by Rachel Boutom, Sneha Kabaria, and Andrea Thomas
Antibiotics have been essential to mankind since the discovery of penicillin, and have since branched out into many classes and thousands of medications. This article will explore the class of antibiotics referred to as “quinolone antibiotics” due to its quinolone nucleus. The quinolone nucleus contains double-ring structure composed of benzene and pyridine rings fused at two adjacent carbon atoms. The benzene ring contains six carbon atoms, while the pyridine ring contains five carbon atoms and a nitrogen atom. There are many variations, four generations, different functions, benefits, and side effects to quinolone antibiotics, and you will learn all about them here.
What is Quinolone?
Quinolone is an antibiotic that works by interfering with DNA replication and bacterial transcription.
The quinolone carries out this function by inhibiting bacterial DNA Gyrase, which is responsible for the negative supercoiling of the DNA, and bacterial Topoisomerase IV, which is an enzyme needed for the separation of strands after replication during cell division. It was first discovered in 1962 as nalidixic acid, which is considered to be the first drug in the quinolone family. From then, there have been four generations of drugs based on their antibacterial spectrum. There is no set standard of classification system to base the drugs on, however there are general properties that differ.
The earlier-generation agents have, in general, more narrow-spectrums than the later ones. In addition, all non-fluorinated drugs in the quinolone class are labeled as first-generation antibiotics. The majority of quinolone antibiotics used today are fluorinated, meaning they have a fluorine atom bonded to the six-carbon ring. These are called fluoroquinolones. Fluoroquinolones are broad-spectrum antibiotics which are effective for both gram negative and gram positive bacteria, and they play an important role in treatment of serious bacterial infections, especially hospital-acquired infections and others in which resistance to older antibacterial classes is suspected.
How is it Synthesized?
All quinolines are synthetic, meaning they do not occur in nature, and thus, must all be synthesized in laboratories. Since the creation of the first quinoline nalidixic acid, over 10,000 analogues and derivative compounds have been developed, and more than 800 million patients have been treated with quinolones. There are many ways of synthesizing this chemical: the Gould-Jacob’s method using esters, hydrolysis, and regiospecific substitution; the Modified Gould-Jacobs method, using Isatoic Anhydride and Sodio-Ethyl Formyl Acetate; and many more.
The newer fluoroquinolone antibiotics also have improved pharmacokinetic parameters compared with the original quinolones. They are rapidly and almost completely absorbed from the gastrointestinal tract. Peak serum concentrations obtained after oral administration are very near those achieved with intravenous administration. Consequently, the oral route is generally preferred in most situations Absorption of orally administered fluoroquinolones is significantly decreased when these agents are coadministered with aluminum, magnesium, calcium, iron or zinc, because of the formation of insoluble drug.
Because the fluoroquinolones have a large volume of distribution, they concentrate in tissues at levels that often exceed serum drug concentrations. Penetration is particularly high in renal, lung, prostate, bronchial, nasal, gall bladder, bile and genital tract tissues. Urine drug concentrations of some fluoroquinolones, such as ciprofloxacin and ofloxacin (Floxin), may be as much as 25 times higher than serum drug concentrations. Consequently, these agents are especially useful in treating urinary tract infections.
Distribution of the fluoroquinolones into respiratory tract tissues and fluids is of particular interest because of the activity of these agents against common respiratory pathogens. Trovafloxacin penetrates noninflamed meninges and may have a future role in the treatment of bacterial meningitis. The long half-lives of the newer fluoroquinolones allow once- or twice-daily dosing.
As with all antibiotic medicines, the potential for the development of antibacterial resistant strains of bacteria is always a threat. This has already been found to be a problem with quinolones. Gram-positive and gram-negative bacteria have been reported to be resistant to quinolones, and there are different mutations that cause this. The resistance appears to be the result of one of three mechanisms: alterations in the quinolone enzymatic targets (DNA gyrase), decreased outer membrane permeability or the development of efflux mechanisms. In addition, cross-resistance between quinolones is to be expected in the future.
One of the largest problems with antibacterial resistance is the degree to which the same medication is used, which leads to the problem of the extent to which the resistant strain is spread and recreated in other places. For a long period of time, the increased potency and effectiveness of the newer generation of fluoroquinolones, as compared to the older quinolones, led to an unregulated increase in their use. As they kept working effectively, their use proportionally increased, with a 40% increase in use in the United States during the 1990s. During this period, the rate of resistance to the two pain fluoroquinolones doubled, specifically in areas such as the intensive care units in hospitals.