Amide alcohol

The amide alcohol (chloramphenicol) antibiotics mainly include chloramphenicol and thiamphenicol. At present, some countries are studying their fluorine-containing compounds in order to obtain drugs with strong membrane permeability, low toxicity and more effective microorganisms. Chloramphenicol is obtained from the culture solution of Streptomyces veneris, and is now produced in large quantities by chemical synthesis. This product is a left-handed body. Chloramphenicol antibiotics can act on the 50S subunit of bacterial ribonucleoprotein, and block the synthesis of proteins, which is a broad-spectrum antibiotic. The 70S ribosomes of bacterial cells are the major cellular components of synthetic proteins, including the 50S and 30S subunits. Chlorpyrifos binds reversibly to the 50S subunit, blocks the action of transpeptidylase, interferes with the amino acid-containing aminoacyl-tRNA terminal and binds to the 50S subunit, thereby hindering the formation of new peptide chains and inhibiting protein synthesis. . Because chloramphenicol can also bind to 70S of human mitochondria, it can also inhibit the protein synthesis of human mitochondria and cause toxicity to human body. Because the binding of chloramphenicol to 70S ribosomes is reversible, it is considered to be a bacteriostatic antibiotic, but it can also sterilize certain bacteria at high drug concentrations, even at lower concentrations of influenza bacilli. Produces a bactericidal effect. [Clinical application] Because chloramphenicol can cause serious toxic and side effects, it is only used for typhoid infection caused by sensitive typhoid strains, influenza bacillus infection, Bacteroides fragilis infection, brain abscess, Streptococcus pneumoniae or meningococcal meninges. Patients who are allergic to penicillin at the same time. Avoid excessive treatment when applied, and patients with a history of hematologic abnormalities should be banned. All patients treated with chloramphenicol must check for white blood cells, reticulocytes, and platelets at the start of treatment and review every 3 to 4 days. If leukopenia occurs, stop the drug immediately. The use of chloramphenicol in infants and young children should be very cautious, unless there is no alternative to other drugs and must be considered when used. Blood concentration monitoring can be performed when conditions permit. Thiamphenicol and chloramphenicol are the same class of antibiotics, only the nitro group on the chloramphenicol benzene ring is replaced by a monosulfone group, and its antibacterial spectrum is similar to that of chloramphenicol. Thiamphenicol is mainly excreted from the kidneys, and the active concentration in urine is higher than that of chloramphenicol, so the dose needs to be reduced when the kidney is dysfunctional. Although there are also hematological toxicity, they are all reversible and do not show aplastic anemia. Some countries believe that their efficacy is better than chloramphenicol, but China believes that the effect is not better than chloramphenicol. [Pharmacological properties] It is a broad-spectrum antibacterial agent. Through fat-soluble, it can diffuse into the bacterial cells, mainly acting on the 50s subunit of the 70s ribosome of the bacteria, inhibiting the transpeptidase, hindering the growth of the peptide chain, inhibiting the formation of the peptide chain, thereby preventing the synthesis of the protein. Bacteria that are highly sensitive at high concentrations or that are highly sensitive to this product are also bactericidal. Chloramphenicol generally acts better against Gram-negative bacteria than Gram-positive bacteria. Sensitive bacteria include Enterobacteriaceae (such as Escherichia coli, Enterobacter aerogenes, Klebsiella, Salmonella, etc.) and Bacillus anthracis, pneumococcus, Streptococcus, Listeria, Staphylococcus, and the like. Chlamydia, Leptospira, and Rickettsia are also sensitive to this product. This product also has a considerable effect on anaerobic bacteria such as Clostridium tetani, Clostridium perfringens, Actinomycetes, Lactobacillus, and Fusobacterium. However, it is not effective against Pseudomonas aeruginosa, Mycobacterium tuberculosis, viruses, and fungi. Bacteria have a slow-developing resistance to chloramphenicol, mainly producing acetyltransferase. Obtained by plasmid delivery. Some strains of certain bacteria (Pseudomonas aeruginosa, Proteus, Klebsiella, etc.) have also changed the permeability of bacterial cell wall, making chloramphenicol unable to enter the cell body and resistant. [Drug resistance] Escherichia coli, dysentery bacillus, and proteus are more common, and typhoid bacillus and staphylococci are rare. Bacterial resistance to chloramphenicol is relatively slow, probably due to the gradual mutation of the gene, but can disappear automatically. Bacteria can also acquire drug resistance through the transfer of R factor, and bacteria that obtain R factor can produce chloramphenicol acetyltransferase to inactivate chloramphenicol. [Pharmacokinetics] This class of drugs is easy to absorb orally, and reaches a peak blood concentration in about 2 hours. It is widely distributed in the body and has a high concentration in the internal organs. It can penetrate into the milk and fetal circulation, and can enter the cerebrospinal fluid through the blood-brain barrier. It can also infiltrate into ascites and pleural effusion. [Contraindications] Newborns can cause gray infant syndrome, so it is banned. Mental patients can cause serious reactions, so they are banned. [Adverse reactions] (1) Bone marrow hematopoietic disorders may have blood cell reduction, severe cases of aplastic anemia, a small number of hemolytic anemia, iron granule anemia. (2) The nervous system shows enhanced central nervous system excitability, mild insomnia, suspicious, melancholy, severe illusion, mania, paralysis, ataxia. There can also be mental disorders. Peripheral neuropathy is more common in the posterior optic nerve and auditory nerve, which can cause vision and hearing impairment. (3) Allergic reactions are mainly drug eruption, exfoliative dermatitis, and drug heat. (4) Digestive system symptoms are nausea, poor appetite, vomiting. Liver damage has jaundice and abnormal liver function. 【Notes】 It includes chloramphenicol, thiamphenicol and odorless chloramphenicol. Chloramphenicol is a broad-spectrum antibiotic that has been used less because it is more toxic to the blood system. External use of its eye drops to prevent eye infections. Note: 1 The main adverse reactions are granulocyte and thrombocytopenia, aplastic anemia and so on. 2 long-term use can cause optic neuritis, ataxia and double infection. 3 Sometimes there is a digestive tract reaction. 4 Newborns can cause gray infant syndrome, so it is banned. 5 mental patients can cause serious reactions, so it is banned. 6 intramuscular injection is likely to cause serious reactions. Thiomycin has an antibacterial spectrum similar to that of chloramphenicol and does not cause aplastic anemia. However, the dose needs to be reduced when the kidney is dysfunctional. Children can take odorless chloramphenicol. [Drug interaction] Compatibility Note: This product injection, in case of strong alkaline and strong acidic solution, is easily destroyed and failed. (1) The antibacterial mechanism of macrolides and lincomycin antibiotics is similar to that of chloramphenicol, which can replace or prevent the combination of chloramphenicol and the 50s subunit of bacterial ribosomes. Antagonistic and not suitable for joint application. (2) Chloramphenicol is a bacteriostatic agent that inhibits the synthesis of bacterial proteins, and has an interference effect on the bactericidal effect of penicillin fungicides. Two classes of drugs should be avoided. (3) Chloramphenicol can antagonize vitamin B6, so that the body's need for B6 is increased, and it can also antagonize the hematopoietic effect of vitamin B12. (4) Chloramphenicol has an inhibitory effect on the drug-metabolizing enzymes of liver microsomes, and can affect the efficacy of other drugs, such as significantly prolonging the anesthesia time of pentobarbital sodium in animals. (5) This product is equivalent to certain bone marrow-inhibiting drugs such as colchicine, phenylbutazone and penicillamine, which can increase toxicity.