22. Quinolones - Introduction Quinolones all are synthetic...

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Unformatted text preview: Introduction Quinolones all are synthetic agents lst agent described was Nalidixic acid in 1960's urinary tract infections frequent resistance Introduction 1980's - Newer agents; 3 licensed in Canada Norfloxacin p.o. Ofloxacin p.o. Ciprofloxacin p.o. and i.v. Chemical Structure Newer agents have: i) Fluorine at position 6 increases activity against Gram negative organisms ii) Piperazine ring at position 7 increases activity against Pseudomonas aeruginosa Mechanism of Action 1) Inhibits activity of bacterial DNA gyrase enzyme is essential for DNA replication 2) Bactericidal for growing bacteria Frequency & Mechanism of Resistance 3 mechanisms: mechanisms: i) Altered DNA gyrase (i.e. altered target) P. aeruginosa, gram neg. bacilli, S. aureus aeruginosa, ii) Altered permeability / penetration iii) Efflux S. aureus, others aureus, 'd resistance to one quinolone resistance to others occurs infrequently; single-step mutation singlechromosomally mediated Spectrum of Activity Highly susceptible organisms: enteric Gram negative bacilli, Neisseria spp., spp., H. influenzae, Campylobacter influenzae, Intermediate susceptible organisms: Pseudomonas aeruginosa, Gram positive cocci aeruginosa, (Staphylococci, Pneumococcus, Enterococci) Pneumococcus, Enterococci) Naturally resistant: most anaerobes, fungi Pharmacology Bioavailability - ofloxacin 100% - ciprofloxacin 70% - norfloxacin 50% impaired by Mg2+, Al+, Ca2+ containing antacids not reduced substantially by food Elimination: t1/2 = 3 to 4 hours administered twice daily most eliminated in urine (80%) some metabolized in liver (20%) Clinical Uses Not recommended as 1st line therapy for any infection Areas for consideration: i) Complicated urinary tract infections ii) Gonorrhea iii) Bacterial gastroenteritis iv) Resistant gram negative infections v) Oral therapy of Pseudomonas aeruginosa vi) Chronic osteomyelitis Clinical Uses Not recommended as 1st line therapy for any infection Areas for consideration: i) Complicated urinary tract infections ii) Gonorrhea iii) Bacterial gastroenteritis iv) Resistant gram negative infections v) Oral therapy of Pseudomonas aeruginosa vi) Chronic osteomyelitis Adverse Effects 1) 2) 3) 4) 5) 6) Gastrointestinal - nausea, diarrhea (3-8%) (3CNS - headache, dizziness, sleep disturbances (5%) Allergy - 1% Ciprofloxacin i.v. - local reactions / phlebitis (2-4%) (2Cartilage damage in immature dogs Fetal wastage in pregnant animals Contraindications 1. Children <18 yrs old - risk / benefit in certain situations (eg. Cystic Fibrosis) eg. Pregnancy Breast-feeding BreastKnown allergy 2. 3. 4. Next Generation Quinolones Cinoxacin Enoxacin Gatifloxacin Grepafloxacin Levofloxacin Trovafloxacin Lomefloxacin Moxifloxacin Norfloxacin Ofloxacin Sparfloxacin Grepafloxacin "Withdrawn from market after a small number of cardiac events associated with its use" Levofloxacin "Vitamin L" Can cause seizures, nightmares, confusion, depression, hallucinations Can cause photosensitivity rash, burning sensation Cartilage? Sparfloxacin Use has been restricted due to phototoxicity problems Used for bacterial pneumonia Trovafloxacin It has been suggested that its use be limited to life threatening infections because of potential liver toxicity ...
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This note was uploaded on 05/09/2010 for the course LMP 232 taught by Professor Crandall during the Spring '10 term at University of Toronto.

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