This document discusses quinolones, a class of synthetic antimicrobial compounds. It begins by introducing nalidixic acid, the first quinolone, and how later fluorination led to more potent fluoroquinolone derivatives. Mechanism of action is described as inhibition of bacterial DNA gyrase and topoisomerase, preventing DNA replication. Adverse effects include tendonitis, CNS effects, and QT prolongation with some agents. Therapeutic uses include urinary tract infections, gonorrhea, respiratory infections, and more. Resistance develops via mutations impairing drug binding or drug efflux.

1. Presented By- Md Shariq Ansari
B.Pharm, Final year
Roll No- 1455250020

2.  ANTIMICROBIAL: These are the agents that kills the microorganisms or
inhibits their growth.
Antimicrobial can be grouped according to the
(i) Microorganisms- i.e. Antibiotics against Bacteria, Antifungal against Fungi.
(ii) Function- Microbicidal, Microbiostatics.
ANTIBIOTICS: These are the substance produced by microorganisms,
which selectively suppress the growth or kill the microorganisms at very low
concentration.
SOURCE OF ANTIBIOTICS:
FUNGI BACTERIA ACTINOMYCETES
Penicillin's (penicillium notatum) Polymyxin B Aminoglycosides
Cephalosporin's (cephalosporium) Tyrothricin Chloramphenicol
Griseofulvin (penicillium gresiofuloum) Bacitracin Erythromycin
Cholistin Tetracycline

3. QUINOLONES
INTRODUCTION:
 Synthetic antimicrobial compounds having quinolone structure (active moiety).
 Bactericidal, broad spectrum antibiotics.
 Primarily active against gram-negative bacteria.
 Most widely used because of their relative safety, their availability in both orally
and parenterally and their favorable pharmacokinetics.
HISTORY:
 The first member Nalidixic Acid was introduced in mid-1960s has usefulness
limited to UTI and G.I.Tract infections because of low potency and high
frequency of bacterial resistance.

4.  In 1980s by fluorination of the quinolone structure at position no 6 & piperazine
substitution at position 7 resulted in derivatives called fluoroquinolones.
CHEMISTRY:

5. NALIDIXIC ACID
(1) It is active against gram negative bacteria especially coliforms:-
E.coli
Proteus
Kleibseilla
Enterobacter
Shigella
Psuedomonas ( Except)
(2) It acts by inhibiting bacterial DNA gyrase
PHARMACOKINETICS:
- Orally absorbed, high plasma protein binding and partly metabolized in liver.
- t½ is about 8 hrs.
- Therapeutic concentrations attained in urine & gut lumen are lethal to common
urinary pathogens & diarrhoea causing coliforms.
Bactericidal
antibiotic

6. ADVERSE EFFECTS:
- G.I. disturbance and rashes mostly occurs.
- Headache, vertigo, visual disturbance are the most common adverse effects.
CONTRAINDICATIONS:
- It is contraindicated in infants.
USES:
- It is primarily used as an Urinary antiseptic.
- Nitrofurantoin should not be given concurrently – Antagonism occurs.
- In the treatment of Diarrhoea caused by coliforms.
Norfloxacin /ciprofloxacin preferred.

7. FLUOROQUINOLONES
INTRODUCTION:
 These are quinolone antimicrobials having one or more fluorine substitutions.
 Fluorination of quinolone structure at position 6 & piperazine substitution at
position 7 resulted in derivatives called fluoroquinolones.
 High potency.
 Broad spectrum antimicrobial activity.
 Slow development of resistance.
 Better tissue penetration .
 Good tolerability.
 Used for wide variety of infectious diseases

8. HISTORY:
- The first generation fluoroquinolones was introduced in 1980s, have one fluoro
substitution.
- In 1990s, compounds with additional fluoro group and other substitution have
been developed- further exceeding antimicrobial activity to gram-positive cocci and
anaerobes.
CLASSIFICATION:
First generation Second generation
Levofloxacin
Lomefloxacin
Moxifloxacin
Sparfloxacin
Gemifloxacin
Prulifloxacin
Norfloxacin
Ciprofloxacin
Ofloxacin
Pefloxacin

9. MECHANISM OFACTION
Quinolones target bacterial DNA gyrase & topoisomerase IV.
 Gram negative bacteria - DNA Gyrase
 Gram positive bacteria - Topoisomerase IV
 Double helical DNA
 Two strands must separate to permit DNA replication / transcription
 “over winding” / excessive positive supercoiling of DNA in front of point of
separation.
 Inhibit protein synthesis.
 DNA Gyrase - introduces negative supercoils into DNA (checks mechanical
hindrance).
 DNA Gyrase has (A & B subunit).
 A subunit - strand cutting function of DNA gyrase.
 A subunit reseals the strand.

10. Quinolones
- Bind to A - subunit with high affinity & interfere with strand cutting &
resealing function.
- Prevent replication of bacterial DNA during bacterial growth & reproduction.
- finally bacterial cell death occurs .

13. Co
ntd
.
Mechanism of resistance-

14. PHARMACOKINETICS
 Rapid oral absorption.
 High tissue penetrability.
 CSF & aqueous levels are low
 Excreted in urine.
 Urinary & biliary concentrations are 10-50 fold higher than in plasma.
 Excreted in urine.
 Metabolized by liver should not be used in hepatic failure, except Pefloxacin &
moxifloxacin.

15. Adverse effects
 Hypersenstivity; rashes including photosensitivity.
 Tendonitis & tendon rupture.
 Generally safe
 Nausea, vomiting, abdominal discomfort, bad taste
 CNS:
 headache, dizziness, rarely hallucinations, delirium.
 & seizures have occurred predominantly in patients receiving theophylline or NSAIDs.
 .QTc prolongation.
 Sparfloxacin.
 Gatifloxacin.
 Moxifloxacin.
 Cautious use in patients who are taking drugs that are known to prolong the QT interval .
 tricyclic antidepressants .
 Phenothiazine.
 class I anti-arrhythmics

16. INTERACTION
- NSAIDs may enhance CNS toxicity of FQ’s
Seizures reported.
Antacids, Sucralfate, Iron salts reduce absorption of FQ,s
THERAPEUTIC USE
1. Urinary tract infection
2. Gonorrhea
3. Typhoid
4. Bone, soft tissues and wound infections.
5. Respiratory infections
6. Tuberculosis

17.  Ceftriaxone
 Most reliable
 Fastest acting bactericidal drug for enteric fever.
 i.v 4g daily 2 days.
 2g daily till 2 days after fever subsides.
 Bone, joint, soft tissue & wound infections.
 Skin & soft tissue infections.
 joint infections