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Like all benzodiazepines, it enhances the inhibitory effect of GABAergic neurons in the cerebral cortex, hippocampus, cerebellum, thalamus and hypothalamus. The existence of specific binding sites benzodiazspinov representing cell membrane protein structures that have a bond with the complex composed of receptor anavar steroid channel. Action lorazepam modulation is “sensitivity” GABA-ergic receptors, which increases the affinity of the receptor to the gamma-aminobutyric acid (GABA), which is the endogenous inhibitory neurotransmitter. The consequence of the activation of benzodiazepine receptor or GABA-A is the increase of chloride ions into the neuron through the receipt chlorine channel. This results in the hyperpolarization of cell membranes, resulting in suppression of neural activity. Clinically lorazepam has anxiolytic and hypnotic effect. Also it has an anticonvulsant and central muscle relaxant effect.

During treatment with Lorafen and within 3 days you can not manage it after completion of road and engage in other potentially hazardous activities that require high concentration and psychomotor speed reactions.

Pharmacokinetics
Absorption
Lorazepam is readily absorbed from the digestive tract. The maximum blood concentration reached after approximately 2 hour. After oral administration of 2 mg of lorazepam. maximum blood concentration is 20 ng / ml.

Distribution
Lorazepam 85% bound to blood proteins. It passes through the blood-brain and placental barriers. Penetrates into breast milk.

Metabolism
The process of biotransformation of lorazepam occurs in the liver. As a result of conjugation with glucuronic acid formed inactive metabolite – glucuronate lorazepam. Biological half-life is about 12 lorazepam hours.

Excretion of
lorazepam is excreted in the urine as glucuronate lorazepam.

Indications for use:

 

  • Neurotic and neurosis-like states, occurring with anxiety, irritability. fatigue. sleep disorders. autonomic disorders.
  • Alcohol withdrawal syndrome (in the complex therapy).
  • Gipertonus skeletal muscle of different genesis.
  • Premedication (preparation for long-term operations and diagnostic procedures).

 

The drug should be used strictly prescribed by a doctor to avoid complications. Attention! The states of mental stress and anxiety associated with everyday problems are not an indication for use of the drug.

Contraindications:

 

  • Hypersensitivity to derivatives of 1,4-benzodiazepines or to any of the substances in the preparation.
  • Severe respiratory failure, regardless of cause.
  • Severe hepatic and renal insufficiency.
  • Myasthenia gravis.
  • Glaucoma.
  • Acute porphyria.
  • Alcohol poisoning.
  • sleep apnea syndrome.
  • Children under 12 years old.

 

Not recommended for use Lorafen drug in patients with psychosis.

In connection with the lactose, Lorafen drug should not be used in patients with hereditary lactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

Due to the sucrose content, Lorafen drug should not be used in patients with hereditary disorders associated with fructose intolerance, syndrome of poor absorption of glucose-galactose or lack of sucrase-isomaltase.

Precautions:
Hepatic and (or) renal insufficiency of mild to moderate severity, chronic respiratory failure, porphyria. depression, suicidal thoughts and attempts in the history of drug, alcohol or drug dependency history, cerebral and spinal ataxia, hyperkinesis. organic brain disease, hypoproteinemia. elderly age.

Not recommended for use Lorafen drug in patients with psychosis.

During treatment with Lorafen and for 3 days after its completion can not drink any alcoholic beverages.

Pregnancy and lactation

Before use of each drug the patient should consult a doctor.

The use of lorazepam in pregnant women is allowed only in the event that its use of the mother is absolute indications, and the use of safer, alternative means is impossible.

Lorazepam penetrates into breast milk. Therefore, if shown the use of the drug in nursing mothers should stop breast-feeding.

Dosing and Administration

The drug must be taken orally, with a little water. The dosage and duration of treatment must be strictly according to the doctor’s instructions.

Adults and children over 12 years
with neurotic and neurosis-like states usually first administered from 2 mg to 3 mg lorazepam daily, divided into 1-3 reception, and then, if necessary, increase the daily dose to maintenance, which often ranges from 2 mg to 6 mg per day, divided into 1-3 receptions.

For relief of symptoms of anxiety can be recommended as a smaller effective dose.

The dosage of lorazepam should be increased gradually, starting with increasing the dose taken in the evening. The maximum you can assign up to 10 mg per day.

When sleep disorders caused by anxiety is usually prescribed once daily at bedtime from 2 mg to 5 mg lorazeiama.

For sedation administered from 2 mg to 5 mg per night before the planned procedure or surgery, and on the day of from 2 mg to 5 mg for 1-2 hours before the procedure or surgery.

Children under 12 years of age
is not recommended lorazepam in children due to lack of data on the safety and efficacy of lorazepam in children aged up to 12 years.

Patients with hepatic and (or) renal insufficiency, mild to moderate severity
must be taken when appointing lorazepam in patients with impaired liver function and (or) renal and mild to moderate severity. The dose is adjusted individually for each patient depending on the patient’s organ failure.

Elderly patients
Elderly patients are more sensitive to drugs acting on the central nervous system. When using lorazepam is recommended in these patients can be prescribed as a lower effective dose. Usually it is sufficient to use half the dose prescribed for adults.

In the symptomatic treatment of anxiety disorders the duration of treatment should be limited to a minimum – it is usually from several days to 2 weeks. In individual cases, anavar steroid the treatment may be extended.The maximum duration of the treatment period, including the phasing out should not exceed 4 weeks. Gradual abolition of the drug should be set individually for each patient. In individual cases, after the evaluation of the patient, the physician may decide to extend the maximum time of treatment.

When you miss a dose Lorafen receiving the drug:
the drug must be taken as soon as possible and continue to regularly taking the drug.

Do not take a double dose to make up the missed dose purpose!

Side effects

From the nervous system (especially in elderly patients): sleepiness, fatigue, dizziness, decreased ability to concentrate, ataxia (gait instability and poor coordination of movements, leading to loss of balance), disorientation, lethargy, muscle atony, blunting of emotions, slowing mental and motor reactions: rarely – headache, euphoria, depression, tremors, depressed mood, catalepsy, amnesia, confusion, dystonic extrapyramidal reactions (uncontrolled movements of the body, including the eyes), myasthenia gravis during the day. dysarthria; rarely -paradoksalnye reaction (aggressive outbursts, fear, suicidal tendencies, muscle spasms, confusion, hallucinations, severe agitation, irritability, anxiety, insomnia).

From the senses: blurred vision (diplopia).

From the side of hematopoiesis: leukopenia, neutropenia, agranulocytosis (chills, pyrexia, sore throat, extreme tiredness or weakness), anemia, thrombocytopenia.

From the digestive system: dry mouth or salivation, heartburn, nausea, vomiting, loss of appetite, constipation or diarrhea; abnormal liver function, increased activity of “liver” transaminases, lactate dehydrogenase, and alkaline phosphatase, jaundice.

From the urogenital system: urinary incontinence, urinary retention, renal dysfunction, increased or decreased libido, dysmenorrhea.

Allergic reactions: skin rash (including erythematous rash.), Itchy skin: very rarely – anaphylactic reactions.

Effect on the fetus: teratogenicity, respiratory failure and suppression of sucking reflex in infants whose mothers used the drug.

Other: addiction, drug dependency, lowering blood blood pressure: rare – respiratory center depression, bulimia, weight loss, tachycardia.

With a sharp decrease in dose or cessation of reception – syndrome “cancel” (irritability, headache, anxiety, excitement, agitation, anxiety, nervousness, sleep disorders spasm of smooth muscles of internal organs and skeletal muscles, myalgia depersonalization, sweating, increased.. sweating, depression, nausea, vomiting, tremors, disorders of perception, including hyperacusis. paresthesia, photophobia, tachycardia, convulsions, hallucinations, psychosis rarely -ostry).

Overdose

The following symptoms may occur as a result lorazepam overdose: drowsiness, disorientation, slurred speech, and in severe cases, loss of consciousness, coma. Danger to life may be poisoning caused by the simultaneous intake of alcohol or lorazepam and lorazepam and other drugs have a depressing effect on the central nervous system.

In case of poisoning lorazepam should take measures aimed at a quick elimination from the body more nevsosavsheysya drug or decrease its absorption from the digestive tract (induced vomiting, reception activated charcoal, gastric lavage – provided the saved consciousness), to monitor basic vital functions (breathing , pulse, arterial blood pressure) and, if necessary, apply appropriate symptomatic treatment.

A specific antidote is flyumazenil.

The inhibitory influence of lorazepam on the central nervous system enhance opioid anlgetiki, drugs for general anesthesia (anesthetics), psychotropic drugs, antidepressants, antihistamines, antihypertensives tsentratnogo action.

  • Drinking alcohol during treatment with lorazepam enhances the inhibitory effects on the central nervous system and can lead to the development of paradoxical reactions such as agitation, aggressive behavior. In addition, alcohol may enhance the sedative effects of lorazepam. up to coma.
  • Lorazepam taken together with other drugs with muscle relaxant action, prolongs and enhances the action of the latter.

 

Pharmacokinetic

 

  • Disulfiram. cimetidine, erythromycin, ketoconazole being an inhibitor of cytochrome P450 isoenzymes inhibit the biotransformation of 1,4-benzodiazepine and enhance their inhibitory effect on the central nervous system.
  • Drugs inducing activity of cytochrome P450 (eg rifampin, phenobarbital, phenytoin, carbamazepine) affect the processes of biotransformation of 1,4-benzodiazepine derivatives and lead to the weakening of their pharmacological action.
  • Theophylline and caffeine may reduce sedative effect of benzodiazepines (including lorazepam). because have a stimulating effect on the central nervous system and are capable of inducing hepatic enzymes responsible for the metabolism of drugs. This effect is caused by theophylline and caffeine may be absent in smokers.
  • Oral contraceptives used along with lorazepam, may enhance its metabolism, half-life of lorazepam may be reduced.

special instructions

Lorafen The drug should be used under strict medical supervision.

  • If after 7-14 days of administration of the drug is observed relief of symptoms of disease or relapse, the patient should seek medical advice.
  • Regular use of benzodiazepine drugs or a similar activity, including lorazepam for several weeks, may reduce the effectiveness of their actions as a result of the development of tolerance.
  • The use of benzodiazepines or medications such actions can lead to mental and physical drug dependence. Drug dependence risk increases with dose and duration of treatment and increases in alcohol-dependent patients with drug dependence, and in patients with addiction to other drugs.
    In the case of drug dependence, abrupt discontinuation of the drug can cause withdrawal syndrome .
    Typical withdrawal symptoms are: headache, irritability, muscle pain, agitation and emotsionatnoe tension, restlessness, confusion and disorientation, sleep disturbances. In severe cases may appear: loss of sense of reality of the (derealization), personality disorder (depersonalization), increased sensitivity to touch (tactile hypersthesia), increased sensitivity to auditory and visual stimuli (acoustic and visual hypersthesia). the feeling of “pins and needles” and numbness in the extremities, hallucinations, convulsions or seizures. The most dangerous may be abrupt discontinuation of treatment carried out for a long time, during which the lorazepam was used at doses higher than average. Withdrawal symptoms are more pronounced then.
    There is evidence that in the case of short-acting benzodiazepines and benzodiazepinopodobnyh drugs, withdrawal symptoms may occur even in the intervals between the reception of a single dose.especially if the drug is used at high doses.
  • After the treatment, there may come a temporary recurrence of symptoms to a greater extent than those who were the cause of the initial treatment (so-called insomnia for “bounce” type). These symptoms are often accompanied by mood changes, anxiety, restlessness, increased motor activity. The patient should be informed of the possibility of insomnia in an “bounce”, this will reduce his anxiety if such symptoms appear after discontinuation of treatment.
    The probability of occurrence of withdrawal syndrome or insomnia such as “bounce” is increased when the drug is stopped suddenly. It is recommended to gradually reduce the dose of the drug, in order to minimize the risk of such symptoms.
  • Lorazepam. as benzodiazepines and drugs of similar action may cause antegrade amnesia. Such a condition occurs most anavar steroid often several hours after taking the drug, especially in large doses. In order to minimize the risk of amnesia, we recommend the use of lorazepam half an hour before bedtime and providing conditions for continuous 7-8 hours of sleep.
  • Lorazepam. as benzodiazepines and drugs of similar action may cause paradoxical reactions such as agitation, irritability, aggression, nightmares, hallucinations, psychoses, somnambulism, depersonalization disorder, pronounced sleep disturbance and other behavioral side effects. These reactions are much more common in elderly patients.
    In the event of such symptoms should immediately discontinue treatment with Lorafen.
  • Lorafen drug should be used with caution in elderly patients (over 65 years), due to increased adverse events in this age group, mainly targeting violation and coordination of movements, which can lead to loss of balance.
  • Lorazepam should be used with caution in patients with chronic respiratory failure patients, since found that benzodiazepines exhibit a depressant effect on the respiratory center.
  • Lorazepam should be used with caution in patients with symptoms of depression. These patients may appear suicidal thoughts. Due to the possibility of intentional overdose, these patients should be prescribed the drug in Lorafen smallest possible doses. Also, benzodiazepines and drugs such actions should not be used as the only drug to treat depression or anxiety associated with depression.Monotherapy with these drugs can enhance suicidal tendencies.
  • Benzodiazepines and similar drugs, proceed with great caution in patients with alcohol, drug or drug addiction in history. These patients while receiving lorazepam should be under strict medical supervision, as They are at risk of addiction, psychic and physical dependence.
  • The drug Lorafen must be used with caution in patients with non-acute form of porphyria. Use of the drug can exacerbate the symptoms of this disease.
  • During prolonged therapy with Lorafen shows periodic blood tests (morphological analysis with smear) and urinalysis.
  • During treatment with Lorafen and 3 days after its completion can not drink any alcoholic beverages.

 

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