Fluoroquinolones

1. DR.VIJAY NAGDEV
H.O. MEDICAL UNIT-I
CHANDKA MEDICAL COLLEGE
LARKANA

2. Background
In 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.

3. Earlier quinolones were useful only for treatment
of UTI.
Fluorinated derivatives achieve bactericidal levels
in blood and tissues so they have improved
antibacterial spectrum.

4. MECHANISM OF ACTION
Fluroquinolones 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


5. 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)

6. RESISTANCE
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
Resistance to one FQL confers cross resistance to all
members of the class.

7. CLASSIFICATION

8. Generations
Drugs Spectrum
1
st
(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 2
nd
generation
with extended Gram+ve
and atypical coverage
4th
*Trovafloxacin Same as 3
rd
generation
with broad anaerobic
coverage

9. Pharmacokinectics
Well absorbed orally with 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.

10. Distribution
[Conc] > serum:
Prostate tissue
Stool
Bile
Lung
Kidneys
 Neutrophils
Macrophages
[Conc] < serum:
Prostatic fluid
Bone
CSF

11. Drug interactions
Drugs increasing levels of FQL FQL increasing the levels of :
Theophyline Antidepressants
NSAIDS Imipramine
corticosteroids Caffene
Theophyline
Warfarin (INR –monitored)

14. Adverse effects.
Generally safe antibiotics
G.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.)

15. Cont.
Tendonitis and tendon rupture is rare but very
serious.
Phototoxicity-avoid excesive sun exposure.
Leukopenia,eosinophilia (rare)
Mild elevation in transaminases (rare)

16. Contraindication
Childrens (not absolute)
Pregnancy
Lactation
Epilepsy
QTc prolongation

17. Commonly used Fluoroquinolones

18. Ciprofloxacin
2
nd
generation fluoroquinolone
Mainly effective against G –ve bacteria :
Enterobacteriacae H. influenzae M. catarrhalis
Campylobacter Pseudomonas N. gonorrheae
Intracellular pathogens
M. Tuberculosis Mycoplasma Chlamydia
Legionella Brucella
Not effective against G+ and anaerobes

19. 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

20. 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

21. Levofloxacin
3
rd
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 pneumonia
Intra-abdominal infections

22. Cont.
Adverse reaction.
Blood glucose disturbances in DM patients
QTC prolongation, torsades de pointes, arrhythmias
Nausea, GI upset
Interstitial nephritis

23. Usual duration same 7-14 days
Available 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