Dexmedetomidine
|
| Systematic (IUPAC) name |
|
(S)-4-[1-(2,3-Dimethylphenyl)ethyl]-3H-imidazole
|
| Clinical data |
| Trade names |
Precedex, Dexdor, Dexdomitor, Sileo |
| AHFS/Drugs.com |
Monograph |
Pregnancy
category |
- US: C (Risk not ruled out)
|
Routes of
administration |
Intravenous infusion only |
| Legal status |
| Legal status |
|
| 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 Y |
| ATC code |
N05CM18 (WHO) |
| PubChem |
CID 68602 |
| IUPHAR/BPS |
521 |
| DrugBank |
DB00633 Y |
| ChemSpider |
4470605 Y |
| UNII |
67VB76HONO Y |
| KEGG |
D00514 Y |
| ChEBI |
CHEBI:4466 Y |
| ChEMBL |
CHEMBL778 Y |
| Chemical data |
| Formula |
C13H16N2 |
| Molar mass |
200.28 g/mol |
SMILES
-
n1cc(nc1)[C@H](c2c(c(ccc2)C)C)C
|
InChI
-
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 Y
-
Key:CUHVIMMYOGQXCV-NSHDSACASA-N Y
|
| (verify) |
Dexmedetomidine, sold under the trade names Precedex among others, is an anxiety reducing, sedative, and pain medication. 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.
Similar to clonidine, it is an agonist of α2-adrenergic receptors in certain parts of the brain.[1] Dexmedetomidine hydrochloride is also used in veterinary medicine for dogs and cats.[2] The drug was developed by Orion Pharma.[3]
Contents
- 1 Medical uses
- 1.1 Intensive care unit sedation
- 1.2 Procedural sedation
- 1.3 Other
- 1.4 Dosage and administration
- 2 Side effects
- 3 Interactions
- 4 Pharmacodynamics
- 5 Pharmacokinetics
- 6 History
- 7 Veterinary use
- 8 References
- 9 External links
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 cooperate 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.[6] From an economic perspective, dexmedetomidine is associated with lower ICU costs.[8] 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.[9] 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.[10][11] Dexmedetomidine is also used for procedural sedation in children.[12]
Other
Dexmedetomidine may be useful for the treatment of the negative cardiovascular effects of acute amphetamines and cocaine intoxication and overdose.[13][14]
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.[15]
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.[16] 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.[17]
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 noradrenergic neurons in the locus ceruleus in the brain stem, thereby increasing the activity of inhibitory gamma-aminobutyric acid neurons in the ventrolateral preoptic nucleus.[18] In contrast, other sedatives like propofol and benzodiazepines directly increase activity of gamma-aminobutyric acid neurons.[19] Sedation by dexemeditomidine mirrors natural sleep.[20] As such, dexmedetomidine provides less amnesia than benzodiazepines.[19] Dexmedetomidine also has analgesic effects at the spinal cord level and other supraspinal sites.[19] 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).[21]
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.[17]
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.[22] More recently, in 2008 the FDA expanded its indication to include nonintubated people requiring sedation for surgical or non-surgical procedures, such as colonoscopy.
Veterinary use
Marketed as Sileo by Zoetis, in the form of an oromucosal gel, it is approved by the FDA for use in dogs for relief of noise aversion.[23]
References
- ^ Cormack JR, Orme RM, Costello TG (2005). "The role of alpha2-agonists in neurosurgery". Journal of Clinical Neuroscience. 12 (4): 375–8. doi:10.1016/j.jocn.2004.06.008. PMID 15925765.
- ^ http://www.dexdomitor.com/
- ^ http://orion.fi/en/Research-and-developement/Achievements/
- ^ Pasin, Laura; Greco, Teresa; Feltracco, Paolo; Vittorio, Annalisa; Neto, Caetano Nigro; Cabrini, Luca; Landoni, Giovanni; Finco, Gabriele; Zangrillo, Alberto (2013-01-01). "Dexmedetomidine as a sedative agent in critically ill patients: a meta-analysis of randomized controlled trials". PLOS ONE. 8 (12): e82913. doi:10.1371/journal.pone.0082913. ISSN 1932-6203. PMC 3877008. PMID 24391726.
- ^ a b Chen, Ken; Lu, Zhijun; Xin, Yi Chun; Cai, Yong; Chen, Yi; Pan, Shu Ming (2015-01-01). "Alpha-2 agonists for long-term sedation during mechanical ventilation in critically ill patients". The Cochrane Database of Systematic Reviews. 1: CD010269. doi:10.1002/14651858.CD010269.pub2. ISSN 1469-493X. PMID 25879090.
- ^ a b MacLaren, Robert; Preslaski, Candice R.; Mueller, Scott W.; Kiser, Tyree H.; Fish, Douglas N.; Lavelle, James C.; Malkoski, Stephen P. (2015-03-01). "A randomized, double-blind pilot study of dexmedetomidine versus midazolam for intensive care unit sedation: patient recall of their experiences and short-term psychological outcomes". Journal of Intensive Care Medicine. 30 (3): 167–175. doi:10.1177/0885066613510874. ISSN 1525-1489. PMID 24227448.
- ^ Li, Bo; Wang, Huixia; Wu, Hui; Gao, Chengjie (2015-04-01). "Neurocognitive dysfunction risk alleviation with the use of dexmedetomidine in perioperative conditions or as ICU sedation: a meta-analysis". Medicine. 94 (14): e597. doi:10.1097/MD.0000000000000597. ISSN 1536-5964. PMC 4554047. PMID 25860207.
- ^ Turunen, Heidi; Jakob, Stephan M.; Ruokonen, Esko; Kaukonen, Kirsi-Maija; Sarapohja, Toni; Apajasalo, Marjo; Takala, Jukka (2015-01-01). "Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation". Critical Care (London, England). 19: 67. doi:10.1186/s13054-015-0787-y. ISSN 1466-609X. PMC 4391080. PMID 25887576.
- ^ Dere, Kamer; Sucullu, Ilker; Budak, Ersel Tan; Yeyen, Suleyman; Filiz, Ali Ilker; Ozkan, Sezai; Dagli, Guner (2010-07-01). "A comparison of dexmedetomidine versus midazolam for sedation, pain and hemodynamic control, during colonoscopy under conscious sedation". European Journal of Anaesthesiology. 27 (7): 648–652. doi:10.1097/EJA.0b013e3283347bfe. ISSN 1365-2346. PMID 20531094.
- ^ Paris A, Tonner PH (2005). "Dexmedetomidine in anaesthesia". Current Opinion in Anaesthesiology. 18 (4): 412–8. doi:10.1097/01.aco.0000174958.05383.d5. PMID 16534267.
- ^ Giovannitti, Joseph A.; Thoms, Sean M.; Crawford, James J. (2015-01-01). "Alpha-2 Adrenergic Receptor Agonists: A Review of Current Clinical Applications". Anesthesia Progress. 62 (1): 31–38. doi:10.2344/0003-3006-62.1.31. ISSN 0003-3006. PMC 4389556. PMID 25849473.
- ^ Ahmed, S. S.; Unland, T; Slaven, J. E.; Nitu, M. E.; Rigby, M. R. (2014). "Successful use of intravenous dexmedetomidine for magnetic resonance imaging sedation in autistic children". Southern Medical Journal. 107 (9): 559–64. doi:10.14423/SMJ.0000000000000160. PMID 25188619.
- ^ Menon DV, Wang Z, Fadel PJ, Arbique D, Leonard D, Li JL, Victor RG, Vongpatanasin W (2007). "Central sympatholysis as a novel countermeasure for cocaine-induced sympathetic activation and vasoconstriction in humans". J Am Coll Cardiol. 50 (7): 626–33. doi:10.1016/j.jacc.2007.03.060. PMID 17692748.
- ^ John R. Richards; Timothy E. Albertson; Robert W. Derlet; Richard A. Lange; Kent R. Olson; B. Zane Horowitz (February 2015). "Treatment of toxicity from amphetamines, related derivatives, and analogues: A systematic clinical review.". Drug & Alcohol Dependence. 150: 1–13. doi:10.1016/j.drugalcdep.2015.01.040.
- ^ "Dosing Guidelines for Precedex" (PDF). Retrieved 2010-11-21.
- ^ Ebert, T. J.; Hall, J. E.; Barney, J. A.; Uhrich, T. D.; Colinco, M. D. (2000-08-01). "The effects of increasing plasma concentrations of dexmedetomidine in humans". Anesthesiology. 93 (2): 382–394. doi:10.1097/00000542-200008000-00016. ISSN 0003-3022. PMID 10910487.
- ^ a b Keating, Gillian M. (2015-07-01). "Dexmedetomidine: A Review of Its Use for Sedation in the Intensive Care Setting". Drugs. 75 (10): 1119–1130. doi:10.1007/s40265-015-0419-5. ISSN 0012-6667. PMID 26063213.
- ^ Nelson, Laura E.; Lu, Jun; Guo, Tianzhi; Saper, Clifford B.; Franks, Nicholas P.; Maze, Mervyn (2003-02-01). "The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects". Anesthesiology. 98 (2): 428–436. doi:10.1097/00000542-200302000-00024. ISSN 0003-3022. PMID 12552203.
- ^ a b c Panzer, Oliver; Moitra, Vivek; Sladen, Robert N. (2009-07-01). "Pharmacology of sedative-analgesic agents: dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral mu antagonists". Critical Care Clinics. 25 (3): 451–469, vii. doi:10.1016/j.ccc.2009.04.004. ISSN 1557-8232. PMID 19576524.
- ^ Huupponen, E.; Maksimow, A.; Lapinlampi, P.; Särkelä, M.; Saastamoinen, A.; Snapir, A.; Scheinin, H.; Scheinin, M.; Meriläinen, P. (2008-02-01). "Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep". Acta Anaesthesiologica Scandinavica. 52 (2): 289–294. doi:10.1111/j.1399-6576.2007.01537.x. ISSN 1399-6576. PMID 18005372.
- ^ "Precedex (Dexmedetomidine hydrochloride) Drug Information: Clinical Pharmacology - Prescribing Information at RxList". RxList. Retrieved 2015-11-16.
- ^ Shehabi, Yahya; Ruettimann, Urban; Adamson, Harriet; Innes, Richard; Ickeringill, Mathieu (2004-12-01). "Dexmedetomidine infusion for more than 24 hours in critically ill patients: sedative and cardiovascular effects". Intensive Care Medicine. 30 (12): 2188–2196. doi:10.1007/s00134-004-2417-z. ISSN 0342-4642. PMID 15338124.
- ^ "Recent Animal Drug Approvals". U.S. Department of Health and Human Services. 2 June 2016. Retrieved 3 July 2016.
For the treatment of noise aversion in dogs
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- Iodocyanopindolol
- Iprocrolol
- Isoxaprolol
- Isamoltane
- Labetalol
- Landiolol
- Levobetaxolol
- Levobunolol
- Levomoprolol
- Medroxalol
- Mepindolol
- Metipranolol
- Metoprolol
- Moprolol
- Nadolol
- Nadoxolol
- Nebivolol
- Nifenalol
- Nipradilol
- Oxprenolol
- Pacrinolol
- Pafenolol
- Pamatolol
- Pargolol
- Penbutolol
- Pindolol
- Practolol
- Primidolol
- Procinolol
- Pronethalol
- Propafenone
- Propranolol
- Ridazolol
- Ronactolol
- Soquinolol
- Sotalol
- Spirendolol
- SR 59230A
- Sulfinalol
- Talinolol
- Tazolol
- Tertatolol
- Tienoxolol
- Tilisolol
- Timolol
- Tiprenolol
- Tolamolol
- Toliprolol
- Xibenolol
- Xipranolol
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- See also: Dopaminergics
- Melatonergics
- Serotonergics
- Monoamine reuptake and release modulators
- Monoamine metabolism modulators
- Monoamine neurotoxins
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