Quinolone

The development of quinolone synthetic antibacterials has gone through three generations. A typical representative of the first generation of quinolones is Nalidixic acid, which was developed in 1962. It is effective against Gram-negative bacteria such as Escherichia coli, but is ineffective against Pseudomonas aeruginosa and Gram-positive bacteria. It is eliminated due to low utilization and resistance. Typical representatives of the second generation of quinolones are Oxolinic acid and Pipemidic acid, which were developed in the late 1970s. In 1979, the use of pipemidic acid in the treatment of Gram-negative bacteria in China was better, and the therapeutic effect on Pseudomonas aeruginosa infection was better than that of nalidixic acid and carbenicillin, but not as good as gentamicin. The disadvantage is that the effect on Gram-positive bacteria is poor, the blood concentration is low, and there is a certain toxic effect of the central nervous system. In the late 1970s, the development of cephalosporins reached its peak, and its price was unbearable for the general patients. The development of the third-generation quinolone-fluoroquinolone synthetic antibacterial drug gave the world a "sufficient road to the mountains and waters. Sense. A fluoroquinolone antibacterial agent refers to a class of quinolone antibacterial agents in which a fluorine atom is substituted at the 6th position of the synthesized quinazoline ring. They are not only 4 to 64 times stronger than the first and second generation quinolones in combating Gram-negative bacteria, but also 8 to 64 times stronger than the first and second-generation quinolones against Gram-positive bacteria. They are well absorbed orally, and have little resistance. Because they are chemical synthetic products, they are relatively cheaper than antibiotics (especially the third-generation cephalosporins). The DNA of bacterial cells is in the form of a double-stranded helix, and the formation of its double helix depends on the DNA helicase. The mechanism of action of quinolones is to inhibit DNA helicase, causing chromosomal damage, so that cells no longer divide and multiply. Because of its unique mechanism of action, it is not affected by plasmid-transfer resistance, so it has no cross-resistance with many antibacterial drugs. The advantages of fluoroquinolone antibacterials are as follows. 1. Antibacterial spectrum is broad, antibacterial activity is strong, and some are comparable to third-generation cephalosporins (such as ofloxacin, etc.). It also has a role in staphylococcus in Gram-positive bacteria and the more difficult methicillin-resistant Staphylococcus aureus (MRSA); it has been extended to Pseudomonas aeruginosa, Haemophilus influenzae and Neisseria gonorrhoeae producing penicillinase; some new fluoroquinolone antibacterials are also effective against mycoplasma and chlamydia. 2. Oral absorption is good, and the tissue is widely distributed. Generally, the peak time of blood in fluoroquinolone after oral administration is 1 to 2 hours, and the plasma protein binding rate is low, about 10% to 40%, and can be widely distributed in tissues such as liver, kidney, skin and lung after administration. 3. Wide range of treatment, has a certain therapeutic effect on intestinal, urinary tract, biliary tract, respiratory infection, prostatitis, osteomyelitis, etc., widely used in the treatment of various infections. 4. Less drug resistance. After 8 years of use in Germany, ofloxacin still inhibits 96.8% of Gram-negative bacteria and 93.3% of Gram-positive bacteria; ciprofloxacin has 91% of Pseudomonas aeruginosa and 95% of golden yellow in the UK Staphylococcus is sensitive to it; investigations in China have shown that the resistance of fluoroquinolones to Pseudomonas aeruginosa has increased in recent years, from 4.4% to 10%. The characteristics of fluoroquinolone antibacterials are as follows. 1. In terms of antibacterial effect, it is generally less effective against Gram-positive bacteria than Gram-negative bacteria. 2. Adverse reactions include gastrointestinal symptoms, generally no need to stop; central nervous system symptoms, such as anxiety, nervousness, insomnia, headache and other ciprofloxacin are more common; rash may also occur; the incidence of liver and kidney dysfunction is generally It is 0.5% to 1.0%. 3. Long-term magnetic resonance imaging (MRI) and ultrasound studies of puppies have shown that there is a loose matrix in the middle layer of osteoarticular cartilage, but observation of nearly 100 cases has not been seen. For safety reasons, this class of drugs should not be long-term. Give breastfeeding women and children and boys in skeletal development. Because this product inhibits DNA replication, pregnant women should also be used with caution. 4. Individual fluoroquinolones (such as lomefloxacin, enoxacin, and sapafloxacin) have long-term mass-produced elderly farmers, and a few will have phototoxic reactions. Several situations in drug interactions. 1. It can affect the antibacterial effect with milk, cheese and drugs containing calcium, magnesium, iron, aluminum, etc. It is generally recommended to take it on an empty stomach. After taking it, the peak time of the blood drug should be delayed by 1 to 2 hours, but absorbed. The total amount is unchanged; the urine is acidic to facilitate its excretion, and precipitation is likely to occur in alkaline urine. 2. The interaction with the scutellaria drugs such as theophylline can be divided into three types: the same as enoxacin can increase the plasma concentration of theophylline by a factor of two; with ciprofloxacin and tosufloxacin. Can increase the plasma concentration of theophylline by 20%; with lomefloxacin, norfloxacin, no effect on the plasma concentration of theophylline. 3. With the non-steroidal antipyretic analgesic fenbufen, it can promote the combination of fenbufen and γ-aminobutyric acid (GABA) receptor to induce epileptic seizures, so those with a history of epilepsy should be used with caution. 4. Care should also be taken with other antibacterial agents. For example, with vancomycin, the nephrotoxicity is increased; with doxorubicin and furoside, the renal function can be decreased (ciprofloxacin); with chloramphenicol, doxycycline, clindamycin and large The antibiotic effect of the cyclic lactone antibiotics is also reduced, and the adverse reactions of the hematopoietic system and the nervous system are also prone to occur.