Quinolones 1. Older (Earlier) quinolones include: Nalidixic acid, oxalinic acid and cinoxacin. 2. Fluorinated derivatives (Fluoroquinolones) include : Ciprofloxacin, norfloxacin, levofloxacin and moxifloxacin.
1St generation: cinoxacin, nalidixic acid, oxolinic acid 2nd generation: Ciprofloxacin,, norfloxacin, ofloxacin, 3rd generation: gemifloxacin, grepafloxacin,levofloxacin , sparfloxacin, moxifloxacin 4th generation: trovafloxacin
Generation
Drug NamesSpectrum
1st
Nalidixic acid Cinoxacin, oxolinic acid
Gram- but not Pseudomonas
2nd
Norfloxacin Ciprofloxacin Ofloxacin
Gram-(including Pseudomonas) some Gram+ (S. aureus) some atypicals
3rd
Levofloxacin Sparfloxacin Moxifloxacin Gemifloxacin grepafloxacin
Same as 2nd generation: extended Gram+ and atypical coverage
4th
*Trovafloxacin
Same as 3rd generation: broad anaerobic coverage
*withdrawn from the market in 1999
Mechanism of action: The quinolone antibiotics target bacterial DNA gyrase and topoisomerase IV. For many gram-positive bacteria (such as S. aureus), topoisomerase IV is the primary activity inhibited by the quinolones. In contrast, for many gram-negative bacteria (such as E. coli) DNA gyrase is the primary quinolone target.
The older quinolones did not achieve systemic antibacterial levels. These agents were useful only for treatment of UTIs. Fluoroquinolones achieve bactericidal levels in blood and tissues, thus they are used for the treatment of systemic and UTIs.
Pharmacokinetics 1.The quinolones are well absorbed after oral administration and are widely distributed in body tissues. 2. The volume of distribution of quinolones is high Quinolone concentrations in cerebrospinal fluid, bone, and prostatic fluid are lower than in serum. 3. Dose adjustments in patients with renal insufficiency are required for cinoxacin, norfloxacin, ciprofloxacin, ofloxacin, 4. A The following fluoroquinolone trovafloxacin, grepafloxacin, should not be used in patients with hepatic failure.
Clinical Uses : UTIs including bacterial prostatitis. Bacterial diarrhea caused by shigella, salmonella, toxigenic E. coli or Campylobacter. They are effective in treatment of gonorrhea .
Fluoroquinolones( except norfloxacin which does not achieve adequate systemic concentrations) have been employed in infections of soft tissues, bones, and joints. In intra-abdominal and respiratory tract infections.
A second line agents for legionellosis. Treatment of tuberculosis and atypical mycobacterial infections. Ofloxacin is approved for treatment of infections caused by Chlamydia trachomatis.
CNS adverse effects occur in about 5% of patients and are usually manifested by mild headache, sleep disturbance, dizziness or mood alteration. Seizures may occur and these patients should be avoided in patients with convulsive or other CNS disorders.
Fluoroquinolones may damage growing cartilage and cause an arthropathy. Thus they are contraindicated in patients under 18 year of age and in pregnant women. Note: . All of these agents can produce arthropathy in several species of immature animals. Traditionally, the use of'quinolones in children has been contraindicated for that reason. However, children with cystic fibrosis given ciprofloxacin, norfloxacin, and nalidixic acid ,the benefits may outweigh the risks of quinolone therapy in children. Since flouroquinolones are excreted in breast milk, they are contraindicated for nursing mothers.
Quinolones And Fluoroquinolones Adverse Effects
Tendonitis/tendon rupture. A few cases of ruptures of the shoulder, hand and Achilles tendon have been reported. CVS: QT-prolongation.The following quinolone antimicrobial agent is not useful in systemic infections: A. Lomefloxacin B. Ofloxacin C. Nalidixic acid D. Moxifloxacin E. Ciprofloxacin
Azoles This group includes: 1. Metronidazole and tinidazole. 2. Antifungal drugs such as clotrimazole.
Metronidazole(Flagyl) Metronidazole is a bacteriostatic it is effective in anaerobic microorganisms and some protozoa. It is well absorbed after oral or rectal administration.
Mechanism of action: In anaerobic bacteria metronidazole is converted into an active form by reduction of its nitro group, this binds to DNA and prevents nucleic acid formatoion.
Clinical Uses: Treatment of sepsis due to anaerobic organisms e.g. Bacteroides species notably : postsurgical infections, intrabdominal infections and septicemia, but also wound and pelvic infection, osteomyelitis and absesses of brain or lung.
Pseudomembraneous colitis. Trichomoniasis. Amoebiasis (Entamoeba histolytica) . Giardiasis (Giardia lamblia) . Acute ulcerative gingivitis and dental infections. Anaerobic vaginosis(Gardnerella vaginalis). Triple therapy in
Adverse effects: GIT: nausea, vomitig, diarrhea and unpleasant metallic taste in the mouth. CNS: headache, dizziness , ataxia and siezure. Rashes, urticaria and angioedema. Peripheral neuropathy.
Antimicrobials effective against anaerobic bacteria include the following except: A. Tobramycin B. Clindamicin C. Chloramphenicol D. Metronidazole
Tinidazole : It is similar to mertronidazole. Longer half life (13 h). Same uses. Same adverse effects. The longer duration of action of tinidazole may be an advantage e. g. in giardiasis, trichomoniasis and acute ulcerative gingivitis in which tinidazole 2g by mouth in a single dose is effective as a course of metronidazole.