Dexmedetomidine

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Dexmedetomidine
Dexmedetomidine skeletal.svg
Systematic (IUPAC) name
(S)-4-[1-(2,3-Dimethylphenyl)ethyl]-3H-imidazole
Clinical data
Trade names Precedex, Dexdor, Dexdomitor
AHFS/Drugs.com monograph
Pregnancy
category
  • US: C (Risk not ruled out)
Legal status
Routes of
administration		 Intravenous infusion only
Pharmacokinetic data
Protein binding 94%
Metabolism Near complete hepatic metabolism to inactive metabolites
Biological half-life 2 hours
Excretion Urinary
Identifiers
CAS Number 113775-47-6 YesY
ATC code N05CM18 (WHO)
PubChem CID: 68602
IUPHAR/BPS 521
DrugBank DB00633 YesY
ChemSpider 4470605 YesY
UNII 67VB76HONO YesY
KEGG D00514 YesY
ChEBI CHEBI:4466 YesY
ChEMBL CHEMBL778 YesY
Chemical data
Formula C13H16N2
Molecular mass 200.28 g/mol
  • n1cc(nc1)[C@H](c2c(c(ccc2)C)C)C
  • InChI=1S/C13H16N2/c1-9-5-4-6-12(10(9)2)11(3)13-7-14-8-15-13/h4-8,11H,1-3H3,(H,14,15)/t11-/m0/s1 YesY
  • Key:CUHVIMMYOGQXCV-NSHDSACASA-N YesY
  (verify)

Dexmedetomidine, sold under the trade names Precedex and Dexdor, among others, is an anxiolytic, sedative, and analgesic medication. Similar to clonidine, it is an agonist of α2-adrenergic receptors in certain parts of the brain.[1] Dexmedetomidine is notable for its ability to provide sedation without risk of respiratory depression (unlike other commonly used sedatives such as propofol, fentanyl, and midazolam) and can provide cooperative or semi-arousable sedation. Dexmedetomidine hydrochloride is also used in veterinary medicine for dogs and cats.[2] The drug was developed by Orion Pharma.[3]

Medical uses

Intensive care unit sedation

Dexmedetomidine is most often used in the intensive care setting for light to moderate sedation. It is not recommended for long term deep sedation. A unique feature of dexmedetomidine is that it has analgesic properties in addition to its role as a hypnotic, but is opioid sparing, and is therefore not associated with significant respiratory depression (unlike propofol).

Many studies suggest dexmedetomidine for sedation in mechanically ventilated adults may reduce time to extubation and ICU stay.[4][5] People on dexmedetomidine are rousable and cooperative, and as such are able to actively cooperative with various procedures.

Compared with other sedatives, some studies suggest dexmedetomidine may be associated with less delirium.[6] However, this finding is not consistent across multiple studies.[5] At the very least, when aggregating many study results together, usage of dexmedetomidine appears to be associated with less neurocognitive dysfunction compared to other sedatives.[7] Whether this has beneficial psychological impact is unclear.[8] From an economic perspective, dexmedetomidine is associated with lower ICU costs.[9] These decreased costs are largely due to a shorter time to extubation.

Procedural sedation

Dexmedetomidine can also be used as sedoanalgesic for procedural sedation, such as during colonoscopy.[10] It can be used as an adjunct with other sedatives like benzodiazepines, opiates, and propofol to enhance sedation and help maintain hemodynamic stability by decreasing the requirement of other sedatives.[11][12] Dexmedetomidine is also used for procedural sedation in children.[13]

Other

Dexmedetomidine may be useful for the treatment of the negative cardiovascular effects of acute amphetamines and cocaine intoxication and overdose.[14][15]

Dosage and administration

Intravenous infusion of dexmedetomidine is commonly initiated with a loading dose followed by a maintenance infusion. There may be great individual variability in the hemodynamic effects (especially on heart rate and blood pressure), as well as the sedative effects of this drug. For this reason, the dose must be carefully adjusted to achieve the desired clinical effect.[16]

Side effects

There are no absolute contraindications to the use of dexmedetomidine. Dexmedetomidine has a biphasic effect on blood pressure with decreased blood pressure observed at lower concentrations and elevated blood pressure at higher concentrations.[17] Rapid IV administration or bolus has been associated with slow heart rate (bradycardia) and low blood pressure (hypotension) due to peripheral α2-receptor stimulation.

Interactions

Dexemedetomidine may enhance the effects of other sedatives and anesthetics when co-administered. Similarly, drugs that lower blood pressure and heart rate, such as beta blockers, may also have enhanced effects when co-administered with dexmedetomidine.[18]

Pharmacodynamics

Dexmedetomidine is a highly selective α2-adrenergic agonist. Unlike opioids and other sedatives such as propofol, dexmedetomidine is able to achieve its effects without causing respiratory depression. Dexmedetomidine induces sedation by decreasing activity of neurons in the locus ceruleus in the brain stem, thereby increasing activity of inhibitory gamma-aminobutyric acid neurons in the ventrolateral preoptic nucleus.[19] In contrast, other sedatives like propofol and benzodiazepines directly increase activity of gamma-aminobutyric acid neurons.[20] Sedation by dexemeditomidine mirrors natural sleep.[21] As such, dexmedetomidine provides less amnesia compared to benzodiazepines.[20] Dexmedetomidine also has analgesic effects at the spinal cord level and other supraspinal sites.[20] Thus, unlike other hypnotic agents like propofol, dexmedetomidine can be used as an adjunct medication to help decrease the opioid requirements of people in pain while still providing similar analgesia.

Pharmacokinetics

Intravenous dexmedetomidine exhibits linear pharmacokinetics with a rapid distribution half-life of approximately 6 minutes and a terminal elimination half-life of approximately 2 hours. Plasma protein binding of dexemedotomindine is ~94% (mostly albumin).[22]

Dexmedetomidine is metabolized by the liver via glucuronidation and cytochrome P450. As such, this drug should be used with caution in people with liver disease.[18]

The majority of metabolized dexmedetomidine is excreted in the urine ~95%.

History

Dexmedetomidine was approved in 1999 by the Food and Drug Administration (FDA) as a short term sedative and analgesic (<24 hours) for critically ill or injured people on mechanical ventilation in the intensive care unit (ICU). The rationale for its use short term was due to concerns over withdrawal side effects, such as rebound high blood pressure. These withdrawal side effects have not been consistently observed in research studies, however.[23] More recently, in 2008 the FDA expanded its indication to include nonintubated people requiring sedation for surgical or non-surgical procedures, such as colonoscopy.

References

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ http://www.dexdomitor.com/
  3. ↑ http://orion.fi/en/Research-and-developement/Achievements/
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ 5.0 5.1 Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  18. ↑ 18.0 18.1 Lua error in package.lua at line 80: module 'strict' not found.
  19. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  20. ↑ 20.0 20.1 20.2 Lua error in package.lua at line 80: module 'strict' not found.
  21. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  22. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  23. ↑ Lua error in package.lua at line 80: module 'strict' not found.

External links

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