Short-term treatment of anxiety (for 2-4 weeks), which can also be associated with insomnia. Treatment of symptoms of sudden alcohol withdrawal. As a tranquilizer and premedication agent. Treatment of increased muscle tone. As an alternative to anticonvulsant treatment for certain types of epilepsy, e.g. clonic seizures of the muscles.
Diazepam acts as an anxiolytic, sedative, hypnotic, anticonvulsant and relaxes skeletal muscle probably by inhibiting the neurotransmitter γ-aminobutyric acid (GABA). It can cause a slight sedation up to the induction of sleep, and even coma, because in o.u.n. works on the limbic, hypothalamus and hill systems. It is believed that the mechanism of the drug's central action relies on the all-spatial interaction of membrane receptors with GABA receptors, which causes the opening of chloride channels and increased chloride ion penetration inside the neuron. The effect of this action is hyperpolarization of membranes and inhibition of neuronal function. Anxiolytic action of diazepam and perhaps a paradoxical stimulating effect o.u.n. they are probably the result of the suppression of the suppression response. The relaxation effect of diazepam on skeletal muscle is based on the inhibition of polysynaptic centripetal pathways. Diazepam can inhibit mono- and polysynaptic rebound, acting as a nerve conduction inhibitor or blocking synaptic signal transduction. The second most likely mechanism of action is the inhibition of motor nerve and muscle function. Diazepam prevents convulsive seizures by increasing presynaptic inhibition and reduces the proliferation of seizure activity, but does not affect normal discharges. In the usual doses, it has a slight effect on the autonomic nervous, respiratory and cardiovascular systems. After oral administration, diazepam is rapidly and almost completely absorbed from the gastrointestinal tract, reaching a maximum concentration in the blood after 30-90 minutes after administration. The blood concentrations of diazepam and its metabolites, which also show pharmacological activity, are dose proportional and show significant individual differences. Diazepam binds to 98-99% plasma proteins. The drug and its metabolites penetrate into the cerebrospinal fluid, across the placenta barrier and into breast milk; in the fetal blood they reach a concentration similar or even higher than in the mother's blood. Diazepam is metabolized in the liver and produces 3 active metabolites: oxazepam, temazepam, demethyldiazepam. The elimination of diazepam is two-phase. Initially there is a fast distribution phase followed by a prolonged phase of elimination by T0,5 ranging from 20 to 50 hours. Diazepam is excreted unchanged in urine unchanged in combination with glucuronic acid, but mainly in the form of metabolites. T0,5 diazepam and its metabolites in healthy volunteers is: diazepam - 20-50 h, demethyldiazepam - 30-200 h, 3-hydroxydiazepam - 5-20 h, oxazepam - 6-20 h. In elderly patients and in patients with impaired liver function and kidneys there is an extension of T0,5 diazepam; also in preterm infants and newborns T0,5 diazepam is longer than in adults and older children.
Contraindications:
Hypersensitivity to benzodiazepines or to any of the excipients.Myasthenia gravis. acute respiratory failure. Sleep apnea syndrome. Severe hepatic failure. Conditions with phobia or obsessions. Chronic psychosis.
Precautions:
The concomitant use of diazepam with alcohol and / or inhibitory drugs o.u.n. Diazepam should be used with extreme caution in patients with a history of alcohol or drug addiction. Diazepam should be avoided in patients who are addicted to drugs that inhibit o.u.n. and alcohol. An exception to the above situation is the treatment of acute withdrawal symptoms. After repeated use for several weeks, some of the benzodiazepine calming effects may be lost.The use of benzodiazepines can lead to mental and physical dependence. The risk of addiction increases with dose and duration of treatment, is greater in patients with a history of alcohol addiction and medications or in patients with personality disorders. Regular monitoring of such patients, avoiding routine prescribing, and gradual dose reduction is very important. During the discontinuation of treatment, the phenomenon of "rebound" may occur temporarily - the severity of symptoms that caused the use of benzodiazepines; they may be accompanied by other symptoms such as mood swings, anxiety, sleep disturbances and insomnia. In the case of benzodiazepines with a short duration of action, the withdrawal effect may occur in the interval between doses, especially when the dose is high. Benzodiazepines may cause amnesia (the risk is greater at higher doses). Symptoms of oblivion may be accompanied by behavior inadequate to the situation. Post-mortem obliteration occurs most often a few hours after taking the drug and therefore, to reduce the risk associated with its occurrence, the patient should be provided with 7-8 hours of uninterrupted sleep. In the event of symptoms of mental and paradoxical reactions (such as anxiety, agitation, irritability, aggression, delusions, anger, rage, nightmares, hallucinations, psychoses, behavioral disorders and other side effects related to behavior), treatment should be discontinued. The probability of such symptoms is greater in children and in elderly patients. Benzodiazepine should not be used in children without a careful assessment of the need to use it; the duration of treatment should be kept to a minimum. Since safety and efficacy have not been established in children less than 6 months of age, diazepam should be used with caution in this group only if alternative treatments are not available. Elderly patients are at risk of falls and hip fractures. Due to the possibility of respiratory depression in patients with chronic respiratory failure, a dose reduction is recommended. Normal precautions should be taken in patients with impaired renal function. Benzodiazepines are not indicated for the treatment of psychotic disorders. They should not be used in monotherapy of depression or anxiety related to depression (increased risk of suicide). In the case of loss of loved ones or bereavement, benzodiazepines may inhibit psychological adjustment. The product contains lactose - should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose. Due to the content of black Caffeine (table 2 mg) and quinoline yellow (table 5 mg), the preparation may cause allergic reactions.
Pregnancy and lactation:
Use during pregnancy, especially in the first and third trimester, should be limited to situations resulting from a significant need. Animal studies have shown harmful effects of benzodiazepines on the fetus. Some studies have reported late behavioral disturbances in newborns exposed to diazepamin utero. If the preparation has been prescribed to a woman during childbearing period, she should be advised to visit a doctor to stop treatment if she intends to become pregnant or suspects that she is pregnant. If, due to the significant need, the woman uses the preparation in late pregnancy or during delivery, the newborn can expect symptoms of pharmacological action of diazepam (lowering of body temperature, pressure, irregular heart activity, lack of sucking reflex, moderate respiratory depression). It should be remembered that in the newborns the ensemble of enzymes responsible for the metabolism of the drug is not yet fully developed (especially in premature babies). In children of mothers who took long-term diazepam during late pregnancy, physical dependence develops and there is a risk of symptoms of withdrawal syndrome after birth. Benzodiazepines are excreted in breast milk - use during breastfeeding is not recommended.
Side effects:
The most common are fatigue, drowsiness, weakness in muscle strength. Frequency unknown: paradoxical reactions (anxiety, agitation, irritability, aggression, delusions, anger, nightmares, hallucinations, psychoses, inadequate behaviors, confusion, emotional hypopnea, decreased alertness, depression,decrease or increase of libido), poor movement, speech impairment, blurred speech, headaches, tremors, dizziness, diplopia, blurred vision, dizziness, heart failure (including cardiac arrest), irregular heart rhythm, hypotension, cardiovascular depression, respiratory depression (including respiratory failure), nausea, dry mouth, excessive salivation, constipation, gastrointestinal disorders, jaundice, increased transaminase and alkaline phosphatase in the blood, skin reactions, urinary incontinence, urinary retention , increased risk of falls and bone fractures (especially in elderly patients). Post-myalema may occur after therapeutic doses, and the risk of its occurrence is higher at higher doses; symptoms of oblivion may be accompanied by behavioral disorders. Long-term use (even therapeutic doses) can lead to mental dependence; sudden withdrawal of the drug may cause a withdrawal effect or "rebound" phenomenon. If addiction develops, sudden discontinuation of the drug causes withdrawal symptoms, such as: headaches, myalgia, increased anxiety, tension, excitement, confusion, irritability; in more severe cases, the following symptoms may occur: loss of sense of reality, personality disorders, hypersensitivity to sound, numbness and tingling of the extremities, hypersensitivity to light, noise and touch, hallucinations, epileptic seizures.
Dosage:
Orally. Adults. Anxiety: 2-10 mg 2-4 times a day. Insomnia associated with anxiety - 5-15 mg a day before falling asleep. Treatment of symptoms of sudden alcohol withdrawal: 10 mg 3-4 times in the first 24 hours, then the dose can be reduced to 5 mg 3-4 times a day. As a premedication agent: 5-15 mg before the procedure. Conditions of increased muscle tone: 2-15 mg per day in divided doses. As an anticonvulsant: 2-10 mg 2-4 times a day. Children over 3 years of age: in anxiety, states of increased muscle tone or as an anticonvulsant: 1-2.5 mg 3-4 times a day or 0.12-0.8 mg / kg or 3.5-24 mg / m2 pc. daily in 3-4 divided doses, then the dose can be gradually increased depending on the effectiveness and severity of side effects. Patients older than 65 years and patients weakened: initially 2-2,5 mg 1-2 times a day, then doses can be increased depending on the patient's response and tolerability. Treatment with diazepam should be as short as possible and should not be longer than 4 weeks in the case of insomnia or 8-12 weeks in the case of anxiety, including the time of gradual withdrawal of the drug. These periods should not be extended without reassessing the patient's condition.