Sulfamethoxazole

Sulfamethoxazole

Systematic (IUPAC) name
4-amino-N-(5-methylisoxazol-3-yl)-benzenesulfonamide
Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy cat.	C (Australia, United States)
Legal status	Prescription Only (S4) (AU) ℞-only
Routes	Oral, IV
Pharmacokinetic data
Protein binding	70%
Metabolism	Hepatic acetylation and glucuronidation
Half-life	10 hours
Excretion	Renal
Identifiers
CAS number	723-46-6 Y
ATC code	J01EC01 QJ01EQ11
PubChem	CID 5329
DrugBank	APRD00076
ChemSpider	5138 Y
UNII	JE42381TNV Y
KEGG	D00447 Y
ChEBI	CHEBI:9332 N
ChEMBL	CHEMBL443 Y
Chemical data
Formula	C10H11N3O3S
Mol. mass	253.279 g/mol
SMILES	eMolecules & PubChem
InChI InChI=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) Y Key:JLKIGFTWXXRPMT-UHFFFAOYSA-N Y
Physical data
Melt. point	169 °C (336 °F)
N(what is this?)  (verify)

Sulfamethoxazole (abbreviated SMZ or SMX)^[1][2][3] is a sulfonamide bacteriostatic antibiotic.

It is most often used as part of a synergistic combination with trimethoprim in a 5:1 ratio in co-trimoxazole (abbreviated SMZ-TMP and SMX-TMP,^[4] or TMP-SMZ and TMP-SMX), also known under trade names such as Bactrim, Septrin, or Septra; in Eastern Europe it is marketed as Biseptol. Its primary activity is against susceptible forms of Streptococcus, Staphylococcus aureus (including MRSA), Escherichia coli, Haemophilus influenzae, and 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,^[5][6][7] and sulfamethazole.^[8]

Mechanism of action

Sulfonamides are structural analogs and competitive antagonists of para-aminobenzoic acid (PABA). They inhibit normal bacterial utilization of PABA for the synthesis of folic acid, an important metabolite in DNA synthesis.^[9] 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.

Tetrahydrofolate synthesis pathway

A TMP-SMZ (also TMP-SMX or TMP-Sulfa) disk is a combination of trimethoprim and sulfamethoxazole 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 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.^{[citation needed]}

Sulfamethoxazole can also cause nausea, severe stomach, or abdomen pains. Headaches commonly occur when taking sulfamethoxazole. Muscle pains sometimes occur when taking this medicine. 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 medicine and get emergency medical help. These are often symptoms of a severe allergic reaction.

Sulfamethoxazole/trimethoprim can lead to a megaloblastic anemia in some patients because it is a folate antagonist.^[10]

Notes

1. ^ Ma, M.; Cheng, Y.; Xu, Z.; Xu, P.; Qu, H.; Fang, Y.; Xu, T.; Wen, L. (2007). "Evaluation of polyamidoamine (PAMAM) dendrimers as drug carriers of anti-bacterial drugs using sulfamethoxazole (SMZ) as a model drug". European journal of medicinal chemistry 42 (1): 93–8. doi:10.1016/j.ejmech.2006.07.015. PMID 17095123. 
2. ^ Garg, S.K.; Ghosh, S.S.; Mathur, V.S. (1986). "Comparative pharmacokinetic study of four different sulfonamides in combination with trimethoprim in human volunteers". International journal of clinical pharmacology, therapy, and toxicology 24 (1): 23–5. PMID 3485584. 
3. ^ SMZ in 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
4. ^ SMZ-TMP in Abstract of "Cutaneous hypersensitivity to sulfamethoxazole-trimethoprim (SMZ TMP) in HIV infected patients" at nlm.nih.gov
5. ^ BIAM, "Sulfamethoxazole"
6. ^ PubChem, "Sulfamethoxazole - Substance Summary"
7. ^ ChemDB, "Sulfamethoxazole"
8. ^ Sulfamethazole in "Clinical Diabetes: Case Study: A 90-Year-Old Man With Confusion and Night Sweats", and "Chronic Granulomatous Disease"
9. ^ Martindale, The extra pharmacopoeia, 30th ed, p. 208
10. ^ USMLE World Step1, Qbank Pharmacology, 2009, Q106

References

• BIAM. "Sulfamethoxazole" (in French), Banque d'Informations Automatisée sur les Médicaments (drugs database), last updated December 21, 2000
• ChemDB. "Sulfamethoxazole", ChemDB, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
• PubChem. "Sulfamethoxazole - Substance Summary", PubChem, National Center for Biotechnology Information (NCBI), National Library of Medicine (NLM), National Institutes of Health (NIH)

External links

• Sulfamethoxazole in the ChemIDplus database