Class quinolones

this ppt gives brief discussion for under graduate examination

1. Quinolones Dr. RAGHU PRASADA M S MBBS,MD ASSISTANT PROFESSOR DEPT. OF PHARMACOLOGY SSIMS & RC. 1

2. Quinolones The quinolones (Qs) and fluoroquinolones (FQs) are a family of broad-spectrum synthetic antimicrobial agents. The parent of the group is nalidixic acid The fluoroquinolones have a fluoro group attached the central ring system.

3. Mechanism of action Qs and FQs are bactericidal drugs. FQs enter into the host cells  active against intracellular pathogens  Legionella spp., Mycoplasma spp. and Chlamydia spp.

4. Mechanism of action They inhibit enzymes called topoisomerase , enzymes needed for supercoiling , replication and separation of circular bacterial DNA. 1. G-VE  DNA Gyrase is a topoisomerase II that catalyzes the negative supercoiling of the circular DNA found in bacteria prevent replication of bacterial DNA 2. G+ve  Topoisomerase IV  relaxation of the supercoiled circular DNA, enabling the separation of the interlinked daughter chromosomes at the end of bacterial DNA replication inhibition of cell division  

5. Classification First Generantion - Norfloxacin , Ciprofloxacin, Ofloxacin , Pefloxacin , Lomefloxacin Second Generation- Levofloxacin , Prulifloxacin , Third Generation- Gatifloxacin , Sparfloxacin , Gemifloxacin Fourth Generation- Moxifloxacin , Trovafloxacin , Alatrofloxacin , Finafloxacin

6. Antimicrobial Spectrum

7. First generation CIPROFLOXACIN The most potent of the fluoroquinolones for P. aeruginosa. Long post-antibiotic effect. Well absorbed from GIT. Administration: orally, IV. Excreted in urine. Potent CYP450 inhibitor

8. First generation CIPROFLOXACIN The most potent of the fluoroquinolones for P. aeruginosa. Long post-antibiotic effect. Well absorbed from GIT. Administration: orally, IV. Excreted in urine. Potent CYP450 inhibitor

9. Second generation Levofloxacin An isomer of Ofloxacin and has largely replaced it clinically. Very well absorbed from GIT. Administration: orally, iv. Excreted unchanged Long post-antibiotic effects. Long-acting (single daily dose)

10. Second generation- Levofloxacin Treatment respiratory tract infections due to S. pneumonia (pneumonia, COPD exacerbation). Used in the treatment of prostitis due to E. coli and of sexually transmitted diseases(gonorrhea), with the exception of syphilis. levofloxacin is utilized in wide range of infections, including skin infections, acute sinusitis, nosocomial pneumonia

11. Fourth generation MOXIFLOXACIN Long-acting (single daily dose). Long post-antibiotic effect. Mostly used for the treatment respiratory tract infections (pneumonia, COPD exacerbation). Used for the treatment severe bacterial infections including sepsis, peritonitis. The most potent fluoroquinolones against M. tuberculosis. Poor activity against P. aeruginosa.

12. Fourth generation FINAFLOXACIN Novel, under phase III Antibacterial activity increases at acidic pH More efficacious in tissue and body compartments acidified due to infection and inflammation Widest spectrum of G+ve , G- ve , anaerobic, and atypical pathogens Very long t 1/2 High safety profile-no incidence of hepato , renal, cardio and phototoxicity .

13. Adverse Effects GI: Nausea, vomiting CNS: HA, dizziness, confusion, insomnia, delerium , hallucinations, seizure (rare) Cardiovascular: QT-prolongation Torsades de pointes (III gen) Endocrine - Blood glucose disturbances in DM patients( levo , moxi ) Musculoskeletal: Rupture of tendon (prolonged use) Hepatotoxicity- Trova , Alatro Photo toxicity- Lome , Pefl , Gati ,

14. Drug interaction Ciprofloxacin is a potent CYP450 inhibitor. Increases plasma levels and toxic effects of anticoagulants, digoxin, theophylline FQs in combination with with class IA and class III antiarrhythmics prolong QT and may cause arrhythmias Antacids has been found to result in six to ten fold decreases in the absorption of oral quinolones .

15. Contraindications Fluoroquinolones generally should not be administered to patients younger than 18 years of age. Fluoroquinolones should not be administerd to pregnant or lactating women. Should not be given to arrythmic patient.

16. Third generation Gemifloxacin has been approved for the treatment of mild to moderate community-acquired pneumonia and acute exacerbation of chronic bronchitis but has increased risk of tendinitis Sparfloxacin - photosensitivity, cardiotoxicity - QTc prolongation Trovafloxacin / Alatrofloxacin - was withdrawn because of the risk of hepatic toxicity. Gatifloxacin was withdrawn because of an increased frequency of hypoglycemia and hyperglycemia , cardiotoxicity - QTc prolongation

17. Urinary antiseptics NALIDIXIC ACID Non flourinated quinolone 98% protein bound, excre - urine G- ve coliforms except pseudomonas PHENAZOPYRIDINE Dye with analgesic effects Relives burning sensation, dysuria , urgency ADR- E pigastric distress, orange coloured urine

18. Urinary antiseptics Nitrofurantoin  niitroanion superoxidedamage bacterial DNA Nitrofuron derivative MOA- blocks acetyl CoA synthesis carbohydrate metabolism BacteriostaticBactericidal Loses its action at p H of 8 E.coli , proteus , St.aureus , E.faecalis Prophylaxis of UTI ADR-Nausea, Ph.neuritis , hepatitis, pulmonary fibrosis, hemolytic anemia D/I- probenacid , nalidixic acid

19. Urinary antiseptics Acidic urine NITROFURANTOIN TETRACYCLINE METHICILLLIN CLOXACILLIN Alkaline urine COTRIMOXAZOLE GENTAMYCIN CEPHALOSPORINS

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