Fluoroquinolones

Presentation on Quinolone and Fluoroquinolones

1. Dr. Sahil Kumar
Department of Pharmacology
Maulana Azad Medical College
FLUOROQUINOLON
ES

2. Parent drug: Nalidixic acid

3. NALIDIXIC ACID
(Quinolone)
•Available for the management of UTI.
•Limited therapeutic ability.
•A/E – GI upset, rashes, neurological
toxicity, hemolysis.
•Bacterial resistance.

4. Structure
Carboxylic acid moiety at position 3
Many new FQs have Fluorine at position 6
Piperazine moiety at position 7

5. Mechanism of Action
DNA GYRASE: Gram negative bacteria (negative
super coiling)
TOPOISOMERASE 4: Gram positive bacteria
(separation of daughter strands)
TOPOISOMERASE 2: Eukaryotic cells

7. Mechanism of Resistance
Unique MOA, so plasmid mediated resistance
less.
Resistance is d/t Chromosomal mutation
producing DNA gyrase/ Topoisomerase 4 with
reduced affinity for FQs.
Reduced permeability/ increased efflux.

9. Fluoroquinolones:
Classification
1
st
Generation FQs:
Norfloxacin
Ciprofloxacin
Ofloxacin
Pefloxacin
2
nd
Generation FQs:
Levofloxacin
Lomefloxacin
Sparfloxacin
Moxifloxacin
Gemifloxacin
Prulifloxacin

10. Structure of various
Fluoroquinolones

11. Pharmacokinetics
Good oral BA : 85-95%
Oral absorption decreased by divalent cations
High tissue penetrability.

12. DRUG T ½ hrORAL BA ORAL DOSE
mg
ROUTE OF
EXCRETION
CIPROFLOXACIN 3-5 70 500 RENAL
GATIFLOXACIN 8 98 400 RENAL
LEVOFLOXACIN 5-7 95 500 RENAL
LOMEFLOXACIN 8 95 400 RENAL
MOXIFLOXACIN 9-10 >85 400 NON RENAL
NORFLOXACIN 3.5-5 80 400 RENAL
OFLOXACIN 5-7 95 400 RENAL
SPARFLOXACIN 18 92 50%RENAL,
50%FECAL
TROVAFLOXACIN 11 88 200 NON RENAL

13. CIPROFLOXACIN
Prototype of FQs.
Most potent 1
st
gen FQ against broad range
of bacteria.
Aerobic gram –ve.

14. Microbiological
Properties
• Rapid bactericidal activity and high potency.
• Relatively long post-antibiotic effect on
Enterobacteriaceae, Pseudomonas and Staph.
• Low frequency of mutational resistance.
• Protective intestinal streptococci, anaerobes spared.
• Active against many β-lact. & AG resistant bacteria.
• Less active at acidic pH.

15. Adverse Drug Reactions
GIT: Nausea, Vomiting, Anorexia. Diarrhea
infrequent.
HYPERSENSITIVITY: Rash
CNS: Headache, Dizziness, Insomnia
JOINTS, CARTILAGE: Reversible Arthropathy,
Tendon Rupture, Tendinitis

18. Drug interactions
Food and Antacids, Iron: Decrease absorption
Theophylline, caffeine, warfarin: increase d/t
Enzyme Inhibition.
NSAIDs may increase CNS toxicity. (Seizures)

19. Therapeutic Uses
UTI : Multi Drug Resistant Pseudomonas.
Norflox 400mg bd
Cipro 500 mg bd
Oflox 400mg bd
Bacterial dysentery: Shigella, Salmonella, E coli,
Campylobacter.
Typhoid: 500 mg bd X 10d
◦Quick defervescence
◦Early abetment of symptoms.
◦Prevention of carrier state.

20. STDs : Chlamydia (7d), Chancroid (3d), PID (14d)
Bone & soft tissue infection: Cipro + Metro.
Respiratory infection: both upper and lower RTI
Tuberculosis: Resistant, atypical( MAC )
Septicemias
Meningitis
Neutropenic patients - prophylaxis.
Conjunctivitis

22. NORFLOXACIN
Less potent than Ciprofloxacin.
Attains lower conc. in tissues.
Used in UTI, dysentery.

23. PEFLOXACIN
Methyl derivative of Norfloxacin.
Passage in CSF greater than in other tissues.
Longer t-half, so accumulates  effective in
systemic inf as well.

24. OFLOXACIN
Less active than Ciprofloxacin against G-ve.
Equally or more potent against G+ve/ anaerobes.
Used in Chlamydial inf, TB, Leprosy.
Comparable to Cipro in therapy of systemic and
mixed infections.

25. LEVOFLOXACIN
Active levo-isomer of Ofloxacin.
100% oral BA.
Used in CAP, Chronic Bronchitis Exacerbation
(90% cure rate)

26. LOMEFLOXACIN
2
nd
generation.
Equal in activity to Ciprofloxacin.
Single daily administration.
High incidence of Phototoxicity and QT
prolongation.

27. MOXIFLOXACIN
2
nd
generation.
Activity against Str. pneumoniae, G+ve including
Beta-lactam and Macrolide resistant ones,
anaerobes.
Pneumonias, bronchitis, sinusitis, otitis media.

28. GEMIFLOXACIN
2
nd
generation.
Another broad spectrum FQ.
CAP, Chronic Bronchitis Exacerbation.

29. PRULIFLOXACIN
2
nd
generation.
Prodrug of Ulifloxacin.
Broad spectrum.
Chronic Bronchitis Exacerbation, UTI

30. Banned/ Withdrawn from
market
Gatifloxacin : QT prolongation, Hypoglycemia
Sparfloxacin : Fatal arrhythmias, phototoxicity
Temafloxacin : Immune hemolytic anemia
Trovafloxacin : Hepatotoxicity
Grepafloxacin : Cardiotoxicity
Clinafloxacin : Phototoxicity

31. Which of the following fluoroquinolones does not
require dose adjustment in a patient with Cr. CL of < 50
mL/min?
(a) Ciprofloxacin
(b) Trovafloxacin
(c) Lomefloxacin
(d) Sparfloxacin
A contraindication to the use of Ciprofloxacin is a history of:
(a) Epilepsy
(b) Deep vein thrombosis
(c) Gout
(d) G-6 PD deficiency

32. Which of the following statements about fluoroquinolones
is FALSE?
(a) Gonococcal resistance to fluoroquinolones may involve
changes in DNA gyrase.
(b) Modification of fluoroquinolones dosage is required in
patients if creatinine clearance is less than 50 mL/min.
(c) A fluoroquinolone is the drug of choice for treatment
of an uncomplicated UTI in a 7 year-old girl.
(d) Fluoroquinolones inhibit relaxation of positively
supercoiled DNA.

33. THANK YOU!