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Sulfonamide is a functional group (a part of a molecule) that is the basis of several groups of medication, which are called sulphonamides, sulfa drugs or sulpha drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame. The and thiazide diuretics are newer drug groups based upon the antibacterial sulfonamides.
Drug allergy to sulfonamides are common. The overall incidence of adverse drug reactions to sulfa antibiotics is approximately 3%, close to penicillin; 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.
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 thiazide (including hydrochlorothiazide, metolazone, and indapamide, among others), loop diuretics (including furosemide, bumetanide, and torsemide), acetazolamide, sulfonylureas (including glipizide, glyburide, among others), and some 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. (2025). 9780199549351, Oxford University Press. ISBN 9780199549351
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. The root word "pronto" was meant to imply "fast acting." (2025). 9781737001379, Jaywalker Publishing. ISBN 9781737001379It had a strong protective action against infections caused by streptococcus, including blood infections, childbed fever, and erysipelas, and a lesser effect on infections caused by other cocci. However, it had no effect at all in the test tube, exerting its antibacterial action only in live animals. Later, it was discovered by Daniel Bovet,Cf. Daniel Bovet, Une chimie qui guérit : Histoire de la découverte des sulfamides, Paris, Payot, coll. « Médecine et sociétés », 1988 (). Federico Nitti, and 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. 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.
The result was a sulfa craze. For several years in the late 1930s, hundreds of manufacturers produced myriad forms of sulfa. This and the lack of testing requirements led to the elixir sulfanilamide disaster in the fall of 1937, during which at least 100 people were poisoned with diethylene glycol. This led to the passage of the Federal Food, Drug, and Cosmetic Act in 1938 in the United States, giving authority to the U.S. Food and Drug Administration (FDA) to oversee the safety of food, drugs, medical devices, and cosmetics. As the first and only effective broad-spectrum antibiotic available in the years before penicillin, heavy use of sulfa drugs continued into the early years of World War II. They are credited with saving the lives of tens of thousands of patients, including Franklin Delano Roosevelt Jr. (son of US President Franklin Delano Roosevelt) and Winston Churchill. Sulfa had a central role in preventing wound infections during the war. American soldiers were issued a first-aid kit containing sulfa pills and powder and were told to sprinkle it on any open wound. Medical Innovations: Antibiotics The National WWII Museum. Accessed 29 July 2021.
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. 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, making them more likely to remain in a soluble form.
Sulfa drugs were shown to improve life expectancy in the years following their wide adoption. Because sulfa drugs were not effective against tuberculosis (TB), researchers could track the differences in mortality rates between conditions sulfa could treat and those it could not. A study of sulfa drugs—a major medical breakthrough in the 1930s—found they significantly reduced U.S. mortality rates for several infectious diseases. Between 1937 and 1943, sulfa drugs lowered maternal mortality by 25–40%, pneumonia mortality by 17–36%, and scarlet fever mortality by 52–67%. Overall, they reduced mortality by 2–4% and increased life expectancy by 0.4 to 0.8 years.
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.
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%.
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. A key component to the allergic response to sulfonamide antibiotics is the arylamine group at N4, found in sulfamethoxazole, sulfasalazine, sulfadiazine, and the anti-retrovirals amprenavir and fosamprenavir. Other sulfonamide drugs do not contain this arylamine group; available evidence suggests that patients who are allergic to arylamine sulfonamides do not cross-react to sulfonamides that lack the arylamine group, and may therefore safely take non-arylamine sulfonamides. It has therefore been argued that the terms "sulfonamide allergy" or "sulfa allergy" are misleading and should be replaced by a reference to a specific drug (e.g., "cotrimoxazole allergy").
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.
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.
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