins in the arms, users can move on to injecting into the groin, where accidental hits to internal arteries can result in leg amputation. In such cases, temazepam is administered as a gel into the eyes, resulting in bilateral blindness.
The severity of withdrawal symptoms is largely related to the size of the previous dose. Epileptic seizures may occur, as well as hallucinations and/or paranoid ideas. Symptoms during abrupt discontinuation of benzodiazepines may also include: depression, chills, loss of appetite, seizures, memory loss, movement problems, nausea, muscle pain, dizziness, feeling weak, sensitivity to noise, photophobia, taste in the mouth.
The duration of withdrawal symptoms varies, and acute symptoms in the first few weeks can progress to prolonged anxiety and insomnia that can last for weeks or months.

Read on to learn how to recover from benzodiazepine addiction.

Visual step-by-step analysis for qualitative detection benzodiazepine in human urine.
Intended only for professional In Vitro Diagnostics.

APPLICATION

Diagnostic test for the company's BZO content SERATEC is secondary in nature, gradual analysis for chemical detection benzodiazepine in human urine at a limit of 300 ng/ml (Oxazepam).

This drug is used to obtain a visual, high-quality result and is intended for use for professional purposes. This test should not be used without proper supervision and is not intended for mass sale into untrusted hands.

This drug provides preliminary analytical results only. A more specific alternative chemical method should be used to obtain final analytical results. Gas chromatography/mass spectrometry has been recognized as a generally accepted method by the National Institute on Drug Prevention. Clinical judgment and physician judgment must be used in any drug detection test, especially when the results of a preliminary test are confirmed.

SCIENTIFIC BACKGROUND

Benzodiazepines are primarily central nervous system depressants and are considered by many to be the most commonly used drug in the United States. They are widely used as anti-stimulants, hypnotics, muscle laxatives and anti-convulsants. They are taken by swallowing or sometimes intravenously (injection).

Benzodiazepines processed by metabolism in the liver. Some of the metabolites benzodiazepines also exhibit pharmacological activity. Duration of action and half-life of varieties benzodiazepine and their metabolites are very different. They range from 2-3 hours and 50-100 hours for some active metabolites. The most common metabolite benzodaisepine- oxazepam, which is excreted together with other metabolites or excreted unchanged in the urine.

Use benzodiazepine may result in drowsiness or confusion (embarrassment). Benzodiazepines increase the effect of other depressants, such as alcohol. Although benzodiazepines have a low degree of acute and chronic toxicity if used under medical supervision; prolonged use of this drug can lead to psychological and physical dependence, so much so that stopping its use results in quite severe withdrawal symptoms.

Urine-based screening tests for life-threatening drugs range from simple immunoassays to complex laboratory tests. The speed and reliability of immunoassays have made them the most common method of testing urine for drugs of abuse. Company test SERATEC to detect the drug BZO ( Benzodiazepine) is based on the occurrence of specific immunochemical reactions of antigens and antibodies, which are used in the analysis of specific compounds in biological media. This test is a fast, intuitive, competitive analysis that can be used to detect benzodiazepine in human urine at a maximum concentration of 300 ng/ml oxyzepam. For a list of other structurally related components detected by this test, please refer to the SPECIFICITY section.

OPERATING PRINCIPLE

Company test SERATEC to detect drugs BZO ( Benzodiazepine) is a sequential immunoassay that pits one chemically labeled drug (paired drug) against a drug that may be present in the urine due to the reduced presence of binding antibodies. The testing device contains a strip of membrane, specially coated with an adjacent drug, on the shaft of the testing device. Painted

(golden) anti-benzodiazepine site of the paired single-clonal colloidal antibody is located on the right edge of the membrane. In the absence of drug in the urine, the gold-colored paired colloidal antibody solution and the urine move upward, chromatographically by vascular action, through the membrane. This solution is transferred to the stationary zone of the paired drug in the area of ​​the testing device rod. The colored (golden) paired colloidal antibody binds to the paired drug, producing a prominent antibody-paired drug reaction band. This explains the formation of visible sediment in the test area when the tested urine does not show drug content. If the drug is present in the urine, it/metabolite antigen fights with the adjacent (paired element) of the drug in the area of ​​the tester rod (“testing device”) to occupy the cell of the precipitated antibody on the anti-benzodiazepine monoclonal antibody-golden colloidal conjugate (paired element). If there is a sufficient amount of the drug, it will occupy the fallen structural cells of the antibody. This will automatically prevent the colored antibody-colloidal gold conjugate from attaching to the drug-paired area of ​​the tester shaft. Therefore, the absence of a colored rod in the test area indicates a positive result.

In addition, a control strip with a differential antigen/antibody reaction is added to the immunochromatographic membrane strip in the control zone (C) to determine whether the test was completed correctly. Such a control strip should always be present, regardless of whether the drug or metabolite is there. This means that urine that shows a negative result will leave two colored stripes, and urine that shows a positive result will leave only one stripe. The presence of this test strip in the control zone also serves as 1) evidence that sufficient volume has been provided and 2) the required influx of test formulation has been achieved.

STORAGE AND SECURITY

The test kit should be stored refrigerated or at room temperature +4 - +30C (38-86 F) in a special closed bag throughout the shelf life.

WARNINGS

• The tests are intended exclusively for In Vitro diagnostics.
• Used for professional purposes only.
• Urine tests may be potentially infectious (contaminated with an infectious disease). Therefore, necessary and effective methods for handling and using tests must be established.
• Avoid cross-contamination of urine samples by using a new test kit and sample dropper for each subsequent sample.
• Do not use the test device if damage is found on the test bag.
• Animal test components (i.e. antibodies) do not pose any danger if used strictly according to instructions.

MATERIALS INCLUDED

• Testing devices with replaceable pipettes.
• Description of instructions

NECESSARY MATERIALS

• Packaging with a set of samples
• Timer

SAMPLE SETUP AND HANDLING

Company test SERATEC to detect BZO ( Benzodiazepine) is manufactured for use with urine samples. Fresh urine does not require special handling or pretreatment. Urine samples should be collected in such a way that they can be tested on the same day, as soon as possible. Samples can be kept refrigerated at +2-8 C for 2 days and frozen at -20 C for a longer period. Samples that have been frozen should be brought to room temperature before sampling. Pre-frozen samples must be thawed to reach room temperature and must be thoroughly mixed before testing.

Attention: All samples and substances that come into contact with them must be treated as potential and probable carriers of infection. Avoid contact with skin by protecting your hands with gloves and appropriate laboratory clothing.

TESTING PROCESS

Read the “Collecting Samples” instructions. The test fixture, patient assays, and control device should be brought to room temperature (20-30 C) before testing. Do not open the sample bag until all preparations for testing have been completed.

1. Remove the testing device from the protective bag (before this, bring the device into the room and let it reach the temperature of the environment in which it is located to avoid condensation and fogging of the membrane). Label each sample with the patient's first and last name or control data according to the test.

2. Pipette the test to the indicated mark (approximately 0.2 ml). Then shake the contents of the pipette well. Use a separate pipette for each test.

3. Read the result 3-8 minutes after submitting the tests. Don't read it after 8 minutes.

DETERMINING RESULTS

Negative result:

Two colored lines appear in the viewing window. The area in the test zone (T) is the drug analysis field; the field in the control zone (C) is a control field that indicates the correct operation of the device. The color intensity of the test field (T) can be either less or greater, in contrast to the control field (C).

Attention: A faintly colored tester field indicates that the benzodiazepine concentration is close to zero. In this case, the test should be repeated or performed using a more specific method.

Positive result

Only one colored stripe appears in the control field (C). The absence of color in the test line (T) indicates a positive result.

Error:

If no lines appear in the test area, the test was performed incorrectly and should be repeated

TEST LIMITATIONS

• This test is designed for use in laboratory tests using human urine only.
• A positive test result only indicates the presence of the drug/metabolite and does not establish or measure the degree of intoxication.
• It is possible that technical or laboratory errors may occur during testing, as well as other significant conditions or factors not mentioned in these instructions (see SPECIFICITY section) that could result in incorrect or inaccurate results.
• If you suspect that the samples have been mixed up, with stickers re-glued, or tampered with, it is imperative to collect new samples.

QUALITY CONTROL

Long-standing laboratory practice demonstrates the need for the use of control substances to ensure the stability of reliable analytical results. High quality control samples are widely available commercially. When testing control samples for positive or negative results, use the same algorithm as for testing with human urine.

TEST CHARACTERISTICS

* to clarify the concentration of benzodiazepine in non-clinical samples, drug-free human urine was diluted with a substance according to Pharmaceutical Standard O 1755 Sigma.

A. Accuracy

Company test accuracy SERATEC for BZO content ( Benzodiazepine) was estimated to be within 300 ng/ml compared to commercially available analogues. 114 urine samples taken from presumably drug-free volunteers were found to be negative in both laboratory tests with 100% accuracy. In a separate analysis, 58 urine specimens obtained from a clinical laboratory where they were tested and tested positive according to widely available GC/MC laboratory tests for at least 1 of 5 derivatives benzodiazepine (Oxazepam, Nordiazepam, Flurazepam, Alprazolam, Triazolam). These samples passed both laboratory tests. 5 Benzodiazepine concentrations ranged from 124 to 2144 ng/mL. 57 samples with concentration level benzodiazepine exceeding acceptable standards showed a positive result after passing both laboratory tests. One of the samples with a content not much higher than the permissible standards showed (+/-) a controversial result after the test SERATEC and a positive (+) result after a routine laboratory test.

Based on data related to clinical samples, the main characteristics of the test were calculated SERATEC:

Diagnostic sensitivity: 98.3%
Diagnostic specificity: 100%
Accuracy of determining positive results: 100%
Accuracy of determining negative results: 99.1%
Reproducibility: 99.4%

B. Reproducibility

Test reproducibility SERATEC to detect Benzodiazepine(BZO) was installed in four different locations using hidden tests. 60 samples containing 150 ng/ml oxazepam showed negative results. 60 tests with a concentration of 600 ng/ml showed a positive result. Of the 60 samples containing oxazepam at the cut-off level of 300 ng/ml, 17% were positive, 1% were negative, and 82% were determined to be equivocal (+/-), thus showing some test instability.

B. Accuracy

The accuracy of the test was determined by latent assays with the following concentrations of oxazepam in the samples: 150, 225, 375, 450 ng/ml, respectively.

1*: including 7 (+/-) results.
2*: the remaining 9 tests showed (+/-) ambiguous (controversial) results.

D. Specificity

Test specificity SERATEC for maintenance benzodiazepine was tested by adding various drugs, drug metabolites and other components that may be found in human urine. All components were prepared in drug-free human urine. The following structurally related components have shown positive results when tested at levels equal to or greater than the concentration values ​​given below.

* - maximum established level of content

The following components were not found to cross-react during the test at concentrations reaching the 100 ng/ml mark.

Acetaminophen, Acetone, Albumin, Amitripcilline, Ampicillin, Aspartame, Aspirin, Atropine, Benzocaine, Benzolegonine, Bilirubin, Caffeine, (+) - Chlorpheniramine, Chlorpromazine, Creatine, Desoxyephedrine, Dexbrompheniramine, Dextromethorphan, 4-Dimethylaminoantipurine, Dopamine, Doxylamine, (- ) - Ephedrine, (+) - Epinephrine, Erythromycin, Ethanol, Furosemide, Glucose, Guaiacol-Glycerol-Ether, Hemoglobin, Imipramine, (+/-) - Isoproterenol, Lidocaine, D-Methamphetamine, Methadone, L-Methamphetamine, (1R ,2S)-(-) N-Methyl-Ephedrine, Methylenedioxymethamphetamine, Methylphenidate, Morphine sulfate, Morphine 3-P-D-glucuronide, Naloxone, Naltrexone, Naphthaleneacetic acid, (+) - Naproxen, (+/-) - Norephedrine, Penicillin G, Pentamin, Pentobarbital, Phenobarbital, Pheniramine, Phenocyacin, Phenylephrine-L, Oxalic acid, Riboflavin, Secobarbital, Soda Chloride, Sulindac, Tenoteclidine, Thioridazine, Trifluorperazine, Trimethobenzamide, Tyramine, Vitamin C.

Having hypnotic, as well as anticonvulsant and sedative effects. Such medications are prescribed to patients who suffer from insomnia, restlessness and anxiety. Most drugs in this group are related to tranquilizers. Today, medications that are benzodiazepine derivatives have achieved a medical breakthrough in eliminating anxiety conditions along with panic attacks, neuroses, obsessive-compulsive disorders and nervous tics.

We will consider a list of benzodiazepine drugs in this article.

Purposes of application and mechanism of action

In medical practice, benzodiazepine derivatives are used to treat various neurological diseases:

• Anxiety disorders. Health authorities advise the use of benzodiazepines for short-term therapy for one month. Dosing directly depends on the level of anxiety, as well as the patient’s age and health status. Such tranquilizers are recommended to be used with caution in older adults due to the risk of excessive levels of sedation and impairment or loss of consciousness.
• Having insomnia. This category of medications helps people fall asleep faster and increases sleep duration. Given that tranquilizers can cause addiction, they should be used for short-term treatment of severe insomnia. Instructions for use with Midazolam are discussed below.
• Providing treatment for alcohol addiction. Benzodiazepines help people with detoxification by reducing the risk of negative consequences during abrupt withdrawal of alcohol-containing fluids. These medications significantly relieve symptoms, and in some cases can even save the life of a particular patient.
• Epilepsy attacks. Some benzodiazepine drugs can be effective in preventing seizures.
• Fighting panic attacks. Benzodiazepines have a rapid anti-anxiety effect, allowing these medications to be used to relieve the anxiety associated with panic disorders.
• Neuroses of various types of genesis.

Benzodiazepines: list of drugs

Today they are widely used in neurology and other areas of medicine. Below is a list of the twenty most popular drugs in this category:

1. "Nitrazepam."
2. "Clonazepam."
3. "Midazolam."
4. "Gidazepam."
5. "Nimetazepam."
6. "Flunitrazepam."
7. "Alprazolam."
8. "Diazepam."
9. "Clobazam."
10. "Midazolam."
11. "Lorazepam."
12. "Clorazapat".
13. "Loprazolam."
14. "Chlordiazepoxide."
15. "Phenazepam."
16. "Triazolam."
17. "Gidazepam."
18. "Bromazepam."
19. "Temazepam."
20. Flurazepam.

Let us consider in more detail the indications for the use of the above drugs, as well as the features of therapeutic courses and recommended dosages of each of these benzodiazepines.

The drug "Midazolam"

According to the instructions for use, Midazolam is prescribed to patients to eliminate insomnia along with the relief of acute epileptic seizures. This medicine is administered intravenously and intramuscularly. For emergency treatment of various seizures in children, the drug "Midazolam" is used intranasally or intrathecally. What other drugs are included in the list of benzodiazepines?

"Gidazepam"

Gidazepam has an anticonvulsant effect. helps eliminate emotional unrest along with anxiety and fears. In pharmacies it is sold in tablets (20 and 50 mg), which should be swallowed without chewing. The daily dose is usually from 75 to 150 mg. The exact dosage must be prescribed by the attending physician.

The drug "Diazepam"

"Diazepam" can be characterized as an anticonvulsant and hypnosedative drug. Its daily dosage ranges from two to fifteen milligrams. At this rate, the medicine will produce a stimulating effect on the body. When consumed more than 15 mg, the drug will have a sedative effect. It should be noted that the maximum dose of this drug should not exceed 60 mg per day. This medicine must be taken orally.

Medicine "Clonazepam"

Clonazepam is available in the form of 2 mg tablets. This drug can reduce the tone of skeletal muscles, causing a hypnotic effect on the human body. The initial daily dose should not exceed 1.5 mg.

"Klobazam"

"Clobazam" belongs to the benzodiazepines with anticonvulsant action. The drug is sold in tablets that have a sedative and anticonvulsant effect. For patients of the adult age category, the daily dosage is from 20 to 30 mg, and for children over three years old, half of this norm should be used.

Lorazepam remedy

Lorazepam has an anti-anxiety and anticonvulsant effect. Take this drug orally at 2-3 mg per day. The duration of the first treatment course should not exceed one week.

"Clorazepate"

"Clorazepate" is an analogue of "Midazolam", it should be taken against the background of partial epileptic seizures, panic disorders and anxiety. The drug is available in capsule form with 5 mg of active ingredient. Young patients under 12 years of age are recommended to consume no more than 60 mg per day, and for adults this dosage can be increased by one and a half times.

The drug "Chlordiazepoxide"

"Chlordiazepoxide" is produced in the form of tablets and dragees. This medicine has anticonvulsant and sedative effects. According to the dosage regimen, it is recommended to take this drug 5-10 mg up to four times a day.

"Phenazepam"

The drug "Phenazepam" and analogues of the drug are distinguished by their anticonvulsant and muscle relaxant, that is, muscle relaxant, effects. In pharmacies this drug is sold in the form of 1 mg tablets. It should be taken half a tablet two to three times a day.

The drug "Gidazepam"

Gidazepam has anti-anxiety and anticonvulsant effects. This remedy is available in the form of tablets of 20 and 50 mg. It should be taken three tablets per day. It is recommended to gradually increase the dosage of this drug.

"Alprazolam"

The drug "Alprazolam" serves as an antidepressant hypnotic, and in addition acts as an anticonvulsant. Alprazolam is produced in the form of 1 mg tablets. Against the background of panic attacks, half a tablet of this drug is prescribed two to three times a day. Many people are prescribed benzodiazepines with anxiolytic effects.

Medication "Bromazepam"

Bromazepam is also produced in tablet form. should be taken against the background of anxiety-depressive conditions and neurological disorders. The dosage of this drug is selected individually. On average, up to 3 mg is prescribed twice a day.

"Loprazolam"

Loprazolam has an anxiolytic, anticonvulsant, hypnotic, sedative and relaxant effect. For the treatment of insomnia, the dose of this drug should be 1 mg at bedtime.

Medicine "Flunitrazepam"

As the instructions for use indicate, Flunitrazepam has a sedative, anticonvulsant and hypnotic effect. These tablets are used to treat insomnia. Adults are recommended 1-2 mg, and elderly and children half this amount before bedtime.

"Temazepam"

The drug "Temazepam" is prescribed to patients to combat neuroses and psychopathy, as well as sleep disorders of various origins. Tablets should be taken orally (up to 30 mg per day) before bedtime.

Other drugs

Flurazepam is used in the treatment of insomnia. This medication helps people fall asleep faster and also reduces the number of times they wake up during the night, thereby increasing their total sleep time. As part of the dosage, up to 30 mg of the drug should be taken immediately before bedtime.

"Midazolam" is released in either a solution for intravenous or intramuscular administration. This medicine is prescribed for short-term treatment of insomnia in patients. This medicine must be taken orally. For insomnia, the average dose should not exceed 15 mg per day. The tablets must be swallowed whole without chewing. Benzodiazepines with hypnotic effects are a very popular therapy.

Nimetazepam is sold in pharmacies in the form of 5 mg tablets. This drug is prescribed to combat sleep disorders, neuroses and schizophrenia. The presented medicine should be used once a day half an hour before bedtime. The daily intake for adults is 5-10 mg per day. Children are allowed up to five milligrams per day.

Triazolam is an analogue of Phenazepam; it is also prescribed to combat insomnia. The drug is available in tablets. It should be noted that the duration of taking this drug should not exceed three months. The maximum dosage is 1 mg half an hour before bedtime.

Nitrazepam effectively copes with phenomena such as seizures and insomnia. This medicine is prescribed as It should be taken up to 5 mg once a day half an hour before bedtime.

Benzodiazepines and withdrawal symptoms

It is well known that short-acting drugs, when discontinued, entail an intense, but short-term reaction of the body, which can begin within 24 hours after stopping treatment.

The time it takes to safely and progressively withdraw from benzodiazepines depends on the individual patient, the type of drug used, and the person's ability to cope with the stress associated with withdrawal, as well as the original reasons for using the drug. . As a rule, withdrawal periods for such drugs vary from four weeks to six months, and in some cases can exceed a year. The mechanism of action of benzodiazepines must be taken into account in therapy.

Excessively rapid removal of such drugs from the body can lead to severe withdrawal symptoms. Therefore, such a process must be carried out under the strict supervision of the attending physician. Correct withdrawal of a medication from use is possible by gradually reducing the dosage.

Thus, given that benzodiazepine-type tranquilizers belong to the category of drugs that have a sedative and anticonvulsant effect, their dosage regimen should be prescribed exclusively by the attending physician. Provided the recommended doses and course of administration are followed, the medications presented are relatively safe and have a high degree of clinical effectiveness. Their side effects, along with toxicity, are usually insignificant. Today, modern medicine cannot yet boast of alternative and more advanced drugs that could become a replacement for this category of drugs.

We reviewed the list of benzodiazepine drugs.