QUINOLONES ANTIBIOTICS FROM CHEMOTHERAPY.ppt

QUINOLONES ANTIBIOTICS FROM CHEMOTHERAPY.ppt

1. QUINOLONES

2. Fluoroquinolones
•Synthetic antimicrobial agents
•Which are developed in 1980s.prior to fluoroquinolones
nalidixic acid,which is a simple quinolone derivative is used
•Later in 1970s another group of quinolones eg.. Oxolinic
acid & cinoxacin was launched.
•In 1980s with the introduction of 6-fluourinated-4-
quinolones such as ciprofloxacin & analogues

3. Generation Drug Names Spectrum
1st
Nalidixic acid
Cinoxacin
Gram- but not
Pseudomonas species
2nd
Norfloxacin
Ciprofloxacin
Ofloxacin
Gram- (including
Pseudomonas species),
some Gram+ (S. aureus)
and some atypicals
3rd
Levofloxacin
Sparfloxacin
Moxifloxacin
Gemifloxacin
Gatifloxacin
Same as 2
nd
generation
with extended Gram+ and
atypical coverage
4th
Trovafloxacin Same as 3
rd
generation
with broad anaerobic
coverage
*withdrawn from the market in 1999

4. •DNA gyrase
(topoisomerase II) nikes
double-stranded DNA,
relaxes supercoils.
•Topoisomerase IV nikes
and unlinks DNA for the
following DNA replication.
•Qs and FQs inhibit both
enzymes so they inhibit
DNA replication
Quinolones And Fluoroquinolones
Mechanism of action

5. First Generation of Quinolones (FGQs)
NN
O
H
3C
CH
3
COOH
Nalidixic acid
Synthetic compounds consisted of an N
1

alkylated 1,4-dihydro-4-oxo-3-pyridinecarboxylic
acid fused to a substituted aromatic ring.
The first quinolone introduced to clinic in 1962 to
fight against G(-) urinary infections :

6. •Well absorbed from GIT.
•Partly metabolized in liver.
•Poor tissue penetration and low plasma
levels.
Cannot be used for the treatment of systemic
infections.
•Excreted in urine. High urine concentration

7. •It is useful in the treatment of uncomplicated
UTI due to gram-negative bacteria and
diarrhoea due to Shigella or Salmonella.
•The most common adverse effects are related
to GI tract, central nervous system (CNS) and
skin.
•Contraindicated in infants

8. Fluoroquinolones
•These are quinolone having one or more fluorine
substitutions.

9. CIPROFLOXACIN (CIFRAN)
•The most potent first generation
fluoroquinolones active against a broad range of
bacteria ,the most susceptible ones are the
aerobic gram-negative bacilli especially
enterobacteriaceae and neisseria
Potent CYP450 inhibitor

10. •Oral Availability % - 60-70%
•Indication - UTI, Gonorrhoea,
Gastroenteritis, skin,
soft tissue, bone and
joint infections
•T1/2 (hours) - 3.3-4.9
•Oral dose - 250 mg. single dose
250-750 mg. BD daily;
200-400 mg. by IV infusion
(over 30-60 min) twice daily

11. USES
1.Urinary tract infections
2.Gonorrhea
3.Chancroid
4.Bacterial gastroenteritis
5.Typhoid
6.Bone, soft tissue, gynecological and wound
infections
7.Respiratory infections

12. USES
8.Tuberculosis
9.Gram negative septicemias
10.Meningitis
11.Prophylactic use – neutropenic patients
12.Conjunctivitis

13. CIPROFLOXACIN - ADR
Gastrointestinal
•Nausea
•Vomiting
•Bad taste
•Anorexia

14. CIPROFLOXACIN - ADR
•CNS
•Dizziness
•Headache
•Restlessness
•Anxiety
•Insomnia
•Impairment of concentration

15. Why Fluoroquinolones cause CNS
toxicity?
N
O
COOH
N
HN
F
H
2N
CH
2
CH
2
CH
2
COOH
Tremor, sleep disorders, anxiety, and convulsions
because of GABA antagonism at the receptor.
Because of low penetration to brain this toxicity is rare.

16. CIPROFLOXACIN - ADR
•Skin/hypersensitivity
•Rash
•Pruritis
•Photosensitivity
•Urticaria
•Swelling
•Tendinitis
•Tendon Rupture

17. Contraindications
•contraindicated in pregnancy
•Should avoid in children (less than 8 years of age) because
quinolones damage the growing cartilages and cause
arthropathy.
•To be avoided in patents with prolonged QTc interval in those
receiving other drugs that prolongs QTc interval (e.g mefloquine
erythromycin)
•Current use of calcium , iron , other preparations containing
divalent cations should be avoided

19. NORFLOXACIN (NORFLOX)
•It is less potent than ciprofloxacin due to less bioavailability
•Is primarily used for UTI & bacterial diarrhoea
•It is not recommended for respiratory & systemic infections,
particularly where gram-positive cocci are involved
•Oral Availability % - 30-40%
•T1/2 (hours) - 3-4
•Oral dose - 400 mg twice daily

20. OFLOXACIN (TARIVID)
•Effective against gram-negative organism
•More active than ciprofloxacin against gram-
positive organism ,chlamydia,mycoplasma.
•It is used in Tuberculosis ,leprosy, Atypical
pneumonia & chlamydial infections.
•Oral Availability % - About 95%
•Indication - Like ciprofloxacin
•T 1/2 (hours) - 5-7
•Oral dose - 200-400 mg. once
daily;

21. PEFLOXACIN (PELOX)
•Similar to ciprofloxacin ,also effective against
mycobacterium leprae
•Oral Availability % - About 90%
•Indication - Like ciprofloxacin
•T 1/2 (hours) - 8-13
•Oral dose - 400 mg. twice daily
400 mg. by
IV infusion
(over 1hour) twice
daily

22. LOMEFLOXACIN (LOMADAY)
•Oral Availability % - About 90%
•Indication - Like Norfloxacin
•T1/2 (hours) - 6-8
•Oral dose - 400 mg once daily
IV 400 mg

23. SPARFLOXACIN (SPARLOX)
•Oral Availability % - > 90%
•Indication - Like ciprofloxacin
preferred in community
acquired pneumonia
•T 1/2 (hours) - 21
•Oral dose - 200-400 mg. in one or
two divided doses per
day 500 mg.

24. LEVOFLOXACIN (TAVANIC)
•Increased activity against streptococcus
pneumoniae,effective against gram –ve bacteria
& anaerobes.
•Oral Availability % - > 90%
•Indication - community acquired
pneumonias,chronic bronchitis,skin,soft
tissue & UTI
•T 1/2 (hours) - 6-8
•Oral dose - 7-14 days

25. GATIFLOXACIN (TEQUIN)
•Oral Availability % - > 95%
•Indication - Ear infections,UTI
preferred in community
acquired pneumonia.

•T 1/2 (hours) - 7-10
•Oral dose - 400 mg OD

26. GEMIFLOXACIN (FACTIVE)
•Oral Availability % - > 70%
•Indication - Like ciprofloxacin
preferred in community
acquired pneumonia
•T 1/2 (hours) - 7
•Oral dose - 300 mg OD

27. FLUOROQUINOLONES
1.CIPROFLOXACIN 500 mg BD
2.NORFLOXACIN 400 mg BD
3.OFLOXACIN 200 mg OD
4.PEFLOXACIN 400 mg BD
5.LOMEFLOXACIN 400 mg OD
6.SPARFLOXACIN 200 mg OD
7.LEVOFLOXACIN 500 mg OD
8.GATIFLOXACIN 400 mg OD
9.MOXIFLOXACIN 400 mg OD
10.GEMIFLOXACIN 300 mg OD

28. THANK YOU