Esmolol
{{Short description|Class II antiarrhythmic drug}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 412885041
| image = Esmolol structure.svg
| tradename = Brevibloc
| Drugs.com = {{drugs.com|monograph|esmolol-hydrochloride}}
| pregnancy_AU = C
| pregnancy_category =
| routes_of_administration = Intravenous
| ATC_prefix = C07
| ATC_suffix = AB09
| legal_AU = S4
| legal_AU_comment = {{cite web | title=Brevibloc esmolol hydrochloride 2.5 g powder for injection for infusion vial (310943) | website=Therapeutic Goods Administration (TGA) | date=26 May 2022 | url=https://www.tga.gov.au/resources/artg/310943 | access-date=29 April 2023}}{{cite web | title=Esmolol Juno (Juno Pharmaceuticals Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=13 January 2023 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/esmolol-juno-juno-pharmaceuticals-pty-ltd | access-date=29 April 2023 | archive-date=18 March 2023 | archive-url=https://web.archive.org/web/20230318031149/https://www.tga.gov.au/resources/prescription-medicines-registrations/esmolol-juno-juno-pharmaceuticals-pty-ltd | url-status=live }}
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| bioavailability =
| protein_bound = 60%
| metabolism = Red blood cell (erythrocytic)
| elimination_half-life = 9 minutes
| excretion = Kidney
| IUPHAR_ligand = 7178
| CAS_number_Ref = {{cascite|changed|CAS}}
| CAS_number = 81147-92-4
| PubChem = 59768
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB00187
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 53916
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = MDY902UXSR
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07916
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 4856
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 768
| IUPAC_name = methyl (RS)-3-
| C=16 | H=25 | N=1 | O=4
| SMILES = O=C(OC)CCc1ccc(OCC(O)CNC(C)C)cc1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C16H25NO4/c1-12(2)17-10-14(18)11-21-15-7-4-13(5-8-15)6-9-16(19)20-3/h4-5,7-8,12,14,17-18H,6,9-11H2,1-3H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = AQNDDEOPVVGCPG-UHFFFAOYSA-N
}}
Esmolol, sold under the brand name Brevibloc, is a cardio selective beta1 receptor blocker with rapid onset,{{cite journal | vauthors = Deng CY, Lin SG, Zhang WC, Kuang SJ, Qian WM, Wu SL, Shan ZX, Yang M, Yu XY | display-authors = 6 | title = Esmolol inhibits Na+ current in rat ventricular myocytes | journal = Methods and Findings in Experimental and Clinical Pharmacology | volume = 28 | issue = 10 | pages = 697–702 | date = December 2006 | pmid = 17235414 | doi = 10.1358/mf.2006.28.10.1037498 | url = http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summaryn_pr?p_JournalId=6&p_RefId=1037498 | access-date = 2008-07-27 | archive-date = 2019-12-10 | archive-url = https://web.archive.org/web/20191210041236/http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summaryn_pr?p_JournalId=6&p_RefId=1037498 | url-status = live | url-access = subscription }} a very short duration of action, and no significant intrinsic sympathomimetic or membrane stabilising activity at therapeutic dosages.
It is a class II antiarrhythmic.{{cite journal | vauthors = Jaillon P, Drici M | title = Recent antiarrhythmic drugs | journal = The American Journal of Cardiology | volume = 64 | issue = 20 | pages = 65J–69J | date = December 1989 | pmid = 2688391 | doi = 10.1016/0002-9149(89)91203-4 }} Esmolol decreases the force and rate of heart contractions by blocking beta-adrenergic receptors of the sympathetic nervous system, which are found in the heart and other organs of the body. Esmolol prevents the action of two naturally occurring substances: epinephrine and norepinephrine.{{cite book | vauthors = Tripathi KD | chapter = Antiadrenergic Drugs and Drugs for Glaucoma | title = Essentials of Medical Pharmacology | edition = 7th | page = 149 }}
It was patented in 1980 and approved for medical use in 1987.{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=462 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA462 |language=en}}
Medical uses
To terminate supraventricular tachycardia,
Episodic atrial fibrillation or flutter,
Arrhythmia during anaesthesia,
To reduce HR and BP during and after cardiac surgery, and
In early treatment of myocardial infarction.
Esmolol is also used in blunting the hemodynamic response to laryngoscopy and intubation.{{cite journal | vauthors = Sharma S, Suthar OP, Tak ML, Thanvi A, Paliwal N, Karnawat R | title = Comparison of Esmolol and Dexmedetomidine for Suppression of Hemodynamic Response to Laryngoscopy and Endotracheal Intubation in Adult Patients Undergoing Elective General Surgery: A Prospective, Randomized Controlled Double-blinded Study | journal = Anesthesia: Essays and Researches | volume = 12 | issue = 1 | pages = 262–266 | date = 2018 | pmid = 29628593 | pmc = 5872877 | doi = 10.4103/aer.AER_226_17 | doi-access = free }}
Pharmacology
=Pharmacodynamics=
Esmolol is a beta blocker, or an antagonist of the β-adrenergic receptors. It is selective for the β1-adrenergic receptor and has no intrinsic sympathomimetic activity.
=Pharmacokinetics=
Esmolol is considered a soft drug,{{Cite journal | doi = 10.1002/(SICI)1098-1128(200001)20:1<58::AID-MED3>3.0.CO;2-X | pmid = 10608921 | title = Soft drug design: General principles and recent applications | journal = Medicinal Research Reviews | volume = 20 | pages = 58–101 | year = 2000 | vauthors = Bodor N, Buchwald P | issue = 1 | s2cid = 25119421 | name-list-style = vanc }} one that is rapidly metabolized to an inactive form. Esmolol is rapidly metabolized by hydrolysis of the ester linkage, chiefly by the esterases in the cytosol of red blood cells and not by plasma cholinesterases or red cell membrane acetylcholinesterase. Total body clearance in man was found to be about 20 L/kg/hr, which is greater than cardiac output; thus the metabolism of esmolol is not limited by the rate of blood flow to metabolizing tissues such as the liver or affected by hepatic or renal blood flow. Esmolol's short duration of action is based on the ester-methyl side chain which allows for quick hydrolysis. Esmolol's structure is reflected in its name, es-molol as in ester-methyl. Plasma cholinesterases and red cell membrane acetylcholinesterase do not have any action. This metabolism results in the formation of a free acid and methanol. The amount of methanol produced is similar to endogenous methanol production. Esmolol has a rapid distribution half-life of about two minutes and an elimination half-life of about nine minutes.{{cn|date=February 2021}}
Esmolol is classified as a beta blocker with low lipophilicity and hence lower potential for crossing the blood–brain barrier.{{cite journal | vauthors = Cojocariu SA, Maștaleru A, Sascău RA, Stătescu C, Mitu F, Leon-Constantin MM | title = Neuropsychiatric Consequences of Lipophilic Beta-Blockers | journal = Medicina (Kaunas) | volume = 57 | issue = 2 | date = February 2021 | page = 155 | pmid = 33572109 | pmc = 7914867 | doi = 10.3390/medicina57020155 | url = | doi-access = free }} This in turn may result in fewer effects in the central nervous system as well as a lower risk of neuropsychiatric side effects.
References
{{reflist}}
{{beta blockers}}
{{Antiarrhythmic agents}}
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Category:N-isopropyl-phenoxypropanolamines