DR.

VIJAY NAGDEV
H.O. MEDICAL UNIT-I
Background
In 1962 nalidixic acid was discovered by George lesher
during synthesis of chloroquine and was named as
quinolone

From nalidixic acid other quinolones were derived by

adding flourine atom and were named as
FLUROQUINOLONES.
 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 ACTION
Fluroquinolones are bactericidal agents

They block bacterial DNA synthesis by inhibiting

bacterial DNA gyrase and topoisomerase IV.

Inhibition of DNA gyrase II 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.

can enter cells easily via porins and are used to treat
intracellular pathogens (Legionella, pneumophila and
Mycoplasma)
RESISTANCE
Resistance to one FQL confers cross resistance to all
members of the class.
Resistance 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
Generations
Drugs Spectrum
1st nalidixic acid Gram- but not
cinoxacin Pseudomonas species
(Quinolone)
norfloxacin Gram- (including
ciprofloxacin Pseudomonas
2nd enoxacin species), some Gram+
(S. aureus) and some
ofloxacin atypicals
levofloxacin Same as 2nd generation
sparfloxacin with extended Gram+
3rd and atypical coverage
moxifloxacin
gemifloxacin
*trovafloxacin Same as 3rd generation
4th with broad anaerobic
coverage
Pharmacokinectics
Well absorbed orally (bioavailability 80-95% almost
equal to i.v.)
Half life 3-10 hours
Oral 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.
Cont…….
[Conc] > serum: [Conc] < serum:
Prostate tissue Prostatic fluid
Stool Bone
Bile CSF
Lung
Kidneys
 Neutrophils
Macrophages
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 antibiotics
G.I-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)
Pregnancy
Lactation
Epilepsy
QTc prolongation
Commonly used Fluoroquinolones
Ciprofloxacin
2nd generation fluoroquinolone
Mainly effective against G – bacteria :
Enterobacteriacae H. influenzae M. catarrhalis
Campylobacter Pseudomonas N. gonorrheae
Intracellular pathogens
M. Tuberculosis Mycoplasma Chlamydia
Legionella Brucella
Not effective against G+ and anaerobes
Clinical uses
1.Urinary tract infections (G- bacteria)
2. Osteomyelitis due to P. aeruginosa
3. Gonorrhea
4. Travellers’ diarrhea- ciprofloxacin commonly used
5. Tuberculosis
6. Prostatitis
7. Community- acquired pneumoniae
8. Diabetic foot infections ( P. aeruginosa )
9.Anthrax
Usual dosage is 7-14 days
Available forms
Oral Parentral Opthalmic
100 mg 200 mg iv 3mg/ml solution
250 mg 400 mg iv 3.3mg/mg
ointment
500 mg

Brand name : ciproxin(bayer),cycin.

Levofloxacin
3rd generati on fluoroquinolone
 Spectrum: Gram-, Gram+ (S. aureus including MRSA & S.
pneumoniae) and Legionella pneumophila, atypical resp. pathogens,
Mycobacterium tuberculosis
 Indications:
 Chronic bronchitis and CAP
• Nosocomial pneumonia
 Intra-abdominal infections

ADRs
 Blood glucose disturbances in DM patients
 QTC prolongation, torsades de pointes, arrhythmias
 Nausea, GI upset
 Interstitial nephritis
Usual duration same 7-14 days
Available forms
Oral Parentral Opthalmic
100 mg 5 mg/ml iv 5mg/ml solution
250 mg 25 mg/ml iv
500mg

Brand name:leflox,l-cin,qumic
Moxifloxacin
 Spectrum: Gram-, Gram+ (S. aureus including MRSA & S.
pneumoniae) & atypicals (L. pneumophila, C pneumonia & M.
pneumoniae), Mycobacterium tuberculosis, gram-negative anaerobes
 Indications:
 Chronic bronchitis
 CAP
 Bacterial conjuctivitis
 Sinusitis
 ADRs
 Blood glucose disturbances in DM patients
 QTC prolongation, torsades de pointes, arrhythmias
 Nausea, GI upset
 Interstitial nephritis
Available forms.
Oral Parentral
400 mg 400 mg iv bag

Brand name :