Dexmedetomidine

Source: Wikipedia, the free encyclopedia.
Dexmedetomidine
Clinical data
Trade namesPrecedex, Dexdor, Igalmi, others
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • AU: B1
intranasal, sublingual
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding94% (mostly albumin)[3]
MetabolismNear complete hepatic metabolism to inactive metabolites
Elimination half-life2–4 hours[5]
ExcretionUrine
Identifiers
  • (S)-4-[1-(2,3-Dimethylphenyl)ethyl]-3H-imidazole
JSmol)
  • Cc2cccc([C@H](C)c1c[nH]cn1)c2C
  • 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 checkY
  • Key:CUHVIMMYOGQXCV-NSHDSACASA-N checkY
  (verify)

Dexmedetomidine, sold under the trade name Precedex among others, is a drug used in humans for sedation.[3] Veterinarians use dexmedetomidine for similar purposes in treating cats, dogs, and horses.[6][7] It is also used in humans to treat acute agitation associated with schizophrenia or bipolar I or II disorder.[4]

Similar to

Orion Pharma
.

Medical uses

Intensive care unit sedation

Studies suggest dexmedetomidine for sedation in

extubation and ICU stay.[9][10]

Compared with other sedatives, some studies suggest dexmedetomidine may be associated with less delirium.[11] However, this finding is not consistent across multiple studies.[10] At the very least, when aggregating many study results together, use of dexmedetomidine appears to be associated with less neurocognitive dysfunction compared to other sedatives.[12] Whether this observation has a beneficial psychological impact is unclear.[11] From an economic perspective, dexmedetomidine is associated with lower ICU costs, largely due to a shorter time to extubation.[13]

Procedural sedation

Dexmedetomidine can also be used for procedural sedation such as during colonoscopy.[14] It can be used as an adjunct with other sedatives like benzodiazepines, opioids, and propofol to enhance sedation and help maintain hemodynamic stability by decreasing the requirement of other sedatives.[15][16] Dexmedetomidine is also used for procedural sedation in children.[17]

It can be used for sedation required for awake fibreoptic nasal intubation in patients with a difficult airway.[18]

Adjunct in general anesthesia

It has also been used as an adjunct infusion during general anesthesia. In this application, it has been shown to decrease post-operative delirium, pain, nausea and opioid use.[19][20][21][22]

Other

Dexmedetomidine may be useful for the treatment of the negative cardiovascular effects of acute

neuroaxial anesthesia for lower limb procedures.[25] It has been successfully used to treat opioid withdrawal symptoms.[26]

In 2022 it was approved by the FDA for the treatment of agitation in schizophrenia and bipolar disorder.[27]

Side effects

There are no known contraindication to the use of dexmedetomidine. It has a biphasic effect on blood pressure with lower readings at lower drug concentrations and higher readings at higher concentrations.[28] Common side effects include: hypotension, hypertension, with slight decreases in heart rate, arrhythmias, and hypoxia.[29][30] Toxic doses may cause first-degree or second-degree atrioventricular block. These adverse events usually occur briefly after administering a loading dose of the drug. Thus, adverse effects may be reduced by omitting a loading dose.[30]

Interactions

Dexmedetomidine 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.[31]

Pharmacology

Pharmacodynamics

Dexmedetomidine is a highly selective

gamma-aminobutyric acid neurons.[34] Through action on this endogenous sleep-promoting pathway the sedation produced by dexmedetomidine more closely mirrors natural sleep (specifically stage 2 non-rapid eye movement sleep), as demonstrated by EEG studies.[33][35] As such, dexmedetomidine provides less amnesia than benzodiazepines.[34] Dexmedetomidine also has analgesic effects at the spinal cord level and other supraspinal sites.[34]

Site Ki (nM) Species Ref
α1 5 Human [36]
α2A 0.0150–2.1 Human [37]
α2B ND Human
α2C 31 Human [38]

Pharmacokinetics

Intravenous dexmedetomidine exhibits linear pharmacokinetics with a rapid

elimination half-life of intravenous dexmedetomidine ranged 2.1 to 3.1 hours in healthy adults and 2.2 to 3.7 hours in ICU patients.[5] Plasma protein binding of dexmedetomidine is about 94% (mostly albumin).[3]

Dexmedetomidine is metabolized by the liver, largely by glucuronidation (34%) as well as by oxidation via CYP2A6 and other Cytochrome P450 enzymes.[5] As such, it should be used with caution in people with liver disease.[31]

The majority of metabolized dexmedetomidine is excreted in the urine (~95%).[medical citation needed]

It can be absorbed sublingually.[27]

History

Dexmedetomidine was approved in 1999 by the US 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 short-term use was due to concerns over withdrawal side effects such as rebound high blood pressure. These effects have not been consistently observed in research studies, however.[40]

Veterinary use

Dexmedetomidine, under the trade name Dexdomitor (Orion Corporation), was approved in the European Union in for use in cats and dogs in 2002, for sedation and induction of general anesthesia.[41] The FDA approved dexmedetomidine for use in dogs in 2006 and cats in 2007.[42]

In 2015, the European Medicines Agency and the FDA approved an oromucosal gel form of dexmedetomidine marketed as Sileo by pharmaceutical company Zoetis for use in dogs for relief of noise aversion.[43][44]

References

  1. ^ "DEXMEDETOMIDINE FRESENIUS (Fresenius Kabi Australia Pty Ltd)". Department of Health and Aged Care. Archived from the original on 2023-03-18.
  2. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  3. ^ a b c d "Precedex- dexmedetomidine hydrochloride injection, solution". DailyMed. 2 March 2022. Archived from the original on 8 April 2022. Retrieved 8 April 2022.
  4. ^ a b "Igalmi- dexmedetomidine film". DailyMed. 14 December 2022. Retrieved 21 January 2023.
  5. ^
    PMID 28105598
    .
  6. PMID 26740702
    .
  7. ^ "Dexdomitor". Archived from the original on 2013-09-27. Retrieved 2013-08-02.
  8. S2CID 79899746
    .
  9. PMID 24391726
    .
  10. ^
    PMID 25879090
    .
  11. ^
    S2CID 25036525
    .
  12. PMID 25860207
    .
  13. PMID 25887576
    .
  14. S2CID 24778669
    .
  15. S2CID 20014479
    .
  16. PMID 25849473
    .
  17. S2CID 43652106
    .
  18. PMID 24442817
    .
  19. S2CID 3117071
    .
  20. PMID 23524149
    .
  21. S2CID 35590020
    .
  22. PMID 35957999
    .
  23. PMID 17692748
    .
  24. PMID 25724076
    .
  25. PMID 24249987
    .
  26. PMID 22346054
    .
  27. ^ a b "FDA Okays First Sublingual Med for Agitation in Schizophrenia, BD". Medscape. Archived from the original on 2022-04-11. Retrieved 2022-04-11.
  28. S2CID 20795504
    .
  29. ^ "Dexmedetomidine Side Effects: Common, Severe, Long Term".
  30. ^
    PMID 16369581
    .
  31. ^
    S2CID 20447722
    .
  32. doi:10.1093/bjaed/mkv047
    .
  33. ^
    S2CID 5034487
    .
  34. ^
    PMID 19576524
    .
  35. S2CID 34923432
    .
  36. PMID 10715142
    .
  37. PMID 10602691
    .
  38. PMID 17630725
    .
  39. PMID 12067004
    .
  40. S2CID 26258023
    .
  41. S2CID 3691570
    .
  42. ^ "Freedom of Information Summary | Supplemental New Animal Drug Application | NADA 141-267 | Dexdomitor". Food and Drug Administration. 16 August 2010. Archived from the original on 2021-08-28. Retrieved 2018-07-01.
  43. ^ "Recent Animal Drug Approvals". U.S. Department of Health and Human Services. 2 June 2016. Archived from the original on 12 July 2016. Retrieved 3 July 2016. For the treatment of noise aversion in dogs
  44. S2CID 42312260
    .

External links
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