Fluoroquinolones are a subgroup of the so-called quinolones. They are used in medicine as antibiotics. At the same time, they belong to the gyrase inhibitors and differ from other substances of this type by their wide spectrum of activity. Modern fluoroquinolones are effective against pathogen enzymes, such as topoisomerase IV, among others.
What are fluoroquinolones?
Fluoroquinolones are used particularly for bacterial infections. Fluoroquinolones are used in human and veterinary medicine. From a chemical point of view, fluoroquinolones have a fluorinated backbone. In addition, they possess a so-called piperazine substituent. Originally, fluoroquinolones were referred to as gyrase inhibitors. However, this term is hardly ever used today. The classification into different groups was made in 1998 and was inspired by recommendations of the PEG. The classification and allocation to different groups is based on various criteria. These include pharmacokinetics, the clinical area of application and the antibacterial spectrum. In the meantime, numerous drugs are no longer available on the market. Instead, new active ingredients have been approved and certain indications expanded. Currently, only the drugs enoxacin, norfloxacin, ciprofloxacin, ofloxacin, moxifloxacin and levofloxacin are available from the fluoroquinolone group. Pipemidic acid is a special quinolone that is not fluorinated. In modern times, however, this substance is no longer of any significance, which is why it is not taken into account. As a result, according to the classification of PEGs in the individual groups I, III and IV, only one active substance remains. For this reason, an indication-related group assignment is advocated from a clinical point of view. However, it should be noted that the individual agents for different indications also differ with regard to their dosage.
Pharmacologic effect
Fluoroquinolones have a bactericidal effect, but this is highly concentration-dependent. Through an interaction with a gyrase and topoisomerase specialized for DNA, various processes in the division and repair of DNA are impeded. In terms of their respective spectrum of action, fluoroquinolones differ greatly from each other. The enzyme gyrase belongs to bacteria and leads to overcoiling of DNA, which is also known as supercoiling. The fluoroquinolones impair this enzyme in its action. As a result, the mechanical energy stored in the chromosomes of bacteria is reduced. At the same time, the length of the chromosomes increases. The result is that the DNA of the bacteria can no longer be replicated without errors. First, this inhibits the growth of the bacteria, which is called the bacteriostatic effect. Then, the cells of the bacteria die, allowing the bactericidal effect to develop. Newer versions of fluoroquinolones also act against bacterial topoisomerase enzymes. In principle, fluoroquinolones have a relatively broad spectrum of activity against many Gram-positive and Gram-negative pathogens. Only certain anaerobes and various streptococci are resistant. From a medical point of view, almost all bacterial infections are indications for fluoroquinolones. The focus is on infections of the urinary and respiratory tract. They are particularly recommended for urinary tract infections in areas where resistance to certain other antibiotics exists.
Medical application and use
Fluoroquinolones are used for a number of conditions and particularly for bacterial infections. To provide a better overview, fluoroquinolones have been divided into two main indication areas, A and B. These are classified according to the indication and dosage of the respective active ingredients. The subdivision is made as a supplement to the group classification. Indication area A includes all orally available fluoroquinolones. Drugs from this group are mainly used for the treatment of mild urinary tract infections. Indication area B comprises those fluoroquinolones which, in higher doses, are also suitable for the treatment of systemic and severe infections. Fluoroquinolones are generally classified into groups introduced by the Paul Ehrlich Society.The fluoroquinolones are subdivided according to both their efficacy and the possible applications of the antibiotics. Group I includes the oral fluoroquinolones, which are used in the context of urinary tract infections. The systemically applicable fluoroquinolones from group II have a very broad spectrum of activity. Group III includes those fluoroquinolones that have better efficacy against atypical and Gram-positive germs. Group IV includes fluoroquinolones with higher efficacy against atypical and Gram-positive germs and against anaerobes.
Risks and side effects
Therapy with fluoroquinolones can result in side effects, which occur on average in approximately four to ten percent of patients. The most common are gastrointestinal complaints, for example diarrhea and nausea, and central nervous effects. Less frequently, behavioral disturbances with increased suicidality are also possible. Tendon ruptures and tendonitis sometimes occur. If corticoids are taken at the same time, the likelihood of tendon ruptures has been observed to increase. For this reason, patients with a history of tendon disorders should refrain from therapy with fluoroquinolones. In addition, fluoroquinolones have a phototoxic potential, which is why contact with sunlight or UV light in general should be avoided. Fluoroquinolones from groups III and IV sometimes prolong the so-called QT interval in the ECG. This increases the likelihood of ventricular arrhythmias occurring. Liver toxic effects from fluoroquinolones have also been observed.
