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Pharmacology of Quinolones ppt satya

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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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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