- Dexmedetomidine
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Dexmedetomidine 
Systematic (IUPAC) name (S)-4-[1-(2,3-dimethylphenyl)ethyl]-3H-imidazole Clinical data AHFS/Drugs.com monograph Pregnancy cat. ? Legal status ? Routes by intravenous infusion only Pharmacokinetic data Protein binding 94% Metabolism near complete hepatic metabolism to inactive metabolites Half-life 2 hours Excretion urinary Identifiers CAS number 113775-47-6 
ATC code N05CM18 PubChem CID 68602 DrugBank APRD00578 ChemSpider 4470605 UNII 67VB76HONO KEGG D00514 ChEBI CHEBI:4466 ChEMBL CHEMBL778 Chemical data Formula C13H16N2 Mol. mass 200.28 g/mol SMILES eMolecules & PubChem - 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
Key:CUHVIMMYOGQXCV-NSHDSACASA-N
(what is this?) (verify)Dexmedetomidine (Precedex) is a sedative medication used by intensive care units and anesthetists. It is relatively unique in its ability to provide sedation without causing respiratory depression. Like clonidine, it is an agonist of α2-adrenergic receptors in certain parts of the brain.[1]
Contents
Indications
Dexmedetomidine is indicated for sedation of critically ill or injured patients in an intensive care unit setting. Its indication in the US was recently expanded to include nonintubated patient requiring sedation for surgery or procedures short-term. It is also useful as an adjunct for sedation and general anesthesia in the setting of certain operations and invasive medical procedures, such as colonoscopy. There are no absolute contraindications to the use of dexmedetomidine. Limiting its usefulness is the caution that the drug cannot be bolused due to concerns about peripheral α2-receptor stimulation with resulting hypotension, combined with its high cost relative to generic medications like propofol, fentanyl and midazolam which can achieve similar clinical effects
Intensive care unit sedation
Compared to midazolam, dexmedetomidine was similarly effective for sedation, but shortened the time to extubation. It was associated with less delirium, tachycardia and hypotension. but more bradycardia. [2] It also seemed to be superior to lorazepam for ventilated patients in the intensive care unit.[3] Compared to midazolam, dexmedetomidine is superior due to reduced intensive care costs. The reduced costs are due to a reduction in intensive care unit stay as well as reduced mechanical ventilation.[4]
Procedural sedation
Dexmedetomidine has sedative, analgesic, sympatholytic, and anxiolytic effects that blunt many of the cardiovascular responses in the perioperative period. It reduces the requirements for volatile anesthetics, sedatives and analgesics without causing significant respiratory depression.[5]
Other
Dexmedetomidine may be useful for the treatment of the deleterious cardiovascular effects of acute cocaine intoxication and overdose.[6] Dexmedetomidine may also offer a new paradigm in the pharmacologic treatment of symptoms of distress (intractable pain, agitation or delirium) at the end of life. Recently, an investigator initiated IND was approved by the FDA to examine the use of dexmedetomidine in treating cancer patients at the end of life who are suffering from intractable pain, agitation or delirium.[7]
Dosage and administration
Intravenous infusion of dexmedetomidine is commonly initiated with a 1 mcg/kg loading dose, administered over 10 minutes, followed by a maintenance infusion of 0.2–1.0 mcg/kg/hour. 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.[8]
See also
- Xylazine, another α2-receptor agonist used in veterinary anesthesia.
- Medetomidine, a racemic mixture of R and S-enantiomers of Dexmedetomidine used in small animal anesthesia.[9]
- Detomidine, a similar compound used largely in large animal anesthesia.
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.
- ^ Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG (2009). "Dexmedetomidine vs Midazolam for Sedation of Critically Ill Patients: A Randomized Trial". JAMA 301 (5): 489–99. doi:10.1001/jama.2009.56. PMID 19188334.
- ^ Pandharipande, PP; Pun, BT; Herr, DL; Maze, M; Girard, TD; Miller, RR; Shintani, AK; Thompson, JL et al. (2007). "Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial". JAMA 298 (22): 2644–53. doi:10.1001/jama.298.22.2644. PMID 18073360.
- ^ O'Connor, M; Bucknall, T; Manias, E (2009). "Sedation Management in Australian and New Zealand Intensive Care Units: Doctors' and Nurses' Practices and Opinions". Am J Crit Care 19 (3): 285–95. doi:10.4037/ajcc2009541. PMID 19770414.
- ^ 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.
- ^ 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.
- ^ Jackson KC, Wang Z, Wohlt P, Fine PG (2006). "Dexmedetomidine a novel analgesic with palliative medicine potential". J Pain and Palliative Care Pharmacotherapy 20 (2): 23–7. doi:10.1080/J354v20n02_05. PMID 16702133.
- ^ "Dosing Guidelines for Precedex®". http://www.precedex.com/wp-content/uploads/2010/02/Dosing_Guide.pdf. Retrieved 2010-11-21.
- ^ PubChem 5311068
External links
Adrenergics Receptor ligands Agonists: 5-FNE • 6-FNE • Amidephrine • Anisodamine • Anisodine • Cirazoline • Dipivefrine • Dopamine • Ephedrine • Epinephrine (Adrenaline) • Etilefrine • Ethylnorepinephrine • Indanidine • Levonordefrin • Metaraminol • Methoxamine • Methyldopa • Midodrine • Naphazoline • Norepinephrine (Noradrenaline) • Octopamine • Oxymetazoline • Phenylephrine • Phenylpropanolamine • Pseudoephedrine • Synephrine • Tetrahydrozoline
Antagonists: Abanoquil • Adimolol • Ajmalicine • Alfuzosin • Amosulalol • Arotinolol • Atiprosin • Benoxathian • Buflomedil • Bunazosin • Carvedilol • CI-926 • Corynanthine • Dapiprazole • DL-017 • Domesticine • Doxazosin • Eugenodilol • Fenspiride • GYKI-12,743 • GYKI-16,084 • Indoramin • Ketanserin • L-765,314 • Labetalol • Mephendioxan • Metazosin • Monatepil • Moxisylyte (Thymoxamine) • Naftopidil • Nantenine • Neldazosin • Nicergoline • Niguldipine • Pelanserin • Phendioxan • Phenoxybenzamine • Phentolamine • Piperoxan • Prazosin • Quinazosin • Ritanserin • RS-97,078 • SGB-1,534 • Silodosin • SL-89.0591 • Spiperone • Talipexole • Tamsulosin • Terazosin • Tibalosin • Tiodazosin • Tipentosin • Tolazoline • Trimazosin • Upidosin • Urapidil • Zolertine
* Note that many TCAs, TeCAs, antipsychotics, ergolines, and some piperazines like buspirone, trazodone, nefazodone, etoperidone, and mepiprazole all antagonize α1-adrenergic receptors as well, which contributes to their side effects such as orthostatic hypotension.Agonists: (R)-3-Nitrobiphenyline • 4-NEMD • 6-FNE • Amitraz • Apraclonidine • Brimonidine • Cannabivarin • Clonidine • Detomidine • Dexmedetomidine • Dihydroergotamine • Dipivefrine • Dopamine • Ephedrine • Ergotamine • Epinephrine (Adrenaline) • Esproquin • Etilefrine • Ethylnorepinephrine • Guanabenz • Guanfacine • Guanoxabenz • Levonordefrin • Lofexidine • Medetomidine • Methyldopa • Mivazerol • Naphazoline • Norepinephrine (Noradrenaline) • Phenylpropanolamine • Piperoxan • Pseudoephedrine • Rilmenidine • Romifidine • Talipexole • Tetrahydrozoline • Tizanidine • Tolonidine • Urapidil • Xylazine • Xylometazoline
Antagonists: 1-PP • Adimolol • Aptazapine • Atipamezole • BRL-44408 • Buflomedil • Cirazoline • Efaroxan • Esmirtazapine • Fenmetozole • Fluparoxan • GYKI-12,743 • GYKI-16,084 • Idazoxan • Mianserin • Mirtazapine • MK-912 • NAN-190 • Olanzapine • Phentolamine • Phenoxybenzamine • Piperoxan • Piribedil • Rauwolscine • Rotigotine • SB-269,970 • Setiptiline • Spiroxatrine • Sunepitron • Tolazoline • Yohimbine
* Note that many atypical antipsychotics and azapirones like buspirone and gepirone (via metabolite 1-PP) antagonize α2-adrenergic receptors as well.βAgonists: 2-FNE • 5-FNE • Amibegron • Arbutamine • Arformoterol • Arotinolol • BAAM • Bambuterol • Befunolol • Bitolterol • Broxaterol • Buphenine • Carbuterol • Cimaterol • Clenbuterol • Denopamine • Deterenol • Dipivefrine • Dobutamine • Dopamine • Dopexamine • Ephedrine • Epinephrine (Adrenaline) • Etafedrine • Etilefrine • Ethylnorepinephrine • Fenoterol • Formoterol • Hexoprenaline • Higenamine • Indacaterol • Isoetarine • Isoprenaline (Isoproterenol) • Isoxsuprine • Labetalol • Levonordefrin • Levosalbutamol • Mabuterol • Methoxyphenamine • Methyldopa • Norepinephrine (Noradrenaline) • Orciprenaline • Oxyfedrine • Phenylpropanolamine • Pirbuterol • Prenalterol • Ractopamine • Procaterol • Pseudoephedrine • Reproterol • Rimiterol • Ritodrine • Salbutamol (Albuterol) • Salmeterol • Solabegron • Terbutaline • Tretoquinol • Tulobuterol • Xamoterol • Zilpaterol • Zinterol
Antagonists: Acebutolol • Adaprolol • Adimolol • Afurolol • Alprenolol • Alprenoxime • Amosulalol • Ancarolol • Arnolol • Arotinolol • Atenolol • Befunolol • Betaxolol • Bevantolol • Bisoprolol • Bopindolol • Bormetolol • Bornaprolol • Brefonalol • Bucindolol • Bucumolol • Bufetolol • Buftiralol • Bufuralol • Bunitrolol • Bunolol • Bupranolol • Burocrolol • Butaxamine • Butidrine • Butofilolol • Capsinolol • Carazolol • Carpindolol • Carteolol • Carvedilol • Celiprolol • Cetamolol • Cicloprolol • Cinamolol • Cloranolol • Cyanopindolol • Dalbraminol • Dexpropranolol • Diacetolol • Dichloroisoprenaline • Dihydroalprenolol • Dilevalol • Diprafenone • Draquinolol • Dropranolol • Ecastolol • Epanolol • Ericolol • Ersentilide • Esatenolol • Esmolol • Esprolol • Eugenodilol • Exaprolol • Falintolol • Flestolol • Flusoxolol • Hydroxycarteolol • Hydroxytertatolol • ICI-118,551 • Idropranolol • Indenolol • Indopanolol • Iodocyanopindolol • Iprocrolol • Isoxaprolol • Isamoltane • Labetalol • Landiolol • Levobetaxolol • Levobunolol • Levocicloprolol • Levomoprolol • Medroxalol • Mepindolol • Metalol • Metipranolol • Metoprolol • Moprolol • Nadolol • Nadoxolol • Nafetolol • Nebivolol • Neraminol • Nifenalol • Nipradilol • Oberadilol • Oxprenolol • Pacrinolol • Pafenolol • Pamatolol • Pargolol • Parodilol • Penbutolol • Penirolol • PhQA-33 • Pindolol • Pirepolol • Practolol • Primidolol • Procinolol • Pronethalol • Propafenone • Propranolol • Ridazolol • Ronactolol • Soquinolol • Sotalol • Spirendolol • SR 59230A • Sulfinalol • TA-2005 • Talinolol • Tazolol • Teoprolol • Tertatolol • Terthianolol • Tienoxolol • Tilisolol • Timolol • Tiprenolol • Tolamolol • Toliprolol • Tribendilol • Trigevolol • Xibenolol • XipranololReuptake inhibitors Selective norepinephrine reuptake inhibitors: Amedalin • Atomoxetine (Tomoxetine) • Ciclazindol • Daledalin • Esreboxetine • Lortalamine • Mazindol • Nisoxetine • Reboxetine • Talopram • Talsupram • Tandamine • Viloxazine; Norepinephrine-dopamine reuptake inhibitors: Amineptine • Bupropion (Amfebutamone) • Fencamine • Fencamfamine • Lefetamine • Levophacetoperane • LR-5182 • Manifaxine • Methylphenidate • Nomifensine • O-2172 • Radafaxine; Serotonin-norepinephrine reuptake inhibitors: Bicifadine • Desvenlafaxine • Duloxetine • Eclanamine • Levomilnacipran • Milnacipran • Sibutramine • Venlafaxine; Serotonin-norepinephrine-dopamine reuptake inhibitors: Brasofensine • Diclofensine • DOV-102,677 • DOV-21,947 • DOV-216,303 • JNJ-7925476 • JZ-IV-10 • Methylnaphthidate • Naphyrone • NS-2359 • PRC200-SS • SEP-225,289 • SEP-227,162 • Tesofensine; Tricyclic antidepressants: Amitriptyline • Butriptyline • Cianopramine • Clomipramine • Desipramine • Dosulepin • Doxepin • Imipramine • Lofepramine • melitracen • Nortriptyline • Protriptyline • Trimipramine; Tetracyclic antidepressants: Amoxapine • Maprotiline • Mianserin • Oxaprotiline • Setiptiline; Others: Cocaine • CP-39,332 • EXP-561 • Fezolamine • Ginkgo biloba • Indeloxazine • Nefazodone • Nefopam • Pridefrine • Tapentadol • Teniloxazine • Tramadol • ZiprasidoneEnzyme inhibitors 3,4-DihydroxystyreneDBHCGS-19281A • SKF-64139 • SKF-7698Nonselective: Benmoxin • Caroxazone • Echinopsidine • Furazolidone • Hydralazine • Indantadol • Iproclozide • Iproniazid • Isocarboxazid • Isoniazid • Linezolid • Mebanazine • Metfendrazine • Nialamide • Octamoxin • Paraxazone • Phenelzine • Pheniprazine • Phenoxypropazine • Pivalylbenzhydrazine • Procarbazine • Safrazine • Tranylcypromine; MAO-A selective: Amiflamine • Bazinaprine • Befloxatone • Befol • Brofaromine • Cimoxatone • Clorgiline • Esuprone • Harmala alkaloids (Harmine, Harmaline, Tetrahydroharmine, Harman, Norharman, etc) • Methylene Blue • Metralindole • Minaprine • Moclobemide • Pirlindole • Sercloremine • Tetrindole • Toloxatone • Tyrima; MAO-B selective: D-Deprenyl • Selegiline (L-Deprenyl) • Ladostigil • Lazabemide • Milacemide • Mofegiline • Pargyline • Rasagiline • Safinamide
* Note that MAO-B inhibitors also influence norepinephrine/epinephrine levels since they inhibit the breakdown of their precursor dopamine.COMTOthers Ferrous Iron (Fe2+) • S-Adenosyl-L-Methionine • Vitamin B3 (Niacin, Nicotinamide → NADPH) • Vitamin B6 (Pyridoxine, Pyridoxamine, Pyridoxal → Pyridoxal Phosphate) • Vitamin B9 (Folic acid → Tetrahydrofolic acid) • Vitamin C (Ascorbic acid) • Zinc (Zn2+)OthersActivity enhancers: BPAP • PPAP; Release blockers: Bethanidine • Bretylium • Guanadrel • Guanazodine • Guanclofine • Guanethidine • Guanoxan; Toxins: Oxidopamine (6-Hydroxydopamine)List of adrenergic drugsCategories:- Imidazoles
- Alpha-adrenergic agonists
- Enantiopure drugs
- 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
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