Dexmedetomidine

Structural formula
General
Non-proprietary name	Dexmedetomidine
other names	( S ) -4- [1- (2,3-Dimethylphenyl) ethyl] -3 H -imidazole
Molecular formula	C 13 H 16 N 2
External identifiers / databases
EC number	601-281-8
ECHA InfoCard	100.119.391
PubChem	5311068
DrugBank	DB00633
Wikidata	Q412133
Drug information
ATC code	Q N05CM18
Drug class	sedative
Mechanism of action	α 2 adrenoreceptor agonist
properties
Molar mass	200.28 g · mol -1
solubility	soluble in water and DMSO
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Hydrochloride	no GHS pictograms
	no GHS pictograms
H and P phrases	H: no H-phrases
	P: no P-phrases
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Dexmedetomidine (trade name: Dexdor ; manufacturer: Orion Corporation ) is the active isomer ( eutomer ) of medetomidine , which is used as a sedative.

Mechanism of action

Dexmedetomidine activated similar to clonidine dose-dependent α ₂ - adrenoceptors and thus decreases the release of noradrenaline . This happens especially in the locus caeruleus in the brain stem, which is involved in the control of attention and alertness. Allegedly, this specific mechanism of action leads to a sleep-like state from which patients can immediately wake up when spoken to and are able to communicate or follow instructions. Furthermore, α ₂ -adrenoceptors of the sympathetic nervous system are activated, which leads to its inhibition ( sympathicolysis ).

Compared to other sedatives

If you consider the use as a sedative in the intensive care unit, the following benefits are advertised:

better controllability of the depth and duration of sedation compared to benzodiazepines
possible long-term use over several weeks in contrast to propofol
Less habituation and dependency development compared to benzodiazepines and opioids .

One disadvantage is the higher price, which is why it is not used that often. And as with clonidine, watch out for bradycardia and decrease in blood pressure.

effect

In addition to its sedative properties, dexmedetomidine presumably also has a pain-relieving ( analgesic ), anxiety-relieving and muscle-relaxing effect through a change in pain management .

As a side effect, the usual low doses in the context of the inhibition of the sympathetic nervous system sympathicolysis lead to a decrease in heart rate and blood pressure . At high concentrations, such as those that can arise briefly from rapid intravenous injection, the peripheral vasoconstricting effect of dexmedetomidine predominates, so that the blood pressure increases.

application

Dexmedetomidine has been approved in Germany for the sedation of adult, intensive care patients since 2011. In the context of studies, there is experience with the use in children in the context of off-label use . In its meeting in June 2018, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency ( EMA) recommended an extension of the authorization for dexmedetomidine: In the future, the sedative should be used to sedate non-intubated patients before and / or during diagnostic or surgical measures, if sedation is necessary (“procedural / awake sedation”). As a rule, the European Commission complies with such a recommendation ( positive vote ).

Contraindications

Contraindications for the use of the substance exist in the case of known intolerance, uncontrolled low blood pressure, AV block II - III and acute cerebrovascular events.

Trade names

Cepedex , Dexdomitor , Dexdor , Dexmopet , Sedadex , Sileo

literature

H. Ihmsen, TI Saari: Dexmedetomidine. In: The anesthesiologist. 61, 2012, pp. 1059-1066, doi: 10.1007 / s00101-012-2114-1 .

Individual evidence

↑ ^a ^b ^c Tocris: dexmedetomidine , accessed on 27 December of 2019.
↑ Dexdor specialist information as of September 2011.
↑ Summary of opinion (post authorization) , PM EMA of June 28, 2018, accessed on July 12, 2018.
↑ Dexdor technical information published by Orion Pharma, as of June 2015.

[Tocris-1] Tocris: dexmedetomidine , accessed on 27 December of 2019.

[FI-2] Dexdor specialist information as of September 2011.

[3] Summary of opinion (post authorization) , PM EMA of June 28, 2018, accessed on July 12, 2018.

[4] Dexdor technical information published by Orion Pharma, as of June 2015.