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One healthy bacterium
could reproduce
into a colony of
more than 2 million…..
in just seven hours…..
DR. V. SATHYA NARAYANAN. M. D.,
PROFESSOR OF PHARMACOLOGY
SRM MCH & RC
SRM UNIVERSITY.
CHENNAI
QUINOLONES
Synthetic antimicrobials having quinolone structure
 Active primarily against GRAM NEGATIVE
BACTERIA
1960’s N...
NALIDIXIC ACID
Active against G-ve bacteria
SPECTRUM : E.coli , proteus ,klebsiella, shigella ,
enterobacter ( not pseud...
NALIDIXIC ACID
USES
 as urinary antiseptic - second line drug for recurrent
UTI
 G –ve diarrhoeas (E.coli, shigella, sal...
FLUOROQUINOLONES
First generation - 1980’s – 1 flouro substitution
Norfloxacin Ofloxacin
Ciprofloxacin Pefloxacin
 II nd...
MECHANISM OF ACTION
 Inhibit bacterial DNA GYRASE( in GRAM --VE)
interfere with strand cutting ,resealing function 
Dam...
Resistance
: Plasmid mediated resistance does not occur
 mutational resistance
 slow to develop
FEATURES OF FQs
Rapidly bactericidal
Concentration dependent bacterial killing
Long postantibiotic effect
Low frequenc...
CIPROFLOXACIN(prototype )
 SPECTRUM OF ACTION :
highly effective on : G-ve bacilli - E.Coli, klebsiella,
proteus , salmo...
PHARMACOKINETICS
Rapid oral absorption
high tissue penetrability
excreted primarily in urine
 ↑urinary, biliary concen...
ADR
Mild - seen in 10 % of patients
Gastrointestinal -nausea , vomiting, bad taste
CNS : dizziness , headache , confusi...
CONTRAINDICATIONS
Pregnancy
 Children <18 yrs old
(cartilage damage in wt bearing joints)
INTERACTIONS
Inhibit cyp450 microsomal enzymes → ↓metabolism
↓
↑Toxicity of sulfonylureas ,
theophylline ,
warfarin
NSAI...
THERAPEUTIC USES
Typhoid fever
UTI
Bacterial gastroenteritis
Chancroid
Gonorrhoea
Anthrax
Bone ,soft tissue infecti...
THERAPEUTIC USES
Diabetic foot
MDR tuberculosis
G-ve septicaemias , meningitis
Conjunctivitis by g-ve bacteria(topical...
IN DENTISTRY
Not indicated for any acute orofacial infections unless
culture & sensitivity reports
Not synergistic with ...
NORFLOXACIN
Less potent
Low concentration in tissues
Indicated in - UTI ,genital tract infections , bacterial
diarrhoea...
PEFLOXACIN
Methyl derivative of norfloxacin
More lipid soluble
Better tissue penetration
Passage into CSF higher than ...
OFLOXACIN
More potent for G+ve infections
Also effective against Chlamydia , Mycoplasma ,
M.leprae , M.tuberculosis
Lip...
LEVOFLOXACIN
Levoisomer
Improved action on Strep .pneumoniae , anaerobes
100 % oral BA
Single daily dose
No cyp 450 i...
LOMEFLOXACIN
II nd generation FQ
More active on some G-ve bacteria , Chlamydia
Single daily dose
↓dose in renal failur...
SPARFLOXACIN
Enhanced action on G +ve bacteria
Strep. Pneumoniae,
staphylococci,
enterococci ,
bacteroides and other ...
SPARFLOXACIN – ADR & DRUG
INTERACTIONS
No CYP 450 interaction
Phototoxicity +( patients advised not to go in sun)
Sligh...
SPARFLOXACIN - Indications
Pneumonia,
Chronic bronchitis,
ENT infections,
Tuberculosis ,
leprosy ,
MAC infection in ...
GATIFLOXACIN – Spectrum & Indications
Strep .pneumoniae,
chlamydia pneumoniae
 atypical respiratory pathogens,
 anaero...
GATIFLOXACIN –
ADR&CONTRAINDICATIONS
ADR – Phototoxicity ,
CNS effects
C/I - hypokalemia
 CAUTION : prolonged Qtc inter...
MOXIFLOACIN
Spectrum -G+ve
β lactam /macrolide resistant bacteria
Atypical respiratory pathogens
Most potent FQ in tub...
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Pharmacology of Quinolones ppt satya

  1. 1. One healthy bacterium could reproduce into a colony of more than 2 million….. in just seven hours…..
  2. 2. DR. V. SATHYA NARAYANAN. M. D., PROFESSOR OF PHARMACOLOGY SRM MCH & RC SRM UNIVERSITY. CHENNAI
  3. 3. QUINOLONES Synthetic antimicrobials having quinolone structure  Active primarily against GRAM NEGATIVE BACTERIA 1960’s Nalidixic acid 1980 ‘s Fluoroquinolones
  4. 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. 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. 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. 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. 8. Resistance : Plasmid mediated resistance does not occur  mutational resistance  slow to develop
  9. 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. 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. 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. 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. 13. CONTRAINDICATIONS Pregnancy  Children <18 yrs old (cartilage damage in wt bearing joints)
  14. 14. INTERACTIONS Inhibit cyp450 microsomal enzymes → ↓metabolism ↓ ↑Toxicity of sulfonylureas , theophylline , warfarin NSAIDs →↑ CNS toxicity of FQs Antacids , iron →↓ Absorption of FQs
  15. 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. 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. 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. 18. NORFLOXACIN Less potent Low concentration in tissues Indicated in - UTI ,genital tract infections , bacterial diarrhoeas Not for RI
  19. 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. 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. 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. 22. LOMEFLOXACIN II nd generation FQ More active on some G-ve bacteria , Chlamydia Single daily dose ↓dose in renal failure ↑ warfarin levels
  23. 23. SPARFLOXACIN Enhanced action on G +ve bacteria Strep. Pneumoniae, staphylococci, enterococci , bacteroides and other anaerobes,  mycobacteriae Single daily dose
  24. 24. SPARFLOXACIN – ADR & DRUG INTERACTIONS No CYP 450 interaction Phototoxicity +( patients advised not to go in sun) Slight prolongation of Qtc interval
  25. 25. SPARFLOXACIN - Indications Pneumonia, Chronic bronchitis, ENT infections, Tuberculosis , leprosy , MAC infection in AIDS
  26. 26. GATIFLOXACIN – Spectrum & Indications Strep .pneumoniae, chlamydia pneumoniae  atypical respiratory pathogens,  anaerobes  Upper Respiratory Infections, Lower Respiratory Infections,  Urinary Tract Infections 
  27. 27. GATIFLOXACIN – ADR&CONTRAINDICATIONS ADR – Phototoxicity , CNS effects C/I - hypokalemia  CAUTION : prolonged Qtc intervral GATIFLOXACIN –NOT USED IN UK & USA
  28. 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
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an interesting ppt starting with some fun facts of bacteria and describe the pharmacology of quinolone group of antimicrobials, the highlight being the common properties of

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