The pharmacological action of diazepam – anxiolytic drug (tranquilizer) benzodiazepine. Diazepam has a pronounced anxiolytic, gipnosedativny, anticonvulsant and muscle relaxant effects. The effect of the drug due to the ability of diazepam to potentiate the central action of gamma-aminobutyric acid -. Primary inhibitory neurotransmitter of the central nervous system
Like all tools benzodiazepine diazepam forms of functional supramolecular unit component – receptor complex benzodiazepine-gamma-aminobutyric acid-hlorionofor, which is posted on the membranes of neurons.
diazepam selectively stimulates the action of gamma-aminobutyric acid receptors in the reticular formation of the brain column, whereby marked decrease in the excitation of the cortex, and thalamus, hypothalamus and limbic system.
Miorelaksiruyuschee action of diazepam is realized due to inhibitory effect on polysynaptic spinal reflexes.
diazepam enhances the stability of the nerve tissue under conditions of hypoxia and increases the pain threshold, inhibits sympathadrenalic and parasympathetic paroxysms.
For characteristic of diazepam dose-dependent effect on the central nervous system: low dose (2-15 mg per day) have a stimulating effect, and high (more than 15 mg per day) – a sedative.
When receiving diazepam, patients have a reduction of emotional stress, fear, anxiety and worry. On the productive psychotic symptoms genesis (including hallucinations and delusions), diazepam has almost no effect. Rarely observed decrease in affective stress.
In patients with alcohol withdrawal syndrome diazepam reduces the severity of tremor, acute state of agitation, negativism, acute alcoholic delirium and hallucinations.
The therapeutic effect of diazepam develops 2-7 days after the start of treatment.
After oral administration, about 75% dose absorbed in the digestive tract. Peak plasma concentrations of the active ingredient observed after 60-90 minutes after ingestion, the concentration equilibrium established within 1-2 weeks continuous therapy. About 98% of diazepam is bound to plasma proteins. In the liver, almost 99% of diazepam is metabolized to produce both active and inactive metabolites.
The active ingredient and its metabolites penetrate the blood-barrier and determined in breast milk.
Excreted diazepam mostly kidneys (up to 70% of the dose), less than 10% is excreted in the feces .Excretion takes place in two phases, the first phase of the half-life of about 3 hours, the second -. 48 hours
Elderly patients the half-life can increase up to 100 hours in patients with impaired renal and hepatic function – up to 4 days. It is also possible to increase the half-life of diazepam in newborn infants.
In the re-admission of diazepam observed its accumulation in the body.
Diazepam is used in monotherapy and combined treatment of patients with neurotic conditions (including in combination with anxiety syndrome, hysteria, hypochondria, neurasthenia and reactive depression), psychosis, dysphoria and organic diseases of the central nervous system.
Diazepam is prescribed for insomnia (mainly with difficulty falling asleep), as well as in combination with other drugs in patients with alcohol withdrawal syndrome (including accompanied by anxiety, restlessness, nervous tension, transient reactive state and psychoneurosis).
Diazepam is used in the treatment of patients with spasm of the skeletal muscles at the local trauma and and patients with spastic states, which are associated with damage to the spinal cord or brain.
Diazepam may be appointed in the treatment of patients with myositis, arthritis, bursitis, osteoarthritis, rheumatoid spondylitis, and progressive chronic polyarthritis, accompanied by stress in skeletal muscle.
in the complex therapy of Diazepam administered to patients with vertebral syndrome, angina pectoris, headache, tension, and hypertension.
Diazepam may be recommended in psychosomatic disorders in obstetrics and gynecology, with menopausal and menstrual disorders.
Diazepam is used for treatment of patients with status epilepticus, tetanus, and various diseases that are accompanied by itching and irritability (eg, eczema).
Diazepam may be recommended for patients with Meniere’s disease.
Diazepam can be used in premedication before surgery and endoscopic manipulation.
? Diazepam intended for oral administration. Tablets are taken regardless of meals, drinking plenty of drinking water. Duration of therapy and diazepam dose determined by the physician individually for each patient.
As an anxiolytic diazepam, usually prescribed in doses of 2.5-10 mg 2 to 4 times a day.
In psychiatric practice in neurotic disorders, which are accompanied by hysteria or hypochondria and when dysphoria and phobias usually prescribed reception diazepam 5-10 mg twice or thrice daily. If necessary, the dose of diazepam is gradually increased to a maximum daily (60 mg diazepam).
When alcohol abstinence syndrome usually prescribed intake of 10 mg of diazepam three times or four times a day on the first day of therapy, and then reduce the dose to 5 mg diazepam three times a day .Debilitated patients, and patients with atherosclerosis are encouraged to nominate receiving 2 mg of diazepam twice a day and, if necessary, and good endurance gradually increase the dose until the optimum effect.
Working patients are usually advised to take diazepam 2.5 mg 1-2 times during the day and 5 mg in the evening.
in neurological practice with spastic states of central origin usually prescribe diazepam intake of 5-10 mg twice or thrice a day.
in cardiology and rheumatology diazepam usually prescribed in combination with other drugs in a dose of 2-5 mg twice or thrice daily. Patients with vertebral syndrome with bedrest may increase the dose to 10 mg of diazepam four times a day.
In the complex treatment of myocardial infarction, the use of diazepam, usually starts with parenteral administration, and then move on to oral diazepam 5-10 mg up to 3 times day.
in gynecological and obstetric practice usually administered in a dose of diazepam receiving 5.2 mg twice or thrice a day.
The maximum daily dose of 60 mg of diazepam.
in pediatric patients with reactive and psychosomatic disorders and spastic conditions of central origin, As a rule, children under 3 years are administered parenteral administration with individual calculation of the dose for children older than 3 years are designated receiving 2.5 mg diazepam. If necessary, gradually increase the dose, careful monitoring of the patient.
Patients older the recommended dose of diazepam reduced by half. With good endurance dose diazepam elderly patients it can be gradually increased.
Diazepam is usually good tolerated by patients, however, during the drug therapy can not exclude the possibility of such undesirable effects caused by diazepam:
From the nervous system: muscle weakness, drowsiness, lethargy, emotional lability, ataxia, decreased concentration, visual disturbances, confusion , depressive states. In addition, possible development of headache, tremor, dysarthria, acute excitation, dizziness, hallucinations, sleep disorders and memory.Diazepam can cause the development of drug dependence and withdrawal symptoms.
From the digestive and hepatobiliary system: violations of the chair, hypersalivation, dry mucous membranes of the mouth, nausea, jaundice, elevated alkaline phosphatase, and hepatic transaminases.
Allergic reactions: skin rash, urticaria.
Other: reduction or an increase in libido, urinary incontinence.
When used in obstetric practice in term and preterm infants may develop muscle weakness, decrease in body temperature and respiratory disorders (dyspnea).
The risk of developing drug dependence is higher in alcohol-dependent patients had a history, as well as patients, who receive high doses of diazepam. In the case of drug dependence with a sharp discontinuation of diazepam may develop the syndrome, which is accompanied by headache and muscle pain, anxiety, irritability, confusion, and emotional stress. In severe cases of withdrawal accompanied by hyperacusis, depersonalization, sensitivity to light, increased tactile sensitivity, seizures, hallucinations, and paresthesias.
Diazepam is not used for the treatment of people with individual intolerance to the active ingredient tablets.
Diazepam is not administered to patients with a tendency to suicide, myasthenia, alcohol dependence (except in cases of acute withdrawal), drug addiction, and epilepsy or seizures in history.
Diazepam is contraindicated in patients with hypercapnia, narrow-angle glaucoma and acute attack of glaucoma, spinal and cerebral ataxia, porphyria and hepatitis.
Diazepam should not be administered to patients with sleep apnea or severe respiratory or cardiac failure.
Use caution, appointing diazepam to patients with impaired renal and hepatic function.
Diazepam in pediatric population should be taken only for the treatment of children over 3 years.
avoid potentially unsafe activities that require attention, while taking diazepam.
is strictly forbidden to use the drug Diazepam in the first and third trimester of pregnancy. In the second trimester of pregnancy Diazepam may be appointed only under the constant supervision of a physician.Women of childbearing age a reliable contraceptive should be adjusted before taking diazepam.
In the period of lactation receiving diazepam is prohibited. If you avoid taking the drug Diazepam should not be, should decide on the abolition of breastfeeding before you start taking the drug.
Drugs that inhibit microsomal oxidation (including oral contraceptives, cimetidine, fluoxetine, metoprolol, valproic acid, disulfiram, isoniazid, propranolol and ketoconazole) during concomitant use increases the half-life of diazepam and enhance its effects.
Diazepam potentiates the effect of alcohol, antipsychotics, sedatives drugs and anti-depressants on the central nervous system.
The drug diazepam enhances the analgesic effects of muscle relaxants and anesthetics.
There is a decrease of diazepam absorption in the combined use with antacids.
with the simultaneous use of diazepam and antihypertensives may be a significant reduction of antithrombin.
Clozapine may increase the risk of respiratory depression in patients receiving diazepam.
Possibly increase the plasma concentrations of nonpolar cardiac glycosides and increased risk of digitalis intoxication while taking these drugs with diazepam.
diazepam reduces the effectiveness of levodopa.
at the same time taking omeprazole increases the half-life of diazepam.
Stimulants, analeptics and drugs that inhibit monoamine oxidase, the combined use reduce the effectiveness of diazepam.
Low-dose theophylline may reduce or modify the sedative effect of diazepam.
When receiving excessive doses of diazepam in patients observed the development of paradoxical excitation, inhibition of cardiac and respiratory activity, areflexia, and apnea and coma.
The specific antidote – a benzodiazepine antagonist – flumazenil. In case of overdose gastric lavage is performed, prescribed enterosorbentnye funds. When diazepam intoxication should monitor the function of the circulatory system and respiratory. If necessary, carry out artificial lung ventilation.
Hemodialysis in overdose diazepam is ineffective.
Tablets Diazepam containing 5 or 10 mg of the active substance in the blister packs of 10 pieces, in a cardboard bundle nested two blister packs.
Tablets Diazepam containing 5 or 10 mg of the active substance in the blister packs of 24 pieces, in a cardboard 1 pack enclosed blister pack.
Diazepam should be stored in rooms where the temperature regime is maintained between 15 and 25 degrees Celsius, for a maximum of 2 years after the release.