Dexdor

Dexdor or dexmedetomidine is a highly selective α2-receptor agonist that is used to provide moderate to mild sedation in adult patients admitted to the intensive care unit.

Indications Dexdor

The drug is indicated for use as a potent sedative during or after intubation.

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Release form

The medicine is a concentrate for infusion solution (100 mcg/ml). It is available in 2 ml ampoules and 5 or 10 ml vials.

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Pharmacodynamics

Dexmedetomidine has a wide variety of pharmacological effects and is a selective α-2-adrenoreceptor agonist. Since the drug reduces the rate of release of norepinephrine from nerve endings, it has a powerful sympatholytic effect on the body. The sedative effect occurs due to a decrease in the excitability of the blue spot, which is the basis of the NA nucleus (located in the brainstem). By affecting this area, Dexdor has a sedative effect (similar to natural sleep) - the drug causes a sedative effect, but the patient at the same time is in an active waking state.

Dexmedetomidine acts as an anesthetic and also has a mild analgesic effect in chronic lower back pain. The strength of the effect will depend on the dosage. If the infusion rate is low, the central effect will predominate, resulting in a decrease in blood pressure and heart rate. Higher dosages have a peripheral, vasoconstrictor effect, increasing blood pressure. In this case, the bradycardic effect is enhanced. Dexmedetomidine has almost no suppression of the respiratory system.

Pharmacokinetics

Dexmedetomidine binds to plasma proteins by 94%. The constant accumulation limit of the substance is 0.85-85 ng/ml. This component binds to α-1-acid glycoprotein, as well as serum albumin. It is metabolized mainly in the liver.

Following intravenous administration of radiolabeled dexmedetomidine, approximately 95% of the labeled drug was recovered in the urine and another 4% in the feces for 9 days. In the urine, the major metabolic products are 2 isomeric N-glucuronides, together accounting for approximately 34% of the total dose, and an additional N-methylated O-glucuronide, which accounts for 14.51% of the dose. The proportion of minor metabolites (carboxylic acid and additional trihydroxy and O-glucuronide substances) separately is 1.11-7.66%. Less than 1% of the unchanged substance remained in the urine. Approximately 28% of all metabolites found in the urine are unidentified polar metabolic products.

Dosing and administration

Adult patients who have undergone intubation and are sedated may be switched to Dexdor. The initial rate of infusion should be 0.7 mcg/kg/h, and then it may be gradually adjusted (the maximum possible dosage is 0.2-1.4 mcg/kg/h) to achieve the required sedation level. For weakened patients, it is advisable to administer infusions at a low rate at the initial stage. It should be noted that dexmedetomidine is a potent substance, so the infusion rate for it is indicated as 1 hour.

Often, the patient does not need a concentrated loading dose. Patients who need to be sedated more quickly can initially receive a loading infusion of 0.5-1 mcg/kg body weight over 20 minutes. In this case, the initial infusion volume will be 1.5-3 mcg/kg/hour over 20 minutes. After the loading infusion, the subsequent rate will be 0.4 mcg/kg/hour. This indicator can be adjusted later.

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Use Dexdor during pregnancy

It is not recommended to take Dexdor during pregnancy. Use is permitted only in cases where the benefit of taking the medicine for the expectant mother is higher than the risk of negative consequences for the child.

Contraindications

Dexdor is contraindicated in cases of hypersensitivity to dexmedetomidine or other components of the drug.

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Side effects Dexdor

Among the most common side effects of dexmedetomidine are: hypertension (15% of patients), decreased blood pressure (25%), and bradycardia (13%). Other side effects include:

• blood system and metabolism: most often hypo- and hyperglycemia; in rare cases, metabolic acidosis or hypoalbuminemia is observed;
• mental disorders: manic and convulsive states; in rare cases – hallucinations;
• cardiovascular system: most often myocardial infarction, coronary heart disease or tachycardia; less often, AVB of the 1st degree develops, as well as a decrease in cardiac output;
• respiratory system: shortness of breath is occasionally observed;
• digestive tract organs: mainly vomiting with nausea, feeling of dryness in the mouth; rarely – flatulence;
• general disorders, as well as local reactions: mainly hyperthermia or withdrawal syndrome; rarely, thirst and lack of therapeutic effect of the drug may be observed.

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Overdose

The highest infusion rate of dexmedetomidine in overdose was 60 mcg/kg/h for 36 min, and 30 mcg/kg/h for 15 min (in a 20-month-old child and an adult, respectively). The most common reactions in overdose included decreased blood pressure, bradycardia, increased sedation, a feeling of drowsiness, and cardiac arrest.

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Interactions with other drugs

The use of Dexdor in combination with sedatives and hypnotics, as well as anesthetics and opioids, may cause potentiation of the effect of their action. Thanks to research, it was possible to identify potentiation of the effect in a situation of combined use with the substances sevoflurane, propofol, isoflurane, midazolam, and alfentanil.

There are no signs of pharmacokinetic interactions between these substances (except sevoflurane) and Dexdor. However, since there is a possibility of pharmacodynamic interactions when these drugs are combined, the dosage of Dexdor or the sedative, anesthetic, opioid or hypnotic combined with it may require reduction.

When combined with Dextdor drugs that cause bradycardic and hypotensive effects, these effects may be enhanced. However, it should be noted that when studying the interaction of this drug with esmolol, the additional effect was moderate.

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Storage conditions

It is recommended to store the drug at a temperature of no more than 25 °C. After the solution has been diluted, it can be stored for a maximum of 24 hours at a temperature of 2-8 °C.

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Shelf life

Dexdor can be used for 3 years from the date of manufacture of the drug.

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