1.
One healthy bacterium
could reproduce
into a colony of
more than 2 million…..
in just seven hours…..

2.
DR. V. SATHYA NARAYANAN. M. D.,
PROFESSOR OF PHARMACOLOGY
SRM MCH & RC
SRM UNIVERSITY.
CHENNAI

3.
QUINOLONES
Synthetic antimicrobials having quinolone structure
 Active primarily against GRAM NEGATIVE
BACTERIA
1960’s Nalidixic acid
1980 ‘s Fluoroquinolones

4.
NALIDIXIC ACID
Active against G-ve bacteria
SPECTRUM : E.coli , proteus ,klebsiella, shigella ,
enterobacter ( not pseudomonas )
 PK : concentration in urine therapeutic for urinary↑ →
infection
ADR GI, Neurological – headache, drowsiness,→
vertigo, G-6 PD deficient develop hemolysis→
C/I – infants
D/I – Antagonism with nitrofurantoin

5.
NALIDIXIC ACID
USES
 as urinary antiseptic - second line drug for recurrent
UTI
 G –ve diarrhoeas (E.coli, shigella, salmonella,
proteus )
 Ampicillin resistant shigella entertis.

6.
FLUOROQUINOLONES
First generation - 1980’s – 1 flouro substitution
Norfloxacin Ofloxacin
Ciprofloxacin Pefloxacin
 II nd generation - 1990’s
Levofloxacin Gatifloxacin
Lomefloxacin Moxifloxacin
Sparfloxacin
Extended to G+ve cocci ,anaerobes, longer t1/2
 III rd generation – trovafloxacin/alatrovafloxacin,
sitafloxacin

7.
MECHANISM OF ACTION
 Inhibit bacterial DNA GYRASE( in GRAM --VE)
interfere with strand cutting ,resealing function 
Damage DNA digestion of DNA
Inhibit topoisomerase IV ( in GRAM +VE)
 Bactericidal

8.
Resistance
: Plasmid mediated resistance does not occur
 mutational resistance
 slow to develop

9.
FEATURES OF FQs
Rapidly bactericidal
Concentration dependent bacterial killing
Long postantibiotic effect
Low frequency of mutational resistance
Sparing of protective intestinal bacteria
Active against many β-lactam, aminoglycoside
resistant bacteria

10.
CIPROFLOXACIN(prototype )
 SPECTRUM OF ACTION :
highly effective on : G-ve bacilli - E.Coli, klebsiella,
proteus , salmonella , shigella , enterobacter
G-ve cocci - N.Gonorrhoeae , N.Meningitides,
 H.influenzae , H.ducreyi , campylobacter , yersinia ,
vibrio cholerae
Moderately effective on : pseudomonas ,
staph.aureus , MRSA , legionella , brucella , listeria ,
B.anthracis , M. tuberculosis

11.
PHARMACOKINETICS
Rapid oral absorption
high tissue penetrability
excreted primarily in urine
 ↑urinary, biliary concentration
Clinically significant postantibiotic effect
Dosage
oral - 250 - 750 mg BD
i.v - 100 - 200 mg
eye drops

12.
ADR
Mild - seen in 10 % of patients
Gastrointestinal -nausea , vomiting, bad taste
CNS : dizziness , headache , confusion, insomnia,
seizures in high doses ,
Impairement of concentration - caution while driving
Hypersensitivity : rash , pruritus , photosensitivity,
urticaria
Tendonitis : tendon rupture

13.
CONTRAINDICATIONS
Pregnancy
 Children <18 yrs old
(cartilage damage in wt bearing joints)

14.
INTERACTIONS
Inhibit cyp450 microsomal enzymes → ↓metabolism
↓
↑Toxicity of sulfonylureas ,
theophylline ,
warfarin
NSAIDs →↑ CNS toxicity of FQs
Antacids , iron →↓ Absorption of FQs

15.
THERAPEUTIC USES
Typhoid fever
UTI
Bacterial gastroenteritis
Chancroid
Gonorrhoea
Anthrax
Bone ,soft tissue infection due to to susceptible
organism
Gynecological infection , wound infections

16.
THERAPEUTIC USES
Diabetic foot
MDR tuberculosis
G-ve septicaemias , meningitis
Conjunctivitis by g-ve bacteria(topical )
Respiratory Infections due to susceptible organisms
Prophylaxis of infections in neutropenics/ cancer
patients

17.
IN DENTISTRY
Not indicated for any acute orofacial infections unless
culture & sensitivity reports
Not synergistic with β lactam , aminoglycosides.
Rapidly progressive or
refractory periodontitis associated with
Enterobacteriaecae - culture & sensitivity test

18.
NORFLOXACIN
Less potent
Low concentration in tissues
Indicated in - UTI ,genital tract infections , bacterial
diarrhoeas
Not for RI

19.
PEFLOXACIN
Methyl derivative of norfloxacin
More lipid soluble
Better tissue penetration
Passage into CSF higher than other FQs→ →
preferred for meningitis
Longer t ½
Cumulation useful in many systemic INF→
Doses reduced in hepatic disease
Alternative to cipro in typhoid

20.
OFLOXACIN
More potent for G+ve infections
Also effective against Chlamydia , Mycoplasma ,
M.leprae , M.tuberculosis
Lipid soluble
High oral BA
cyp450 inhibition less
↓dose in renal failure
Indications RI ,ENT infection , NGU, gonorrhoea ,→
tuberculosis , leprosy , atypical pneumonia

21.
LEVOFLOXACIN
Levoisomer
Improved action on Strep .pneumoniae , anaerobes
100 % oral BA
Single daily dose
No cyp 450 interaction
Uses typhoid, RI ,ENT infection ,renal , skin /soft→
tissue infections

22.
LOMEFLOXACIN
II nd generation FQ
More active on some G-ve bacteria , Chlamydia
Single daily dose
↓dose in renal failure
↑ warfarin levels

23.
SPARFLOXACIN
Enhanced action on G +ve bacteria
Strep. Pneumoniae,
staphylococci,
enterococci ,
bacteroides and other anaerobes,
 mycobacteriae
Single daily dose

24.
SPARFLOXACIN – ADR & DRUG
INTERACTIONS
No CYP 450 interaction
Phototoxicity +( patients advised not to go in sun)
Slight prolongation of Qtc interval

25.
SPARFLOXACIN - Indications
Pneumonia,
Chronic bronchitis,
ENT infections,
Tuberculosis ,
leprosy ,
MAC infection in AIDS

26.
GATIFLOXACIN – Spectrum & Indications
Strep .pneumoniae,
chlamydia pneumoniae
 atypical respiratory pathogens,
 anaerobes
 Upper Respiratory Infections,
Lower Respiratory Infections,
 Urinary Tract Infections


27.
GATIFLOXACIN –
ADR&CONTRAINDICATIONS
ADR – Phototoxicity ,
CNS effects
C/I - hypokalemia
 CAUTION : prolonged Qtc intervral
GATIFLOXACIN –NOT USED IN UK & USA

28.
MOXIFLOACIN
Spectrum -G+ve
β lactam /macrolide resistant bacteria
Atypical respiratory pathogens
Most potent FQ in tuberculosis
URI /LRI, not good for UTI
ADR similar ,predispose to seizures , arrhythmias→
Long acting