Dormicum ( Midazolam ) – Benzodiazepine

 

Dormicum is a drug that consists of a common substance known as midazolam. It comes from a group of medicines called benzodiazepines, that have hypnotic, sedative and skeletal muscle relaxant properties. Dormicum is mainly used to treat insomnia or to prepare patients for surgery.

Characteristics of the substance Midazolam

The hypnotic from the group of benzodiazepine derivatives.

Dormicum ( Midazolam )- a white or slightly yellowish crystalline substance, insoluble in water. Midazolam hydrochloride is soluble in water.

 

Pharmacology

Pharmacological action – hypnotic, sedative.

Interacts with specific benzodiazepine receptors located in the postsynaptic GABAA receptor complex, increases the sensitivity of GABA receptors to the mediator (GABA). This increases the frequency of opening ion channels for incoming currents of chloride ions, hyperpolarization of the membrane occurs and neuronal activity is inhibited. Prevents re-uptake of GABA, contributing to its accumulation in the synaptic cleft. There is evidence that excessive accumulation of GABA in neuronal synapses causes induction of general anesthesia.

 

When ingested quickly and completely absorbed from the digestive tract, has the effect of “first passage” through the liver (30-60% of Dormicum – midazolam is metabolized). Cmax in the blood is reached within 1 hour (eating increases the time to reach Cmax). With the / m introduction, the absorption is fast and complete, Cmax is achieved within 30 -45 minutes, bioavailability is more than 90%. In blood, 95-98% binds to proteins, mainly albumin. Quickly distributed in the body. The volume of distribution is 1-3,1 l / kg. Passes through the histogematic barriers, incl. GEB, placental, penetrates into breast milk in small amounts. In the cerebrospinal fluid penetrates slowly and in small amounts. It is subjected to biotransformation in the liver by hydroxylation with the participation of the cytochrome P450 3A4 isoenzyme. The main metabolites, 1-hydroxymidazolam, also called alpha-hydroxyimidazoles (about 60%), and 4-hydroxy-midazolam (5% or less) have pharmacological activity, but lower than the parent compound. Excreted by the kidneys in the form of glucuronic conjugates (less than 1% unchanged). T1 / 2 – 1.5-3 hours. T1 / 2 may increase in patients over 60 years of age, in patients with congestive heart or liver failure, in obese patients (due to increased distribution of midazolam in adipose tissue), in newborns.

Dormicum ( Midazolam ) is characterized by a rapid onset and a short duration of the hypnotic effect. Shortens the phase of falling asleep and increases the overall duration and quality of sleep, without changing the phase of paradoxical sleep. Quickly causes the onset of sleep (after 20 minutes), practically does not have the effect of aftereffect.

 

Has sedative, central muscle relaxant, anxiolytic, anticonvulsant and amnestic effects.

 

Sedation in adults with I / m introduction develops after 15 minutes, with / in the introduction after 1.5-5 minutes. The time to achieve maximum sedation with a / m injection of 30-60 minutes. When IV introduction for introductory anesthesia, the effect is manifested after 1.5-3 minutes, and against a background of drug premedication after 0.75-1.5 minutes. Time of withdrawal from anesthesia – 2 hours (up to 6 hours).

 

 

In the study of reproduction in rats with the introduction of Dormicum midazolam in doses up to 10 times higher than the dose for intravenous administration in humans – 0.35 mg / kg, the effects on fertility in males and female rats were not revealed. Administration of midazolam in the same doses in rats did not lead to adverse effects during pregnancy and during breastfeeding.

 

In the study of teratogenicity in rabbits and rats at doses 5-10 times higher than the dose for humans – 0.35 mg / kg, there was no teratogenic effect.

 

The formation of physical dependence (from mild to moderate severity) in monkeys after taking Dormicum (midazolam ) for 5-10 weeks is shown.

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Application of substance Dormicum ( Midazolam )

Insomnia (falling asleep and / or early awakening) – inside, premedication before diagnostic and surgical procedures (inside, in / m), long sedation with intensive therapy (IM), anesthesia with inhalation anesthesia or as a sleeping pill in combined anesthesia in / in), ataralgesia in children (in / m in combination with ketamine).

 

Contraindications

Hypersensitivity, sleep disorders in psychoses and severe depression, myasthenia gravis, pregnancy (I trimester), childbirth, breast-feeding, children’s age (for oral use).

 

Restrictions on the use

Organic brain damage, cardiac and / or respiratory and / or hepatic insufficiency, sleep apnea, pregnancy (II and III trimester), children’s age (for induction anesthesia).

There are other medicines that can treat Insomnia as well. One the best is Ambien.

Application in pregnancy and lactation

Contraindicated in the first trimester of pregnancy and during childbirth. In the second and third trimester it is possible if the expected effect of therapy exceeds the potential risk to the fetus.

 

The action category for the fetus by FDA is D.

 

For the duration of treatment, breastfeeding should be discontinued.

 

Side effects of the Dormicum  Midazolam

Inside, parenterally.

From the nervous system and sensory organs: drowsiness, lethargy, muscle weakness, blunting of emotions, decreased reaction speed, headache, dizziness, ataxia, diplopia, anterograde amnesia (dose-dependent), paradoxical reactions (agitation, psychomotor agitation, aggressiveness, etc.) .

 

Other: dyspeptic phenomena, skin reactions, local reactions (erythema and pain at the injection site, thrombophlebitis, thrombosis).

 

Possible development of tolerance, drug dependence, withdrawal syndrome, the phenomenon of “recoil” (see “Precautions”).

In parenteral administration: a decrease in the respiratory volume and / or respiratory rate (in 23.3% of patients after IV and in 10.8% after IM), temporary respiratory arrest (in 15.4% of patients after IV and / or the heart, sometimes leading to death – the effects are dose-dependent and are observed mainly in elderly patients with chronic diseases with concomitant use with narcotic analgesics, as well as with rapid IV introduction; laryngospasm, dyspnea; excessive sedation, convulsions (in premature and newborn children), withdrawal syndrome (with sudden withdrawal of long-term IV use); vasodilation, lowering of blood pressure, tachycardia; nausea, vomiting, hiccough, constipation; allergic, incl. skin (rash, hives, itching) and anaphylactoid reactions.

 

Interaction

Potentiates the effects of tranquilizers, antidepressants, other hypnotics, analgesics, anesthetics, neuroleptics, narcotic drugs, alcohol (mutually). A solution of midazolam is incompatible in one syringe with alkaline solutions. In / in the administration of Dormicum midazolam reduces the minimum alveolar concentrations of halothane required for general anesthesia. In / m administration of midazolam during premedication may necessitate a reduction in the dose of thiopental sodium by 15%.

 

Itraconazole, fluconazole, erythromycin, saquinavir increase T1 / 2 midazolam, administered parenterally (with the appointment of large doses of Dormicum or prolonged induction, it is necessary to reduce its dose). The systemic effect of Dormicum is enhanced by inhibitors of the isoenzyme CYP3A4: ketoconazole, itraconazole and fluconazole (co-administration is not recommended), erythromycin, saquinavir, diltiazem and verapamil (simultaneous administration requires a 50% reduction in midazolam dose), roxithromycin, azithromycin, cimetidine and ranitidine meaningful interaction is unlikely). Inductors of the isoenzyme CYP3A4 (carbamazepine, phenytoin, rifampicin) reduce the systemic effect of Dormicum (ingestion) and necessitate an increase in its doses.

 

Overdose

Symptoms: muscle weakness, lethargy, confusion, paradoxical reactions, amnesia, deep sleep; at very high doses – depression of respiration and cardiac activity, apnea, areflexia, coma.

 

Treatment: induction of vomiting and the appointment of activated charcoal (if the patient is conscious), gastric lavage through the probe (if the patient is unconscious), ventilation, maintaining the functions of the cardiovascular system. Introduction of a specific antidote antagonist of benzodiazepine flumazenil receptors (in hospital settings).

 

 

Precautions for the substance Dormicum Midazolam

In / in the introduction should be carried out only in medical institutions in the presence of resuscitative equipment, as well as trained personnel for its use (due to the possibility of suppressing the contractile function of the myocardium and stopping breathing). Temazepam can be used to treat insomnia as well.

 

After parenteral administration, patients should be under observation for at least 3 hours. It should be borne in mind that too fast IV administration (especially in children with unstable cardiovascular and neonatal conditions) can cause apnea, hypotension, bradycardia, cardiac arrest or breathing.

 

The development of paradoxical reactions is most often observed in children and elderly and senile patients.

 

Care should be taken when driving vehicles, as well as in performing work that requires increased concentration and precise coordination of movements, within a day after the application of midazolam.

 

Do not take alcoholic beverages, or use other drugs that cause CNS depression, within 24 hours after taking Dormicum .

 

With repeated use within a few weeks, there may be an addiction (hypnotic effect may be somewhat weakened), as well as drug dependence, incl. when taking therapeutic doses. With a sharp cessation of treatment, there may be a withdrawal syndrome (headache and muscle pain, anxiety, stress, in severe cases – depersonalization, hallucinations, etc.), as well as the development of the phenomenon of “recoil” – a temporary increase in the initial symptoms (insomnia).