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FLUROQUINOLONES - Dr. A. ELAMARAN

This PPT mainly concentrates on UG Pharmacology for BVSc students

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FLUROQUINOLONES - Dr. A. ELAMARAN

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  1. Nalidixic acid Ciprofloxacin Enrofloxacin Levofloxacin Moxifloxacin FLUROQUINOLONES Clinical Uses AMR PK & PD Dr. A. ELAMARAN, M.V.Sc., PGDEVP Assistant Professor of VPT Veterinary College & Research Institute Orathanadu – 614 625 dranbuelmaran@gmail.com 99 62 21 73 74 Adverse effects Drug interactions & CI

  2. What is Quinolones?! Nalidixic acid (Year: 1962 AD) URINARY ANTISEPTICS Oxolinic acid Rosoxacin Cinaxacin Flumequine & Congeners Clinical uses: UT and GIT infections Poor penetration into the body tissues • COOH @ position 3 & C=O @ position 4 - essential for antibacterial activity • Synthetic antibacterial having • 4-quinolone structure • Amphoteric in nature • Available in parenteral and oral formulations FIRST GENERATION FLUROQUINOLONES Limited action; only against very few Gm -Ve

  3. ?Quinolones to Fluroquinolones Addition of piperazine ring at position 7 – increases the tissue penetration & improves spectrum including Pseudomonas. + F • Substitution at postion 6 with fluorine called fluoroquinolines (FQ) - Enhance the activity against Gr-ve, Gr+ve, mycoplasma and chlamydia. Substitution of ‘O’ at position 8 – Improves activity against Gr+ve and anaerobic org. without affecting the bactericidal profile. Moxifloxacin

  4. ?Why do we have so much love on FQ in our practice F L U R O Q U I N O L O N E S • Good oral absorbtion • Deep distribution all over the body & deep penetration, • even to the tissues and cells • (Hence, Intra cellular organisms also susceptible) • (but not able to cross BBB (except Ofloxacin) • Newer FQs are having very broad spectrum; Bactericidal • (Gm +Ve, Gm –Ve, Atypical organisms) • High potency & Concentration dependent; • (Hence, Single dose for 24 hrs may well followed) • Very well tolerated by the host

  5. GENERATIONS OF FLUROQUINOLONES (Based on period of discovery & Antibacterial spectrum)

  6. GENERATIONS OF FLUROQUINOLONES Spectrum Uses: Pseudomonal infection GI tract infections Cystic fibrosis Resistant TB Uncomplicated UTI Intra abdominal infections

  7. How FQ acts on bacteria? InhibitingBacterial DNA gyrase (Topoisomerase II) in Gm -Ve / Topoisomerase IV in Gm +Ve Nucleic acid synthesis is inhibited ?

  8. On Gram Negative Bacteria; Bacterial Circular DNA Part of Double helix DNA Unwinding of DNA strands & +Ve super coiling Topoisomerase II (DNA Gyrase) Fluroquinolone Inhibits Bactericidal in action DNA gyrase – Endonuclease domain make nick and form –Ve super coiling DNA gyrase –Ligase domain add glue and resealing the coiling TI II / DNA gyrase – Endonuclease domain & DNA ligase domain

  9. On Gram Positive Bacteria; Monther DNA & Daughter DNAs are twisted Bacterial Circular DNA In terminal stages of DNA Replication Fluroquinolone Inhibits Separation of Daughter DNA by nicking & resealing Topoisomerase IV Bactericidal in action Mother and daughter DNAs

  10. How the bacteria oppose and survive against FQ?! Bacteria X FQ Increased efflux pump Decreased permeability Mutation of enzymes Mostly Chromosomal mediated resistance ! Other class drugs are plasmid mediated resistance

  11. Pharmacokinetics • Concentration dependent AB • PAE & Eagle effect Absorption • >90% Oral absorption • Peak plasma concentrations @ 1 hour in dogs. • Presence of Divalent & Trivalent cations(Al3+, Ca2+, Fe2+ & Mg2+) tend to chelate with FQ – delayed absorbtion. • (Avoid Milk, Yoghurt & antacids etc?! During the course of FQ) Distribution • Deep penetration- CNS, bone, and prostate • Not BBB; Except Ofloxacin • Norfloxacin has poor distribution and penetration; Only used as urinary antiseptics • Parent drug & Active metabolite – Effects the action • Ex: Enrofloxacin • Ciprofloxacin • (FQs are CyP450 inhibitor) • Hence, NSAID,Warfarin Excretion Metabolism Most follows Renal excretion Pefloxacin from 30 & Most of the 40 FQ like Moxifloxacin Trevofloxacin follows biliary excretion 40 has longest t1/2

  12. Clinical uses Respiratory Infections, Inhaled anthrax, TB GI & Abdominal infections Ophthalmic infections Prostitis in male; UTI STD Infections of Bone, Joint & Soft tissues • Alternate to Aminoglycosides • Synergistic with B- lactams Mastitis

  13. Tendinitis & Tendon rupture ( Esp. in young animals) Antiarthrogenic effect - Damages growing cartilages Adverse Effects Contraindicated in young animals , Pregnant animals Superinfection Pseudomembranous colitis Dizziness, Seizures Enro. causes extreme in humans; only for veterinary purpose Retinal degeneration in cats QT Prolongation Max. with Moxifloxacin Cl. difficile

  14. Learning Outcome • Who are all FQ? -floxacin • MOA, Classifications of Diff. generations of FQ & Spectrum • Clinical uses, Adverse effects & Contraindications ? Thank You!

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