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Dr.
T.R.RAMANUJAM. M.D., |
Professor & Head, Dept
of Pharmacology,
Sri Ramachandra Medical College & Research Institute,
Porur
,
Chennai - 600
116
SOUTH INDIA.
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Introduction |
The interest of the
medical community in flouroquinolones has not decreased despite more than
ten years of continuous and growing use of these agents.
This constant need for new anti microbials has produced a variety of
newer flouroquinolones termed as I, II, III, and IV
generation as well as a handful of
relatively similar compounds .
With I generation compounds like
Nalidixic acid, Pipemidic acid, and cinoxacin by virtue of their limited
activity against Gram negative organisms with poor plasma concentration and high
urinary concentration are
indicated only in uncomplicated urinary tract infections. With older
quinolones many of the organisms are not covered or inadequately covered,
Gram positive organisms, Atypical intracellular pathogens, Mycobacteriae and
anaerobic organisms are excluded
and because of poor blood concentrations they are not suitable for systemic
infections and hence the search for newer quinolones to cover the Gram
positive
organisms including
resistant strains of Streptococci pneumoniae, Enterococci, Staphylococci
epidermides, Staphylococci aureus
,Mycobactriae, Chlamydiae, Mycoplasmae and Legionellae species.
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DEVELOPMENT OF NEWER
QUINOLONES
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Major factors that are
likely to determine the
development of newer Quinolones
include;
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Greater clinical efficacy
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Less toxic with greater safety
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Lower tendency for induction of resistance
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Short effective duration of therapy
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Better patient compliance
-
Better cost-benefit ratio.
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Substantial progress has
been made recently in the development of Safe & Effective agents
primarily because of the advances made in ;
The first and key
discovery was the identification of the enzyme DNA Gyrase or Toposiomerase
II and IV and the second major advantage contributing to the rapid expansion
was the ability to chemically manipulate the nucleus of 4-Quinolones.
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Classification of
Flouroquinolones
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I Generation
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II
Generation
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-
Nalidixic
acid
-
Oxolinic
acid
-
Cinoxacin
-
Pipedemic
acid
-
Flumequine
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-
Norfloxacin
-
Ciprofloxacin
-
Enoxacin
-
Fleroxacin
-
Lomefloxacin
-
Ofloxacin
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Levofloxacin
-
Rufloxacin
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III
Generation
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IV Generation
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-
Sparfloxacin
-
Tosufloxacin
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Gatifloxacin
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Pazufloxacin
-
Grepafloxacin
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- Trovafloxacin
- Clinafloxacin
- Sitafloxacin
- Moxifloxacin
- Gemifloxacin
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Earlier
compounds like Nalidixic acid, Norfloxacin, Pefloxacin, Ofloxacin and
ciprofloxacin enjoyed great success particularly in Gram negative infections. They
are excluded for use in children (except- Ciprofloxacin in cystic fibrosis,
and Nalidixic acid for UTI in children) because of the fear of
Chondrotoxicity. The newer generation of quinolones has greater activity
against –
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- pneumococci,
Str.pneumoniae, MRSA, Staph aureus,
S.epidermides, Enterococci,
anaerobic organisms and IC
pathogens like Chlamydiae, Mycoplasmae, legionellae, Mycobactriae etc.,
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Newer
quinolones are;
-
Levofloxacin
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Trovafloxacin
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Grepafloxacin
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Sparfloxacin and
the
following quinolones are undergoing various phases of clinical trials viz.,
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Moxifloxacin
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Clinafloxacin
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Gatifloxacin
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Sitafloxacin
-
Gemifloxacin.
Quinolones
in earlier phases of development are;
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Ecinofloxacin
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Balofloxacin
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Nadifloxacin etc.,
-
Prulifloxacin
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MAJOR
CLINICAL INDICATION:
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Bacterial
infections of ;
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Respiratory
tract- Acute Exacerbation of Chronic Bronchitis, (AECB), Pneumonia.
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Urinary Tract
Infection (uncomplicated
& complicated).
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Skin,
Soft tissue, bone and joint
.
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Gastro
Intestinal Tract – diarrhoea due to E.coli, Salmonellosis, Shiegellae,
Campylobacter, Aeromonas, Vibrio, Plesiomonas
shigelloides. Intra abdominal infection,
Post surgical infection and obstetric and gynecological infections – Excellent
with Trovafloxacin.
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Central
Nervous System Infections (Trovafloxacin has greater penetrability into CNS)
.
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Immuno
compromised patients
.
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