1 / 23

Quinolones

Quinolones. A group of synthetic, bactericidal antibacterial agents Basic chemical structure of Quinolones. Essential for antibacterial activity. Substitution with fluoride to get fluoroquinolone. Addition of Piperazine ring in Ciprofloxacin and enrofloxacin.

kroot
Download Presentation

Quinolones

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Quinolones A group of synthetic, bactericidal antibacterial agents Basic chemical structure of Quinolones

  2. Essential for antibacterial activity Substitution with fluoride to get fluoroquinolone Addition of Piperazine ring in Ciprofloxacin and enrofloxacin Substitution with oxygen atom Improves activity against anaerobes Change to a carbon from a nitrogen decreases some adverse CNS effects

  3. Properties • Amphoteric compounds and exist as zwitter ions at physiological PH • Exhibit poor water solubility • Form needle shaped crystals in concentrated urine

  4. ClassificationBased upon their evolution pattern (chronology) 1st generation Quinolones: Nalidixic acid Oxolinic acid Flumequine 2nd generation Quinolones (1st generation Fluoroquinolones): Ofloxacin Norfloxacin

  5. Classification Enrofloxacin Ciprofloxacin 3rd generation quinolones (2nd generation Fluoroquinolones): Levofloxacin Gatifloxacin

  6. Mechanism of action Interference with the action of DNA-gyrase (Topoisomerase-II) enzyme Reduction in the supercoiling occurs with consequent disruption of DNA replication Degradation of DNA into small fragments by the action of exonucleases

  7. Bacterial resistance • Alteration in bacterial DNA-gyrase enzyme with a decreased affinity for Quinolones • Reduced permeability of bacterial membranes to Quinolones

  8. Pharmacokinetics Good rate and extent of absorption after oral administration in monogastric animals and pre-ruminating calves Mg+2 and Ca+2 ions decrease the absorption of Quinolones after oral administration

  9. Pharmacokinetics Distribute well into all body tissues and fluids including CNS, bones and prostrate Also get accumulated in macrophages and leucocytes Enrofloxacin undergoes de-ethylation to form Ciprofloxacin

  10. Pharmacokinetics Renal excretion is the major route of elimination Alkaline urine increases their re-absorption Fluoroquinolones appear in the milk of lactating animals in high concentration

  11. Antimicrobial spectrum 1st generation Quinolones: • Extended gram negative spectrum 1st generation Fluoroquinolones: • Broader spectrum • Effective against a wide range of gram negative & gram positive bacteria, Mycoplasma & Chlamydia • Ineffective against streptococcus & anaerobes

  12. Antimicrobial spectrum 2nd generation Fluoroquinolones: • More broader than 1st generation Fluoroquinolones • Also effective against streptococcus & anaerobes • Concentration dependent antibacterial activity • Significant post-antibiotic effect

  13. Clinical applications Older Quinolones: primarily used as urinary antiseptics Fluoroquinolones: used against intra-cellular pathogens treatment of deep-seated infections meningo-encephalitis, osteomyelitis & arthritis

  14. Clinical applications Oxolinic acid: Treatment of bacterial diseases of fish Enrofloxacin: respiratory infections such as Mycoplasmosis and Pasteurellosis

  15. Clinical applications Flumequine: Treatment of gram negative enteric infections (such as Colibacillosis) in poultry and livestock Ciprofloxacin: Treatment of typhoid in humans

  16. Adverse effects 1. Chondrodestruction: • Chelation of Mg+2 in cartilages • Chondrodestruction & joint growth • Disorders • Affects growing animals, particularly dogs & foals

  17. Adverse effects 2. Seizures: Fluoroquinolones can lower the threshold to seizures 3. crystalluria: Can cause crystalluria in dogs due to their low solubility in acidic urine

  18. Contraindications • Growing dogs under 12 to 18 months of age • Patients suffering from seizure disorders • Patients with renal insufficiency • Lactating animals

  19. Drug interactions • Mg+2, Ca+2, Al+3 & non-systemic antacids • Fluorinated Quinolones with NSAIDS • Quinolones with β-lactams • Quinolones with Aminoglycosides • Quinolones with Clindamycin • Quinolones with Metronidazole

More Related