Tolbutamid

Tolbutamid
(IUPAC) ime
	N-[(butilamino) karbonil]-4-metilbenzensulfonamid
Klinički podaci
AHFS/Drugs.com	Monografija
MedlinePlus	a682481
Identifikatori
CAS broj	64-77-7
ATC kod	A10BB03 V04CA01
PubChem	5505
DrugBank	APRD00267
ChemSpider	5304
UNII	982XCM1FOI
KEGG	D00380
ChEBI	CHEBI:27999
ChEMBL	CHEMBL782
Hemijski podaci
Formula	C12H18N2O3S
Mol. masa	270.35 g/mol
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C12H18N2O3S/c1-3-4-9-13-12(15)14-18(16,17)11-7-5-10(2)6-8-11/h5-8H,3-4,9H2,1-2H3,(H2,13,14,15) ; Key: JLRGJRBPOGGCBT-UHFFFAOYSA-N
Farmakokinetički podaci
Vezivanje za proteine plazme	96%
Metabolizam	Hepatički (CYP2C19-posredovano)
Poluvreme eliminacije	4.5 do 6.5 sata
Izlučivanje	Renalno
Farmakoinformacioni podaci
Licenca	US FDA:link
Trudnoća	C(AU) C(US)
Pravni status	POM (UK) ℞-only (SAD)
Način primene	Oralo

Tolbutamid je prva generacija blokatora kalijumskog kanala, sulfonilurejskih oralnih hipoglikemskih lekova. On je u prodaju pod imenom Orinaza. Ovaj lek se primenjuje za kontrolu tipa II dijabetes, ako dijeta nije efektivna. Tolbutamid stimuliše sekreciju insulina iz pankreasa. Pošto gušterača mora da sintetiše insulin da bi ovaj lek bio delotvoran, on nije efektivan u kontroli tipa I dijabetesa. On se ne koristi rutinski zbog povišene učestalosti nepoželjnih efekata u poređenju sa novijom, drugom generacijom sulfonilureja, poput gliburida. On ima generalno kratko vreme dejstva usled brzog metabolizma, te je stoga bezbedan za upotrebu kod starijih dijabetičara.^[6]^[7]

Nuspojave

Hipoglikemija
Uvećanje telesne težine
Hipersenzitivnost
Interakcije lekova: povećana hipoglikemija sa cimetidinom, insulinom, salicilatima, sulfonamidima

Salicilati zamenjuju tolbutamid na njegovom mestu vezivanje u na proteinima plazme, što dovodi do povišenog nivoa slobodnog tolbutamida, te to hipoglikemijskog šoka.

Sinteza

Postoji više načina pripreme tolbutamida. Najkraći sintetički put je adicija para-toluensulfonamida do butil izocijanata:^[8]

Reference

↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit
↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.
↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit
↑ Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.
↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit
↑ Hardman JG, Limbird LE, Gilman AG. (2001). Goodman & Gilman's The Pharmacological Basis of Therapeutics (10 izd.). New York: McGraw-Hill. DOI:10.1036/0071422803. ISBN 0-07-135469-7.
↑ Pdr Staff (2009). PDR: Physicians Desk Reference 2010 (Physicians' Desk Reference (Pdr)). Rozelle, N.S.W: Thomson Reuters. ISBN 1-56363-748-0.
↑ Ruschig, H.; Avmuller, W.; Korger, G.; Wagner, H.; Scholtz, J.; Bander, A.; 1961, U.S. Patent 2,976,317.

Literatura

Diabetes Prevention Program Research Group. "Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin." Journal of the American Medical Association 346: 393-402. 2000.
Jeremy A. Greene. Prescribing by Numbers: Drugs and the Definition of Disease. Johns Hopkins University Press: Baltimore, MD. 2007.
William L. Lawrence. "Science in Review: Drug for the Treatment of Diabetes Tested And Found of Great Importance." New York Times February 24, 1957.

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Vanjske veze

	Portal Medicina
	Portal Hemija

[1] Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit

[2] Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.

[3] Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit

[4] Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.

[5] Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit

[Goodman_Gilman-6] Hardman JG, Limbird LE, Gilman AG. (2001). Goodman & Gilman's The Pharmacological Basis of Therapeutics (10 izd.). New York: McGraw-Hill. DOI:10.1036/0071422803. ISBN 0-07-135469-7.

[PDR-7] Pdr Staff (2009). PDR: Physicians Desk Reference 2010 (Physicians' Desk Reference (Pdr)). Rozelle, N.S.W: Thomson Reuters. ISBN 1-56363-748-0.

[8] Ruschig, H.; Avmuller, W.; Korger, G.; Wagner, H.; Scholtz, J.; Bander, A.; 1961, U.S. Patent 2,976,317.

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