Fluoroquinolones

In the 1960s, high antimicrobial activity of nalidixic acid was detected. Then oxolinic acid was synthesized, with the same spectrum of action, but more active (2–4 times in vitro ). In continuation of these studies, a number of 4-quinolone derivatives were synthesized, among which compounds containing a fluorine atom (position red) in position 6 and a piperazine ring, with or without additional substitutions, were found to be especially active in position 6 (marked in blue). them. These compounds were called fluoroquinolones ; they can also be called second generation quinolones .

1. By the number of fluorine atoms in the molecule: monofluoroquinolones, difluoroquinolones and trifluoroquinolones;
2. Generational classification - includes quinolones with and without fluorine atom (first generation): ^{[1] [2]}

• First generation: nalidixic acid , oxolinic acid , pipemidic acid (do not contain a fluorine atom, do not apply to fluoroquinolones in the strict sense).
• Second generation: ciprofloxacin , norfloxacin , ofloxacin , pefloxacin , lomefloxacin .
• Third generation: sparfloxacin , levofloxacin .
• Fourth generation: moxifloxacin , gemifloxacin , gatifloxacin , sitafloxacin , trovafloxacin , delafloxacin .

Of the preparations of the fluoroquinolone group, lomefloxacin , ofloxacin , ciprofloxacin , levofloxacin , sparfloxacin and moxifloxacin are included in the List of Essential and Essential Medicines .

By inhibiting two vital microbial cell enzymes - DNA gyrase and topoisomerase-4 , fluoroquinolones disrupt DNA synthesis, which leads to the death of bacteria (bactericidal effect) ^{[3] [4]} . In addition, antibacterial activity is due to the effect on bacteria RNA , on the stability of their membranes, and the effect on other vital processes of bacterial cells ^[4] .

Compared with nalidixic and oxolinic acid, fluoroquinolones have a wider spectrum of action. First-generation drugs are active against most gram-negative bacteria : Pseudomonas aeruginosa , Haemophilus influenzae and Escherichia coli , Vibrio cholerae , Shigella , Salmonella , Meningococcus , Gonococcus ) They are also active against campylobacter , Legionella , Mycoplasmas and Chlamydia , and some gram-positive bacteria : pneumococci and many strains of staphylococci . They do not act on anaerobic bacteria.

Many fluoroquinolones ( ofloxacin ^[5] , ciprofloxacin and later ^[6] ) are effective against mycobacterium tuberculosis .

The high bactericidal activity of fluoroquinolones made it possible to develop for many of them topical dosage forms in the form of eye and ear drops .

Fluoroquinolones are rapidly and well absorbed in the digestive tract . The maximum concentration in the blood is achieved on average 1-3 hours after ingestion . They bind little to blood plasma proteins and relatively easily penetrate into all organs and tissues, creating high concentrations in them ^[3] ; penetrate into the cells of the body, affecting intracellular bacteria ( chlamydia , mycobacteria , etc.) ^[4]

Food can slow the absorption of quinolones , but does not have a significant effect on bioavailability . Fluoroquinolones pass the hematoplacental barrier , and also penetrate into breast milk in small amounts, so they are not prescribed for pregnant and lactating women. They are excreted from the body by the kidneys, mainly unchanged, and create high concentrations in the urine . ^[four]

With impaired renal function, the excretion of quinolones is significantly slowed down.

• From the gastrointestinal tract - heartburn , pain in the epigastric region , impaired appetite , nausea, vomiting, diarrhea .
• From the side of the central nervous system - ototoxicity (negative impact on the hearing and the functioning of the vestibular apparatus), drowsiness, insomnia, headache, dizziness, visual impairment, paresthesia , tremors , convulsions.
• On the part of the immune system - transient (temporary, rapidly passing) immunodeficiency .
• Allergic reactions - rash, itching, angioedema ; photosensitization (most common for lomefloxacin and sparfloxacin ).

Rare and very rare

• From the musculoskeletal system - arthropathy , arthralgia , myalgia , tendonitis , tendovaginitis , tendon rupture.
• From the side of the kidneys - crystalluria , transient nephritis .
• From the side of the heart - lengthening of the QT interval on the electrocardiogram , in very rare cases: tachycardia , rapidly appearing and quickly passing pains in the heart region, arterial thrombosis of the extremities (in general, it passes or is treated with a routine ).
• Others - candidiasis of the oral mucosa and / or vaginal candidiasis, pseudomembranous colitis .

Severe cerebral atherosclerosis , glucose-6-phosphate dehydrogenase deficiency , an allergic reaction to fluoroquinolone drugs. Pregnancy, breast-feeding , childhood.

Fluoroquinolones have long been considered fairly safe drugs, but in 2016 the FDA warned of their serious side effects, calling for the maximum restriction of their use. ^{[7] [8]}

• Mashkovsky M. D. Medicines. - 15th ed. - M .: New Wave, 2005 .-- S. 842-850. - 1200 s. - ISBN 5-7864-0203-7 .
• Padeiskaya E.N., Yakovlev S.V. Antimicrobial agents of the fluoroquinolone group in clinical practice. - M. , 1998.
• Yakovlev S.V. A new generation of fluoroquinolones - new possibilities for treating community-acquired infections of the respiratory tract // Antibiotics and chemotherapy. - 2001. - No. 6 . - S. 38-42 .

• Quinolones and the Clinical Laboratory // CDC, Healthcare-associated Infections