Presentation on theme: "Fluoroquinolones Mark S. Johnson, Pharm.D., BCPS Associate Professor and Director of Postgraduate Education."— Presentation transcript:
Fluoroquinolones Mark S. Johnson, Pharm.D., BCPS Associate Professor and Director of Postgraduate Education
Fluoroquinolones Very popular class of antibiotics due to spectrum of coverage (gram positive, gram negative, atypicals), unique mechanism of action resulting in inhibition of bacterial DNA gyrase and topoisomerase IV, excellent PO bioavailability, fairly well tolerated – Has led to overprescribing, resistance Nalidixic acid was first quinolone (1962) – Had limited antibacterial activity – Associated with rapid development of bacterial resistance – Was only useful for lower UTI’s – Synthesis led to the evolution of the fluoroquinolones.
Fluoroquinolones Mechanism of action – Block bacterial DNA synthesis by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV Inhibition of DNA gyrase prevents the relaxation of positively supercoiled DNA that is required for normal transcription and replication Inhibition of topoisomerase IV interferes with separation of replicated chromosomal DNA into the respective daughter cells during cell division – Bactericidal
Fluoroquinolones Resistance Resistance mediated by – Mutations in DNA gyrase – Change in outer bacterial membrane permeability – Variant of an aminoglycoside acetyltransferase
Fluoroquinolones PKS Absorption – Excellent BA (80-95%) Distribution – Widely distributed in body fluids and tissues Elimination – Mainly by renal tubular secretion or glomerular filtration – Moxifloxacin—hepatic metabolism, some urinary excretion – Gemifloxacin—both renal and hepatic
Fluoroquinolones Drug Interactions Drug interactions: – Quinolones’ absorption reduced by: di-, tri-valent cations (antacids, Ca supplements, iron, MVI, diary products, etc), sucralfate, ddi – Space out as far apart as can (at least 2h, but more better) – Quinolones can inhibit metabolism of: theophylline, caffeine, warfarin
Fluoroquinolones 2 nd generation Ciprofloxacin (Cipro, Cipro XR, Proquin XR) Coverage: pseudomonas coverage, good gram – coverage (E. coli, salmonella, Shigella, Neirsseria, Legionella), some gram + ( no strep pneumo), Atypical coverage – Good for UTIs, pyelonephritis, prostatitis, osteomyelitis, anthrax, infectious diarrhea, travelers diarrhea, typhoid fever, intra-abdominal infections (with metronidazole), possible RTI’s, possible skin – Dosing: – PO 250-500-750mg BID – XR 500-1000mg QD – IV 400mg Q8-12h – Ophthalmic solution 0.3%
Fluoroquinolones 2 nd generation Ofloxacin (Floxin) Coverage similar to ciprofloxacin (except Pseudomonas) Used for: primarily for UTI’s and nongonococcal urethritis and cervicitis Dosing 200-400mg PO BID Ophthalmic Solution 0.3% (Ocuflox)
Fluoroquinolones 2 nd generation Norfloxacin (Noroxin) Used for UTI’s, prostatitis Dosing: PO 400mg BID
Fluoroquinolones 3 rd Generation Levofloxaxin (Levaquin) – L-isomer of ofloxacin – Improved Gram + coverage and similar Gram –, some Pseudomonas coverage – Used for CAP, COPD exacerbations, sinusitis, skin infections, complicated UTIs “Respiratory fluoroquinolone” – Dosing: 250mg-750mg PO/IV Q24h Ophthalmic solution (Iquix 1.5%, Quixin 0.5%)
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