Table of Contents
PPT Slide
Mechanism of action of fluoroquinolones: the basics...
2 key enzymes in DNA replication:
Ternary complex DNA - enzyme - fluoroquinolone
Resistance to fluoroquinolones: the basics
Fluoroquinolones are the first entirely man-made
antibiotics: do we understand our molecule ?
Chemistry and Activity
The pharmacophore common to all fluoroquinolones
From chloroquine to nalidixic acid...
Nalidixic acid *
From nalidixic acid to the 1st fluoroquinolone
(1 of 4)
From nalidixic acid to the 1st fluoroquinolone
(1 of 4)
From nalidixic acid to the 1st fluoroquinolone
(1 of 4)
From nalidixic acid to the 1st fluoroquinolone
(1 of 4)
From norfloxacin to the other 1st generation fluoroquinolones:
pefloxacin
From norfloxacin to the other 1st generation fluoroquinolones:
ofloxacin
From norfloxacin to the other 1st generation fluoroquinolones:
ciprofloxacin
"1st generation" fluoroquinolones
The "first generation" of fluoroquinolones
From ofloxacin to levofloxacin...
The present "first generation" of fluoroquinolones
...
How to improve the chemotherapeutic usefulness
of the "first generation" fluoroquinolones
The “second generation” fluoroquinolones
The “third generation” fluoroquinolones
1. maintenance of anti - Gram (-) activity
Gram (-) activity (E. coli)
2. improving Gram (+) activity (S. pneumoniae)
Activity against S. pneumoniae
3. obtaining activity against anaerobes ...
Activity against B. fragilis
Is there a SAR for emergence of resistance ?
Is there a SAR for emergence of resistance ?
Fluoroquinolones with a C8-methoxy
Toxicity
Frequent side effects of fluoroquinolones: is there
a SAR ?
SAR of frequent side effects
Fluoroquinolones with low or no drug interactions..
Fluoroquinolones with high phototoxicity ...
Rare side effects of fluoroquinolones:
Rare side effects of fluoroquinolones: cardiac
toxicity
Cardiac toxicity QT prolongation: is there any
SAR ?
Cardiac toxicity QT prolongation: is there any
SAR ?
Other severe toxicities
Which part of the molecule is the culprit ?
Pharmacokinetics
SAR of pharmacokinetic parameters
SAR of main pharmacokinetic parameters: how to
get a long half life
SAR of main pharmacokinetic parameters: biodisponibility
SAR of main pharmacokinetic parameters: volume
of distribution
Resistance: do not forget the correct dosing...
Pharmacokinetic parameters in relation with efficacy
Indications of new fluoroquinolones
Shall we have a very bright future ? |