Pharmacology of Quinolones and Fluoroquinolones Topics Discussed- 1. Introduction 2. Mechanism of Action 3. Antibacterial Spectrum 4. Pharmacokinetics 5. Adverse Effects 6. Drug Interactions 7. Therapeutic Uses 8. Discussion of some fluoroquinolones

1. Quinolones and
Fluoroquinolones
-Prajwal Waman Ghatol

2. Introduction
Mechanism Of Action
Antibacterial Spectrum
Pharmacokinetics
Adverse Effects
Drug Interactions
Therapeutic Uses
Discussion of some fluroquinolones
What will we
learn?

3. 01.
02.
These are synthetic antimicrobials
having a quinolone structure and are
active primarily against gram-
negative bacteria, though the newer
fluorinated compounds also inhibit
gram- positive ones.
Introduction The first member Nalidixic acid
introduced in mid-l960s had
usefulness limited to urinary and g.i.
tract infections because of low
potency, modest blood and tissue
levels, restricted spectrum and high
frequency of bacterial resistance.

4. 03.
04.
Introduction
Fluoroquinolones (FQs) have high
potency, expanded spectrum, slow
development of resistance, better
tissue penetration and good
tolerability.
Fluoroquinolones (FQs) are synthetic,
fluorinated analogues of nalidixic acid. The
important FQs are norfloxacin,
ciprofloxacin, pefloxacin (first-generation
FQs), ofloxacin, levofloxacin, gemifloxacin
and moxifloxacin (second-generation FQs)

5. Classification
In addition, two other FQs
Pazufloxacin and Balofloxacin are
available in India.

6. Mechanism of Action
FQs inhibit bacterial DNA synthesis
(bactericidal). They inhibit DNA gyrase,
thus blocking DNA replication in gram-
negative bacteria. Inhibition of
topoisomerase IV in gram-positive
bacteria prevents separation of
replicated DNA.

7. Antibacterial Spectrum
Ciprofloxacin is the prototype drug. It is highly effective against aerobic gram-negative
organisms – E. coli, Enterobacter, Proteus, Klebsiella, Salmonella, Shigella,, H. influenzae, N.
gonorrhoeae, N. meningitidis, V. cholerae and Campylobacter jejuni.
It has activity against S. aureus, Pseudomonas aeruginosa and M. tuberculosis.
Most of the anaerobes, Bacteroides fragilis, C. difficile, etc. are resistant to ciprofloxacin. Newer
FQs like levofloxacin, gemifloxacin and moxifloxacin have greater activity against streptococci
and some activity against anaerobes.

8. Pharmacokinetics
Ciprofloxacin is administered by oral, i.v. or topical routes. It is
well absorbed from the gut, but food delays its absorption. It is widely
distributed in the body, and reaches high concentration in kidney, lung,
prostatic tissue, bile, macrophages, etc. It is excreted mainly in urine.

9. Adverse Effects
1. The The common adverse effects are related to the GI
tract, e.g. nausea, vomiting and abdominal discomfort.
2. CNS effects include headache, dizziness, insomnia,
confusion, hallucinations and convulsions.
3. Hypersensitivity reactions include skin rashes, urticaria,
itching, eosinophilia and photosensitivity.

10. Adverse Effects
3. Tenosynovitis and tendon rupture can occur especially in
athletes.
4. Moxifloxacin can cause prolongation of QT interval.
5. FQs are contraindicated in pregnancy.
6. FQs have caused cartilage damage in immature animals –
hence, they should be avoided in young children.

11. Hypersensitivity reactions
Tenosynovitis
Contraindicated in Pregnancy

12. Drug Interactions
Ciprofloxacin increases the plasma concentration of
theophylline, warfarin, etc., by inhibiting their metabolism.
Nonsteroidal anti-inflammatory drugs (NSAIDs) may potentiate
CNS side effects of FQs – confusion, irritability and rarely
convulsions may occur. Like tetracyclines, absorption of FQs is
reduced by antacids, ferrous salts and sucralfate.

13. Therapeutic Uses
1. UTI : FQs are one of the most commonly used AMAs for UTI. They are
effective against gram-negative bacilli, such as E. coli, Proteus and
Enterobacter.
2. PROSTATITIS: FQs are used in prostatitis as an alternative to cotrimoxazole.
3. BACTERIAL DIARRHOEAS: FQs are effective for a variety of GI infections
caused by E. coli, Shigella, Salmonella, etc. For traveller’s diarrhoea (due to E.
coli), FQs are as effective as cotrimoxazole.
4. TYPHOID FEVER : Ciprofloxacin (750 mg orally b.d. for 10 days) is the
preferred drug for treatment of typhoid. It is bactericidal and causes rapid
resolution of symptoms. Levofloxacin or ofloxacin can also be used.

14. Therapeutic Uses
4. SEXUALLY TRANSMITTED DISEASES : ■
 Gonococcal infections
 Chancroid
 Chlamydial cervicitis and urethritis
5. SKIN, SOFT-TISSUE AND BONE INFECTIONS : FQs can be used in combination
with an agent effective against anaerobes especially in diabetic foot infections.
6. Ciprofloxacin can be used to ERADICATE MENINGOCOCCI from nasopharynx,
thus eliminating the carrier state, but the preferred drug is rifampin.
7. MYCOBACTERIAL INFECTIONS: In MDR-TB, atypical mycobacterial infections in
AIDS patients and leprosy, FQs are used in combination with other AMAs.

15. Therapeutic Uses
8. Prophylaxis and treatment of infections in neutropenic patients:
FQs can be used.
9. Ciprofloxacin, levofloxacin, moxifloxacin and ofloxacin are used
topically for conjunctivitis due to susceptible organisms.
10. RESPIRATORY INFECTIONS: Newer FQs (levofloxacin and
moxifloxacin) are highly effective for community-acquired
pneumonia and chronic bronchitis.
11. ANTHRAX: Ciprofloxacin is the preferred drug for treatment and
prophylaxis of anthrax.

18. Thank you!