glibenclamide
{{Short description|Chemical compound}}
{{Distinguish|gliclazide|glipizide}}
{{Use dmy dates|date=March 2024}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 461120828
| image = Glibenclamide.svg
| width = 275
| alt =
| image2 = Glibenclamide-4YVP-ball-and-stick.png
| alt2 =
| caption =
| USAN = Glyburide
| pronounce =
| tradename = Diabeta, Glynase, Micronase, others
| Drugs.com = {{drugs.com|monograph|glyburide}}
| MedlinePlus = a684058
| DailyMedID = Glyburide
| pregnancy_AU = C
| pregnancy_AU_comment =
| pregnancy_category=
| routes_of_administration = By mouth
| class =
| ATCvet =
| ATC_prefix = A10
| ATC_suffix = BB01
| ATC_supplemental =
| legal_AU = S4
| legal_AU_comment =
| legal_BR =
| legal_BR_comment =
| legal_CA =
| legal_CA_comment =
| legal_DE =
| legal_DE_comment =
| legal_NZ =
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment =
| legal_US = Rx-only
| legal_EU = Rx-only
| legal_EU_comment =
| legal_UN =
| legal_UN_comment =
| legal_status =
| bioavailability =
| protein_bound = Extensive
| metabolism = Liver hydroxylation (CYP2C9-mediated)
| metabolites =
| onset =
| elimination_half-life = 10 hours
| duration_of_action =
| excretion = Kidney and bile duct
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 10238-21-8
| CAS_supplemental =
| PubChem = 3488
| IUPHAR_ligand = 2414
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01016
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 3368
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = SX6K58TVWC
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00336
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 5441
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 472
| NIAID_ChemDB =
| PDB_ligand =
| synonyms =
| IUPAC_name = 5-chloro-N-[2-[4-(cyclohexylcarbamoylsulfamoyl)
phenyl]ethyl]-2-methoxybenzamide
| C=23 | H=28 | Cl=1 | N=3 | O=5 | S=1
| SMILES = O=C(NC1CCCCC1)NS(=O)(=O)c2ccc(cc2)CCNC(=O)c3cc(Cl)ccc3OC
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C23H28ClN3O5S/c1-32-21-12-9-17(24)15-20(21)22(28)25-14-13-16-7-10-19(11-8-16)33(30,31)27-23(29)26-18-5-3-2-4-6-18/h7-12,15,18H,2-6,13-14H2,1H3,(H,25,28)(H2,26,27,29)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ZNNLBTZKUZBEKO-UHFFFAOYSA-N
| density =
| density_notes =
| melting_point = 169
| melting_high = 170
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}}
Glibenclamide, also known as glyburide, is an antidiabetic medication used to treat type 2 diabetes. It is recommended that it be taken together with diet and exercise. It may be used with other antidiabetic medication. It is not recommended for use by itself in type 1 diabetes. It is taken by mouth.{{cite web |title=Glyburide Monograph for Professionals |url=https://www.drugs.com/monograph/glyburide.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=18 March 2019 |archive-date=31 March 2019 |archive-url=https://web.archive.org/web/20190331042659/https://www.drugs.com/monograph/glyburide.html |url-status=live }}
Common side effects include nausea and heartburn. Serious side effects may include angioedema and low blood sugar. It is generally not recommended during pregnancy but can be used during breastfeeding.{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=692|edition=76}} It is in the sulfonylureas class of medications and works by increasing the release of insulin from the pancreas.
Glibenclamide was discovered in 1969 and approved for medical use in the United States in 1984.{{cite book |title=Diabetes in Clinical Practice: Questions and Answers from Case Studies |date=2007 |publisher=John Wiley & Sons |isbn=9780470059135 |page=342 |url=https://books.google.com/books?id=fs0M4dPuNtUC&pg=PA342}} It is available as a generic medication. In 2021, it was the 214th most commonly prescribed medication in the United States, with more than 2{{nbsp}}million prescriptions.{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}{{cite web | title = Glyburide - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Glyburide | access-date = 14 January 2024 | archive-date = 12 April 2020 | archive-url = https://web.archive.org/web/20200412071308/https://clincalc.com/DrugStats/Drugs/Glyburide | url-status = live }}
Medical uses
Glibenclamide is used to lower the blood sugar level in patients with type 2 diabetes mellitus, which is not controlled by diet and exercise alone.
It is not as good as either metformin or insulin in those who have gestational diabetes.{{cite journal | vauthors = Balsells M, García-Patterson A, Solà I, Roqué M, Gich I, Corcoy R | title = Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis | journal = BMJ | volume = 350 | pages = h102 | date = January 2015 | pmid = 25609400 | pmc = 4301599 | doi = 10.1136/bmj.h102 }}
Side effects
Frequently reported side effects include: nausea, heartburn, weight gain, and bloating.{{cite web |title=Glyburide: MedlinePlus Drug Information |url=https://medlineplus.gov/druginfo/meds/a684058.html |website=MedlinePlus |access-date=29 October 2019 |archive-date=14 April 2019 |archive-url=https://web.archive.org/web/20190414144129/https://medlineplus.gov/druginfo/meds/a684058.html |url-status=live }} The medication is also a major cause of medication-induced hypoglycemia. The risk is greater than with other sulfonylureas.{{cite journal | vauthors = Gangji AS, Cukierman T, Gerstein HC, Goldsmith CH, Clase CM | title = A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin | journal = Diabetes Care | volume = 30 | issue = 2 | pages = 389–394 | date = February 2007 | pmid = 17259518 | doi = 10.2337/dc06-1789 | title-link = doi | doi-access = free }}
Contraindications
Glibenclamide may be not recommended in those with G6PD deficiency, as it may cause acute hemolysis.{{cite journal | vauthors = Meloni G, Meloni T | title = Glyburide-induced acute haemolysis in a G6PD-deficient patient with NIDDM | journal = British Journal of Haematology | volume = 92 | issue = 1 | pages = 159–160 | date = January 1996 | pmid = 8562390 | doi = 10.1046/j.1365-2141.1996.275810.x | s2cid = 41227257 }}
=Pregnancy and breastfeeding=
It is generally not recommended during pregnancy but can be used during breastfeeding.
Mechanism of action
The medication, a sulfonylurea, works by binding to and inhibiting the ATP-sensitive potassium channels (KATP) inhibitory regulatory subunit sulfonylurea receptor 1 (SUR1){{cite journal | vauthors = Serrano-Martín X, Payares G, Mendoza-León A | title = Glibenclamide, a blocker of K+(ATP) channels, shows antileishmanial activity in experimental murine cutaneous leishmaniasis | journal = Antimicrobial Agents and Chemotherapy | volume = 50 | issue = 12 | pages = 4214–4216 | date = December 2006 | pmid = 17015627 | pmc = 1693980 | doi = 10.1128/AAC.00617-06 }} in pancreatic beta cells. This inhibition causes cell membrane depolarization, opening voltage-dependent calcium Channels.{{cite journal | vauthors = He Y, Chang Y, Peng Y, Zhu J, Liu K, Chen J, Wu Y, Ji Z, Lin Z, Wang S, Gupta S, Zang N, Pan S, Huang K | display-authors = 6 | title = Glibenclamide Directly Prevents Neuroinflammation by Targeting SUR1-TRPM4-Mediated NLRP3 Inflammasome Activation In Microglia | journal = Molecular Neurobiology | volume = 59 | issue = 10 | pages = 6590–6607 | date = October 2022 | pmid = 35972671 | doi = 10.1007/s12035-022-02998-x | s2cid = 242029244 }}
This results in an increase in intracellular calcium in the pancreatic beta cell and subsequent stimulation of insulin release.{{Cite web | publisher = Wolters Kluwer N.V. | title = Glyburide | url = https://www.wolterskluwer.com/en/solutions/lexicomp | website = Lexicomp | access-date = 3 June 2023 | archive-date = 2 June 2023 | archive-url = https://web.archive.org/web/20230602191128/https://www.wolterskluwer.com/en/solutions/lexicomp | url-status = live }}
After a stroke, the blood–brain barrier is broken and glibenclamide can reach the central nervous system. Glibenclamide has been shown to bind more efficiently to the ischemic hemisphere.{{cite journal | vauthors = Ortega FJ, Gimeno-Bayon J, Espinosa-Parrilla JF, Carrasco JL, Batlle M, Pugliese M, Mahy N, Rodríguez MJ | display-authors = 6 | title = ATP-dependent potassium channel blockade strengthens microglial neuroprotection after hypoxia-ischemia in rats | journal = Experimental Neurology | volume = 235 | issue = 1 | pages = 282–296 | date = May 2012 | pmid = 22387180 | doi = 10.1016/j.expneurol.2012.02.010 | hdl-access = free | s2cid = 4828181 | hdl = 2445/34278 }} Moreover, under ischemic conditions SUR1, the regulatory subunit of the KATP- and the NCCa-ATP-channels, is expressed in neurons, astrocytes, oligodendrocytes, endothelial cells{{cite journal | vauthors = Simard JM, Woo SK, Schwartzbauer GT, Gerzanich V | title = Sulfonylurea receptor 1 in central nervous system injury: a focused review | journal = Journal of Cerebral Blood Flow and Metabolism | volume = 32 | issue = 9 | pages = 1699–1717 | date = September 2012 | pmid = 22714048 | pmc = 3434627 | doi = 10.1038/jcbfm.2012.91 }} and by reactive microglia.
According to the research, this and other sulphonylurea drugs also have extra hepatic effects. It works by inhibiting the enzyme Carnityl Acyl Transferase I (CAT-I) indirectly, which is present in the mitochondria. This prevents the transport of long chain fatty acids into the mitochondria for beta-oxidation. This prevents hyperglycemia for which it is prescribed.{{cite journal | vauthors = Chen S, Ogawa A, Ohneda M, Unger RH, Foster DW, McGarry JD | title = More direct evidence for a malonyl-CoA-carnitine palmitoyltransferase I interaction as a key event in pancreatic beta-cell signaling | journal = Diabetes | volume = 43 | issue = 7 | pages = 878–883 | date = July 1994 | pmid = 8013751 | doi = 10.2337/diab.43.7.878 | s2cid = 25251669 }}{{cite journal | vauthors = Lehtihet M, Welsh N, Berggren PO, Cook GA, Sjoholm A | title = Glibenclamide inhibits islet carnitine palmitoyltransferase 1 activity, leading to PKC-dependent insulin exocytosis | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 285 | issue = 2 | pages = E438–E446 | date = August 2003 | pmid = 12684219 | doi = 10.1152/ajpendo.00057.2003 | s2cid = 175394 }}
History
It was developed in 1966 in a cooperative study between Boehringer Mannheim (now part of Roche) and Hoechst (now part of Sanofi-Aventis).{{cite journal | vauthors = Marble A | title = Glibenclamide, a new sulphonylurea: whither oral hypoglycaemic agents? | journal = Drugs | volume = 1 | issue = 2 | pages = 109–115 | year = 1971 | pmid = 4999930 | doi = 10.2165/00003495-197101020-00001 | s2cid = 13181386 }}
Society and culture
= Brand names =
Glibenclamide is available as a generic medication, is manufactured by many pharmaceutical companies and is sold under many brand names including Gliben-J, Daonil,{{Cite web |title=Daonil |url=https://www.news-medical.net/drugs/Daonil.aspx |access-date=26 June 2023 |website=News-Medical.net |language=en |archive-date=26 June 2023 |archive-url=https://web.archive.org/web/20230626042956/https://www.news-medical.net/drugs/Daonil.aspx |url-status=live }} Diabeta,{{Cite web |title=DiaBeta (Glyburide Tablets): Uses, Dosage, Side Effects, Interactions, Warning |url=https://www.rxlist.com/diabeta-drug.htm |access-date=26 June 2023 |website=RxList |language=en |archive-date=26 June 2023 |archive-url=https://web.archive.org/web/20230626042955/https://www.rxlist.com/diabeta-drug.htm |url-status=live }} Euglucon, Gilemal, Glidanil, Glybovin, Glynase, Maninil, Micronase and Semi-Daonil. It is also available in a fixed-dose combination drug with metformin that is sold under various trade names, e.g. Bagomet Plus, Benimet, Glibomet, Gluconorm, Glucored, Glucovance, Metglib and many others.{{Cite web | publisher = Wolters Kluwer N.V. | title = Glyburide and metformin | url = https://www.wolterskluwer.com/en/solutions/lexicomp | website = Lexicomp | access-date = 3 June 2023 | archive-date = 2 June 2023 | archive-url = https://web.archive.org/web/20230602191128/https://www.wolterskluwer.com/en/solutions/lexicomp | url-status = live }}
References
{{Reflist}}
{{Oral hypoglycemics}}
{{Ion channel modulators}}
{{Portal bar | Medicine}}
Category:Disulfiram-like drugs
Category:Potassium channel blockers
Category:1-(Benzenesulfonyl)-3-cyclohexylureas