Quinolones

Nucleic Acid Synthesis Inhibitors

Quinolones

• Quinolones were first developed in the 1960s

and can be classified into generations based on
antimicrobial activity.

• First Nalidixic acid in 1962.

Generational Classification
• First Generation
Gram-negative, but
Pseudomonas spp.
• Second Generation
Gram-negative, some gram
positive and mycobacteria.
• Third and Fourth
Generation
Have increased activity against
gram-positive pathogens
including S. pneumoniae.
They are also active against
many agents causing zoonotic
infection and against
mycobacteria.
Generational Classification
• First Generation • Third Generation
▫ Cinoxacin ▫ Gatifloxacin
▫ Nalidixic Acid ▫ Grepafloxacin
▫ Oxolinic acid ▫ Pazufloxacin
▫ Sparfloxacin
• Second Generation ▫ Tosufloxacin
▫ Ciprofloxacin
▫ Enoxacin
• Fourth Generation
▫ Fleroxacin
▫ Clinafloxacin
▫ Lomefloxacin
▫ Gemifloxacin
▫ Levofloxacin
▫ Moxifloxacin
▫ Norfloxacin
▫ Trovafloxacin
▫ Ofloxacin
▫ rulfloxacin
Mechanism of action:
The fluoroquinolones
act by inhibiting type 2
bacterial DNA
topoisomerases, DNA
gyrase and
topoisomerase IV.
They bind to and trap
the enzyme-DNA
complex. This blocks
DNA synthesis and cell
growth and ultimately
has a lethal effect on
the cell.
Mechanism of resistance
Resistance to quinolones may develop during
therapy via mutations in the bacterial
chromosomal genes encoding DNA gyrase or
topoisomerase IV, or by active transport of the
drug out of the bacteria
Spectrum of activity
 The fluoroquinolones are potent bactericidal agents against:

 E. coli and various species of Salmonella, Shigella, Enterobacter,

Campylobacter, and Neisseria

 Ciprofloxacin is more active than norfioxacin against P. aeruginosa

 Fluoroquinolones also have good activity against staphylococci,

including methicillin­resistant strains

 Several intracellular bacteria are inhibited by fluoroquinolones these

include species of Chlamydia, Mycoplasma, Legionella, Brucella, and
Mycobacterium (including Mycobacterium tuberculosis)
Pharmacokinetics
 The quinolones are well absorbed after oral administration and are widely
distributed in body tissues, The volume of distribution of quinolones is high.
Quinolone concentrations in CSF, bone, and prostatic fluid are lower than in
serum

 Routes of elimination differ among the quinolones. Renal clearance

predominates for ofloxacin, lomefloxacin, and cinoxacin; pefloxacin, nalidixic
acid, sparfloxacin, grepafloxacin, and trovafloxacin are predominantly elim­
inated nonrenally.

 Dose adjustments in patients with renal insufficiency are required for

cinoxacin, norfloxacin, ciprofloxacin, ofloxacin, enoxacin, and lomefloxacin but
not for nalidixic acid, grepafloxacin, trovafloxacin, and pefloxacin. None 'of the
agents is efficiently' removed by peritoneal or hemodialysis.

 A fluoroquinolone other than trovafloxacin, grepafloxacin, or pefloxacin should

be used in patients with hepatic failure.
Therapeutic indications:
 Urinary Tract Infections.
▫ Nalidixic acid and cinoxacin are useful only for urinary tract
infections caused by susceptible microorganisms. The
fluoroquinolones are sig­nificantly more potent and have a much
broader spectrum of antimicrobial activity.
 Prostatitis.
▫ Norfloxacin, ciprofloxacin, and ofloxacin all have been effective in
uncontrolled trials for the treatment of pros­tatitis caused by
sensitive bacteria.
 Sexually Transmitted Diseases (STDs).
 Pelvic inflammatory disease (PID); Primary
cause of Infertility in females
 Gastrointestinal and Abdominal Infections
Therapeutic indications:
 Respiratory Tract Infections.
▫ The major limitation of the use of quinolones for the treatment of
community-acquired pneumonia and bronchitis had been the
poor in vitro activity of ciprofloxacin, ofloxacin, and norfloxacin
against S. pneumoniae ­
 Bone, joints and soft tissue infections  
 Other Infections.
▫ The quinolones may be used as part of multiple-drug regimens
for the treatment of multidrug-resistant tuberculosis and for the
treatment of atypical mycobacterial infections as well as
Mycobacterium avium complex infections in AIDS
Therapeutic indications:
 In neutropenic cancer patients with fever, the
combination of a quinolone with an aminoglycoside is
comparable to ,B-Iactam aminoglycoside combinations
but is less effective when used as a single drug.

 Ciprofloxacin plus amoxicillin-clavulanate recently has

been shown to be effective as an oral empiric therapy for
fever in low-risk patients with granulocytopenia
secondary to cancer chemotherapy

 Invasive Otitis Media

Adverse effects:

 Generally well tolerated; the most common adverse reactions

are gastrointestinal tract, mostly mild nausea, vomiting, and/or
abdominal discomfort.

 Diarrhea and antibiotic-associated colitis have been unusual

 Central nervous system side effects, predominately mild

headache and dizziness

 Rarely, hallucinations, delirium, and seizures, predominantly in

patients who also receive theophylline or a nonsteroidal
antiinflammatory drug
Adverse effects:

Rashes, including photosensitivity reactions.

 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 have had
few, and reversible, joint symptoms. Therefore, in some
cases the benefits may outweigh the risks of quinolone
therapy in children.
 Adverse effects:

 Arthralgias and joint swelling have developed in children

receiving fluoroquinolones; therefore, these drugs are not
generally recommended for use in prepubertal children or
pregnant women.

 Serious hepatic damage, including liver failure resulting in death,

observed with patients receiving trovafloxacin. For this reason, the
use of trovafloxacin has been restricted to serious or life-
threatening in­fections where the benefits of therapy outweigh the
risk

Tendon repture; Dysglycemia; Hypersensitivity reactions;

Hallucinations; Seizures
Contraindications
Quinolone Doses Preferred Uses
Norloxacin 400mg OD/BD UTI
Bacterial Diarrheoas
Ciprofloxacin 250-750mg BD UTI
Typhoid
Bacterial diarrheoas
Gonorrhea…etc
Ofloxacin 200-400mg BD Tuberculosis
Leprosy
Atypical Pneumonia
Chlamydial infections
Levofloxacin 500mg OD Community aquired pnumonia
Bronchitis, UTI
Skin & soft tissue infections
Gatifloxacin Community aquired pnumonia
Bronchitis, UTI
Gonnococcal infections
Moxifloxacin Community aquired pnumonia
Bronchitis, Sinusitis, otitis media
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