Dr.U.P.RathnakarMD.DIH.PGDHM

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Chemotherapy

Quinolones & Fluoroquinolones,

July 2011

Fluoro-[quinolones]Quinolone Fluoroquinolone

FluoroquinoloneFluoroquinolone

FluoroquinoloneFluoroquinolone

QuinolonesNalidixic Acid

 

I generationClass I

Norfloxacin

Class II

Ofloxacin Ciprofloxacin

Table No. 1

II generation

LevofloxacinSparfloxacin

Gatifloxacin[Banned in indiaWEF 3/11]

Moxifloxacin

III generation 

TrovafloxacinGemifloxacin

Quinolones & Fluoroquinolones: Classification

DNA separation +ve supercoiling

DNA gyrase[G-ve]

-ve supercoils

TopoisomeraseIV [G+ve]

Separates daughter strands

-Ve supercoiling by nicking and sealing coiled strands and facilitate copyingSeparates daughter DNA strands after replication

FQInhibit

FQ-MOA

MOAConcn. dependent

• Concentration-dependent killing-PAE

[FQ]

• Time dependent: As long as concn exceeds MIC –No PAE

[Betalactams]

Resistance

• Enzymes with less affinity• Decreased permeation of drug• Increased efflux

FQ-PK[Cipro]

• Orally absorbed• Food delays• High tissue penetrability-Cipro• Excreted in urine-high concentrations

Quinolones:Spectrum[Bactericidal]

Quinolones

[Nalidixic acid]• Narrow G-ve

coverage• Ecoli,

Shigella, Klebsiella

• GIT & UTI

• Class I[Norflox]• Narrow G-ve

coverage• Low tissue concn.• Ecoli, Shigella,

Klebsiella• Not G+ve

• GIT & UTI• Class II [Ciproflox]• Aerobic G-Ve• E.Coli, Enterobacter,

Salmonella, Shigella, Proteus, H.Influenza

• Nisseriae, Vibrio, Yersinia• H.Ducreyi• Pseudomonas, Staph, Myco• Not Strepto and pneumo

• Second+• G+ve-Strepto

and pneumococci• Atypical-

Mycoplasma, Chlamydia• Myco• Atypical Myco• Less to

pseudomonas

• Third+• Improved

G+ve• Anaerobes

IGeneration

IIGeneration

IIIGeneration

Gemiflox

ADE• GIT Discomfort• CNS toxicity- mild headache and dizziness, Rarely,

hallucinations, delirium, and seizures[NSAIDs worsen]• Phototoxicity• Tendonitis• Cartilage damage in young animals[???????]• Enzyme inhibitor [DI-Theo, Warfarin]• Chelation[Antacids, Sucralfate, Iron]• CI in pregnancy• QTc prolongation-Gatiflox

ADE

• Fluoroquinolones are associated with an increased risk of tendonitis and tendon rupture.

Over 60 years of ageTaking steroids (corticosteroids)Kidney, heart, or lung transplant recipient

'Gatifloxacin-ADEs

• 'Gatifloxacin was banned in India on the 18th of March along with Tegaserod. A statement from the health ministry said: 'The use of the following drugs is likely to involve certain risks to human beings, whereas safer alternatives to the said drugs are available.' The move comes after international studies revealed that Gatifloxacin posed 17 times higher risk of developing serious hyperglycemia (high blood sugar) than other antibiotics in elderly patients"

Table No. 1

Quinolones: Uses

Nalidixic acid•Un-complicated UTIs & GIT [G-ve]

  •Not for use in systemic infections

I generation

Class I [Norflox] • Uncomplicated urinary tract infection and Inf of GIT• Not for use in systemic infection

Class II [Cipro]• UTI-Complicated & Uncomplicated• PPNG Infections• Chancroid• GE• Typhoid• Respiratory-Mycoplasma• TB• Meningitis

Fluoroquinolones-uses

II generation[Respiratory]•Same as for second generation•Community acquired pneumonia•TB, MAC

III generation• Consider for treatment of intra-abdominal infections [Anaerobic]•Severe infections

FQUses

• Enteric fever:

1. Cipro -500-750mg.oral/10days[4-8 weeks for carriers]

2. Others Ceftriaxone--DOC Chloramphenicol Co-trimoxazole Ampicillin/Amoxicillin

FQUses

• Other Infections• Myco bacteria [MDR TB]- and Atypical Myco

[M.Avium] -Moxi, Cipro, Ofloxacin• Leprosy [Ofloxacin]