Midazolam

Мидазолам Constitutional formula

The description is actual on 02.07.2015

  • Latin name: Midazolamum
  • ATH code: N05CD08
  • Chemical formula: C18H13ClFN3
  • CAS code: 59467-70-8

Chemical name

8-Hlor-6-(2-ftorfenit) - 1-метил-4H-имидазо[1,5-a] [1,4] benzodiazepine (in the form of a hydrochloride or a maleate)

Chemical properties

Midazolam is carried to a class of benzodiazepine sedatives. Substance was synthesized in the 76th year of the 20th century the American scientists Valzer and Freier.

Midazolam is safer, than other benzodiazepines. After its use at patients thrombophlebitis develops less often. Properties of this substance attentively studied since the end 70 to the 90th years, its high performance at treatment of attacks of epilepsy was not found yet. At the moment means is most widely used in anesthesiology. In the USA substance is used as a medicine for a lethal injection for the persons sentenced to death.

Substance is appointed most often for premedication before operative measures as it possesses fast time of recovery, high performance and a hypotoxicity. It is convenient that medicine often causes an ecmnesia that blocks unpleasant memories of patients of a preparation for surgery. However in benzodiazepine dependence means can cause attacks and the mixed overdoses in patients.

Form of production of Midazolam

Medicine is let out in the form of a hydrochloride or maleic acid ester. Maleic acid ester is white or yellowish crystals, badly insoluble in water. The Midazolam hydrochloride in water is dissolved well, and most often it is used in medical practice.

Pharmacological action

Somnolent, anksiolitichesky, sedative, anticonvulsant, anamnestic, myorelaxation.

Pharmacodynamics and pharmacokinetics

As well as other representatives of this number of drugs, Midazolam enters interaction with specific benzodiazepine receptors which are in a postsynaptic receptor complex of piperidic acid. Substance raises degree of sensitivity of these receptors to influence to the GAMK-mediator, increases the frequency of opening of channels for chlorine ions, activity of neurons almost completely oppresses. Midazolam also leads to accumulation of piperidic acid in a synaptic gap and thus supports the general anesthesia at the sufficient level.

Medicine reduces backfilling time, increases duration and quality of a dream, does not mention a paradoxical dream.

If medicine is taken orally, then active ingredient quickly gets to a system blood stream, is almost completely acquired by a digestive tract. Midazolam reaches the maximum concentration within an hour. It should be noted that the speed of achievement of Cmax depends on meal.

At intravenous administration means is acquired even quicker, practically all administered drug is metabolized (biological availability higher than 90%). The maximum concentration in blood – through half of hour (at most 45 minutes). Sedation can be observed in one and a half minutes after an injection (15 minutes at intramuscular introduction).

Extent of linkng of substance with proteins of plasma (albumine) reaches 98%. Medicine is capable to break hematoencephalic, placental barriers, to get into breast milk. In a liver about 45% of means undergo reactions of a metabolism – a hydroxylation with participation of system of P450 3A4 cytochrome. 2 active metabolites are as a result formed: 1 hydroxymidazolams (60%) and 4-hydroxy-midazolam (less than 5%).

Medicine is brought out of an organism through kidneys in the form of metabolites and it is insignificant – in not changed look. An elimination half-life – from one to 3 hours.

At elderly people, newborns, with a serious illness of a liver, obesity and congestive heart failure pharmacokinetic indicators are a little changed, the elimination half-life, as a rule, increases.

Amnesia at adult patients comes through half of hour — hour at intravenous or intramuscular administration. Cases of anamnestic activity of means are registered and at oral administration.

Most often after Midazolam to the patient enter narcotic analgetics or other drugs for the general anesthesia. Due to the insufficient number of clinical tests and short duration of influence of medicine on the person it is impossible to draw a conclusion on carcinogenicity of Midazolam.

Substance does not show mutagen activity, fertility influences. Systematic reception of means can lead to development of physical dependence and a withdrawal.

Indications to use

Drug is used:

  • for premedication of patients before operative measures (tablets and injections);
  • at disturbances of a sleep pattern, problems with backfilling, early raising (tablet);
  • for the patient's sedation when carrying out an intensive care (intramuscular injections);
  • as an introduction anesthesia at an inhalation or combined anesthesia (intravenously);
  • as a part of complex therapy for treatment of an ataralgeziya at children (+ Ketaminum, intramusculary).

Contraindications

Midazolam, as well as other representatives of group of benzodiazepines demand care in use.

It is impossible to appoint them:

  • to pregnant women (1 trimester) and the feeding women;
  • at mental disorders, psychoses, depressions;
  • to alcoholics;
  • at an allergy to Midazolam or benzodiazepines;
  • to patients with drug addiction;
  • at a myasthenia;
  • to children (for the tableted form).

Extra care should be observed:

  • on 2 and 3 trimesters of pregnancy;
  • at organic lesions of a brain;
  • to persons with cordial, respiratory (apnoea) or a liver failure;
  • if substance is used for an introduction anesthesia at children.

Side effects

At reception of tablets the following side reactions can be shown:

  • weakness, drowsiness and general slackness;
  • obtusion of feelings and emotions, decrease in speed of psychomotor reactions;
  • head pains, ataxy;
  • depression;
  • dizziness, diplopia;
  • depending on a dosage, there is a probability of developing of amnesia;
  • aggression, agitation, excitement and other paradoxical reactions (the probability of development is higher at alcoholics, addicts, elderly people and children, at parenteral administration);
  • indigestion;
  • enanthesis, allergic reactions;
  • hypotonia;
  • development of tolerance, withdrawal and dependence on drug.

At patients, 60 years are more senior the risk of falling, fractures of a hip and memory impairment increases.

At long use of benzodiazepines memory considerably worsens, and the patient of it can not notice. It is proved that final recovery of normal thought processes happens later half of year after the end of reception of this substance.

At intravenous and intramuscular administration, except the reactions listed earlier also sometimes are shown:

  • laryngospasm;
  • oppression of respiratory functions, up to an apnoea or heart;
  • otdyshka, spasms, excessive sedation;
  • abstinence, vazodilatation;
  • hypotension, increase in ChSS;
  • lock, vomiting;
  • small tortoiseshell, enanthesis and itch;
  • anaphylactic reactions, anaphylactoid reactions;
  • at a combination to fentanyl the risk of development of an apnoea and an anoxemia increases.

Midazolam, application instruction (Way and dosage)

The dosage and the mode of reception is defined by the attending physician.

Inside means is appointed on 7,5-15 mg a day, before withdrawal to a dream. The tablet cannot be divided or chewed.

Duration of treatment should not exceed 14 it, it is preferable – several days. To the patients belonging to risk group, it is necessary to begin treatment with the minimum dosages.

In anesthesiology and when carrying out an intensive care medicine is used intramusculary or intravenously, rektalno (children), inside.

The mode of dosing depends on necessary effect and specific features of the patient.

For premedication:

  • intramusculary enter 100-150 mkg on weight kg for half an hour to an anesthesia;
  • intravenously enter on 50-100 mkg on 1 kg of weight in 10 minutes.

The dosage of 150-200 mkg on kg of weight is usually used in combination with analgetics for creation of an anesthesia. The state is supported by additional intravenous injections.

Overdose

Symptoms of overdose are: the general weakness and especially weakness in muscles, confusion of consciousness, development of paradoxical reactions, a deep sleep, amnesia, apnoea, a lump, lack of breath or heartbeat, an areflexia.

As treatment it is recommended to cause vomiting (to wash out a stomach), to give to the victim enterosorbents (after reception of tablets), artificial ventilation of the lungs, stimulation of cardiac performance. Reception of antagonists of benzodiazepine receptors is shown.

Interaction

Midazolam cannot be combined with the oppressing TsNS means and inhibitors of an isoenzyme CYP3A4 (darunavir, to alprazola, difengidramin, amprenavir, zopiklon, an aprepitant, indinavir, atazanavir, tramadol, atorvastatin, buprenorphine, Verapamil, a haloperidol, clonazepam, Propofol, topiramat).

At a means combination with vorikonazoly it is recommended to correct the Midazolam dosage.

Caffeine in a dosage of 250 mg is capable to lower considerably sedation from means.

Substance strengthens the effect of drugs for an anesthesia and anesthetics: bupivacaine, valproic acid, Hydroxyzinum, diazepam, diltiazem, Ketaminum, Lidocaine.

Ketokonazol considerably increases plasma concentration and reduces plasma clearance of drug, thus sedation amplifies and to last much longer.

Terms of sale

According to the recipe.

Storage conditions

Store drugs on the basis of Midazolam far from children, at a temperature not higher than 30 degrees.

Period of validity

5 years.

Special instructions

It is necessary to use medicine for intravenous injections with extra care, it is exclusive in the conditions of a hospital and specially trained personnel.

After an injection it is necessary to watch the patient attentively within 3 hours.

It is necessary to be careful when using means by pregnant women, elderly patients, persons with drug or alcohol addiction, at small children or people with unstable mentality.

Midazolam and its active metabolites can collect in an organism. Especially at patients with sore kidneys or a liver.

During treatment by means it is better to refrain from driving or other transport.

During the day after taking the medicine it is not recommended to take alcohol or other substances, the oppressing TsNS. It is necessary to remember a possibility of development of a withdrawal, sleeplessness, medicinal dependence.

Newborn

At treatment it is necessary to be means of newborn children especially careful. It is impossible to use substance more than 72 hours, to enter struyno intravenously.

Trade names of Midazolam: Flormidal, Dormikum, Fulsed.

About Midazolam

Synonyms of Midazolam have few responses as most often substance is used for premedication of patients in the conditions of a hospital. However from those that are available, responses with the main positive. Other side reactions, except those that were listed above drugs have no.

The Midazolam price where to buy

It is possible to buy Midazolam in specialized pharmacy chain in the presence of the recipe with a stamp. The price of drug Dormikum makes about 715-770 rubles, for 5 ampoules, on 3 ml.

Section: Active ingredients
PAY ATTENTION! Information on active ingredients on the website is help generalizing, collected from public sources and can form the basis for making decision on use of these substances it is not aware of treatment. Before substance Midazolam use surely consult with the attending physician.
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