Sulfonamide (medicine)
Sulfonamide is a
Sulfonamide drugs were the first broadly effective antibacterials to be used systemically, and paved the way for the antibiotic revolution in medicine.
Function
In bacteria, antibacterial sulfonamides act as
Sulfonamides are used to treat allergies and coughs, as well as having antifungal and antimalarial functions. The moiety is also present in other medications that are not antimicrobials, including
Sulfasalazine, in addition to its use as an antibiotic, is also used in the treatment of inflammatory bowel disease.[5]
History
Sulfonamide drugs were the first broadly effective antibacterials to be used systemically, and paved the way for the antibiotic revolution in medicine. The first sulfonamide, trade-named Prontosil, was a prodrug. Experiments with Prontosil began in 1932 in the laboratories of Bayer AG, at that time a component of the huge German chemical trust IG Farben. The Bayer team believed that coal-tar dyes which are able to bind preferentially to bacteria and parasites might be used to attack harmful organisms in the body. After years of fruitless trial-and-error work on hundreds of dyes, a team led by physician/researcher Gerhard Domagk[6] (working under the general direction of IG Farben executive Heinrich Hörlein) finally found one that worked: a red dye synthesized by Bayer chemist Josef Klarer that had remarkable effects on stopping some bacterial infections in mice.[7] The first official communication about the breakthrough discovery was not published until 1935, more than two years after the drug was patented by Klarer and his research partner Fritz Mietzsch.[citation needed]
Prontosil, as Bayer named the new drug, was the first medicine ever discovered that could effectively treat a range of bacterial infections inside the body. It had a strong protective action against infections caused by
The result was a sulfa craze.
The sulfanilamide compound is more active in the
Many thousands of molecules containing the sulfanilamide structure have been created since its discovery (by one account, over 5,400 permutations by 1945), yielding improved formulations with greater effectiveness and less toxicity. Sulfa drugs are still widely used for conditions such as acne and urinary tract infections, and are receiving renewed interest for the treatment of infections caused by bacteria resistant to other antibiotics.[citation needed]
Preparation
Sulfonamides are prepared by the reaction of a
Varieties
Side effects
Sulfonamides have the potential to cause a variety of
Approximately 3% of the general population have adverse reactions when treated with sulfonamide antimicrobials. Of note is the observation that patients with HIV have a much higher prevalence, at about 60%.[17]
Hypersensitivity reactions are less common in nonantibiotic sulfonamides, and, though controversial, the available evidence suggests those with hypersensitivity to sulfonamide antibiotics do not have an increased risk of hypersensitivity reaction to the nonantibiotic agents.
Two regions of the sulfonamide antibiotic chemical structure are implicated in the hypersensitivity reactions associated with the class.
- The first is the N1 heterocyclic ring, which causes a type I hypersensitivity reaction.
- The second is the N4 amino nitrogen that, in a stereospecific process, forms reactive metabolites that cause either direct cytotoxicity or immunologic response.
The nonantibiotic sulfonamides lack both of these structures.[21]
The most common manifestations of a hypersensitivity reaction to sulfa drugs are rash and hives. However, there are several life-threatening manifestations of hypersensitivity to sulfa drugs, including Stevens–Johnson syndrome, toxic epidermal necrolysis, agranulocytosis, hemolytic anemia, thrombocytopenia, fulminant hepatic necrosis, and acute pancreatitis, among others.[22]
See also
- Dihydropteroate synthase
- Elixir sulfanilamide
- Hellmuth Kleinsorge (1920–2001) German medical doctor
- PABA
- Timeline of antibiotics
References
- PMID 16350088.
- ^ "SULFONAMIDE CLASS ANTIBIOTICS". chemicalland21.com. Retrieved 17 January 2014.
- ^ a b "Sulfa Drugs Allergy -- Sulfa Bactrim Drug Allergies". allergies.about.com. Retrieved 17 January 2014.
- ISBN 9780321735515
- ISBN 978-0199549351.
- PMID 3525495.
- ISBN 978-0-307-35228-6.
- ISBN 2-228-88108-2).
- ^ Tréfouël, J.; Tréfouël, Th.; Nitti, F.; Bovet, D. (23 November 1935). "Activité du p. aminophénylsulfamide sur l'infection streptococcique expérimentale de la souris et du lapin". C. R. Soc. Biol. 120: 756.
- ^ "History of medicine". Encyclopædia Britannica. Retrieved 17 January 2014.
- ^ "Bad Health—Elixir Sulfanilamide". The Blog of Bad. 9 February 2009. Retrieved 17 January 2014.
- ^ "History of WWII Medicine". Archived from the original on 14 October 1999. Retrieved 4 April 2014.
- ^ "Medicine: Prontosil". Time. 28 December 1936. Retrieved 28 March 2014.
- OCLC 1066656753.
- ^ Medical Innovations: Antibiotics The National WWII Museum. Accessed 29 July 2021.
- ^ "Trade of Sulfonamides". Massachusetts Institute of Technology. Retrieved 26 October 2013.
- S2CID 8493824.
- PMID 15242722.
- S2CID 20386434.
- ^ Veroni M. "ALLERGIES TO SULFONAMIDE ANTIBIOTICS AND CROSS-REACTIVITIES" (PDF). Western Australian Therapeutic Advisory Group. Archived from the original (PDF) on 3 March 2011. Retrieved 7 February 2014.
- S2CID 25623592.
- ^ Harrison's Principles of Internal Medicine, 13th Ed. McGraw-Hill Inc. 1994. p. 604.
External links
- List of sulfonamides
- A History of the Fight Against Tuberculosis in Canada (Chemotherapy)
- Presentation speech, Nobel Prize in Physiology and Medicine, 1939
- The History of WW II Medicine
- "Five Medical Miracles of the Sulfa Drugs". Popular Science, June 1942, pp. 73–78.
- A history of antibiotics