Quinolones are synthetic antimicrobials that are active against gram-negative bacteria. The first quinolone was nalidixic acid introduced in the 1960s. Fluoroquinolones were later developed, adding fluorine substitutions to increase potency and spectrum of activity against both gram-positive and gram-negative bacteria as well as some anaerobes. Ciprofloxacin is a first-generation fluoroquinolone that is highly potent and active against a broad range of bacteria, especially aerobic gram-negatives. It has good tissue penetration and a low risk of bacterial resistance developing.

1. QUINOLONES Synthetic antimicrobials having a quinolone structure Active against gram-ve bacteria First member was Nalidixic acid introduced in 1960’s There usefulness is limited to urinary and g.i tract infections because of -Low potency -Modest blood and tissue levels -Limited spectrum -High frequency of bacterial resistance

5. FLUOROUINOLONES These are quinolone antimicrobials having one or more Fluorine substitutions. First generation Fluoroquinolones (introduced in 1980s) Norfloxacin Ofloxacin Ciprofloxacin Pefloxacin Second generation Fluoroquinolones (1990s) Lomefloxacin Levofloxacin Sparfloxacin Gatifloxacin Moxifloxacin

7. FQs binds to A subunit with high affinity and interfere with its strand cutting and resealing function. In gram +ve bacteria -inhibit Topoisomerase IV which nicks and seperates daughter DNA strands after DNA replication. In host cell topoispmerase II is present which has very low affinity for FQs- hence low toxicity to host cells.

9. MIC - < 0.1 µg/ml for Neisseria and enterobacteriaceae. Gram +ve are inhibited at relatively higher concentrations. Highly susceptible E.Coli Enterobacter Salmonella typhi Shigella Proteus Moderately susceptible P.Aeruginosa S. Aureus S. Epidermidis Listeria Brucella

11. PHARMACOKINETICS A- oral, but food delays absorption and first pass metabolism occurs. D - plasma protein bound Prominent feature- high tissue penetrability: concentrates in lung, sputum, muscle, bone. but CSF and aqueous levels are lower. E - urine