Pharmacodynamics and pharmacokinetics
Pharmacodynamics
A benzodiazepine-type tranquilizer . Has a sedative and anxiolytic effect. It also has muscle relaxant and anticonvulsant activity.
The effect of the drug is associated with an increase in GABA processes in the brain. It has an effect mainly on the retinal activating formation of the brain, reducing the influence of impulses from sensory type receptors on the limbic system and weakening emotional coloring.
Pharmacokinetics
Absorbed relatively slowly, but completely. Reaction with plasma proteins reaches 97%. The maximum concentration is reached on average after 2-3 hours. The drug is able to penetrate the placenta, the blood-brain barrier and be excreted in breast milk. Transformed in the liver to form inactive derivatives. The half-life can range from 5-15 hours. Excreted by the kidneys and through the intestines. Elimination from the body after cessation of therapy is rapid.
Is there a difference
The difference between Phenazepam and Nozepam is the composition of additional components. Due to their inactive constituents, benzodiazepines act slightly differently :
- Nozepam has a more pronounced sedative effect;
- Phenazepam has a stronger relaxing and hypnotic effect.
But not all patients note these properties. Some indicate that Nozepam is better at helping people fall asleep than Phenazepam. Which drug will be more effective depends on the individual sensitivity of the body.
Contraindications
Coma , acute alcohol poisoning, shock, myasthenia gravis , acute poisoning with drugs that suppress the nervous system ( hypnotics, narcotic and psychotropic drugs ), decompensated obstructive chronic pulmonary disease, angle-closure glaucoma , acute pulmonary failure, severe depression , lactation and pregnancy , age less 6 years old, hypersensitivity to the components of the drug.
Side effects
- Reactions from nervous activity: in the initial period of treatment, dizziness, drowsiness, difficulty concentrating, fatigue, ataxia , unsteadiness of gait and impaired coordination of movements, dulling of emotions, lethargy, slowing of mental and motor reactions are possible; more rarely develop euphoria , headache , tremor, depression , depressed mood, memory impairment, stupor, extrapyramidal reactions of dystonic type, muscle weakness, weakness, dysarthria , confusion, paradoxical reactions (for example, psychomotor agitation, aggressive outbursts, fear, muscle spasms , suicidal tendencies, hallucinations , irritability, acute agitation, insomnia , anxiety).
- Hematopoietic reactions: neutropenia, leukopenia, anemia, agranulocytosis, thrombocytopenia.
- Digestive reactions: vomiting, dry mouth, heartburn, drooling, nausea, constipation, anorexia, diarrhea, increased concentrations enzymes , liver dysfunction, jaundice.
- Reactions from the genitourinary system: urinary retention, impaired renal function, increased or decreased libido, urinary incontinence, dysmenorrhea .
- Effect on the fetus: depression of nervous activity, teratogenicity , respiratory failure or inhibition (if the mother of the newborn used Nozepam) of the sucking reflex.
- Allergic reactions: itching , rash.
- Other reactions: drug dependence, addiction, decreased blood pressure, depression of the respiratory center, bulimia , blurred vision, tachycardia , weight loss, anterograde amnesia .
- If the dose is suddenly reduced or the dose is stopped, withdrawal syndrome may occur (headache, dysphoria , irritability, anxiety, agitation, excitement, fear, sleep disturbance, nervousness, spasm of smooth muscles and skeletal muscles, increased sweating, depersonalization, depression , vomiting, nausea, tremor, paresthesia , perceptual disturbances, photophobia, convulsions, tachycardia, acute psychosis , hallucinations).
Nitrazepam, Lorazepam, Nozepam, Phenazepam, Diazepam, Flurazepam, Triazolam
2) different chemical structures
Zolpidem, Zopiclone
Based on the duration of action, benzodiazepines can be divided into groups:
1) short-term action (t1\2 =1.5–3 hours): triazolam
2) medium duration (t1\2 =12–18 hours): lorazepam, nozepam; (t1\2 =24 hours): nitrazepam
3) long-acting (t1\2 =30–40 hours): phenazepam, flurazepam, diazepam
Barbituric acid derivatives
Derivatives of barbituric acid are produced in the form of sodium salts, highly soluble in water. The lipophilicity of drugs is determined by the degree of polarity of radicals - this determines the speed of development and duration of the effect.
The mechanism of action of barbiturates: having penetrated the synapses, in which the role of mediators is played by GABA and glutamic acid (GLA), barbiturates have two main effects: firstly, they stimulate specific barbiturate receptors, structurally and functionally related to GABA receptors, and an increase in affinity is observed GABA receptors for GABA and the opening of channels of the postsynaptic membrane of GABAergic synapses for chlorine ions, which penetrate into the cells and increase the concentration of negative charges on the internal surface of the cell membrane, which leads to hyperpolarization of the neuron membrane, as a result of which the cells are not excited, inhibition occurs; secondly, they inhibit the activity of GLA receptors, which leads to the closure of sodium channels of the postsynaptic membrane of GLA-ergic synapses and the difficulty of its depolarization, inhibition develops.
Both mechanisms lead to a decrease in neuronal excitability, activation of inhibitory processes in the central nervous system and the development of a hypnotic effect. However, a sedative effect occurs first.
General pharmacological features of barbiturates:
- the inhibitory effect on the central nervous system is dose-dependent: small doses - sedation; medium - sleeping pills; large - narcotic
- the therapeutic breadth of action is small: the use of 3-4 tablets of the drug simultaneously can lead to severe depression of the central nervous system
— the mechanism of action of barbiturates is mainly realized at the level of the ascending sections of the reticular pharmacy: its activating effect on the cerebral cortex is suppressed
- barbiturates suppress (shorten) the duration of the REM sleep phase - sleep is non-physiological; long-term use of barbiturates as hypnotics is accompanied by a deficiency of the paradoxical phase, which subsequently leads to neuroses, irritability and psychosis (rarely)
- with long-term use of barbiturates, addiction may occur (due to the induction of microsomal liver enzymes); to reproduce the previous effect, the dose of the drug must be increased (by 1-2 tablets), which increases the likelihood of mental and physical dependence
- the hypnotic effect of barbiturates, which are recommended for use for insomnia, usually develops quickly (after 10-20-30 minutes) and lasts up to 4-6 hours
- side effects manifest themselves in the form of drowsiness, fatigue. Dyspeptic symptoms (nausea, vomiting), allergic reactions (urticaria, dermatitis), as well as changes in the blood (neutropenia, thrombocytopenia, etc.) are possible.
- after waking up, aftereffects may occur due to the ability of barbiturates to be deposited in adipose tissue.
In case of an overdose of barbiturates or in the case of their suicidal use, symptoms of poisoning are observed: clinical depression of the central nervous system up to coma (similar to anesthesia). Against this background, pathology of the respiratory system (pulmonary edema, atelectasis) and kidneys often occurs. Death occurs from paralysis of the respiratory and vasomotor centers.
Treatment : gastric lavage, adsorbents, forced diuresis, artificial ventilation. Intravenously - specific antidote - bemegride
(10 - 70 ml of 0.5% solution)
(not currently used)
Of the barbituric acid derivatives, taking into account the peculiarities of their pharmacological properties, only a few drugs are currently used.
Phenobarbital
It has limited use as a hypnotic (at a dose of 0.1) and is one of the anticonvulsants (at a dose of 0.01-0.05).
Benzodiazepine derivatives
Benzodiazepine derivatives are safer
drugs compared to barbiturates due to their lesser effect on the phase structure of sleep.
The mechanism of hypnotic action is similar to that of barbiturates, however, the affinity of GABA receptors for GABA increases as a result of the drugs binding not to barbiturates, but to benzodiazepine receptors. In this case, the effect is more noticeable: the channels for chlorine open to a greater extent, hyperpolarization of the postsynaptic membrane occurs and inhibition develops.
Benzodiazepines are characterized
: sedative, anxiolytic (elimination of anxiety, fear), hypnotic, muscle-relaxing and anticonvulsant effects.
Benzodiazepines differ markedly from barbiturates: they are characterized by easy awakening; there is practically no effect on the phase structure of sleep; the risk of physical dependence is low, although it does exist, especially with long-term use; the risk of overdose is much lower.
It is used mainly for neurotic sleep disorders.
Nitrazepam (radedorm)
The effect of the drug appears after 20 - 40 minutes and lasts up to 6 - 8 hours. Waking up is usually easy, but lethargy, muscle weakness and dizziness sometimes occur.
Adverse reactions when using nitrazepam are also ataxia (impaired coordination of movements), tolerance (due to the induction of microsomal enzymes), the development of mental and physical dependence and withdrawal syndrome (with long-term use). The latter is manifested by irritability, sweating, a feeling of fear, nervousness, etc.
Flunitrazepam (Rohypnol)
Close to nitrazepam in chemical structure and action. Additionally contains a fluorine atom. Has a sedative, hypnotic, anticonvulsant effect. Side effects are similar to other benzodiazepines, and addiction and withdrawal symptoms are also possible.
Triazolam (somneton)
Has a pronounced hypnotic effect. It is quickly absorbed in the gastrointestinal tract and quickly excreted from the body (T1/2 -1.5-3 hours). Compared to nitrazepam, the effect is shorter and daytime sleepiness is also less pronounced, but other adverse reactions of benzodiazepines may occur.
Phenazepam
It is a highly active drug from the group of tranquilizers (anxiolytics). It has a tranquilizing, anticonvulsant, muscle relaxant and hypnotic effect. It is also prescribed to relieve alcohol withdrawal.
Side effects: ataxia, drowsiness, muscle weakness, dizziness can often be observed.
Instructions for use of Nozepam (Method and dosage)
Instructions for use of Nozepam recommend taking the drug orally with water. Choose the smallest effective dosage and short duration of therapy if possible.
For neurotic conditions complicated by increased irritability, agitation, fear, anxiety, adults are prescribed a single dose of 10-30 mg. In the case of outpatient treatment, the usual daily dose is usually 20-30 mg, divided into 2-3 doses. In severe cases, the dosage is increased to 15 mg in the first two doses and to 15-30 mg in the evening. The highest daily dose is 120 mg. Doses over 60 mg are prescribed only if hospital treatment is possible.
For sleep disorders (insomnia) caused by anxiety, 10-25 mg of Nozepam is recommended an hour before bedtime. The largest single dose in this case is 50 mg. In the evening, the drug should not be taken directly after a meal, as its effect slows down and, depending on the duration of sleep, residual reactions may occur (fatigue, impaired concentration the next morning).
When treating alcohol withdrawal syndrome, take 15-30 mg of Nozepam 3-4 times a day. In elderly or weakened patients, with insufficiency of the liver, kidneys, heart or lungs, as well as with organic brain damage, a daily dose of 10 mg is set, divided into two doses; if necessary, it is increased to 15 mg per day.
14 days after the start of therapy, you should ensure that there are indications for continuing use of the drug, since it is undesirable to exceed the duration of continuous treatment of 4 weeks. Taking beyond this period may cause mental and physical dependence on the drug. If long-term treatment is necessary, stop taking the medication for several days, and then return to its use at an individually selected therapeutic dose.
The use of the drug is stopped slowly, gradually reducing the dose. Abrupt cessation of taking Nozepam can provoke withdrawal symptoms: anxiety, agitation, sleep disturbance.
Instructions for use
Tazepam is approved for use only under the supervision of a physician. The dosage of the drug is calculated individually depending on the nature of the patient’s disease. The standard dose of the drug for severe anxiety disorders is 30 mg per day for an adult. This dose should be divided into 3 doses. The tablets are taken without chewing, with a small amount of water.
For the treatment of emotional lability after suffering stress, it is best to calculate the course of treatment and select the dosage by titrating the dose. In this case, treatment begins with a minimum dosage and is gradually increased until the pathological condition is completely relieved, after which the dose increase stops. This method of selecting treatment allows you to minimize the risk of overdose and reduce the risk of side effects.
It must be remembered that Tazepam is an emergency drug for anxiety conditions, and it is not used for long-term treatment of acute psychopathic disorders (in such cases, other drugs from the group of benzodiazepine derivatives are used). The maximum duration of treatment with the drug is 2 weeks. If there is no effect within two weeks, it is necessary to discontinue this medication and change therapy.
Discontinuation of the medication should occur gradually, especially if the course lasts more than one week. A gradual reduction in dosage and frequency of administration helps to avoid the patient's withdrawal syndrome.
For sleep disorders, this drug is used to a limited extent in case of ineffectiveness of other medications and only as an adjuvant. The standard dosage of the drug is 10 mg per day (can be increased to 30 mg per day). If the maximum dosage is ineffective, the drug should be discontinued.
It is not recommended to combine the use of Tazepam and narcotic analgesics, as this increases the risk of developing drug and drug dependence.
Since oxazepam affects consciousness and coordination of movements, during treatment it is not recommended to drive vehicles or work with mechanisms that require increased concentration.
Overdose
In case of an overdose of oxazepam, the following symptoms may appear: a state of disorientation, drowsiness, loss of consciousness, slurred speech, coma . Particularly life-threatening are poisonings caused by the combined use of alcohol and oxazepam , or other drugs that suppress nervous activity and oxazepam .
In case of overdose, actions are taken aimed at eliminating the drug from the body or reducing its absorption in the digestive system (gastric lavage, administration of Activated Carbon ), they also monitor vital functions (pulse, respiration, blood pressure) and, if necessary, carry out symptomatic treatment.
Flumazenil is a specific antidote for oxazepam .
When treating an intentional overdose, it must be remembered that the patient could take several different drugs at the same time.
Possible side effects and overdose
When using Tazepam, a number of side effects may occur, which should be kept in mind before prescribing the drug.
Undesirable effects from taking are divided into several groups depending on the reacting organs and systems:
- From the digestive system - dyspeptic disorders, which are manifested by nausea, lack of appetite, less often vomiting or diarrhea. Nausea occurs quite often, but it quickly goes away with symptomatic therapy or after stopping the course of treatment with the drug.
- From the nervous system side, patients most often experience drowsiness, a slower reaction to external stimuli, and slight dizziness. Less commonly, disorientation in space, confusion, headaches, and a feeling of lack of strength when performing physical labor occur.
- On the part of the female reproductive system, when taken, menstrual irregularities may occasionally occur.
- On the part of liver function, laboratory tests may increase the activity of transaminases (liver enzymes), alkaline phosphatase, and bile pigments. In addition, icteric conditions may occur.
- From the excretory system, acute urinary retention or incontinence may occur.
- The mental status in very rare cases can change paradoxically - aggression, excessive anxiety, insomnia, psychomotor agitation, auditory and visual hallucinations occur. Such conditions often occur after drinking alcohol while being treated with medication. In such cases, it is necessary to discontinue the drug and prescribe symptomatic treatment of the resulting pathological condition.
With an overdose of oxazepam, the above side effects increase many times over. In addition, patients experience dysarthria (speech impairment), antegrade amnesia (memory loss for current events and all subsequent ones), impaired sexual function and libido.
In case of overdose, symptomatic therapy and detoxification of the body are recommended. There is a specific antidote - Flumazenil. If an overdose of Tazepam is detected, it is necessary to administer this antidote as soon as possible, then the success of treatment will be the highest.
Interaction
When used together with oral contraceptives , the effectiveness of Nozepam decreases.
When used simultaneously with Zidovudine, bioavailability increases and the frequency of headaches increases.
When used together with Phenytoin, there is a risk of reducing the level of oxazepam in the blood.
When used together with ethanol, its inhibitory effect on the nervous system increases.
special instructions
The medicine should be used with caution if there is a tendency to hypotension , an increased risk of drug dependence, insufficiency of liver or kidney function, in the elderly, with ataxia of the spinal and cerebral type, a tendency to abuse psychotropic drugs, hyperkinesis , organic diseases of the brain, hypoproteinemia, psychosis , night apnea.
Oxazepam is not recommended for long-term use due to the possibility of drug dependence.
With long-term treatment, it is necessary to monitor blood counts and liver function.
Any change in dosage should be made under the supervision of a physician.
During treatment with the drug, it is prohibited to drive vehicles.
Indications and contraindications
Tazepam has the following indications for use:
- psycho-emotional disorders that are accompanied by anxiety, excessive worry;
- sleep disturbances manifested by restlessness.
This medicine is not recommended for regular use for everyday stress associated with work, study or everyday life. In such cases, it is necessary to use medications from other pharmacological groups with a similar sedative effect.
The drug is prohibited for use by persons who have had anaphylactic reactions in the past when taking benzodiazepine anxiolytic drugs.
Before using the medicine, it is necessary to conduct an individual sensitivity test. If rashes or other anaphylactoid-type reactions occur, you should refrain from taking this drug, as well as other benzodiazepine drugs.
Tazepam is not used if the patient has the following conditions:
- severe respiratory failure of any etiology;
- nocturnal apnea attacks of neurological origin;
- severe impairment of liver or kidney function, which is accompanied by liver or kidney failure, respectively;
- severe depression, which is accompanied by suicidal tendencies;
- alcoholic delirium, alcohol intoxication or taking other psychotropic substances that suppress or stimulate the activity of the central nervous system.
This product is approved for use only by persons over 18 years of age, since the effect of the drug on the children's body has not been sufficiently studied.
The drug has special pharmacokinetic properties, such as penetration through the blood-brain and placental barriers, and accumulation of the main active substance in breast milk. Since the effect of oxazepam on the fetus and the newborn is unknown, this drug is not recommended for use during pregnancy and lactation.
Analogs
Level 4 ATC code matches:
Bromazepam
Helex
Rudotel
Relium
Tazepam
Xanax
Elenium
Valium Roche
Alprazolam
Tofisopam
Diazepam
Grandaxin
Mezapam
Sibazon
Seduxen
Relanium
Lorazepam
Analogues of Nozepam: Tazepam, Grandaxin, Oxazepam, Relanium, Sibazon, Oxazepam-Ferein, Phenazepam, Diazepam, Elenium.
During pregnancy and lactation
Nozepam has a toxic effect on the fetus and increases the risk of congenital malformations when used in the first trimester of pregnancy. The use of therapeutic dosages at a later date may cause suppression of the nervous activity of the newborn. Systematic use during pregnancy can provoke physical dependence with the appearance of withdrawal syndrome in the newborn.
Use immediately before or during childbirth causes decreased muscle tone, respiratory depression, hypothermia , hypotension and suppresses the sucking reflex in the newborn. The drug is contraindicated during breastfeeding.
Comparative characteristics
Like Phenazepam, Nozepam contains a benzodiazepine active ingredient and is a tranquilizer. Indications for the use of drugs are:
- increased nervous excitability;
- sleep disorder;
- depression;
- muscle hypertonicity;
- tremor of the limbs;
- nervous tic;
- epilepsy;
- alcohol withdrawal syndrome.
Medications have a sedative and relaxing effect, helping to quickly eliminate increased nervous excitability (the calming effect appears 15-20 minutes after taking the tablet). But you should not take medications for more than 2 weeks - addiction may develop and discontinuation of the drug will provoke the appearance of depressive symptoms.
Phenazepam and Nozepam are contraindicated in the following cases:
- COPD and asthma;
- glaucoma;
- alcoholism;
- addiction;
- recent stroke;
- kidney diseases;
- pregnancy and lactation.
Medicines are prohibited for children under 18 years of age.
If you compare Nozepam and Phenazepam, you can see that the drugs have a similar composition and have the same effect on the body.
