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BENZODIAZEPINE DERIVATIVES AND PREPARATIONS OF OTHER CHEMICAL STRUCTURES

NITRAZEPAM (pharmacological analogues: eunoctine, radedorm, mogadon, neozepam) - similar in action to tranquilizers such as diazepam. Nitrazepam has sedative and anticonvulsant properties. Of the benzodiazepine derivatives, nitrazepam has the most pronounced hypnotic effect, induces sleep lasting 6-8 hours, and has little effect on the structure of sleep. Nitrazepam is used for sleep disorders (adults are prescribed 0.005-0.01 g), and for some forms of epilepsy in children. Side effects when using nitrazepam: drowsiness and dizziness, nausea; tachycardia, ataxia, lethargy. Nitrazepam is contraindicated in myasthenia gravis, pregnancy, liver and kidney diseases. Release form of n itrazepam: tablets of 0.01 g. List B.

Recipe example n itrazepam in Latin:

Rp.: Tab. Nltrazepami 0.01 N. 10

TRIAZOLAM- similar in action to nitrazepam, but more effective. Triazolam has a hypnotic effect in doses of 0.25-0.5 mg. Side effects when using triazolam and contraindications are the same as for nitrazepam. Triazolam release form: tablets of 0.25 mg and 0.5 mg. List B.

FLURAZEPAM HYDROCHLORIDE (pharmacological analogues: dalmador, dalman, fludan) - has a hypnotic effect: it reduces the time of falling asleep and the frequency of night awakenings, increases the total duration of sleep to 7-8 hours. Dalman is used for all types of insomnia. Dalman is prescribed 30 mg orally the night beforenom, elderly and weakened patients - 15 mg. Side effects during use flurazepam hydrochloride- see nitrazepam. Release form of flurazepam hydrochloride: capsules of 15 mg and 30 mg. List B.

FLUNITRAZEPAM (pharmacological analogues: Rohypnol) - has a hypnotic and sedative effect, and also has anticonvulsant, anxiolytic (anti-anxiety), muscle relaxant properties. Flunitrazepam is used as a hypnotic (prescribed orally in the form of tablets), as well as in anesthesiology for premedication and induction of anesthesia (in doses of 1 to 2 mg intramuscularly or intravenously, slowly). Side effects of flunitrazepam: see nitrazepam. With parenteral administration of flunitrazepam, respiratory depression and a slight decrease in blood pressure(especially carefully when administered to elderly people). Flunitrazepam is contraindicated in severe forms myasthenia gravis, during pregnancy, during lactation. Relative contraindication is old age sick. Release form of flunitrazepam: tablets of 1 mg and ampoules of 1 ml (1 mg of the drug). List B.

Recipe example lunitrazepam in Latin:

Rp.: Tab. Rohypnoli 0.001 N. 10

D.S. 1/2 - 1 tablet 30 minutes before bedtime.

RELADORM- combination drug, consisting of sibazone (10 mg) and cyclobarbital (100 mg). Reladorm has a pronounced hypnotic effect, sleep occurs 20-30 minutes after taking the drug and lasts 7-8 hours. Reladorm also has anxiolytic, muscle relaxant and anticonvulsant effects. Side effects of reladorm: possible headache, skin allergic reactions. Reladorm is contraindicated in cases of liver and kidney dysfunction, and during pregnancy. Release form reladorma: tablets. List B.

Recipe example p eladorma in Latin:

Rp.: Tab. Reladorm N. 10

D.S. 1 tablet 30 minutes before bedtime.

Compound

Pharmacological action

Nitrazepam is a benzodiazepine hypnotic. Exhibits pronounced hypnotic, anxiolytic, sedative, anticonvulsant and muscle relaxant pharmacological effects.

Pharmacodynamics

The mechanism of action of the drug is to activate the benzodiazepine receptors of the GABA-benzodiazepine-chlorionophore complex, which increases the sensitivity of GABA receptors to the mediator (GABA) and stimulates the intracellular permeability of the cytoplasmic membrane for chlorine ions, thereby ensuring the inhibitory effect of GABA in the central nervous system. Nitrazepam inhibits the ability of brain neurons to excite, as well as conditioned and polysynaptic spinal reflexes.

Thus, the drug improves the process of falling asleep and shortens its duration, inhibiting the intensity of the manifestation of emotional, vegetative and motor stimuli that interfere with normal physiological sleep. During treatment with Nitrazepam, an increase in the depth and duration of sleep, a decrease in the frequency of awakenings and inhibition of the REM sleep phase were noted.

The effect of the drug is observed 20–40 minutes after administration and lasts 6–8 hours.

Pharmacokinetics

Nitrazepam, entering the body, is quickly and completely absorbed. The drug is 80% bioavailable. Cmax of Nitrazepam in the blood is observed 2–3 hours after administration. After entering the body, the drug predominantly binds to plasma proteins (87%). Nitrazepam is able to pass through the BBB, the placental barrier, and is also excreted in breast milk.

Nitrazepam is biotransformed in the liver, ultimately forming pharmacologically inactive metabolites (acetyl derivatives).

Vd of Nitrazepam is within the limit of 1.9 l/kg. T1/2 is approximately 26 hours. The drug is excreted by the kidneys mainly in the form of metabolites (95%), only 5% of it is excreted in its original form. Nitrazepam practically does not accumulate in the body and is quickly eliminated after completion of therapy.

Directions for use

The drug is taken orally with a small amount of water.

As a sleeping pill - once 30 minutes before expected sleep. The following doses of the drug are used, depending on age category patient:

When the drug is used for the treatment of neuroses and epilepsy as an anxiolytic and anticonvulsant, the following dosage regimen is used:

• adults: 5–10 mg 2–3 times/day (the highest therapeutic effectiveness is observed when using 2/3 of the drug at night), IRR is 30 mg;
• gerontological group: 2.5–5 mg 2–3 times/day;
• pediatric group (DM):

up to 1 year – 2.5–7.5 mg;

1–6 years – 5–10 mg;

6–14 years – 7.5–15 mg.

When prescribing the drug to children, the above DM is divided into 3 doses, while the amount of the drug for evening reception should exceed the daily dose. When determining children's doses of Nitrazepam, it is better to calculate it required quantity based on the child’s body weight. Thus, for children up to 30 kg, 0.3–1 mg/kg/day in 3 divided doses is recommended.

The course of treatment with the drug is quite long and varies from 30 to 45 calendar days.

The above recommended doses of the drug for various pathologies are indicative and are individually adjusted by the attending physician, taking into account the particularities clinical condition the patient, the etiopathogenesis of the existing disease and the individual therapeutic response of the patient’s body to the drug.

Side effects

The consequences of Nitrazepam therapy can be expressed in the following negative consequences For various organs and systems of the patient’s body:

Pregnancy

There is no data on the effect of the drug on the fetus and the body of women during pregnancy, therefore Nitrazepam is not prescribed to pregnant women.

The ability of the drug to penetrate into breast milk– therefore, during lactation you should not take it or you should stop lactation.

Drug interactions

Nitrazepam enhances the effect of drugs that have a depressant effect on the central nervous system.

Increases the toxic effects of anticonvulsants and ethanol.

Potentiates pharmacological action antihypertensive drugs.

When taking GOC, probenecid and cimetidine during therapy with Nitrozepam, a slowdown in its elimination is observed (T1/2 is prolonged), as a result of which the drug accumulates in the body and this can lead to excessive manifestation sedative effect.

Rifampicin, on the contrary, stimulates the excretion of Nitrozepam.

Overdose

In case of an overdose of the drug, symptoms of excessive central nervous system depression are observed:

• lethargy;
• asthenia;
• drowsiness;
• deep sleep;
• fog of consciousness;
• decreased pain sensitivity;
• ataxia;
• lack of reflexes (areflexia);
• excessive decrease in blood pressure;
• respiratory and cardiac depression;
• coma.

If you have these symptoms, you should seek medical help.

Treatment of overdose with Nitrozepam includes the following measures:

• intensive gastric lavage;
• intake of adsorbents;
• fluid replenishment by intravenous administration (if necessary);
• symptomatic therapy aimed at maintaining vital important functions body.

Nitrazepam has a specific antidote - flumazenil, approved for use exclusively in hospital settings.

Release form

Pills white with a yellowish tint, spherical or flat-cylindrical in shape with a chamfer.

Blister No. 10 – (2) – cardboard packs.

Storage conditions

Store in accordance with the requirements for drugs in List B. In a dark, dry, cool place (no more than 25 o C), away from children.

Nosological classification (ICD-10)

Schizophrenia (F20)

Manic episode (F30)

Phobic anxiety disorders(F40)

Mixed anxiety and depressive disorder(F41.2)

Other neurotic disorders(F48)

Insomnia of non-organic etiology (F51.0)

What is it intended for? medicine"Nitrazepam"? Instructions for use of the drug, its pharmacological characteristics, analogues, synonyms and indications will be presented in this article. In addition, you will find out whether this medication has contraindications, side effects, what is its cost, release form, composition, what patients and specialists think about it.

The drug "Nitrazepam": release form and composition of the medication

In what form can the mentioned drug be purchased? Tablets are its only form of release. The active substance of the drug is nitrazepam. As for the auxiliaries, these include lactose monohydrate (that is, milk sugar), potato starch, magnesium stearate and talc.

You can purchase the drug in jars made of dark glass (20 pieces each), as well as in cell packs of 10 tablets.

Pharmacological characteristics of the drug

What is the medicine Nitrazepam? The instructions for use of the drug state that it is psychotropic synthetic agent, which is used in the treatment of sleep disorders caused by various reasons.

The therapeutic effect of the drug is due to its composition. Active ingredient(nitrazepam) is capable of having pronounced anticonvulsant, muscle relaxant, hypnotic, anxiolytic and central effects.

The anxiolytic effect of the drug manifests itself in the elimination emotional stress, as well as easing anxiety. The sedative effect of the drug we are considering is expressed in the disappearance of symptoms of neurotic origin (such signs include anxiety and fear).

The drug "Nitrazepam": mechanism of action

According to experts, this drug, or rather, its active substance, is capable of increasing the depth and duration of sleep, reducing the impact of motor, emotional and vegetative stimuli, which, in fact, are main reason disturbances in the process of falling asleep.

The mechanism of action of this drug is associated with an increase in the inhibitory effect of GABA on the central nervous system due to an increase in the sensitivity of GABA receptors to the mediator, which occurs as a result of stimulation of benzodiazepine receptors.

After taking the drug, sleep occurs within 25-40 minutes and lasts about 6-8 hours. Pay attention! The medication may cause drug dependence and addiction. In this regard, it is sold in pharmacies only with a prescription from a specialist.

Pharmacokinetics of the drug

The binding of the drug to plasma proteins is about 80%. The half-life lasts on average 26 hours. The medication is excreted in the form of metabolites (to a greater extent).

Indications for the use of sleeping pills

For what purpose do doctors prescribe Nitrazepam tablets? Indications for the use of this medication include sleep disorders of various origins, including difficulty falling asleep and early morning or night awakenings.

Included complex therapy the mentioned medication is used for:

• epilepsy in young children (from 4 months to 2 years);
• encephalopathies accompanied by myoclonic epileptic seizures;
• chronic alcoholism, neuroses, psychopathy and organic lesions CNS.

Contraindications to the use of sleeping pills

In what cases is it prohibited to use the drug "Nitrazepam"? The instructions for use of the drug contain the following list of contraindications:

• acute intoxication medical supplies that produce a depressant effect on the central nervous system, including analgesics (narcotics) and hypnotics;
• acute intoxication due to alcohol intake with weakening of important body functions;
• hypercapnia;
• closed-angle glaucoma (with a predisposition to the disease and in the stage of acute attacks);
• myasthenia gravis;
• swallowing disorders in young children;
• pregnancy period, especially in the first trimester, as well as during breastfeeding;
• chronic obstructive and severe respiratory failure;
• drug addiction and alcoholism;
• severe depression (to avoid the development of suicidal symptoms);
• temporal lobe epilepsy;
• hypersensitivity to active and auxiliary substances.

Taking the drug during pregnancy

Can pregnant women take the drug Nitrazepam? A prescription with this medication can only be prescribed to a patient in the first trimester. However, this increases the risk of birth defects at the baby's. More long-term use medication can lead to drug dependence and withdrawal syndrome in the newborn.

Use of the drug before childbirth causes decreased muscle tone, hypotension, hypothermia and respiratory depression in the fetus.

Taking medication carefully

In what cases is constant monitoring necessary for a patient after taking Nitrazepam? A prescription with this drug should be prescribed by a doctor with extreme caution if the patient has at least one of the following abnormalities:

• liver, respiratory, and kidney failure;
• established or assumed;
• organic diseases brain;
• psychoses;
• history of drug dependence;
• cerebral and spinal ataxia;
• hyperkinesis;
• tendency to abuse psychotropic drugs medicines;
• hypoproteinemia.

In what cases is a reduced dosage of Nitrazepam required? The instructions for this medication state that when using it in old age, you must follow special caution. Such people should take small doses of the medicine.

Methods of using the drug

How should I use Nitrazepam? The instructions for use state that this sleeping pill should be taken once a day half an hour before bedtime.

The dosage of the drug is as follows:

• children under one year old - about 1.25-2.5 mg;
• child from 1 to 6 years old - approximately 2.5-5 mg;
• children from 6 to 14 years old - no more than 5 mg;
• adults - about 5-10 mg, but not more than 20 mg;
• elderly people - 2.5-5 mg.

As an antiepileptic and anxiolytic drug, the mentioned medicine is prescribed before three times 5-10 mg per day, but not more than 30 mg per day.

Important! The drug “Nitrazepam”, its analogues are not recommended for use long time without special instructions. This is due to the fact that there is a danger of mental and physical dependence, which develops after several weeks of daily use of therapeutic dosages.

With the simultaneous use of the mentioned drug with narcotic analgesics, an increase in dependence is very often observed. With the development of reactions such as aggressiveness (increased), acute conditions agitation, hallucinations, feelings of fear, suicidal tendencies, increased muscle spasms, difficulty falling asleep and light sleep, medication treatment must be suspended.

Side effects from taking the medication

Does Nitrazepam have side effects? Reviews from patients about it say that at the very beginning of therapy, the medication can cause a feeling of slowed mental and motor reactions, dullness of emotions, dizziness, uncertainty when walking, ataxia, lethargy, decreased concentration and gait disturbance.

Slightly less often, the drug causes such paradoxical reactions as outbursts of aggression, fear, acute agitation, confusion, suicidal tendencies, hallucinations, insomnia, irritability and other central nervous system disorders.

According to reviews, this medication often causes the development of the following side effects: headache, uncontrolled body movements, depression, catalepsy, depressed mood, weakness, tremors, myasthenia gravis, euphoria, confusion and dysarthria.

In addition, judging by patient reviews, the drug "Nitrazepam" can cause the following disorders: increased or decreased libido, leukopenia, urinary incontinence or retention, anemia, heartburn, loss of appetite, thrombocytopenia, dysmenorrhea, liver dysfunction, vomiting, itching, nausea, disorders agranulocytosis (excessive fatigue, hyperthermia, sore throat, chills, weakness), neutropenia, skin rash, dry mouth, drooling, diarrhea or constipation.

Overdose symptoms

What signs of overdose may occur in case of uncontrolled use of the drug Nitrazepam? Reviews from experts say that an increased dosage of the medication can cause quite serious disorders, which manifest themselves in the form of a decreased response to painful stimuli, drowsiness, severe weakness, confusion, decreased reflexes, deep sleep, paradoxical arousal, tremor, collapse, bradycardia and coma.

Withdrawal syndrome

The drug "Nitrazepam" (including drug analogues) should never be stopped too abruptly. Otherwise, the patient may develop withdrawal syndrome. As a rule, this is expressed in the appearance of the following signs:

• irritability;
• tachycardia;
• excitement, excitement or anxiety;
• depression;
• sleep disturbances and nervousness;
• depersonalization;
• increased sweating;
• feeling of fear;
• spasms skeletal muscles and smooth muscles internal organs;
• headache;
• nausea and vomiting;
• paresthesia;
• tremor;
• hyperesthesia;
• dysphoria;
• photophobia;
• hallucinations;
• convulsions;
• acute psychosis.

Interaction of the drug with other drugs

The drug "Nitrazepam", the price of which is presented below, cannot be used simultaneously with drugs that have a depressant effect on the central nervous system, as well as with ethanol-containing drugs and ethanol.

When used simultaneously with anticonvulsants, there is a possibility of increased toxic effects.

When used simultaneously with estrogen-containing oral contraceptives, the concentration of nitrazepam in the blood increases.

When taken simultaneously with rifampicin, excretion increases active substance from the body.

When used simultaneously with cimetidine, the concentration of nitrazepam in the blood increases, which entails an increased sedative effect.

(information for specialists)

Registration number

Trade name of the drug: Nitrazepam

International generic name - Nitrazepam

Dosage form: pills

Composition per tablet:
Active substances: Nitrazepam - 5 mg
Excipients: Milk sugar (lactose), potato starch, low molecular weight medical polyvinylpyrrolidone (povidone), talc, magnesium stearate, Primogel (sodium carboxymethyl starch) - a sufficient amount to obtain a tablet weighing 100 mg.

Description: Tablets are white with a yellowish-greenish tint, spherical or flat-cylindrical in shape with a chamfer.

Pharmacotherapeutic group: sleeping pill

ATX code N05CD02

Pharmacological properties
The drug belongs to the list of potent drugs according to the minutes of the PCKN meeting.
Sleeping pill from the group of benzodiazepines has a depressant effect on the nervous system (CNS), which is realized mainly in the thalamus, hypothalamus and limbic system. Enhances inhibitory effect gamma-aminobutyric acid(GABA), which is one of the main mediators of pre- and postsynaptic inhibition of impulse transmission in the central nervous system.
The drug also has anxiolytic, sedative, muscle relaxant, and anticonvulsant effects. The hypnotic effect occurs 20-40 minutes after taking the drug and lasts 6-8 hours. Under the influence of the drug, the depth and duration of sleep increases. Sleep and awakening occur physiologically.
The drug passes well through the blood-brain barrier, the placenta, and penetrates into breast milk, which must be taken into account when prescribing the drug to pregnant and lactating women.

Pharmacokinetics
Absorption from the gastrointestinal tract is fast and complete. Bioavailability - from 54% to 98% (depending on dosage form). When taken simultaneously with food, absorption slows down and maximum plasma concentration decreases by approximately 30%. With a single oral dose of 10 mg of nitrazepam, the average maximum concentration is 0.08-0.1 mcg/ml and is achieved after 1-4 hours. Communication with plasma proteins is about 85-90%. The distribution phase of the active substance in the body varies greatly and ranges from 1.7 to 3.5 hours. The volume of distribution increases with the age of patients and amounts to 1.3-2. 6 l/kg. It penetrates well through histohematic barriers, including the blood-brain barrier and the placental barrier, and is found in mother's milk.
Metabolized in the liver by reduction of the nitro group and subsequent acetylation with the formation of inactive acetyl derivatives. The half-life is 16-48 hours (depending on the age and body weight of patients) from cerebrospinal fluid- 68 hours. The main metabolites are 7-amino-nitrazepam, 7-acetamino-nitrazepam, 2-amino-5-nitrobenzophenone and hydroxy-2-amino-5-nitrobenzophenone, excreted by the kidneys (65-71%) and with feces(14-20%). About 1-5% is excreted unchanged by the kidneys.
Accumulation upon repeated administration is minimal (applies to benzodiazepines with a short or medium half-life), elimination after cessation of treatment is rapid.

Indications for use

Nitrazepam is a drug from the group of benzodiazepine hypnotics.

Composition and release form

The drug is produced in tablets, their shape is spherical or flat-cylindrical, the color is white with a green or yellow-green tint, and there is a chamfer on the surface. The medicine is supplied in cell packaging to the pharmaceutical market or in a polymer jar made of tinted glass. The active compound is nitrazepam.

Auxiliary components Nitrazepam: low molecular weight polyvinylpyrrolidone, milk sugar, talc, Primogel is present, potato starch, magnesium stearate is added. Sleeping pills are sold by prescription.

Pharmacological action

The sleeping pill Nitrazepam belongs to the group of benzodiazepines. It has a muscle relaxant, anxiolytic (anti-anxiety) effect, and also has an anticonvulsant effect.

The drug enhances the inhibitory effect of GABA on the transmission of nerve impulses, in addition, it has a stimulating effect on benzodiazepine receptors, reduces the excitability of subcortical structures (thalamus, limbic system, hypothalamus), and also inhibits spinal reflexes.

Main mechanism hypnotic effect consists of inhibition of the reticular formation located in the brain stem. The drug reduces the impact of motor, emotional, and vegetative stimuli that disrupt the process of falling asleep.

Under the influence of the pharmaceutical drug, the duration of sleep, as well as its depth, increases. The anxiolytic effect is substantiated by the influence of nitrazepam on the limbic system and manifests itself in a decrease in fear, emotional stress, in addition, anxiety and restlessness are weakened.

The sedative effect of Nitrazepam is due to its effect on the reticular formation and the nuclei of the thalamus, which is manifested by a decrease in neurotic symptoms, in particular anxiety and fear.

The drug Nitrazepam causes anticonvulsant effect due to activation of presynaptic inhibition. The effect of the pharmaceutical product begins after using the tablets in thirty minutes and lasts up to eight hours. Absorption of the drug from the gastrointestinal tract is complete. Bioavailability - up to 98%. Protein binding - 90%. Metabolized in hepatocytes. The half-life lasts from 16 to 68 hours. Excreted by the kidneys, as well as in the stool.

Indications for use

The drug Nitrazepam is indicated for use in sleep disorders of different origins In addition, the medicine is effective for encephalopathy accompanied by myoclonic seizures, West syndrome, neuroses, psychopathy, as well as psychoses of an endogenous nature, chronic alcoholism, organic lesions of the central nervous system and as a so-called premedication.

Contraindications for use

I will list the situations in which the use of the pharmaceutical drug Nitrazepam is contraindicated:

Hypersensitivity to the components of the drug;
State of coma or shock;
Alcohol intoxication in acute form;
Acute intoxication medications that have a depressant effect on the central nervous system;
Lactation period;
Myasthenia;
Respiratory failure acute;
Severe depression, as suicidal tendencies are not excluded;
Pregnancy;
Drug addiction, alcoholism;
Angle-closure glaucoma;
Epilepsy.

The pharmaceutical drug Nitrazepam is prescribed with caution for hepatic, respiratory or renal failure, in old age, hyperkinesis, history of drug addiction, organic pathology brain, hypoproteinemia, psychosis, sleep apnea.

Application and dosage

The drug Nitrazepam is used orally as a pharmaceutical sleeping pill an hour before bedtime in an average dosage of 5-10 mg, the maximum single dosage is 20 milligrams. As an anti-anxiety and antiepileptic drug, the highest daily dose is 30 mg.

Side effect

The use of Nitrazepam causes the following: side effects: drowsiness, a typical feeling of fatigue, possible dizziness, a decrease in concentration, ataxia is noted, there may be uncertainty when walking, lethargy, in addition, dulling of emotions, as well as a slowdown in mental and motor reactions.

Among other negative reactions, one can note: the presence of a headache, euphoria is characteristic, depression, tremors are observed, depressed mood is recorded, catalepsy is possible, in addition, amnesia, confusion, weakness, extrapyramidal reactions are not excluded, in addition, laboratory changes in the form of leukopenia, anemia, neutropenia, as well as agranulocytosis.

Other side effects: drooling, allergic reactions, heartburn, nausea, drug dependence, vomiting, loss of appetite, urinary incontinence, constipation or diarrhea, dysmenorrhea, liver dysfunction, increased liver enzymes, urinary retention, changes in libido, decreased blood pressure, depersonalization, depression respiratory center, bulimia, double vision, weight loss, tachycardia.

Drug overdose

Symptoms of Nitrazepam overdose: drowsiness, decreased reflexes, confusion, deep sleep, paradoxical arousal, stupor, ataxia, decreased response to pain, blurred vision, lethargy, tremor, bradycardia, coma, shortness of breath, decreased blood pressure. The patient's stomach is washed and prescribed symptomatic treatment.

Special instructions

During treatment with the pharmaceutical drug Nitrazepam, the patient is prohibited from drinking alcoholic beverages. It is not recommended to use the medication for a long time. The drug may cause drug addiction when taking tablets daily for several weeks, even when used in therapeutic doses.

Analogs

Eunoktin, Mogadon, Nitrazadone, Radedorm 5, Nitram, Berlidorm 10, Nitrosan, Berlidorm 5, Neozepam.

Conclusion

It is recommended to take the pharmaceutical drug Nitrazepam only as prescribed by a specialist.