Sulfonamide (medicine)

Source: Wikipedia, the free encyclopedia.
For chemistry of the functional group, see Sulfonamide.

Sulfonamide functional group
Hydrochlorothiazide is a sulfonamide and a thiazide.
Furosemide is a sulfonamide, but not a thiazide.
Sulfamethoxazole is an antibacterial sulfonamide.

Sulfonamide is a

thiazide diuretics are newer drug groups based upon the antibacterial sulfonamides.[1][2]

adverse drug reactions to sulfa antibiotics is approximately 3%, close to penicillin;[3]
hence medications containing sulfonamides are prescribed carefully.

Sulfonamide drugs were the first broadly effective antibacterials to be used systemically, and paved the way for the antibiotic revolution in medicine.

Function

Main article: Dihydropteroate synthase inhibitor

In bacteria, antibacterial sulfonamides act as

folate synthesis. Sulfonamides are therefore bacteriostatic and inhibit growth and multiplication of bacteria, but do not kill them. Humans, in contrast to bacteria, acquire folate (vitamin B9) through the diet.[4]

Structural similarity between sulfanilamide (left) and PABA (center) is the basis for the inhibitory activity of sulfa drugs on tetrahydrofolate (right) biosynthesis.

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

COX-2 inhibitors (e.g., celecoxib
).

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

Jacques and Thérèse Tréfouël, a French research team led by Ernest Fourneau at the Pasteur Institute, that the drug was metabolized into two parts inside the body, releasing from the inactive dye portion a smaller, colorless, active compound called sulfanilamide.[9] The discovery helped establish the concept of "bioactivation" and dashed the German corporation's dreams of enormous profit; the active molecule sulfanilamide (or sulfa) had first been synthesized in 1906 and was widely used in the dye-making industry; its patent had since expired and the drug was available to anyone.[10]

The result was a sulfa craze.

first-aid kit containing sulfa pills and powder and were told to sprinkle it on any open wound.[15]

The sulfanilamide compound is more active in the

protonated form. The drug has very low solubility and sometimes can crystallize in the kidneys, due to its first pKa of around 10.[clarification needed] This is a very painful experience, so patients are told to take the medication with copious amounts of water. Newer analogous compounds prevent this complication because they have a lower pKa, around 5–6,[citation needed
] making them more likely to remain in a soluble form.

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

sulfonyl chloride with ammonia or an amine. Certain sulfonamides (sulfadiazine or sulfamethoxazole) are sometimes mixed with the drug trimethoprim, which acts against dihydrofolate reductase. As of 2013, the Republic of Ireland is the largest exporter worldwide of sulfonamides, accounting for approximately 32% of total exports.[16]

Varieties

Main article: List of sulfonamides

Side effects

Person with Stevens–Johnson syndrome
Allergic urticaria on the skin induced by an antibiotic

Sulfonamides have the potential to cause a variety of

DRESS syndrome, and a not quite as serious SCARs reaction, acute generalized exanthematous pustulosis. Any one of these SCARs may be triggered by certain sulfonamides.[3]

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.

cotrimoxazole allergy").[20]

Two regions of the sulfonamide antibiotic chemical structure are implicated in the hypersensitivity reactions associated with the class.

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

References

  1. PMID 16350088
    .
  2. ^ "SULFONAMIDE CLASS ANTIBIOTICS". chemicalland21.com. Retrieved 17 January 2014.
  3. ^ a b "Sulfa Drugs Allergy -- Sulfa Bactrim Drug Allergies". allergies.about.com. Retrieved 17 January 2014.
  4. ISBN 9780321735515
  5. ISBN 978-0199549351
    .
  6. PMID 3525495
    .
  7. ISBN 978-0-307-35228-6
    .
  8. ISBN 2-228-88108-2
    ).
  9. ^ 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.
  10. ^ "History of medicine". Encyclopædia Britannica. Retrieved 17 January 2014.
  11. ^ "Bad Health—Elixir Sulfanilamide". The Blog of Bad. 9 February 2009. Retrieved 17 January 2014.
  12. ^ "History of WWII Medicine". Archived from the original on 14 October 1999. Retrieved 4 April 2014.
  13. ^ "Medicine: Prontosil". Time. 28 December 1936. Retrieved 28 March 2014.
  14. OCLC 1066656753
    .
  15. ^ Medical Innovations: Antibiotics The National WWII Museum. Accessed 29 July 2021.
  16. ^ "Trade of Sulfonamides". Massachusetts Institute of Technology. Retrieved 26 October 2013.
  17. S2CID 8493824
    .
  18. PMID 15242722
    .
  19. S2CID 20386434
    .
  20. ^ 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.
  21. S2CID 25623592
    .
  22. ^ Harrison's Principles of Internal Medicine, 13th Ed. McGraw-Hill Inc. 1994. p. 604.

External links

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