Fluoroquinolones

Dr. T.R.RAMANUJAM. M.D.,

Professor & Head, Dept of Pharmacology,
Sri Ramachandra Medical College & Research Institute,   
Porur ,   
Chennai - 600 116 
SOUTH INDIA. 

• Introduction
• Newer quinolones
• Pharmacological aspects of newer quinolones
• Major clinical applications
• Adverse effects
• Drug Interactions
• Pharmacological outline of Sparfloxacin
• Further Developements of Quinolones
• Conclusion

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.

DEVELOPMENT OF NEWER QUINOLONES

Major factors that are likely to determine the development of newer Quinolones include;

• Greater clinical efficacy
• Less toxic with greater safety
• Lower tendency for induction of resistance
• Short effective duration of therapy
• Better patient compliance
• Better cost-benefit ratio.

Substantial progress has been made recently in the development of Safe & Effective agents primarily because of the advances made in ;

• Chemistry
• Molecular mechanisms of quinolones
• Factors leading to development of resistance etc.,

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.

Classification of Flouroquinolones

I Generation

• Nalidixic acid
• Oxolinic acid
• Cinoxacin
• Pipedemic acid
• Flumequine

II Generation

• Norfloxacin
• Ciprofloxacin
• Enoxacin
• Fleroxacin
• Lomefloxacin
• Ofloxacin
• Levofloxacin
• Rufloxacin

III Generation

• Sparfloxacin
• Tosufloxacin
• Gatifloxacin
• Pazufloxacin
• Grepafloxacin

IV Generation

• Trovafloxacin
• Clinafloxacin
• Sitafloxacin
• Moxifloxacin
• Gemifloxacin

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 –

• pneumococci, Str.pneumoniae, MRSA, Staph aureus, S.epidermides, Enterococci, anaerobic organisms and IC pathogens like Chlamydiae, Mycoplasmae, legionellae, Mycobactriae etc.,
• Newer quinolones are;
  
  -         Levofloxacin
  -         Trovafloxacin
  -         Grepafloxacin
  -         Sparfloxacin and the following quinolones are undergoing various phases of clinical trials viz.,
  -         Moxifloxacin
  -         Clinafloxacin
  -         Gatifloxacin
  -         Sitafloxacin
  -         Gemifloxacin.
  
  Quinolones in earlier phases of development are;
  
  -         Ecinofloxacin
  -         Balofloxacin
  -         Nadifloxacin etc.,
  -         Prulifloxacin

MAJOR CLINICAL INDICATION:

Bacterial infections of ;

• Respiratory tract- Acute Exacerbation of Chronic Bronchitis, (AECB), Pneumonia.
• Urinary Tract Infection (uncomplicated & complicated).
• Skin, Soft tissue, bone and joint.
• 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.
• Central Nervous System Infections (Trovafloxacin has greater penetrability into CNS).
• Immuno compromised patients.