DR.VIJAY NAGDEV H.O. MEDICAL UNIT-
ICHANDKA MEDICAL COLLEGE LARKANA
BackgroundIn 1962 nalidixic acid was discovered by
George lesher during synthesis of chloroquine and was named as quinolone
Fluoroquinolones were derived by adding flourine atom in nalidixic acid.
Earlier quinolones were useful only for treatment of UTI.
Fluorinated derivatives achieve bactericidal levels in blood and tissues so they have improved antibacterial spectrum.
MECHANISM OF ACTIONFluroquinolones are bactericidal agents
They block bacterial DNA synthesis by inhibiting bacterial DNA gyrase and topoisomerase IV.
Inhibition of DNA gyrase prevents the relaxation of positively supercoiled DNA that is required for normal transcription and replication
Cont….Inhibition of topoisomeraseIV interferes with
separation of replicated chromosomal DNA into the respective daughter cells during cell division.
They can enter cells easily via porins and are
used to treat intracellular pathogens (Legionella, pneumophila and Mycoplasma)
RESISTANCEResistance is due to • one or more point mutations in the
quinolone binding region of the target enzyme
OR to a change in the permeability of the organism
Resistance to one FQL confers cross resistance to all members of the class.
CLASSIFICATION
Generations Drugs Spectrum
1st
(Quinolone)
Nalidixic acid
Cinoxacin
Gram-ve but not Pseudomonas species
2nd
Norfloxacin
Ciprofloxacin
Enoxacin
Ofloxacin
Gram- ve(including Pseudomonas species), some Gram+ (S. aureus) and some atypicals
3rd
Levofloxacin
Sparfloxacin
Moxifloxacin
Gemifloxacin
Same as 2nd generation with extended Gram+ve and atypical coverage
4th*Trovafloxacin Same as 3rd generation
with broad anaerobic coverage
PharmacokinecticsWell absorbed orally with bioavailability 80-
95% almost equal to i.v.Half life 3-10 hoursOral absorption impaired by divalent
cations(Antacids containg Mg, Ca,or AL ).Most of fluoroquinolones eleminated by renal
mechanism so adjustment required in patients with creatinine clearance <50 ml/min.
Limited CSF penetration.
Distribution [Conc] > serum:
Prostate tissueStoolBileLungKidneys NeutrophilsMacrophages
[Conc] < serum: Prostatic fluidBoneCSF
Drug interactions Drugs increasing levels of FQL
FQL increasing the levels of :
Theophyline Antidepressants
NSAIDS Imipramine
corticosteroids Caffene
Theophyline
Warfarin (INR –monitored)
Adverse effects.Generally safe antibioticsG.I.T-nausea,vomiting,diarrhea and antibiotic
associated colitis have been reported.CNS-confusion,insomnia,dizziness,anxiety,and
seizures(displacement of GABA from its receptors).
CVS-torsade de pointes,prolonged QTc interval.May damage growing cartilage resulting in
arthropathy(but that’s reversible so may b used in psudomonal infections in C.F where benefit outweighs the risk.)
Cont.Tendonitis and tendon rupture is rare but
very serious.Phototoxicity-avoid excesive sun exposure.Leukopenia,eosinophilia (rare)Mild elevation in transaminases (rare)
Contraindication Childrens (not absolute)PregnancyLactationEpilepsyQTc prolongation
Commonly used Fluoroquinolones
Ciprofloxacin 2nd generation fluoroquinoloneMainly effective against G –ve bacteria :Enterobacteriacae H. influenzae M. catarrhalisCampylobacter Pseudomonas N. gonorrheaeIntracellular pathogensM. Tuberculosis Mycoplasma ChlamydiaLegionella BrucellaNot effective against G+ and anaerobes
Clinical uses1.Urinary tract infections (G- bacteria)2. Osteomyelitis due to P. aeruginosa 3. Gonorrhea4. Travellers’ diarrhea- ciprofloxacin
commonly used5. Tuberculosis6. Prostatitis7. Community- acquired pneumoniae 8. Diabetic foot infections ( P. aeruginosa )9.Anthrax
Usual duration is 7-14 days Available forms
Brand name : ciproxin(bayer),cycin.
Oral Parentral Opthalmic
100 mg 200 mg iv 3mg/ml solution
250 mg 400 mg iv 3.3mg/mg ointment
500 mg
Levofloxacin 3rd generation fluoroquinolone
Spectrum: Gram-ve, Gram+ve (S. aureus including MRSA & S. pneumoniae) and Legionella pneumophila, atypical resp. pathogens,
Mycobacterium tuberculosis
Indications:Chronic bronchitis and CAP• Nosocomial pneumoniaIntra-abdominal infections
Cont. Adverse reaction.Blood glucose disturbances in DM patientsQTC prolongation, torsades de pointes, arrhythmiasNausea, GI upsetInterstitial nephritis
Usual duration same 7-14 daysAvailable forms
Brand name:leflox,l-cyn,qumic
Oral Parentral Opthalmic
100 mg 5 mg/ml iv 5mg/ml solution
250 mg 25 mg/ml iv
500mg