Sulfonamides represent synthetic chemical antibiotics that prevent bacteria from multiplying. Today, they are rarely used in humans because of their rather weak mode of action and many side effects. To prevent resistance, combination preparations of sulfonamides with diaminopyrimidines are usually used.
What are sulfonamides?
Sulfonamides represent synthetic chemical antibiotics that prevent bacteria from multiplying. Sulfonamides are used as antibiotics because of their antimicrobial activity. Today, they have been largely displaced by penicillins, which are more effective. Nevertheless, they are still often used for uncomplicated urinary tract diseases. They are still used particularly frequently in veterinary medicine. Sulfonamides have the characteristic atomic group SO2NHR. With the aid of this atomic group, they exert their effect against bacteria. Of the large number of sulfonamides, only a few are still used in humans today. These include the drugs sulfamethoxazole, sulfamerazine, silver sulfadiazine or sulfadiazine. The effectiveness of sulfanilamide against bacteria was discovered by the pathologist Gerhard Domagk in 1935. Sulfanilamide was marketed as an antibiotic under the brand name Prontosil. However, Prontosil was only effective in vivo (in the organism) because it could only be converted into its effective form in the organism. As early as the Second World War, the first sulfonamides were replaced by the more effective penicillins. However, they were not completely displaced and are still used today for certain infections.
Pharmacologic action
The efficacy of sulfonamides is based on interfering with the formation of folic acid. In doing so, they occupy key active sites in the corresponding enzymes that are responsible for folic acid formation. Folic acid, in turn, ensures the synthesis of nucleotides. This reaction takes place in all organisms. The nucleotides are necessary for the construction of nucleic acids. Bacteria, unlike eukaryotic cells, produce folic acid as part of their metabolism. However, eukaryotic organisms, including humans, must absorb folic acid through food. This explains the specific toxic effect of sulfonamides against bacteria. However, there are also bacteria that do not produce folic acid. These bacterial strains are resistant to sulfonamides. However, the sulfonamides alone do not kill the bacteria. However, by inhibiting the formation of nucleic acids, they prevent the formation of new bacteria through cell division. The organism’s immune system now destroys the existing bacteria. This shortens the duration of infection.
Medical application and use
Sulfonamides are effective against various strains of bacteria, such as the intestinal bacteria Pseudomonas, Escherichia coli, Shigella or Salmonella. Furthermore, they show efficacy against streptococci, staphylococci, Pneumocystis jirovecii, Neisseria, Toxoplasma gondii, Plasmodia or Neospora caninum. The drug cotrimoxazole is used to treat uncomplicated urinary tract infections. Cotrimoxazole represents a combination of sulfamethoxazole with trimethoprim. The drug is used as a combination drug to prevent resistance to sulfonamides. Both the sulfonamides and trimethoprim block the formation of folic acid. However, they intervene in the same metabolic pathway at different sites. The combination of the two agents also produces a synergistic bacteriocidal effect, which means that the bacteria are actually killed. However, sulfamethoxazole is used alone to treat Pneumocystis jirovecii. Furthermore, it is used for other respiratory infections and gastrointestinal infections. Silver sulfadiazine is used for antibiotic treatment of wounds and burns. It is applied on the spot. Sulfadiazine, in turn, is given orally for plasmodia, Toxoplasma gondii, or Pneumocystis jiroveci. The drug sulfamerazine is used for respiratory diseases, diseases of the ear, nose and throat, and urinary tract infections. Sulfamerazine is also used here mostly in combination with trimethoprim. It is applied in the form of tablets or by infusion. While sulfonamides are only rarely used in humans, they are considered common antibiotics in veterinary medicine. There they are widely used against gastrointestinal infections, respiratory tract infections and urinary tract infections.In poultry, they have long been used to control coccidia.
Risks and side effects
Sulfonamides, as mentioned earlier, are rarely used in humans today. One reason, in addition to the greater efficacy of penicillins, is the occurrence of side effects. Their use may cause skin rashes, nausea, vomiting, loss of appetite, diarrhea, depression, or even psychosis. During pregnancy, the use of sulfonamides is dangerous. The bilirubin breakdown of the fetus is disturbed, so that a dangerous hyperbilirubinemia can occur in the newborn. Sulfonamides often produce an allergy on the skin. In combination with sunlight, a phototoxic reaction can be triggered. The skin reacts with itching, redness, scaling and dehydration. Furthermore, blood count changes may occur. In the case of hereditary methemoglobinemia, severe hemolytic crises can be triggered under certain circumstances. A side effect is also the lowering of the aqueous humor pressure in the eye. Therefore, today the treatment of glaucoma is often done with eye drops containing modified sulfonamides. Sulfonamides must not be administered together with some medications because of undesirable interactions. For example, when sulfonamides are used at the same time as local anesthetics such as procaine or tetracaine, their effect is reversed. Adverse interactions also occur with urotropin, which is used as a food preservative. Adverse interactions also take place with phenylbutazone, an antirheumatic drug. Simultaneous use of sulfonamides with cyclosporine A threatens kidney damage. Clear contraindications exist in cases of intolerance to sulfonamides, renal disease and the so-called long-QT syndrome. Long-QT syndrome is a heart disease caused by ion channel disturbances. It is characterized by cardiac arrhythmias that can lead to ventricular fibrillation. Antibiotics such as sulfonamides can cause or exacerbate the condition.
