Sulfamethoxazole

Structural formula
General
Non-proprietary name	Sulfamethoxazole
other names	4-Amino- N - (5-methyl-1,2-oxazol-3-yl) benzene sulfonamide ( IUPAC ) ; N 1 - (5-methyl-3-isoxazolyl) sulfanilamide; 3- ( p -aminophenylsulfonamido) -5-methylisoxazole; Abacin;
Molecular formula	C 10 H 11 N 3 O 3 S
Brief description	crystalline solid
External identifiers / databases
EC number	211-963-3
ECHA InfoCard	100.010.877
PubChem	5329
ChemSpider	5138
DrugBank	DB01015
Wikidata	Q415843
Drug information
ATC code	J01 EC01
Drug class	Sulfonamides
properties
Molar mass	253.28 g mol −1
Physical state	firmly
Melting point	167 ° C
pK s value	5.6
solubility	slightly soluble in water (0.61 g l −1 at 37 ° C)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 315-317-319-335
	P: 261-280-305 + 351 + 338
Toxicological data	2300 mg kg −1 ( LD 50 , mouse , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Sulphamethoxazole is an antibiotic from the group of sulphonamides , which is mainly used to fight urinary tract infections and pneumonia .

As a finished medicinal product (D, A, CH), sulfamethoxazole is only available in a fixed combination with trimethoprim . This fixed combination in a ratio of 5: 1 is also called cotrimoxazole .

Special indications are the control of Pneumocystis jirovecii (formerly: Pneumocystis carinii ), Nocardia asteroides and Stenotrophomonas maltophilia .

Mechanism of action

Sulfamethoxazole is a competitive inhibitor of dihydropteroate synthase . The natural substrate of this enzyme is para-aminobenzoic acid (PABA). The thus inhibited enzyme reaction is an essential step in bacterial folic acid synthesis. Folic acid is required for the synthesis of DNA . This inhibition does not affect humans because they do not synthesize folic acid themselves, but take it in through food.

Pharmacokinetics

Sulfamethoxazole has a plasma half-life of nine to eleven hours.

Side effects

The side effects of sulfamethoxazole are the same as those of sulfonamides, with skin problems being the most common. Skin reactions of various kinds, mostly rashes , are observed in 2–3 percent of those treated. Side effects affecting the blood count, which can affect all cell lines, are dangerous: leukopenia , anemia , and thrombocytopenia are possible. Side effects on the central nervous system can lead to ataxia or convulsions , psychoses and depression . Nausea and vomiting, loss of appetite and diarrhea are more common. A liver involvement can for transaminases and renal involvement to creatinine lead.

In the usual combination with trimethoprim , sulfamethoxazole can lead to a prolongation of the QT time in the heart and should therefore not be used in patients with longQT syndrome .

Contraindications

The combination of sulfamethoxazole and trimethoprim must not be used in cases of known hypersensitivity to the ingredients, including erythema multiforme exudativum , pre-existing blood count changes, glucose-6-phosphate dehydrogenase deficiency, severe renal insufficiency , severe liver damage, porphyria , premature babies and newborns with hyperbilirubinemia . In the case of mild kidney and liver dysfunction, dysfunction of the thyroid gland and newborns under five weeks of age, it should only be used in exceptional cases and under careful supervision.

Trade names

Combination preparations

Bactrim (A, CH), Drylin (D), Escoprim (CH), Eusaprim (D, A), Kepinol (D), Lagatrim (CH), Nopil (CH), TMS forte (D), numerous generics (D, A, CH)

Environmental relevance

After absorption into the body, sulfamethoxazole is partly excreted unmetabolized and not completely broken down even in sewage treatment plants . In this way, the substance ends up in surface waters such as rivers. Typical concentrations are in the two- to three-digit nanograms per liter range, but can even be several micrograms per liter.

Individual evidence

↑ Entry on sulfamethoxazole. In: Römpp Online . Georg Thieme Verlag, accessed on December 28, 2014.
↑ ^a ^b ^c Entry on sulfamethoxazole in the ChemIDplus database of the United States National Library of Medicine (NLM) .
^ Carsten jewelry, Bernd Engels, Tanja Schirmeister, Reinhold Fink: Chemistry for medical professionals. Pearson Studium, 2008, ISBN 978-3-8273-7286-4 , p. 654.
↑ ^a ^b data sheet sulfamethoxazole from Sigma-Aldrich , accessed on May 13, 2017 ( PDF ).
^ William Martindale, Wynn Westcott: The extra pharmacopoeia. 30th edition. Pharmaceutical Press, London 1993, ISBN 0-85369-210-6 , p. 208.
↑ BL Lee, T. Delahunty, S. Safrin: The hydroxylamine of sulfamethoxazole and adverse reactions in patients with acquired immunodeficiency syndrome. In: Clinical Pharmacology and Therapeutics . 56 (2), 1994, pp. 184-189.
↑ Entry on sulfamethoxazole in the Hazardous Substances Data Bank , accessed February 1, 2017.
↑ Elissavet Kassotaki, Gianluigi Buttiglieri, Laura Ferrando-Climent, Ignasi Rodriguez-Roda, Maite Pijuan: Enhanced sulfamethoxazole degradation through ammonia oxidizing bacteria co-metabolism and fate of transformation products. In: Water Research . Vol. 94, May 1, 2016, pp. 111–119. doi: 10.1016 / j.watres.2016.02.022 .
↑ Robert Loos, Bernd Manfred Gawlik, Giovanni Locoro, Erika Rimaviciute, Serafino Contini, Giovanni Bidoglio: EU-wide survey of polar organic persistent pollutants in European river waters. In: Environmental Pollution . Vol. 157, No. 2, February 2009, pp. 561-568. doi: 10.1016 / j.envpol.2008.09.020 .

[roempp-1] Entry on sulfamethoxazole. In: Römpp Online . Georg Thieme Verlag, accessed on December 28, 2014.

[ChemIDplus-2] Entry on sulfamethoxazole in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[Schmuck-3] Carsten jewelry, Bernd Engels, Tanja Schirmeister, Reinhold Fink: Chemistry for medical professionals. Pearson Studium, 2008, ISBN 978-3-8273-7286-4 , p. 654.

[Sigma-4] ta sheet sulfamethoxazole from Sigma-Aldrich , accessed on May 13, 2017 ( PDF ).

[5] William Martindale, Wynn Westcott: The extra pharmacopoeia. 30th edition. Pharmaceutical Press, London 1993, ISBN 0-85369-210-6 , p. 208.

[6] BL Lee, T. Delahunty, S. Safrin: The hydroxylamine of sulfamethoxazole and adverse reactions in patients with acquired immunodeficiency syndrome. In: Clinical Pharmacology and Therapeutics . 56 (2), 1994, pp. 184-189.

[7] Entry on sulfamethoxazole in the Hazardous Substances Data Bank , accessed February 1, 2017.

[8] Elissavet Kassotaki, Gianluigi Buttiglieri, Laura Ferrando-Climent, Ignasi Rodriguez-Roda, Maite Pijuan: Enhanced sulfamethoxazole degradation through ammonia oxidizing bacteria co-metabolism and fate of transformation products. In: Water Research . Vol. 94, May 1, 2016, pp. 111–119. doi: 10.1016 / j.watres.2016.02.022 .

[9] Robert Loos, Bernd Manfred Gawlik, Giovanni Locoro, Erika Rimaviciute, Serafino Contini, Giovanni Bidoglio: EU-wide survey of polar organic persistent pollutants in European river waters. In: Environmental Pollution . Vol. 157, No. 2, February 2009, pp. 561-568. doi: 10.1016 / j.envpol.2008.09.020 .