Sulfonamide (medicine)

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

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.

[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.

Later, it was discovered by Daniel Bovet,[8] 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.

[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.

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.

[18] 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.

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.