View source for Sulfamethoxazole

{{Drugbox
| Watchedfields = changed
| verifiedrevid = 470473080
| IUPAC_name = 4-Amino-''N''-(5-methylisoxazol-3-yl)-benzenesulfonamide

<!--Clinical data-->
| tradename =  
| Drugs.com = {{drugs.com|CONS|sulfamethoxazole}}
| pregnancy_AU = C
| pregnancy_US = C
| legal_AU = S4
| legal_CA = Rx-only
| legal_UK = POM
| legal_US = Rx-only
| routes_of_administration = Oral, IV

<!--Pharmacokinetic data-->
| protein_bound = 70%
| metabolism = [[Liver|Hepatic]] [[acetylation]] and [[glucuronidation]]
| elimination_half-life = 10 hours
| excretion = [[Kidney|Renal]]

<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 723-46-6
| ATC_prefix = J01
| ATC_suffix = EC01
| ATC_supplemental =   {{ATCvet|J01|EQ11}}
| PubChem = 5329
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
 | DrugBank = DB01015
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5138
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = JE42381TNV
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00447
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 9332
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 443
| NIAID_ChemDB = 006897

<!--Chemical data-->
| C=10 | H=11 | N=3 | O=3 | S=1 
| molecular_weight = 253.279 [[Gram|g]]/[[Mole (unit)|mol]]
| 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 = 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)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = JLKIGFTWXXRPMT-UHFFFAOYSA-N
| melting_point = 169
}}
__NOTOC__
{{Main|Sulfamethoxazole-Trimethoprim}}
{{CMG}}

==Overview==
'''Sulfamethoxazole''' (abbreviated '''SMZ''' or '''SMX''')<ref>{{cite journal |pmid=17095123 |year=2007 |last1=Ma |first1=M. |last2=Cheng |first2=Y. |last3=Xu |first3=Z. |last4=Xu |first4=P. |last5=Qu |first5=H. |last6=Fang |first6=Y. |last7=Xu |first7=T. |last8=Wen |first8=L. |title=Evaluation of polyamidoamine (PAMAM) dendrimers as drug carriers of anti-bacterial drugs using sulfamethoxazole (SMZ) as a model drug |volume=42 |issue=1 |pages=93–8 |doi=10.1016/j.ejmech.2006.07.015 |journal=European journal of medicinal chemistry}}</ref><ref>{{cite journal |pmid=3485584 |year=1986 |last1=Garg |first1=S.K. |last2=Ghosh |first2=S.S. |last3=Mathur |first3=V.S. |title=Comparative pharmacokinetic study of four different sulfonamides in combination with trimethoprim in human volunteers |volume=24 |issue=1 |pages=23–5 |journal=International journal of clinical pharmacology, therapy, and toxicology}}</ref><ref>SMZ in [http://gateway.nlm.nih.gov/MeetingAbstracts/ma?f=102235045.html Abstract of "Rat model of concurrent Pneumocystis carinii (Pc), Toxoplasma gondii (Tg), and Mycobacterium avium complex (MAC) infections for assessment of multiple prophylaxis"] at ncbi.nlm.nih.gov</ref> is a [[Sulfonamide (medicine)|sulfonamide]] [[bacteriostatic]] [[antibiotic]].

It is most often used as part of a synergistic combination with [[trimethoprim]] in a 5:1 ratio in [[Trimethoprim/sulfamethoxazole|co-trimoxazole]] (abbreviated SMZ-TMP and SMX-TMP,<ref>SMZ-TMP in [http://gateway.nlm.nih.gov/MeetingAbstracts/ma?f=102213827.html Abstract of "Cutaneous hypersensitivity to sulfamethoxazole-trimethoprim (SMZ TMP) in HIV infected patients"] at nlm.nih.gov</ref> or TMP-SMZ and TMP-SMX), also known under [[trade names]] such as [[Co-trimoxazole|Bactrim]], [[Septrin]], or [[Septra]]; in [[Eastern Europe]] it is marketed as Biseptol. Its primary activity is against susceptible forms of ''[[Streptococcus]]'', ''[[Staphylococcus aureus]]'' (including [[Methicillin-resistant Staphylococcus aureus|MRSA]]), ''[[Escherichia coli]]'', ''[[Haemophilus influenzae]]'', and [[Mouth|oral]] [[anaerobes]]. It is commonly used to treat [[urinary tract infections]]. In addition it can be used as an alternative to [[amoxicillin]]-based antibiotics to treat [[sinusitis]]. It can also be used to treat [[toxoplasmosis]] and it is the drug of choice for ''[[Pneumocystis pneumonia]]'', which affects primarily patients with HIV.

Other names include: sulfamethylisoxazol, sulfisomezole, MS 53, RO 4 2130<ref name=pubchem>PubChem. [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=602530&viewopt=PubChem&ncount=15 "Sulfamethoxazole - Substance Summary"], ''[[PubChem]]'', [[National Center for Biotechnology Information]] (NCBI), [[National Library of Medicine]] (NLM), [[National Institutes of Health]] (NIH)</ref><ref name=chemdb>ChemDB. [http://chemdb.niaid.nih.gov/struct_search/all/url_search.asp?aids_no=006897 "Sulfamethoxazole"], ''ChemDB'', [[National Institute of Allergy and Infectious Diseases]] (NIAID), [[National Institutes of Health]] (NIH)</ref> and sulfamethazole.<ref>Sulfamethazole in [http://clinical.diabetesjournals.org/cgi/content/full/21/2/95 "Clinical Diabetes: Case Study: A 90-Year-Old Man With Confusion and Night Sweats"], and [http://www.info4pi.org/aboutPI/index.cfm?section=aboutPI&content=syndromes&area=7 "Chronic Granulomatous Disease"]</ref>

== Mechanism of action ==
Sulfonamides are structural analogs and competitive antagonists of [[4-Aminobenzoic acid|''para''-aminobenzoic acid]] (PABA). They inhibit normal bacterial utilization of PABA for the synthesis of [[folic acid]], an important metabolite in [[DNA synthesis]].<ref>Martindale, ''The extra pharmacopoeia'', 30th ed, p. 208</ref> The effects seen are usually bacteriostatic in nature. Folic acid is not synthesized in humans, but is instead a dietary requirement. This allows for the selective toxicity to bacterial cells (or any cell dependent on synthesizing folic acid) over human cells. Bacterial resistance to sulfamethoxazole is caused by mutations in the enzymes involved in folic acid synthesis that prevent the drug from binding to it.

[[Image:THFsynthesispathway.png|frame|none|Tetrahydrofolate synthesis pathway]]

A TMP-SMZ (also TMP-SMX or TMP-Sulfa) disk is a combination of trimethoprim and sulfamethoxazole(combination of both is known as cotrimoxazole) that acts synergistically for bactericidal action. A bacterial culture impregnated with a  trimethoprim and sulfamethoxazole disk may be used to help identify an organism as ''[[Gardnerella vaginalis]]''; it is sensitive to the TMP-SMZ disk.

==Side effects==
The most common [[adverse drug reaction|side effect]] of sulfamethoxazole/trimethoprim is gastrointestinal upset. Allergies to sulfa-based medications typically cause skin rashes, hives, or trouble breathing or swallowing and warrant immediate discontinuation of the medication and contact with doctor immediately. Sulfamethoxazole/trimethoprim is also known to increase blood concentrations of the drug [[warfarin]] (U.S. brand name: Coumadin) and can cause an unexpected increase in clotting time and uncontrolled bleeding. [[Neutropenia]] and [[thrombocytopenia]] also are rare adverse effects to be monitored if a patient is placed on long-term therapy. Sulfamethoxazole is also a [[Stevens-Johnson syndrome]] (SJS) inducing substance.

Sulfamethoxazole can also cause nausea or severe stomach or abdominal pain. Headaches commonly occur when taking sulfamethoxazole. Muscle pain sometimes occurs when taking this medication. If symptoms persist, one should contact his/her physician. If trouble breathing or swelling of the face, mouth, or tongue occurs, one should discontinue the medication and get emergency medical help. These are often symptoms of a severe allergic reaction ([[anaphylaxis]]).

Sulfamethoxazole/trimethoprim can lead to a megaloblastic anemia in some patients because it is a folate antagonist.<ref>USMLE World Step1, Qbank Pharmacology, 2009, Q106</ref>

==See also==
*[[Sulfisoxazole]]

==Notes==
{{Reflist|2}}

[[Category:Aromatic amines]]
[[Category:Isoxazoles]]
[[Category:Sulfonamide antibiotics]]
[[Category:Drug]]