Sulfonamides are synthetic drugs with antibacterial activity. They were the first substances of this type introduced into medicine. Currently, they are prescribed by doctors less and less because of the frequent allergic reactions associated with them. However, multi-component preparations containing these chemical compounds in their composition are still popular. What is worth knowing about sulfonamides?
Contents:
- Sulfonamides - mechanism of action
- Sulfonamides - history of discovery
- Sulfonamides currently used in medicine
- Sulfonamides - side effects
- Cotrimoxazole - a combination of trimethoprim with sulfamethoxazole
- Cotrimoxazole - advantages of using
- Kotrimoxazole - contraindications to use
Sulfonamidesis a group that includes all therapeutic substances that contain a sulfamide group in their structure. Conventionally, this name is used to denote a set of antimicrobials of this particular chemical nature. There are also anticonvulsants and diuretics (thiazides), which are classified as sulfonamides in terms of the structure of the compound.
Despite their antibacterial activity, sulfonamides are typically not referred to as antibiotics. This name has traditionally been reserved for groups of substances whose chemical structure is derived from compounds produced by microorganisms. For this reason, sulfonamides, being fully synthetic drugs, are classified aschemotherapy .
Antibacterial substances from this group are used less and less in medicine. It is associated with the prevalence of sulfa allergy.
Their use is also associated with quite common side effects. For this reason, drugs of this type are prescribed with caution by doctors. Sulfonamides do have some advantages, however.
Their low price is particularly important. It makes preparations of this type still popular antimicrobial drugs in developing countries.
Sulfonamides - mechanism of action
The action of sulfonamides is based on the fact that they selectively disrupt metabolic processes in bacterial cells, while not harming humans. These drugs are enzyme inhibitorsDHPS, which is needed for the synthesis of folic acid. As a result, its production is blocked.
Human cells do not have the ability to synthesize folic acid. In our body, it plays the role of a vitamin, i.e. a compound that we must provide with food. Bacteria, on the other hand, produce it themselves. For this reason, blocking the enzyme needed for the synthesis of folic acid is detrimental to microorganisms with high safety in relation to the cells of our body.
Folic acid is a substance that is essential in the process of DNA replication. When it is deficient, cells cannot divide. By blocking its synthesis, sulfonamides also inhibit the multiplication of bacteria. This action is referred to as bacteriostatic. These drugs do not have the ability to kill microorganisms.
Sulfonamides - history of discovery
Sulfa drugs were the first antibacterial substances discovered. They were introduced to the medical field on a large scale and paved the way for the antibiotic revolution in medicine. The first sulfonamide was introduced into medicine under the trade name Prontosil.
The experiments leading to the launch of the first sulfa drug began in 1932 in Bayer laboratories. The research team assumed that tar dyes, which have the ability to bind to bacteria, could be used to combat them in the human body.
After years of fruitless trial and error over hundreds of substances, Gerhard Domagka and his colleagues confirmed the activity of a certain red dye. The compound had the ability to inhibit some bacterial infections in mice.
Prontosil, as the substance was named, was the first drug discovered capable of treating a range of bacterial infections in the body. It was effective, inter alia, against streptococci. Researchers did not associate its activity with the presence of a sulfamide structure.
Interestingly, the compound itself had no effect against bacteria on laboratory glassware. The antimicrobial effect was only visible in the organisms of living animals and humans. This perplexed the scientists because there was no rational explanation for these results.
In later years, a research team led by Ernest Fourneau of the Pasteur Institute discovered that the dye introduced into the treatment was a prodrug. This means that this substance undergoes metabolic changes in our body, leading to the formation of a real active drug.
Prontosil in the organisms of animals released from its structure a tiny colorless molecule with the structuresulfonamide. It was she who had the ability to inhibit the multiplication of bacteria.
Sulfa drugs played an important role in the first years of World War II. They saved the lives of tens of thousands of patients. American soldiers were issued a first aid kit containing a powdered chemotherapeutic agent, instructed to sprinkle each open wound.
It is believed that the sulfonamides were responsible for the further life of Winston Churchill and the son of President Franklin Roosevelt.
Sulfonamides currently used in medicine
Due to numerous side effects of this group of drugs, few compounds of sulphonamide nature are currently used in medicine. We can list the following drugs:
- salazopyrin used in ulcerative colitis
- co-trimoxazole - a preparation containing sulfomethoxazole and trimethoprim, which is a substance with a different nature of action
- silver sulfadiazine, used as an ointment to treat infected burn wounds
Sulfonamides - side effects
With sulfonamides, side effects occur in approximately 3% of the general patient population. This is a very high percentage. For some groups of patients, the inconvenience of using these drugs is much more frequent.
For people with HIV, the incidence of adverse reactions following administration of sulfonamides is approximately 60%.
Sulfonamides can cause various adverse reactions, including:
- urinary tract disorders
- hematopoietic disorders related to bone marrow damage
- hypersensitivity reactions
- gastrointestinal complaints such as anorexia, nausea or vomiting
- nephrotoxic effects
- inflammation of the nerves leading to ataxia, hallucinations, depression and psychosis
The use of high doses of sulfonamides may cause a severe allergic reaction. The most serious of these are classified as severe drug-induced cutaneous reactions (SCARs). They include such serious states as
- Stevens-Johnson syndrome
- toxic epidermal necrolysis
These are medical situations that pose a serious threat to the patient's life.
Drug allergy - causes, symptoms and treatment of drug allergies
Permanent drug erythema: causes, symptoms, treatment
Cotrimoxazole - a combination of trimethoprim with sulfamethoxazole
Sulfonamides are drugs that are rarely prescribed by doctors in developed countries. The two-component preparation, cotrimoxazole, still enjoys some popularity due to the effectiveness of thispreparation. Trade names are Bactrim or Biseptol.
The name co-trimoxazole describes the combination of trimethoprim with sulfamethoxazole. Both of these substances are bacteriostatic chemotherapeutics.
Used together, in one preparation, they have a significantly greater therapeutic effect than those given separately. This is because these drugs inhibit other steps in the folic acid synthesis pathway. Thanks to this, they mutually enhance each other's action.
The substance content in the preparation is in the proportion of one (trimethoprim) to five (sulfamethaxazole). Thanks to this concentration of ingredients, after being absorbed into the body, they reach the concentration in the blood and tissues required for the maximum synergistic effect between the two drugs.
Cotrimoxazole is used to treat various types of bacterial infections. Examples of frequent indications are:
- urinary tract infections
- skin infections with methicillin-resistant staphylococcus aureus (MRSA)
- travelers' diarrhea
- respiratory tract infections
- damn
Cotrimoxazole - advantages of using
Cotrimoxazole (Biseptol) can be administered both orally and intravenously.
This preparation is included in the list of essential medicines of the World He alth Organization (WHO). Its advantage is high availability and low price.
Cotrimoxazole is effective against many microorganisms, including: .
- Escherichia coli
- Proteus mirabilis
- Klebsiella pneumoniae
- Enterobacterspp.
- Citrobacterspp.
- Haemophilus influenzae
- Hafniaspp.
- Legionellaspp.
- Pasteurellaspp.
- Providenciaspp.
- Serratiaspp.
- Salmonellaspp.
- Shigellaspp.
- Staphylococcus aureus
- Staphylococcus epidermidis
- Staphylococcus saprophyticus
- Streptococcus pneumoniae
- Vibriospp.
- Yersiniaspp.
Kotrimoxazole - contraindications to use
- hypersensitivity to trimethoprim or sulfonamides
- pregnancy - especially the third trimester
- severe liver failure
- significant damage to the liver parenchyma
- jaundice
- serious hematological disorders
- severe chronic renal failure
The preparation should not be given to newborns during the first 6 weeks of life.
About the author
Sara Janowska, MA in pharmacyPhD student of interdisciplinary studiesdoctoral studies in the field of pharmaceutical and biomedical sciences at the Medical University of Lublin and the Institute of Biotechnology in Białystok. A graduate of pharmaceutical studies at the Medical University of Lublin with a specialization in Plant Medicine. She obtained a master's degree defending a thesis in the field of pharmaceutical botany on the antioxidant properties of extracts obtained from twenty species of mosses. Currently, in his research work, he deals with the synthesis of new anti-cancer substances and the study of their properties on cancer cell lines. For two years she worked as a master of pharmacy in an open pharmacy.
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