QUINOLONES---DNA GYRASE

INHIBITORS
Dr. Afsheen Siddiqi
QUINOLONES
1-FIRST GENERATION
Nalidixic acid

2-SECOND GENERATION

Ciprofloxacin, Norfloxacin
Ofloxacin
3-THIRD GENERATION
Gatifloxacin, Levofloxacin
Moxifloxacin, Sparfloxacin
4-FOURTH GENERATION
Trovafloxacin
CLASSIFICATION ACCORDING TO
ANTIMICROBIAL SPECTRUM
 Least activity against G + ve & G – ve organism
Norfloxacin
 Excellent activity against G – ve & moderate activity against G + ve
organism
Ciprofloxacin
Enoxacin
Lomefloxacin
Levofloxacin
Ofloxacin
Pefloxacin
 Improved activity against G + ve organisms

Gatifloxacin
Gemifloxacin
Moxifloxacin
FLUOROQUINOLONES

Are synthetic flourinated analogs of NALIDIXIC ACID - used mainly for recurrent urinary tract
infections (UTIs).
Newer fluorinated quinolones - greater potency, broader spectrum of antimicrobial activity,
systemic effects.
New compounds - more active against G+ organisms, yet retain favorable activity against G-
microorganisms.
A. Mechanism of action
- they enter the bacterium by passive diffusion via water channels.
- inhibit bacterial topoisomerases which are necessary for DNA synthesis
DNA gyrase (TOPO II) &Topoisomerase IV .Inhibition of topoisomerase IV interferes with
seperation of replicated chromosomal DNA into the respective daughter cells during cell
division

Since DNA gyrase is a bacteriospecific target for antimicrobial therapy,

cross-resistance with other antimicrobial drugs is rare, but this is
increasing in the case of multidrug-resistant organisms.

Bactericidal
MECHANISM OF RESISTANCE
 Staphlococci , pseudomonas & serratia are resistant
 MECHANISM

1-Mutation in quinolone bind region of target enzyme

2-Change in permeability of organism
3-Plasmid mediated resistance
PHARMACOKINETICS
 Well absorbed orally
 Absorption is impaired by di- & trivalent cations in
antacids
 Renal excretion
Antimicrobial spectrum
C. Examples of clinically useful fluoroquinolones
Ciprofloxacin - frequently used.
F. Adverse reactions - well tolerated

1-Connective tissue problems: They should be

avoided in pregnancy, in nursing mothers, and in
children under 18 years - because articular cartilage
erosion (arthropathy)
2-QT prolongation
3-Tendinitis ,rare but serious complication
DRUG INTERACTIONS
With antacids Impaired absorption of quinolones
With theophylline Ciprofloxacin & ofloxacin increase
serum level of theophylline by
inhibiting its metabolism
Warfarin , caffeine & cyclosporin Third & fourth generation quinolones
raise the serum levels of these drugs