Chinolones and fluoroquinolones

The group of antibacterial medications called quinolones are used in clinical practice since early 1960 years. Action mechanism of this category of medicines is fundamentally different from other antibacterial preparations, which ensures their high activity against microorganisms resistant other antibiotics such beta-lactams, macrolides and others.
Quinolone class includes two main groups of drugs, principally differing in structure, activity, pharmacokinetics and indications: non-fluorinated Quinolones and fluoroquinolones. According to the classification proposed by R. Quintiliani (1999), Quinolone are divided into four generations:

First-generation

  • cinoxacin (removed from clinical use)
  • flumequine (veterinary use)
  • nalidixic acid (genotoxic carcinogen)
  • oxolinic acid
  • piromidic acid
  • pipemidic acid
  • rosoxacin

Second-generation
The second-generation class is sometimes subdivided into "Class 1" and "Class 2".

  • ciprofloxacin
  • enoxacin
  • fleroxacin
  • lomefloxacin
  • nadifloxacin
  • norfloxacin
  • ofloxacin
  • pefloxacin
  • rufloxacin

Third-generation
Unlike the first-and second-generations, the third-generation is active against streptococci.

  • balofloxacin
  • gatifloxacin
  • grepafloxacin
  • levofloxacin
  • moxifloxacin
  • pazufloxacin
  • sparfloxacin
  • temafloxacin
  • tosufloxacin

Fourth-generation

  • clinafloxacin
  • gemifloxacin
  • sitafloxacin
  • trovafloxacin
  • prulifloxacin

In development

  • garenoxacin
  • delafloxacin

Action mechanism:
Quinolones and fluoroquinolones exert bactericidal effect. Action mechanism is associated with acting on two enzymes topoisomerase II (DNA-gyrase) and topoisomerase IV. Suppression of topoisomerase functions leads to irreversible changes in microorganism and its death. Fluoroquinolones inhibit DNA synthesis in microbial cell without affection DNA in cells of macroorganism.

Spectrum of activity
Non-fluorinated Quinolones act on gram-negative bacteria Enterobacteriaceae ((E.coli, Enterobacter spp., Proteus spp., Klebsiella spp., Shigella spp., Salmonella spp.) as well as Haemophillus spp. and Neisseria spp
Fluoroquinolones possess a broad spectrum of antibacterial activity. They are active against many gram-positive aerobic bacteria (Staphylococcus spp.), majority of gram-negative strains including .coli, Shigella spp., Salmonella spp., Enterobacter spp., Klebsiella spp., Proteus spp., Serratia spp., Providencia spp., Citrobacter spp., M.morganii, Vibrio spp., Haemophilus spp., Neisseria spp., Pasteurella spp., Pseudomonas spp., Legionella spp., Brucella spp., Listeria spp.

In addition, fluoroquinolone tend to be active against bacteria resistant to quinolones I generation. Fluoroquinolones III and, especially, IV generation are highly active against pneumococci. They are more active than preparations of II generation against intracellular pathogens (Chlamydia spp., Mycoplasma spp., M.tuberculosis, fast-growing atypical mycobacteria (M.avium, etc.) and anaerobic bacteria (moxifloxacin). The activity against Gram-negative bacteria is not reduced. III and IV generation quinolones are active against several bacteria that are resistant to fluoroquinolones II generation. Due to their high effectiveness in the treatment of of lower and upper respiratory tract infections, they are sometimes called "respiratory" fluoroquinolone.
Many enterococci, Corynebacterium spp., Campylobacter spp., H.pylori, U.urealyticum are resistant to fluoroquinolones.

Indications
I generation Quinolone antibiotics

  • Urinary tract Infections: acute cystitis, preventive therapy of chronic infections. They are not used in acute pyelonephritis.
  • Enteric infections: shigellosis, bacterial enterocolitis (nalidixic acid).

Fluoroquinolones

  • Upper respiratory tract infections : sinusitis, particularly those caused by multiresistant strains of malignant external otitis.
  • Infections: exacerbation of chronic bronchitis, community-acquired and nosocomial pneumonia, legionellosis.
  • Enteric infections: shigellosis, typhoid fever, generalized salmonellosis, yersiniosis, cholera.
  • Anthrax.
  • Intra-abdominal infections.
  • Pelvic infections.
  • Infections of the urogenital system (cystitis, pyelonephritis).
  • Prostatitis.
  • Gonorrhea.
  • Infections of skin, soft tissues, bones and joints.
  • Eye infections
  • Meningitis caused by gram-negative microflora (ciprofloxacin).
  • Sepsis.
  • Bacterial infections in patients with cystic fibrosis.
  • Neutropenic fever.
  • Tuberculosis (ciprofloxacin, ofloxacin and lomefloxacin in combination therapy with drug-resistant tuberculosis).

Norfloxacin is used only in intestinal infections, infections of the urinary tract and prostate.

Contraindications

  • Reactions of hypersensitivity or individual intolerance to any Fluoroquinolones
  • Deficiency of G6PD
  • Epilepsy
  • Decrease of convulsive threshold (associated with cerebral trauma, stroke, inflammatory processes in CNS)
  • Patients under 18 years of age
  • Pregnancy
  • Breastfeeding

Fluoroquinolones should be used with caution in: atherosclerosis of cerebral blood vessels, disorders of cerebrovascular circulations, chronic renal failure, organic damage of central nervous system.

Quinolones and fluoroquinolones side effects

  • Gastrointestinal tract: heartburn, pain in the epigastric region, appetite disorders, nausea, vomiting, diarrhea.
  • CNS: ototoxicity, drowsiness, insomnia, headache, dizziness, visual disturbances, paresthesia, tremors, convulsions.
  • Allergic reactions: rash, itching, angioedema, photosensitivity (the most typical lomefloxacin and sparfloxacin).
  • Hematologic reactions: thrombocytopenia, leukopenia, in patients with deficiency of glucose-6-phosphate dehydrogenase - hemolytic anemia.
  • Hepatobiliary system: cholestatic jaundice, hepatitis. Musculoskeletal system: arthropathy, arthralgia, myalgia, tendonitis, abscess, rupture of tendons.
  • Kidneys: crystalluria, transient nephritis.
  • Cardiovascular diseases: lengthening the QT interval on the electrocardiogram.
  • Other: most often - candidiasis of the oral mucosa and / or vaginal candidiasis, pseudomembranous colitis.

Drugs interactions
Simultaneously application of fluoroquinolones with antacids and other medications containing magnesium ions, zinc, iron, bismuth, may decrease the bioavailability of quinolones due to the formation of chelate unabsorbed complexes.

Pipemidinic acid, ciprofloxacin, norfloxacin and pefloxacin can slow the elimination of methylxanthines (theophylline, caffeine) and increase the risk of toxic effects.

The risk of neurotoxic effects of quinolones is increased in combination with NSAIDs, derivatives of nitroimidazole and methylxanthine.

Quinolone can show antagonism with nitrofurans derivatives, that is why the combination of these two groups of medicines is not recommended.

Quinolone I generation, ciprofloxacin and norfloxacin may interfere with the metabolism of indirect anticoagulants in the liver, which leads to an increase of prothrombin time and the risk of bleeding.

Fluoroquinolones should be used with caution with drugs that prolong QT because of high risk of cardiac arrhythmias.

In simultaneous use with glucocorticoids, fluorquinolones increase the risk of tendon rupture, especially in elderly patients.

If you are using ciprofloxacin, norfloxacin and pefloxacin in conjunction with drugs that alkalify urine (carbonic anhydrase inhibitors, citrate, sodium bicarbonate), there is an increased risk of crystalluria and nephrotoxic effects.

Simultaneous application of fluorquinolones with azlocillin and cimetidine may result in decrease of fluoroquinolones excretion and increase of their blood levels.

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