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Revision as of 18:12, 9 January 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 462732654 of page Sulfamethoxazole for the Chem/Drugbox validation project (updated: 'DrugBank').		Latest revision as of 20:14, 5 December 2024 edit Citation bot (talk | contribs)Bots5,418,794 edits Added doi-broken-date. | Use this bot. Report bugs. | #UCB_CommandLine
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			{{Short description|Chemical compound}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
			{{Redirect|Trib|the newspaper referred to as "The Trib"|Chicago Tribune}}
	{{Drugbox		{{Drugbox
	| Verifiedfields = changed		| Watchedfields = changed
	| verifiedrevid = 416110220		| verifiedrevid = 470473080
	| IUPAC_name = 4-amino-''N''-(5-methylisoxazol-3-yl)-benzenesulfonamide		| IUPAC_name = 4-Amino-''N''-(5-methylisoxazol-3-yl)-benzenesulfonamide
	| image = Sulfamethoxazole.png		| image = Sulfamethoxazole-skeletal.svg
	| image2 = Sulfamethoxazole.gif		| image2 = Sulfamethoxazole-from-xtal-3D-bs-17.png
	<!--Clinical data-->		<!--Clinical data-->
	| tradename =		| tradename = Gantanol
	| Drugs.com = {{drugs.com|CONS|sulfamethoxazole}}		| Drugs.com = {{drugs.com|CONS|sulfamethoxazole}}
			| pregnancy_AU = C
	| pregnancy_category = C <small>(Australia, United States)</small>
	| legal_AU = s4		| pregnancy_US = C
			| legal_AU = S4
	| legal_status = ℞-only
			| legal_CA = Rx-only
			| legal_UK = POM
			| legal_US = Rx-only
	| routes_of_administration = Oral, IV		| routes_of_administration = Oral, IV
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	| protein_bound = 70%		| protein_bound = 70%
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	| elimination_half-life = 10 hours		| elimination_half-life = 10 hours
	| excretion = ]		| excretion = ]
	<!--Identifiers-->		<!--Identifiers-->
	| CASNo_Ref = {{cascite|correct|CAS}}
	| CAS_number_Ref = {{cascite|correct|??}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 723-46-6		| CAS_number = 723-46-6
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	| KEGG_Ref = {{keggcite|correct|kegg}}		| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D00447		| KEGG = D00447
	| ChEBI_Ref = {{ebicite|changed|EBI}}		| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 9332		| ChEBI = 9332
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 443		| ChEMBL = 443
			| NIAID_ChemDB = 006897
	<!--Chemical data-->		<!--Chemical data-->
	| C=10 | H=11 | N=3 | O=3 | S=1		| C=10 | H=11 | N=3 | O=3 | S=1
			| SMILES = Nc1ccc(cc1)S(=O)(=O)Nc2cc(C)on2
	| molecular_weight = 253.279 ]/]
	| smiles = O=S(=O)(Nc1noc(c1)C)c2ccc(N)cc2
	| InChI = 1/C10H11N3O3S/c1-7-6-10(12-16-7)13-17(14,15)9-4-2-8(11)3-5-9/h2-6H,11H2,1H3,(H,12,13)
	| InChIKey = JLKIGFTWXXRPMT-UHFFFAOYAI
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C10H11N3O3S/c1-7-6-10(12-16-7)13-17(14,15)9-4-2-8(11)3-5-9/h2-6H,11H2,1H3,(H,12,13)		| StdInChI = 1S/C10H11N3O3S/c1-7-6-10(12-16-7)13-17(14,15)9-4-2-8(11)3-5-9/h2-6H,11H2,1H3,(H,12,13)
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	| melting_point = 169		| melting_point = 169
	}}		}}
			<!-- Definition and medical uses -->
			'''Sulfamethoxazole''' ('''SMZ''' or '''SMX''') is an ]. It is used for ]s such as ], ], and ] and is effective against both ] and ] such as '']'' and '']''.<ref name = drugbank>{{cite web|title=Sulfamethoxazole|url=http://www.drugbank.ca/drugs/DB01015|website=DrugBank|access-date=5 November 2015}}</ref>
			<!-- Side effect and mechanism -->
			Common ] include ], ], ], and skin ]. It is a ] and ]. It resembles a component of ]. It prevents folic acid synthesis in the bacteria that must synthesize their own folic acid. Mammalian cells, and some bacteria, do not synthesize but require preformed folic acid (vitamin B9); they are therefore insensitive to sulfamethoxazole.<ref name=":1">{{Cite book | vauthors = Brunton L, Chabner BA, Knollman B
			|title=Goodman and Gilman's The pharmacological Basis of Therapeautics |year=2011|isbn=9780071624428|location=The McGraw-Hill Companies, Inc.|pages=1463–1469 }}</ref>
			<!-- History, society and culture -->
			It was introduced to the United States in 1961.<ref>{{cite book | chapter = Sulfamethoxazole |title=Pharmaceutical Manufacturing Encyclopedia | edition = 3rd | volume = 4 |publisher=William Andrew Publishing | chapter-url = https://books.google.com/books?id=_J2ti4EkYpkC&q=gantanol+manufacturer&pg=PA3104 |isbn=9780815518563 |date=2013-10-22}}</ref> It is now mostly used in combination with ] (abbreviated ]).<ref>{{cite book | vauthors = Kemnic TR, Coleman M | chapter = Trimethoprim Sulfamethoxazole. | date = November 2022 | title = StatPearls . | location = Treasure Island (FL) | publisher = StatPearls Publishing | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK513232/ | pmid = 30020604 }}</ref> The SMX-TMP combination is on the WHO Model List of Essential medicines as a first-choice treatment for urinary tract infections.<ref>{{cite journal | vauthors = Roth L, Adler M, Jain T, Bempong D | title = Monographs for medicines on WHO's Model List of Essential Medicines | journal = Bulletin of the World Health Organization | volume = 96 | issue = 6 | pages = 378–385 | date = June 2018 | pmid = 29904220 | pmc = 5996216 | doi = 10.2471/blt.17.205807 | doi-broken-date = 5 December 2024 }}</ref> Other names include: sulfamethalazole and sulfisomezole.<ref name=pubchem>{{cite web | url = https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=602530&viewopt=PubChem&ncount=15 | title = Sulfamethoxazole - Substance Summary | work = ] | publisher = ] (NCBI), ] (NLM), ] (NIH) }}</ref><ref name=chemdb>{{cite web | work = ChemDB | url = http://chemdb.niaid.nih.gov/struct_search/all/url_search.asp?aids_no=006897 | title = Sulfamethoxazole | archive-url = https://archive.today/20121215080222/http://chemdb.niaid.nih.gov/struct_search/all/url_search.asp?aids_no=006897 | archive-date=2012-12-15 | publisher = ] (NIAID), ] (NIH) }}</ref>
			==Side effects==
			The most common ] of sulfamethoxazole are ] (nausea, vomiting, anorexia) and allergic skin reactions (such as ] and ]).<ref name = USPI>{{cite web|title=Bactrim USPI | date = November 2013 |url= http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017377s074lbl.pdf | work = Caraco Pharmaceutical Laboratories, Ltd. |publisher= U.S. Food and Drug Administration }}</ref> There have been rare instances where severe adverse reactions have resulted in fatalities. These include ] (SJS), ], ], ], ], and other blood ]s.<ref name = USPI/>
			Allergic reactions to Sulfonamides have been shown to include the entire Gel-Coombs spectrum of hyperactivity reactions.<ref name="pmid23943179">{{cite journal | vauthors = Wulf NR, Matuszewski KA | title = Sulfonamide cross-reactivity: is there evidence to support broad cross-allergenicity? | journal = American Journal of Health-System Pharmacy | volume = 70 | issue = 17 | pages = 1483–1494 | date = September 2013 | pmid = 23943179 | doi = 10.2146/ajhp120291 }}</ref> Type 1 reactions include immunoglobulin E (IgE)-mediated reactions such as urticaria, angioedema, and anaphylaxis. In contrast, non-type 1 hypersensitivities are believed to be caused by metabolites of sulfonamides.<ref name="pmid11895621">{{cite journal | vauthors = Choquet-Kastylevsky G, Vial T, Descotes J | title = Allergic adverse reactions to sulfonamides | journal = Current Allergy and Asthma Reports | volume = 2 | issue = 1 | pages = 16–25 | date = January 2002 | pmid = 11895621 | doi = 10.1007/s11882-002-0033-y | s2cid = 19624750 }}</ref> Therefore, the liver and kidney are the determining factors of these other hypersensitivity reactions;<ref name="pmid11895621"/> alterations in kidney or liver functions may increase or decrease the frequencies of these reactions. One study has shown the allergic reaction rate to be about 3.0% over 359 courses of therapy.<ref name = toxnet>{{cite web|work = Toxnet | title = Sulfamethoxazole | publisher = U.S. National Library of Medicine |url=http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~alRB8X:3}}</ref> Of the allergic reactions, skin rashes, ] and drug fever were the most common, while serious reactions were less common.
			Sulfamethoxazole is contraindicated in people with a known hypersensitivity to trimethoprim or sulfonamides.<ref name="pmid23943179"/>
			== Mechanism of action ==
			Sulfamethoxazole, a ], is a structural analog of ] (PABA). They compete with PABA to bind to ] and inhibit conversion of PABA and dihydropteroate diphosphate to dihydrofolic acid, or dihydrofolate. Inhibiting the production of dihydrofolate intermediate interferes with the normal bacterial synthesis of ] (folate). Folate is an essential metabolite for bacterial growth and replication because it is used in ], primarily at ] and purine biosynthesis, and amino acids synthesis, including serine, glycine and methionine.<ref>{{Cite web | vauthors = Mercer MA | date = September 2022 |title = Sulfonamides and Sulfonamide Combinations Use in Animals | work = Merck Veterinary Manual|url = http://www.merckvetmanual.com/mvm/pharmacology/antibacterial_agents/sulfonamides_and_sulfonamide_combinations.html |access-date = 2015-11-05}}</ref> Hence, blockage of folate production inhibits the folate-dependent metabolic processes for bacterial growth. Since it inhibits bacterial growth, sulfamethoxazole is considered a ] antibiotic.<ref name = drugbank />
			]Sulfonamides are selective against bacteria because they interfere with the synthesis of folate, a process which does not occur in humans. Humans do not synthesize folate, and must acquire it through diet.<ref>{{Cite web | vauthors = Werth BJ | date = September 2022 |title = Sulfonamides - Infectious Diseases|url = http://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/sulfonamides|website = Merck Manuals Professional Edition|access-date = 2015-11-05}}</ref>
			== Pharmacokinetics ==
			'''Absorption'''
			Sulfamethoxazole is well-absorbed when administered topically. It is rapidly absorbed when it is orally administered.<ref name = drugbank>{{cite web|title=Sulfamethoxazole|url=http://www.drugbank.ca/drugs/DB01015|website=DrugBank|access-date=5 November 2015}}</ref>
			'''Distribution'''
			Sulfamethoxazole distributes into most body tissues as well as into sputum, vaginal fluid, and middle ear fluid.<ref name = USPI/><ref name = toxnet /> It also crosses the placenta. About 70% of the drug is bound to plasma proteins. Its Tmax (or time to reach maximum drug concentration in plasma) occurs 1 to 4 hours after oral administration. The mean serum half-life of sulfamethoxazole is 10 hours.<ref name = USPI /> However, the half-life of the drug noticeably increases in people with creatinine clearance rates equal to or less than 30 mL/minute. A half-life of 22–50 hours has been reported for people with creatinine clearances of less than 10 mL/minute.<ref name = toxnet />
			'''Metabolism'''
			Sulfamethoxazole is metabolized in the human liver to at least 5 metabolites. These metabolites are the N4-acetyl-, N4-hydroxy-, 5-methylhydroxy-, N4-acetyl-5-methylhydroxy-sulfamethoxazole metabolites, and an N-glucuronide conjugate. The ] is responsible for the formation of the N4-hydroxy metabolite. In vitro studies suggest sulfamethoxazole is not a substrate of the P-glycoprotein transporter.<ref name = USPI/>
			'''Excretion'''
			Sulfamethoxazole is primarily renally excreted via glomerular filtration and tubular secretion.<ref name = USPI/> About 20% of the sulfamethoxazole in urine is the unchanged drug, about 15–20% is the N-glucuronide conjugate, and about 50–70 % is the acetylated metabolite.<ref name = toxnet /> Sulfamethoxazole is also excreted in human milk.<ref name = USPI/>
			== See also ==
			*]
			*]
			==Notes==
			{{Reflist|30em}}
			== External links ==
			{{SulfonamideAntiBiotics}}
			]
			]
			]
			]
			]
			]