2 English reference sulfanilamide
Sulfonamides
Sulfanilamide drug
Sulfonamides are the first class of chemotherapy drugs that can effectively prevent and treat systemic bacterial infections. Most of them have been replaced by antibiotics and quinolones in clinic, but sulfonamides still occupy a certain position in anti-infective drugs because of their good efficacy, convenient use, stable nature and low price for some infectious diseases (such as meningitis and plague). The combination of sulfanilamide drugs and sulfanilamide synergist trimethoprim can obviously enhance the curative effect and increase the antibacterial range.
3 The structure and classification of sulfonamides are synthetic sulfonamides derivatives. The hydrogen atom (R 1) on the sulfonamide group of sulfanilamide molecule is replaced by heterocyclic ring, so that sulfanilamide drugs which are easily absorbed by oral administration and used for systemic infection are obtained, such as sulfadiazine, sulfaisoxazole, sulfamethoxazole, etc. If the hydrogen atom (R2) is substituted at the para-amino group in the amino phenyl iodide molecule, sulfonamide drugs, such as sulfasalazine, which are difficult to be absorbed orally and used for intestinal infection, can be obtained. In addition, there are sulfadiazine silver and other external sulfonamides.
4 Pharmacological characteristics of sulfonamides ① Broad antibacterial spectrum, good antibacterial activity against Staphylococcus aureus, hemolytic streptococcus, meningococcus, Shigella, Escherichia coli, typhoid Bacillus, aerogenes and Proteus, and effective against a few fungi, chlamydia and protozoa (plasmodium and Toxoplasma gondii are also effective);
② Bacteria have cross resistance to various sulfonamides;
③ Some sulfonamides can be used locally, which is not easy to be absorbed by intestine or easily absorbed by oral administration. The latter is completely absorbed, with high blood concentration and wide tissue distribution.
④ Sulfadiazine (SD) and sulfamethoxazole? Azole (SMZ) has good meningeal permeability and high drug concentration in cerebrospinal fluid.
⑤ It is mainly inactivated by liver metabolism, and its acetylation solubility is low, which is easy to cause hematuria, crystallized urine and renal damage;
⑥ There are many adverse reactions, such as nausea, vomiting, rash, fever, hemolytic anemia, granulocytopenia, liver damage and kidney damage.
5 Mechanism of action of sulfonamides sulfonamides are bacteriostatic drugs, which inhibit the growth and reproduction of bacteria by interfering with folic acid metabolism. Different from human and mammalian cells, bacteria sensitive to sulfonamides can't directly use folic acid in the surrounding environment, but can only use p-aminobenzoic acid (PABA) and dihydropteridine to synthesize dihydrofolate in bacteria under the catalysis of dihydrofolate synthase, and then form tetrahydrofolate under the action of dihydrofolate reductase. The active form of tetrahydrofolate is a carbon unit transporter, which plays an important role in the formation of purine and pyrimidine nucleotides. The structure of sulfonamides is similar to PABA, which can compete with PABA for dihydrofolate synthase and hinder the synthesis of dihydrofolate, thus affecting the generation of nucleic acids and inhibiting the growth and reproduction of bacteria.
6 Characteristics of various sulfonamides 6. 1 Sulfamides used for systemic infection are easily absorbed by oral administration and can be used to treat systemic infection. According to the length of plasma t 1/2, drugs can be divided into three categories: short-acting drugs (< 10 hour), medium-acting drugs (10 ~ 24 hour) and long-acting drugs (>). Short-acting and medium-acting sulfonamides have strong antibacterial ability and high concentration in blood or other body fluids, so they are most commonly used in clinic. Long-acting sulfonamides have weak antibacterial activity, low blood concentration and common allergic reactions, which have been eliminated by many countries.
Sulfamethoxazole (SIZ), also known as sulfamethoxazole/sulfamethoxazole/sulfamethoxazole/Jundeqing, is a short-acting sulfonamide with a plasma t 1/2 of 5-7 hours and a low acetylation rate. The highest concentration in urine can reach 1000 ~ 2000 mg/L, which is suitable for the treatment of urinary tract infection. It is not easy to precipitate crystals in urine. Take medicine four times a day, and digestive tract reactions are more common.
Sulfadiazine (SD) is an intermediate sulfanilamide, which is easily absorbed by oral administration. The plasma concentration reached its peak at 3 ~ 4 hours after administration, and the plasma t 1/2 was 10 ~ 13 hours. Strong antibacterial ability, the lowest plasma protein binding rate is about 25%, and it is easy to penetrate the blood-brain barrier, and the concentration of cerebrospinal fluid can reach 40% ~ 80% of the plasma concentration. It is the first choice for the treatment of epidemic cerebrospinal meningitis and is also suitable for the treatment of urinary tract infection. However, it is easy to precipitate crystals in urine, so attention should be paid to the damage to the kidney.
Sulfamethoxazole (SMZ), also known as sulfamethoxazole, is an intermediate sulfonamide, and the plasma t 1/2 is 10 ~ 12 hours. The antibacterial effect is similar to SIZ. The protein binding rate is high (60% ~ 80%), the concentration of cerebrospinal fluid is lower than SD, and the concentration of urine is lower than SIZ but close to SD, which is also suitable for the treatment of urinary tract infection. In acidic urine, crystals will precipitate and damage the kidneys, so pay attention to alkalizing urine. Sulfamethoxazole (SMD) is a long-acting sulfonamide, and the plasma t 1/2 is 30 ~ 40 hours. Weak antibacterial ability. Can be maintained in the body for a long time, and taken once a day. Low acetylation rate, high solubility in urine and difficult crystallization.
Sulfadoxine (SDM') is also called sulfadoxine; It is a long-acting sulfonamide, and the plasma t 1/2 is 150 ~ 200 hours. Can be maintained in the body for the longest time, and is taken once every 3 to 7 days. Weak antibacterial ability, suitable for mild infection and prevention of streptococcus infection, and also effective for malaria.
6.2 sulfasalazine (sulfasalazine salicylate), a sulfonamide used for intestinal infection, has less oral absorption and special affinity for connective tissue, and releases sulfapyridine from intestinal wall connective tissue, which has antibacterial, anti-inflammatory and immunosuppressive effects. It is suitable for the treatment of nonspecific colitis, and can prevent the attack after long-term administration. Because of the long course of treatment, nausea, vomiting, rash and drug fever are prone to occur.
6.3 Silver sulfadiazine, a sulfanilamide drug for external use, can exert the antibacterial effects of SD and silver nitrate, has a broad antibacterial spectrum, has a strong inhibitory effect on Pseudomonas aeruginosa, has a convergent effect, can promote wound healing, and is suitable for second or third degree burns.
Sulfametron (SML), also known as methanesulfonamide, is a sulfanilamide drug, so its antibacterial effect is not affected by pus and necrotic tissue. It is effective for Pseudomonas aeruginosa, Staphylococcus aureus and tetanus. It can quickly penetrate into wound and eschar, promote the growth and healing of wound epithelium, and improve the survival rate of skin grafting. It is suitable for burns and large-area post-traumatic infection.
Sulfadiazine (SA) is almost neutral in its sodium salt solution (15% ~ 30%), and there is almost no * * * when it is applied locally, so it has strong permeability. Can be used for treating trachoma, conjunctivitis and keratitis.
7 Principles of use of sulfonamides In daily life, many diseases are caused by infection with pathogenic bacteria. Sulfonamides play a very important role in clinical treatment because of their broad antibacterial spectrum, convenient use, stable properties and low price.
However, there are still many adverse reactions of these drugs. It may lead to allergic reaction, causing patients to have drug fever and rash, and in severe cases, erythema multiforme and exfoliative dermatitis may occur. It may also cause bone marrow suppression: thrombocytopenia and leukopenia, leading to hemoglobinuria, hemolytic anemia and aplastic anemia, which can be fatal in severe cases; In addition, it may also cause liver and kidney damage; And symptoms of digestive tract discomfort, such as nausea and vomiting. A few patients will have dizziness, headache, fatigue, listlessness, insomnia and other mental symptoms after taking the medicine. Therefore, it is suggested that the following seven principles should be paid attention to when applying sulfonamides:
1, we must strictly control the indications and contraindications of drug use, and should ban the use of sulfanilamide allergy and megaloblastic anemia. Pregnant women and lactating women should avoid using it. Babies younger than 2 months are also absolutely forbidden. Elderly patients should avoid using it. If there are indications, the advantages and disadvantages must be weighed before using it.
2. The first dose of sulfanilamide should be doubled to achieve the purpose of rapid bacteriostasis, and then the maintenance dose (that is, the normal dose) should be used, and the minimum dose should be used 2-3 times after the symptoms disappear. In order to maintain the efficacy for a long time and prevent bacteria from rebounding. Remember not to arbitrarily increase the dosage, increase the frequency of medication or extend the course of treatment during medication to prevent drug accumulation poisoning;
3. During the medication, the patient's blood picture and urine picture should also be closely monitored; Check liver and kidney function regularly; When necessary, the patient's blood drug concentration can be determined to avoid adverse drug reactions. And tell patients to drink more water, keep high urine flow, take sulfonamides for more than a week to reduce the possibility of crystallized urine, and if necessary, take sodium bicarbonate to alkalize urine;
4, sulfonamides can inhibit the synthesis of B vitamins in the intestine, so those who use sulfonamides for more than a week should be given vitamin B at the same time to prevent its deficiency;
5. Because sulfonamides can cause a few patients to have mental symptoms such as dizziness, headache, fatigue, discomfort and insomnia, they should not be engaged in aerial work and driving during the medication;
6. Sulfanilamide has a good effect on streptococcus and other bacteria, but it is powerless against other bacteria. Moreover, some bacteria that can be subdued will soon develop drug resistance after a period of time. Once drug resistance occurs, all sulfonamides will fail, and other antibacterial drugs need to be replaced quickly;