Flunitrazepam (Flunitrazepamum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Sleeping Pills

Included in the formulation
АТХ:

N.05.C.D.   Benzodiazepine derivatives

N.05.C.D.03   Flunitrazepam

Pharmacodynamics:

The drug is a benzodiazepine derivative, has an anxiolytic (relieves emotional tension, reduces anxiety, fear, anxiety) and sedative effect, central muscle relaxant activity and anticonvulsant properties. It alleviates the symptoms of acute alcohol withdrawal.

The mechanism is realized due to the potentiation of GABAergic processes in the cerebral cortex, hippocampus, cerebellum, thalamus and hypothalamus.

The mechanism of action is associated with the stimulation of benzodiazepine (ω) receptors whose agonist flunitrazepam is an. There are 3 subtypes of ω-receptors - ω1, ω2, ω3. The hypnotic effect of the drug is due to the preferential binding to ω1-receptors. Stimulation of benzodiazepine receptors located on the γ-subunit of the GABAA receptor is accompanied by an increase in the affinity (sensitivity) of GABA receptors to GABA and an increase in the efficacy of this mediator. At the same time, GABA activity does not increase, which causes the absence of narcotic effect in benzodiazepines. With an increase in the sensitivity of GABA receptors to GABA under the influence of flunitrazepam, the frequency of opening of the chlorine channels increases,As a result, a greater number of negatively charged chlorine ions enter the neuron, which leads to hyperpolarization of the neuronal membrane and the development of inhibitory processes.

Reduces the excitability of the subcortical structures of the brain, inhibits polysynaptic spinal reflexes. Sleeping effect develops rapidly and lasts 6-8 hours. It also has sedative, anxiolytic, miorelaxing (central) and anticonvulsant action. Reduces psychomotor activity, causes amnesia.

Pharmacokinetics:After oral administration at a dose of 1 mg, the maximum concentration is noted after 0.75-2 hours and is 6-11 ng / ml. Bioavailability is 70-90%. Eating food reduces the speed and degree of absorption. Binding to blood proteins - 78%. Daily intake is accompanied by a moderate cumulation in the plasma. With multiple admission, the equilibrium concentration of flunitrazepam in plasma is reached after 5 days and at a dose of 2 mg is at least 3-4 ng / ml. The equilibrium concentration of pharmacologically active N-demethyl-metaboliteslithium is almost identical to that of the starting material. The total plasma clearance is 120-140 ml / min. The volume of distribution in the equilibrium state is 3-5 l / kg.Rapidly penetrates into the cerebrospinal fluid. Slowly passes through the placental barrier, penetrates into breast milk. Metabolised in the liver (10-15% at the first pass). The main metabolites in the plasma are 7-aminoflunitrazepam and N-desmethylfluniterazepam, in urine - 7-aminoflunitrazeps. It is excreted primarily by the kidneys mainly in the form of metabolites and with feces. The half-life of flunitrazepam is 16-35 h, half-life N-demethylflunitreazepam - 28 h.
Indications:Sleep disorders of various origins, premedication, introduction to anesthesia, maintenance of anesthesia.
ICD-10

V.F30-F39.F30   Manic episode

V.F40-F48.F41.0   Panic disorder [episodic paroxysmal anxiety]

V.F40-F48.F41.1   Generalized anxiety disorder

V.F40-F48.F41.2   Mixed anxiety and depressive disorder

V.F40-F48.F43   Reaction to severe stress and adaptation disorders

V.F40-F48.F43.1   Post-Traumatic Stress Disorder

V.F40-F48.F43.2   Disorder of adaptive reactions

V.F40-F48.F45   Somatoform disorders

V.F40-F48.F48.0   Neurasthenia

V.F50-F59.F51.0   Insomnia inorganic etiology

VI.G40-G47.G47.0   Disturbances of falling asleep and maintaining sleep [insomnia]

Contraindications:Hypersensitivityhypercapnia, severe respiratory failure, sleep apnea syndrome, severe renal and / or hepatic impairment, myasthenia gravis, acute ethanol poisoning, hypnotics, analgesics, antipsychoticor antidepressantand means, lithium; drug addiction, chronic alcoholism in the anamnesis, pregnancy, breast-feeding, early childhood (including newborns).
Carefully:Organic brain damage, cerebral circulation disorders, coma, shock, chronic heart failure, respiratory failure, liver failure, chronic renal failure, child age, advanced age.
Pregnancy and lactation:Flunitrazepam is contraindicated in pregnancy and lactation (breastfeeding).
Dosing and Administration:

Inside adults - 1-2 mg for 20 minutes before sleep, elderly patients - 0.5-2 mg, children and adolescents 0.5-1.5 mg. The course of treatment is from 2-5 days to 2-3 weeks (not more than 4 weeks, including a period of gradual cancellation).

Parenterally, in a dose of 0,015-0,03 mg / kg for premedication for 30-60 minutes before the beginning of anesthesia intramuscularly, for injection into anesthesia - intravenously slowly at a rate of 2 mg / min.

Side effects:

From the side nervous system and sense organs: headache, dizziness, fatigue, weakness, impaired concentration, confusion, slowing of physical and mental reactions, muscle weakness, paresthesia, anterograde amnesia (may be accompanied by strange behavior), disorientation upon awakening, paradoxical reactions (anxiety, hallucinations, agitation, irritability, aggressiveness, delirium, fits of rage, nightmarish dreams, psychosis), sleep disturbance, drowsiness during the day, manifestation of latent depression, fatigue, ataxia, dip opium seizures aftereffect.

Other: leukopenia, agranulocytosis, difficulty breathing, hypotension, dyspeptic phenomena, skin rash, angioedema, retention of urination, changes in libido.

Overdose:

Symptoms: drowsiness, confusion, lethargy, ataxia, muscle hypotension, arterial hypotension, respiratory depression, coma, possible fatal outcome.

Treatment: induction of vomiting, gastric lavage, intake of activated carbon, ensuring airway patency, monitoring vital signs,introduction of a specific antagonist of benzodiazepine flumazenil receptors (in hospital settings).

Interaction:

When used simultaneously with drugs that exert a depressing effect on the central nervous system (with barbiturates, antidepressants, antipsychotics, tranquilizers, opioid analgesics, antihistamines and sedatives, clonidine), ethanol exacerbates the CNS. The risk of drug dependence increases with the simultaneous use of other hypnotics, psychotropic drugs, as well as ethanol.

When used simultaneously with inhibitors of microsomal liver enzymes, the effects of flunitrazepam may be enhanced.

Aminophylline: antagonism with anxiolytic and hypnotics of flunitrazepam.

Erythromycin: A moderate increase in AUC flunitrazepam.

Special instructions:

Possible addiction, drug dependence, withdrawal and "recoil" syndrome.

The risk of drug dependence increases with the simultaneous use of other sleeping pills, psychotropic drugs, alcohol.With a sharp cancellation of flunitrazepam, as well as with drug dependence on flunitrazepam, the development of withdrawal syndrome (the resumption of sleep disorders in a more pronounced form, anxiety, irritability, headache, tremor, excessive sweating, convulsions and hallucinations) is possible.

After parenteral administration, patients should be under medical supervision for 24 hours. In the event of a paradoxical reaction to flunitrazepam, it should be canceled.

Flunitrazepam is recommended to be injected into a vein of large caliber. Intraarterial administration should be avoided.

Children under the age of 14 years are used only in absolute indications.

During the treatment should not drink alcohol.

Impact on the ability to drive vehicles and manage mechanisms.

Patients receiving flunitrazepam, it is necessary to refrain from engaging in potentially dangerous activities requiring increased attention and rapid psychomotor reactions.

Instructions
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