One bacterium can reproduce into over 2 million in 7 hours. Quinolones are synthetic antimicrobials active against gram-negative bacteria. Nalidixic acid was the first quinolone developed in the 1960s, while later fluoroquinolones in the 1980s were more potent and had broader spectra. Fluoroquinolones work by inhibiting bacterial DNA gyrase and topoisomerase IV, and are generally well-absorbed with few resistance issues. Common uses include urinary tract infections and respiratory, gastrointestinal, and skin infections. Adverse effects can include nausea, tendon damage, and interactions with other drugs.

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

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

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

21. 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

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

31. 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

33. 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

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

42. 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

49. 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

51. 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

55. 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

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

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

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

85. 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

92. 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

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

100. 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

106. 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

116. 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

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

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

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

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

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

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

141. 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