The document outlines the competencies and learning objectives regarding fluoroquinolones, detailing their antibacterial spectrum, mechanism of action, resistance, clinical uses, and adverse effects. It categorizes fluoroquinolones into first and second generations, discusses their pharmacokinetics, and lists specific examples along with their applications in various infections. The document also addresses benefits, resistance mechanisms, and potential drug interactions associated with fluoroquinolones.

1. FLUOROQUINOLONES

2. COMPETENCY &
SPECIFIC LEARNING
OBJECTIVES
• COMPETENCY - PH1.42, PH1.43
The student should able to
Describe the Antibacterial spectrum, MOA,
resistance, Uses & adverse effects of
Fluoroquinolones

3. SPECIFIC LEARNING OBJECTIVES
At the end of the class, the student should able
to:
• Classify Fluoroquinolones (FQ) with examples.
• Describe the mechanism, spectrum, resistance and
pharmacokinetics of FQ.
• Describe the clinical uses, adverse effects, interactions
and contraindications of FQ.
• Compare and contrast between I & II generation FQ

4. Quinolones – accidental discovery
Quinine
Chloroquine
Mefloquine
Quinolones
1960’s
GEORGE LESHER & Co workers
Distillate of chloroquine

5. QUINOLONES
SYNTHETIC ANTIMICROBIALS
QUINOLONE STRUCTURE
GRAM NEGATIVE BACTERIA
FLUORINATED COMPOUNDS – ALSO GRAM
POSTIVE ONES.

6. N
N
O
H3C
CH3
COOH
Nalidixic acid
N
N
H
N
F
O
CH3
CO2H
Norfloxacin - Noroxin®
Ciprofloxacin - Cipro®
N
N
H
N
F
O
CO2H
STRUCTURE

7. NALIDIXIC ACID
SPECTRUM – Gram negative bacteria.
E. Coli, proteus, klebsiella,
Enetrobacter, Shigella.
BACTERICIDAL DRUG
metabolism – liver
t1/2 – 8 hours.
excretion – urine.
1.Resistance – rapid
2.Potency –low
3.Spectrum – limited
4.Resistance – high
5.For gi&urinary
infections
6.Tissue levels - low
HIGH CONCENTRATION – URINE ( 20 – 50 TIMES)

8. ADVERSE EFFECTS
GIT, rashes.
Neurological – headache, drowsiness, vertigo, visual
disturbances, seizures.
Long term use – Parkinsonism like symptoms.
Leucopenia, biliary stasis.
Phototoxicity - Rare
G6PD deficiency – Hemolysis.
C/I - INFANTS.

9. USES
URINARY ANTISEPTIC.
DIARRHOEA – proteus, E.coli, shigella, salmonella.
Ampicillin resistant shigella enteritis.

10. FLUROQUINOLONES
Quinolones with one or more substitutions.
I Generation - 1980
II Generation -1990
N
N
H
N
F
O
CH3
CO2H
Norfloxacin - Noroxin®
Ciprofloxacin - Cipro®
N
N
H
N
F
O
CO2H

11. Quinolones
Fluoroquinolone
(1970’s)
- Fluorine addition at C 6
- increased activity against
the DNA gyrase
- increased penetration into
the bacterial cell
Ciprofloxacin introduced
Piperazine group was added to C-7
Improved gram -ve & +ve coverage
Better serum and tissue levels
1st quinolone to be used for
conditions other then UTI’s
1987

12. FLUROQUINOLONES
I Norfloxacin II Lomefloxacin
Ciprofloxacin Sparfloxacin
Ofloxacin Levofloxacin
Pefloxacin Moxifloxacin
Gatifloxacin
III Gemifloxacin
Plurifloxacin
Sitafloxacin,
Pazufloxacin
Balofloxacin

13. MECHANISM OF ACTION
Inhibit
DNA gyrase
DNA Topoisomerase IV

14. DNA gyrase
MECHANISM OF ACTION

15. Fluoroquinolone: Mechanism of Action
Cell Wall
Cell Membrane
DNA Gyrase
DNA Topoisomerase IV
fq fq
fq
fq
fq
fq fq
Fluoroquinolone
DNA
Excessive positive
supercoiliing
DNA
digestion

16. MECHANISM OF ACTION
DNA gyrase Nicks double stranded DNA.
Introduce negative supercoils.
Reseals the nicked ends.
Prevents excessive positive supercoiling
RESISTANCE
MUTATION OF DNA gyrase - Reduce affinity to FQs.
Reduced permeability of drugs

17. Efflux Pump
Chrosomal
mutation
Resistance to
FQ
Altered DNA gyrase
Altered
Topoisomerase IV

18. CIPROFLOXACIN
MOST POTENT DRUG
Aerobic gram negative bacilli
Enterobactericeae
Neisseria
HIGHLY SUSCEPTIBLE
E. Coli Neisseria
K. Pneumoniae H. influenza
Enterobacter H. ducreyi
S. Typhi & other salmonella C.jejuni
Shigella Y. enterocolitica
Proteus. V. cholerae

19. MODERATIVELY SENSITIVE
Pseudomonas
S. Aureus ( MRSA)
S. Epidermidis
branhemella catarrhalis
legionalla
Brucella
Listeria
Mycobact. Tuberculosis
LOW
S. Pyogens. Faecalis,
mycoplasma
Clamydia
Mycobact. Kansasii / avium

20. SPECIAL FEATURES
Rapid bactericidal activity
High potency
Long post – antibiotic effect
Mutational resistance – Low frequency
Plasmid type mutants – Low
Intestinal streptococci & anaerobes – Protected.
Against β lactam & aminoglycoside resistant bacteria
Acidic pH - Less active

21. RESISTANCE
Bacteroids
Clostridia
Anaerobic cocci.

22. PHARMACOKINETICS
Oral absorption good. food delays absorption.
High tissue penetrability
Lung, sputum, muscle, bone, prostate & phagocytes
concentration – high.
Excretion – glomerular filtration, tubular secretion.
Urinary / biliary concentration - 10-50 fold more

23. ADVERSE EFFECTS
safety - good.
GIT - Nausea, vomiting, bad taste, anorexia.
CNS - Headache, dizziness, restlessness, anxiety, insomnia,
impairement of concentration & dexterity, tremor.
Seizures – rare. (?GABA RECEPTOR binding)
Skin - Rash, pruritis, photosensitivity, urticaria, swelling of
lips etc.,
Tendonitis & tendon rupture.
bothers

24. C/I – PREGNANCY
ARTHROPATHY -- IMMATURE ANIMALS
CARTILAGE DAMAGE (?)
Drug interactions
Inhibits metabolism – Theophylline (CYP 450 1A2)
Caffeine
Warfarin
NSAIDS enhance fluroquinolones toxicity
Antacids, sucralfate, Iron salts – Reduce absorption of FQs.

25. THERAPEUTIC USES
(1) UTI – complicated / uncomplicated
- High cure rates.
(2) Chancroid - 500 mg BD x 3 days.
(3) Gonorrhoea - 500mg single dose.
(4) Bacterial gastroenteritis –E.Coli
Shigella
Salmonella
C. Jejuni
Travellors diarrhoea (ETEC)
Decrease stool volume – Cholera.

26. (5) TYPHOID - 1st drug of choice.
500 mg – 750 mg BD x 10 days.
(or)
200 mg IV BD.
advantages (1) quick defervescence
(2) Relief of symptoms early.
Complications, relapse – low
(3) Prevention of carrier state
Cidal action
good penetration
biliary / Intestinal concentration.
For typhoid carriers. 750 mg BD – 4- 8weeks.
92% Eradication.

27. (6) Bone, soft tissue, gynaecological & wound infections – by
resistant staphlococci.
Gram negative bacteria.
+ metronidazole / clindamycin -- Diabetic foot.
(7) Respiratory infections.
Mycoplasma
Legionella
B. catarrhalis
Inhalational anthrax - US FDA
Tuleremia.

28. (8) Tuberculosis - Combination therapy
- Resistant TB.
(9) Gram negative septicaemias.
Ciprofloxacin + III gen. cephalsporin /Aminoglycoside.
(10) Meningitis - gram negative organisms
Immunocompromised.
CSF shunts.
(11) Prophylaxis – Neutropenia / cancer patients.
(12) Conjunctivitis – Gram negative bacteria.
Topical therapy

29. NORFLOXACIN
Less protent than ciprofloxacin
Use – Urinary / genital tract infections.
Bacterial diarrhoeas.
PEFLOXACIN
Methyl derivative of norfloxacin.
More lipid soluble.
Oral – complete absorption.
High CSF concentration.
T1/2 – long.
Alternative to ciprofloxacin in typhoid.

30. OFLOXACIN
Intermediate between ciprofloxacin & norfloxacin.
More portent than cipro - gram positive & anaerobes.
Chlamydia, mycoplasma.

31. PK – Lipid soluble
Plasma concentration – High.
Excretion – Urine ( unchanged)
Use – Systemic & mixed infections.
For chronic bronchitis.
Respiratory / ENT infections.
Gonorrhoea – 200mg single dose.
Non gonococcal urethritis / cervicitis.
TB / leprosy.

32. Levo isomer
More activity – strep. pneumonia.
- Gm + ve & Gm - ve
TB, Anaerobes.
OBA – 100% single dose. 500 mg oral
For community acquired pneumonia.
Exacerbation of chronic bronchitis.
Sinusitis.
Enteric fever.
Pyelonephritis.
Skin & soft tissue infection.
LEVOFLOXACIN
Difluronated quinolone
Equal to Ciprofloxacin
More active against gram negative
bacteria & Chlamydia.
T1/2 – long, single dose.
Dose – 400mg 0.3% eye drops.
Phototoxicity
QTc prolongation
LOMEFLOXACIN

33. Increased activity – gram positive
bacteroide fragilis &
anaerobes,mycobacteria.
Phototoxic reactions
Slight prolongation of QTc interval - 3%
Dose : 200, 400 mg single dose
0.3% eye drops.
• pneomonia
• Exacerbations of chronic bronchitis
• Sinusitis / ENT infections
• Tuberculosis / leprosy
• MAC infection – AIDS patients
• Chlamydial infections
SPARFLOXACIN
Str.pnemonia
Atypical respiratory pathogens
Anaerobes
Myco. Tuberculosis
QTc prolongation.
swelling of face.
•Community acquired pneumonia.
•Exacerbation of chronic bronchitis.
• other URI/LRI.
GATIFLOXACIN

34. MOXIFLOXACIN
Long activity drug
High activity – St. pneumoniae
Other gram positive ones
some anaerobes
TB – most potent.
Use – Pneumonia.
Bronchitis.
Sinusitis
Otitis media
Dose – 400 mg OD 0.5% eye drops.

35. CIPRO NORFL PEFL OFL
1.Oral bioavailability (%) 60-80 35-45 90-100 85-95
2. Plasma protein binding (%) 20-35 15 20-30 25
3. Vol. of distribution (L/kg) 3-4 2 2 1.5
4. Percent metabolized 20 25 85 5-10
5. Elimination t1/2 3-5 4-6 8-14 5-8
6. Routes of administration oral, i.v. oral oral, i.v. oral
7. Dose (mg BD) oral: 250-750 400 400 200-400
iv : 100-200 - 400 200

36. LEVO LOME SPAR GATI
1.Oral bioavailability (%) ~100 >90 90 96
2. Plasma protein binding (%) 25 10 40 20
3. Vol. of distribution (L/kg) 1.3 1.7-2.5 3.6 -
4. Percent metabolized 5 20 60 <5
5. Elimination t1/2 8 6-9 15-20 8
6. Routes of administration oral,i.v. oral oral oral,i.v.
7. Dose (mg BD) oral: 500 400 200-400 200-400
(OD) (OD) (OD) (OD)
iv : 500 - - 200-400